Process for the preparation of a sulfonamide derivative

This application claims priority with respect to US Provisional Application No. 61/120275 filed December 5, 2008 and US Provisional Application No. 61/181180 filed May 26, 2009. All of these applications are incorporated herein by reference in their entirety.

The present invention relates to compounds that selectively inhibit the activity of anti-apoptotic Bcl-2 family proteins, compositions containing this compound, and methods of treating diseases in which the anti-apoptotic Bcl-2 protein is expressed in the meantime.

Anti-apoptotic Bcl-2 family proteins are involved in several diseases and are being studied as potential therapeutic target. These targets for intervention therapy include, for example, the Bcl-2 family proteins Bcl-2, Bcl-X._LAnd Bcl-w are included. Inhibitors of Bcl-2 family proteins were recently reported in co-owned PCT / US / 2004/36770 published as WO 2005/049593 and PCT / US / 2004/37911 published as WO 2005/049594. Has been done. Although this technique teaches inhibitors with high binding to the target protein, compound binding affinity is only one of several parameters considered. One goal is to produce compounds that preferentially or selectively bind to one protein over another. To demonstrate this selectivity, it is well known that one compound not only exhibits a high binding affinity for a particular protein, but also a lower binding affinity for another member.

A general measure of the binding affinity of an anti-apoptotic protein inhibitor is the balance between the binding and dissociation process between the protein and the inhibitor (K)._i). Inhibition constant (K_i) Is the dissociation constant of an enzyme-inhibitor complex or protein / small molecule complex , the small molecule that inhibits the binding of one protein to another. Therefore, K_iA large value indicates a low binding affinity, and K_iA small value indicates a high binding affinity.

A general measure of the cellular activity of anti-apoptotic protein inhibitors is the concentration that elicits a cellular effect of 50% (EC).₅₀).

<p num="0006"><patcit num="1"><text>PCT / US2004 / 36770</text></patcit><patcit num="2"><text>International Publication No. 2005/049593</text></patcit><patcit num="3"><text>PCT / US2004 / 37911</text></patcit><patcit num="4"><text>International Publication No. 2005/049594</text></patcit></p>

<p num="0007"> Therefore, we find that the compounds taught in the art are useful in the treatment of various cancers and immune disorders, but they are anti-apoptotic Bcl-X._LNot as selective for anti-apoptotic Bcl-2 protein as for protein, resulting in anti-apoptotic Bcl-X such as thrombocytopenia_LIt has been found to result in the potential for high side effects characterized by protein inhibition.</p><p num="0008"> Therefore, the present invention is anti-apoptotic Bcl-X._LMore anti-apoptotic to protein Bcl-2 protein binds and inhibits its activity significantly higher than that of the compounds taught in PCT / US / 2004/36770 and PCT / US / 2004/37911. Includes a range of compounds that are sex and exhibit unexpected properties.</p>

<p num="0009">(Gist of the invention) Therefore, one embodiment of the present invention is useful as a selective inhibitor of one or more anti-apoptotic protein family members in formula (I).</p><p num="0010"><chemistry num="1"><img id="000002" he="29" wi="158" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(In the formula, A¹Is N or C (A)²) And; A², B¹, D¹And E¹One or two or three of them or each is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NR¹C (O) NHR¹, NR¹C (O) N (R)¹)₂, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CN, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; Y¹Is H, CN, NO₂, C (O) OH, F, Cl, Br, I, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, R¹⁷, OR¹⁷, C (O) R¹⁷, C (O) OR¹⁷, SR¹⁷, NH₂, NHR¹⁷, N (R)¹⁷)₂, NHC (O) R¹⁷, C (O) NH₂, C (O) NHR¹⁷, C (O) N (R)¹⁷)₂, NHS (O) R¹⁷Or NHSO₂R¹⁷Is; or B¹And Y¹Is imidazole or triazole along with the atoms to which they are attached; A², D¹And E¹One or two or each of them is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NHC (O) NHR¹, N (CH₃) C (O) N (CH₃) R¹, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; R¹Is R², R³, R⁴Or R⁵Is; R^1AIs C₁-C₆-Alkyl, C₃-C₆-Alkenyl or C₃-C₆-Alkyne; R²Is uncondensed or arene, heteroarene or R^2AIs phenyl condensed with; R^2AIs a cycloalkane or a heterocycloalkane; R³Is uncondensed or benzene, heteroarene or R^3AHeteroaryl condensing with; R^3AIs a cycloalkane or a heterocycloalkane; R⁴Are cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is uncondensed or arene, heteroarene or R.^4ACondensed with; R^4AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁶, NC (R^6A) (R^6B), R⁷, OR⁷, SR⁷, S (O) R⁷, SO₂R⁷, NHR⁷, N (R)⁷)₂, C (O) R⁷, C (O) NH₂, C (O) NHR⁷, NHC (O) R⁷, NHSO₂R⁷, NHC (O) OR⁷, SO₂NH₂, SO₂NHR⁷, SO₂N (R⁷)₂, NHC (O) NH₂, NHC (O) NHR⁷, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NH₂, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NHR¹, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁶Is C₂-C₅-Spiroalkyl, each of which is unsubstituted or OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH (CH)₃) Or N (CH₃)₂Replaced by; R^6AAnd R^6BAre independently selected alkyls, or R with N to which they are attached^6CIs; R^6CAre aziridine-1-yl, azetidine-1-yl, pyrrolidine-1-yl or piperidine-1-yl, which are not replaced or O, C (O), CNOH, CNOCH, respectively.₃, S, S (O), SO₂Or one CH replaced by NH₂Has a part; R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is; R⁸Is uncondensed or arene, heteroarene or R^8AIs phenyl condensed with; R^8AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁹Is uncondensed or arene, heteroarene or R^9AHeteroaryl condensing with; R^9AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has moieties and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^10ACondensed with; R^10AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3¹², OR¹², NHR¹², N (R)¹²)₂, C (O) NH₂, C (O) NHR¹², C (O) N (R)¹²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R¹²Is R¹³, R¹⁴, R¹⁵Or R¹⁶Is; R¹³Is uncondensed or arene, heteroarene or R^13AIs phenyl condensed with; R^13AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁴Are heteroaryl, each of which is uncondensed or arene, heteroarene or R^14ACondensed with; R^14AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁵Are cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes, each of which is uncondensed or arene, heteroarene or R.^15ACondensed with; R^15AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁶Is alkyl, alkenyl or alkynyl; R¹⁷Is R¹⁸, R¹⁹, R²⁰Or R²¹Is; R¹⁸Is uncondensed or arene, heteroarene or R^18AIs phenyl condensed with; R^18AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁹Is uncondensed or arene, heteroarene or R^19AHeteroaryl condensing with; R^19AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^20ACondensed with; R^20AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3²², OR²², NHR²², N (R)²²)₂, C (O) NH₂, C (O) NHR²², C (O) N (R)²²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R²²Is R²³, R²⁴Or R²⁵Is; R²³Is uncondensed or arene, heteroarene or R^23AIs phenyl condensed with; R^23AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁴Is uncondensed or arene, heteroarene or R^24AHeteroarene condensed with; R^24AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁵Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^25ACondensed with; R^25AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; Z¹Is R²⁶Or R²⁷And each of them is R²⁸, R²⁹Or R³⁰Replaced by, each of which is F, Cl, Br, I, CH₂R³⁷, CH (R)³¹) (R³⁷), C (R³¹) (R^31A) (R³⁷), C (O) R³⁷, OR³⁷, SR³⁷, S (O) R³⁷, SO₂R³⁷, NHR³⁷Or N (R)³²) R³⁷Replaced by; R²⁶Is a phenyl that is uncondensed or condensed with arene or heteroarene; R²⁷Is a heteroarene that is not condensed or is condensed with an arene or a heteroarene; R²⁸Is uncondensed or arene, heteroarene or R^28AIs phenyl condensed with; R^28AIs a cycloalkane, cycloalkene, heterocycloalkene or heterocycloalkene, R²⁹Is heteroaryl or R^29AIs; R^29AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁰Are cycloalkyl or cycloalkenyl, respectively, O, C (O), CNOH, CNOCH, which are not replaced or are independently selected.₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^30ACondensed with; R^30AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³¹And R^31AAre independently F, Cl, Br or alkyl, or together with C₂-C₅-Spiroalkyl; R³²Is R³³, C (O) R³³Or C (O) OR³³Is; R³³Is R³⁴Or R³⁵Is; R³⁴Is uncondensed or aryl, heteroaryl or R^34AIs phenyl condensed with; R^34AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁵Is not replaced or R³⁶It is an alkyl substituted with; R³⁶Is uncondensed or arene, heteroarene or R^36AIs phenyl condensed with; R^36AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁷Is R³⁸, R³⁹Or R⁴⁰And each of them is F, Cl, Br, I, R⁴¹, OR⁴¹, NHR⁴¹, N (R)⁴¹)₂, NHC (O) OR⁴¹, SR⁴¹, S (O) R⁴¹Or SO₂R⁴¹Replaced by; R³⁸Is uncondensed or arene, heteroarene or R^38AIs phenyl condensed with; R^38AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁹Is uncondensed or arene, heteroarene or R^39AHeteroaryl condensing with; R^39AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁰Is C₃-C₈-Cycloalkyl or C₄-C₈-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^40ACondensed with; R^40AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴¹Is R⁴², R⁴³, R⁴⁴Or R⁴⁵Is; R⁴²Is uncondensed or arene, heteroarene or R^42AIs phenyl condensed with; R^42AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴³Is uncondensed or arene, heteroarene or R^43AHeteroaryl condensing with; R^43AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁴Is C₃-C₉-Cycloalkyl or C₄-C₇-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^44ACondensed with; R^44AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R⁴⁶, OR⁴⁶, NHR⁴⁶, N (R)⁴⁶)₂, C (O) NH₂, C (O) NHR⁴⁶, C (O) N (R)⁴⁶)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁴⁶Is R⁴⁷, R⁴⁸Or R⁴⁹Is; R⁴⁷Is uncondensed or arene, heteroarene or R^47AIs phenyl condensed with; R^47AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁸Is heteroaryl or R^48AIs; R^48AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁹Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^49ACondensed with; R^49AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁶And R²⁷The part represented by is an independently selected R^50A, OR^50A, SR^50A, S (O) R^50A, SO₂R^50AOr NHR^50AIs further replaced by one, two or three of R^50AIs R^51A, R^52A, R^53AOr R^54AIs; R^51AIs uncondensed or benzene, heteroarene or R^51AAPhenyl that is condensed with R^51AAIs a cycloalkane, cycloalkene, or heterocycloalkene heterocycloalkene, R^52AIs heteroaryl; R^53AIs C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl; each is undone or independently selected O, C (O), CNOH, CNOCH₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^53AACondensed with; R^53AAAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R^54AAre alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R^55AA, OR^55AA, SR^55AA, S (O) R^55AA, SO₂R^55AA, NHR^55AA, N (R)^55AA)₂, C (O) R^55AA, C (O) NH₂, C (O) NHR^55AA, NHC (O) R^55AA, NHSO₂R^55AA, NHC (O) OR^55AA, SO₂NH₂, SO₂NHR^55AA, SO₂N (R^55AA)₂, NHC (O) NH₂, NHC (O) NHR^55AA, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, F, Cl, Br or I substituted with one, two or three substituents; R^55AAAlkyl, alkenyl, alkynyl, phenyl, heteroaryl or R^56AIs; R^56AIs C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkyl, each of which is non-replaced or independently selected O, C (O), CNOH, CNOCH₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N; R², R³, R⁴, R⁶, R^6C, R⁸, R^8A, R⁹, R¹⁰, R¹³, R¹⁴, R¹⁵, R¹⁸, R¹⁹, R²⁰, R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹, R³⁰, R³⁴, R³⁶, R³⁸, R³⁹, R⁴⁰, R⁴², R⁴³, R⁴⁴, R⁴⁷, R⁴⁸And R⁴⁹The part represented by is not independently replaced, further not replaced, 1, 2, 3, 4 or 5 independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S (O) R⁵⁰, SO₂R⁵⁰, C (O) R⁵⁰, CO (O) R⁵⁰, OC (O) R⁵⁰, OC (O) OR⁵⁰, NH₂, NHR⁵⁰, N (R)⁵⁰)₂, C (O) NH₂, C (O) NHR⁵⁰, C (O) N (R)⁵⁰)₂, C (O) NHOH, C (O) NHOR⁵⁰, C (O) NHSO₂R⁵⁰, C (O) NR⁵⁵SO₂R⁵⁰, SO₂NH₂, SO₂NHR⁵⁰, SO₂N (R⁵⁰)₂, CF₃, CF₂CF₃, C (O) H, C (O) OH, C (N) NH₂, C (N) NHR⁵⁰, C (N) N (R)⁵⁰)₂, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituted or further substituted with substituents; R⁵⁰Is R⁵¹, R⁵², R⁵³Or R⁵⁴Is; R⁵¹Is uncondensed or arene, heteroarene or R^51BIs phenyl condensed with; R^51BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵²Is heteroaryl; R⁵³Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^53BCondensed with; R^53BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵⁴Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁵⁵, OR⁵⁵, SR⁵⁵, S (O) R⁵⁵, SO₂R⁵⁵, NHR⁵⁵, N (R)⁵⁵)₂, C (O) R⁵⁵, C (O) NH₂, C (O) NHR⁵⁵, NHC (O) R⁵⁵, NHSO₂R⁵⁵, NHC (O) OR⁵⁵, SO₂NH₂, SO₂NHR⁵⁵, SO₂N (R⁵⁵)₂, NHC (O) NH₂, NHC (O) NHR⁵⁵, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, F, Cl, Br or I substituted with substituents; R⁵⁵Alkyl, alkenyl, alkynyl, phenyl, heteroaryl or R⁵⁶Is; Are the alkyl, alkenyl, and alkynyl substituted? OCH₃Replaced by; R⁵⁶Is C₃-C₈-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N. ) With respect to a compound having or a therapeutically acceptable salt, a prodrug or a salt of a prodrug.</p><p num="0011"> Other embodiments of the invention serve as a selective inhibitor of the anti-apoptotic Bcl-2 protein formula (II).</p><p num="0012"><chemistry num="2"><img id="000003" he="79" wi="156" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(During the ceremony, R¹⁰⁰Is R²⁶As described for the substituents above; n is 0, 1, 2 or 3; A¹Is N or C (A)²) And; A², B¹, D¹And E¹One, two or three or each of them is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NR¹C (O) NHR¹, NR¹C (O) N (R)¹)₂, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CN, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; Y¹Is H, CN, NO₂, C (O) OH, F, Cl, Br, I, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, R¹⁷, OR¹⁷, C (O) R¹⁷, C (O) OR¹⁷, SR¹⁷, NH₂, NHR¹⁷, N (R)¹⁷)₂, NHC (O) R¹⁷, C (O) NH₂, C (O) NHR¹⁷, C (O) N (R)¹⁷)₂, NHS (O) R¹⁷Or NHSO₂R¹⁷Is; or B¹And Y¹Is imidazole or triazole along with the atoms to which they are attached; A², D¹And E¹One or two or each of them is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NHC (O) NHR¹, N (CH₃) C (O) N (CH₃) R¹, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; R¹Is R², R³, R⁴Or R⁵Is; R^1AIs C₁-C₆-Alkyl, C₃-C₆-Alkenyl or C₃-C₆-Alkyne; R²Is uncondensed or arene, heteroarene or R^2AIs phenyl condensed with; R^2AIs a cycloalkane or a heterocycloalkane; R³Is uncondensed or benzene, heteroarene or R^3AHeteroaryl condensing with; R^3AIs a cycloalkane or a heterocycloalkane; R⁴Are cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is uncondensed or arene, heteroarene or R.^4ACondensed with; R^4AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁶, NC (R^6A) (R^6B), R⁷, OR⁷, SR⁷, S (O) R⁷, SO₂R⁷, NHR⁷, N (R)⁷)₂, C (O) R⁷, C (O) NH₂, C (O) NHR⁷, NHC (O) R⁷, NHSO₂R⁷, NHC (O) OR⁷, SO₂NH₂, SO₂NHR⁷, SO₂N (R⁷)₂, NHC (O) NH₂, NHC (O) NHR⁷, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NH₂, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NHR¹, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁶Is C₂-C₅-Spiroalkyl, each of which is unsubstituted or OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH (CH)₃) Or N (CH₃)₂Replaced by; R^6AAnd R^6BAre independently selected alkyls, or R with N to which they are attached^6CIs; R^6CAre aziridine-1-yl, azetidine-1-yl, pyrrolidine-1-yl or piperidine-1-yl, which are not replaced or O, C (O), CNOH, CNOCH, respectively.₃, S, S (O), SO₂Or one CH replaced by NH₂Has a part; R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is; R⁸Is uncondensed or arene, heteroarene or R^8AIs phenyl condensed with; R^8AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁹Is uncondensed or arene, heteroarene or R^9AHeteroaryl condensing with; R^9AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has moieties and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^10ACondensed with; R^10AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3¹², OR¹², NHR¹², N (R)¹²)₂, C (O) NH₂, C (O) NHR¹², C (O) N (R)¹²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R¹²Is R¹³, R¹⁴, R¹⁵Or R¹⁶Is; R¹³Is uncondensed or arene, heteroarene or R^13AIs phenyl condensed with; R^13AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁴Are heteroaryl, each of which is uncondensed or arene, heteroarene or R^14ACondensed with; R^14AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁵Are cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes, each of which is uncondensed or arene, heteroarene or R.^15ACondensed with; R^15AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁶Is alkyl, alkenyl or alkynyl; R¹⁷Is R¹⁸, R¹⁹, R²⁰Or R²¹Is; R¹⁸Is uncondensed or arene, heteroarene or R^18AIs phenyl condensed with; R^18AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁹Is uncondensed or arene, heteroarene or R^19AHeteroaryl condensing with; R^19AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^20ACondensed with; R^20AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3²², OR²², NHR²², N (R)²²)₂, C (O) NH₂, C (O) NHR²², C (O) N (R)²²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R²²Is R²³, R²⁴Or R²⁵Is; R²³Is uncondensed or arene, heteroarene or R^23AIs phenyl condensed with; R^23AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁴Is uncondensed or arene, heteroarene or R^24AHeteroarene condensed with; R^24AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁵Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^25ACondensed with; R^25AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁰Are cycloalkyl or cycloalkenyl, respectively, O, C (O), CNOH, CNOCH, which are not replaced or are independently selected.₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^30ACondensed with; R^30AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; respectively F, Cl, Br, I, CH₂R³⁷, CH (R)³¹) (R³⁷), C (R³¹) (R^31A) (R³⁷), C (O) R³⁷, OR³⁷, SR³⁷, S (O) R³⁷, SO₂R³⁷, NHR³⁷Or N (R)³²) R³⁷Replaced by; R³¹And R^31AAre independently F, Cl, Br or alkyl, or together with C₂-C₅-Spiroalkyl; R³²Is R³³, C (O) R³³Or C (O) OR³³Is; R³³Is R³⁴Or R³⁵Is; R³⁴Is uncondensed or aryl, heteroaryl or R^34AIs phenyl condensed with; R^34AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁵Is not replaced or R³⁶It is an alkyl substituted with; R³⁶Is uncondensed or arene, heteroarene or R^36AIs phenyl condensed with; R^36AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁷Is R³⁸, R³⁹Or R⁴⁰And each of them is F, Cl, Br, I, R⁴¹, OR⁴¹, NHR⁴¹, N (R)⁴¹)₂, NHC (O) OR⁴¹, SR⁴¹, S (O) R⁴¹Or SO₂R⁴¹Replaced by; R³⁸Is uncondensed or arene, heteroarene or R^38AIs phenyl condensed with; R^38AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁹Is uncondensed or arene, heteroarene or R^39AHeteroaryl condensing with; R^39AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁰Is C₃-C₈-Cycloalkyl or C₄-C₈-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^40ACondensed with; R^40AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴¹Is R⁴², R⁴³, R⁴⁴Or R⁴⁵Is; R⁴²Is uncondensed or arene, heteroarene or R^42AIs phenyl condensed with; R^42AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴³Is uncondensed or arene, heteroarene or R^43AHeteroaryl condensing with; R^43AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁴Is C₃-C₉-Cycloalkyl or C₄-C₇-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^44ACondensed with; R^44AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R⁴⁶, OR⁴⁶, NHR⁴⁶, N (R)⁴⁶)₂, C (O) NH₂, C (O) NHR⁴⁶, C (O) N (R)⁴⁶)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁴⁶Is R⁴⁷, R⁴⁸Or R⁴⁹Is; R⁴⁷Is uncondensed or arene, heteroarene or R^47AIs phenyl condensed with; R^47AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁸Is heteroaryl or R^48AIs; R^48AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁹Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^49ACondensed with; R^49AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R², R³, R⁴, R⁶, R^6C, R⁸, R^8A, R⁹, R¹⁰, R¹³, R¹⁴, R¹⁵, R¹⁸, R¹⁹, R²⁰, R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹, R³⁰, R³⁴, R³⁶, R³⁸, R³⁹, R⁴⁰, R⁴², R⁴³, R⁴⁴, R⁴⁷, R⁴⁸And R⁴⁹The part represented by is not independently replaced, further not replaced, 1, 2, 3, 4 or 5 independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S (O) R⁵⁰, SO₂R⁵⁰, C (O) R⁵⁰, CO (O) R⁵⁰, OC (O) R⁵⁰, OC (O) OR⁵⁰, NH₂, NHR⁵⁰, N (R)⁵⁰)₂, C (O) NH₂, C (O) NHR⁵⁰, C (O) N (R)⁵⁰)₂, C (O) NHOH, C (O) NHOR⁵⁰, C (O) NHSO₂R⁵⁰, C (O) NR⁵⁵SO₂R⁵⁰, SO₂NH₂, SO₂NHR⁵⁰, SO₂N (R⁵⁰)₂, CF₃, CF₂CF₃, C (O) H, C (O) OH, C (N) NH₂, C (N) NHR⁵⁰, C (N) N (R)⁵⁰)₂, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituted or further substituted with substituents; R⁵⁰Is R⁵¹, R⁵², R⁵³Or R⁵⁴Is; R⁵¹Is uncondensed or arene, heteroarene or R^51BIs phenyl condensed with; R^51BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵²Is heteroaryl; R⁵³Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^53BCondensed with; R^53BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵⁴Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁵⁵, OR⁵⁵, SR⁵⁵, S (O) R⁵⁵, SO₂R⁵⁵, NHR⁵⁵, N (R)⁵⁵)₂, C (O) R⁵⁵, C (O) NH₂, C (O) NHR⁵⁵, NHC (O) R⁵⁵, NHSO₂R⁵⁵, NHC (O) OR⁵⁵, SO₂NH₂, SO₂NHR⁵⁵, SO₂N (R⁵⁵)₂, NHC (O) NH₂, NHC (O) NHR⁵⁵, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, F, Cl, Br or I substituted with substituents; R⁵⁵Alkyl, alkenyl, alkynyl, phenyl, heteroaryl or R⁵⁶Is; Are the alkyl, alkenyl, and alkynyl substituted? OCH₃Replaced by; R⁵⁶Is C₃-C₈-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N. ) With respect to a compound having or a therapeutically acceptable salt, a prodrug or a salt of a prodrug.</p><p num="0013"> Other embodiments of the invention are useful formulas (III) as selective inhibitors of the anti-apoptotic Bcl-2 protein.</p><p num="0014"><chemistry num="3"><img id="000004" he="92" wi="160" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(During the ceremony, R¹⁰⁰Is R²⁶As described for the substituents above; n is 0, 1, 2 or 3; A¹Is N or C (A)²) And; A², B¹, D¹And E¹One or two or three of them or each is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NR¹C (O) NHR¹, NR¹C (O) N (R)¹)₂, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CN, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; Y¹Is H, CN, NO₂, C (O) OH, F, Cl, Br, I, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, R¹⁷, OR¹⁷, C (O) R¹⁷, C (O) OR¹⁷, SR¹⁷, NH₂, NHR¹⁷, N (R)¹⁷)₂, NHC (O) R¹⁷, C (O) NH₂, C (O) NHR¹⁷, C (O) N (R)¹⁷)₂, NHS (O) R¹⁷Or NHSO₂R¹⁷Is; or B¹And Y¹Is imidazole or triazole along with the atoms to which they are attached; A², D¹And E¹One or two of or each of these are independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NHC (O) NHR¹, N (CH₃) C (O) N (CH₃) R¹, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; R¹Is R², R³, R⁴Or R⁵Is; R^1AIs C₁-C₆-Alkyl, C₃-C₆-Alkenyl or C₃-C₆-Alkyne; R²Is uncondensed or arene, heteroarene or R^2AIs phenyl condensed with; R^2AIs a cycloalkane or a heterocycloalkane; R³Is uncondensed or benzene, heteroarene or R^3AHeteroaryl condensing with; R^3AIs a cycloalkane or a heterocycloalkane; R⁴Are cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is uncondensed or arene, heteroarene or R.^4ACondensed with; R^4AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁶, NC (R^6A) (R^6B), R⁷, OR⁷, SR⁷, S (O) R⁷, SO₂R⁷, NHR⁷, N (R)⁷)₂, C (O) R⁷, C (O) NH₂, C (O) NHR⁷, NHC (O) R⁷, NHSO₂R⁷, NHC (O) OR⁷, SO₂NH₂, SO₂NHR⁷, SO₂N (R⁷)₂, NHC (O) NH₂, NHC (O) NHR⁷, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NH₂, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NHR¹, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁶Is C₂-C₅-Spiroalkyl, each of which is unsubstituted or OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH (CH)₃) Or N (CH₃)₂Replaced by; R^6AAnd R^6BAre independently selected alkyls, or R with N to which they are attached^6CIs; R^6CAre aziridine-1-yl, azetidine-1-yl, pyrrolidine-1-yl or piperidine-1-yl, which are not replaced or O, C (O), CNOH, CNOCH, respectively.₃, S, S (O), SO₂Or one CH replaced by NH₂Has a part; R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is; R⁸Is uncondensed or arene, heteroarene or R^8AIs phenyl condensed with; R^8AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁹Is uncondensed or arene, heteroarene or R^9AHeteroaryl condensing with; R^9AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has moieties and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^10ACondensed with; R^10AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3¹², OR¹², NHR¹², N (R)¹²)₂, C (O) NH₂, C (O) NHR¹², C (O) N (R)¹²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R¹²Is R¹³, R¹⁴, R¹⁵Or R¹⁶Is; R¹³Is uncondensed or arene, heteroarene or R^13AIs phenyl condensed with; R^13AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁴Are heteroaryl, each of which is uncondensed or arene, heteroarene or R^14ACondensed with; R^14AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁵Are cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes, each of which is uncondensed or arene, heteroarene or R.^15ACondensed with; R^15AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁶Is alkyl, alkenyl or alkynyl; R¹⁷Is R¹⁸, R¹⁹, R²⁰Or R²¹Is; R¹⁸Is uncondensed or arene, heteroarene or R^18AIs phenyl condensed with; R^18AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁹Is uncondensed or arene, heteroarene or R^19AHeteroaryl condensing with; R^19AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^20ACondensed with; R^20AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3²², OR²², NHR²², N (R)²²)₂, C (O) NH₂, C (O) NHR²², C (O) N (R)²²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R²²Is R²³, R²⁴Or R²⁵Is; R²³Is uncondensed or arene, heteroarene or R^23AIs phenyl condensed with; R^23AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁴Is uncondensed or arene, heteroarene or R^24AHeteroarene condensed with; R^24AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁵Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^25ACondensed with; R^25AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁰Are cycloalkyl or cycloalkenyl, respectively, O, C (O), CNOH, CNOCH, which are not replaced or are independently selected.₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has moieties and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^30ACondensed with; R^30AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; respectively F, Cl, Br, I, CH₂R³⁷, CH (R)³¹) (R³⁷), C (R³¹) (R^31A) (R³⁷), C (O) R³⁷, OR³⁷, SR³⁷, S (O) R³⁷, SO₂R³⁷, NHR³⁷Or N (R)³²) R³⁷Replaced by; R³¹And R^31AAre independently F, Cl, Br or alkyl, or together with C₂-C₅-Spiroalkyl; R³²Is R³³, C (O) R³³Or C (O) OR³³Is; R³³Is R³⁴Or R³⁵Is; R³⁴Is uncondensed or aryl, heteroaryl or R^34AIs phenyl condensed with; R^34AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁵Is not replaced or R³⁶It is an alkyl substituted with; R³⁶Is uncondensed or arene, heteroarene or R^36AIs phenyl condensed with; R^36AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁷Is R³⁸, R³⁹Or R⁴⁰And each of them is F, Cl, Br, I, R⁴¹, OR⁴¹, NHR⁴¹, N (R)⁴¹)₂, NHC (O) OR⁴¹, SR⁴¹, S (O) R⁴¹Or SO₂R⁴¹Replaced by; R³⁸Is uncondensed or arene, heteroarene or R^38AIs phenyl condensed with; R^38AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁹Is uncondensed or arene, heteroarene or R^39AHeteroaryl condensing with; R^39AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁰Is C₃-C₈-Cycloalkyl or C₄-C₈-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^40ACondensed with; R^40AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴¹Is R⁴², R⁴³, R⁴⁴Or R⁴⁵Is; R⁴²Is uncondensed or arene, heteroarene or R^42AIs phenyl condensed with; R^42AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴³Is uncondensed or arene, heteroarene or R^43AHeteroaryl condensing with; R^43AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁴Is C₃-C₉-Cycloalkyl or C₄-C₇-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^44ACondensed with; R^44AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R⁴⁶, OR⁴⁶, NHR⁴⁶, N (R)⁴⁶)₂, C (O) NH₂, C (O) NHR⁴⁶, C (O) N (R)⁴⁶)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁴⁶Is R⁴⁷, R⁴⁸Or R⁴⁹Is; R⁴⁷Is uncondensed or arene, heteroarene or R^47AIs phenyl condensed with; R^47AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁸Is heteroaryl or R^48AIs; R^48AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁹Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced with N or replaced, each of which is uncondensed or arene, heteroarene or R.^49ACondensed with; R^49AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R², R³, R⁴, R⁶, R^6C, R⁸, R^8A, R⁹, R¹⁰, R¹³, R¹⁴, R¹⁵, R¹⁸, R¹⁹, R²⁰, R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹, R³⁰, R³⁴, R³⁶, R³⁸, R³⁹, R⁴⁰, R⁴², R⁴³, R⁴⁴, R⁴⁷, R⁴⁸And R⁴⁹The part represented by is not independently replaced, further not replaced, 1, 2, 3, 4 or 5 independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S (O) R⁵⁰, SO₂R⁵⁰, C (O) R⁵⁰, CO (O) R⁵⁰, OC (O) R⁵⁰, OC (O) OR⁵⁰, NH₂, NHR⁵⁰, N (R)⁵⁰)₂, C (O) NH₂, C (O) NHR⁵⁰, C (O) N (R)⁵⁰)₂, C (O) NHOH, C (O) NHOR⁵⁰, C (O) NHSO₂R⁵⁰, C (O) NR⁵⁵SO₂R⁵⁰, SO₂NH₂, SO₂NHR⁵⁰, SO₂N (R⁵⁰)₂, CF₃, CF₂CF₃, C (O) H, C (O) OH, C (N) NH₂, C (N) NHR⁵⁰, C (N) N (R)⁵⁰)₂, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituted or further substituted with substituents; R⁵⁰Is R⁵¹, R⁵², R⁵³Or R⁵⁴Is; R⁵¹Is uncondensed or arene, heteroarene or R^51BIs phenyl condensed with; R^51BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵²Is heteroaryl; R⁵³Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^53BCondensed with; R^53BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵⁴Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁵⁵, OR⁵⁵, SR⁵⁵, S (O) R⁵⁵, SO₂R⁵⁵, NHR⁵⁵, N (R)⁵⁵)₂, C (O) R⁵⁵, C (O) NH₂, C (O) NHR⁵⁵, NHC (O) R⁵⁵, NHSO₂R⁵⁵, NHC (O) OR⁵⁵, SO₂NH₂, SO₂NHR⁵⁵, SO₂N (R⁵⁵)₂, NHC (O) NH₂, NHC (O) NHR⁵⁵, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, F, Cl, Br or I substituted with substituents; R⁵⁵Alkyl, alkenyl, alkynyl, phenyl, heteroaryl or R⁵⁶Is; Are the alkyl, alkenyl, and alkynyl substituted? OCH₃Replaced by; R⁵⁶Is C₃-C₈-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N. ) With respect to a compound having or a therapeutically acceptable salt, a prodrug or a salt of a prodrug.</p><p num="0015"> Other embodiments of the invention serve as a selective inhibitor of the anti-apoptotic Bcl-2 protein formula (IV).</p><p num="0016"><chemistry num="4"><img id="000005" he="81" wi="157" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(During the ceremony, R¹⁰⁰Is R²⁶As described for the substituents above; n is 0, 1, 2 or 3; A¹Is N or C (A)²) And; A², B¹, D¹And E¹One or two or three of them or each is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NR¹C (O) NHR¹, NR¹C (O) N (R)¹)₂, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CN, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; Y¹Is H, CN, NO₂, C (O) OH, F, Cl, Br, I, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, R¹⁷, OR¹⁷, C (O) R¹⁷, C (O) OR¹⁷, SR¹⁷, NH₂, NHR¹⁷, N (R)¹⁷)₂, NHC (O) R¹⁷, C (O) NH₂, C (O) NHR¹⁷, C (O) N (R)¹⁷)₂, NHS (O) R¹⁷Or NHSO₂R¹⁷Is; or B¹And Y¹Is imidazole or triazole along with the atoms to which they are attached; A², D¹And E¹One or two or each of them is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NHC (O) NHR¹, N (CH₃) C (O) N (CH₃) R¹, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; R¹Is R², R³, R⁴Or R⁵Is; R^1AIs C₁-C₆-Alkyl, C₃-C₆-Alkenyl or C₃-C₆-Alkyne; R²Is uncondensed or arene, heteroarene or R^2AIs phenyl condensed with; R^2AIs a cycloalkane or a heterocycloalkane; R³Is uncondensed or benzene, heteroarene or R^3AHeteroaryl condensing with; R^3AIs a cycloalkane or a heterocycloalkane; R⁴Are cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is uncondensed or arene, heteroarene or R.^4ACondensed with; R^4AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁶, NC (R^6A) (R^6B), R⁷, OR⁷, SR⁷, S (O) R⁷, SO₂R⁷, NHR⁷, N (R)⁷)₂, C (O) R⁷, C (O) NH₂, C (O) NHR⁷, NHC (O) R⁷, NHSO₂R⁷, NHC (O) OR⁷, SO₂NH₂, SO₂NHR⁷, SO₂N (R⁷)₂, NHC (O) NH₂, NHC (O) NHR⁷, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NH₂, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NHR¹, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁶Is C₂-C₅-Spiroalkyl, each of which is unsubstituted or OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH (CH)₃) Or N (CH₃)₂Replaced by; R^6AAnd R^6BAre independently selected alkyls, or R with N to which they are attached^6CIs; R^6CAre aziridine-1-yl, azetidine-1-yl, pyrrolidine-1-yl or piperidine-1-yl, which are not replaced or O, C (O), CNOH, CNOCH, respectively.₃, S, S (O), SO₂Or one CH replaced by NH₂Has a part; R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is; R⁸Is uncondensed or arene, heteroarene or R^8AIs phenyl condensed with; R^8AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁹Is uncondensed or arene, heteroarene or R^9AHeteroaryl condensing with; R^9AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has moieties and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^10ACondensed with; R^10AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3¹², OR¹², NHR¹², N (R)¹²)₂, C (O) NH₂, C (O) NHR¹², C (O) N (R)¹²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R¹²Is R¹³, R¹⁴, R¹⁵Or R¹⁶Is; R¹³Is uncondensed or arene, heteroarene or R^13AIs phenyl condensed with; R^13AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁴Are heteroaryl, each of which is uncondensed or arene, heteroarene or R^14ACondensed with; R^14AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁵Are cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes, each of which is uncondensed or arene, heteroarene or R.^15ACondensed with; R^15AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁶Is alkyl, alkenyl or alkynyl; R¹⁷Is R¹⁸, R¹⁹, R²⁰Or R²¹Is; R¹⁸Is uncondensed or arene, heteroarene or R^18AIs phenyl condensed with; R^18AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁹Is uncondensed or arene, heteroarene or R^19AHeteroaryl condensing with; R^19AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^20ACondensed with; R^20AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3²², OR²², NHR²², N (R)²²)₂, C (O) NH₂, C (O) NHR²², C (O) N (R)²²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R²²Is R²³, R²⁴Or R²⁵Is; R²³Is uncondensed or arene, heteroarene or R^23AIs phenyl condensed with; R^23AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁴Is uncondensed or arene, heteroarene or R^24AHeteroarene condensed with; R^24AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁵Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^25ACondensed with; R^25AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁰Are cycloalkyl or cycloalkenyl, respectively, O, C (O), CNOH, CNOCH, which are not replaced or are independently selected.₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^30ACondensed with; R^30AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; respectively F, Cl, Br, I, CH₂R³⁷, CH (R)³¹) (R³⁷), C (R³¹) (R^31A) (R³⁷), C (O) R³⁷, OR³⁷, SR³⁷, S (O) R³⁷, SO₂R³⁷, NHR³⁷Or N (R)³²) R³⁷Replaced by; R³¹And R^31AAre independently F, Cl, Br or alkyl, or together with C₂-C₅-Spiroalkyl; R³²Is R³³, C (O) R³³Or C (O) OR³³Is; R³³Is R³⁴Or R³⁵Is; R³⁴Is uncondensed or aryl, heteroaryl or R^34AIs phenyl condensed with; R^34AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁵Is not replaced or R³⁶It is an alkyl substituted with; R³⁶Is uncondensed or arene, heteroarene or R^36AIs phenyl condensed with; R^36AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁷Is R³⁸, R³⁹Or R⁴⁰And each of them is F, Cl, Br, I, R⁴¹, OR⁴¹, NHR⁴¹, N (R)⁴¹)₂, NHC (O) OR⁴¹, SR⁴¹, S (O) R⁴¹Or SO₂R⁴¹Replaced by; R³⁸Is uncondensed or arene, heteroarene or R^38AIs phenyl condensed with; R^38AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁹Is uncondensed or arene, heteroarene or R^39AHeteroaryl condensing with; R^39AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁰Is C₃-C₈-Cycloalkyl or C₄-C₈-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^40ACondensed with; R^40AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴¹Is R⁴², R⁴³, R⁴⁴Or R⁴⁵Is; R⁴²Is uncondensed or arene, heteroarene or R^42AIs phenyl condensed with; R^42AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴³Is uncondensed or arene, heteroarene or R^43AHeteroaryl condensing with; R^43AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁴Is C₃-C₉-Cycloalkyl or C₄-C₇-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^44ACondensed with; R^44AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R⁴⁶, OR⁴⁶, NHR⁴⁶, N (R)⁴⁶)₂, C (O) NH₂, C (O) NHR⁴⁶, C (O) N (R)⁴⁶)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁴⁶Is R⁴⁷, R⁴⁸Or R⁴⁹Is; R⁴⁷Is uncondensed or arene, heteroarene or R^47AIs phenyl condensed with; R^47AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁸Is heteroaryl or R^48AIs; R^48AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁹Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^49ACondensed with; R^49AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R², R³, R⁴, R⁶, R^6C, R⁸, R^8A, R⁹, R¹⁰, R¹³, R¹⁴, R¹⁵, R¹⁸, R¹⁹, R²⁰, R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹, R³⁰, R³⁴, R³⁶, R³⁸, R³⁹, R⁴⁰, R⁴², R⁴³, R⁴⁴, R⁴⁷, R⁴⁸And R⁴⁹The part represented by is not independently replaced, further not replaced, 1, 2, 3, 4 or 5 independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S (O) R⁵⁰, SO₂R⁵⁰, C (O) R⁵⁰, CO (O) R⁵⁰, OC (O) R⁵⁰, OC (O) OR⁵⁰, NH₂, NHR⁵⁰, N (R)⁵⁰)₂, C (O) NH₂, C (O) NHR⁵⁰, C (O) N (R)⁵⁰)₂, C (O) NHOH, C (O) NHOR⁵⁰, C (O) NHSO₂R⁵⁰, C (O) NR⁵⁵SO₂R⁵⁰, SO₂NH₂, SO₂NHR⁵⁰, SO₂N (R⁵⁰)₂, CF₃, CF₂CF₃, C (O) H, C (O) OH, C (N) NH₂, C (N) NHR⁵⁰, C (N) N (R)⁵⁰)₂, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituted or further substituted with substituents; R⁵⁰Is R⁵¹, R⁵², R⁵³Or R⁵⁴Is; R⁵¹Is uncondensed or arene, heteroarene or R^51BIs phenyl condensed with; R^51BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵²Is heteroaryl; R⁵³Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^53BCondensed with; R^53BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵⁴Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁵⁵, OR⁵⁵, SR⁵⁵, S (O) R⁵⁵, SO₂R⁵⁵, NHR⁵⁵, N (R)⁵⁵)₂, C (O) R⁵⁵, C (O) NH₂, C (O) NHR⁵⁵, NHC (O) R⁵⁵, NHSO₂R⁵⁵, NHC (O) OR⁵⁵, SO₂NH₂, SO₂NHR⁵⁵, SO₂N (R⁵⁵)₂, NHC (O) NH₂, NHC (O) NHR⁵⁵, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, F, Cl, Br or I substituted with substituents; R⁵⁵Alkyl, alkenyl, alkynyl, phenyl, heteroaryl or R⁵⁶Is; Are the alkyl, alkenyl, and alkynyl substituted? OCH₃Replaced by; R⁵⁶Is C₃-C₈-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N. ) With respect to a compound having or a therapeutically acceptable salt, a prodrug or a salt of a prodrug.</p><p num="0017"> Other embodiments of the invention are useful formulas (V) as selective inhibitors of the anti-apoptotic Bcl-2 protein.</p><p num="0018"><chemistry num="5"><img id="000006" he="90" wi="157" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(During the ceremony, R¹⁰⁰Is R²⁶As described for the substituents above; n is 0, 1, 2 or 3; A¹Is N or C (A)²) And; A², B¹, D¹And E¹One or two or three of them or each is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NR¹C (O) NHR¹, NR¹C (O) N (R)¹)₂, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CN, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; Y¹Is H, CN, NO₂, C (O) OH, F, Cl, Br, I, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, R¹⁷, OR¹⁷, C (O) R¹⁷, C (O) OR¹⁷, SR¹⁷, NH₂, NHR¹⁷, N (R)¹⁷)₂, NHC (O) R¹⁷, C (O) NH₂, C (O) NHR¹⁷, C (O) N (R)¹⁷)₂, NHS (O) R¹⁷Or NHSO₂R¹⁷Is; or B¹And Y¹Is imidazole or triazole along with the atoms to which they are attached; A², D¹And E¹One or two or each of them is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NHC (O) NHR¹, N (CH₃) C (O) N (CH₃) R¹, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; R¹Is R², R³, R⁴Or R⁵Is; R^1AIs C₁-C₆-Alkyl, C₃-C₆-Alkenyl or C₃-C₆-Alkyne; R²Is uncondensed or arene, heteroarene or R^2AIs phenyl condensed with; R^2AIs a cycloalkane or a heterocycloalkane; R³Is uncondensed or benzene, heteroarene or R^3AHeteroaryl condensing with; R^3AIs a cycloalkane or a heterocycloalkane; R⁴Are cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is uncondensed or arene, heteroarene or R.^4ACondensed with; R^4AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁶, NC (R^6A) (R^6B), R⁷, OR⁷, SR⁷, S (O) R⁷, SO₂R⁷, NHR⁷, N (R)⁷)₂, C (O) R⁷, C (O) NH₂, C (O) NHR⁷, NHC (O) R⁷, NHSO₂R⁷, NHC (O) OR⁷, SO₂NH₂, SO₂NHR⁷, SO₂N (R⁷)₂, NHC (O) NH₂, NHC (O) NHR⁷, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NH₂, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NHR¹, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁶Is C₂-C₅-Spiroalkyl, each of which is unsubstituted or OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH (CH)₃) Or N (CH₃)₂Replaced by; R^6AAnd R^6BAre independently selected alkyls, or R with N to which they are attached^6CIs; R^6CAre aziridine-1-yl, azetidine-1-yl, pyrrolidine-1-yl or piperidine-1-yl, which are not replaced or O, C (O), CNOH, CNOCH, respectively.₃, S, S (O), SO₂Or one CH replaced by NH₂Has a part; R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is; R⁸Is uncondensed or arene, heteroarene or R^8AIs phenyl condensed with; R^8AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁹Is uncondensed or arene, heteroarene or R^9AHeteroaryl condensing with; R^9AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has moieties and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^10ACondensed with; R^10AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3¹², OR¹², NHR¹², N (R)¹²)₂, C (O) NH₂, C (O) NHR¹², C (O) N (R)¹²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R¹²Is R¹³, R¹⁴, R¹⁵Or R¹⁶Is; R¹³Is uncondensed or arene, heteroarene or R^13AIs phenyl condensed with; R^13AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁴Are heteroaryl, each of which is uncondensed or arene, heteroarene or R^14ACondensed with; R^14AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁵Are cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes, each of which is uncondensed or arene, heteroarene or R.^15ACondensed with; R^15AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁶Is alkyl, alkenyl or alkynyl; R¹⁷Is R¹⁸, R¹⁹, R²⁰Or R²¹Is; R¹⁸Is uncondensed or arene, heteroarene or R^18AIs phenyl condensed with; R^18AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁹Is uncondensed or arene, heteroarene or R^19AHeteroaryl condensing with; R^19AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^20ACondensed with; R^20AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3²², OR²², NHR²², N (R)²²)₂, C (O) NH₂, C (O) NHR²², C (O) N (R)²²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R²²Is R²³, R²⁴Or R²⁵Is; R²³Is uncondensed or arene, heteroarene or R^23AIs phenyl condensed with; R^23AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁴Is uncondensed or arene, heteroarene or R^24AHeteroarene condensed with; R^24AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁵Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^25ACondensed with; R^25AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁰Are cycloalkyl or cycloalkenyl, respectively, O, C (O), CNOH, CNOCH, which are not replaced or are independently selected.₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^30ACondensed with; R^30AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; respectively F, Cl, Br, I, CH₂R³⁷, CH (R)³¹) (R³⁷), C (R³¹) (R^31A) (R³⁷), C (O) R³⁷, OR³⁷, SR³⁷, S (O) R³⁷, SO₂R³⁷, NHR³⁷Or N (R)³²) R³⁷Replaced by; R³¹And R^31AAre independently F, Cl, Br or alkyl, or together with C₂-C₅-Spiroalkyl; R³²Is R³³, C (O) R³³Or C (O) OR³³Is; R³³Is R³⁴Or R³⁵Is; R³⁴Is uncondensed or aryl, heteroaryl or R^34AIs phenyl condensed with; R^34AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁵Is not replaced or R³⁶It is an alkyl substituted with; R³⁶Is uncondensed or arene, heteroarene or R^36AIs phenyl condensed with; R^36AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁷Is R³⁸, R³⁹Or R⁴⁰And each of them is F, Cl, Br, I, R⁴¹, OR⁴¹, NHR⁴¹, N (R)⁴¹)₂, NHC (O) OR⁴¹, SR⁴¹, S (O) R⁴¹Or SO₂R⁴¹Replaced by; R³⁸Is uncondensed or arene, heteroarene or R^38AIs phenyl condensed with; R^38AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁹Is uncondensed or arene, heteroarene or R^39AHeteroaryl condensing with; R^39AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁰Is C₃-C₈-Cycloalkyl or C₄-C₈-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^40ACondensed with; R^40AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴¹Is R⁴², R⁴³, R⁴⁴Or R⁴⁵Is; R⁴²Is uncondensed or arene, heteroarene or R^42AIs phenyl condensed with; R^42AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴³Is uncondensed or arene, heteroarene or R^43AHeteroaryl condensing with; R^43AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁴Is C₃-C₉-Cycloalkyl or C₄-C₇-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^44ACondensed with; R^44AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R⁴⁶, OR⁴⁶, NHR⁴⁶, N (R)⁴⁶)₂, C (O) NH₂, C (O) NHR⁴⁶, C (O) N (R)⁴⁶)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁴⁶Is R⁴⁷, R⁴⁸Or R⁴⁹Is; R⁴⁷Is uncondensed or arene, heteroarene or R^47AIs phenyl condensed with; R^47AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁸Is heteroaryl or R^48AIs; R^48AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁹Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^49ACondensed with; R^49AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R², R³, R⁴, R⁶, R^6C, R⁸, R^8A, R⁹, R¹⁰, R¹³, R¹⁴, R¹⁵, R¹⁸, R¹⁹, R²⁰, R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹, R³⁰, R³⁴, R³⁶, R³⁸, R³⁹, R⁴⁰, R⁴², R⁴³, R⁴⁴, R⁴⁷, R⁴⁸And R⁴⁹The part represented by is not independently replaced, further not replaced, 1, 2, 3, 4 or 5 independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S (O) R⁵⁰, SO₂R⁵⁰, C (O) R⁵⁰, CO (O) R⁵⁰, OC (O) R⁵⁰, OC (O) OR⁵⁰, NH₂, NHR⁵⁰, N (R)⁵⁰)₂, C (O) NH₂, C (O) NHR⁵⁰, C (O) N (R)⁵⁰)₂, C (O) NHOH, C (O) NHOR⁵⁰, C (O) NHSO₂R⁵⁰, C (O) NR⁵⁵SO₂R⁵⁰, SO₂NH₂, SO₂NHR⁵⁰, SO₂N (R⁵⁰)₂, CF₃, CF₂CF₃, C (O) H, C (O) OH, C (N) NH₂, C (N) NHR⁵⁰, C (N) N (R)⁵⁰)₂, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituted or further substituted with substituents; R⁵⁰Is R⁵¹, R⁵², R⁵³Or R⁵⁴Is; R⁵¹Is uncondensed or arene, heteroarene or R^51BIs phenyl condensed with; R^51BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵²Is heteroaryl; R⁵³Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^53BCondensed with; R^53BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵⁴Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁵⁵, OR⁵⁵, SR⁵⁵, S (O) R⁵⁵, SO₂R⁵⁵, NHR⁵⁵, N (R)⁵⁵)₂, C (O) R⁵⁵, C (O) NH₂, C (O) NHR⁵⁵, NHC (O) R⁵⁵, NHSO₂R⁵⁵, NHC (O) OR⁵⁵, SO₂NH₂, SO₂NHR⁵⁵, SO₂N (R⁵⁵)₂, NHC (O) NH₂, NHC (O) NHR⁵⁵, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, F, Cl, Br or I substituted with substituents; R⁵⁵Alkyl, alkenyl, alkynyl, phenyl, heteroaryl or R⁵⁶Is; Are the alkyl, alkenyl, and alkynyl substituted? OCH₃Replaced by; With respect to a compound having or a therapeutically acceptable salt, a prodrug or a salt of a prodrug.</p><p num="0019"> R⁵⁶Is C₃-C₈-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N.</p><p num="0020"> Another embodiment is A¹Is C (A)²) And; A²For compounds of formula (I), formula (II), formula (III), formula (IV) or formula (V) where is H.</p><p num="0021"> Another embodiment is A¹Is C (A)²) And; A²Is H; B¹Is NHR¹With respect to a compound of formula (I), formula (II), formula (III), formula (IV) or formula (V).</p><p num="0022"> Another embodiment is A¹Is C (A)²) And; A²Is H; B¹Is NHR¹Is; D¹For compounds of formula (I), formula (II), formula (III), formula (IV) or formula (V) where is H.</p><p num="0023"> Another embodiment is A¹Is C (A)²) And; A²Is H; B¹Is NHR¹Is; D¹Is H; E¹For compounds of formula (I), formula (II), formula (III), formula (IV) or formula (V) where is H.</p><p num="0024"> Another embodiment is A¹Is C (A)²) And; A²Is H; B¹Is NHR¹Is; D¹Is H; E¹Is H; Y¹Is NO₂With respect to a compound of formula (I), formula (II), formula (III), formula (IV) or formula (V).</p><p num="0025"> Yet another embodiment 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; Benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N-((4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) benzamide; 2- (benzyloxy) -4-(4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4- () (Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (2-phenylethoxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (phenylthio) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenylthio) -N-((4-((Tetrahydro-2H-) Pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) -3-Nitrophenyl) Sulfonyl) -2- (Phenylthio) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (phenylsulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (phenylsulfinyl) benzamide; 2-Benzyl-4- (4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-) 2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 2-Benzyl-4- (4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((Tetrahydro-2H-pyran-)- 4-Ilmethyl) amino) phenyl) sulfonyl) benzamide; 2-Benzyl-4- (4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-yl) Ilpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (2-phenylethyl) benzamide; 2- (benzylamino) -4-(4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4- ((3-nitro-4- () (Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 2-anilino-4-(4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-) 2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 2-anilino-4-(4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-methoxy-N-((3-nitro-4-((tetrahydro-) 2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indazole-5-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indazole-5-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) -2- (1,2,3,4-tetrahydroquinoline-6-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((1-1-yl) Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) -2- (1,2,3,4-tetrahydroquinoline-6-yloxy) benzamide; 4- (4-((4'-Chloro-4- (pyrrolidin-1-ylmethyl) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4) -Iloxy) -N-((3-Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-pyrrolidine-1-ylethyl) -1,1'-biphenyl-2-yl (methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((1-1-yl) Cyclopentyl piperidine-4-yl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) -3-isobutylpiperazin-1-yl) -N-((3-nitro-4-((tetrahydro-) 2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4- (2,4-dioxo-3-azabicyclo) (3.2) .0) hepta-3-yl) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4- (4-methyl-6-oxo-1,4) , 5,6-tetrahydropyridazine-3-yl) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4- (3,3-dimethyl-2-oxoazetidine-1) -Il) Phenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4- (4-nitro-2H-1,2,3) -Triazole-2-yl) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N-((2- (2-piperidine-1-ylethoxy) ) Phenyl) Sulfonyl) Benzamide; 4-(4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-((((1-ethylpyrrolidine-2-yl) yl) ) Methyl) amino) carbonyl) -4-methoxyphenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1-naphthyloxy) -N-((3-nitro-4) -((Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (2-naphthyloxy) -N-((3-nitro-4) -((Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) -3-Nitrophenyl) Sulfonyl) -2- (2-naphthyloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (2-naphthyloxy) -N-((4-((Tetrahydro) -2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (quinoline-7-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (quinoline-6-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (isoquinoline-5-yloxy) -N-((3-nitro-) 4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (isoquinoline-5-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (quinoline-6-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (1H-indole-6-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (isoquinoline-7-yloxy) -N-((4-((( 3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (isoquinoline-7-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4-4-yloxy) ((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4-4-yl) ((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-methoxyphenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-methylphenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4-4-yl) ((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4-4-yloxy) ((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-((Trifluoromethyl) sulfonyl) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4-4-yloxy) ((3-Morpholine-4-ylpropyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; N-((3-((Chloro (difluoro) methyl) sulfonyl) -4-((3- (dimethylamino) propyl) amino) phenyl) sulfonyl) -4- (4-((2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 2- (1H-Indol-4-yloxy) -4-(4-((2- (4-Methoxyphenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1- Il) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4,4-Dimethyl-2- (4- (trifluoromethyl) phenyl) cyclohexa-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4,4-Dimethyl-2- (4- (trifluoromethoxy) phenyl) cyclohexa-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4,4-Dimethyl-2- (3- (trifluoromethyl) phenyl) cyclohexa-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (3-Fluorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Fluorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; N-((3-((Chloro (difluoro) methyl) sulfonyl) -4-((1-methylpiperidin-4-yl) amino) phenyl) sulfonyl) -4- ((2- (4-chlorophenyl) ) -4,4-Dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (phenoxymethyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) Phenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (pyridin-3-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (pyridin-3-yloxy) -N-((4-((( Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-(((1R) -3- (dimethylamino)) -1-((Phenylthio) methyl) propyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (pyridin-4-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) -3-Nitrophenyl) Sulfonyl) -2- (Pyridine-3-yloxy) Benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) -3-Nitrophenyl) Sulfonyl) -2- (Pyridine-4-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((2- (4-methylpiperazin-1-) Il) ethyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (4-methylpiperazin-1-) Il) propyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl)) (methyl) ) Amino) -3-nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4-(4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-(((1-methylpiperidine-4-yl)) Methyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4-(4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((1-methylpiperidine-4-yl) amino) ) -3-Nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-cyano-4-((3- (dimethylamino)) Propyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((3-pyrrolidin-1-yl) methyl) Ilpropyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3- (Trifluoromethyl) Phenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (isopropyl (methyl) amino) propyl) ) Amino) -3-nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4- (3- (dimethylamino) propoxy) -3- Nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((2- (4-Methylpiperazin-1-yl) ethyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((3- (4-Methylpiperazin-1-yl) propyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((3-Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((3- (4-Methylpiperazin-1-yl) propyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4- (3- (3- ( Dimethylamino) propoxy) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((2- (4-Methylpiperazin-1-yl) ethyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((3-Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((((1-Methylpiperidin-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((((1-Methylpiperidin-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4- (3- (3- ( Dimethylamino) propoxy) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4- (4-Methylpiperazin-1-yl) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((3-Nitro-4-((1- (2,2,2-trifluoroethyl) piperidine-4-yl) amino) phenyl) sulfonyl) benzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-(((4) -(Dimethylamino) -1-methylpiperidin-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (2,3-dihydro-1,4-benzodioxin-5- Iloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 5- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -1,1'-biphenyl-2-carboxamide; 5- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-Nitrophenyl) Sulfonyl) -1,1'-biphenyl-2-carboxamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4-(4-((4'-Chloro-4- (3-piperidin-1-ylpropoxy) -1,1'-biphenyl-2-yl) methyl) piperazin-1-yl) -N-((3) -Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4-(4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-4- (3- (dimethylamino) propoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N- ((4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (3-piperidin-1-ylpropoxy) -1,1'-biphenyl-2-yl) methyl) piperazin-1-yl) -2-phenoxy-N -((4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (3- (dimethylamino) propoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N- ((4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N- ((4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N- ((4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-4-yl) ((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((1- (2,2,2-trifluoroethyl) piperidine-4-yl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4-(4-((4'-Chloro-4- (2-pyrrolidine-1-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-4- (2- (diisopropylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (2,3-dihydro-1H-indole-5-yloxy)- N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohepta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3) -Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cycloocta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3) -Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclopenta-1-ene-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3) -Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclopent-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((4-((1-methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cycloocta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohepta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclopenta-1-ene-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((4-((1-methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohepta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((1-1-yl) Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((2- (dimethylamino) ethyl) amino)) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) -3-Nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((4- (dimethylamino) butyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((1- (phenylsulfonyl)) Piperidine-4-yl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((1- (quinoline-8) -yl) -Ilsulfonyl) piperidine-4-yl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N-((4-((1- (phenylsulfonyl)) Piperidine-4-yl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N-((4-((1- (quinoline-8) -Ilsulfonyl) piperidine-4-yl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-(((1S) -3- (dimethylamino)) -1-thien-2-ylpropyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((thien-2-ylmethyl)) Amino) Phenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N-((4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((2- (1H-1) -yl) , 2,3-Triazole-1-yl) ethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-Nitro-4-((2- (2H-1) -yl) , 2,3-Triazole-2-yl) ethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (2-naphthyloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((2- (2-oxo) Pyridine-1 (2H) -yl) ethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-Nitro-4-((2- (Pyridine-2) -yl) -Iloxy) ethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((2-Pyridine-4-yl) Ilethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3- (trifluoromethyl) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((3-cyano-4-yl) ((3- (Dimethylamino) propyl) amino) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((3-Nitro-4-((1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((4-Methylpiperazin-1-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4- (1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((( 3-Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; N-((4-((((4-Aminotetrahydro-2H-pyran-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) -4- (4-((2- (4-chlorophenyl)-) 4,4-Dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(3S) -tetrahydro-2H-pyran-3-ylmethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(3R) -tetrahydro-2H-pyran-3-ylmethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[4- (4-Chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxy-1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -3-fluoro-2- (1H-indole) -5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -3-fluoro-2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxy-1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; N-[(4-{[(3S, 4R) -1-benzyl-3-hydroxypiperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4- (4-) Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; N-[(4-{[(4-Aminotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl)- 4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(4-{[1- (2-Methoxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2-Hydroxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(4-{[1- (2-Methoxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Hydroxypropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide; 4- [4-({4'-Chloro-3- [3- (dimethylamino) propyl] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Hydroxypropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-5-Iloxy) Benzamide; 4- {4-[(4'-Chloro-4-morpholine-4-yl-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Diethylamino) cyclohexyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Dimethylamino) Cyclohexyl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Diethylamino) cyclohexyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[4 -(Dimethylamino) tetrahydro-2H-pyran-4-yl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; N-({4-[(2-aminocyclohexyl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-ene -1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- [4-({4'-Chloro-4- [3- (dimethylamino) propa-1-inyl] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole-4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(3-Nitro-4-{[1- (4,4,4-trifluorobutyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[2-yl] (4-Hydroxy-1-methylpiperidin-4-yl) ethyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-2-yl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[4'-Chloro-4- (2-hydroxyethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (Cyclopropylmethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (4,4,4-trifluorobutyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[4'-Chloro-4- (2-hydroxyethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[3- (3-oxopiperazin-1-yl) propyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(3-Nitro-4-{[3- (3-oxopiperazine-1-yl) propyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2,3-dihydro-1H-indene-2-yl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2,3-dihydro-1H-indene-2-yl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1-Morpholine-4-ylcyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-2-ylmethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-4-ylmethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[4 -(Hydroxymethyl) tetrahydro-2H-pyran-4-yl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (2-Hydroxyethyl) piperazine-1-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(3S) -1-methylpyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Fluoropropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-5-Iloxy) Benzamide; 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; N-[(4-{[(4-Aminotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- [4-{[2- (4-chlorophenyl)- 4,4-Dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) -Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Hydroxymethyl) Tetrahydro-2H-pyran-4-yl] amino} -3-nitrophenyl) Sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Hydroxymethyl) Tetrahydro-2H-pyran-4-yl] amino} -3-nitrophenyl) Sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Hydroxy-1-tetrahydro-2H-pyran-4-ylethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4-({1- [2- (1H-pyrazol-1-yl) ethyl] piperidine-4-yl} amino) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Methylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Methylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-chlorophenyl) -5-morpholin-4-ylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; N-[(4-{[(1-Aminocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa- 1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxopyrrolidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-5-yloxy) -N-({{ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- {4-[(1R) -1- (4'-chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- {4-[(1S) -1- (4'-chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(3-morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(cyclohexylmethylmethyl) ) Amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Morpholine-4-ylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-3-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Morpholine-4-ylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylamino) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(3-Methyloxetane-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methoxycyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1,1-dioxide thiomorpholine-4-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxopiperidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxoimidazolidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(2-Pyridine-4-ylethyl) Amino] Phenyl} Sulfonyl) Benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-Morpholine-4-yl-3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (4-Methoxypiperidine-1-yl) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-pyrrolidine-1-ylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (3-oxopiperazine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({4-[(4-methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-dioxide tetrahydrothien-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 1-Dioxide tetrahydrothien-3-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3- (trifluoromethyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [2- ({4- [2- ( 1,3-Dioxolane-2-yl) ethyl] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(3-Nitro-4-{[2- (3-oxopiperazine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methyl-5-oxopyrrolidine-3-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methyl-6-oxopiperidine-3-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (piperidine-1-ylamino) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (piperidine-1-ylamino) phenyl] sulfonyl} benzamide; 4- (4-{[4- (4-Chlorophenyl) -1-methyl-1H-pyrazole-5-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N- ({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Methyloxetane-3-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(1-oxide tetrahydro-2H-thiopyran-4-yl) methyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1,3-thiazole-5-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(2-tetrahydro-2H-pyran-4-ylethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(3-Nitro-4-{[2- (trifluoromethoxy) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(4-{[2- (2-Methoxyethoxy) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[3- (Methylsulfonyl) propyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1,1-dioxide thiomorpholine-4-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (2-tetrahydro-2H-pyran-4-ylethyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4- (1,4) -Dioxane-2-ylmethoxy) -3-nitrophenyl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(4-{[2- (2-Methoxyethoxy) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 1-Dioxide tetrahydrothien-3-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (trifluoromethoxy) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-Dioxide tetrahydro-2H-thiopyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(2,,, 2-Difluoroethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(4,,, 4-Difluorocyclohexyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[4- (4-Chlorophenyl) -1-isopropyl-6-oxo-1,6-dihydropyridine-3-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(Tetrahydro-2H-pyran-4-ylmethyl) amino] carbonyl} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (2-tetrahydro-2H-pyran-4-ylethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4- [3- (Methylsulfonyl) propoxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Methoxypropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Methoxypropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Cyanoethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Cyanoethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[(( 3R) -4-hydroxy-1-adamantyl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[Cis -4-Hydroxy-1-adamantyl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-({3-Nitro-4-[(3,3,3-trifluoropropyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-({3-Nitro-4-[(3,3,3-trifluoropropyl) amino] phenyl} sulfonyl) benzamide; N-({5-bromo-6-[(tetrahydro-2H-pyran-4-ylmethyl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-dioxide tetrahydrothien-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4- (Methylamino) -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; N-{[5-bromo-6- (tetrahydro-2H-pyran-4-ylmethoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[4- (4-Chlorophenyl) -6-isopropoxypyridine-3-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-({ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[6- (Tetrahydro-2H-pyran-4-ylmethoxy) -5- (1,3-thiazole-2-yl) pyridin-3-yl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(2-Methoxyethyl) amino] carbonyl} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide; N-({4-[(1-Acetylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(4-{[1- (Methylsulfonyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(1,1, 4-dioxane-2-ylmethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; N-({4-[(1-Acetylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[1- (Methylsulfonyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-{[3-nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-({3-Nitro-4-[(2,2,2-trifluoroethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-({3-Nitro-4-[(2,2,2-trifluoroethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-{[(Tetrahydro-2H-pyran-4-ylmethyl) amino] carbonyl} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2R)) -1,4-dioxane-2-ylmethoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2S)) -1,4-dioxane-2-ylmethoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; N-({5-bromo-6-[(tetrahydro-2H-pyran-4-ylmethyl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Morpholine-4-ylethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N- ({5-cyano-6-) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] pyridine-3-yl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) oxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[4- (4-Chlorophenyl) -1- (3-hydroxypropyl) -1,2,5,6-tetrahydropyridin-3-yl] methyl} piperazine-1-yl) -2- (1H-indol-4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; Benzyl4-({[4-({[4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl)) -2- (1H-indole-5-yloxy) benzoyl] amino} sulfonyl) -2-nitrophenyl] amino} methyl) piperidine-1-carboxylate; N-{[3- (aminocarbonyl) -4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexi Sa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1-Methyl-1H-imidazol-5-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Morpholine-4-ylsulfonyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(1,1, 1-Dioxide thiomorpholine-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; N-{[5-bromo-6- (tetrahydro-2H-pyran-4-ylmethoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[6-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -5- (1,3-thiazole-2-yl) pyridin-3-yl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-cyano-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-cyano-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3,,, 3-Dimethylbutyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1S) ) -1- (Hydroxymethyl) -3-methylbutyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(2R) -tetrahydrofuran-ylmethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1R) ) -1- (Hydroxymethyl) -2-methylpropyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methoxyphenyl) amino] -3-nitrophenyl} sulfonyl) benzamide; N-[(4-{[2- (1,3-benzodioxole-5-yl) ethyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl) ethyl] ) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[3- (2-oxopyrrolidine-1-yl) propyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Hydroxyphenyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; N-{[4-({2- [4- (aminosulfonyl) phenyl] ethyl} amino) -3-nitrophenyl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4 -Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1H-imidazol-1-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[(1S) -1-phenylethyl] amino} phenyl) sulfonyl] benzamide; N-({2-chloro-5-fluoro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[2- (2-Methoxyethoxy) ethyl] thio} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(4-{[2- (2-Methoxyethoxy) ethyl] thio} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Methylsulfonyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Methylsulfonyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(2,,, 2-Dimethyltetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Morpholine-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) oxy] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Morpholine-4-ylbut-2-inyl) oxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-ethynyl-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Morpholine-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3-3-yl] Hydroxy-4-methoxyphenyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (2,3-dihydro-1H) -Indole-4-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1-1-yl] Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (pyridin-3-ylamino) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(1-Tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) -2- (pyridin-3-ylamino) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(1-Tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) -2- (pyridin-3-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1,2,3,4-tetrahydroisoquinoline-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4) -Iloxy) -N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-([(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Fluorotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[6-[(4-4-yl) Fluorotetrahydro-2H-pyran-4-yl) methoxy] -5- (trifluoromethyl) pyridin-3-yl] sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Cyclopropylmorpholin-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) , 4-difluorocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide; N-[(5-Chloro-6-{[(4-fluorotetrahydro-2H-pyran-4-yl) methyl] amino} pyridin-3-yl) sulfonyl] -4- (4-{[2- (4) -Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; Trans-N-({5-chloro-6-[(4-Methoxycyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[4- (2,2-difluoroethyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N- ({5-fluoro-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-((4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; N-[(5-Chloro-6-{[1- (cyanomethyl) -4-fluoropiperidine-4-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4-{[2- (4-) Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydrofuran-3-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; Trans-N-({5-chloro-6-[(4-hydroxycyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-[(5-Chloro-6-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] oxy} pyridin-3-yl) sulfonyl] -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-[(5-chloro-6-{[(2S) -4- (N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridine- 3-Il) Sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-[(5-chloro-6-{[(2R) -4- (N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridine- 3-Il) Sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; N-[(5-chloro-6-{[(2S) -4-(N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-[(5-chloro-6-{[(2R) -4-(N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-([(3R) -1- (cyanomethyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({(3R) -1- [2- (2-methoxyethoxy) ethyl] pyrrolidine-3-yl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-([(3R) -1- (N, N-dimethylglycyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[4- (cyanomethyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-[(4-{[(4-Cyclopropylmorpholine-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(3-nitro-4-{[(4-oxetane-3-ylmorpholine-2-yl) methyl] amino} phenyl) sulfonyl] benzamide; N-{[5-chloro-6-({(3R) -1- [2-fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} oxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide ; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({(3R) ) -1- [2-Fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-((4-[(1-1-yl] Cyclopropylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[(2R) -4- (N, N-dimethylglycyl) morpholin-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[(2S) -4- (N, N-dimethylglycyl) morpholin-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(tetrahydro-3-ylmethyl) amino] phenyl} sulfonyl) benzamide; Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({5-fluoro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4 -(4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; N-{[5-chloro-6-({(3R) -1- [2-fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} methoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide ; N-[(5-Chloro-6-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4) -Iloxy) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4- (1,4) -Dioxane-2-ylmethoxy) -3-nitrophenyl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4 -{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[(1,4-dioxane-2-ylmethyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(1-cyclopropylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-({4-[(4-morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(4-methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-[(4-{[(1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[({(2R) -4- [2- (2-methoxyethoxy) ethyl] morpholine-2-yl} methyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(4,4-difluorocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; N-[(4-{[(4-Acetylmorpholine-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-benzimidazol-4-yloxy) -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[4- (methylsulfonyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[6-({4- Fluoro-1- [2-fluoro-1- (fluoromethyl) ethyl] piperidine-4-yl} methoxy) -5- (trifluoromethyl) pyridine-3-yl] sulfonyl} -2- (1H-indazole-4) -Iloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (2-tetra-2-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-[(4-{[(4-cyanocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(4,4-difluorocyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4 -Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[4- (4-chlorophenyl)) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Tetrahydro-2H-pyran-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxy-4- (4-{(S-phenylpropanoid)] [(1S,, 2S, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide; N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropanoid)] [(1S, 2S) , 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide; N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropyl)] [(1S, 2S) , 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide; N-({4-[(3-morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropyl)] [(1S, 2S,, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide; 4- [4-(2-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} benzyl) piperazine-1-yl] -N-({4 -[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide; 4- [4-(2-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} benzyl) piperazin-1-yl] -N-({3 -Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -2-phenoxy-N-({4- [(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -2-phenoxy-N-({4- [(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) benzamide; 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -N-({4- [(3-morpholine-4-ylpropyl) amino ] -3-Nitrophenyl} Sulfonyl) -2-phenoxybenzamide; 4- (4- {2-[(4R, 7S) -2,3,3a, 4,7,7a-hexahydro-1H-4,7-methanoinden-5-yl] benzyl} piperazine-1-yl)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- [4- (2- {5-[(1R, 5S) -8-azabicyclo [3.2.1] octa-8-ylmethyl] thien-2-yl} benzyl) piperazine-1-yl] -N-( {3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- [4- (2- {5-[(1R, 5S) -8-azabicyclo [3.2.1] octa-8-ylmethyl] thien-2-yl} benzylidene) piperidine-1-yl] -N-( {3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- [4- (3- {5-[(1R, 5S) -8-azabicyclo [3.2.1] octa-8-ylmethyl] thien-2-yl} benzyl) piperazine-1-yl] -N-( {3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; With respect to compounds having the formula I and the therapeutically acceptable salts, prodrugs, prodrug salts and metabolites.</p><p num="0026"> Other embodiments include bladder cancer, brain tumor, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia, follicular lymphoma, T cells or Treat B-cell-derived lymphoid malignancies, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small cell lung cancer or spleen cancer For a composition comprising an excipient and a therapeutically effective amount of a compound of formula (I).</p><p num="0027"> Other embodiments include bladder cancer, brain tumor, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia, follicular lymphoma, T in patients. Lymphatic malignancies derived from cells or B cells, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small cell lung cancer or spleen cancer A method of treatment comprising administering to a patient a therapeutically effective amount of formula (I).</p><p num="0028"> Other embodiments include bladder cancer, brain tumor, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia, follicular lymphoma, T in patients. Lymphatic malignancies derived from cells or B cells, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small cell lung cancer or spleen cancer A method of treatment comprising administering to a patient a therapeutically effective amount of a compound of formula (I) and a therapeutically effective amount of one additional therapeutic agent or two or more additional therapeutic agents.</p>

Variable parts herein are represented by identifiers (capital letters with numbers and / or superscripts of the alphabet) and can be specifically represented.

It maintains the proper valence for all parts and this combination, and the monovalent part with two or more atoms is lined from left to right and bonded through its left end. It means that the divalent part is also understood to be drawn from left to right.

It is also understood that a particular embodiment of the variable portion of the specification may be the same as or different from other particular embodiments having the same identifier.

As used herein, the term "alkenyl" means a linear or branched hydrocarbon chain containing 2 to 10 carbons and containing at least one carbon-carbon double bond. "C_x-C_yThe term "alkyl" means a linear or branched hydrocarbon chain containing x to y carbon atoms and containing at least one carbon-carbon double bond. "C₃-C₆The term "alkenyl" means an alkenyl group containing 3-6 carbon atoms. Representative examples of alkenyl include, but are not limited to, porcine-2,3-dienyl, ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl, 2 -Includes heptenyl, 2-methyl-1-heptenyl and 3-decenyl.

The term "alkenylene" means a divalent group derived from a linear or branched chain hydrocarbon of 2 to 4 carbon atoms and includes at least one carbon-carbon double bond. "C_x-C_yThe term "alkylene" means a divalent group derived from a linear or branched hydrocarbon chain containing at least one carbon-carbon double bond and containing x to y carbon atoms. Typical examples of alkenylene are, but are not limited to, -CH = CH- and -CH.₂CH = CH- is included.

As used herein, the term "alkyl" means a linear or branched saturated hydrocarbon chain containing 1 to 10 carbon atoms. "C_x-C_yThe term "alkyl" means a linear or branched-chain saturated hydrocarbon containing x to y carbon atoms. For example, "C₁-C₆"Alkyl" means a linear or branched-chain saturated hydrocarbon containing 2 to 6 carbon atoms. Representative examples of alkyl are, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl. , N-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl and n-decyl.

The term "alkylene" means a divalent group derived from a linear or branched saturated hydrocarbon chain of 1 to 10 carbon atoms, eg 1 to 4 carbon atoms. "C_x-C_yThe term "alkylene" means a divalent group derived from a linear or branched-chain saturated hydrocarbon containing x to y carbon atoms. For example, "C₂-C₆"Alkylene" means a linear or branched chain saturated hydrocarbon containing 2 to 6 carbon atoms. Typical examples of alkylene are, but are not limited to, -CH₂-, -CH₂CH₂-, -CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂-And-CH₂CH (CH)₃) CH₂-Includes.

As used herein, the term "alkynyl" means a linear or branched chain hydrocarbon group containing 2 to 10 carbon atoms and at least one carbon-carbon triple bond. "C_x-C_yThe term "alkynyl" means a linear or branched chain hydrocarbon group containing x to y carbon atoms. For example, "C₃-C₆"Alkynyl" means a linear or branched chain hydrocarbon group containing 3 to 6 carbon atoms and containing at least one carbon-carbon triple bond. Representative examples of alkynyl include, but are not limited to, acetylenyl, 1-propynyl, 2-propynyl, 3-butynyl, 2-pentynyl and 1-butynyl.

As used herein, the term "alkynylene" is a divalent group derived from a linear or branched hydrocarbon group containing 2 to 10 carbon atoms and at least one carbon-carbon triple bond. Means.

The term "aryl" as used herein means phenyl.

As used herein, the term "cyclic moiety" refers to benzene, phenyl, phenylene, cycloalkane, cycloalkyl, cycloalkylene, cycloalkene, cycloalkene, cycloalkynelen, cycloalkyne, cycloalkyne, cycloalkynelen, heteroarene, It means heteroaryl, heterocycloalkane, heterocycloalkyl, heterocycloalkene, heterocycloalkene and spiroalkyl.

As used herein, the terms "cycloalkylene," cycloalkyl, or "cycloalkane" mean a monocyclic or bridging hydrocarbon ring system. A monocyclic cycloalkyl is a carbon ring system containing 3 to 10 carbon atoms, 0 heteroatoms and 0 double bonds. Examples of monocyclic systems include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. A single ring consists of one, two or three carbon atoms, each containing one or two alkylene bridges, each bonded to two non-adjacent carbon atoms in the ring system. Can be done. Typical examples of such a bridged cycloalkyl ring system are, but are not limited to, bicyclo [3.1.1] heptane, bicyclo [2.2.1] heptane, bicyclo [2.2.2] octane, bicyclo [3.2.1]. ] Octane, Bicyclo [3.2.2] Nonane, Bicyclo [3.3.1] Nonane, Bicyclo [4.2.1] Nonane, Tricyclo [3.3.1.0]^3,7] Nonane (octahydro-2,5-methanopentalene or noradamatanane) and tricyclo [3.3.1.1^3,7] Decane (adamantane) is included. The monocyclic and bridging cycloalkyl may be attached to the parent molecule moiety via any substitutable atom contained within the ring system.

As used herein, the terms "cycloalkeneylene," "cycloalkene," or "cycloalkene" mean a monocyclic or cross-linked hydrocarbon ring system. Monocyclic cycloalkenyl has 4 to 10 carbon atoms and 0 heteroatoms. A 4-membered ring system has one double bond, a 5- or 6-membered ring system has one or two double bonds, and a 7- or 8-membered ring system has 1, 2 Or it has 3 double bonds and the 9- or 10-membered ring has 1, 2, 3 or 4 double bonds. Representative examples of monocyclic cycloalkenyl groups include, but are not limited to, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl. A monocyclic cycloalkenyl ring comprises one or two alkylene bridges, each consisting of one, two or three carbon atoms, each bonded to two non-adjacent carbon atoms in the ring system. Can be done. Representative examples of bridging cycloalkenyl groups include, but are not limited to, bicyclo [2.2.1] hepta-2-ene, 4,5,6,7-tetrahydro-3aH-indene, octahydronaphthalenyl. And 1,6-dihydro-pentalene is included. The monocyclic and crosslinked cycloalkenyl may be attached to the parent molecule moiety via any substitutable atom contained within the ring system.

As used herein, the terms "cycloalkyne," "cycloalkynyl," or "cycloalkynylene" mean a monocyclic or bridging hydrocarbon ring system. Monocyclic cycloalkynyl has 8 or more carbon atoms, 0 heteroatoms and one or more triple bonds. A monocyclic cycloalkynyl ring comprises one or two alkylene bridges, each consisting of one, two or three carbon atoms, each bonded to two non-adjacent carbon atoms in the ring system. Can be done. The monocyclic and bridging cycloalkynyls may be attached to the parent molecule moiety via any substitutable atom contained within the ring system.

As used herein, the terms "heteroarene," "heteroaryl," or "heteroarylene" have at least one carbon atom and one or more independently selected nitrogen, oxygen, or sulfur atoms. It means a 5-membered or 6-membered aromatic ring. The heteroarene of the present invention is linked via any adjacent atom in the ring. However, the appropriate valence is maintained. Representative examples of heteroaryls include, but are not limited to, furanyl (including, but not limited to, furan-2-yl), imidazolyl (including, but not limited to, 1H-imidazol-1-yl). ), Isooxazolyl, isothiazolyl, oxadiazolyl, 1,3-oxazolyl, pyridinyl (eg, pyridine-4-yl, pyridine-2-yl, pyridine-3-yl), pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, tetrazolyl, thiadiazolyl , 1,3-Thiazolyl, thienyl (including, but not limited to, thien-2-yl, thien-3-yl), triazolyl and triazinyl.

As used herein, the terms "heterocycloalkane", "heterocycloalkyl" or "heterocycloalkylene" are at least one heteroatom and zero independently selected from the group consisting of O, N and S. Means a monocyclic or cross-linked 3-, 4-, 5-, 6-, 7- or 8-membered ring containing a double bond. The monocyclic and bridged heterocycloalkanes are attached to the parent molecule moiety via any substitutable carbon atom or any substitutable nitrogen atom contained within the ring. The nitrogen and sulfur heteroatoms in the heterocycle may be optionally oxidized and the nitrogen atoms may be quaternized in some cases. Representative examples of heterocycloalkane groups include, but are not limited to, 8-azabicyclo [3.2.1] octane, 3-azabicyclo [3.2.2] nonane, morpholinyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, dioxolanyl, Tetrahydrofuranyl, thiomorpholinyl, 1,4-dioxanyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxetanyl, piperazinyl, imidazolidinyl, azetidine, azepanyl, aziridinyl, diazepanyl, dithiolanyl, dithianol, isooxazolidinyl, isothiazolidinyl, oxadiazo Includes lydinyl, oxazolidinyl, pyrazolidinyl, tetrahydrothienyl, thiadiazolidinyl, thiazolidinyl, thiomorpholinyl, trithianyl and trithianyl.

As used herein, the terms "heterocycloalkene", "heterocycloalkene" or "heterocycloalkeneylene" are at least one heteroatom and one or one independently selected from the group consisting of O, N and S. Means a monocyclic or bridging 3-, 4-, 5-, 6-, 7- or 8-membered ring containing multiple double bonds. The monocyclic and bridged heterocycloalkenes are attached to the parent molecule moiety via any substitutable carbon atom or any substitutable nitrogen atom contained within the ring. The nitrogen and sulfur heteroatoms in the heterocycle may be optionally oxidized and the nitrogen atoms may be quaternized in some cases. Representative examples of heterocycloalkene groups include, but are not limited to, 1,4,5,6-tetrahydropyridazinyl, 1,2,3,6-tetrahydropyridinyl, dihydropyranyl, imidazolinyl. , Isothiazolinyl, oxadiazolinyl, isooxazolinyl, oxazolinyl, pyranyl, pyrazolinyl, pyrrolinyl, thiadiazolinyl, thiazolinyl and thiopyranyl.

As used herein, the term "phenylene" means a divalent group formed by removing a hydrogen atom from phenyl.

As used herein, the term "spiroalkyl" means an alkylene with both ends bonded to the same carbon atom, an example of which is C.₂-Spiroalkyl, C₃-Spiroalkyl, C₄-Spiroalkyl, C₅-Spiroalkyl, C₆-Spiroalkyl, C₇-Spiroalkyl, C₈-Spiroalkyl, C₉-Spiroalkyl, etc.

As used herein, the term "spiroheteroalkyl" is independently selected for O, C (O), CNOH, CNOCH.₃, S, S (O), SO₂Or one or two CHs replaced by NH₂Means a spiroalkyl having a moiety and one or two CH moieties that have not been replaced or have been replaced by N.

As used herein, the term "spiroheteroalkenyl" is an independently selected O, C (O), CNOH, CNOCH.₃, S, S (O), SO₂Or one or two CHs replaced by NH₂Means a spiroalkenyl having a moiety and one or two CH moieties that are not replaced or replaced by N, and O, C (O), CNOH, CNOCH that are not replaced or are independently selected.₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It also means a spiroalkenyl having a moiety and one or two CH moieties replaced by N.

As used herein, the term "spirocyclo" refers to 2 on the same carbon atom forming a cycloalkane, heterocycloalkane, cycloalkene or heterocycloalkene ring together with the carbon atom to which they are attached. Means one substituent.

"C" as used herein₂-C₅-The term "spiroalkyl" is C₂-Spiroalkyl, C₃-Spiroalkyl, C₄-Spiroalkyl and C₅-Mean spiroalkyl.

"C" as used herein₂The term "-spiroalkyl" has the same CH at both ends.₂It means eta-1,2-ylene that replaces the hydrogen atom in the part.

"C" as used herein₃The term "-spiroalkyl" has the same CH at both ends.₂It means propa-1,3-ylene that replaces the hydrogen atom in the part.

"C" as used herein₄The term "-spiroalkyl" has the same CH at both ends.₂It means porcine-1,4-ylene that replaces the hydrogen atom in the part.

"C" as used herein₅The term "-spiroalkyl" has the same CH at both ends.₂It means penta-1,5-ylene that replaces the hydrogen atom in the part.

"C" as used herein₆The term "-spiroalkyl" has the same CH at both ends.₂It means hexa-1,6-ylene that replaces the hydrogen atom in the part.

The term "NH-protecting group" as used herein refers to trichloroethoxycarbonyl, tribromoethoxycarbonyl, benzyloxycarbonyl, para-nitrobenzylcarbonyl, ortho-bromobenzyloxycarbonyl, chloroacetyl, dichloroacetyl, trichloroacetyl, tri. Fluoroacetyl, phenylacetyl, formyl, acetyl, benzoyl, tert-amyloxycarbonyl, tert-butoxycarbonyl, para-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyl-oxycarbonyl, 4- (phenylazo) benzyloxycarbonyl, 2 -Frufuryl-oxycarbonyl, diphenylmethoxycarbonyl, 1,1-dimethylpropoxy-carbonyl, isopropoxycarbonyl, phthaloyl, succinyl, alanyl, leucyl, 1-adamantyloxycarbonyl, 8-quinolyloxycarbonyl, benzyl, diphenylmethyl, tri Phenylmethyl, 2-nitrophenylthio, methanesulfonyl, para-toluenesulfonyl, N, N-dimethylaminomethylene, benzylidene, 2-hydroxybenzylidene, 2-hydroxy-5-chlorobenzylidene, 2-hydroxy-1-naphthyl-methylene , 3-Hydroxy-4-pyridylmethylene, cyclohexylidene, 2-ethoxycarbonylcyclohexylidene, 2-ethoxycarbonylcyclopentylidene, 2-acetylcyclohexylidene, 3,3-dimethyl-5-oxycyclo-hexylidene, diphenyl It means phosphoryl, dibenzylphosphoryl, 5-methyl-2-oxo-2H-1,3-dioxol-4-yl-methyl, trimethylsilyl, triethylsilyl and triphenylsilyl.

The term "C (O) OH protective group" as used herein refers to methyl, ethyl, n-propyl, isopropyl, 1,1-dimethylpropyl, n-butyl, tert-butyl, phenyl, naphthyl, benzyl, diphenyl. Methyl, triphenylmethyl, para-nitrobenzyl, para-methoxybenzyl, bis (para-methoxyphenyl) methyl, acetylmethyl, benzoylmethyl, para-nitrobenzoylmethyl, para-bromobenzoylmethyl, para-methanesulfonylbenzoylmethyl, 2-Tetrahydropyranyl 2-Tetrahydrofuranyl, 2,2,2-trichloro-ethyl, 2- (trimethylsilyl) ethyl, acetoxymethyl, propionyloxymethyl, pivaloyloxymethyl, phthalimidemethyl, succinimidemethyl, cyclopropyl, cyclobutyl , Cyclopentyl, Cyclohexyl, methoxymethyl, methoxyethoxymethyl, 2- (trimethylsilyl) ethoxymethyl, benzyloxymethyl, methylthiomethyl, 2-methylthioethyl, phenylthiomethyl, 1,1-dimethyl-2-propenyl, 3-methyl- It means 3-butenyl, allyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, diethylisopropylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, diphenylmethylsilyl and tert-butylmethoxyphenylsilyl.

The term "OH or SH protective group" as used herein refers to benzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, Methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, 1,1-dimethylpropoxycarbonyl, isopropoxycarbonyl, isobutyloxycarbonyl, diphenylmethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2,2,2-tribromoethoxy Carbonyl, 2- (trimethylsilyl) ethoxycarbonyl, 2- (phenylsulfonyl) ethoxycarbonyl, 2- (triphenylphosphonio) ethoxycarbonyl, 2-flufuryloxycarbonyl, 1-adamantyloxycarbonyl, vinyloxycarbonyl, allyloxycarbonyl , S-benzylthiocarbonyl, 4-ethoxy-1-naphthyloxycarbonyl, 8-quinolyloxycarbonyl, acetyl, formyl, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, methoxyacetyl, phenoxyacetyl, pivaloyl, benzoyl , Methyl, tert-butyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 1,1-dimethyl-2-propenyl, 3-methyl-3-butenyl, allyl, benzyl (phenylmethyl), para-methoxy Benzyl, 3,4-dimethoxybenzyl, diphenylmethyl, triphenylmethyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiopyranyl, methoxymethyl, methylthiomethyl, benzyloxymethyl, 2-methoxyethoxymethyl, 2,2,2-Trichloro-ethoxymethyl, 2- (trimethylsilyl) ethoxymethyl, 1-ethoxyethyl, methanesulfonyl, para-toluenesulfonyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, diethylisopropylsilyl, tert-butyldimethylsilyl, tert-butyl It means diphenylsilyl, diphenylmethylsilyl and tert-butylmethoxyphenylsilyl. Compound Geometric isomers can be present in the compounds of the present invention. The compounds of the present invention can contain carbon-carbon double bonds or carbon-nitrogen double bonds in an E-type or Z-type structure. Here, the term "type E" is on the opposite side of the carbon-carbon or carbon-nitrogen double bond, as determined by the Cahn-Ingold-Prelog Priority Rule. Representing a higher substituent, the term "Z-type" refers to a higher substituent on the same side of a carbon-carbon or carbon-nitrogen double bond. The compounds of the present invention can also exist as a mixture of "E-type" and "Z-type" isomers. Substituents around cycloalkyl or heterocycloalkyl are specified by the cis or trans structure. In addition, the present invention considers various isomers and mixtures thereof obtained by the arrangement of substituents around the adamantane ring system. The two substituents around a single ring in the adamantane ring system are specified by a Z-type or E-type relative structure. For example, CD Jones, M. Kaselj, RN Salvatore, WJle Noble J. Org. Chem. 1998, 63, pp. 2758-2760 and EL Eliel, and SH Wilen. (1994) Stereochemistry of Organic Compounds. New York, NY: John Wiley &amp; Sons See, Inc.

The compounds of the present invention contain carbon atoms that are asymmetrically substituted in an R-type or S-type structure. The terms "R-type" and "S-type" are as defined in IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, pp. 13-10. Compounds with asymmetrically substituted carbon atoms in equal amounts of R- and S-type structures have a racemic structure for these carbon atoms. Atoms in which one structure is in excess of the other are in greater amounts, preferably about 85% -90% excess, more preferably about 95% -99% excess, and even more preferably about 99% excess. The structure that exists in is assigned. Accordingly, the present invention includes racemic mixtures, relative and absolute stereoisomers, and mixtures of relative and absolute stereoisomers.

Compounds of the invention, including NH, C (O) OH, OH or SH moieties, may have prodrug-forming moieties attached to it. The prodrug-forming moiety is removed in vivo by metabolic processes to release compounds with free hydroxyl, amino or carboxylic acids. Prodrugs are useful in regulating pharmacokinetic properties such as solubility and / or hydrophobicity, absorption in the gastrointestinal tract, bioavailability, tissue permeability and clearance rate. Isotope enriched or labeled compounds The compounds of the present invention are present in an isotope-labeled or enriched form containing one or more atoms having an atomic mass or mass number different from the atomic mass or mass number most abundant in nature. Can be done. The isotope may be a radioactive isotope or a non-radioactive isotope. Isotopes of atoms such as hydrogen, carbon, phosphorus, sulfur, fluorine, chlorine and iodine are not limited to, but are limited to.²H,³H,¹³C,¹⁴C,¹⁵N,¹⁸0、³²P,³⁵S,¹⁸F,³⁶Cl and¹²⁵I is included. Compounds containing other isotopes of the above and / or other atoms are within the scope of the invention.

In other embodiments, the isotope-labeled compound is deuterium (²H), tritium (³H) or¹⁴Contains C isotope. The isotope-labeled compound of the present invention can be prepared by a general method well known to those skilled in the art. Such isotope-labeled compounds are conveniently replaced by readily available isotope-labeled reagents and the procedures disclosed in the examples and schemes disclosed herein are carried out. Can be prepared. In some cases, the compound is treated with an isotope-labeled reagent to exchange normal atoms for its isotope, eg, D.₂SO₄/ D₂Hydrogen can be exchanged for deuterium by the action of deuterium such as O. In addition to the above, related procedures and intermediates are described, for example, Lizondo, J et al., Drugs Fut, 21 (11), 1116 (1996); Brickner, SJ et al., J Med Chem, 39 (3), 673 (1996). ); Mallesham, B et al., Org Lett, 5 (7), 963 (2003); PCT Publication WO1997010223, WO2005099353, WO1995007271, WO2006008754; U.S. Pat. No. 7,538,189; No. 7534814; No. 7531685; No. 7528131; No. 7521421; 7514068; 7511013 and US Patent Application Publication No. 20090137457; 20090131485; 20090131363; 20090118238; 20090111840; 20090105338; 20090105307; 20090105147 No.; No. 20090093422; No. 20090088416 and No. 20090082471. These methods are incorporated herein by reference.

The isotope-labeled compounds of the present invention can be used as a standard for determining the efficacy of Bcl-2 inhibitors in binding assays. Isotope-containing compounds have been used in pharmaceutical studies to examine the metabolic fate of compounds in vivo by assessing the mechanism of action and metabolic pathways of non-isotope-labeled parent compounds (Blake et al., et al. J.Pharm.Sci.64, 3, pp. 367-391 (1975)). Because the compound that is active in vivo is administered to the patient, or because the metabolites produced from the parent compound are found to be toxic or carcinogenic (Foster et al., Advances in Drug Research Vol. 14, pp. 2-36). , Academic press, London, 1985; Kato et al., J.Labelled Comp.Radiopharmaceut., 36 (10): 927-932 (1995); Kushner et al., Can.J.Physiol.Pharmacol., 77, 79-88 Page (1999), such metabolic studies are important in the design of safe and effective therapeutic agents.

In addition, drugs containing non-radioisotopes, such as deuterated drugs, called "heavy drugs", can be used to treat diseases and conditions associated with Bcl-2 activity. .. Increasing the amount of isotopes present in the compound beyond its natural abundance is referred to as enrichment. Examples of enrichments are about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, Includes 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96 to about 100 mol%. In mammals, including rodents and dogs, up to about 15% of normal atoms have been replaced with heavy isotopes and retained for days to weeks with minimal adverse effects observed (Czajka DM and). Finkel AJ, Ann.NYAcad.Sci. 1960 84:770; Thomson JF, Ann.New York Acad.Sci 1960 84:736; Czakja DM et al., Am.J. Physiol. 1961 201: 357). Acute replacement with as much as 15% -23% deuterium in human body fluids has been shown to be non-toxic (Blagojevic N et al., Dosimetry &amp; Treatment Planning for Neutron Capture Therapy, Zamenhof R. , Solares G and Harling O Eds. 1994. Advanced Medical Publishing, Madison Wis. pp. 125-134; Diabetes Metab. 23:251 (1997)).

Stable isotope labeling of drugs can alter their physicochemical properties such as pKa and lipophilicity. If isotope substitutions affect the regions involved in ligand-receptor interactions, these effects and alterations can affect the pharmacodynamic response of the drug molecule. Some of the physical properties of stable isotope-labeled molecules differ from those of unlabeled molecules, but their chemical and biological properties are one important exception: the mass of heavy isotopes. Due to its large size, any bond containing a heavy isotope and another atom is the same except that it is stronger than the same bond between the light isotope and that atom. Therefore, isotopic uptake at the site of metabolic or enzymatic conversion delays the reaction and potentially alters the pharmacokinetic profile or efficacy for non-isotopic compounds. Amides, esters and prodrugs Prodrugs are derivatives of active drugs designed to improve any identified and undesired physical or biological property. Its physical properties are usually related to solubility (excess or inadequate lipid solubility or water solubility) or stability, but the biological properties in question are themselves physicochemical properties. Includes overly fast metabolism or inadequate bioavailability that may be associated with.

Prodrugs are: a) Esters of active drugs, hemiesters, carbonates, nitrates, amides, hydroxamic acids, carbamate, imine, Mannig base and enamine formation, b) Functionality of drugs with azo, glycosides, peptides and ether functional groups. Chemicals, c) Usually prepared by use in the form of polymers, salts, complexes, phosphoramides, acetals, hemiacetals and ketals of the drug. See, for example, Andrews Korolkovas's, "Essentials of Medicinal Chemistry," John Wiley-Interscience Publications, John Wiley and Sons, New York (1988), pp. 97-118. This is incorporated herein by reference in its entirety.

The ester can be prepared from a substrate of formula (I) containing a hydroxyl group or a carboxy group by a general method known to those skilled in the art. Typical reactions of these compounds are substitution reactions that replace one of the heteroatoms with another, such as:

<chemistry num="6"><img id="000007" he="31" wi="158" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>Is.

The amide can be prepared in a similar manner from the substrate of formula (I) containing an amino group or a carboxy group. Esters can also be reacted with amines or ammonia to form amides.

<chemistry num="7"><img id="000008" he="33" wi="160" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> Another method of making an amide from a compound of formula (I) is to heat the carboxylic acid and the amine together.

<chemistry num="8"><img id="000009" he="26" wi="159" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> In Schemes 2 and 3 above, R and R'are independently the substrates of formula (I), alkyl or hydrogen.

A in the compound of formula (I)¹, B¹, D¹, E¹, Y¹And Z¹Suitable groups are independently selected. The embodiments described in the present invention can be combined. Considering such combinations, they are within the scope of the present invention. For example, A¹, B¹, D¹, E¹, Y¹And Z¹The embodiment for any of¹, B¹, D¹, E¹, Y¹And Z¹Can be combined with embodiments defined for any other of the.

Accordingly, one embodiment of the invention relates to a compound or therapeutically acceptable salt, prodrug or salt of the prodrug that is useful as a selective inhibitor of one or more anti-apoptotic protein family members. The compound is of formula (I)

<chemistry num="9"><img id="000010" he="29" wi="159" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(During the ceremony, A¹Is N or C (A)²) And; A², B¹, D¹And E¹One or two or three of them or each is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NR¹C (O) NHR¹, NR¹C (O) N (R)¹)₂, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CN, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; Y¹Is H, CN, NO₂, C (O) OH, F, Cl, Br, I, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, R¹⁷, OR¹⁷, C (O) R¹⁷, C (O) OR¹⁷, SR¹⁷, NH₂, NHR¹⁷, N (R)¹⁷)₂, NHC (O) R¹⁷, C (O) NH₂, C (O) NHR¹⁷, C (O) N (R)¹⁷)₂, NHS (O) R¹⁷Or NHSO₂R¹⁷Is; or B¹And Y¹Is imidazole or triazole along with the atoms to which they are attached; A², D¹And E¹One or two or each of them is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NHC (O) NHR¹, N (CH₃) C (O) N (CH₃) R¹, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; R¹Is R², R³, R⁴Or R⁵Is; R^1AIs C₁-C₆-Alkyl, C₃-C₆-Alkenyl or C₃-C₆-Alkyne; R²Is uncondensed or arene, heteroarene or R^2AIs phenyl condensed with; R^2AIs a cycloalkane or a heterocycloalkane; R³Is uncondensed or benzene, heteroarene or R^3AHeteroaryl condensing with; R^3AIs a cycloalkane or a heterocycloalkane; R⁴Are cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is uncondensed or arene, heteroarene or R.^4ACondensed with; R^4AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁶, NC (R^6A) (R^6B), R⁷, OR⁷, SR⁷, S (O) R⁷, SO₂R⁷, NHR⁷, N (R)⁷)₂, C (O) R⁷, C (O) NH₂, C (O) NHR⁷, NHC (O) R⁷, NHSO₂R⁷, NHC (O) OR⁷, SO₂NH₂, SO₂NHR⁷, SO₂N (R⁷)₂, NHC (O) NH₂, NHC (O) NHR⁷, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NH₂, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NHR¹, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁶Is C₂-C₅-Spiroalkyl, each of which is unsubstituted or OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH (CH)₃) Or N (CH₃)₂Replaced by; R^6AAnd R^6BAre independently selected alkyls, or R with N to which they are attached^6CIs; R^6CAre aziridine-1-yl, azetidine-1-yl, pyrrolidine-1-yl or piperidine-1-yl, which are not replaced or O, C (O), CNOH, CNOCH, respectively.₃, S, S (O), SO₂Or one CH replaced by NH₂Has a part; R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is; R⁸Is uncondensed or arene, heteroarene or R^8AIs phenyl condensed with; R^8AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁹Is uncondensed or arene, heteroarene or R^9AHeteroaryl condensing with; R^9AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has moieties and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^10ACondensed with; R^10AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3¹², OR¹², NHR¹², N (R)¹²)₂, C (O) NH₂, C (O) NHR¹², C (O) N (R)¹²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R¹²Is R¹³, R¹⁴, R¹⁵Or R¹⁶Is; R¹³Is uncondensed or arene, heteroarene or R^13AIs phenyl condensed with; R^13AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁴Are heteroaryl, each of which is uncondensed or arene, heteroarene or R^14ACondensed with; R^14AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁵Are cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes, each of which is uncondensed or arene, heteroarene or R.^15ACondensed with; R^15AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁶Is alkyl, alkenyl or alkynyl; R¹⁷Is R¹⁸, R¹⁹, R²⁰Or R²¹Is; R¹⁸Is uncondensed or arene, heteroarene or R^18AIs phenyl condensed with; R^18AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁹Is uncondensed or arene, heteroarene or R^19AHeteroaryl condensing with; R^19AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^20ACondensed with; R^20AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3²², OR²², NHR²², N (R)²²)₂, C (O) NH₂, C (O) NHR²², C (O) N (R)²²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R²²Is R²³, R²⁴Or R²⁵Is; R²³Is uncondensed or arene, heteroarene or R^23AIs phenyl condensed with; R^23AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁴Is uncondensed or arene, heteroarene or R^24AHeteroarene condensed with; R^24AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁵Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^25ACondensed with; R^25AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; Z¹Is R²⁶Or R²⁷And each of them is R²⁸, R²⁹Or R³⁰Replaced by, each of which is F, Cl, Br, I, CH₂R³⁷, CH (R)³¹) (R³⁷), C (R³¹) (R^31A) (R³⁷), C (O) R³⁷, OR³⁷, SR³⁷, S (O) R³⁷, SO₂R³⁷, NHR³⁷Or N (R)³²) R³⁷Replaced by; R²⁶Is a phenyl that is uncondensed or condensed with arene or heteroarene; R²⁷Is a heteroarene that is not condensed or is condensed with an arene or a heteroarene; R²⁸Is uncondensed or arene, heteroarene or R^28AIs phenyl condensed with; R^28AIs a cycloalkane, cycloalkene, heterocycloalkene or heterocycloalkene, R²⁹Is heteroaryl or R^29AIs; R^29AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁰Are cycloalkyl or cycloalkenyl, respectively, O, C (O), CNOH, CNOCH, which are not replaced or are independently selected.₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^30ACondensed with; R^30AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³¹And R^31AAre independently F, Cl, Br or alkyl, or together with C₂-C₅-Spiroalkyl; R³²Is R³³, C (O) R³³Or C (O) OR³³Is; R³³Is R³⁴Or R³⁵Is; R³⁴Is uncondensed or aryl, heteroaryl or R^34AIs phenyl condensed with; R^34AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁵Is not replaced or R³⁶It is an alkyl substituted with; R³⁶Is uncondensed or arene, heteroarene or R^36AIs phenyl condensed with; R^36AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁷Is R³⁸, R³⁹Or R⁴⁰And each of them is F, Cl, Br, I, R⁴¹, OR⁴¹, NHR⁴¹, N (R)⁴¹)₂, NHC (O) OR⁴¹, SR⁴¹, S (O) R⁴¹Or SO₂R⁴¹Replaced by; R³⁸Is uncondensed or arene, heteroarene or R^38AIs phenyl condensed with; R^38AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁹Is uncondensed or arene, heteroarene or R^39AHeteroaryl condensing with; R^39AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁰Is C₃-C₈-Cycloalkyl or C₄-C₈-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^40ACondensed with; R^40AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴¹Is R⁴², R⁴³, R⁴⁴Or R⁴⁵Is; R⁴²Is uncondensed or arene, heteroarene or R^42AIs phenyl condensed with; R^42AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴³Is uncondensed or arene, heteroarene or R^43AHeteroaryl condensing with; R^43AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁴Is C₃-C₉-Cycloalkyl or C₄-C₇-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^44ACondensed with; R^44AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R⁴⁶, OR⁴⁶, NHR⁴⁶, N (R)⁴⁶)₂, C (O) NH₂, C (O) NHR⁴⁶, C (O) N (R)⁴⁶)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁴⁶Is R⁴⁷, R⁴⁸Or R⁴⁹Is; R⁴⁷Is uncondensed or arene, heteroarene or R^47AIs phenyl condensed with; R^47AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁸Is heteroaryl or R^48AIs; R^48AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁹Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^49ACondensed with; R^49AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁶And R²⁷The part represented by is an independently selected R^50A, OR^50A, SR^50A, S (O) R^50A, SO₂R^50AOr NHR^50AIs further replaced by one, two or three of R^50AIs R^51A, R^52A, R^53AOr R^54AIs; R^51AIs uncondensed or benzene, heteroarene or R^51AAPhenyl that is condensed with R^51AAIs a cycloalkane, cycloalkene, or heterocycloalkene heterocycloalkene, R^52AIs heteroaryl; R^53AIs C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl; each is undone or independently selected O, C (O), CNOH, CNOCH₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^53AACondensed with; R^53AAAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R^54AAre alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R^55AA, OR^55AA, SR^55AA, S (O) R^55AA, SO₂R^55AA, NHR^55AA, N (R)^55AA)₂, C (O) R^55AA, C (O) NH₂, C (O) NHR^55AA, NHC (O) R^55AA, NHSO₂R^55AA, NHC (O) OR^55AA, SO₂NH₂, SO₂NHR^55AA, SO₂N (R^55AA)₂, NHC (O) NH₂, NHC (O) NHR^55AA, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, F, Cl, Br or I substituted with one, two or three substituents; R^55AAAlkyl, alkenyl, alkynyl, phenyl, heteroaryl or R^56AIs; R^56AIs C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkyl, each of which is non-replaced or independently selected O, C (O), CNOH, CNOCH₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N; R², R³, R⁴, R⁶, R^6C, R⁸, R^8A, R⁹, R¹⁰, R¹³, R¹⁴, R¹⁵, R¹⁸, R¹⁹, R²⁰, R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹, R³⁰, R³⁴, R³⁶, R³⁸, R³⁹, R⁴⁰, R⁴², R⁴³, R⁴⁴, R⁴⁷, R⁴⁸And R⁴⁹The part represented by is not independently replaced, further not replaced, 1, 2, 3, 4 or 5 independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S (O) R⁵⁰, SO₂R⁵⁰, C (O) R⁵⁰, CO (O) R⁵⁰, OC (O) R⁵⁰, OC (O) OR⁵⁰, NH₂, NHR⁵⁰, N (R)⁵⁰)₂, C (O) NH₂, C (O) NHR⁵⁰, C (O) N (R)⁵⁰)₂, C (O) NHOH, C (O) NHOR⁵⁰, C (O) NHSO₂R⁵⁰, C (O) NR⁵⁵SO₂R⁵⁰, SO₂NH₂, SO₂NHR⁵⁰, SO₂N (R⁵⁰)₂, CF₃, CF₂CF₃, C (O) H, C (O) OH, C (N) NH₂, C (N) NHR⁵⁰, C (N) N (R)⁵⁰)₂, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituted or further substituted with substituents; R⁵⁰Is R⁵¹, R⁵², R⁵³Or R⁵⁴Is; R⁵¹Is uncondensed or arene, heteroarene or R^51BIs phenyl condensed with; R^51BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵²Is heteroaryl; R⁵³Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^53BCondensed with; R^53BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵⁴Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁵⁵, OR⁵⁵, SR⁵⁵, S (O) R⁵⁵, SO₂R⁵⁵, NHR⁵⁵, N (R)⁵⁵)₂, C (O) R⁵⁵, C (O) NH₂, C (O) NHR⁵⁵, NHC (O) R⁵⁵, NHSO₂R⁵⁵, NHC (O) OR⁵⁵, SO₂NH₂, SO₂NHR⁵⁵, SO₂N (R⁵⁵)₂, NHC (O) NH₂, NHC (O) NHR⁵⁵, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, F, Cl, Br or I substituted with substituents; R⁵⁵Alkyl, alkenyl, alkynyl, phenyl, heteroaryl or R⁵⁶Is; Are the alkyl, alkenyl, and alkynyl substituted? OCH₃Replaced by; R⁵⁶Is C₃-C₈-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N. ) Have.

Another embodiment of the present invention is a compound of formula (I). (In the formula, A¹Is N or C (A)²) And; A², B¹, D¹And E¹One or two or three of them or each is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NR¹C (O) NHR¹, NR¹C (O) N (R)¹)₂, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CN, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; Y¹Is H, CN, NO₂, C (O) OH, F, Cl, Br, I, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, R¹⁷, OR¹⁷, C (O) R¹⁷, C (O) OR¹⁷, SR¹⁷, NH₂, NHR¹⁷, N (R)¹⁷)₂, NHC (O) R¹⁷, C (O) NH₂, C (O) NHR¹⁷, C (O) N (R)¹⁷)₂, NHS (O) R¹⁷Or NHSO₂R¹⁷Is; or B¹And Y¹Is imidazole or triazole along with the atoms to which they are attached; A², D¹And E¹One or two or each of them is independently selected R¹, OR¹, SR¹, S (O) R¹, SO₂R¹, C (O) R¹, C (O) OR¹, OC (O) R¹, NHR¹, N (R)¹)₂, C (O) NHR¹, C (O) N (R)¹)₂, NHC (O) R¹, NHC (O) OR¹, NHC (O) NHR¹, N (CH₃) C (O) N (CH₃) R¹, SO₂NHR¹, SO₂N (R¹)₂, NHSO₂R¹, NHSO₂NHR¹Or N (CH₃) SO₂N (CH₃) R¹And the rest are independently selected H, F, Cl, Br, I, CF₃, C (O) OH, C (O) NH₂Or C (O) OR^1AIs; R¹Is R², R³, R⁴Or R⁵Is; R^1AIs C₁-C₆-Alkyl, C₃-C₆-Alkenyl or C₃-C₆-Alkyne; R²Is uncondensed or arene, heteroarene or R^2AIs phenyl condensed with; R^2AIs a cycloalkane or a heterocycloalkane; R³Is uncondensed or benzene, heteroarene or R^3AHeteroaryl condensing with; R^3AIs a cycloalkane or a heterocycloalkane; R⁴Are cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is uncondensed or arene, heteroarene or R.^4ACondensed with; R^4AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁶, NC (R^6A) (R^6B), R⁷, OR⁷, SR⁷, S (O) R⁷, SO₂R⁷, NHR⁷, N (R)⁷)₂, C (O) R⁷, C (O) NH₂, C (O) NHR⁷, NHC (O) R⁷, NHSO₂R⁷, NHC (O) OR⁷, SO₂NH₂, SO₂NHR⁷, SO₂N (R⁷)₂, NHC (O) NH₂, NHC (O) NHR⁷, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NH₂, NHC (O) CH (CH)₃) NHC (O) CH (CH)₃) NHR¹, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁶Is C₂-C₅-Spiroalkyl, each of which is unsubstituted or OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH (CH)₃) Or N (CH₃)₂Replaced by; R^6AAnd R^6BAre independently selected alkyls, or R with N to which they are attached^6CIs; R^6CAre aziridine-1-yl, azetidine-1-yl, pyrrolidine-1-yl or piperidine-1-yl, which are not replaced or O, C (O), CNOH, CNOCH, respectively.₃, S, S (O), SO₂Or one CH replaced by NH₂Has a part; R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is; R⁸Is uncondensed or arene, heteroarene or R^8AIs phenyl condensed with; R^8AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁹Is uncondensed or arene, heteroarene or R^9AHeteroaryl condensing with; R^9AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has moieties and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^10ACondensed with; R^10AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3¹², OR¹², NHR¹², N (R)¹²)₂, C (O) NH₂, C (O) NHR¹², C (O) N (R)¹²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R¹²Is R¹³, R¹⁴, R¹⁵Or R¹⁶Is; R¹³Is uncondensed or arene, heteroarene or R^13AIs phenyl condensed with; R^13AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁴Are heteroaryl, each of which is uncondensed or arene, heteroarene or R^14ACondensed with; R^14AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁵Are cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes, each of which is uncondensed or arene, heteroarene or R.^15ACondensed with; R^15AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁶Is alkyl, alkenyl or alkynyl; R¹⁷Is R¹⁸, R¹⁹, R²⁰Or R²¹Is; R¹⁸Is uncondensed or arene, heteroarene or R^18AIs phenyl condensed with; R^18AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R¹⁹Is uncondensed or arene, heteroarene or R^19AHeteroaryl condensing with; R^19AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁰Is C₃-C₁₀-Cycloalkyl or C₄-C₁₀-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^20ACondensed with; R^20AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²¹Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3²², OR²², NHR²², N (R)²²)₂, C (O) NH₂, C (O) NHR²², C (O) N (R)²²)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R²²Is R²³, R²⁴Or R²⁵Is; R²³Is uncondensed or arene, heteroarene or R^23AIs phenyl condensed with; R^23AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁴Is uncondensed or arene, heteroarene or R^24AHeteroarene condensed with; R^24AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁵Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^25ACondensed with; R^25AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; Z¹Is R²⁶Or R²⁷And each of them is R²⁸, R²⁹Or R³⁰Replaced by, each of which is F, Cl, Br, I, CH₂R³⁷, CH (R)³¹) (R³⁷), C (R³¹) (R^31A) (R³⁷), C (O) R³⁷, OR³⁷, SR³⁷, S (O) R³⁷, SO₂R³⁷, NHR³⁷Or N (R)³²) R³⁷Replaced by; R²⁶Is a phenyl that is uncondensed or condensed with arene or heteroarene; R²⁷Is a heteroarene that is not condensed or is condensed with an arene or a heteroarene; R²⁸Is uncondensed or arene, heteroarene or R^28AIs phenyl condensed with; R^28AIs a cycloalkane, cycloalkene, heterocycloalkene or heterocycloalkene, R²⁹Is heteroaryl or R^29AIs; R^29AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁰Are cycloalkyl or cycloalkenyl, respectively, O, C (O), CNOH, CNOCH, which are not replaced or are independently selected.₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^30ACondensed with; R^30AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³¹And R^31AAre independently F, Cl, Br or alkyl, or together with C₂-C₅-Spiroalkyl; R³²Is R³³, C (O) R³³Or C (O) OR³³Is; R³³Is R³⁴Or R³⁵Is; R³⁴Is uncondensed or aryl, heteroaryl or R^34AIs phenyl condensed with; R^34AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁵Is not replaced or R³⁶It is an alkyl substituted with; R³⁶Is uncondensed or arene, heteroarene or R^36AIs phenyl condensed with; R^36AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁷Is R³⁸, R³⁹Or R⁴⁰And each of them is F, Cl, Br, I, R⁴¹, OR⁴¹, NHR⁴¹, N (R)⁴¹)₂, NHC (O) OR⁴¹, SR⁴¹, S (O) R⁴¹Or SO₂R⁴¹Replaced by; R³⁸Is uncondensed or arene, heteroarene or R^38AIs phenyl condensed with; R^38AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R³⁹Is uncondensed or arene, heteroarene or R^39AHeteroaryl condensing with; R^39AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁰Is C₃-C₈-Cycloalkyl or C₄-C₈-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^40ACondensed with; R^40AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴¹Is R⁴², R⁴³, R⁴⁴Or R⁴⁵Is; R⁴²Is uncondensed or arene, heteroarene or R^42AIs phenyl condensed with; R^42AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴³Is uncondensed or arene, heteroarene or R^43AHeteroaryl condensing with; R^43AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁴Is C₃-C₉-Cycloalkyl or C₄-C₇-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^44ACondensed with; R^44AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁵Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R⁴⁶, OR⁴⁶, NHR⁴⁶, N (R)⁴⁶)₂, C (O) NH₂, C (O) NHR⁴⁶, C (O) N (R)⁴⁶)₂, OH, (O), C (O) OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I substituted with substituents; R⁴⁶Is R⁴⁷, R⁴⁸Or R⁴⁹Is; R⁴⁷Is uncondensed or arene, heteroarene or R^47AIs phenyl condensed with; R^47AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁸Is heteroaryl or R^48AIs; R^48AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁴⁹Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^49ACondensed with; R^49AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²⁶And R²⁷The part represented by is OR^50AHas been further replaced by R^50AIs R^51AIs; R^51AIs a phenyl condensed with heteroarene, R², R³, R⁴, R⁶, R^6C, R⁸, R^8A, R⁹, R¹⁰, R¹³, R¹⁴, R¹⁵, R¹⁸, R¹⁹, R²⁰, R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹, R³⁰, R³⁴, R³⁶, R³⁸, R³⁹, R⁴⁰, R⁴², R⁴³, R⁴⁴, R⁴⁷, R⁴⁸And R⁴⁹The part represented by is not independently replaced, further not replaced, 1, 2, 3, 4 or 5 independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S (O) R⁵⁰, SO₂R⁵⁰, C (O) R⁵⁰, CO (O) R⁵⁰, OC (O) R⁵⁰, OC (O) OR⁵⁰, NH₂, NHR⁵⁰, N (R)⁵⁰)₂, C (O) NH₂, C (O) NHR⁵⁰, C (O) N (R)⁵⁰)₂, C (O) NHOH, C (O) NHOR⁵⁰, C (O) NHSO₂R⁵⁰, C (O) NR⁵⁵SO₂R⁵⁰, SO₂NH₂, SO₂NHR⁵⁰, SO₂N (R⁵⁰)₂, CF₃, CF₂CF₃, C (O) H, C (O) OH, C (N) NH₂, C (N) NHR⁵⁰, C (N) N (R)⁵⁰)₂, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituted or further substituted with substituents; R⁵⁰Is R⁵¹, R⁵², R⁵³Or R⁵⁴Is; R⁵¹Is uncondensed or arene, heteroarene or R^51BIs phenyl condensed with; R^51BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵²Is heteroaryl; R⁵³Is C₃-C₆-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, each of which is uncondensed or arene, heteroarene or R.^53BCondensed with; R^53BAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R⁵⁴Are alkyl, alkenyl or alkynyl, each of which is unsubstituted or independently selected R of 1, 2 or 3⁵⁵, OR⁵⁵, SR⁵⁵, S (O) R⁵⁵, SO₂R⁵⁵, NHR⁵⁵, N (R)⁵⁵)₂, C (O) R⁵⁵, C (O) NH₂, C (O) NHR⁵⁵, NHC (O) R⁵⁵, NHSO₂R⁵⁵, NHC (O) OR⁵⁵, SO₂NH₂, SO₂NHR⁵⁵, SO₂N (R⁵⁵)₂, NHC (O) NH₂, NHC (O) NHR⁵⁵, OH, (O), C (O) OH, (O), N₃, CN, NH₂, CF₃, OCF₃, CF₂CF₃, OCF₂CF₃, F, Cl, Br or I substituted with substituents; R⁵⁵Alkyl, alkenyl, alkynyl, phenyl, heteroaryl or R⁵⁶Is; Are the alkyl, alkenyl, and alkynyl substituted? OCH₃Replaced by; R⁵⁶Is C₃-C₈-Cycloalkyl or C₄-C₆-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N. ) Regarding.

In one embodiment of equation (I), A¹Is N or C (A)²) And; A², B¹, D¹And E¹One or two or three of them or each is selected independently R¹, OR¹, SR¹, SO₂R¹, NHR¹, N (R)¹)₂Or C (O) NHR¹And the rest are independently selected H, F, Cl, Br or I; Y¹Is H, CN, NO₂, F, Cl, Br, I, CF₃, R¹⁷, NHC (O) R¹⁷Or C (O) NH₂Is; R¹Is R², R³, R⁴Or R⁵Is; R²Is phenyl; R³Is heteroaryl; R⁴Are cycloalkyl, heterocycloalkyl or heterocycloalkenyl, each of which is uncondensed or R^4ACondensed with; R^4AIs a cycloalkane; R⁵Are alkyl or alkynyl, each of which is unsubstituted or independently selected as one, two or three R⁶, R⁷, OR⁷, SR⁷, SO₂R⁷, N (R)⁷)₂, OH, CN, CF₃, F, Cl, Br or I substituted with substituents; R⁶Is C₂-C₅-Spiroalkyl; R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is; R⁸Is not condensed or R^8AIs phenyl condensed with; R^8AIs a heterocycloalkane; R⁹Is heteroaryl; R¹⁰Is C₃-C₁₀-Cycloalkyl, each of which is undone or independently selected O, S (O), SO₂Or one or two CHs replaced by NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N; R¹¹Are alkyl, each of which is unsubstituted or one, two or three independently selected ORs¹², F, Cl, Br or I substituted with substituents; R¹²Is R¹⁶Is; R¹⁶Is alkyl; R¹⁷Is R¹⁹Or R²¹Is; R¹⁹Is uncondensed or arene, heteroarene or R^19AHeteroaryl condensing with; R^19AAre cycloalkanes, cycloalkenes, heterocycloalkenes or heterocycloalkenes; R²¹Is an alkynyl; Z¹Is R²⁶And each of them is R³⁰Replaced by, each of which is F, Cl, Br, I, CH₂R³⁷Or CH (R³¹) (R³⁷) Has been replaced; R²⁶Is phenyl; R³⁰Are cycloalkyl, each of which is not replaced or is replaced by NH.₂Has a part; R³¹And R^31AIs independently alkyl; R³⁷Is R³⁸, R³⁹Or R⁴⁰And each of them is F, Cl, Br, I, NHR⁴¹Or R⁴¹Replaced by; R³⁸Is phenyl; R³⁹Is heteroaryl; R⁴⁰Is C₃-C₈-Cycloalkyl or C₄-C₈-Cycloalkenyl, O, C (O), CNOH, CNOCH, respectively, which are non-replaced or independently selected₃, S, S (O), SO₂Or one or two CHs replaced by NH₂Have a part; R⁴¹Is R⁴², R⁴³Or R⁴⁴Is; R⁴²Is phenyl; R⁴³Is heteroaryl; R⁴⁴Is C₃-C₉-Cycloalkyl or C₄-C₇-Cycloalkenyl, each replaced by one or two CHs that are not replaced or are replaced by an independently selected NH₂It has a moiety and one or two CH moieties that are not replaced or replaced by N, and each of them is not condensed or R^44ACondensed with; R^44AIs a cycloalkane; R²⁶The part represented by is an independently selected R^50A, OR^50A, SR^50A, S (O) R^50A, SO₂R^50AOr NHR^50AIt has been further replaced by one, two or three of; R^50AIs R^51A, R^52AOr R^54AIs; R^51AIs uncondensed or benzene, heteroarene or R^51AAIs phenyl condensed with; R^51AAIs a heterocycloalkane; R^52AIs heteroaryl; R^54AAre alkyl, each of which is undone or independently elected R^55AAOr OR^55AAReplaced by one, two or three; R^55AAIs phenyl; R², R³, R⁴, R⁶, R^6C, R⁸, R^8A, R⁹, R¹⁰, R¹³, R¹⁴, R¹⁵, R¹⁸, R¹⁹, R²⁰, R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹, R³⁰, R³⁴, R³⁶, R³⁸, R³⁹, R⁴⁰, R⁴², R⁴³, R⁴⁴, R⁴⁷, R⁴⁸And R⁴⁹The part represented by is not independently replaced, further not replaced, 1, 2, 3, 4 or 5 independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S (O) R⁵⁰, SO₂R⁵⁰, C (O) R⁵⁰, CO (O) R⁵⁰, NH₂, NHR⁵⁰, SO₂NH₂, OH, (O), CN, CF₃, OCF₃, F, Cl, Br or I substituted or further substituted with substituents; R⁵⁰Is R⁵¹, R⁵²Or R⁵⁴Is; R⁵¹Is uncondensed or arene, heteroarene or R^51BIs phenyl condensed with; R^51BIs a heterocycloalkane; R⁵²Is heteroaryl; R⁵³Is C₃-C₆-Cycloalkyl, each replaced by one or two CHs that are not replaced or are replaced by an independently selected O₂Has parts and one or two CH parts that have not been replaced or have been replaced by N; R⁵⁴Are alkyl, each of which is unsubstituted or independently selected as one, two or three R⁵⁵, OR⁵⁵, N (R)⁵⁵)₂, OH, CN, F, Cl, Br or I substituted with substituents; R⁵⁵Is alkyl or phenyl; Is the alkyl substituted or OCH₃Replaced by; R⁵⁶Is C₃-C₈-Cycloalkyl, each replaced by one or two CHs that are not replaced or are replaced by an independently selected NH₂It has parts and one or two CH parts that have not been replaced or have been replaced by N.

In one embodiment of equation (I), A¹Is N. In another embodiment of formula (I), A¹Is C (A)²). In another embodiment of formula (I), A¹Is C (A)²) And A²Is H.

In one embodiment of equation (I), B¹Is R¹, OR¹, SR¹, SO₂R¹, NHR¹, N (R)¹)₂Or C (O) NHR¹Is. In another embodiment of formula (I), B¹Is NHR¹Is. In another embodiment of formula (I), B¹Is NHR¹And A¹Is C (A)²) And A²Is H. In another embodiment of formula (I), B¹Is OR¹Is. In another embodiment of formula (I), B¹Is OR¹And A¹Is C (A)²) And A²Is H.

In one embodiment of equation (I), D¹And E¹Is H. In another embodiment of formula (I), B¹Is NHR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H. In another embodiment of formula (I), B¹Is OR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H.

In one embodiment of equation (I), Y¹Is H, CN, NO₂, F, Cl, Br, I, CF₃, R¹⁷, NHC (O) R¹⁷Or C (O) NH₂Is. In another embodiment of formula (I), Y¹Is NO₂Is. In another embodiment of formula (I), Y¹Is Cl. In another embodiment of formula (I), B¹Is NHR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H and Y¹Is NO₂Is. In another embodiment of formula (I), B¹Is OR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H and Y¹Is Cl.

In one embodiment of equation (I), R¹Is R², R³, R⁴Or R⁵Is. In another embodiment of formula (I), R¹Is R²And R²Is phenyl.

In one embodiment of equation (I), R¹Is R³And R³Is heteroaryl. In another embodiment of formula (I), R³Is triazolyl.

In one embodiment of equation (I), R¹Is R⁴Is. In another embodiment of formula (I), R¹Is R⁴And R⁴Is cycloalkyl. In another embodiment of formula (I), R¹Is R⁴And R⁴Is cyclohexyl. In another embodiment of formula (I), R¹Is R⁴And R⁴Is a heterocycloalkyl. In another embodiment of formula (I), R¹Is R⁴And R⁴Is 8-azabicyclo [3.2.1] octane, azetidinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl or tetrahydrothiophenyl. In another embodiment of formula (I), R¹Is R⁴And R⁴Is a heterocycloalkenyl. In another embodiment of formula (I), R¹Is R⁴And R⁴Is tetrahydropyridazinyl.

In one embodiment of equation (I), R¹Is R⁵Is. In another embodiment of formula (I), R¹Is R⁵And R⁵Is alkyl or alkynyl. In another embodiment of formula (I), R¹Is R⁵And R⁵Is an unsubstituted alkyl. In another embodiment of formula (I), R¹Is R⁵And R⁵Is one, two or three independently selected R⁶, R⁷, OR⁷, SR⁷, SO₂R⁷, N (R)⁷)₂, OH, CN, CF₃, F, Cl, Br or I alkyl substituted with substituents. In another embodiment of formula (I), R¹Is R⁵And R⁵Is R⁷It is an alkyl substituted with.

In one embodiment of equation (I), R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is. In another embodiment of formula (I), R⁷Is R⁸And R⁸Is not condensed or R^8APhenyl that is condensed with R^8AIs a heterocycloalkane. In another embodiment of formula (I), R⁷Is R⁸And R⁸Is uncondensed phenyl. In another embodiment of formula (I), R⁷Is R⁹And R⁹Is heteroaryl. In another embodiment of formula (I), R⁷Is R⁹And R⁹Furanyl, imidazolyl, isothiazolyl, isooxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl or 1, 2,3-Triazolyl. In another embodiment of formula (I), R⁷Is R⁹And R⁹Are pyridinyl, thiazolyl, imidazolyl and 1,2,3-triazolyl. In another embodiment of formula (I), R⁷Is R¹⁰And R¹⁰Is C₃-C₁₀-Cycloalkyl. In another embodiment of formula (I), R⁷Is R¹⁰And R¹⁰Is C₆Or C₁₀-Cycloalkyl. In another embodiment of formula (I), R⁷Is R¹⁰And R¹⁰Is cyclohexyl or adamantanyl. In another embodiment of formula (I), R⁷Is R¹⁰And R¹⁰Morphorinyl, piperazinyl, piperidinyl, tetrahydro-2H-pyranyl, 1,2-dihydropyridinyl, pyranyl, pyridin-1 (H) -yl, pyrrolidinyl, oxetanyl, thiomorpholinyl, imidazolidinyl, tetrahydrothiophenyl, dioxolanyl, tetrahydrothio It is pyranyl, dioxanyl or tetrahydrofuranyl. In another embodiment of formula (I), R⁷Is R¹⁰And R¹⁰Are morpholinyl, piperazinyl, piperidinyl, tetrahydro-2H-pyranyl, 1,2-dihydropyridinyl, pyrrolidinyl, oxetanyl, thiomorpholinyl, imidazolidinyl, tetrahydrothiophenyl, dioxolanyl, tetrahydrothiopyranyl, dioxanyl or tetrahydrofuranyl. In another embodiment of formula (I), R⁷Is R¹¹And R¹¹Is an alkyl that has not been substituted or has been substituted. In another embodiment of formula (I), R⁷Is R¹¹And R¹¹Is an unsubstituted alkyl. In another embodiment of formula (I), R⁷Is R¹¹And R¹¹Is the substituted alkyl. In another embodiment of formula (I), R⁷Is R¹¹And R¹¹Is one, two or three independently selected ORs¹², F, Cl, Br or I alkyl substituted with substituents. In another embodiment of formula (I), R⁷Is R¹¹And R¹¹Is OR¹²Alkyl substituted with, R¹²Is R¹⁶And R¹⁶Is alkyl.

In one embodiment of equation (I), R¹⁷Is R¹⁹Or R²¹Is. In another embodiment of formula (I), R¹⁷Is R¹⁹And R¹⁹Is heteroaryl. In another embodiment of formula (I), R¹⁷Is R¹⁹And R¹⁹Is thiazolyl. In another embodiment of formula (I), R¹⁷Is R²¹And R²¹Is an alkynyl. In another embodiment of formula (I), R¹⁷Is R²¹And R²¹Is ethynyl.

Yet another embodiment 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; Benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N-((4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) benzamide; 2- (benzyloxy) -4-(4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4- () (Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (2-phenylethoxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (phenylthio) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenylthio) -N-((4-((Tetrahydro-2H-) Pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) -3-Nitrophenyl) Sulfonyl) -2- (Phenylthio) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (phenylsulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (phenylsulfinyl) benzamide; 2-Benzyl-4- (4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-) 2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 2-Benzyl-4- (4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((Tetrahydro-2H-pyran-)- 4-Ilmethyl) amino) phenyl) sulfonyl) benzamide; 2-Benzyl-4- (4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-yl) Ilpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (2-phenylethyl) benzamide; 2- (benzylamino) -4-(4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4- ((3-nitro-4- () (Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 2-anilino-4-(4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-) 2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 2-anilino-4-(4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-methoxy-N-((3-nitro-4-((tetrahydro-) 2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indazole-5-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indazole-5-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) -2- (1,2,3,4-tetrahydroquinoline-6-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((1-1-yl) Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) -2- (1,2,3,4-tetrahydroquinoline-6-yloxy) benzamide; 4- (4-((4'-Chloro-4- (pyrrolidin-1-ylmethyl) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4) -Iloxy) -N-((3-Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-pyrrolidin-1-ylethyl) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((1-1-yl) Cyclopentyl piperidine-4-yl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) -3-isobutylpiperazin-1-yl) -N-((3-nitro-4-((tetrahydro-) 2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4- (2,4-dioxo-3-azabicyclo) (3.2) .0) hepta-3-yl) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4- (4-methyl-6-oxo-1,4) , 5,6-tetrahydropyridazine-3-yl) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4- (3,3-dimethyl-2-oxoazetidine-1) -Il) Phenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4- (4-nitro-2H-1,2,3) -Triazole-2-yl) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N-((2- (2-piperidine-1-ylethoxy) ) Phenyl) Sulfonyl) Benzamide; 4-(4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-((((1-ethylpyrrolidine-2-yl) yl) ) Methyl) amino) carbonyl) -4-methoxyphenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1-naphthyloxy) -N-((3-nitro-4) -((Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (2-naphthyloxy) -N-((3-nitro-4) -((Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) -3-Nitrophenyl) Sulfonyl) -2- (2-naphthyloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (2-naphthyloxy) -N-((4-((Tetrahydro) -2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (quinoline-7-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (quinoline-6-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (isoquinoline-5-yloxy) -N-((3-nitro-) 4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (isoquinoline-5-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (quinoline-6-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (1H-indole-6-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (isoquinoline-7-yloxy) -N-((4-((( 3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (isoquinoline-7-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4-4-yloxy) ((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4-4-yl) ((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-methoxyphenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-methylphenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4-4-yl) ((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4-4-yloxy) ((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-((Trifluoromethyl) sulfonyl) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4-4-yloxy) ((3-Morpholine-4-ylpropyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; N-((3-((Chloro (difluoro) methyl) sulfonyl) -4-((3- (dimethylamino) propyl) amino) phenyl) sulfonyl) -4- (4-((2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 2- (1H-Indol-4-yloxy) -4-(4-((2- (4-Methoxyphenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1- Il) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4,4-Dimethyl-2- (4- (trifluoromethyl) phenyl) cyclohexa-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4,4-Dimethyl-2- (4- (trifluoromethoxy) phenyl) cyclohexa-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4,4-Dimethyl-2- (3- (trifluoromethyl) phenyl) cyclohexa-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (3-Fluorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Fluorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; N-((3-((Chloro (difluoro) methyl) sulfonyl) -4-((1-methylpiperidin-4-yl) amino) phenyl) sulfonyl) -4- ((2- (4-chlorophenyl) ) -4,4-Dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (phenoxymethyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) Phenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (pyridin-3-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (pyridin-3-yloxy) -N-((4-((( Tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-(((1R) -3- (dimethylamino)) -1-((Phenylthio) methyl) propyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -2- (pyridin-4-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) -3-Nitrophenyl) Sulfonyl) -2- (Pyridine-3-yloxy) Benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) -3-Nitrophenyl) Sulfonyl) -2- (Pyridine-4-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((2- (4-methylpiperazin-1-) Il) ethyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (4-methylpiperazin-1-) Il) propyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl)) (methyl) ) Amino) -3-nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4-(4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-(((1-methylpiperidine-4-yl)) Methyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4-(4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((1-methylpiperidine-4-yl) amino) ) -3-Nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-cyano-4-((3- (dimethylamino)) Propyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((3-pyrrolidin-1-yl) methyl) Ilpropyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3- (Trifluoromethyl) Phenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (isopropyl (methyl) amino) propyl) ) Amino) -3-nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4- (3- (dimethylamino) propoxy) -3- Nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((2- (4-Methylpiperazin-1-yl) ethyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((3- (4-Methylpiperazin-1-yl) propyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((3-Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((3- (4-Methylpiperazin-1-yl) propyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4- (3- (3- ( Dimethylamino) propoxy) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((2- (4-Methylpiperazin-1-yl) ethyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((3-Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((((1-Methylpiperidin-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((((1-Methylpiperidin-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4- (3- (3- ( Dimethylamino) propoxy) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4- (4-Methylpiperazin-1-yl) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((3-Nitro-4-((1- (2,2,2-trifluoroethyl) piperidine-4-yl) amino) phenyl) sulfonyl) benzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-(((4) -(Dimethylamino) -1-methylpiperidin-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (2,3-dihydro-1,4-benzodioxin-5- Iloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 5- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) phenyl) sulfonyl) -1,1'-biphenyl-2-carboxamide; 5- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-Nitrophenyl) Sulfonyl) -1,1'-biphenyl-2-carboxamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4-(4-((4'-Chloro-4- (3-piperidin-1-ylpropoxy) -1,1'-biphenyl-2-yl) methyl) piperazin-1-yl) -N-((3) -Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4-(4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-4- (3- (dimethylamino) propoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N- ((4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (3-piperidin-1-ylpropoxy) -1,1'-biphenyl-2-yl) methyl) piperazin-1-yl) -2-phenoxy-N -((4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (3- (dimethylamino) propoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N- ((4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N- ((4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N- ((4-((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-4-yl) ((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-) Nitro-4-((1- (2,2,2-trifluoroethyl) piperidine-4-yl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4-(4-((4'-Chloro-4- (2-pyrrolidine-1-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-4- (2- (diisopropylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (2,3-dihydro-1H-indole-5-yloxy)- N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohepta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3) -Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cycloocta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3) -Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclopenta-1-ene-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3) -Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclopent-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((4-((1-methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cycloocta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohepta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclopenta-1-ene-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((4-((1-methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohepta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((1-1-yl) Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((2- (dimethylamino) ethyl) amino)) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3-morpholine-4-ylpropyl) amino) ) -3-Nitrophenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((4- (dimethylamino) butyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((1- (phenylsulfonyl)) Piperidine-4-yl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((1- (quinoline-8) -yl) -Ilsulfonyl) piperidine-4-yl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N-((4-((1- (phenylsulfonyl)) Piperidine-4-yl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N-((4-((1- (quinoline-8) -Ilsulfonyl) piperidine-4-yl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-(((1S) -3- (dimethylamino)) -1-thien-2-ylpropyl) amino) -3-nitrophenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((thien-2-ylmethyl)) Amino) Phenyl) Sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxy-N-((4-((Tetrahydro-2H-pyran-) 4-Ilmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((2- (1H-1) -yl) , 2,3-Triazole-1-yl) ethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-Nitro-4-((2- (2H-1) -yl) , 2,3-Triazole-2-yl) ethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (2-naphthyloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((2- (2-oxo) Pyridine-1 (2H) -yl) ethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-Nitro-4-((2- (Pyridine-2) -yl) -Iloxy) ethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((3-nitro-4-((2-Pyridine-4-yl) Ilethyl) amino) phenyl) sulfonyl) -2-phenoxybenzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3- (trifluoromethyl) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((3-cyano-4-yl) ((3- (Dimethylamino) propyl) amino) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((3-Nitro-4-((1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((4-Methylpiperazin-1-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4- (1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((( 3-Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; N-((4-((((4-Aminotetrahydro-2H-pyran-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) -4- (4-((2- (4-chlorophenyl)-) 4,4-Dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(3S) -tetrahydro-2H-pyran-3-ylmethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(3R) -tetrahydro-2H-pyran-3-ylmethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[4- (4-Chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxy-1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -3-fluoro-2- (1H-indole) -5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -3-fluoro-2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxy-1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; N-[(4-{[(3S, 4R) -1-benzyl-3-hydroxypiperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4- (4-) Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; N-[(4-{[(4-Aminotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl)- 4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(4-{[1- (2-Methoxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2-Hydroxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(4-{[1- (2-Methoxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Hydroxypropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide; 4- [4-({4'-Chloro-3- [3- (dimethylamino) propyl] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Hydroxypropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-5-Iloxy) Benzamide; 4- {4-[(4'-Chloro-4-morpholine-4-yl-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Diethylamino) cyclohexyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Dimethylamino) Cyclohexyl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Diethylamino) cyclohexyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[4 -(Dimethylamino) tetrahydro-2H-pyran-4-yl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; N-({4-[(2-aminocyclohexyl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-ene -1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- [4-({4'-Chloro-4- [3- (dimethylamino) propa-1-inyl] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole-4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(3-Nitro-4-{[1- (4,4,4-trifluorobutyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[2-yl] (4-Hydroxy-1-methylpiperidin-4-yl) ethyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-2-yl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[4'-Chloro-4- (2-hydroxyethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (Cyclopropylmethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (4,4,4-trifluorobutyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[4'-Chloro-4- (2-hydroxyethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[3- (3-oxopiperazin-1-yl) propyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(3-Nitro-4-{[3- (3-oxopiperazin-1-yl) propyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2,3-dihydro-1H-indene-2-yl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2,3-dihydro-1H-indene-2-yl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1-Morpholine-4-ylcyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-2-ylmethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-4-ylmethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[4 -(Hydroxymethyl) tetrahydro-2H-pyran-4-yl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (2-Hydroxyethyl) piperazine-1-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(3S) -1-methylpyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Fluoropropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-5-Iloxy) Benzamide; 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; N-[(4-{[(4-Aminotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- [4-{[2- (4-chlorophenyl)- 4,4-Dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) -Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Hydroxymethyl) Tetrahydro-2H-pyran-4-yl] amino} -3-nitrophenyl) Sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Hydroxymethyl) Tetrahydro-2H-pyran-4-yl] amino} -3-nitrophenyl) Sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Hydroxy-1-tetrahydro-2H-pyran-4-ylethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4-({1- [2- (1H-pyrazol-1-yl) ethyl] piperidine-4-yl} amino) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Methylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Methylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-chlorophenyl) -5-morpholin-4-ylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; N-[(4-{[(1-Aminocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa- 1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxopyrrolidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-5-yloxy) -N-({{ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- {4-[(1R) -1- (4'-chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- {4-[(1S) -1- (4'-chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(3-morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(cyclohexylmethylmethyl) ) Amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Morpholine-4-ylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-3-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohexe -1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Morpholine-4-ylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylamino) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(3-Methyloxetane-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methoxycyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1,1-dioxide thiomorpholine-4-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxopiperidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxoimidazolidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(2-Pyridine-4-ylethyl) Amino] Phenyl} Sulfonyl) Benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-Morpholine-4-yl-3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (4-Methoxypiperidine-1-yl) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-pyrrolidine-1-ylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (3-oxopiperazine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({4-[(4-methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-dioxide tetrahydrothien-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 1-Dioxide tetrahydrothien-3-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3- (trifluoromethyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [2- ({4- [2- ( 1,3-Dioxolane-2-yl) ethyl] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(3-Nitro-4-{[2- (3-oxopiperazine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methyl-5-oxopyrrolidine-3-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methyl-6-oxopiperidine-3-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (piperidine-1-ylamino) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (piperidine-1-ylamino) phenyl] sulfonyl} benzamide; 4- (4-{[4- (4-Chlorophenyl) -1-methyl-1H-pyrazole-5-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N- ({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Methyloxetane-3-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(1-oxide tetrahydro-2H-thiopyran-4-yl) methyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1,3-thiazole-5-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(2-tetrahydro-2H-pyran-4-ylethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(3-Nitro-4-{[2- (trifluoromethoxy) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(4-{[2- (2-Methoxyethoxy) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[3- (Methylsulfonyl) propyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1,1-dioxide thiomorpholine-4-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (2-tetrahydro-2H-pyran-4-ylethyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4- (1,4) -Dioxane-2-ylmethoxy) -3-nitrophenyl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(4-{[2- (2-Methoxyethoxy) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 1-Dioxide tetrahydrothien-3-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (trifluoromethoxy) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-Dioxide tetrahydro-2H-thiopyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(2,,, 2-Difluoroethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(4,,, 4-Difluorocyclohexyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[4- (4-Chlorophenyl) -1-isopropyl-6-oxo-1,6-dihydropyridine-3-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(Tetrahydro-2H-pyran-4-ylmethyl) amino] carbonyl} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (2-tetrahydro-2H-pyran-4-ylethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4- [3- (Methylsulfonyl) propoxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Methoxypropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Methoxypropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Cyanoethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Cyanoethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[(( 3R) -4-hydroxy-1-adamantyl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[Cis -4-Hydroxy-1-adamantyl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-({3-Nitro-4-[(3,3,3-trifluoropropyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-({3-Nitro-4-[(3,3,3-trifluoropropyl) amino] phenyl} sulfonyl) benzamide; N-({5-bromo-6-[(tetrahydro-2H-pyran-4-ylmethyl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-dioxide tetrahydrothien-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4- (Methylamino) -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; N-{[5-bromo-6- (tetrahydro-2H-pyran-4-ylmethoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[4- (4-Chlorophenyl) -6-isopropoxypyridine-3-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-({ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[6- (Tetrahydro-2H-pyran-4-ylmethoxy) -5- (1,3-thiazole-2-yl) pyridin-3-yl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(2-Methoxyethyl) amino] carbonyl} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide; N-({4-[(1-Acetylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(4-{[1- (Methylsulfonyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(1,1, 4-dioxane-2-ylmethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; N-({4-[(1-Acetylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[1- (Methylsulfonyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-{[3-nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-({3-Nitro-4-[(2,2,2-trifluoroethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-({3-Nitro-4-[(2,2,2-trifluoroethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-{[(Tetrahydro-2H-pyran-4-ylmethyl) amino] carbonyl} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2R)) -1,4-dioxane-2-ylmethoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2S)) -1,4-dioxane-2-ylmethoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; N-({5-bromo-6-[(tetrahydro-2H-pyran-4-ylmethyl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Morpholine-4-ylethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N- ({5-cyano-6-) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] pyridine-3-yl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) oxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[4- (4-Chlorophenyl) -1- (3-hydroxypropyl) -1,2,5,6-tetrahydropyridin-3-yl] methyl} piperazine-1-yl) -2- (1H-indol-4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; Benzyl4-({[4-({[4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl)) -2- (1H-indole-5-yloxy) benzoyl] amino} sulfonyl) -2-nitrophenyl] amino} methyl) piperidine-1-carboxylate; N-{[3- (aminocarbonyl) -4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexi Sa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1-Methyl-1H-imidazol-5-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Morpholine-4-ylsulfonyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(1,1, 1-Dioxide thiomorpholine-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; N-{[5-bromo-6- (tetrahydro-2H-pyran-4-ylmethoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[6-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -5- (1,3-thiazole-2-yl) pyridin-3-yl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-cyano-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-cyano-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3,,, 3-Dimethylbutyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1S) ) -1- (Hydroxymethyl) -3-methylbutyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(2R) -tetrahydrofuran-ylmethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1R) ) -1- (Hydroxymethyl) -2-methylpropyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methoxyphenyl) amino] -3-nitrophenyl} sulfonyl) benzamide; N-[(4-{[2- (1,3-benzodioxole-5-yl) ethyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl) ethyl] ) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[3- (2-oxopyrrolidine-1-yl) propyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Hydroxyphenyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; N-{[4-({2- [4- (aminosulfonyl) phenyl] ethyl} amino) -3-nitrophenyl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4 -Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1H-imidazol-1-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[(1S) -1-phenylethyl] amino} phenyl) sulfonyl] benzamide; N-({2-chloro-5-fluoro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[2- (2-Methoxyethoxy) ethyl] thio} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(4-{[2- (2-Methoxyethoxy) ethyl] thio} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Methylsulfonyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Methylsulfonyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(2,,, 2-Dimethyltetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Morpholine-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) oxy] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Morpholine-4-ylbut-2-inyl) oxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-ethynyl-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Morpholine-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3-3-yl] Hydroxy-4-methoxyphenyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (2,3-dihydro-1H) -Indole-4-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1-1-yl] Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (pyridin-3-ylamino) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(1-Tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) -2- (pyridin-3-ylamino) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(1-Tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) -2- (pyridin-3-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1,2,3,4-tetrahydroisoquinoline-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4) -Iloxy) -N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-([(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Fluorotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[6-[(4-4-yl) Fluorotetrahydro-2H-pyran-4-yl) methoxy] -5- (trifluoromethyl) pyridin-3-yl] sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Cyclopropylmorpholin-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) , 4-difluorocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide; N-[(5-Chloro-6-{[(4-fluorotetrahydro-2H-pyran-4-yl) methyl] amino} pyridin-3-yl) sulfonyl] -4- (4-{[2- (4) -Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; Trans-N-({5-chloro-6-[(4-Methoxycyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[4- (2,2-difluoroethyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N- ({5-fluoro-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-((4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; N-[(5-Chloro-6-{[1- (cyanomethyl) -4-fluoropiperidine-4-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4-{[2- (4-) Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydrofuran-3-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; Trans-N-({5-chloro-6-[(4-hydroxycyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-[(5-Chloro-6-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] oxy} pyridin-3-yl) sulfonyl] -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-[(5-chloro-6-{[(2S) -4- (N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridine- 3-Il) Sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-[(5-chloro-6-{[(2R) -4- (N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridine- 3-Il) Sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; N-[(5-chloro-6-{[(2S) -4-(N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-[(5-chloro-6-{[(2R) -4-(N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-([(3R) -1- (cyanomethyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-(((3R) -1- [2- (2-methoxyethoxy) ethyl] pyrrolidine-3-yl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-([(3R) -1- (N, N-dimethylglycyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[4- (cyanomethyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-[(4-{[(4-Cyclopropylmorpholine-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(3-nitro-4-{[(4-oxetane-3-ylmorpholine-2-yl) methyl] amino} phenyl) sulfonyl] benzamide; N-{[5-chloro-6-(((3R) -1- [2-fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} oxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide ; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({(3R) ) -1- [2-Fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-((4-[(1-1-yl] Cyclopropylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[(2R) -4- (N, N-dimethylglycyl) morpholin-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[(2S) -4- (N, N-dimethylglycyl) morpholin-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(tetrahydro-3-ylmethyl) amino] phenyl} sulfonyl) benzamide; Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({5-fluoro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4 -(4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; N-{[5-chloro-6-({(3R) -1- [2-fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} methoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide ; N-[(5-Chloro-6-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4) -Iloxy) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4- (1,4) -Dioxane-2-ylmethoxy) -3-nitrophenyl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4 -{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[(1,4-dioxane-2-ylmethyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(1-cyclopropylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-({4-[(4-morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(4-methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-[(4-{[(1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[({(2R) -4- [2- (2-methoxyethoxy) ethyl] morpholine-2-yl} methyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(4,4-difluorocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; N-[(4-{[(4-Acetylmorpholine-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-benzimidazol-4-yloxy) -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[4- (methylsulfonyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[6-({4- Fluoro-1- [2-fluoro-1- (fluoromethyl) ethyl] piperidine-4-yl} methoxy) -5- (trifluoromethyl) pyridine-3-yl] sulfonyl} -2- (1H-indazole-4) -Iloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (2-tetra-2-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-[(4-{[(4-cyanocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(4,4-difluorocyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4 -Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[4- (4-chlorophenyl)) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Tetrahydro-2H-pyran-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; N-({3-Nitro-4-[(Tetrahydro-2H-Pyran-4-ylmethyl) Amino] Phenyl} Sulfonyl) -2-Phenoxy-4- (4-{(3-Phenylpropanoid) [1S, 2S , 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide; N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropanoid)] [(1S, 2S) , 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide; N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropyl)] [(1S, 2S) , 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide; N-({4-[(3-morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropyl)] [(1S, 2S,, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide; 4- [4-(2-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} benzyl) piperazine-1-yl] -N-({4 -[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide; 4- [4-(2-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} benzyl) piperazin-1-yl] -N-({3 -Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -2-phenoxy-N-({4- [(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -2-phenoxy-N-({4- [(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) benzamide; 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -N-({4- [(3-morpholine-4-ylpropyl) amino ] -3-Nitrophenyl} Sulfonyl) -2-phenoxybenzamide; 4- (4- {2-[(4R, 7S) -2,3,3a, 4,7,7a-hexahydro-1H-4,7-methanoinden-5-yl] benzyl} piperazine-1-yl)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- [4- (2- {5-[(1R, 5S) -8-azabicyclo [3.2.1] octa-8-ylmethyl] thien-2-yl} benzyl) piperazine-1-yl] -N-( {3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- [4- (2- {5-[(1R, 5S) -8-azabicyclo [3.2.1] octa-8-ylmethyl] thien-2-yl} benzylidene) piperidine-1-yl] -N-( {3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide; 4- [4- (3- {5-[(1R, 5S) -8-azabicyclo [3.2.1] octa-8-ylmethyl] thien-2-yl} benzyl) piperazine-1-yl] -N-( {3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide With respect to compounds having the formula I and the therapeutically acceptable salts, prodrugs, prodrug salts and metabolites.

In another aspect, the invention is a compound of formula (II).

<chemistry num="10"><img id="000011" he="90" wi="158" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(In the formula, A¹, B¹, D¹, E¹, Y¹, R³⁰And R³⁷Is as described herein for equation (I), where n is 0, 1, 2 or 3; this is R.²⁶Explains the number of substituents above, R¹⁰⁰Is R²⁶The above substituents are as described. ) Also provided are therapeutically acceptable salts thereof, prodrugs, prodrug salts and metabolites.

In one embodiment of equation (II), A¹Is N. In another embodiment of formula (II), A¹Is C (A)²). In another embodiment of formula (II), A¹Is C (A)²) And A²Is H.

In one embodiment of equation (II), B¹Is R¹, OR¹, SR¹, SO₂R¹, NHR¹, N (R)¹)₂Or C (O) NHR¹Is. In another embodiment of equation (II), B¹Is NHR¹Is. In another embodiment of equation (II), B¹Is NHR¹And A¹Is C (A)²) And A²Is H. In another embodiment of formula (II), B¹Is OR¹Is. In another embodiment of equation (II), B¹Is OR¹And A¹Is C (A)²) And A²Is H.

In one embodiment of equation (II), D¹And E¹Is H. In another embodiment of formula (II), B¹Is NHR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H. In another embodiment of formula (II), B¹Is OR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H.

In one embodiment of equation (II), Y¹Is H, CN, NO₂, F, Cl, Br, I, CF₃, R¹⁷, NHC (O) R¹⁷Or C (O) NH₂Is. In another embodiment of equation (II), Y¹Is NO₂Is. In another embodiment of equation (II), B¹Is NHR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H and Y¹Is NO₂Is. In another embodiment of equation (II), Y¹Is Cl. In another embodiment of equation (II), B¹Is OR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H and Y¹Is Cl.

In one embodiment of equation (II), R¹Is R², R³, R⁴Or R⁵Is. In another embodiment of equation (II), R¹Is R²And R²Is phenyl.

In one embodiment of equation (II), R¹Is R³And R³Is heteroaryl. In another embodiment of equation (II), R³Is triazolyl.

In one embodiment of equation (II), R¹Is R⁴Is. In another embodiment of equation (II), R¹Is R⁴And R⁴Is cycloalkyl. In another embodiment of equation (II), R¹Is R⁴And R⁴Is cyclohexyl. In another embodiment of equation (II), R¹Is R⁴And R⁴Is a heterocycloalkyl. In another embodiment of equation (II), R¹Is R⁴And R⁴Is 8-azabicyclo [3.2.1] octane, azetidinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl or tetrahydrothiophenyl. In another embodiment of equation (II), R¹Is R⁴And R⁴Is a heterocycloalkenyl. In another embodiment of equation (II), R¹Is R⁴And R⁴Is tetrahydropyridazinyl.

In one embodiment of equation (II), R¹Is R⁵Is. In another embodiment of equation (II), R¹Is R⁵And R⁵Is alkyl or alkynyl. In another embodiment of equation (II), R¹Is R⁵And R⁵Is an unsubstituted alkyl. In another embodiment of equation (II), R¹Is R⁵And R⁵Is one, two or three independently selected R⁶, R⁷, OR⁷, SR⁷, SO₂R⁷, N (R)⁷)₂, OH, CN, CF₃, F, Cl, Br or I alkyl substituted with substituents. In another embodiment of equation (II), R¹Is R⁵And R⁵Is R⁷It is an alkyl substituted with.

In one embodiment of equation (II), R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is. In another embodiment of equation (II), R⁷Is R⁸And R⁸Is not condensed or R^8APhenyl that is condensed with R^8AIs a heterocycloalkane. In another embodiment of equation (II), R⁷Is R⁸And R⁸Is uncondensed phenyl. In another embodiment of equation (II), R⁷Is R⁹And R⁹Is heteroaryl. In another embodiment of equation (II), R⁷Is R⁹And R⁹Furanyl, imidazolyl, isothiazolyl, isooxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinel 2,3-Triazolyl. In another embodiment of equation (II), R⁷Is R⁹And R⁹Are pyridinyl, thiazolyl, imidazolyl and 1,2,3-triazolyl. In another embodiment of equation (II), R⁷Is R¹⁰And R¹⁰Is C₃-C₁₀-Cycloalkyl. In another embodiment of equation (II), R⁷Is R¹⁰And R¹⁰Is C₆Or C₁₀-Cycloalkyl. In another embodiment of equation (II), R⁷Is R¹⁰And R¹⁰Is cyclohexyl or adamantanyl. In another embodiment of equation (II), R⁷Is R¹⁰And R¹⁰Morphorinyl, piperazinyl, piperidinyl, tetrahydro-2H-pyranyl, 1,2-dihydropyridinyl, pyranyl, pyridin-1 (H) -yl, pyrrolidinyl, oxetanyl, thiomorpholinyl, imidazolidinyl, tetrahydrothiophenyl, dioxolanyl, tetrahydrothio It is pyranyl, dioxanyl or tetrahydrofuranyl. In another embodiment of equation (II), R⁷Is R¹⁰And R¹⁰Are morpholinyl, piperazinyl, piperidinyl, tetrahydro-2H-pyranyl, 1,2-dihydropyridinyl, pyrrolidinyl, oxetanyl, thiomorpholinyl, imidazolidinyl, tetrahydrothiophenyl, dioxolanyl, tetrahydrothiopyranyl, dioxanyl or tetrahydrofuranyl. In another embodiment of equation (II), R⁷Is R¹¹And R¹¹Is an alkyl that has not been substituted or has been substituted. In another embodiment of equation (II), R⁷Is R¹¹And R¹¹Is an unsubstituted alkyl. In another embodiment of equation (II), R⁷Is R¹¹And R¹¹Is the substituted alkyl. In another embodiment of equation (II), R⁷Is R¹¹And R¹¹Is one, two or three independently selected OR¹², F, Cl, Br or I alkyl substituted with substituents. In another embodiment of equation (II), R⁷Is R¹¹And R¹¹Is OR¹²Alkyl substituted with, R¹²Is R¹⁶And R¹⁶Is alkyl.

In one embodiment of equation (II), R¹⁷Is R¹⁹Or R²¹Is. In another embodiment of equation (II), R¹⁷Is R¹⁹And R¹⁹Is heteroaryl. In another embodiment of equation (II), R¹⁷Is R¹⁹And R¹⁹Is thiazolyl. In another embodiment of equation (II), R¹⁷Is R²¹And R²¹Is an alkynil. In another embodiment of equation (II), R¹⁷Is R²¹And R²¹Is ethynyl.

Yet another embodiment 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((1-1-yl) Cyclopentyl piperidine-4-yl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4-4-yl) ((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4-4-yl) ((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-((Trifluoromethyl) sulfonyl) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; N-((3-((Chloro (difluoro) methyl) sulfonyl) -4-((3- (dimethylamino) propyl) amino) phenyl) sulfonyl) -4- (4-((2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; N-((3-((Chloro (difluoro) methyl) sulfonyl) -4-((1-methylpiperidin-4-yl) amino) phenyl) sulfonyl) -4- ((2- (4-chlorophenyl) ) -4,4-Dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((2- (4-Methylpiperazin-1-yl) ethyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((3- (4-Methylpiperazin-1-yl) propyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((3-Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4- (3- (3- ( Dimethylamino) propoxy) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((((1-Methylpiperidin-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4- (4-Methylpiperazin-1-yl) -3-nitrophenyl) sulfonyl) benzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-(((4) -(Dimethylamino) -1-methylpiperidin-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (2,3-dihydro-1H-indole-5-yloxy)- N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-((4-((1-methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohepta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4-(4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3- (trifluoromethyl) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((3-cyano-4-yl) ((3- (Dimethylamino) propyl) amino) phenyl) sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((3-Nitro-4-((1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-((4-((4-Methylpiperazin-1-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(3S) -tetrahydro-2H-pyran-3-ylmethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(3R) -tetrahydro-2H-pyran-3-ylmethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[4- (4-Chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxy-1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -3-fluoro-2- (1H-indole) -5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -3-fluoro-2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; N-[(4-{[(3S, 4R) -1-benzyl-3-hydroxypiperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4- (4-) Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; N-[(4-{[(4-Aminotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl)- 4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(4-{[1- (2-Methoxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -5-fluoro-2- (1H-indole) -5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -5-fluoro-2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Hydroxypropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-5-Iloxy) Benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Diethylamino) cyclohexyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[4 -(Dimethylamino) tetrahydro-2H-pyran-4-yl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; N-({4-[(2-aminocyclohexyl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-ene -1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[2-yl] (4-Hydroxy-1-methylpiperidin-4-yl) ethyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-2-yl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (Cyclopropylmethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (4,4,4-trifluorobutyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[3- (3-oxopiperazin-1-yl) propyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2,3-dihydro-1H-indene-2-yl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1-Morpholine-4-ylcyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-2-ylmethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-4-ylmethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[4 -(Hydroxymethyl) tetrahydro-2H-pyran-4-yl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (2-Hydroxyethyl) piperazine-1-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(3S) -1-methylpyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Fluoropropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-5-Iloxy) Benzamide; 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; N-[(4-{[(4-Aminotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- [4-{[2- (4-chlorophenyl)- 4,4-Dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) -Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Hydroxymethyl) Tetrahydro-2H-pyran-4-yl] amino} -3-nitrophenyl) Sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Hydroxy-1-tetrahydro-2H-pyran-4-ylethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4-({1- [2- (1H-pyrazol-1-yl) ethyl] piperidine-4-yl} amino) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Methylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-chlorophenyl) -5-morpholin-4-ylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; N-[(4-{[(1-Aminocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa- 1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxopyrrolidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-5-yloxy) -N-({{ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(3-morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(cyclohexylmethylmethyl) ) Amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Morpholine-4-ylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-3-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylamino) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(3-Methyloxetane-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methoxycyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1,1-dioxide thiomorpholine-4-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxopiperidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxoimidazolidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(2-Pyridine-4-ylethyl) Amino] Phenyl} Sulfonyl) Benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-Morpholine-4-yl-3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (4-Methoxypiperidine-1-yl) -3-nitrophenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -5-pyrrolidine-1-ylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (3-oxopiperazine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-dioxide tetrahydrothien-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 1-Dioxide tetrahydrothien-3-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3- (trifluoromethyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [2- ({4- [2- ( 1,3-Dioxolane-2-yl) ethyl] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methyl-5-oxopyrrolidine-3-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methyl-6-oxopiperidine-3-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (piperidine-1-ylamino) phenyl] sulfonyl} benzamide; 4- (4-{[4- (4-Chlorophenyl) -1-methyl-1H-pyrazole-5-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N- ({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Methyloxetane-3-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(1-oxide tetrahydro-2H-thiopyran-4-yl) methyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1,3-thiazole-5-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(2-tetrahydro-2H-pyran-4-ylethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (2-tetrahydro-2H-pyran-4-ylethyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4- (1,4) -Dioxane-2-ylmethoxy) -3-nitrophenyl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(4-{[2- (2-Methoxyethoxy) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (trifluoromethoxy) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(2,,, 2-Difluoroethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(4,,, 4-Difluorocyclohexyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[4- (4-Chlorophenyl) -1-isopropyl-6-oxo-1,6-dihydropyridine-3-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(Tetrahydro-2H-pyran-4-ylmethyl) amino] carbonyl} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Methoxypropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Cyanoethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[(( 3R) -4-hydroxy-1-adamantyl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[(( 3R) -4-hydroxy-1-adamantyl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-({3-Nitro-4-[(3,3,3-trifluoropropyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4- (Methylamino) -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; N-{[5-bromo-6- (tetrahydro-2H-pyran-4-ylmethoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[4- (4-Chlorophenyl) -6-isopropoxypyridine-3-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-({ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[6- (Tetrahydro-2H-pyran-4-ylmethoxy) -5- (1,3-thiazole-2-yl) pyridin-3-yl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(2-Methoxyethyl) amino] carbonyl} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide; N-({4-[(1-Acetylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(4-{[1- (Methylsulfonyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(1,1, 4-dioxane-2-ylmethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-{[3-nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-({3-Nitro-4-[(2,2,2-trifluoroethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-{[(Tetrahydro-2H-pyran-4-ylmethyl) amino] carbonyl} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2R)) -1,4-dioxane-2-ylmethoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2S)) -1,4-dioxane-2-ylmethoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; N-({5-bromo-6-[(tetrahydro-2H-pyran-4-ylmethyl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Morpholine-4-ylethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N- ({5-cyano-6-) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] pyridine-3-yl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) oxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide; Benzyl4-({[4-({[4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl)) -2- (1H-indole-5-yloxy) benzoyl] amino} sulfonyl) -2-nitrophenyl] amino} methyl) piperidine-1-carboxylate; N-{[3- (aminocarbonyl) -4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexi Sa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1-Methyl-1H-imidazol-5-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Morpholine-4-ylsulfonyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(1,1, 1-Dioxide thiomorpholine-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-cyano-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3,,, 3-Dimethylbutyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1S) ) -1- (Hydroxymethyl) -3-methylbutyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(2R) -tetrahydrofuran-ylmethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1R) ) -1- (Hydroxymethyl) -2-methylpropyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methoxyphenyl) amino] -3-nitrophenyl} sulfonyl) benzamide; N-[(4-{[2- (1,3-benzodioxole-5-yl) ethyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl) ethyl] ) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[3- (2-oxopyrrolidine-1-yl) propyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Hydroxyphenyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; N-{[4-({2- [4- (aminosulfonyl) phenyl] ethyl} amino) -3-nitrophenyl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4 -Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1H-imidazol-1-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[(1S) -1-phenylethyl] amino} phenyl) sulfonyl] benzamide; N-({2-chloro-5-fluoro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[2- (2-Methoxyethoxy) ethyl] thio} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Methylsulfonyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(2,,, 2-Dimethyltetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Morpholine-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-({3-Nitro-4-[(1-Tetrahydro-2H-pyran-4-ylpiperidin-4-yl) omega) shea] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Morpholine-4-ylbut-2-inyl) oxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3-3-yl] Hydroxy-4-methoxyphenyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide With respect to compounds having formula II and the therapeutically acceptable salts, prodrugs, prodrug salts and metabolites.

In another aspect, the invention is a compound of formula (III).

<chemistry num="11"><img id="000012" he="92" wi="159" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(In the formula, A¹, B¹, D¹, E¹, Y¹, R³⁰And R³⁷Is as described herein for equation (I), where n is 0, 1, 2 or 3; this is R.²⁶Explains the number of substituents above, R¹⁰⁰Is R²⁶The above substituents are as described. ) Also provided are therapeutically acceptable salts, prodrugs, prodrug salts and metabolites.

In one embodiment of formula (III), A¹Is N. In another embodiment of formula (III), A¹Is C (A)²). In another embodiment of formula (III), A¹Is C (A)²) And A²Is H.

In one embodiment of formula (III), B¹Is R¹, OR¹, SR¹, SO₂R¹, NHR¹, N (R)¹)₂Or C (O) NHR¹Is. In another embodiment of formula (III), B¹Is NHR¹Is. In another embodiment of formula (III), B¹Is NHR¹And A¹Is C (A)²) And A²Is H. In another embodiment of formula (III), B¹Is OR¹Is. In another embodiment of formula (III), B¹Is OR¹And A¹Is C (A)²) And A²Is H.

In one embodiment of formula (III), D¹And E¹Is H. In another embodiment of formula (III), B¹Is NHR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H. In another embodiment of formula (III), B¹Is OR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H.

In one embodiment of formula (III), Y¹Is H, CN, NO₂, F, Cl, Br, I, CF₃, R¹⁷, NHC (O) R¹⁷Or C (O) NH₂Is. In another embodiment of formula (III), Y¹Is NO₂Is. In another embodiment of formula (III), B¹Is NHR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H and Y¹Is NO₂Is. In another embodiment of formula (III), Y¹Is Cl. In another embodiment of formula (III), B¹Is OR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H and Y¹Is Cl.

In one embodiment of formula (III), R¹Is R², R³, R⁴Or R⁵Is. In another embodiment of formula (III), R¹Is R²And R²Is phenyl.

In one embodiment of formula (III), R¹Is R³And R³Is heteroaryl. In another embodiment of formula (III), R³Is triazolyl.

In one embodiment of formula (III), R¹Is R⁴Is. In another embodiment of formula (III), R¹Is R⁴And R⁴Is cycloalkyl. In another embodiment of formula (III), R¹Is R⁴And R⁴Is cyclohexyl. In another embodiment of formula (III), R¹Is R⁴And R⁴Is a heterocycloalkyl. In another embodiment of formula (III), R¹Is R⁴And R⁴Is 8-azabicyclo [3.2.1] octane, azetidinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl or tetrahydrothiophenyl. In another embodiment of formula (III), R¹Is R⁴And R⁴Is a heterocycloalkenyl. In another embodiment of formula (III), R¹Is R⁴And R⁴Is tetrahydropyridazinyl.

In one embodiment of formula (III), R¹Is R⁵Is. In another embodiment of formula (III), R¹Is R⁵And R⁵Is alkyl or alkynyl. In another embodiment of formula (III), R¹Is R⁵And R⁵Is an unsubstituted alkyl. In another embodiment of formula (III), R¹Is R⁵And R⁵Is one, two or three independently selected R⁶, R⁷, OR⁷, SR⁷, SO₂R⁷, N (R)⁷)₂, OH, CN, CF₃, F, Cl, Br or I alkyl substituted with substituents. In another embodiment of formula (III), R¹Is R⁵And R⁵Is R⁷It is an alkyl substituted with.

In one embodiment of formula (III), R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is. In another embodiment of formula (III), R⁷Is R⁸And R⁸Is not condensed or R^8APhenyl that is condensed with R^8AIs a heterocycloalkane. In another embodiment of formula (III), R⁷Is R⁸And R⁸Is uncondensed phenyl. In another embodiment of formula (III), R⁷Is R⁹And R⁹Is heteroaryl. In another embodiment of formula (III), R⁷Is R⁹And R⁹Furanyl, imidazolyl, isothiazolyl, isooxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinel 2,3-Triazolyl. In another embodiment of formula (III), R⁷Is R⁹And R⁹Are pyridinyl, thiazolyl, imidazolyl and 1,2,3-triazolyl. In another embodiment of formula (III), R⁷Is R¹⁰And R¹⁰Is C₃-C₁₀-Cycloalkyl. In another embodiment of formula (III), R⁷Is R¹⁰And R¹⁰Is C₆Or C₁₀-Cycloalkyl. In another embodiment of formula (III), R⁷Is R¹⁰And R¹⁰Is cyclohexyl or adamantanyl. In another embodiment of formula (III), R⁷Is R¹⁰And R¹⁰Morphorinyl, piperazinyl, piperidinyl, tetrahydro-2H-pyranyl, 1,2-dihydropyridinyl, pyranyl, pyridin-1 (H) -yl, pyrrolidinyl, oxetanyl, thiomorpholinyl, imidazolidinyl, tetrahydrothiophenyl, dioxolanyl, tetrahydrothio It is pyranyl, dioxanyl or tetrahydrofuranyl. In another embodiment of formula (III), R⁷Is R¹⁰And R¹⁰Are morpholinyl, piperazinyl, piperidinyl, tetrahydro-2H-pyranyl, 1,2-dihydropyridinyl, pyrrolidinyl, oxetanyl, thiomorpholinyl, imidazolidinyl, tetrahydrothiophenyl, dioxolanyl, tetrahydrothiopyranyl, dioxanyl or tetrahydrofuranyl. In another embodiment of formula (III), R⁷Is R¹¹And R¹¹Is an alkyl that has not been substituted or has been substituted. In another embodiment of formula (III), R⁷Is R¹¹And R¹¹Is an unsubstituted alkyl. In another embodiment of formula (III), R⁷Is R¹¹And R¹¹Is the substituted alkyl. In another embodiment of formula (III), R⁷Is R¹¹And R¹¹Is one, two or three independently selected OR¹², F, Cl, Br or I alkyl substituted with substituents. In another embodiment of formula (III), R⁷Is R¹¹And R¹¹Is OR¹²Alkyl substituted with, R¹²Is R¹⁶And R¹⁶Is alkyl.

In one embodiment of formula (III), R¹⁷Is R¹⁹Or R²¹Is. In another embodiment of formula (III), R¹⁷Is R¹⁹And R¹⁹Is heteroaryl. In another embodiment of formula (III), R¹⁷Is R¹⁹And R¹⁹Is thiazolyl. In another embodiment of formula (III), R¹⁷Is R²¹And R²¹Is an alkynyl. In another embodiment of formula (III), R¹⁷Is R²¹And R²¹Is ethynyl.

Yet another embodiment 4- (4-((4'-Chloro-4- (pyrrolidin-1-ylmethyl) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4) -Iloxy) -N-((3-Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-pyrrolidin-1-ylethyl) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3-3-yl) Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -N-((4-((3- (dimethylamino) propyl) amino)) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4-((3-3-yl) (Dimethylamino) propyl) amino) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4-4-yloxy) ((3-Morpholine-4-ylpropyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4-4-yloxy) ((Tetrahydro-2H-pyran-4-ylmethyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4-4-yloxy) ((3-Morpholine-4-ylpropyl) amino) -3-((trifluoromethyl) sulfonyl) phenyl) sulfonyl) benzamide; 2- (1H-Indol-4-yloxy) -4-(4-((2- (4-Methoxyphenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1- Il) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4,4-Dimethyl-2- (4- (trifluoromethyl) phenyl) cyclohexa-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4,4-Dimethyl-2- (4- (trifluoromethoxy) phenyl) cyclohexa-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4,4-Dimethyl-2- (3- (trifluoromethyl) phenyl) cyclohexa-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (3-Fluorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Fluorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-((3-nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((3- (4-Methylpiperazin-1-yl) propyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((2- (4-Methylpiperazin-1-yl) ethyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((3-Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((((1-Methylpiperidin-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -N-((4- (3- (3- ( Dimethylamino) propoxy) -3-nitrophenyl) sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((3-Nitro-4-((1- (2,2,2-trifluoroethyl) piperidine-4-yl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((4'-Chloro-3- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohepta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3) -Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cycloocta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3) -Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclopenta-1-ene-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((3) -Nitro-4-((3-pyrrolidin-1-ylpropyl) amino) phenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclopent-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-((4-((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-((4-((1-methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cycloocta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohepta-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclopenta-1-ene-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4-((2- (4-Chlorophenyl) cyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((4) -((1-Methylpiperidin-4-yl) amino) -3-nitrophenyl) sulfonyl) benzamide; 4- (4- (1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((( 3-Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide; N-((4-((((4-Aminotetrahydro-2H-pyran-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) -4- (4-((2- (4-chlorophenyl)-) 4,4-Dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxy-1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2-Hydroxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(4-{[1- (2-Methoxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Hydroxypropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide; 4- [4-({4'-Chloro-3- [3- (dimethylamino) propyl] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- {4-[(4'-Chloro-4-morpholine-4-yl-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Dimethylamino) Cyclohexyl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Diethylamino) cyclohexyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- [4-({4'-Chloro-4- [3- (dimethylamino) propa-1-inyl] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole-4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(3-Nitro-4-{[1- (4,4,4-trifluorobutyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[4'-Chloro-4- (2-hydroxyethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[4'-Chloro-4- (2-hydroxyethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(3-Nitro-4-{[3- (3-oxopiperazin-1-yl) propyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2,3-dihydro-1H-indene-2-yl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Hydroxymethyl) Tetrahydro-2H-pyran-4-yl] amino} -3-nitrophenyl) Sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Methylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- {4-[(1R) -1- (4'-chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- {4-[(1S) -1- (4'-chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Morpholine-4-ylamino) -3-nitrophenyl] sulfonyl} benzamide; 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({4-[(4-methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(3-Nitro-4-{[2- (3-oxopiperazine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (piperidine-1-ylamino) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(3-Nitro-4-{[2- (trifluoromethoxy) ethyl] amino} phenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(4-{[2- (2-Methoxyethoxy) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[3- (Methylsulfonyl) propyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1,1-dioxide thiomorpholine-4-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 1-Dioxide tetrahydrothien-3-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-Dioxide tetrahydro-2H-thiopyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (2-tetrahydro-2H-pyran-4-ylethoxy) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4- [3- (Methylsulfonyl) propoxy] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Methoxypropyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Cyanoethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-({3-Nitro-4-[(3,3,3-trifluoropropyl) amino] phenyl} sulfonyl) benzamide; N-({5-bromo-6-[(tetrahydro-2H-pyran-4-ylmethyl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-dioxide tetrahydrothien-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide; N-({4-[(1-Acetylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[1- (Methylsulfonyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-({3-Nitro-4-[(2,2,2-trifluoroethyl) amino] phenyl} sulfonyl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide; 4- (4-{[4- (4-Chlorophenyl) -1- (3-hydroxypropyl) -1,2,5,6-tetrahydropyridin-3-yl] methyl} piperazine-1-yl) -2- (1H-indol-4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; N-{[5-bromo-6- (tetrahydro-2H-pyran-4-ylmethoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[6-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -5- (1,3-thiazole-2-yl) pyridin-3-yl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-cyano-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(4-{[2- (2-Methoxyethoxy) ethyl] thio} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Methylsulfonyl) phenyl] sulfonyl} benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-ethynyl-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Morpholine-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide; N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide; With respect to compounds having formula (III) and therapeutically acceptable salts, prodrugs, prodrug salts and metabolites.

In another aspect, the invention is a compound of formula (IV).

<chemistry num="12"><img id="000013" he="75" wi="159" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(In the formula, A¹, B¹, D¹, E¹, Y¹, R³⁰And R³⁷Is as described herein for equation (I), where n is 0, 1, 2 or 3; this is R.²⁶Explains the number of substituents above, R¹⁰⁰Is R²⁶The above substituents are as described. ) Also provided are therapeutically acceptable salts, prodrugs, prodrug salts and metabolites.

In one embodiment of equation (IV), A¹Is N. In another embodiment of formula (IV), A¹Is C (A)²). In another embodiment of formula (IV), A¹Is C (A)²) And A²Is H.

In one embodiment of equation (IV), B¹Is R¹, OR¹, SR¹, SO₂R¹, NHR¹, N (R)¹)₂Or C (O) NHR¹Is. In another embodiment of formula (IV), B¹Is NHR¹Is. In another embodiment of formula (IV), B¹Is NHR¹And A¹Is C (A)²) And A²Is H. In another embodiment of formula (IV), B¹Is OR¹Is. In another embodiment of formula (IV), B¹Is OR¹And A¹Is C (A)²) And A²Is H.

In one embodiment of equation (IV), D¹And E¹Is H. In another embodiment of formula (IV), B¹Is NHR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H. In another embodiment of formula (IV), B¹Is OR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H.

In one embodiment of equation (IV), Y¹Is H, CN, NO₂, F, Cl, Br, I, CF₃, R¹⁷, NHC (O) R¹⁷Or C (O) NH₂Is. In another embodiment of formula (IV), Y¹Is NO₂Is. In another embodiment of formula (IV), B¹Is NHR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H and Y¹Is NO₂Is. In another embodiment of formula (IV), Y¹Is Cl. In another embodiment of formula (I), B¹Is OR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H and Y¹Is Cl.

In one embodiment of equation (IV), R¹Is R², R³, R⁴Or R⁵Is. In another embodiment of formula (IV), R¹Is R²And R²Is phenyl.

In one embodiment of equation (IV), R¹Is R³And R³Is heteroaryl. In another embodiment of formula (IV), R³Is triazolyl.

In one embodiment of equation (IV), R¹Is R⁴Is. In another embodiment of formula (IV), R¹Is R⁴And R⁴Is cycloalkyl. In another embodiment of formula (IV), R¹Is R⁴And R⁴Is cyclohexyl. In another embodiment of formula (IV), R¹Is R⁴And R⁴Is a heterocycloalkyl. In another embodiment of formula (IV), R¹Is R⁴And R⁴Is 8-azabicyclo [3.2.1] octane, azetidinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl or tetrahydrothiophenyl. In another embodiment of formula (IV), R¹Is R⁴And R⁴Is a heterocycloalkenyl. In another embodiment of formula (IV), R¹Is R⁴And R⁴Is tetrahydropyridazinyl.

In one embodiment of equation (IV), R¹Is R⁵Is. In another embodiment of formula (IV), R¹Is R⁵And R⁵Is alkyl or alkynyl. In another embodiment of formula (IV), R¹Is R⁵And R⁵Is an unsubstituted alkyl. In another embodiment of formula (IV), R¹Is R⁵And R⁵Is one, two or three independently selected R⁶, R⁷, OR⁷, SR⁷, SO₂R⁷, N (R)⁷)₂, OH, CN, CF₃, F, Cl, Br or I alkyl substituted with substituents. In another embodiment of formula (IV), R¹Is R⁵And R⁵Is R⁷It is an alkyl substituted with.

In one embodiment of equation (IV), R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is. In another embodiment of formula (IV), R⁷Is R⁸And R⁸Is not condensed or R^8APhenyl that is condensed with R^8AIs a heterocycloalkane. In another embodiment of formula (IV), R⁷Is R⁸And R⁸Is uncondensed phenyl. In another embodiment of formula (IV), R⁷Is R⁹And R⁹Is heteroaryl. In another embodiment of formula (IV), R⁷Is R⁹And R⁹Furanyl, imidazolyl, isothiazolyl, isooxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinel 2,3-Triazolyl. In another embodiment of formula (IV), R⁷Is R⁹And R⁹Are pyridinyl, thiazolyl, imidazolyl and 1,2,3-triazolyl. In another embodiment of formula (IV), R⁷Is R¹⁰And R¹⁰Is C₃-C₁₀-Cycloalkyl. In another embodiment of formula (IV), R⁷Is R¹⁰And R¹⁰Is C₆Or C₁₀-Cycloalkyl. In another embodiment of formula (IV), R⁷Is R¹⁰And R¹⁰Is cyclohexyl or adamantanyl. In another embodiment of formula (IV), R⁷Is R¹⁰And R¹⁰Morphorinyl, piperazinyl, piperidinyl, tetrahydro-2H-pyranyl, 1,2-dihydropyridinyl, pyranyl, pyridin-1 (H) -yl, pyrrolidinyl, oxetanyl, thiomorpholinyl, imidazolidinyl, tetrahydrothiophenyl, dioxolanyl, tetrahydrothio It is pyranyl, dioxanyl or tetrahydrofuranyl. In another embodiment of formula (IV), R⁷Is R¹⁰And R¹⁰Are morpholinyl, piperazinyl, piperidinyl, tetrahydro-2H-pyranyl, 1,2-dihydropyridinyl, pyrrolidinyl, oxetanyl, thiomorpholinyl, imidazolidinyl, tetrahydrothiophenyl, dioxolanyl, tetrahydrothiopyranyl, dioxanyl or tetrahydrofuranyl. In another embodiment of formula (IV), R⁷Is R¹¹And R¹¹Is an alkyl that has not been substituted or has been substituted. In another embodiment of formula (IV), R⁷Is R¹¹And R¹¹Is an unsubstituted alkyl. In another embodiment of formula (IV), R⁷Is R¹¹And R¹¹Is the substituted alkyl. In another embodiment of formula (IV), R⁷Is R¹¹And R¹¹Is one, two or three independently selected OR¹², F, Cl, Br or I alkyl substituted with substituents. In another embodiment of formula (IV), R⁷Is R¹¹And R¹¹Is OR¹²Alkyl substituted with, R¹²Is R¹⁶And R¹⁶Is alkyl.

In one embodiment of equation (IV), R¹⁷Is R¹⁹Or R²¹Is. In another embodiment of formula (IV), R¹⁷Is R¹⁹And R¹⁹Is heteroaryl. In another embodiment of formula (IV), R¹⁷Is R¹⁹And R¹⁹Is thiazolyl. In another embodiment of formula (IV), R¹⁷Is R²¹And R²¹Is an alkynyl. In another embodiment of formula (IV), R¹⁷Is R²¹And R²¹Is ethynyl.

Yet another embodiment 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-([(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[4- (2,2-difluoroethyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-[(5-chloro-6-{[(2S) -4- (N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridine- 3-Il) Sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-[(5-chloro-6-{[(2R) -4- (N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridine- 3-Il) Sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-([(3R) -1- (cyanomethyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({(3R) -1- [2- (2-methoxyethoxy) ethyl] pyrrolidine-3-yl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-([(3R) -1- (N, N-dimethylglycyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[4- (cyanomethyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-[(4-{[(4-Cyclopropylmorpholine-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(3-nitro-4-{[(4-oxetane-3-ylmorpholine-2-yl) methyl] amino} phenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[(2R) -4- (N, N-dimethylglycyl) morpholin-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[(2S) -4- (N, N-dimethylglycyl) morpholin-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(tetrahydro-3-ylmethyl) amino] phenyl} sulfonyl) benzamide; Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({5-fluoro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4 -(4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4 -{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[(1,4-dioxane-2-ylmethyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(1-cyclopropylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-({4-[(4-morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(4-methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-[(4-{[(1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[({(2R) -4- [2- (2-methoxyethoxy) ethyl] morpholine-2-yl} methyl) amino] -3-nitrophenyl} sulfonyl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(4,4-difluorocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; N-[(4-{[(4-Acetylmorpholine-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-benzimidazol-4-yloxy) -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-{[4-({[4- (methylsulfonyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide; Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-[(4-{[(4-cyanocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(4,4-difluorocyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide With respect to compounds having formula (IV) and therapeutically acceptable salts, prodrugs, prodrug salts and metabolites.

In another aspect, the invention is a compound of formula (V).

<chemistry num="13"><img id="000014" he="91" wi="155" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(In the formula, A¹, B¹, D¹, E¹, Y¹, R³⁰And R³⁷Is as described herein for equation (I), where n is 0, 1, 2 or 3; this is R.²⁶Explains the number of substituents above, R¹⁰⁰Is R²⁶The above substituents are as described. ) Also provided are therapeutically acceptable salts, prodrugs, prodrug salts and metabolites.

In one embodiment of equation (V), A¹Is N. In another embodiment of equation (V), A¹Is C (A)²). In another embodiment of equation (V), A¹Is C (A)²) And A²Is H.

In one embodiment of equation (V), B¹Is R¹, OR¹, SR¹, SO₂R¹, NHR¹, N (R)¹)₂Or C (O) NHR¹Is. In another embodiment of equation (V), B¹Is NHR¹Is. In another embodiment of equation (V), B¹Is NHR¹And A¹Is C (A)²) And A²Is H. In another embodiment of equation (V), B¹Is OR¹Is. In another embodiment of equation (V), B¹Is OR¹And A¹Is C (A)²) And A²Is H.

In one embodiment of equation (V), D¹And E¹Is H. In another embodiment of equation (V), B¹Is NHR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H. In another embodiment of equation (V), B¹Is OR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H.

In one embodiment of equation (V), Y¹Is H, CN, NO₂, F, Cl, Br, I, CF₃, R¹⁷, NHC (O) R¹⁷Or C (O) NH₂Is. In another embodiment of equation (V), Y¹Is NO₂Is. In another embodiment of equation (V), B¹Is NHR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H and Y¹Is NO₂Is. In another embodiment of equation (V), Y¹Is Cl. In another embodiment of formula (I), B¹Is OR¹And A¹Is C (A)²) And A²Is H and D¹And E¹Is H and Y¹Is Cl.

In one embodiment of equation (V), R¹Is R², R³, R⁴Or R⁵Is. In another embodiment of equation (V), R¹Is R²And R²Is phenyl.

In one embodiment of equation (V), R¹Is R³And R³Is heteroaryl. In another embodiment of equation (V), R³Is triazolyl.

In one embodiment of equation (V), R¹Is R⁴Is. In another embodiment of equation (V), R¹Is R⁴And R⁴Is cycloalkyl. In another embodiment of equation (V), R¹Is R⁴And R⁴Is cyclohexyl. In another embodiment of equation (V), R¹Is R⁴And R⁴Is a heterocycloalkyl. In another embodiment of equation (V), R¹Is R⁴And R⁴Is 8-azabicyclo [3.2.1] octane, azetidinyl, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl or tetrahydrothiophenyl. In another embodiment of equation (V), R¹Is R⁴And R⁴Is a heterocycloalkenyl. In another embodiment of equation (V), R¹Is R⁴And R⁴Is tetrahydropyridazinyl.

In one embodiment of equation (V), R¹Is R⁵Is. In another embodiment of equation (V), R¹Is R⁵And R⁵Is alkyl or alkynyl. In another embodiment of equation (V), R¹Is R⁵And R⁵Is an unsubstituted alkyl. In another embodiment of equation (V), R¹Is R⁵And R⁵Is one, two or three independently selected R⁶, R⁷, OR⁷, SR⁷, SO₂R⁷, N (R)⁷)₂, OH, CN, CF₃, F, Cl, B or I alkyl substituted with substituents. In another embodiment of equation (V), R¹Is R⁵And R⁵Is R⁷It is an alkyl substituted with.

In one embodiment of equation (V), R⁷Is R⁸, R⁹, R¹⁰Or R¹¹Is. In another embodiment of equation (V), R⁷Is R⁸And R⁸Is not condensed or R^8APhenyl that is condensed with R^8AIs a heterocycloalkane. In another embodiment of equation (V), R⁷Is R⁸And R⁸Is uncondensed phenyl. In another embodiment of equation (V), R⁷Is R⁹And R⁹Is heteroaryl. In another embodiment of equation (V), R⁷Is R⁹And R⁹Furanyl, imidazolyl, isothiazolyl, isooxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinel 2,3-Triazolyl. In another embodiment of equation (V), R⁷Is R⁹And R⁹Are pyridinyl, thiazolyl, imidazolyl and 1,2,3-triazolyl. In another embodiment of equation (V), R⁷Is R¹⁰And R¹⁰Is C₃-C_1O-Cycloalkyl. In another embodiment of equation (V), R⁷Is R¹⁰And R¹⁰Is C₆Or C₁₀-Cycloalkyl. In another embodiment of equation (V), R⁷Is R¹⁰And R¹⁰Is cyclohexyl or adamantanyl. In another embodiment of equation (V), R⁷Is R¹⁰And R¹⁰Morphorinyl, piperazinyl, piperidinyl, tetrahydro-2H-pyranyl, 1,2-dihydropyridinyl, pyranyl, pyridin-1 (H) -yl, pyrrolidinyl, oxetanyl, thiomorpholinyl, imidazolidinyl, tetrahydrothiophenyl, dioxolanyl, tetrahydrothio It is pyranyl, dioxanyl or tetrahydrofuranyl. In another embodiment of equation (V), R⁷Is R¹⁰And R¹⁰Are morpholinyl, piperazinyl, piperidinyl, tetrahydro-2H-pyranyl, 1,2-dihydropyridinyl, pyrrolidinyl, oxetanyl, thiomorpholinyl, imidazolidinyl, tetrahydrothiophenyl, dioxolanyl, tetrahydrothiopyranyl, dioxanyl or tetrahydrofuranyl. In another embodiment of equation (V), R⁷Is R¹¹And R¹¹Is an alkyl that has not been substituted or has been substituted. In another embodiment of equation (V), R⁷Is R¹¹And R¹¹Is an unsubstituted alkyl. In another embodiment of equation (V), R⁷Is R¹¹And R¹¹Is the substituted alkyl. In another embodiment of equation (V), R⁷Is R¹¹And R¹¹Is one, two or three independently selected OR¹², F, Cl, Br or I alkyl substituted with substituents. In another embodiment of equation (V), R⁷Is R¹¹And R¹¹Is OR¹²Alkyl substituted with, R¹²Is R¹⁶And R¹⁶Is alkyl.

In one embodiment of equation (V), R¹⁷Is R¹⁹Or R²¹Is. In another embodiment of equation (V), R¹⁷Is R¹⁹And R¹⁹Is heteroaryl. In another embodiment of equation (V), R¹⁷Is R¹⁹And R¹⁹Is thiazolyl. In another embodiment of equation (V), R¹⁷Is R²¹And R²¹Is an alkynyl. In another embodiment of equation (V), R¹⁷Is R²¹And R²¹Is ethynyl.

Yet another embodiment N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Fluorotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[6-[(4-4-yl) Fluorotetrahydro-2H-pyran-4-yl) methoxy] -5- (trifluoromethyl) pyridin-3-yl] sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Cyclopropylmorpholin-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) , 4-difluorocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide; N-[(5-Chloro-6-{[(4-fluorotetrahydro-2H-pyran-4-yl) methyl] amino} pyridin-3-yl) sulfonyl] -4- (4-{[2- (4) -Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; Trans-N-({5-chloro-6-[(4-Methoxycyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N- ({5-fluoro-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide; N-[(5-Chloro-6-{[1- (cyanomethyl) -4-fluoropiperidine-4-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4-{[2- (4-) Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydrofuran-3-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; Trans-N-({5-chloro-6-[(4-hydroxycyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-[(5-Chloro-6-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] oxy} pyridin-3-yl) sulfonyl] -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-[(5-chloro-6-{[(2S) -4-(N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-[(5-chloro-6-{[(2R) -4-(N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; N-{[5-chloro-6-({(3R) -1- [2-fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} oxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide ; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({(3R) ) -1- [2-Fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-((4-[(1-1-yl] Cyclopropylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide; N-{[5-chloro-6-({(3R) -1- [2-fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} methoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide ; N-[(5-Chloro-6-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4) -Iloxy) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4- (1,4) -Dioxane-2-ylmethoxy) -3-nitrophenyl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4 -{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[6-({4- Fluoro-1- [2-fluoro-1- (fluoromethyl) ethyl] piperidine-4-yl} methoxy) -5- (trifluoromethyl) pyridine-3-yl] sulfonyl} -2- (1H-indazole-4) -Iloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (2-tetra-2-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4 -Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[4- (4-chlorophenyl)) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide; 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Tetrahydro-2H-pyran-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide; With respect to compounds having the formula (V) and the therapeutically acceptable salts, prodrugs, prodrug salts and metabolites.

Pharmaceutical composition, combination therapy, method of treatment and administration Other embodiments include pharmaceutical compositions comprising compounds and excipients of formula (I).

Yet another embodiment is a method of treating mammalian cancer, comprising administering to it a therapeutically effective amount of a compound having formula (I).

Yet another embodiment is a method of treating a mammalian autoimmune disease, comprising administering to it a therapeutically effective amount of a compound having formula (I).

Yet another embodiment is a composition for treating a disease in which the anti-apoptotic Bcl-2 protein is expressed in the meantime, comprising an excipient and a therapeutically effective amount of a compound having formula (I). Regarding things.

Yet another embodiment is a method of treating a disease of a patient in which the anti-apoptotic Bcl-2 protein is expressed in the meantime, which comprises administering to the patient a therapeutically effective amount of a compound having formula (I). Regarding the method.

Yet other embodiments include bladder cancer, brain tumor, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia, follicular lymphoma, T cells. Alternatively, it is a composition for treating lymphocytic malignant disease derived from B cells, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer. With respect to compositions comprising excipients and compounds having a therapeutically effective amount of formula (I).

Yet other embodiments include bladder cancer, brain tumor, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia, follicular lymphoma, in patients. A method of treating T-cell or B-cell-derived lymphoid malignancies, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer. Top A method comprising administering to a patient an effective amount of a compound having formula (I).

Yet another embodiment is a composition for treating a disease in which the anti-apoptotic Bcl-2 protein is expressed in the meantime, with an excipient and a therapeutically effective amount of a compound having formula (I) and a therapeutically effective amount. Concerning a composition comprising an effective amount of one additional therapeutic agent or two or more additional therapeutic agents.

Yet another embodiment is a method of treating a disease of a patient in which the anti-apoptotic Bcl-2 protein is expressed in the meantime, the compound having a therapeutically effective amount of formula (I) and one of the therapeutically effective amounts. Concerning methods involving administration of an additional therapeutic agent or two or more additional therapeutic agents to a patient.

Yet other embodiments include bladder cancer, brain tumor, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia, follicular lymphoma, T cells. Or treat B-cell-derived lymphoid malignancies, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small cell lung cancer or spleen cancer A composition comprising an excipient and a therapeutically effective amount of a compound having formula (I) and a therapeutically effective amount of one additional therapeutic agent or two or more additional therapeutic agents. Regarding.

Yet other embodiments include bladder cancer, brain tumor, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia, follicular lymphoma, in patients. Lymphatic malignancies derived from T or B cells, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small cell lung cancer or spleen cancer A method comprising administering to a patient a therapeutically effective amount of a compound having formula (I) and a therapeutically effective amount of one additional therapeutic agent or two or more additional therapeutic agents. Regarding.

Metabolites of compounds with formula I made during in vitro or in vivo metabolism may also be useful in treating diseases associated with the anti-apoptotic Bcl-2 protein.

Certain precursor compounds that can be metabolized in vitro or in vivo to form compounds with formula I may also be useful in treating diseases associated with the expression of the anti-apoptotic Bcl-2 protein.

The compound having formula I can exist as an acid addition salt, a base addition salt or a zwitterion. The salt of the compound is prepared upon isolation or subsequent purification of the compound. The acid addition salt of a compound is the result of the reaction of the compound with an acid. For example, acetates, adipates, alginates, bicarbonates, citrates, asparaginates, benzoates, benzenesulfonates, bicarbonates, butyrates, succinates, camphors of compounds and their rodrugs. Sulfonate, digluconate, formate, fumarate, glycerophosphate, glutamate, hemisulfate, heptaneate, hexanate, hydrochloride, hydrobromide, hydroiodide, lactobion Acids, lactates, maleates, mesitylane sulfonates, methanesulfonates, naphthylene sulfonates, nicotinates, oxalates, pamonates, pectinates, persulfates, phosphates, Picphosphates, propionates, succinates, tartrates, thiocyanates, trichloroacetates, trifluoroacetates, para-toluenesulfonates and undecanoates are incorporated herein. The base addition salt of a compound is the result of the reaction of the compound with cationic hydroxides, carbonates or bicarbonates such as lithium, sodium, potassium, calcium and magnesium.

Compounds having formula I are administered, for example, buccal, intraocular, oral, osmotic, parenteral (intramuscular, intraperitoneal, intrasternal, intravenous, subcutaneous), transrectal, topical, transdermal or transvaginal. be able to.

The therapeutically effective amounts of a compound having formula I are the recipient of treatment, the disorder to be treated and its severity, the composition containing the compound, the duration of administration, the route of administration, the duration of treatment, the efficacy of the compound, its clearance rate and It depends on whether other drugs are co-administered. The amount of a compound of the invention having formula I used to make a composition that is administered daily to a patient in a single or divided dose is from about 0.03 to about 200 mg / kg body weight. The single dose composition comprises these amounts or a combination of divisors thereof.

Compounds with formula I can be administered with or without excipients. Excipients include, for example, encapsulating substances or auxiliaries, such as absorption enhancers, antioxidants, binders, buffers, coatings, colorants, excipients, disintegrants, emulsifiers, bulking agents, fillers, etc. Includes flavoring agents, moisturizers, lubricants, fragrances, preservatives, propellants, release agents, sterilizers, sweeteners, solubilizers, wetting agents and mixtures thereof.

Excipients for the preparation of compositions comprising compounds having formula I administered orally in solid dosage form include, for example, agar, alginic acid, aluminum hydroxide, benzyl alcohol, benzyl benzoate, 1,3-butylene glycol. , Carbomer, caster oil, cellulose, cellulose acetate, cocoa butter, corn starch, corn oil, cotton seed oil, crospovidone, diglyceride, ethanol, ethyl cellulose, ethyl laurate, ethyl oleate, fatty acid ester, gelatin, germ oil, glucose, glycerol, Lakkasei oil, hydroxypropyl methylcellulose, isopropanol, isotonic saline, lactose, magnesium hydroxide, magnesium stearate, malt, mannitol, monoglyceride, olive oil, peanut oil, potassium phosphate salt, potato starch, povidone, propylene glycol, Ringer solution , Saflower oil, sesame oil, sodium carboxylmethylcellulose, sodium phosphate salt, sodium lauryl sulfate, sodium sorbitol (sodium) sorbitol), soybean oil, stearic acid, stearyl fumarate, sucrose, surfactants, talc, tragacant, tetrahydrofurfuryl alcohol, triglycerides, water and mixtures thereof. Excipients for the preparation of compositions comprising compounds of the invention having formula I administered intraocularly or orally in liquid dosage form include, for example, 1,3-butylene glycol, caster oil, corn oil, and the like. Includes cotton seed oil, ethanol, sorbitan fatty acid esters, germ oil, lacquer oil, glycerol, isopropanol, olive oil, polyethylene glycol, propylene glycol, sesame oil, water and mixtures thereof. Excipients for the preparation of compositions containing compounds of the invention having formula I administered osmotic include, for example, chlorofluorohydrocarbons, ethanol, water and mixtures thereof. Excipients for the preparation of compositions comprising compounds of the invention having formula I administered parenterally include, for example, 1,3-butanediol, castor oil, corn oil, cottonseed oil, dextrose, germ oil. Includes, lacquer oil, liposomes, oleic acid, olive oil, peanut oil, ringer solution, safflower oil, sesame oil, soybean oil, USP or isotonic saline, water and mixtures thereof. Excipients for the preparation of compositions containing compounds of the invention with formula I administered transrectally or transvaginally include, for example, cocoa butter, polyethylene glycol, waxes and mixtures thereof.

Compounds having formula (I) include the following: alkylating agents, angiogenesis inhibitors, antibodies, metabolic antagonists, anti-thread fission agents, antiproliferative agents, antiviral agents, aurora kinase inhibitors, and others. Inhibitors of apoptosis promoters (eg, Bcl-xL, Bcl-w and Bfl-1), activators of cell death receptor pathways, Bcr-Abl kinase inhibitors, BiTE (bispecific T cell binding) antibodies, antibodies Drug complex, biological reaction modifier, cyclin-dependent kinase inhibitor, cell cycle inhibitor, cyclooxygenase-2 inhibitor, DVD, leukemia virus cancer gene homologous (ErbB2) receptor inhibitor, growth factor inhibitor, Heat shock protein (HSP) -90 inhibitor, histon deacetylase (HDAC) inhibitor, hormone therapy, immunopharmaceutical, inhibitor of apoptotic protein (IAP) inhibitor, insertion antibiotic, kinase inhibitor, kinesin inhibitor , Jak2 inhibitor, mammalian target inhibitor of rapamycin, mitogen-activated extracellular signal regulatory kinase inhibitor of microRNA, polyvalent binding protein, non-steroidal anti-inflammatory drug (NSAID), poly ADP (adenosine diphosphate) -Ribose polymerase (PARP) inhibitor, platinum-based chemotherapeutic agent, polo-like kinase (Plk) inhibitor, phosphoinositide-3 kinase (PI3K) inhibitor, proteosome inhibitor, purine analog, pyrimidine analog, receptor tyrosine kinase Inhibitors, ethinoid / deltoid plant alkaloids, small molecule inhibitory ribonucleic acid (siRNA), topoisomerase inhibitors, ubiquitin ligase inhibitors, etc. and useful in combination with one or more of these agents Conceivable.

BiTE antibodies are bispecific antibodies that direct T cells to attack cancer cells by binding to two cells at the same time. T cells then attack the target cancer cells. Examples of BiTE antibodies include adecatumumab (Micromet MT201), blinatumomab (Micromet MT103) and the like. Without being bound by theory, one of the mechanisms by which T cells induce apoptosis in target cancer cells is due to the exocytosis of cytotoxic granule components, including perforin and granzyme B. In this regard, Bcl-2 has been shown to attenuate the induction of apoptosis by both perforin and granzyme B. These data suggest that inhibition of Bcl-2 may enhance T cell-induced cytotoxic effects when targeting cancer cells (VR Sutton, DLVaux and JATrapani, J. et al.). of Immunology 1997, 158 (12), p. 5783).

SiRNA is a molecule that has an endogenous RNA base or a chemically modified nucleotide. This modification does not disrupt cell activity, but rather confers high stability and / or high cellular potency. Examples of chemical modifications include the group of phosphorothioates, 2'-deoxynucleotides, 2'-OCH.₃Included are contained ribonucleotides, 2'-F-ribonucleotides, 2'-methoxyethyl ribonucleotides, combinations thereof and the like. siRNAs can have different lengths (eg 10-200 bp) and structures (eg hairpins, single / double strands, bulges, nicks / gaps, mismatches) and are intracellularly processed and active genes. Provide silencing. Double-stranded siRNAs (dsRNAs) can have the same number of nucleotides on their respective strands (blunt ends) or asymmetric ends (overhangs). The 1-2 nucleotide overhang may be present on the sense and / or antisense strands and at the 5'-and / or 3'-ends of a given strand. For example, siRNAs that target Mcl-1 are ABT-263 (ie, N-(4-(((2- (4-chlorophenyl) -5,5-dimethyl-1)) in multiple tumor cell lines. -Cyclohex-1-en-1-yl) methyl) piperazin-1-yl) benzoyl) -4-(((1R) -3- (morpholin-4-yl) -1-((phenylsulfanyl) methyl) propyl) ) Amino) -3-((trifluoromethyl) sulfonyl) benzenesulfonamide) or ABT-737 (ie, N- (4- (4-((4'-chloro (1,1'-biphenyl))-2- Methyl) piperazin-1-yl) benzoyl) -4-(((1R) -3- (dimethylamino) -1-((phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide) activity (Tse et al., Cancer Research 2008, 68 (9), p. 3421 and references cited therein).

A multivalent binding protein is a binding protein that contains two or more antigen binding sites. Multivalent binding proteins are engineered to have three or more antigen binding sites, which are usually non-naturally occurring antibodies. The term "multispecific binding protein" means a binding protein that can bind to two or more related or unrelated targets. A bivariable domain (DVD) binding protein is a tetravalent or polyvalent binding protein binding protein that contains two or more antigen binding sites. These DVDs may be unispecific (ie, capable of binding one antigen) or multispecific (ie, capable of binding two or more antigens). A DVD-binding protein containing two heavy chain DVD polypeptides and two light chain DVD polypeptides is referred to as DVD Ig. DVD Each half of Ig contains one heavy chain DVD polypeptide, one light chain DVD polypeptide and two antigen binding sites. Each binding site contains one heavy chain variable domain and one light chain variable domain, with a total of 6 CDRs per antigen binding site involved in antigen binding. Multispecific DVDs include DVD binding proteins that bind DLL4 and VEGF, C-met and EFGR or ErbB3 and EGFR.

Alkylating agents include Altretamine, AMD-473, AP-5280, Apadicon, Bendamustine, Brostalicin, Busulfane, Carbocon, Carmustine (BCNU), Chlorambucil, CLORETAZINE® (Laromustine, VNP 40101M), Cyclophosphamide, Decarbazine, estramstine, hotemustine, gluphosphamide, iphosphamide, KW-2170, lomustine (CCNU), maphosphamide, melphalan, mitobronitol, mitractor, nimustine, nitrogen mustard N-oxide, lanimustine, temozolomide, thiotepa, TREANDA (registered trademark) (Bendamustine), Treosulfane, lofosfamide, etc. are included.

Angiogenesis inhibitors include endothelial-specific receptor tyrosine kinase (Tie-2) inhibitor, epidermal growth factor receptor (EGFR) inhibitor, insulin growth factor-2 receptor (IGFR-2) inhibitor, matrix metalloproteinase. Proteinase-2 (MMP-2) inhibitor, matrix metalloproteinase-9 (MMP-9) inhibitor, platelet-derived growth factor receptor (PDGFR) inhibitor, thrombospondin analog, vascular endothelial growth factor receptor tyrosine Includes kinase (VEGFR) inhibitors and the like.

Metabolic antagonists include ALIMTA® (pemetrexed disodium, LY231514, MTA), 5-azacitidine, XELODA® (capecitabine), carmofur, LEUSTAT® (cladribin), clofarabine, citarabine, citalabine. Okphosphert, citocin arabinoside, decitabine, deferroxamine, doxifluidine, eflornitin, EICAR (5-ethynyl-1-β-D-ribofuranosylimidazol-4-carboxamide), enocitabine, etonylcitidine, fludalabine, alone or in combination with leucovorin 5-Fluorouracil, GEMZAR (registered trademark) (gemcitabine), hydroxyurea, ALKERAN (registered trademark) (melphalan), mercaptopurine, 6-mercaptopurine riboside, methotrexate, mycophenolic acid, nerarabine, noratorexide, ocphosphat, peritrexol , Pentostatin, larcitrexed, ribavirin, triapine, trimetrexate, S-1, thiazofulin, tegafur, TS-1, bidarabin, UFT and the like.

Antiviral agents include ritonavir, hydroxychloroquine and the like.

Aurora kinase inhibitors include ABT-348, AZD-1152, MLN-8054, VX-680, Aurora A-specific kinase inhibitors, Aurora B-specific kinase inhibitors and pan-aurora kinase inhibitors.

Bcl-2 protein inhibitors include AT-101 ((-) gosipole), GENASENSE® (G3139 or oblimersen (Bcl-2-targeted antisense oligonucleotide)), IPI-194, IPI-565, N. -(4- (4-((4'-Chloro (1,1'-biphenyl) -2-yl) methyl) piperazin-1-yl) benzoyl) -4-(((1R) -3- (dimethylamino) )-1-((Phenylsulfanyl) methyl) propyl) amino) -3-nitrobenzenesulfonamide) (ABT-737), N- (4- (4-((2- (4-chlorophenyl) -5,5-) Dimethyl-1-cyclohexa-1-ene-1-yl) methyl) piperazin-1-yl) benzoyl) -4-(((1R) -3- (morpholin-4-yl) -1-((phenylsulfanyl)) Includes methyl) propyl) amino) -3-((trifluoromethyl) sulfonyl) benzenesulfonamide (ABT-263), GX-070 (Obatoclux) and the like.

Bcr-Abl kinase inhibitors include DASATINIB® (BMS-354825), GLEEVEC® (imatinib) and the like.

CDK inhibitors include AZD-5438, BMI-1040, BMS-032, BMS-387, CVT-2584, flavopyridol, GPC-286199, MCS-5A, PD0332991, PHA-690509, seliciclib (CYC-202,). R-Roscobitin), ZK-304709, etc. are included.

COX-2 inhibitors include ABT-963, ARCOXIA® (etricoxib), BEXTRA® (valdecoxib), BMS347070, CELEBREX® (celecoxib), COX-189 (lumiracoxib), CT- 3, DERAMAXX® (deracoxib), JTE-522, 4-methyl-2- (3,4-dimethylphenyl) -1- (4-sulfamoylphenyl-1H-pyrrole), MK-663 (etricoxib) ), NS-398, Parecoxib, RS-57067, SC-58125, SD-8381, SVT-2016, S-2474, T-614, VIOXX® (Rofecoxib), etc.

EGFR inhibitors include ABX-EGF, anti-EGFR immunoliposome, EGF-vacant, EMD-7200, ERBITUX® (cetuximab), HR3, IgA antibody, IRESSA® (gefitinib), TARCEVA® ) (Erlotinib or OSI-774), TP-38, EGFR fusion protein, TYKERB® (lapatinib) and the like.

ErbB2 receptor inhibitors include CP-724-714, CI-1033 (canertinib), HERCEPTIN® (trastuzumab), TYKERB® (lapatinib), OMNITARG® (2C4, petuzumab), TAK-165, GW-572016 (ionafarnib), GW-282974, EKB-569, PI-166, dHER2 (HER2 vaccine), APC-8024 (HER-2 vaccine), anti-HER / 2neu bispecific antibody, B7 Includes .her2IgG3, AS HER2 trifunctional bispecific antibody, mAB AR-209, mAB 2B-1 and more.

Histone deacetylase inhibitors include depsipeptides, LAQ-824, MS-275, trapoxins, suberoylanilide hydroxamic acid (SAHA), TSA, valproic acid and the like.

HSP-90 inhibitors include 17-AAG-nab, 17-AAG, CNF-101, CNF-1010, CNF-2024, 17-DMAG, gerdanamycin, IPI-504, KOS-953, MYCOGRAB® ) (Human recombinant antibody against HSP-90), NCS-683664, PU24FCl, PU-3, Radicicol, SNX-2112, STA-9090 VER49009, etc.

Inhibitors of apoptotic protein inhibitors include HGS1029, GDC-0145, GDC-0152, LCL-161, LBW-242 and the like.

Antibody-drug conjugates include anti-CD22-MC-MMAF, anti-CD22-MC-MMAE, anti-CD22-MCC-DM1, CR-011-vcMMAE, PSMA-ADC, MEDI-547, SGN-19Am SGN-35, SGN. -75 etc. are included.

Activators of the cell death receptor pathway include TRAIL, antibodies or other agents that target TRAIL or death receptors (eg, DR4 and DR5), such as Apomab, konatumumab, ETR2-ST01, GDC0145, (lexatumumab). , HGS-1029, LBY-135, PRO-1762 and trastuzumab.

Kinesin inhibitors include Eg5 inhibitors such as AZD4877, ARRY-520; CENPE inhibitors such as GSK923295A.

JAK-2 inhibitors include CEP-701 (less aultinib), XL019 and INCB018424.

MEK inhibitors include ARRY-142886, ARRY-438162 PD-325901, PD-98059 and the like.

mTOR inhibitors include ATP competitive TORC1 / TORC2 inhibitors including AP-23573, CCI-779, everolimus, RAD-001, rapamycin, temsirolimus, PI-103, PP242, PP30, Torin1.

Non-steroidal anti-inflammatory drugs include AMIGESIC® (Salsalate), DOLOBID® (Diclofenac), MOTRIN® (ibuprofen), ORUDIS® (Ketoprofen), RELAFEN® (Nabmeton), FELDENE® (Pyroxycam), Ibuprofen Cream, ALEVE® (Naproxen) and NAPROSYN® (Naproxen), VOLTAREN® (Diclofenac), INDOCIN® (Indomethacin) ), CLINOLIL® (Slindak), TOLECTIN® (Tormethin), LODINE® (Etodrak), TORADL® (Ketrolac), DAYPRO® (Oxaprosin), etc. ..

PDGFR inhibitors include C-451, CP-673, CP-868596 and the like.

Platinum-based chemotherapeutic agents include cisplatin, ELOXATIN® (oxaliplatin) eptaplatin, donaplatin, nedaplatin, PARAPLATIN® (carboplatin), satraplatin, picoplatin and the like.

Polo-like kinase inhibitors include BI-2536 and the like.

Phosphoinositide-3 kinase (PI3K) inhibitors include wortmanin, LY294002, XL-147, CAL-120, ONC-21, AEZS-127, ETP-45658, PX-866, GDC-0941, BGT226, BEZ235, XL765, etc. Is included.

Thrombospondin analogs include ABT-510, ABT-567, ABT-898, TSP-1 and the like.

VEGFR inhibitors include AVASTIN® (bevacizumab), ABT-869, AEE-788, ANGIOZYME® (Ribozyme Pharmaceuticals (Boulder, CO.) And Chiron (Emeryville, CA), which inhibit angioplasty. ), Axitinib (AG-13736), AZD-2171, CP-547,632, IM-862, MACUGEN (Pegaptamib), NEXAVAR® (Soraphenib, BAY43-9006), Pazopanib (GW-786034), Bataranib (PTK-) 787, ZK-222584), SUTENT® (Snitinib, SU-11248), VEGF Trap, ZACTIMA® (Bandetanib, ZD-6474), GA101, Ofatumumab, ABT-806 (mAb-806), ErbB3 specific Target antibody, BSG2-specific antibody, DLL4-specific antibody, C-met-specific antibody and the like.

Antibiotics include the inserted antibiotics acralubicin, actinomycin D, amurubicin, anamycin, adriamycin, BLENOXANE® (bleomycin), daunorubicin, CAELYX® or MYOCET® (lipocalyzed doxorubicin), elsamitorcin. , Epirubicin, glalbuicin, ZAVEDOS® (idarubicin), mitomycin C, nemorubicin, neocartinostatin, pepromycin, pyrarubicin, rebeccamycin, stimalamar, streptozocin, VALST AR® (barrubicin), dinostatin, etc. Is done.

Topotecanase inhibitors include acralubicin, 9-aminocamptothecin, amonafide, amsacrine, becatecarin, verotecan, BN-80915, CAMPTOSAR® (irinotecan hydrochloride), camptothecin, CARDIOXANE® (dexrazoxin), diflomotecin, edotecan. , ELLENCE® or PHARMORUBICIN® (epirubicin), etoposide, exatecan, 10-hydroxycamptothecin, gimatecan, lurtotecan, mitoxanthrone, oratecin, pirarubicin, pixantron, rubitecan, sobzoxane, SN-38, tafluposide, topotecan Etc. are included.

Antibodies include AVASTIN® (bevacizumab), CD40-specific antibody, chTNT-1 / B, denosumab, ERBITUX® (cetuximab), HUMAX-CD4® (zanolimumab), IGF1R-specific Antibodies such as Linzzumab, PANORX® (Edrecolomab), RENCAREX® (WX G250), RITUXAN® (Rituximab), ticilimumab, trussujimab, CD20 antibodies types I and II.

For hormone treatments, ARIMIDEX (registered trademark) (anastrozole), AROMASIN (registered trademark) (exemethan), aldoxyphene, CASODEX (registered trademark) (bicalutamide), CETROTIDE (registered trademark) (cetrorelinx), degarelix, Deslorerin, DESOPAN (registered trademark) (trilostane), dexamethasone, DROGENIL (registered trademark) (fulutamide), EVISTA (registered trademark) (laroxyphene), AFEMA (trademark) (fadrozole), FARESTON (registered trademark) (tremifen), FASLODEX ( Registered Trademarks) (Fulvestrant), FEMARA® (Letrozole), Formestan, Glucocorticoids, HECTOROL® (Doxelcalciferol), RENAGEL® (Seberamar Carbonate), Lasofoxy Fen, leuprolide acetate, MEGACE (registered trademark) (megesterol), MIFEPREX (registered trademark) (mifepriston), NILANDRON (trademark) (nirutamide), NOLVADEX (registered trademark) (tamoxyphene citrate), PLENAXIS (trademark) ( Avalerix), Prednison, PROPECIA® (finasteride), letrozole, SUPREFACT® (buserelin), TRELSTAR® (luteinizing hormone-releasing hormone (LHRH)), VANTAS® (histrelin implant) ), VETORYL® (trilostan or modrastan), ZOLADEX® (phoslerin, goserelin), etc.

Delutoids and retinoids include theocalcitol (EB1089, CB1093), lexacalcitol (KH1060), fenretinide, PANRETIN® (ariretinoin), ATRAGEN® (liposomal tretinoin), TARGRETIN®. (Bexarotene), LGD-1550, etc. are included.

PARP inhibitors include ABT-888 (veliparib), olaparib, KU-59436, AZD-2281, AG-014699, BSI-201, BGP-15, INO-1001, ONO-2231 and the like.

Plant alkaloids include, but are not limited to, vincristine, vinblastine, vindesine, vinorelbine and the like.

Proteasome inhibitors include VELCADE® (bortezomib), MG132, NPI-0052, PR-171 and the like.

Examples of immunosuppressants include interferon and other immunosuppressants. Interferon includes interferon α, interferon α-2a, interferon α-2b, interferon β, interferon γ-1a, ACTIMMUNE® (interferon γ-1b) or interferon γ-n1, and combinations thereof. Other drugs include ALFAFERONE® (IFN-α), BAM-002 (oxidized glutathione), BEROMUN® (tasonermin), BEXXAR® (toshitsumomab), CAMPATH® (registered trademark). Alemtuzumab), CTLA4 (cytotoxic lymphocyte antigen 4), decarbazine, denirokin, epratuzumab, GRANOCYTE® (lenograstim), lentinan, leukocyte α-interferon, imikimod, MDX-010 (anti-CTLA-4), melanoma vaccine, Mitsumomab, Morgramostim, MYLOTARG (Gemtuzumab ozogamicin), NEUPOGEN (Philgrastim), Onco VAC-CL, OVAREX (registered trademark) (olegobomab), pentumomab (Y-muHMFG1), PROVENGE (registered trademark) (Ciploisel-T), Sargaramostim, Sizophyllan, Teseroykin, THERACYS (registered trademark) (Bacillus Calmette- Guerin)), Ubenimex, VIRULIZIN® (Immunotherapy, Lorus Pharmaceuticals), Z-100 (Maruyama's Specific Substance (SSM)), WF-10 (Tetrachlorodecaoxide (TCDO)), PROLEUKIN (Registered) Includes Trademarks) (Ardes Roykin), ZADAXIN® (Timalfacin), ZENAP AX® (Dakrizumab), ZEVALIN® (90Y-Ibritumomab tiuxetan).

Biological response modifiers are agents that modify the defense mechanisms of biological or biological responses such as survival, growth or differentiation of tissue cells so that they have antitumor activity. Includes Krestin, Lentinan, Sizophyllan, Pisibanir PF-3512676 (CpG-8954), Ubenimex and more.

Cytarabine analogs include cytarabine (ara C or arabinoside C), cytosine arabinoside, doxifluridine, FLUDARA® (fludarabine), 5-FU (5-fluorouracil), floxuridine, GEMZAR® (registered trademark). Includes gemcitabine), TOMUDEX® (latitrexed), TROXATYL® (triacetyluridinetroxacitabine) and the like.

Purine analogs include LANVIS® (thioguanine) and PURI-NETHOL® (mercaptopurine).

Antimitotic agents include batablin, epothilone D (KOS-862), N- (2-((4-hydroxyphenyl) amino) pyridine-3-yl) -4-methoxybenzenesulfonamide, ixavepyrone (BMS247550). , Paclitaxel, TAXOTERE® (docetaxel), PNU100940 (109881), Patsupiron, XRP-9881 (Larotaxel), Benzene, ZK-EPO (Synthetic Epothilone), etc.

Ubiquitin ligase inhibitors include MDM2 inhibitors such as Natrin and NEDD8 inhibitors such as MLN4924.

The compound of the present invention can also be used as a radiosensitizer that enhances the efficacy of radiotherapy. Examples of radiotherapy include external beam radiotherapy, remote therapy, brachytherapy and sealed, unsealed source radiotherapy and the like.

In addition, compounds having formula (I) include other chemotherapeutic agents such as ABRAXANE (ABI-007), ABT-100 (farnesyl transferase inhibitor), ADVEXIN® (Ad5CMV-p53 vaccine), ALTOCOR. (Registered trademark) or MEVACOR (registered trademark) (lovastatin), AMPLIGEN (registered trademark) (poly I: poly C12U, synthetic RNA), APTOSYN (registered trademark) (excislind), AREDIA (registered trademark) (pamidronic acid), Algravin, L-asparaginase, atamestane (1-methyl-3,17-dione-androsta-1,4-diene), AVAGE® (tazarotene), AVE-8062 (combreastatin derivative) BEC2 (mitumomab), Vincristine or Kakexin (tumor necrosis factor), cambaccin (vacuum), CEAVAC (registered trademark) (cancer vaccine), CELEUK (registered trademark) (celmoloikin), CEPLENE (registered trademark) (histamine dihydrochloride), CERVARIX (registered) Trademarks) (Human Papillomavirus Vaccine), CHOP® (C: CYTOXAN® (Cyclophosphamide); H: ADRIAMYCIN® (Hydroxydoxorubicin); O: Vincristine (ONCOVIN®) P: Prednison), CYPAT (Ciproterone acetate), Combrestatin A4P, DAB (389) EGF (catalytic and translocation domain of diphtheria toxin fused via His-Ala linker to human epidermal growth factor) or TransMID-107R (difteria toxin), dacarbazine, doxorubicin, 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), enyluracil, EVIZON (squalamine lactate), DIMERICINE (T4N5 liposome lotion), disco del molide, DX-8951f (exatecan mesylate), Enza Staulin, EPO906 (Epityron B), GARDASIL (registered trademark) (tetravalent human papillomavirus (6, 11, 16, 18 type) recombinant vaccine), GASTRIMMUNE (registered trademark), GENASENSE (registered trademark), GMK (ganglioside complex) Vaccine), GVAX® (Prostatic Cancer Vaccine), Halofdinone, Histerelin, Hydroxycarbamide, Ivandronic Acid, IGN-101, IL-13-PE38, IL-13-PE38QQR (Cintredekimbeth Dotox), IL- 13-Exatecan exatecan, interferon-α, interferon-γ, JUNOVAN or MEPACT (mifamultide), ronafarnib, 5,10-Methylenetetrahydrofolic acid, myrtehosine (hexadecylphosphocholine), NEOVASTAT® (AE-941), NEUTREXIN® (trimethrexate glucuronate), NIPENT® (pentostatin), ONCONASE ( Registered Trademark) (Ribovonuclease Enzyme), ONCOPHAGE® (Melanoma Vaccine Treatment), ONCOVAX® (IL-2 Vaccine), ORATHECIN® (Rubitecan), OSIDEM® (antibody-based Korean ginseng containing OVAREX® MAb (mouse monoclonal antibody), paclitaxel, PANDIMEX (20 (S) protopanaxadiol (aPPD) and 20 (S) protopanaxatriol (aPPT)) Aglyconsaponin from), Panitumumab, PANVAC®-VF (Cancer Vaccine Under Study), Peguas Pargase, PEG Interferon A, Phenoxodiol, Procarbazine, Levimasat, REMOVAB® (Katsumakisomab), REVLIMID (Registered Trademark) (Lenalidemid), RSR13 (Ephaproxial), SOMATULINE (Registered Trademark) LA (Lane Leotide), SORIATANE (Registered Trademark) (Acitretin), Staurosporin (Streptomyces staurospores), Tarabostat ( PT100), TARGRETIN (registered trademark) (bexarotene), TAXOPREXIN (registered trademark) (DHA-pacrytaxel), TELCYTA (registered trademark) (camphosfamide, TLK286), temiriphen, TEMODAR (registered trademark) (temozolomid), tesmilifen, Salidamide, THERATOPE® (STn-KLH), Chimitac (2-amino-3,4-Dihydro-6-methyl-4-oxo-5- (4-pyridylthio) quinazoline dihydrochloride), TNFERADE (Adenovector: DNA carrier containing the gene for tumor necrosis-α), TRACLEER® ) Or ZAVESCA® (Bosentan), Tretinoin (Retin-A), Tetlandrin, TRISENOX® (arsenic trioxide), VIRULIZIN®, Ukrain (greater celandine plant) , Vitaxin (anti-αβ3 antibody), XCYTRIN (registered trademark) (motexafingadrinium), XINLAY (trademark) (atracentan), XYOTAX (trademark) (pacritaxel polygourmetax), YONDELIS (registered trademark) (travectedin), It can be used in combination with ZD-6126, ZINECARD (registered trademark) (dexrazoxane), ZOMETA (registered trademark) (zoredronic acid), sorbicin, etc.

data Determining the usefulness of compounds having formula I as binding agents for anti-apoptotic Bcl-2 and Bcl-xL proteins and their inhibitors was performed using a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. The Tb-anti-GST antibody was purchased from Invitrogen (catalog number PV4216).

Probe synthesis All reagents used were obtained from suppliers unless otherwise specified. Diisopropylethylamine (DIEA), dichloromethane (DCM), N-methylpyrrolidone (NMP), 2- (1H-benzotriazole-1-yl) -1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) Peptide synthesis reagents containing, N-hydroxybenzotriazole (HOBt) and piperidine are available from Applied Biosystems, Inc. (ABI), Foster City, CA or American. Obtained from Bioanalytical, Natick, MA. Preloaded 9-fluorenylmethyloxycarbonyl (Fmoc) amino acid cartridges (Fmoc-Ala-OH, Fmoc-Cys (Trt) -OH, Fmoc-Asp (tBu) -OH, Fmoc-Glu (tBu) -OH, Fmoc -Phe-OH, Fmoc-GIy-OH, Fmoc-His (Trt) -OH, Fmoc-Ile-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Met-OH, Fmoc-Asn (Trt) -OH, Fmoc-Pro-OH, Fmor-Gln (Trt) -OH, Fmoc-Arg (Pbf) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Thr (tBu) -OH, Fmoc- Val-OH, Fmoc-Trp (Boc) -OH, Fmoc-Tyr (tBu) -OH) were obtained from ABI or Anaspec, San Jose, CA. Peptide synthesis resin (Fmoc-Rink amide MBHA resin) and Fmoc-Lys (Mtt) -OH are Novabiochem, San Obtained from Diego, CA. The monoisomer 6-carboxyfluorescein succinimidyl ester (6-FAM-NHS) was obtained from Anaspec. Trifluoroacetic acid (TFA) was obtained from Oakwood Products, West Columbia, SC. Thioanisole, phenol, triisopropylsilane (TIS), 3,6-dioxa-1,8-octanedithiol (DODT) and isopropanol were obtained from Aldrich Chemical Co., Milwaukee, WI. Matrix-assisted laser desorption / ionization mass spectra (MALDI-MS) were recorded on Applied Biosystems Voyager DE-PRO MS. Electrospray mass spectra (ESI-MS) were recorded in both cation and anion modes using the Finnigan SSQ7000 (Finnigan Corp., San Jose, CA).

Basic procedure for solid phase peptide synthesis (SPPS) Peptides were synthesized using an ABI433A peptide synthesizer in a 250 μmol scale Fastmoc coupling cycle in a Wang resin / vessel preloaded with at most 250 μmol. A preloaded cartridge containing 1 mmol of standard Fmoc-amino acid (1 mmol Fmoc-Lys (Mtt) -OH placed in the cartridge), excluding the fluorophore binding position, was used while monitoring conductivity feedback. .. N-terminal acetylation was performed with 1 mmol acetic acid in the cartridge under standard coupling conditions.

Removal of 4-methyltrityl (Mtt) from lysine The resin from the synthesizer was washed 3 times with dichloromethane and kept wet. 150 mL of 95: 4: 1 dichloromethane: triisopropylsilane: trifluoroacetic acid was run through a resin bed for 30 minutes. The mixture turned dark yellow, then faded to pale yellow. 100 mL of DMF was flushed through the bed for 15 minutes. The resin was then washed 3 times with DMF and filtered. The ninhydrin test strongly showed that it was the primary amine.

Resin labeling with 6-carboxyfluorescein-NHS (6-FAM-NHS) The resin was treated with 2 equivalents of 6-FAM-NHS in 1% DIEA / DMF and stirred or shaken overnight at ambient temperature. When complete, the resin was drained, washed 3 times with DMF and 3 times with (1% DCM and 1% methanol) and dried to give an orange resin. This was negative in the ninhydrin test.

Basic procedure for cleavage and deprotection of resin-bound peptides Resin resin the peptide by shaking at ambient temperature for 3 hours in a cleavage cocktail consisting of 80% TFA, 5% water, 5% thioanisole, 5% phenol, 2.5% TIS and 2.5% EDT (1 mL / 0.1 g resin). Separated from. The resin was removed by filtration and rinsed twice with TFA. Evaporate the TFA from the filtrate, precipitate the product with ether (10 mL / 0.1 g resin), collect by centrifugation, wash twice with ether (10 mL / 0.1 g resin) and dry to give the crude peptide. It was.

Basic procedure for purification of peptides Unipoint® analysis software (Gilson, registered trademark) using a radial compression column with two 25 × 100 mm segments filled with crude peptides filled with Delta-Pak C18 15 μm particles with a pore size of 100 Å. Inc., Middleton, WI) was run, eluted by one of the gradient methods listed below, and purified on a Gilson preparative HPLC apparatus. 1-2 ml of crude peptide solution (90% DMSO / 10 mg / mL in water) was purified per infusion. Peaks containing the products obtained from each operation were collected and lyophilized. All preparative operations were performed at 20 mL / min with buffer A: 0.1% TFA-water and buffer B: acetonitrile eluate.

Basic procedure for HPLC analysis For HPLC analysis, 120 Å with HPLC 3D ChemStation software version A.03.04 (Hewlett-Packard.Palo Alto, CA) using a Hewlett-Packard 1200 series instrument equipped with a diode array detector and a Hewlett-Packard 1046A fluorescence detector. Using a 4.6 × 250 mm YMC column packed with ODS-AQ 5 μm particles having the pore size of the above, equilibration was performed in advance for 7 minutes under the starting conditions, and then elution was carried out by one of the gradient methods listed below. The eluents were buffer A: 0.1% TFA-water and buffer B: acetonitrile. The flow rate was 1 mL / min for all gradient liquids.

F-Bak: Peptide probe: Acetyl- (SEQ ID NO: 1) GQVGRQLAIIGDK (6-FAM)-(SEQ ID NO: 2) INR-NH₂ The Fmoc-Rink amide MBHA resin was extended to give a protected resin-bound peptide (1.020 g) using a basic peptide synthesis procedure. The Mtt group was removed as described above, labeled with 6-FAM-NHS, cleaved and deprotected to give the crude product as an orange solid (0.37 g). The product was purified by RP-HPLC. Fractions across the main peak were tested by RP-HPLC analysis, pure fractions were isolated and lyophilized to give the title compound (0.0802 g) as a yellow solid from the main peak; MALDI-MS m / z = 2137.1 ((M + H)^l)。

Peptide probe F-Bak: Acetyl- (SEQ ID NO: 1) GQVGRQLAIIGDK (6-FAM)-(SEQ ID NO: 2) INR-NH₂Alternative synthesis of The protected peptide was subjected to Fastmoc (1 mmol Fmoc-Lys (4-methyltrityl) weighed into the cartridge) using a preloaded 1 mmol amino acid cartridge, excluding fluorescein (6-FAM) -labeled lysine. 0.25 mmol of Applied Biosystems 433A automated peptide synthesizer operating in a coupling cycle Incorporated into Fmoc-Rink amide MBHA resin (Novabiochem). The N-terminal acetyl group was incorporated by placing 1 mmol acetic acid in the cartridge and coupling as described above. Selective removal of the 4-methyltrityl group was performed by running a solution of 95: 4: 1 DCM: TIS: TFA (v / v / v) through the resin over 15 minutes and then quenching with a dimethylformamide flow. The monoisomer 6-carboxyfluorescein-NHS was reacted with the lysine side chain in DMF containing 1% DIEA and its completion was confirmed by the ninhydrin test. The peptide is cleaved from the resin and the side chains are 80: 5: 5: 5: 2.5: 2.5 TFA: water: phenol: thioanisole: triisopropylsilane: 3,6-dioxa-1,8-octanedithiol (v / It was treated with v / v / v / v / v) to deprotect, and the crude peptide was recovered by precipitation with diethyl ether. The crude peptide was purified by reverse phase high performance liquid chromatography, and its purity and identity were measured by reverse phase high performance liquid chromatography analysis and matrix-assisted laser desorption mass spectrometry (m / z = 2137.1 ((M + H)).⁺)) Confirmed.

Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay Representative compounds were serially diluted in dimethyl sulfoxide (DMSO) starting at 50 μM (2 x starting concentration; 10% DMSO) and 10 μL was transferred to a 384-well plate. 10 μL of protein / probe / antibody mix was then added to each well at the final concentrations listed in Table 1.

<tables num="1"><img id="000015" he="53" wi="158" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></tables>

The samples were then mixed on a shaker for 1 minute and incubated at room temperature for an additional 3 hours. For each assay, probes / antibodies and proteins / probes / antibodies were included in each assay plate as negative and positive controls, respectively. Fluorescence was measured with an Envision (Perkin Elmer) using a 340/35 nm excitation filter and a 520/525 (F-Bak peptide) and 495/510 nm (Tb-labeled antihistidine antibody) emission filter.

Inhibition constants for compounds and ABT-737 according to the invention (K_i) And binding selectivity ratios for each (Bcl-X)_L K: Bcl-2K_i) Is shown in Table 2 below. Inhibition constant (K_i) Is the dissociation constant of the enzyme-inhibitor complex or protein / small molecule complex. This small molecule inhibits the binding of one protein to another. K for a compound_iIf is represented by a "&gt;" specific number (greater than), it is a binding affinity value (eg, Bcl-X)._LIs greater than the detection limit of the assay used. If the binding selectivity ratio for a compound is expressed as "&gt;" a particular number (greater than), it is Bcl-X for Bcl-2 of a particular compound._LIt shall mean that the selectivity for is at least as large as the indicated numerical value. K for a compound_iWhen is expressed as a "&lt;" specific number (less than), it means that the binding affinity value (eg, for Bcl-2) is less than the detection limit of the assay used. The inhibition constant was determined using Wang's equation (Wang ZX., An Exact Mathematical Expression For Describing Competitive Binding Of Two Different Ligands To A Protein Molecule.FEBS Lett. 1995, 360: 111-4).

<tables num="2"><img id="000016" he="243" wi="147" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></tables><img id="000017" he="243" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000018" he="244" wi="151" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000019" he="244" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000020" he="243" wi="149" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000021" he="243" wi="149" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000022" he="244" wi="151" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000023" he="243" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000024" he="244" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000025" he="246" wi="149" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000026" he="244" wi="152" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000027" he="14" wi="151" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" />

Table 2 shows that compounds with formula I are useful for functionally inhibiting the anti-apoptotic Bcl-2 protein. This is because these compounds have a relatively small affinity for anti-apoptotic Bcl-xL proteins, thereby resulting in high binding selectivity ratios (Bcl-xL K) ranging from&gt; 2 to&gt; 263,263._i/ Bcl-2K_i) Is also surprisingly shown. This selectivity for the Bcl-2 protein is significantly greater than the compounds previously disclosed in PCT US 2004/36770 and PCT US 2004/37911 as illustrated in ABT-737 in Table 2.

For some compounds (eg, 192 and 193), the assay detected activity against both Bcl-2 and Bcl-XL under the conditions described above in the experimental description for the FRET assay. There wasn't. As will be appreciated by those skilled in the art, the upper and lower limits of detection in the assay will be affected by the assay conditions, specifically for FRET assays, by the concentration of probe used. The compounds shown in Examples 192 and 193 have a K greater than the detection limit in the assay scheme used.₁The values indicate that its affinity for Bcl-2 and Bcl-XL is less than the detection limit of the assay. However, they may still have an affinity for one or both of the proteins, and we anticipate that they will also have selectivity for Bcl-2.

Platelet cell viability assay Platelet-rich plasma (PRP) (prepared in-house according to conventional technology), ABT-737 (4-(4-((4'-chloro-1,1'-biphenyl-2-yl) methyl) piperazine-1) -Il) -N-((4-(((1R) -3- (dimethylamino) -1-((phenylthio) methyl) propyl) amino) -3-nitrophenyl) sulfonyl) benzamide) or the compound of the present invention Incubated at various concentrations for 5 hours at 37 ° C. After incubation, platelets were equilibrated to room temperature for 20 minutes, then an equal volume of Cell Titer Glo reagent (Promega Corporation) was added. The samples were mixed for 2 minutes and then equilibrated at room temperature for an additional 10 minutes. The luminescence generated from the sample was quantified with an LJL Analyst plate reader. I c₅₀The value is the concentration of compound required to inhibit 50% of cell survival.

FL5.12 / Bcl-2 cell viability assay FL5.12 is an IL-3-dependent pro-apoptotic mouse cell line that undergoes apoptosis by IL-3 withdrawal as a result of upregulation of pro-apoptotic Bcl-2 proteins such as Bim and Puma. Stable overexpression of the anti-apoptotic Bcl-2 protein (FL5.12 / Bcl-2) protects against apoptosis induced by IL-3 withdrawal by Zequestration of Bim and Puma [Refs. Harada et al., PNAS 101 , 15313 (2004); Certo et al., Cancer Cell 9, 351 (2006)]. The ability of a compound to kill FL5.12 / Bcl-2 cells during IL-3 withdrawal is a direct measure of the compound's ability to inhibit anti-apoptotic Bcl-2 protein function.

Wild-type FL5.12 / Bcl-2 overexpressing stable transfectants, 2 mM L-glutamine, 10% FBS, 1 mM sodium pyruvate, 2 mM HEPES, 1% penicillin / streptomycin (Invitrogen), 57 μM β- Incubate in RPMI-1640 with ME and 10% WEHI-3B conditioned medium (source of IL-3) and 5% CO₂It was held at 37 ° C below. 1x10 then before being subjected to a cytotoxicity assay⁶Cells / ml were washed with 1 x PBS and resuspended in 10% WEHI-3B-free medium for 48 hours. Cells were then treated for an additional 24 hours in the presence of various concentrations of labeled compound. Cell viability was evaluated by the Cell Titre Glo assay (Promega Corp.) according to the manufacturer's recommendations.

Data analysis was performed using GraphPad Prism 4.0. The results are shown in Table 3 below.

<tables num="3"><img id="000028" he="143" wi="151" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></tables><img id="000029" he="244" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000030" he="244" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000031" he="244" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000032" he="244" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000033" he="244" wi="151" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000034" he="244" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000035" he="243" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /><img id="000036" he="181" wi="150" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" />

Table 3 shows that compounds with formula I are useful in functionally inhibiting the anti-apoptotic Bcl-2 protein in the context of cells. FL5.12 is an IL-3-dependent prolymphocyte mouse cell line that undergoes apoptosis during IL-3 withdrawal as a result of upregulation of pro-apoptotic Bcl-2 family proteins such as Bim and Puma. Stable overexpression of the anti-apoptotic Bcl-2 protein (FL5.12 / Bcl-2) protects against apoptosis induced by IL-3 withdrawal by Zequestration of Bim and Puma (Refs. Harada et al., PNAS 2004). Year, 101, 15313; Certo et al., Cancer Cell 2006, 9, 351). The ability of a compound to kill FL5.12 / Bcl-2 cells during IL-3 withdrawal is a direct measure of the compound's ability to inhibit anti-apoptotic Bcl-2 protein function. Low EC₅₀As demonstrated by the values, the compounds of formula I are very effective in killing FL5.12 / Bcl-2 cells under IL-3 withdrawal.

The compounds of the present invention bind to the anti-apoptotic Bcl-2 protein with high affinity and strongly inhibit the function of the anti-apoptotic Bcl-2 protein in the cell association, thus expressing the anti-apoptotic Bcl-2 protein in the meantime. It is expected to be useful in the treatment of diseases.

The anti-apoptotic Bcl-xL protein has been disclosed in other literature (Cell March 23, 2007, 128, 1173-1176) as a major regulator of circulating platelet survival in animals. Gene mutations to the Bcl-xL protein that reduce the stability and half-life of the Bcl-xL protein cause a decrease in platelet viability and longevity in mice carrying these mutations. A potent pharmacological inhibitor of Bcl-xL, ABT-737 causes a rapid concentration-dependent decrease in circulating platelets after injection into C57BL / 6 mice or Beagle dogs (Cell March 23, 2007, 128). , 1173-1176; Cell Death Differ. May 2007; 14 (5), 943-51). Therefore, without being bound by theory, the compounds of the present invention with low affinity for Bcl-xL may exhibit lower levels of platelet apoptosis than previously reported compounds with high Bcl-xL affinity. Be expected.

The effect of compounds on platelet survival can be directly assessed in Exvivo by testing the viability of isolated canine platelets in the presence of compounds of varying concentrations. The data in Table 3 show that the compounds of formula I were isolated in Exvivo as compared to the compounds previously disclosed in PCT US 2004/36770 and PCT US 2004/37911 as exemplified by ABT-737. Significantly less or ineffective (higher EC) on the viability of canine platelets₅₀Value) indicates that. In addition, functional selectivity ratios for compounds of formula I (canine platelet EC)₅₀: FL5.12 / Bcl-2EC₅₀) Ranges from 32 to 4849, which is significantly greater than that for the compounds previously disclosed in PCT US 2004/36770 and PCT US 2004/37911 as exemplified by ABT-737.

Compounds with formula I bind to the anti-apoptotic Bcl-2 protein and anti-apoptotic BcI-X_LDue to its relatively low binding to proteins, this compound is useful as a drug for the treatment of cancers with few side effects of thrombocytopenia (ie, they have few circulating platelets) and autoimmune and immune disorders. .. Bcl-X in thrombocytopenia_LInvolvement is disclosed in Cell March 23, 2007, 128, pp. 1173-1176. Bcl-X, as described herein and elsewhere._LABT-737, a potent inhibitor of ABT-737, causes a dose-dependent decrease in circulating platelets after injection into C57BL / 6 mice or dogs (Cell Death Differ. May 2007; 14 (5), pp. 943-51). ). Low Bcl-X_LCompounds with affinity show little or no reduction in circulating platelets. Therefore, although not bound by theory, the compounds of the present invention having a low affinity for BcI-XL have a higher Bcl-X._LIt can be expected to exhibit lower levels of platelet apoptosis than previously reported compounds with affinity. EC in Table 2₅₀The data show the effect of administration of the compounds of the invention on canine platelets in comparison with ABT-737.

Bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular carcinoma, lymphoblastic leukemia, follicular lymphoma, lymphoid derived from T cells or B cells Bcl-2 protein in malignant diseases, melanoma, myeloid leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, spleen cancer, etc. The involvement of is described in co-owned PCT US 2004/36770 published as WO 2005/049593 and PCT US 2004/37911 published as WO 2005/049594.

The involvement of the Bcl-2 protein in immune and autoimmune diseases is described in Current Allergy and Asthma Reports 2003, 3, 378-384; British Journal of Haematology 2000, 110 (3), 584-90; Blood 2000, 95 (4), pp. 1283-92; and New England Journal of Medicine 2004, 351 (14), pp. 1409-1418.

The involvement of the Bcl-2 protein in arthritis is disclosed in co-owned US Provisional Application No. 60 / 988,479.

The involvement of the Bcl-2 protein in bone marrow transplant rejection is disclosed in co-owned US Provisional Application No. 11 / 941,196 (currently US Patent Application Publication No. 20080182845A1).

Overexpression of the Bcl-2 protein correlates with chemotherapy, clinical outcomes, disease exacerbations, overall prognosis, or resistance to combinations thereof in various cancers and disorders of the immune system. Cancers include, but are not limited to, blood and solid tumor types such as acoustic neuroma, acute leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma). , Stellate cell tumor, myelogenous and promyelogenous), acute T-cell leukemia, basal cell carcinoma, bile duct cancer, bladder cancer, brain tumor, breast cancer (including estrogen receptor positive breast cancer), bronchial cancer, Berkit Lymphoma, cervical cancer, chondrosarcoma, spondyloma, chorionic villi, chronic leukemia, chronic lymphocytic leukemia, chronic myelogenous (granular) leukemia, chronic myelogenous leukemia, colon cancer, colonic rectal cancer, cranial pharyngoma, cyst Adenocarcinoma, abnormal growth changes (dysplasia and metamorphosis), embryonic cancer, endometrial cancer, endothelial sarcoma, lining tumor, epithelial tumor, erythrocytosis, esophageal cancer, estrogen receptor-positive breast cancer, essential platelets Hememia, Ewing tumor, fibrosarcoma, gastric cancer Carcinoma), embryonic testicular cancer, gestational chorionic villus disease, glial blastoma, head and neck cancer, heavy chain disease, hemangioblastoma, liver cancer, hepatocellular carcinoma, hormone-insensitive prostate cancer, smooth myoma, liposarcoma , Lung cancer (including small cell lung cancer and non-small cell lung cancer), lymphangiogenic endothelio-sarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (diffuse large cell B-cell lymphoma, follicular lymphoma, Sarcomas including Hodgkin's and non-Hodgkin's sarcomas), bladder, chest, colon, lung, ovary, pancreas, prostate, skin and uterine malignant tumors and hyperproliferative disorders, T-cell or B-cell-derived lymphoid malignancies, leukemia , Medullary carcinoma, medullary blastoma, melanoma, medullary carcinoma, mesodermoma, multiple myeloma, myeloid leukemia, myeloma, mucinous sarcoma, neuroblastoma, oligosarcoma, oral cancer, osteosarcoma , Ovarian cancer, pancreatic cancer, papillary adenocarcinoma, papillary cancer, peripheral T-cell sarcoma, pine sarcoma, true erythrocytosis, prostate cancer (including hormone-insensitive (refractory) prostate cancer), rectal cancer, renal cells Cancer, retinoblastoma, horizontal print myoma, sarcoma, sebaceous adenocarcinoma, seminoma, skin cancer, small cell lung cancer, solid tumor (canceroma and sarcoma), gastric cancer (stomach) Cancer), squamous cell carcinoma, synovial tumor, sweat adenocarcinoma, testicular cancer (including germ cell testicular cancer), thyroid cancer, Waldenström macroglobulinemia, testicular cancer, uterine cancer, Wilms tumor, etc.

Compounds with formula I include fetal rhombic myoma, pediatric acute lymphoblastoma, pediatric acute myeloid leukemia, pediatric follicular rhombic myoma, pediatric undifferentiated epidermoid, pediatric undifferentiated large cell lymphoma, Ewing family of tumors such as pediatric undifferentiated myeloid cell tumor, pediatric atypical malformation / labdoid tumor of the central nervous system, pediatric mixed acute leukemia, pediatric Berkit lymphoma, undifferentiated neuroectodermal tumor, pediatric diffuse Undifferentiated Wilms tumor, pediatric histology favorable histology Wilms tumor, pediatric glial blastoma, pediatric myeloid blastoma, pediatric neuroblastoma, pediatric neuroblastoma-derived myeloid leukocytosis, pediatric Expresses Bcl-2 protein from pediatric cancers or neoplasms, including pediatric T-cells such as pre-B cell carcinoma (such as leukemia), pediatric osteosarcoma, pediatric lovedoid kidney tumor, pediatric rhombic myoma, and lymphoma and skin cancer It is also expected to inhibit the growth of cells.

Autoimmune disorders include acquired immunodeficiency syndrome (AIDS), autoimmune lymphoproliferative syndrome, hemolytic anemia, inflammatory and thrombocytopenia, acute or chronic immune disorders associated with organ transplantation, Addison's disease, allergic Diseases, alopecia, circular alopecia, atherosclerosis / arteriosclerosis, atherosclerosis, arthritis (including osteoarthritis, juvenile chronic arthritis, septic arthritis, Lime's arthritis, psoriatic arthritis and reactive arthritis) ), Autoimmune bullous disease, β-lipoproteinemia, acquired immunodeficiency-related disease, acute immune disease associated with organ transplantation, acquired limb thianose, acute and chronic parasitic or infectious processes, acute pancreatitis , Acute renal failure, Acute rheumatic fever, Acute transverse myelitis, Adenocarcinoma, Air ectopic contraction, Adult (acute) respiratory distress syndrome, AIDS dementia, Alcoholic liver cirrhosis, Alcohol liver injury, Alcohol hepatitis, Allergic conjunctivitis, allergic contact dermatitis, allergic rhinitis, allergies and asthma, allogeneic transplant rejection, α-1-antitrypsin deficiency, Alzheimer's disease, muscle atrophic lateral sclerosis, anemia, angina, tonic Spondylitis-related lung disease, anterior horn cell disease, antibody-mediated cell toxicity, antiphospholipid syndrome, antireceptor hypersensitivity reaction, aortic aneurysm and peripheral aneurysm, aortic dissection, arterial hypertension, arteriosclerosis, arteriovenous fistula , Arthropathy, asthenia, asthma, ataxia, atopic allergy, atrial fibrillation (persistent or paroxysmal), atrial flutter, atrioventricular block, atrophic autoimmune hypothyroidism, autoimmune hemolytic Anemia, autoimmune hepatitis, autoimmune hepatitis 1 (classical autoimmune or rupoid hepatitis), autoimmune-mediated hypoglycemia, autoimmune neutrophilia, autoimmune thrombocytopenia, autoimmune Thyroid disease, B-cell lymphoma, bone transplant rejection, bone marrow transplant (BMT) rejection, obstructive bronchitis, leg blockage, burns, malaise, cardiac arrhythmia, cardiac dysfunction syndrome (cardiac stun)syndrome), heart tumor, myocardial myopathy, cardiopulmonary bypass inflammatory reaction, cartilage transplant rejection reaction, cerebral cortex degeneration, cerebral disease, disordered or multisource atrial tachycardia, chemotherapy-related disease, chlamydia, bile stagnation, chronic Alcohol addiction, chronic active hepatitis, chronic fatigue syndrome, chronic immune disorders associated with organ transplantation, chronic eosinophil pneumonia, chronic inflammatory lesions, chronic mucocutaneous candidiasis, chronic obstructive pulmonary disease (COPD), chronic salicylic acid Salt poisoning, colorectal common varied immunodeficiency (common variable hypogamma globulinaemia), conjunctivitis, connective tissue disease-related interstitial lung disease, contact dermatitis, Coombs test positive hemolytic anemia , Pulmonary heart, Kreuzfeld-Jakob disease, idiopathic autoimmune hepatitis, idiopathic interstitial pneumonia, culture-negative sepsis, cystic fibrosis, cytokine treatment-related disease, Crohn's disease, fist fighter dementia, demyelination disease, Deng hemorrhagic fever, dermatitis, dermatitisscleroderma), skin lesions, dermatomyositis / polymyositis-related lung disease, diabetes, diabetic acidosis arteriosclerotic disease, true diabetes, diffuse Levy body disease, dilated myocardial myopathy, dilated congestive myocardial myopathy, discoid Red spot dermatomyositis, basal nucleus disease, disseminated intravascular coagulation, middle-aged Down syndrome, drug-induced interstitial lung disease, drug-induced hepatitis, CNS dopamine, drug-induced drug induction that blocks receptors Sexual motor disorders, drug hypersensitivity, eczema, encephalomyositis, endocarditis, endocrine disorders, enteritis synovitis, laryngeal inflammation, Epsteiner virus infection, limb erythema, extrapyramidal and cerebral disorders, Familial blood cell phagocytic lymphohistiocytosis, fetal thoracic transplant rejection, Friedrich ataxia, functional peripheral arterial disorder, female infertility, fibrosis, fibrous lung disease, fungal septicemia, gas necrosis, Gastric ulcer, giant cell arteritis, glomerular nephritis, glomerular nephritis, Good Pasture syndrome, thyroidomatic autoimmune hypothyroidism (Hashimoto thyroiditis), gouty arthritis, tissue incompatibility of any organ or tissue Transplant-to-host rejection, gram-negative bacterial sepsis, gram-positive bacterial sepsis, granules caused by intracellular organisms, group B lytic bacterium (GBS) infection, Graves disease, hemoziderin deposit-related lung disease, hairy cell leukemia, hairy cells Leukemia, Hallelfoldenspatz's disease, Hashimoto thyroiditis, hay fever, cardiac transplant rejection, hemochromatosis, hematopoietic malignancies (leukemia and lymphoma), hemolytic anemia, hemolytic urotoxicity syndrome / thrombolytic thrombocytopenia Purple spot disease, bleeding, Henoch Schoenlein purple spot disease, hepatitis A, hepatitis B, hepatitis C, HIV infection / HIV neuropathy, Hodgkin's disease, parathyroid dysfunction, Huntington chorea, hyperactivity disorder, hypersensitivity Reaction, irritable pneumonia, hyperthyroidism, hypomotor dyskinesia, hypothalamic-pituitary-adrenal axisEvaluation), idiopathic Addison's disease, idiopathic leukocytopenia, idiopathic pulmonary fibrosis, idiopathic thrombocytopenia, idiopathic liver disease, infantile spinal muscle atrophy, infection, aortic inflammation, inflammatory colitis , Insulin-dependent true diabetes, interstitial pneumonia, iris-like body inflammation / grape membrane inflammation / optic neuritis, ischemia-reperfusion injury, ischemic cerebral infarction, juvenile malignant anemia, juvenile rheumatoid arthritis, juvenile spinal cord Sexual muscle atrophy, Kaposi sarcoma, Kawasaki disease, renal transplant rejection, Legionella, Leishmania, Hansen's disease, corticospinal lesions, linear IgA disease, lipidemia, liver transplant rejection, Lime's disease, lymphoedema , Lymphocytic pulmonary disease, malaria, idiopathic male infertility or NOS, malignant histocytoproliferative disorder, malignant melanoma, meningitis, meningitis bacillemia, microscopic vasculitis of the kidney, migraine, mitochondria Organ disorders, mixed connective tissue disease, mixed connective tissue disease-related lung disease, monoclonal immunoglobulinemia, multiple myeloma, polyline degeneration (Mencel, Dujuline-Thomas, Sidreger and Mashad Joseph), muscle pain Sexual encephalitis / royal free disease, severe myasthenia, microvascular inflammation of the kidney, mycobacteria abium intracellulare, human tuberculosis, myelodystrophy syndrome, myocardial infarction, myocardial ischemia, nasopharyngeal cavity Cancer, neonatal chronic lung disease, nephritis, nephrosis, nephrosis syndrome, neurodegenerative disease, neurogenic type I muscle atrophy, neutrophiliac fever, non-alcoholic fatty hepatitis, abdominal aorta and its branch obstruction, obstruction Sexual arterial disorder, organ transplant rejection, testicular inflammation / supraclavicular inflammation, testicular inflammation / spermatitis, organ hypertrophy, osteoarthritis, osteoporosis, ovarian disorder, pancreatic transplant rejection, parasite disease , Secondary thyroid transplant rejection, Parkinson's disease, pelvic inflammatory disease, vulgaris vulgaris, deciduous cyst, aspergillus, perennial rhinitis, peritoneal disease, peripheral atherosclerotic disease, peripheral vasculopathy, peritonitis, malignant Anemia, crystal-induced vasculitis, pneumocystiscarini pneumonia, pneumonia, POEMS syndrome (multiple neuropathies, organ hypertrophy, endocrine disorders, monoclonal immunoglobulinemia and cutaneous symptom syndrome), postperfusion syndrome, post-pump syndrome, MI post-cardiac incision syndrome, post-infection interstitial lung disease, early ovarian dysfunction, primary biliary cirrhosis, primary scleroderma, primary mucinous edema, primary pulmonary hypertension, primary sclerosing cholangitis , Primary vasculitis, progressive nuclear paralysis, psoriasis, psoriasis type 1, psoriasis type 2, psoriasis arthritis, pulmonary hypertension following scleroderma, pulmonary symptoms of nodular polyarteritis, after inflammation Interstitial lung disease, radiation fibrosis, radiation therapy, Reynaud phenomenon and Reynaud's disease, Leftham's disease, regular and narrow QRS tachycardia, Reiter's disease, renal disease NOS, renovascular hypertension, reperfusion injury, restraint Type myocardial myopathy, rheumatoid arthritis-related interstitial lung disease, rheumatic spondylitis, sarcoidosis, Schmidt syndrome, scleroderma, senile butoh disease, Levy body senile dementia, blood loss syndrome, septic shock, serum Reaction-negative arthropathy, shock, sickle redemia, Sjogren's disease-related lung disease, Sjogren's syndrome, skin allogeneic transplant rejection, skin change syndrome, small bowel transplant rejection, sperm autoimmunity, multiple sclerosis (all subtypes) ), Spinal dyskinesia, spinal cerebral degeneration, spondylosis, sporadic polyendocrine gland dysfunction type I (sporadic), polyendocrine gland dysfunction type II, Still's disease, scleroderma, cerebral infarction, cerebrum Structural lesions, subacute sclerosing panencephalitis, sympathetic ophthalmitis, fainting, cardiovascular syphilis, systemic anaphylaxis, systemic inflammatory reaction syndrome, systemic onset juvenile rheumatoid arthritis, systemic erythematosus, systemic erythematosus Pulmonary disease, systemic sclerosis, systemic sclerosis-related interstitial lung disease, T cells or FABALL, hypersensitivity / arteritis, capillary dilatation, Th2 and Th1 mediated diseases, thromboangiitis obliterans, thrombocytopenia, thyroiditis, toxicity, toxin shock syndrome, transplantation, trauma / bleeding, type 2 self Immune hepatitis (anti-LKM antibody hepatitis), type B insulin resistance associated with melanosis, type III hypersensitivity reaction, type IV hypersensitivity, ulcerative colitis arthritis, ulcerative colitis, unstable angina, urinary poison Disease, urinary septicemia, urticaria, vasculitis, cardiovalvular disease, venous aneurysm, vasculitis, angiitis diffuse lung disease, venous disease, venous thrombosis, ventricular fibrillation, leukoplakia acute liver Diseases, viral and fungal infections, viral encephalitis / aseptic meningitis, virus-related blood cell phagocytosis syndrome, Wegener's granulomatosis, Wernicke Korsakov syndrome, Wilson's disease, heterologous transplant rejection of any organ and tissue, Elsina and Salmonella Includes related arthritis and the like. Schemes and experiments The following scheme is presented to provide what is considered the most useful and easily understood explanation of the procedures and conceptual aspects of the invention. The compound of the present invention can be prepared by a synthetic chemical method. An example is shown below. The order of the steps in these methods can be changed, reagents, solvents and reaction conditions can be replaced with those specifically mentioned, and vulnerable areas can be protected and deprotected as needed. Please understand that you can.

The following abbreviations shall have the indicated meanings. ADDP means 1,1'-(azodicarbonyl) dipiperidin; AD-mix-β means (DHQD)₂PHAL, K₃Fe (CN)₆, K₂CO₃And K₂SO₄) Means a mixture; 9-BBN means 9-borabicyclo (3.3.1) nonane; Boc means tert-butoxycarbonyl; (DHQD)₂PHAL means hydroquinidine 1,4-phthalazinediyldiethyl ether; DBU means 1,8-diazabicyclo (5.4.0) undec-7-ene; DIBAL means diisobutylaluminum hydride; DIEA means diisopropyl. DMAP means N, N-dimethylaminopyridine; DMF means N, N-dimethylformamide; dmpe means 1,2-bis (dimethylphosphino) ethane; DMSO means DMSO Means; dppb means 1,4-bis (diphenylphosphino) -butane; dppe means 1,2-bis (diphenylphosphino) ethane; dppf means 1,1'-bis (diphenylphos) Fino) Ferrocene; dppm means 1,1-bis (diphenylphosphino) methane; EDAC / HCl means 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride; Fmoc Means fluorenylmethoxycarbonyl; HATU means O- (7-azabenzotriazol-1-yl) -N, N'N'N'-tetramethyluronium hexafluorophosphate; HMPA means hexamethylphospho Means luamide; IPA means isopropyl alcohol; MP-BH₃Means macroporous triethylammonium methylpolystyrene cyanoborohydride; TEA means triethylamine; TFA means trifluoroacetic acid; THF means tetrahydrofuran; NCS means N-chlorosuccinimide; NMM Means N-methylmorpholin; NMP means N-methylpyrrolidine; PPh₃Means triphenylphosphine.

<chemistry num="14"><img id="000037" he="49" wi="159" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> The compound of formula (4) can be prepared as shown in Scheme 1 and can be used as described in Scheme 7 to prepare a compound of formula (I) representing the compound of the present invention. .. R is alkyl and R¹⁰⁰Is R²⁶As described above for substituents, compounds of formula (I) with n of 1, 2 or 3 are R in a solvent such as, but not limited to, ether or tetrahydrofuran.³⁷CH²MgX¹(X¹Is a halide. ) Can be used to convert to the compound of formula (2). The compounds of formula (3) are NaH and R.⁵⁰X²(X²Is a halide and R^50aIs as described herein. ) And other strong bases can be used to prepare from the compound of formula (2). Treatment of the compound of formula (3) with an aqueous solution of NaOH or LiOH gives the compound of formula (4).

<chemistry num="15"><img id="000038" he="59" wi="157" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> As shown in Scheme 2, the compound of formula (5) can be reacted with the compound of formula (6) and the reducing agent to provide the compound of formula (7). Examples of reducing agents include sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, polymer-supported cyanoborohydride and the like. Reactions are generally carried out in solvents such as, but not limited to, methanol, tetrahydrofuran and dichloromethane or mixtures thereof. The compound of formula (8) can be prepared from the compound of formula (7) as shown in Scheme 1 and used as shown in Scheme 7 to prepare the compound of formula (I).

<chemistry num="16"><img id="000039" he="59" wi="158" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> When the compound of formula (9) is reacted with the compound of formula (10) in which X is a halide or triflate and the base, the compound of formula (11) is obtained. Bases useful in this reaction include triethylamine, diisopropylethylamine and the like. R⁴¹Is R³⁷The compounds of formula (13), as described herein for the above substituents, are the compounds of formula (11) and formula (11) using Suzuki coupling conditions known to those of skill in the art and readily available in the literature. It can be prepared from the compound of (12). The compound of formula (14) can be prepared from the compound of formula (13) as shown in Scheme 1 and used as shown in Scheme 7 to prepare the compound of formula (I).

<chemistry num="17"><img id="000040" he="84" wi="159" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> As shown in Scheme 4, the compounds of formula (17) are alkyl in R and R using Suzuki coupling conditions known to those of skill in the art and readily available in the literature.⁴¹Can be prepared from compounds of formula (15) and compounds of formula (16), as described herein. The compound of formula (17) can be, but not limited to, LiAlH in a solvent such as diethyl ether or THF.₄It can be reduced to the compound of the formula (18) by using a reducing agent such as. The compound of formula (19) can be prepared from the compound of formula (18) using Dess-Martin peryodinane or Swern oxidation conditions known to those of skill in the art and readily available in the literature. The compound of formula (19) can be reacted with the compound of formula (5) and the reducing agent to obtain the compound of formula (20). Examples of reducing agents include sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, polymer-supported cyanoborohydride and the like. Reactions are generally carried out in solvents such as, but not limited to, methanol, tetrahydrofuran, 1,2-dichloroethane and dichloromethane or mixtures thereof. The compound of formula (21) can be prepared from the compound of formula (20) as shown in Scheme 1 and used as shown in Scheme 7 to prepare the compound of formula (I).

<chemistry num="18"><img id="000041" he="43" wi="158" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> As shown in Scheme 5, the compound of formula (22) in which R is alkyl is this compound (X).¹Is Cl, Br, I or CF₃SO₃-. ) And formula R^50A-OH and the catalyst can be converted to the compound of formula (23) by reacting with or without the first base. Examples of catalysts include copper (I) trifluoromethanesulfonate toluene complex, PdCl.₂, Pd (OAc)₂And Pd₂(dba)₃Is included. Examples of the first base include triethylamine, N, N-diisopropylethylamine, Cs.₂CO₃, Na₂CO₃, K₃PO₄And mixtures of these are included.

The compound of formula (22) is this compound (X).¹Is Cl, F or NO₂Is) and the formula R^50AThe -OH compound can also be reacted with the first base to convert it to the compound of formula (23). Examples of the first base include triethylamine, N, N-diisopropylethylamine, Cs.₂CO₃, Na₂CO₃, K₃PO₄And mixtures of these are included.

<chemistry num="19"><img id="000042" he="114" wi="159" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> The compound of formula (18) can be reacted with mesylate chloride and a base such as, but not limited to, triethylamine, followed by Nt-butoxycarbonylpiperazine to give the compound of formula (24). The compound of formula (25) can be prepared by reacting the compound of formula (24) with triethylsilane and trifluoroacetic acid. Compounds of formula (25), but not limited to, compounds of formula (26) and HK in solvents such as dimethyl sulfoxide.₂PO₄The compound of formula (27) can be obtained by reacting with. The compound of formula (28) can be prepared from the compound of formula (27) as shown in Scheme 1 and used as shown in Scheme 7 to prepare the compound of formula (I).

<chemistry num="20"><img id="000043" he="37" wi="159" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> As shown in Scheme 7, a compound of formula (32) that can be prepared as described herein can be converted to a compound of formula (33) by reacting this compound with ammonia. The compound of formula (33) is the compound of formula (4), (8), (14), (21), (23), (28) or (38) with or without the first base. It can be converted to the compound of formula (I) by reacting with the compound and the coupling agent. Examples of coupling agents include 1-ethyl-3- [3- (dimethylamino) propyl] -carbodiimide hydrochloride, 1,1'-carbonyldiimidazole and benzotriazole-1-yl-oxytripyrrolidinophosphonium hexa. Includes fluorophosphate. Examples of the first base include triethylamine, N, N-diisopropylethylamine, 4- (dimethylamino) pyridine and mixtures thereof.

<chemistry num="21"><img id="000044" he="41" wi="156" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> The compound of formula (33) prepared as shown in Scheme 7 can also be converted to the compound of formula (I) by reacting this compound with the compound of formula (34) and the first base. Examples of the first base include, but are not limited to, sodium hydride, triethylamine, N, N-diisopropylethylamine, 4- (dimethylamino) pyridine and mixtures thereof.

<chemistry num="22"><img id="000045" he="71" wi="159" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> As shown in Scheme 9, the compound of formula (35) (L is bond, alkyl, O, S, S (O), S (O)₂, NH, etc. ) Is reacted with the compound of formula (36) to obtain the compound of formula (37). The reaction is generally carried out at a high temperature in a solvent such as dimethyl sulfoxide, but is not limited to these, and may require the use of bases such as potassium phosphate and potassium carbonate. The compound of formula (38) can be prepared from the compound of formula (37) as shown in Scheme 1 and used as shown in Scheme 7 to prepare the compound of formula (I).

<chemistry num="23"><img id="000046" he="53" wi="157" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> Y is R³⁷The compounds of formula (39), as described herein for the above substituents, are those of formula (39A) using Suzuki coupling conditions known to those of skill in the art and readily available in the literature. X is a halide or triflate.) And YB (OH)₂Can be prepared from. The compound of formula (39) can be reacted with a reducing agent such as tert-butylpiperazin-1-carboxylate and sodium triacetoxyborohydride to give the compound of formula (40). The reaction is generally, but not limited to, carried out in a solvent such as methylene chloride. The compound of formula (41) is obtained from the compound of formula (40) by converting the latter into a solvent such as N, N-dimethylformamide.⁵⁰It can be prepared by reacting with X (X is a halide) and NaH, and then the resulting material can be treated with triethylsilane and trifluoroacetic acid in dichloromethane. The compound of formula (41) is formulated in Scheme 9 (CH).₂R³⁷Is as shown in equation (41). ) Can be used.

<chemistry num="24"><img id="000047" he="56" wi="159" file="JP6034412B2_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> Substituted piperazine-2-one (R) as shown in Scheme 11⁵⁰Is alkyl. ) Is reacted with a compound of formula (6a) and a reducing agent such as sodium triacetoxyborohydride in dichloromethane to obtain a compound of formula (42). The compound of formula (42) can be reduced to a compound of formula (43) in a solvent such as tetrahydrofuran, but not limited to, using a reducing agent such as lithium aluminum hydride. .. The compound of formula (43) is in Scheme 9 (CH).₂R³⁷Is as shown in Equation (43). ) Can be used.

The following examples provide what is considered to be the most useful and easily understood description of the procedures and conceptual aspects of the invention. The exemplified compounds are named using ACD / ChemSketch Version 5.06 (June 5, 2001, Advanced Chemistry Development Inc., Toronto, Ontario) or ChemDraw® Ver. 9.0.5 (Cambridge Soft, Cambridge, MA). did. The intermediate was named using ChemDraw® Ver. 9.0.5 (Cambridge Soft, Cambridge, MA).

<p num="0253"> Example 1 4- {4- (4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-4) -Ilmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 1A tert-Butyl 4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-carboxylate CH₂Cl₂Together with 4'-chlorobiphenyl-2-carbaldehyde (Example 27C) (4.1 g), tert-butylpiperazin-1-carboxylate (4.23 g) and sodium triacetoxyborohydride (5.61 g) in (60 mL). Was stirred for 24 hours. The reaction was quenched with methanol and poured into ether. The solution was washed with water and brine, concentrated and chromatographed on silica gel with 2-25% ethyl acetate / hexane.</p><p num="0254"> Example 1B 1-((4'-chlorobiphenyl-2-yl) methyl) piperazine CH Example 1A (3.0 g) and triethylsilane (1 mL)₂Cl₂The reaction was concentrated in (30 mL) and trifluoroacetic acid (30 mL) for 2 hours, then taken up on ether and concentrated again. The product was used without further purification.</p><p num="0255"> Example 1C Methyl 4-fluoro-2-phenoxybenzoate Methyl 2-bromo-4-fluorobenzoate (1 g), phenol (0.565 g), cesium carbonate (1.96 g), copper (I) triflate toluene complex (0.087 g) and ethyl acetate (0.034 mL) in toluene (12 mL) Was stirred at 110 ° C for 24 hours. The reaction was cooled and chromatographed on silica gel with 5% ethyl acetate / hexane.</p><p num="0256"> Example 1D Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoate Example 1C (630 mg), Example 1B and K₂CO₃(707 mg) was stirred in dimethyl sulfoxide at 125 ° C. for 5 hours. The reaction was cooled and chromatographed on silica gel with 10% ethyl acetate / hexane.</p><p num="0257"> Example 1E 4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoic acid Example 1D (600 mg) was stirred in 25 mL 2: 1 dioxane / 1M NaOH at 60 ° C. for 24 hours. Cool the solution and NaH₂PO₄The pH was adjusted to 4 with the solution and concentrated hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract is washed with brine and dehydrated (Na₂SO₄), Filtered and concentrated.</p><p num="0258"> Example 1F 3-Nitro-4-((tetrahydro-2H-pyran-4-yl) methylamino) benzenesulfonamide 4-Fluoro-3-nitrobenzenesulfonamide (2.18 g), (tetrahydropyran-4-yl) methylamine (1.14 g) and triethylamine (1 g) were stirred in tetrahydrofuran (30 mL) for 24 hours. Dilute the solution with ethyl acetate and NaH₂PO₄Wash with solution and brine and dehydrate (Na₂SO₄), Filtered and concentrated. The product was mixed with ethyl acetate.</p><p num="0259"> Example 1G 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide CH Example 1E (90 mg), Example 1F (45 mg), 1-Ethyl-3- [3- (dimethylamino) propyl] -carbodiimide hydrochloride (65 mg) and 4-dimethylaminopyridine (22 mg)₂Cl₂Stirred in (4 mL) for 24 hours. The reaction was cooled and chromatographed on silica gel with 20-100% ethyl acetate / hexane.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.55 (brs, 1H), 8.63 (t, 1H), 8.47 (d, 1H), 7.75 (d, 1H), 7.46 (m, 6H), 7.35 (m, 2H), 7.24 (m, 3H) , 7.15 (d, 1H), 6.99 (dd, 1H), 6.82 (d, 2H), 6.75 (d, 1H), 6.38 (d, 1H), 3.86 (br d, 2H), 3.49 (m, 2H) , 3.37 (br s, 2H), 3.15 (br s, 4H), 2.34 (br s, 4H), 1.91 (br s, 4H), 1.64 (br d, 2H), 1.29 (m, 3H).</p><p num="0260"> Example 2 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-phenoxy-N-({4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) benzamide Example 2A 4-((Tetrahydro-2H-pyran-4-yl) methylamino) benzenesulfonamide 4-Aminobenzenesulfonamide (6.80 g), tetrahydropyran-4-carboxardhideide (4.96 g) and sodium triacetoxyborohydride (16.74 g) in tetrahydrofuran (300 mL) and acetic acid (15 mL) were stirred for 24 hours. .. The reaction mixture was concentrated and taken up in ethyl acetate. The resulting solution was washed with water and brine, concentrated and chromatographed on silica gel with 50% ethyl acetate / hexane.</p><p num="0261"> Example 2B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-phenoxy-N-({4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) benzamide The compound of this example was produced by using Example 2A instead of Example 1F in Example 1G.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆/ D₂O) δ 7.54 (d, 1H), 7.46 (m, 8H), 7.36 (m, 4H), 7.24 (d, 1H), 7.13 (dd, 1H), 6.93 (d, 2H), 6.75 (d, 1H) ), 6.55 (d, 2H), 6.30 (d, 1H), 3.86 (dd, 2H), 3.36 (s, 2H), 3.28 (t, 2H), 3.10 (br s, 4H), 2.96 (d, 2H) ), 2.32 (br s, 4H), 1.76 (m, 1H), 1.64 (d, 2H), 1.20 (m, 2H).</p><p num="0262"> Example 3 2- (benzyloxy) -4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4- [ (Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 3A Methyl 2- (benzyloxy) -4-fluorobenzoate Methyl 4-fluoro-2-hydroxybenzoate (2.00 g), benzyl bromide (1.54 mL) and cesium carbonate (4.60 g) in N, N-dimethylformamide (50 mL) were stirred for 24 hours. The reaction was taken up in ether, washed with 3 × 1 M NaOH solution and brine, and then concentrated to give the pure product.</p><p num="0263"> Example 3B Methyl 2- (benzyloxy) -4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoate The compound of this example was produced by using Example 3A instead of Example 1C in Example 1D.</p><p num="0264"> Example 3C 2- (benzyloxy) -4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 3B.</p><p num="0265"> Example 3D 2- (benzyloxy) -4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4- [ (Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 3C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 10.90 (br s, 1H), 8.66 (m, 1H), 8.59 (s, 1H), 7.82 (d, 1H), 7.33-7.55 (m, 12H), 7.18-7.27 (m, 3H), 6.61 (s, 1H), 6.56 (d, 1H), 5.22 (s, 2H), 3.86 (br d, 2H), 3.40 (m, 2H), 3.31 (m, 8H), 2.34 (br s, 4H), 1.91 (br s, 2H), 1.64 (br d, 2H), 1.29 (m, 3H).</p><p num="0266"> Example 4 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (2-phenylethoxy) benzamide Example 4A Methyl 4-fluoro-2-phenetoxybenzoate Methyl 4-fluoro-2-hydroxybenzoate (1.00 g) and phenethyl alcohol (0.64 mL) were added to triphenylphosphine (1.54 g) and diisopropylazodicarboxylate (1.04 mL) in tetrahydrofuran (20 mL) at 0 ° C. , The reaction was stirred at room temperature for 24 hours. The mixture was chromatographed on silica gel with 5% ethyl acetate / hexane.</p><p num="0267"> Example 4B Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2-phenetoxybenzoate This Example compound was prepared by substituting Example 1C of Example 1D with Example 4A.</p><p num="0268"> Example 4C 4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2-phenetoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 4B.</p><p num="0269"> Example 4D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (2-phenylethoxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 4C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 10.75 (br s, 1H), 8.66 (m, 2H), 7.91 (d, 1H), 7.47 (m, 6H), 7.20-7.40 (m, 8H), 6.53 (d, 1H), 6.47 (s) , 1H), 4.35 (t, 2H), 4.03 (m, 1H), 3.85 (br d, 2H), 3.38 (s, 2H), 3.25 (m, 8H), 3.13 (t, 2H), 2.36 (br s, 4H), 2.21 (br s, 2H), 1.62 (br d, 2H), 1.20 (m, 2H), 1.17 (m, 1H).</p><p num="0270"> Example 5 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (phenylthio) benzamide Example 5A Methyl 4-fluoro-2- (phenylthio) benzoate 5-Fluoro-2- (methoxycarbonyl) phenylboronic acid (1.00 g), 2- (phenylthio) isoindoline-1,3-dione (0.86 g) and (2-hydroxy-3,5-diisopropylbenzoyloxy) copper (0.29 g) was stirred in dioxane (15 mL) at 50 ° C. for 24 hours. The reaction mixture was chromatographed on silica gel with 5% ethyl acetate / hexane.</p><p num="0271"> Example 5B Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenylthio) benzoate This Example compound was prepared by substituting Example 1C of Example 1D with Example 5A.</p><p num="0272"> Example 5C 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenylthio) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 5B.</p><p num="0273"> Example 5D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (phenylthio) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 5C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.95 (br s, 1H), 8.59 (m, 2H), 7.93 (d, 1H), 7.63 (d, 1H), 7.15-7.50 (m, 14H), 6.73 (d, 1H), 6.18 (s) , 1H), 3.82 (dd, 2H), 3.36 (m, 4H), 3.32 (m, 2H), 2.94 (br s, 4H), 2.30 (br s, 4H), 1.64 (m, 1H), 1.61 ( m, 2H), 1.25 (m, 2H).</p><p num="0274"> Example 6 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (phenylthio) -N-({4-[(tetrahydro-2H-) Pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 5C and Example 1F with Example 2A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆/ D₂O) δ 7.65 (d, 2H), 7.55 (d, 1H), 7.33-7.48 (m, 12H), 7.24 (m, 2H), 6.73 (d, 1H), 6.66 (d, 2H), 6.17 (d) , 1H), 3.85 (dd, 2H), 3.34 (s, 2H), 3.26 (t, 2H), 2.98 (d, 2H), 2.92 (br s, 4H), 2.25 (br s, 4H), 1.78 ( m, 1H), 1.63 (d, 2H), 1.20 (m, 2H).</p><p num="0275"> Example 7 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4-[(3-morpholine-4-ylpropyl) amino ] -3-Nitrophenyl} Sulfonyl) -2- (Phenylthio) Benzamide Example 7A 4- (3-morpholinopropylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine in Example 1F with 3- (N-morpholinyl) -1-propylamine.</p><p num="0276"> Example 7B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4-[(3-morpholine-4-ylpropyl) amino ] -3-Nitrophenyl} Sulfonyl) -2- (Phenylthio) Benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 5C and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 10.20 (br s, 1H), 8.69 (m, 1H), 8.57 (d, 1H), 7.95 (dd, 2H), 7.71 (m, 1H), 7.31-7.51 (m, 10H), 7.12-7.26 (m, 3H), 6.68 (dd, 1H), 6.07 (m, 1H), 4.06 (s, 2H), 3.68 (m, 4H), 3.50 (m, 2H), 3.32 (m, 6H), 2.88 ( m, 4H), 2.27 (m, 4H), 1.91 (m, 2H).</p><p num="0277"> Example 8 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (phenylsulfonyl) benzamide Example 8A Methyl 4-fluoro-2- (phenylsulfonyl) benzoate Example 5A (0.30g) and KMnO₄(1.80 g) was stirred in acetic acid (40 mL) at 60 ° C. for 24 hours. The reaction mixture was filtered through a silica gel filler, concentrated and chromatographed on silica gel with 50% ethyl acetate / hexane.</p><p num="0278"> Example 8B Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenylsulfonyl) benzoate This Example compound was prepared by substituting Example 1C of Example 1D with Example 8A.</p><p num="0279"> Example 8C 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenylsulfonyl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 8B.</p><p num="0280"> Example 8D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (phenylsulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 8C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.95 (br s, 1H), 8.54 (s, 1H), 8.41 (dd, 1H), 7.90 (m, 2H), 7.82 (d, 1H), 7.76 (d, 1H), 7.66 (m, 1H) ), 7.46 (m, 5H), 7.40 (m, 4H), 7.11 (m, 2H), 6.67 (dd, 1H), 6.62 (m, 1H), 4.36 (m, 1H), 3.82 (dd, 2H) , 3.39 (m, 6H), 3.19 (m, 6H), 2.37 (br s, 4H), 1.91 (m, 1H), 1.63 (m, 2H), 1.26 (m, 2H).</p><p num="0281"> Example 9 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (phenylsulfinyl) benzamide Example 9A Methyl 4-fluoro-2- (phenylsulfinyl) benzoate OXONE® (Dupont) (5.60 g), acetic acid (30 mL), water (30 mL) and CH₂Cl₂It was added in portions to Example 5A (1.00 g) in a (20 mL) mixture over 1 hour and the reaction was stirred for an additional hour. The reaction mixture was taken up in ethyl acetate and Na₂S₂O₃Washed with solution, water and brine, concentrated and chromatographed on silica gel with 5-25% ethyl acetate / hexane.</p><p num="0282"> Example 9B Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenylsulfinyl) benzoate This Example compound was prepared by substituting Example 1C of Example 1D with Example 9A.</p><p num="0283"> Example 9C 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenylsulfinyl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 9B.</p><p num="0284"> Example 9D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (phenylsulfinyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 9C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆/ D₂O) δ 8.51 (s, 1H), 7.85 (dd, 2H), 7.64 (d, 2H), 7.48 (m, 8H), 7.32 (m, 1H), 7.23 (m, 1H), 7.14 (m, 4H) ), 6.97 (d, 1H), 3.85 (dd, 2H), 3.35 (d, 2H), 3.34 (m, 6H), 3.27 (t, 2H), 2.74 (br s, 4H), 1.93 (m, 1H) ), 1.64 (d, 2H), 1.28 (m, 2H).</p><p num="0285"> Example 10 2-Benzyl-4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-) 2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 10A Methyl 2-benzyl-4-fluorobenzoate 5-Fluoro-2- (methoxycarbonyl) phenylboronic acid (1.00 g), benzyl bromide (0.50 mL), K₂CO₃(1.75g) and [1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium (II) (PdCl₂(Dppf)) (0.17 g) was stirred in tetrahydrofuran (20 mL) at 60 ° C. for 24 hours. The reaction mixture was chromatographed on silica gel with 2% ethyl acetate / hexane.</p><p num="0286"> Example 10B Methyl 2-benzyl-4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 1C of Example 1D with Example 10A.</p><p num="0287"> Example 10C 2-Benzyl-4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid The example compounds, actual were prepared Example 1D ofExample1E substituting Example 10B.</p><p num="0288"> Example 10D 2-Benzyl-4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-) 2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 10C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆/ D₂O) δ 8.55 (d, 1H), 7.90 (d, 1H), 7.38-7.56 (m, 10H), 7.25 (m, 2H), 6.96 (d, 2H), 6.83 (s, 2H), 6.75 (d , 1H), 4.06 (s, 2H), 3.85 (dd, 2H), 3.48 (s, 2H), 3.37 (d, 2H), 3.25 (t, 2H), 3.20 (br s, 4H), 2.44 (br s, 4H), 1.91 (m, 1H), 1.63 (d, 2H), 1.29 (m, 2H).</p><p num="0289"> Example 11 2-Benzyl-4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4- [(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 10C and Example 1F with Example 2A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.70 (br s, 1H), 7.48 (m, 6H), 6.88 (m, 6H), 6.62 (m, 6H), 6.42 (dd, 2H), 3.83 (dd, 4H), 3.24 (m, 6H) ), 2.96 (m, 4H), 1.82 (m, 2H), 1.63 (m, 3H), 1.18 (m, 4H).</p><p num="0290"> Example 12 2-Benzyl-4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4-[(3-morpholine-4-yl) Ilpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 10C and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.90 (br s, 1H), 8.80 (m, 1H), 8.54 (d, 1H), 7.91 (dd, 1H), 7.48 (m, 7H), 7.40 (d, 2H), 7.26 (d, 2H) ), 6.97 (dd, 2H), 6.86 (m, 2H), 6.76 (d, 1H), 4.04 (m, 5H), 3.72 (m, 4H), 3.56 (m, 2H), 3.40 (m, 8H) , 3.21 (m, 4H), 2.34 (m, 2H), 1.98 (m, 2H).</p><p num="0291"> Example 13 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (2-phenylethyl) benzamide Example 13A Methyl 4-fluoro-2-phenethylbenzoate Methyl 2-bromo-4-fluorobenzoate (1.00g), (E) -styrylboronic acid (0.89g), tetrakis (triphenylphosphine) palladium (0) (0.50g) and K₃PO₄(2.28 g) was stirred in dioxane (17 mL) at 90 ° C for 24 hours. The reaction mixture was chromatographed on silica gel with 1-5% ethyl acetate / hexane. The product in methanol (10 ml) was added to 20 wt% fresh dry 5% Pd-C and H in a pressure bottle.₂Stirred underneath for 4 days. The mixture was filtered through a nylon membrane and concentrated.</p><p num="0292"> Example 13B Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2-phenethylbenzoate This Example compound was prepared by substituting Example 1C of Example 1D with Example 13A.</p><p num="0293"> Example 13C 4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2-phenethyl benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 13B.</p><p num="0294"> Example 13D 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -N- (3-nitro-4-((tetrahydro-2H-pyran-4-yl) methylamino) Phenylsulfonyl) -2-phenethylbenzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 13C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆/ D₂O) δ 8.62 (d, 1H), 7.95 (d, 1H), 7.91 (m, 1H), 7.35-7.52 (m, 6H), 7.19 (m, 2H), 7.13 (m, 2H), 6.99 (m) , 4H), 6.83 (d, 1H), 6.70 (d, 1H), 6.65 (s, 1H), 3.80 (m, 2H), 3.24 (m, 2H), 3.18 (t, 2H), 3.11 (br s) , 4H), 2.91 (t, 2H), 2.48 (m, 2H), 2.38 (br s, 4H), 1.81 (m, 1H), 1.54 (d, 2H), 1.23 (m, 2H).</p><p num="0295"> Example 14 2- (Benzylamino) -4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4- [ (Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 14A Methyl 2- (benzylamino) -4-fluorobenzoate CH₂Cl₂Methyl 2-amino-4-fluorobenzoate (0.90 g), benzaldehyde (0.54 mL), sodium triacetoxyborohydride (1.58 g) and acetic acid (0.3 mL) in (20 mL) were stirred for 3 hours. The reaction was quenched with methanol, concentrated and chromatographed on silica gel with 5% ethyl acetate / hexane.</p><p num="0296"> Example 14B Methyl 2- (benzylamino) -4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 1C of Example 1D with Example 14A.</p><p num="0297"> Example 14C 2- (benzylamino) -4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 14B.</p><p num="0298"> Example 14D 2- (Benzylamino) -4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4- [ (Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 14C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆/ D₂O) δ 8.58 (d, 1H), 7.92 (d, 1H), 7.87 (m, 1H), 7.59 (d, 2H), 7.48 (m, 2H), 7.43 (m, 4H), 7.20-7.29 (m) , 8H), 6.15 (d, 1H), 4.32 (s, 2H), 3.85 (m, 2H), 3.49 (m, 2H), 3.33 (m, 2H), 3.26 (t, 2H), 3.12 (br s) , 4H), 2.39 (br s, 4H), 1.90 (m, 1H), 1.62 (d, 2H), 1.27 (m, 2H).</p><p num="0299"> Example 15 2-Anilino-4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-) 2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 15A Methyl 4-fluoro-2- (phenylamino) benzoate Methyl 2-bromo-4-fluorobenzoate (1.00 g) in toluene (12 mL), aniline (0.47 mL), palladium (II) acetate (0.048 g), 2,2'-bis (diphenylphosphino) -1, 1'-binaphthyl (0.214g) and Cs₂CO₃(2.08 g) was stirred at 90 ° C for 24 hours. The reaction was concentrated and chromatographed on silica gel with 5-50% ethyl acetate / hexane.</p><p num="0300"> Example 15B Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenylamino) benzoate This Example compound was prepared by substituting Example 1C of Example 1D with Example 15A.</p><p num="0301"> Example 15C 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenylamino) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 15B.</p><p num="0302"> Example 15D 2-Anilino-4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-) 2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 15C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.55 (br s, 1H), 8.56 (m, 2H), 7.92 (d, 1H), 7.72 (d, 1H), 7.47 (m, 6H), 7.25 (m, 4H), 7.12 (d, 2H) ), 6.95 (m, 2H), 6.53 (s, 1H), 6.38 (dd, 1H), 3.81 (dd, 2H), 3.37 (br s, 4H), 3.12 (br s, 4H), 2.41 (br s) , 4H), 1.91 (m, 1H), 1.61 (br d, 2H), 1.23 (m, 4H).</p><p num="0303"> Example 16 2-Anilino-4- {4-[(4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4- [(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 15C and Example 1F with Example 2A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆/ D₂O) δ 7.78 (d, 1H), 7.52 (d, 2H), 7.47 (m, 6H), 7.36 (m, 3H), 7.27 (m, 3H), 7.11 (m, 2H), 6.90 (m, 1H) ), 6.61 (s, 1H), 6.53 (d, 1H), 6.31 (d, 1H), 4.46 (s, 1H), 3.82 (m, 2H), 3.37 (s, 2H), 3.26 (t, 2H) , 3.05 (br s, 4H), 2.93 (d, 2H), 2.37 (br s, 4H), 1.77 (m, 1H), 1.63 (d, 2H), 1.20 (m, 2H).</p><p num="0304"> Example 17 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-methoxy-N-({3-nitro-4-[(tetrahydro-) 2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 17A Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2-methoxybenzoate Methyl 4-bromo-2-methoxybenzoic acid (700 mg), Example 1B (983 mg), K₃PO₄(909 mg), tris (dibenzylideneacetone) dipalladium (0) (78 mg) and 2- (di-t-butylphosphino) biphenyl (102 mg) in 1,2-dimethoxyethane (10 mL) at 80 ° C. Stirred for 24 hours. The reaction mixture was chromatographed on silica gel with 20-50% ethyl acetate / hexane.</p><p num="0305"> Example 17B 4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2-methoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 17A.</p><p num="0306"> Example 17C 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-methoxy-N-({3-nitro-4-[(tetrahydro-) 2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 17B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 10.81 (br s, 1H), 8.64 (m, 2H), 7.96 (d, 1H), 7.20-7.54 (m, 10H), 6.52 (d, 1H), 6.46 (s, 1H), 3.90 (s , 3H), 3.40 (m, 4H), 3.27 (br s, 4H), 2.39 (br s, 4H), 1.91 (m, 1H), 1.62 (br d, 2H), 1.27 (m, 4H).</p><p num="0307"> Example 18 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3-3-yl] Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide Example 18A Methyl 4,4-dimethyl-2- (trifluoromethylsulfonyloxy) cyclohex-1-encarboxylate 5,5-Dimethyl-2-methoxycarbonylcyclohexanone (38.5 g) was added dropwise at 0 ° C. to a suspension of hexane-washed NaH (17 g) in dichloromethane (700 mL). After stirring for 30 minutes, the mixture was cooled to -78 ° C and trifluoromethanesulfonic anhydride (40 mL) was added. The reaction mixture was warmed to room temperature and stirred for 24 hours. The organic layer was washed with brine, dehydrated and concentrated to give the product.</p><p num="0308"> Example 18B Methyl 2- (4-chlorophenyl) -4,4-dimethylcyclohexa-1-encarboxylate Example 18A (62.15g), 4-chlorophenylboronic acid (32.24g), CsF (64g) and tetrakis (triphenylphosphine) palladium (0) in 2: 1 1,2-dimethoxyethane / methanol (600mL). (2 g) was heated to 70 ° C for 24 hours. The mixture was concentrated. Ether (4 x 200 mL) was added and the mixture was filtered. The combined ether solution was concentrated to give the product.</p><p num="0309"> Example 18C (2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methanol LiBH₄Methanol (25 mL) was added slowly with a syringe to a mixture of (13 g), Example 18B (53.8 g) and ether (400 mL). The mixture was stirred at room temperature for 24 hours. The reaction was quenched with 1N HCl while ice-cooled. The mixture was diluted with water and extracted with ether (3 x 100 mL). The extract was dehydrated and concentrated. The crude product was chromatographed on silica gel with 0-30% ethyl acetate / hexane.</p><p num="0310"> Example 18D Methyl 2-bromo-4- (piperazine-1-yl) benzoate This Example compound was prepared by replacing Example 1B of Example 1D with piperazine and Example 1C with methyl 2-bromo-4-fluorobenzoate.</p><p num="0311"> Example 18E Methyl 2-bromo-4- (4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate CH MsCl (7.5 mL) using a syringe₂Cl₂It was added to Example 18C (29.3g) and triethylamine (30mL) in (500mL) at 0 ° C. and the mixture was stirred for 1 minute. Example 18D (25 g) was added and the reaction was stirred at room temperature for 24 hours. The suspension was washed with brine, dehydrated and concentrated. The crude product was chromatographed on silica gel with 10-20% ethyl acetate / hexane.</p><p num="0312"> Example 18F Methyl 4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -2-phenoxybenzoate Examples 18E (500 mg), phenol (195 mg), Cs in toluene (2 mL)₂CO₃(674 mg), 1-naphthoic acid (356 mg), copper (I) triflate-toluene complex (45 mg), ethyl acetate (0.016 mL) and 4A sheave (50 mg) were stirred at 105 ° C for 24 hours. The reaction was cooled and taken up in ethyl acetate (100 mL) and water (40 mL). Separate the layers and separate the organic layer into 2 x Na₂CO₃Washed with solution and brine, dehydrated and concentrated. The crude product was chromatographed on silica gel with 20% ethyl acetate / hexane.</p><p num="0313"> Example 18G 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 18F.</p><p num="0314"> Example 18H 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3-3-yl] Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 18G and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.10 (br s, 1H), 8.76 (m, 1H), 8.46 (d, 1H), 7.76 (dd, 1H), 7.50 (d, 1H), 7.35 (d, 2H), 7.23 (d, 2H) ), 7.06 (dd, 2H), 6.99 (dd, 1H), 6.81 (d, 2H), 6.74 (d, 1H), 6.34 (s, 1H), 3.62 (m, 4H), 3.46 (m, 2H) , 3.13 (m, 4H), 2.76 (m, 2H), 2.48 (m, 2H), 2.22 (m, 6H), 1.97 (m, 2H), 1.82 (m, 2H), 1.40 (t, 2H), 1.06 (m, 7H), 0.94 (s, 3H).</p><p num="0315"> Example 19 4- (4-{[2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3-3-yl] Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide Example 19A Methyl 5,5-dimethyl-2- (trifluoromethylsulfonyloxy) cyclohex-1-encarboxylate This Example compound was prepared by replacing 5,5-dimethyl-2-methoxycarbonylcyclohexanone in Example 18A with 4,4-dimethyl-2-methoxycarbonylcyclohexanone.</p><p num="0316"> Example 19B Methyl 2- (4-chlorophenyl) -5,5-dimethylcyclohexa-1-encarboxylate This Example compound was prepared by substituting Example 18A of Example 18B with Example 19A.</p><p num="0317"> Example 19C (2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methanol This Example compound was prepared by substituting Example 18B of Example 18C with Example 19B.</p><p num="0318"> Example 19D Methyl 2-bromo-4- (4-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 18C of Example 18E with Example 19C.</p><p num="0319"> Example 19E Methyl 4-(4-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by substituting Example 18E of Example 18F with Example 19D.</p><p num="0320"> Example 19F 4- (4-((2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 19E.</p><p num="0321"> Example 19G 4- (4-{[2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3-3-yl] Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 19F and substituting Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.10 (br s, 1H), 8.71 (m, 1H), 8.42 (d, 1H), 7.73 (dd, 1H), 7.53 (d, 1H), 7.34 (d, 2H), 7.21 (dd, 2H) ), 7.10 (d, 2H), 6.96 (dd, 1H), 6.78 (d, 2H), 6.70 (d, 1H), 6.32 (s, 1H), 3.61 (m, 4H), 3.44 (m, 2H) , 3.09 (m, 4H), 2.71 (m, 2H), 2.44 (m, 4H), 2.21 (m, 4H), 1.96 (m, 2H), 1.79 (m, 2H), 1.47 (t, 2H), 1.17 (m, 3H), 1.08 (m, 4H), 0.95 (s, 3H).</p><p num="0322"> Example 20 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-5-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 20A Ethyl 2- (1H-indazole-5-yloxy) -4-fluorobenzoate Ethyl 2,4-difluorobenzoate (1.14g), K₃PO₄(1.30 g) and 5-hydroxyindazole (0.90 g) were stirred in diglyme (12 mL) at 110 ° C. for 24 hours. The reaction was cooled and poured into ether. The solution was washed 3 times with 1M NaOH solution and brine and dehydrated. The solution was then concentrated and the crude product was chromatographed on silica gel with 20% ethyl acetate / hexane.</p><p num="0323"> Example 20B tert-Butyl 4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-carboxylate This Example compound was prepared by substituting Example 18D of Example 18E with Nt-butoxycarbonylpiperazine.</p><p num="0324"> Example 20C 1-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine This Example compound was prepared by substituting Example 1A of Example 1B with Example 20B.</p><p num="0325"> Example 20D Ethyl 2- (1H-indazole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate Example 20A (330mg), Example 20C (335mg) and HK₂PO₄(191 mg) was stirred in dimethyl sulfoxide (5 mL) at 140 ° C. for 24 hours. The reaction was diluted with ethyl acetate, washed 3 times with water, washed with brine, dehydrated and concentrated. The crude product was chromatographed on silica gel with 30% ethyl acetate / hexane.</p><p num="0326"> Example 20E 2- (1H-indazole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 20D.</p><p num="0327"> Example 20F 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-5-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 20E and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.03 (br s, 1H), 11.25 (br s, 1H), 8.70 (m, 1H), 8.48 (d, 1H), 7.94 (dd, 1H), 7.68 (dd, 1H), 7.52 (m, 2H), 7.34 (d, 2H), 7.06 (m, 4H), 6.96 (dd, 1H), 6.88 (d, 1H), 6.23 (s, 1H), 3.61 (m, 4H), 3.44 (m, 2H) ), 3.05 (m, 4H), 2.73 (m, 2H), 2.42 (m, 4H), 2.18 (m, 4H), 1.99 (m, 2H), 1.91 (d, 2H), 1.78 (m, 2H) , 1.39 (t, 2H), 1.17 (m, 2H), 0.93 (s, 6H).</p><p num="0328"> Example 21 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 21A 4- (1-Methylpiperidin-4-ylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by substituting the (tetrahydropyran-4-yl) methylamine of Example 1F with 4-amino-N-methylpiperidine.</p><p num="0329"> Example 21B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 20E and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 12.80 (br s, 1H), 10.70 (br s, 1H), 8.34 (s, 1H), 8.02 (d, 1H), 7.87 (d, 1H), 7.70 (dd, 1H), 7.55 (m, 2H), 7.36 (d, 2H), 7.06 (m, 2H), 6.95 (m, 1H), 6.72 (d, 1H), 6.62 (d, 1H), 6.24 (s, 1H), 3.35 (m, 4H) ), 3.18 (m, 2H), 3.00 (m, 2H), 2.80 (m, 4H), 2.73 (m, 2H), 2.20 (m, 4H), 1.99 (m, 2H), 1.91 (s, 3H) , 1.54 (m, 1H), 1.41 (t, 2H), 1.22 (m, 2H), 1.09 (s, 6H).</p><p num="0330"> Example 22 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3-3-yl] Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2- (1,2,3,4-tetrahydroquinoline-6-yloxy) benzamide Example 22A Ethyl 4-fluoro-2- (1,2,3,4-tetrahydroquinoline-6-yloxy) benzoate This Example compound was prepared by replacing the 5-hydroxyindazole of Example 20A with 5-hydroxy-1,2,3,4-tetrahydroquinoline.</p><p num="0331"> Example 22B Ethyl 4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -2- (1,2,3,4-tetrahydroquinoline) -6-yloxy) benzoate This Example compound was prepared by substituting Example 20A of Example 20D with Example 22A.</p><p num="0332"> Example 22C 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -2- (1,2,3,4-tetrahydroquinoline- 6-Iloxy) Benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 22B.</p><p num="0333"> Example 22D 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3-3-yl] Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2- (1,2,3,4-tetrahydroquinoline-6-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 22C and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 10.95 (br s, 1H), 8.83 (m, 1H), 8.60 (d, 1H), 7.90 (dd, 1H), 7.46 (d, 1H), 7.35 (d, 2H), 7.21 (dd, 2H) ), 7.06 (d, 2H), 6.62 (m, 2H), 6.42 (d, 1H), 6.11 (d, 1H), 5.61 (br s, 1H), 4.02 (m, 1H), 3.61 (m, 4H) ), 3.48 (m, 2H), 3.17 (m, 2H), 3.07 (m, 4H), 2.74 (m, 2H), 2.63 (m, 2H), 2.44 (m, 4H), 2.19 (m, 4H) , 1.97 (m, 4H), 1.79 (m, 4H), 1.41 (t, 2H), 1.17 (m, 4H), 0.94 (s, 6H).</p><p num="0334"> Example 23 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1-1-yl] Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1,2,3,4-tetrahydroquinoline-6-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 22C and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.10 (br s, 1H), 8.71 (m, 1H), 8.42 (d, 1H), 7.73 (dd, 1H), 7.53 (d, 1H), 7.34 (d, 2H), 7.21 (dd, 2H) ), 7.10 (d, 2H), 6.96 (dd, 1H), 6.78 (d, 2H), 6.70 (d, 1H), 6.32 (s, 1H), 3.61 (m, 4H), 3.44 (m, 2H) , 3.09 (m, 4H), 2.71 (m, 2H), 2.44 (m, 4H), 2.21 (m, 4H), 1.96 (m, 2H), 1.79 (m, 2H), 1.47 (t, 2H), 1.17 (m, 3H), 1.08 (m, 4H), 0.95 (s, 3H).</p><p num="0335"> Example 24 4- (4-{[4'-Chloro-4- (pyrrolidin-1-ylmethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 24A Methyl 5-formyl-2- (trifluoromethylsulfonyloxy) benzoate 150 mL CH of trifluoromethanesulfonic anhydride (7.74 mL)₂Cl₂Methyl 5-formyl-2-hydroxybenzoate (7.5 g) in the mixture was added at 0 ° C., the reaction was stirred and warmed to room temperature over 3 hours. CH reactant₂Cl₂Dilute with (150 mL), wash with 3 x brine, Na₂SO₄It was dehydrated and concentrated. The product was used without further purification.</p><p num="0336"> Example 24B Methyl 4'-chloro-4-formylbiphenyl-2-carboxylate Example 24A (14.5 g), 4-chlorophenylboronic acid (6.88 g) CsF (12.2 g) and tetrakis (triphenylphosphine) palladium (0) were stirred at 70 ° C. for 24 hours. The reaction was cooled, filtered and concentrated. The crude product was taken in ethyl acetate (250 mL), washed with 3 x 1M NaOH and brine, concentrated and chromatographed on silica gel with 10% ethyl acetate / hexane.</p><p num="0337"> Example 24C Methyl 4'-chloro-4- (pyrrolidin-1-ylmethyl) biphenyl-2-carboxylate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehyde of Example 1A with Example 24B and tert-butylpiperazin-1-carboxylate with pyrrolidine.</p><p num="0338"> Example 24D (4'-chloro-4- (pyrrolidin-1-ylmethyl) biphenyl-2-yl) methanol DIBAL in hexane (1M, 5.9mL), CH₂Cl₂Addition to Example 24C (650 mg) in (30 mL) at 0 ° C. and the reaction was stirred for 20 minutes. Methanol (2 mL) and 1M NaOH (10 mL) were added slowly to quench the reaction and the resulting solution was extracted twice with ethyl acetate. Wash the extract with brine and Na₂SO₄It was dehydrated and concentrated. The product was used without further purification.</p><p num="0339"> Example 24E 4'-Chloro-4- (pyrrolidin-1-ylmethyl) biphenyl-2-carbaldehyde CH Dess-Martin Peryoginan (1.30g)₂Cl₂Example 24D (770 mg) in (30 mL) was added at room temperature and the reaction was stirred for 24 hours. The reaction mixture was concentrated and chromatographed on silica gel with 1% triethylamine in 25% ethyl acetate / hexane.</p><p num="0340"> Example 24F Methyl 2- (1H-indole-4-yloxy) -4-fluorobenzoate This Example compound was prepared by replacing the 5-hydroxyindazole of Example 20A with 4-hydroxyindole and the ethyl 2,4-difluorobenzoate with methyl 2,4-difluorobenzoate.</p><p num="0341"> Example 24G tert-Butyl 4- (3- (1H-indole-4-yloxy) -4- (methoxycarbonyl) phenyl) piperazin-1-carboxylate This Example compound was prepared by replacing Example 20A of Example 20D with Example 24F and Example 20C with tert-butylpiperazin-1-carboxylate.</p><p num="0342"> Example 24H Methyl 2- (1H-indole-4-yloxy) -4- (piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 1A of Example 1B with Example 24G.</p><p num="0343"> Example 24I Methyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4- (pyrrolidin-1-ylmethyl) biphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2 carboxaldehyde of Example 1A with Example 24E and tert-butylpiperazin-1-carboxylate with Example 24H.</p><p num="0344"> Example 24J 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4- (pyrrolidin-1-ylmethyl) biphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 24I.</p><p num="0345"> Example 24K 4- (4-{[4'-Chloro-4- (pyrrolidin-1-ylmethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 24J.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.52 (br s, 1H), 11.26 (s, 1H), 10.68 (br s, 1H), 8.61 (dd, 1H), 8.49 (s, 1H), 8.19 (br s, 1H), 7.66 (d , 2H), 7.54 (m, 3H), 7.36 (m, 2H), 7.28 (s, 1H), 7.24 (d, 1H), 7.05 (d, 1H), 6.95 (dd, 1H), 6.75 (d, 1H), 6.35 (m, 2H), 6.26 (s, 1H), 4.38 (m, 3H), 3.85 (dd, 2H), 3.61 (m, 4H), 3.24 (m, 4H), 3.09 (m, 4H) ), 2.85 (m, 2H), 2.35 (m, 2H), 2.02 (m, 2H), 1.87 (m, 4H), 1.60 (m, 2H), 1.25 (m, 2H).</p><p num="0346"> Example 25 4- (4-{[4'-Chloro-4- (2-pyrrolidin-1-ylethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 25A Methyl 4'-chloro-4- (2-oxoethyl) biphenyl-2-carboxylate Lithium diisopropylamide (2M, 3.3 mL) was added to a solution of (methoxymethyl) diphenylphosphine oxide (1.62 g) at -78 ° C in 40 mL tetrahydrofuran, stirred for 3 minutes, and then Example 24B (1.57 g) was added. , The solution was warmed to room temperature. NaH (230 mg) and 40 mL N, N-dimethylformamide were added and the mixture was heated to 60 ° C for 1 hour. Cool the reactants and NaH₂PO₄It was poured into the solution. The resulting solution was extracted twice with ether and the combined extracts were washed twice with water and brine and concentrated. A crude mixture of enol ether was taken in 1M HCl (50 mL) and dioxane (50 mL) and stirred at 60 ° C. for 3 hours. Cool the reactants and LVDS₃It was poured into the solution. The resulting solution was extracted twice with ether and the combined extracts were washed with water and brine and concentrated. The product was used without further purification.</p><p num="0347"> Example 25B Methyl 4'-chloro-4- (2- (pyrrolidin-1-yl) ethyl) biphenyl-2-carboxylate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 25A and tert-butylpiperazin-1-carboxylate with pyrrolidine.</p><p num="0348"> Example 25C (4'-chloro-4- (2- (pyrrolidin-1-yl) ethyl) biphenyl-2-yl) methanol This Example compound was prepared by substituting Example 24C of Example 24D with Example 25B.</p><p num="0349"> Example 25D 4'-Chloro-4- (2- (pyrrolidin-1-yl) ethyl) biphenyl-2-carbaldehyde This Example compound was prepared by substituting Example 24D of Example 24E with Example 25C.</p><p num="0350"> Example 25E Methyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4- (2- (pyrrolidin-1-yl) ethyl) biphenyl-2-yl) methyl) piperazine-1 -Il) Benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2 carboxaldehyde of Example 1A with Example 25D and tert-butylpiperazin-1-carboxylate with Example 24H.</p><p num="0351"> Example 25F 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4- (2- (pyrrolidin-1-yl) ethyl) biphenyl-2-yl) methyl) piperazine-1- Indole) Benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 25E.</p><p num="0352"> Example 25G 4- (4-{[4'-Chloro-4- (2-pyrrolidin-1-ylethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 25F.¹1 H NMR (300MHZ, dimethyl sulfoxide-d₆) δ 11.15 (s, 1H), 8.47 (t, 1H), 8.42 (s, 1H), 7.68 (dd, 1H), 7.58 (d, 1H), 7.44 (m, 4H), 7.22 (m, 3H) , 7.10 (d, 1H), 6.92 (m, 2H), 6.68 (d, 1H), 6.34 (d, 1H), 6.26 (s, 2H), 3.87 (dd, 2H), 3.61 (m, 4H), 3.10-3.24 (m, 11H), 2.97 (m, 4H), 2.31 (m, 4H), 1.89 (m, 4H), 1.61 (m, 2H), 1.26 (m, 2H).</p><p num="0353"> Example 26 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1-1-yl] Cyclopentyl piperidine-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 26A Ethyl 2- (1H-indole-5-yloxy) -4-fluorobenzoate This Example compound was prepared by replacing 5-hydroxyindazole of Example 20A with 5-hydroxyindole.</p><p num="0354"> Example 26B Ethyl 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 20A of Example 20D with Example 26A.</p><p num="0355"> Example 26C 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 26B.</p><p num="0356"> Example 26D 4- (1-Cyclopentyl piperidine-4-ylamino) -3-nitrobenzene sulfonamide This Example compound was prepared by substituting the (tetrahydropyran-4-yl) methylamine of Example 1F with 1-cyclopentylpiperidin-4-amine.</p><p num="0357"> Example 26E 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1-1-yl] Cyclopentyl piperidine-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 26D.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.13 (br s, 1H), 8.52 (s, 1H), 8.14 (d, 1H), 7.80 (d, 1H), 7.52 (d, 1H), 7.35 (m, 4H), 7.04 (m, 4H) ), 6.80 (d, 1H), 6.61 (d, 1H), 6.36 (s, 1H), 6.14 (s, 1H), 5.76 (s, 1H), 3.84 (m, 2H), 3.24 (m, 4H) , 2.99 (m, 4H), 2.85 (m, 2H), 2.71 (m, 2H), 2.16 (m, 6H), 1.95 (m, 4H), 1.50-1.70 (m, 6H), 1.38 (m, 2H) ), 1.17 (m, 2H), 0.93 (s, 6H).</p><p num="0358"> Example 27 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] -3-isobutylpiperazin-1-yl} -N-({3-nitro-4-[(tetrahydro-) 2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 27A Methyl 2-bromo-4-methylpentanoate Add KBr (17.6 g) to concentrated HBr (48%) (20 mL) in water (214 mL), cool to 0 ° C, then add sodium nitrite (5.2 g) in bulk, then DL-leucine (DL-leucine) 5.2 g) was added in portions. The reaction was mechanically stirred at 0 ° C for 1.5 hours and then extracted with 2 x 200 mL ethyl acetate. The combined organic layer was washed with brine and Na.₂SO₄Dehydrated with. After filtering and concentrating, the resulting oil is CH₂Cl₂/ 2.0M (TMS) CHN in ether (30mL) dissolved in methanol₂Then, it was treated at room temperature for 10 minutes. The reaction was concentrated and then purified by flash chromatography with 97.5 / 2.5 hexane / ethyl acetate.</p><p num="0359"> Example 27B 3-Isobutylpiperazin-2-one Example 27A (2.2 g) in ethanol (15 mL) was added dropwise to a reflux stirring solution of ethane-1,2-diamine (13.2 mL) in ethanol (60 mL) over 2.5 hours. Heating was continued for an additional 2.5 hours, then NaOEt in ethanol was added (21% by weight, 4.0 mL) and heated for an additional 90 minutes. The reaction was then cooled and concentrated. After mixing with ether, the title compound was used without purification.</p><p num="0360"> Example 27C 4'-chlorobiphenyl-2-carbaldehyde 2-Bromobenzaldehyde (2.3 ml) and tetrakis (triphenylphosphine) palladium (0) (0.35 g) in toluene (50 mL), 4-chlorophenylboronic acid (4.0 g) and 2 M Na₂CO₃(70 ml) was added. The mixture was heated under reflux for 1 hour. The reaction was cooled, diluted with water and extracted with ethyl acetate. The organic layer was washed with brine and the combined aqueous layer was back-extracted with ethyl acetate. Na the organic layer together₂SO₄Dehydrated with. The crude material was purified by flash chromatography with 97.5 / 2.5 hexane / ethyl acetate.</p><p num="0361"> Example 27D 4-((4'-chlorobiphenyl-2-yl) methyl) -3-isobutylpiperazin-2-one This Example compound was prepared by replacing the tert-butylpiperazin-1-carboxylate of Example 1A with Example 27B.</p><p num="0362"> Example 27E 1-((4'-chlorobiphenyl-2-yl) methyl) -2-isobutylpiperazine A borane-methyl sulfide complex (10 M in tetrahydrofuran) (0.24 mL) was added to a solution of Example 27D in tetrahydrofuran (3.6 mL). The reaction was heated under reflux for 16 hours and then cooled in an ice / water bath. Methanol (5 mL) was added carefully and the mixture was stirred cold for 75 minutes. 4N HCl in dioxane (0.65 mL) was then added and the reaction was heated under reflux for 60 minutes. After cooling to room temperature, 1N NH₄OH (2.6 mL) was added and the reaction was stirred for 15 minutes. The reaction was then concentrated, redissolved in methanol, concentrated, redissolved in toluene and concentrated. Crude solid CHCl₃/ Slurryed in methanol, the solid was filtered off, and the filtrate was concentrated to give the title compound.</p><p num="0363"> Example 27F Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) -3-isobutylpiperazin-1-yl) -2-phenoxybenzoate This Example compound was prepared by substituting Example 1B of Example 1D with Example 27E.</p><p num="0364"> Example 27G 4- (4-((4'-chlorobiphenyl-2-yl) methyl) -3-isobutylpiperazin-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 27F.</p><p num="0365"> Example 27H 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] -3-isobutylpiperazin-1-yl} -N-({3-nitro-4-[(tetrahydro-) 2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide CH Example 27G (13mg), Example 1F (7mg), 1-Ethyl-3- [3- (dimethylamino) propyl] -carbodiimide hydrochloride (8mg) and 4-dimethylaminopyridine (5mg)₂Cl₂Stirred in (1 mL) for 24 hours. The product is 20-100% CH by preparative HPLC using a C18 column, 250 x 50 mm, 10 μ.₃The product was obtained as a trifluoroacetic acid salt by eluting with a gradient of 0.1% trifluoroacetic acid in CN vs. water and purifying.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.62 (br s, 1H), 9.10 (br s, 1H), 8.65 (t, 1H), 8.47 (d, 1H), 7.77 (dd, 1H), 7.70 (br s, 1H), 7.50 (m) , 5H), 7.39 (m, 3H), 7.25 (m, 2H), 7.18 (d, 1H), 7.01 (dd, 1H), 6.83 (m, 2H), 6.76 (m, 1H), 6.40 (br s) , 1H), 4.70 and 4.15 (both v br s, total 1H), 3.85 (dd, 2H), 3.60 (v br s, 1H), 3.32, 3.27, 3.24, 3.06 (total m, total 11H), 1.90 ( m, 1H), 1.62 (m, 3H), 1.30 (m, 4H), 0.70 (br m, 6H).</p><p num="0366"> Example 28 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[4- (2,4-dioxo-3-azabicyclo] [3.2 .0] hepta-3-yl) phenyl] sulfonyl} -2-phenoxybenzamide This Example compound was replaced with Example 27G of Example 27H with Example 1E and Example 1F was replaced with 4- (2,4-dioxo-3-azabicyclo [3.2.0] heptane-3-yl) benzenesulfonamide. Prepared by replacing with.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.87 (br s, 1H), 9.58 (br s, 1H), 7.93 (d, 2H), 7.71 (br s, 1H), 7.54 (m, 7H), 7.35 (m, 5H), 7.10 (dd) , 1H), 6.89 (d, 2H), 6.78 (dd, 1H), 6.42 (s, 1H), 4.37 (br s, 1H), 3.78 (br s, 1H), 3.43 (m, 4H), 3.22, 3.00, 2.85 (total v br s, total 6H), 2.62 (m, 2H), 2.18 (m, 2H).</p><p num="0367"> Example 29 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[4- (4-methyl-6-oxo-1,4) , 5,6-tetrahydropyridazine-3-yl) phenyl] sulfonyl} -2-phenoxybenzamide This Example compound was replaced with Example 27G of Example 27H with Example 1E and Example 1F was replaced with 4- (4-methyl-6-oxo-1,4,5,6-tetrahydropyridazine-3-yl). Prepared by replacing with benzenesulfonamide.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.87 (br s, 1H), 11.20 (s, 1H), 9.58 (br s, 1H), 7.90 (d, 2H), 7.83 (d, 2H), 7.50 (m, 5H), 7.32 (m, 5H), 7.08 (dd, 1H), 6.85 (d, 2H), 6.76 (dd, 1H), 6.43 (s, 1H), 4.38 (br s, 1H), 3.80 (br s, 1H), 3.60 (m) , 2H), 3.40 (m, 2H), 3.21,3.00,2.84 (total br s, total 6H), 2.75 (dd, 1H), 2.28 (d, 1H), 1.08 (d, 3H).</p><p num="0368"> Example 30 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[4- (3,3-dimethyl-2-oxoazetidine-1) -Il) Phenyl] Sulfonyl} -2-phenoxybenzamide This Example compound was prepared by replacing Example 27G of Example 27H with Example 1E and Example 1F with 4- (3,3-dimethyl-2-oxoazetidine-1-yl) benzenesulfonamide.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.62 (br s, 1H), 9.58 (br s, 1H), 7.80 (d, 2H), 7.72 (br s, 1H), 7.50 (m, 5H), 7.40 (m, 4H), 7.33 (m) , 3H), 7.08 (dd, 1H), 6.85 (d, 2H), 6.76 (dd, 1H), 6.41 (s, 1H), 4.38 (br s, 1H), 3.77 (br s, 1H), 3.58 ( s, 2H), 3.45 (m, 2H), 3.21,3.00,2.84 (total br s, total 6H), 1.32 (s, 6H).</p><p num="0369"> Example 31 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[4- (4-nitro-2H-1,2,3) -Triazole-2-yl) phenyl] sulfonyl} -2-phenoxybenzamide This Example compound was replaced with Example 27G of Example 27H with Example 1E and Example 1F with 4- (4-nitro-2H-1,2,3-triazole-2-yl) benzenesulfonamide. Prepared.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.98 (br s, 1H), 9.58 (br s, 1H), 9.11 (s, 1H), 8.21 (d, 2H), 8.05 (d, 2H), 7.70 (br s, 1H), 7.50 (m) , 5H), 7.39 (m, 2H), 7.30 (m, 1H), 7.24 (m, 2H), 7.00 (dd, 1H), 6.82 (d, 2H), 6.78 (dd, 1H), 6.43 (s, 1H), 4.38 (br s, 1H), 3.77 (br s, 1H), 3.45 (m, 2H), 3.21,3.00, 2.84 (total br s, total 6H).</p><p num="0370"> Example 32 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-phenoxy-N-{[2- (2-piperidine-1-ylethoxy) ) Phenyl] sulfonyl} benzamide This Example compound was prepared by replacing Example 27G of Example 27H with Example 1E and Example 1F with 2- (2- (piperidine-1-yl) ethoxy) benzenesulfonamide.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.65 (br s, 1H), 9.77 (br s, 1H), 8.95 (br s, 1H), 7.80 (dd, 1H), 7.70 (br s, 1H), 7.68 (m, 1H), 7.50 ( m, 5H), 7.36 (m, 5H), 7.23 (d, 1H), 7.15 (m, 2H), 6.90 (d, 2H), 6.78 (dd, 1H), 6.42 (s, 1H), 4.40 (m) , 3H), 3.80 (br s, 1H), 3.40, 3.20 3.00, 2.90 (total v br m, 13H in total), 1.63 (m, 5H), 1.27 (v br s, 1H).</p><p num="0371"> Example 33 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[3-({[(1-ethylpyrrolidine-2-yl) yl) ) Methyl] amino} carbonyl) -4-methoxyphenyl] sulfonyl} -2-phenoxybenzamide This Example compound was replaced with Example 27G of Example 27H with Example 1E and Example 1F was replaced with N-((1-ethylpyrrolidine-2-yl) methyl) -2-methoxy-5-sulfamoylbenzamide. Prepared by replacing with.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.75 (br s, 1H), 9.70 (br s, 1H), 9.25 (br s, 1H), 8.62 (t, 1H), 8.25 (d, 1H), 7.90 (dd, 1H), 7.70 (br s, 1H), 7.50 (m, 5H), 7.40 (m, 2H), 7.10 (m, 5H), 7.09 (dd, 1H), 6.85 (d, 2H), 6.76 (dd, 1H), 6.40 (s) , 1H), 4.39 (br s, 1H), 3.96 (s, 3H), 3.77 (br s, 1H), 3.60 (m, 4H), 3.55-2.80 (envelope, 10H), 2.12 (m, 1H), 2.00 (m, 1H), 1.85 (m, 2H), 1.23 (t, 3H).</p><p num="0372"> Example 34 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1-naphthyloxy) -N-({3-nitro-4) -[(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 34A Methyl 2-bromo-4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 1C of Example 1D with methyl 2-bromo-4-fluorobenzoate.</p><p num="0373"> Example 34B Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (naphthalene-1-yloxy) benzoate This Example compound was prepared by substituting Example 18E of Example 18F with Example 34A and replacing phenol with 1-naphthol.</p><p num="0374"> Example 34C 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (naphthalene-1-yloxy) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 34B.</p><p num="0375"> Example 34D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1-naphthyloxy) -N-({3-nitro-4) -[(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 34C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.82 (br s, 1H), 9.50 (br s, 1H), 8.58 (t, 1H), 8.29 (d, 1H), 8.18 (d, 1H), 7.85 (d, 1H), 7.70 (br s) , 1H), 7.50 (m, 8H), 7.38 (m, 4H), 7.20 (dd, 1H), 6.82 (m, 2H), 6.55 (s, 1H), 6.45 (d, 1H), 4.38 (br s) , 1H), 3.85 (dd, 2H), 3.78 (br s, 1H), 3.27 (m, 6H), 3.22,3.02,2.85 (all br s, total 6H), 1.84 (m, 1H), 1.60 (m) , 2H), 1.29 (m, 2H).</p><p num="0376"> Example 35 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (2-naphthyloxy) -N-({3-nitro-4) -[(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 35A 1- (Difluoromethylsulfonyl) -2-fluorobenzene This Example compound was prepared by substituting Example 18E of Example 18F with Example 34A and replacing phenol with 2-naphthol.</p><p num="0377"> Example 35B 4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (naphthalene-2-yloxy) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 35A.</p><p num="0378"> Example 35C 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (2-naphthyloxy) -N-({3-nitro-4) -[(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 35B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.80 (br s, 1H), 9.55 (br s, 1H), 8.50 (t, 1H), 8.39 (d, 1H), 7.83 (m, 2H), 7.69 (br s, 1H), 7.64 (d , 1H), 7.50 (m, 6H), 7.37 (m, 5H), 7.18 (dd, 1H), 7.00 (d, 1H), 6.81 (dd, 1H), 6.77 (d, 1H), 6.56 (d, 1H), 4.38 (br s, 1H), 3.85 (dd, 2H), 3.78 (br s, 1H), 3.27 (m, 6H), 3.22,3.02,2.85 (all br s, total 6H), 1.84 (m) , 1H), 1.60 (m, 2H), 1.29 (m, 2H).</p><p num="0379"> Example 36 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4-[(3-morpholine-4-ylpropyl) amino ] -3-Nitrophenyl} Sulfonyl) -2- (2-naphthyloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 35B and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.80 (br s, 1H), 9.61 (br s, 2H), 8.57 (t, 1H), 8.40 (d, 1H), 7.83 (m, 2H), 7.66 (m, 2H), 7.50 (m, 6H), 7.40 (m, 5H), 7.18 (dd, 1H), 7.02 (d, 1H), 6.81 (d, 1H), 6.57 (s, 1H), 4.38 (br s, 1H), 4.00 (m, 2H), 3.80 (br s, 1H), 3.40 (m, 8H), 3.30-2.80 (envelope, 10H), 1.92 (m, 2H).</p><p num="0380"> Example 37 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (2-naphthyloxy) -N-({4- [(tetrahydro) -2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 35B and Example 1F with Example 163A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.82 (br s, 1H), 9.58 (br s, 1H), 8.03 (d, 1H), 7.90 (m, 2H), 7.70 (d, 1H), 7.69 (br s, 1H), 7.65 (dd) , 1H), 7.50 (m, 7H), 7.36 (m, 3H), 7.18 (m, 2H), 7.05 (d, 1H), 6.81 (dd, 1H), 6.75 (d, 1H), 6.56 (d, 1H), 4.38 (br s, 1H), 3.83 (dd, 2H), 3.78 (br s, 1H), 3.23 (m, 4H), 3.22,3.02,2.85 (all br s, total 6H), 3.15 (m) , 2H), 1.80 (m, 1H), 1.55 (m, 2H), 1.22 (m, 2H).</p><p num="0381"> Example 38 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (quinoline-7-yloxy) benzamide Example 38A Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (quinoline-7-yloxy) benzoate This Example compound was prepared by substituting Example 18E of Example 18F with Example 34A and replacing phenol with quinoline-7-ol.</p><p num="0382"> Example 38B 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (quinoline-7-yloxy) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 38A.</p><p num="0383"> Example 38C 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (quinoline-7-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 38B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.80 (d, 1H), 8.48 (t, 1H), 8.35 (d, 1H), 8.32 (d, 1H), 7.90 (d, 1H), 7.74 (m, 1H), 7.59 (m, 2H) , 7.50 (m, 4H), 7.45 (dd, 1H), 7.38 (d, 2H), 7.30 (m, 2H), 6.95 (d, 1H), 6.86 (dd, 1H), 6.83 (d, 1H), 6.71 (d, 1H), 4.38 (br s, 1H), 3.85 (dd, 2H), 3.78 (br s, 1H), 3.30-2.80 (envelope, 12H), 1.84 (m, 1H), 1.60 (m, 2H), 1.25 (m, 2H).</p><p num="0384"> Example 39 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (quinoline-6-yloxy) benzamide Example 39A Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (quinoline-6-yloxy) benzoate This Example compound was prepared by substituting Example 18E of Example 18F with Example 34A and replacing phenol with quinoline-6-ol.</p><p num="0385"> Example 39B 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (quinoline-6-yloxy) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 39A.</p><p num="0386"> Example 39C 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (quinoline-6-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 39B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) 11.90 (br s, 1H), 9.65 (br s, 1H), 8.80 (d, 1H), 8.46 (t, 1H), 8.35 (d, 1H), 7.90 (d, 1H), 7.72 (m, 1H) ), 7.50 (m, 6H), 7.45 (dd, 1H), 7.37 (m, 4H), 7.02 (d, 1H), 6.83 (dd, 1H), 6.79 (d, 1H), 6.63 (d, 1H) , 4.38 (br s, 1H), 3.85 (dd, 2H), 3.78 (br s, 1H), 3.40-2.80 (envelope 12H), 1.87 (m, 1H), 1.62 (m, 2H), 1.26 (m, 2H).</p><p num="0387"> Example 40 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy) -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 40A 1- (triisopropylsilyl) -1H-indole-5-ol 5-Benzyloxy-indole (1.0 g) was treated with NaH (135 mg) in tetrahydrofuran and triisopropylsilyl chloride (1.0 g) for 1 hour, purified by flash chromatography (98/2 ethyl acetate / hexane) and then purified. Debenzylation was performed in ethanol (35 mL) using a Pearlman catalyst (0.19 g) and a hydrogen balloon.</p><p num="0388"> Example 40B Methyl 2- (1H-indole-5-yloxy) -4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 18E of Example 18F with Example 34A and replacing phenol with Example 40A. In this example, the crude material by ether formation was desilylated with tetrabutylammonium fluoride in tetrahydrofuran / water 95/5 prior to purification.</p><p num="0389"> Example 40C 2- (1H-indole-5-yloxy) -4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 40B.</p><p num="0390"> Example 40D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy) -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 40C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.40 (br s, 1H), 11.17 (s, 1H), 9.50 (v br s, 1H), 8.61 (t, 1H), 8.57 (d, 1H), 7.77 (dd, 1H), 7.70 (br s, 1H), 7.50 (m, 5H), 7.36 (m, 5H), 7.10 (s, 1H), 7.08 (d, 1H), 6.83 (dd, 1H), 6.69 (dd, 1H), 6.37 (m) , 1H), 6.21 (d, 1H), 4.30 (br s, 1H), 3.84 (dd, 2H), 3.70 (br s, 1H), 3.30 (m, 6H), 3.20, 2.95, 2.80 (all br s) , Total 6H), 1.86 (m, 1H), 1.60 (m, 2H), 1.25 (m, 2H).</p><p num="0391"> Example 41 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (isoquinoline-5-yloxy) -N-({3-nitro- 4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 41A Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (isoquinoline-5-yloxy) benzoate This Example compound was prepared by substituting Example 18E of Example 18F with Example 34A and replacing phenol with isoquinoline-5-ol.</p><p num="0392"> Example 41B 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (isoquinoline-5-yloxy) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 41A.</p><p num="0393"> Example 41C 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (isoquinoline-5-yloxy) -N-({3-nitro- 4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 41B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.90 (br s, 1H), 9.55 (v br s, 1H), 9.26 (s, 1H), 8.47 (m, 2H), 8.14 (d, 1H), 7.99 (d, 1H), 7.65 (br s, 1H), 7.60 (d, 1H), 7.45 (m, 6H), 7.29 (m, 4H), 6.80 (m, 2H), 6.60 (m, 2H), 4.38 (br s, 1H), 3.85 ( dd, 2H), 3.78 (br s, 1H), 3.24 (m, 6H), 3.22,3.00,2.85 (all br s, total 6H), 1.87 (m, 1H), 1.62 (m, 2H), 1.26 ( m, 2H).</p><p num="0394"> Example 42 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-Nitrophenyl) Sulfonyl] -2- (isoquinoline-5-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 41B and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.90 (br s, 1H), 9.38 (v br s, 1H), 9.22 (s, 1H), 8.54 (t, 1H), 8.45 (d, 1H), 8.16 (d, 1H), 7.96 (d) , 1H), 7.62 (br s, 1H), 7.56 (d, 1H), 7.50 (d, 1H), 7.45 (m, 5H), 7.29 (m, 4H), 6.80 (m, 2H), 6.60 (m) , 2H), 4.23 (br s, 1H), 3.78 (br s, 1H), 3.40 (m, 2H), 3.35-2.80 (envelope, 8H), 3.08 (m, 2H), 2.72, 2.70 (both s, 6H in total), 1.87 (m, 2H).</p><p num="0395"> Example 43 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-Nitrophenyl) Sulfonyl] -2- (quinoline-6-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 39B and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.96 (br s, 1H), 9.38 (v br s, 1H), 8.77 (dd, 1H), 8.51 (t, 1H), 8.35 (d, 1H), 8.05 (d, 1H), 7.90 (d) , 1H), 7.70 (br s, 1H), 7.50 (m, 6H), 7.38 (m, 5H), 6.98 (d, 1H), 6.83 (dd, 1H), 6.79 (d, 1H), 6.63 (d) , 1H), 4.38 (br s, 1H), 3.78 (br s, 1H), 3.42 (m, 2H), 3.35-2.80 (envelope, 8H), 3.15 (m, 2H), 2.81, 2.79 (both s, 6H in total), 1.93 (m, 2H).</p><p num="0396"> Example 44 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 40C and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.40 (br s, 1H), 11.18 (s, 1H), 9.30 (v br s, 1H), 8.66 (t, 1H), 8.60 (d, 1H), 7.85 (dd, 1H), 7.52 (d) , 1H), 7.50 (m, 5H), 7.40 (m, 4H), 7.30 (br s, 1H), 7.14 (s, 1H), 7.10 (d, 1H), 6.84 (dd, 1H), 6.67 (dd) , 1H), 6.39 (m, 1H), 6.20 (s, 1H), 4.35 (br s, 1H), 3.78 (br s, 1H), 3.40 (m, 2H), 3.35-2.80 (envelope, 8H), 3.10 (m, 2H), 2.78, 2.76 (both s, total 6H), 1.95 (m, 2H).</p><p num="0397"> Example 45 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 45A 1- (Triisopropylsilyl) -1H-Indole-4-ol 4-Benzyloxy-indole (1.0 g) was treated with NaH (135 mg) in tetrahydrofuran and triisopropylsilyl chloride (1.0 g) for 1 hour, purified by flash chromatography (98/2 ethyl acetate / hexane) and then purified. Debenzylation was performed in ethanol (35 mL) using a Pearlman catalyst (0.19 g) and a hydrogen balloon.</p><p num="0398"> Example 45B Methyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 18E of Example 18F with Example 34A and replacing phenol with Example 45A. Here, prior to purification, the crude material by ether formation was desilylated with tetra-n-butylammonium fluoride in tetrahydrofuran / water 95/5.</p><p num="0399"> Example 45C 2- (1H-indole-4-yloxy) -4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 45B.</p><p num="0400"> Example 45D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({3- nitro-4 - [(tetrahydro -2H- pyran-4-ylmethyl) A amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 45C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.50 (br s, 1H), 11.24 (s, 1H), 9.50 (v br s, 1H), 8.61 (t, 1H), 8.47 (d, 1H), 7.70 (br s, 1H), 7.64 ( dd, 1H), 7.50 (m, 5H), 7.30 (m, 4H), 7.15 (d, 2H), 7.04 (d, 2H), 6.92 (dd, 1H), 6.75 (dd, 1H), 6.33 (m) , 2H), 6.23 (s, 1H), 4.30 (br s, 1H), 3.84 (dd, 2H), 3.70 (br s, 1H), 3.30 (m, 6H), 3.20, 2.95, 2.80 (all br s) , Total 6H), 1.86 (m, 1H), 1.60 (m, 2H), 1.25 (m, 2H).</p><p num="0401"> Example 46 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 45C and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.50 (v br s, 1H), 11.24 (s, 1H), 9.30 (br s, 1H), 8.66 (t, 1H), 8.53 (d, 1H), 7.85 (dd, 1H), 7.55 (d) , 1H), 7.50 (m, 5H), 7.39 (m, 2H), 7.30 (m, 2H), 7.148 (d, 1H), 7.10 (d, 1H), 6.96 (dd, 1H), 6.72 (dd, dd, 1H), 6.41 (d, 1H), 6.32 (s, 1H), 6.23 (s, 1H), 4.35 (br s, 1H), 3.78 (br s, 1H), 3.40 (m, 2H), 3.35-2.80 (Envelope, 8H), 3.10 (m, 2H), 2.78,2.76 (both s, total 6H), 1.95 (m, 2H).</p><p num="0402"> Example 47 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-indole-6-yloxy) benzamide Example 47A 1- (triisopropylsilyl) -1H-indole-6-ol 6-Benzyloxy-indole (1.0 g) was treated with NaH (135 mg) in tetrahydrofuran and triisopropylsilyl chloride (1.0 g) for 1 hour, purified by flash chromatography (98/2 ethyl acetate / hexane) and then purified. Debenzylation was performed in ethanol (35 mL) using a Pearlman catalyst (0.19 g) and a hydrogen balloon.</p><p num="0403"> Example 47B Methyl 2- (1H-indole-6-yloxy) -4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 18E of Example 18F with Example 34A and replacing phenol with Example 47A. In this example, the crude material by ether formation was desilylated with tetrabutylammonium fluoride in tetrahydrofuran / water 95/5 prior to purification.</p><p num="0404"> Example 47C 2- (1H-indole-6-yloxy) -4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 47B.</p><p num="0405"> Example 47D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-indole-6-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 47C and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.50 (v br s, 1H), 11.00 (s, 1H), 9.38 (br s, 1H), 8.64 (t, 1H), 8.58 (d, 1H), 7.75 (dd, 1H), 7.65 (br s, 1H), 7.55 (d, 1H), 7.50 (m, 5H), 7.39 (m, 2H), 7.30 (m, 2H), 7.00 (d, 1H), 6.90 (s, 1H), 6.70 (m) , 2H), 6.42 (m, 1H), 6.30 (s, 1H), 4.35 (br s, 1H), 3.78 (br s, 1H), 3.40 (m, 2H), 3.35-2.80 (envelope, 8H), 3.10 (m, 2H), 2.78, 2.76 (both s, total 6H), 1.95 (m, 2H).</p><p num="0406"> Example 48 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (isoquinoline-7-yloxy) -N-({4- [( 3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 48A This Example compound was prepared by substituting Example 18E of Example 18F with Example 34A and replacing phenol with isoquinoline-7-ol.</p><p num="0407"> Example 48B 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (isoquinoline-7-yloxy) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 48A.</p><p num="0408"> Example 48C 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (isoquinoline-7-yloxy) -N-({4- [( 3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 48B and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.98 (v br s, 1H), 9.70 (v br s, 2H), 9.10 (s, 1H), 8.56 (t, 1H), 8.42 (d, 1H), 8.13 (d, 1H), 7.93 ( d, 1H), 7.81 (d, 1H), 7.70 (br s, 1H), 7.60 (m, 2H), 7.50 (m, 5H), 7.40 (d, 2H), 7.35 (m, 1H), 7.14 ( d, 1H), 6.84 (m, 2H), 6.70 (d, 1H), 4.38 (br s, 1H), 4.00 (m, 2H), 3.80 (br s, 1H), 3.40 (m, 4H), 3.30 -2.80 (envelope, 10H), 3.20 (m, 4H), 1.92 (m, 2H).</p><p num="0409"> Example 49 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (isoquinoline-7-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 48B and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.98 (v br s, 1H), 9.40 (br s, 2H), 9.10 (s, 1H), 8.56 (t, 1H), 8.40 (d, 1H), 8.13 (d, 1H), 7.93 (d) , 1H), 7.81 (d, 1H), 7.70 (br s, 1H), 7.60 (m, 2H), 7.50 (m, 5H), 7.40 (d, 2H), 7.35 (m, 1H), 7.14 (d) , 1H), 6.84 (m, 2H), 6.70 (d, 1H), 4.38 (br s, 1H), 3.78 (br s, 1H), 3.42 (m, 2H), 3.35-2.80 (envelope, 8H), 3.15 (m, 2H), 2.81, 2.79 (both s, total 6H), 1.93 (m, 2H).</p><p num="0410"> Example 50 4- (4-{[2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 50A Methyl 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 34A of Example 40B with Example 19D.</p><p num="0411"> Example 50B 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 50A.</p><p num="0412"> Example 50C 4- (4-{[2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 50B and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.98 (br s, 1H), 11.20 (s, 1H), 9.70 (v br s, 1H), 9.35 (v br s, 1H), 8.71 (t, 1H), 8.62 (d, 1H), 7.86 (dd, 1H), 7.54 (d, 1H), 7.40 (m, 4H), 7.12 (m, 4H), 6.87 (dd, 1H), 6.70 (dd, 1H), 6.40 (m, 1H), 6.20 ( d, 1H), 3.98 (m, 2H), 3.50,3.40,3.30 (total m, total 12H), 3.19 (m, 2H), 3.00 (m, 4H), 2.75 (br s, 2H), 2.23 (br m, 2H), 1.97 (br m, 2H), 1.43 (br t, 2H), 0.98 (s, 6H).</p><p num="0413"> Example 51 4- (4-{[2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (Dimethylamino) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 50B and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.42 (br s, 1H), 11.20 (s, 1H), 9.40 (v br s, 1H), 9.30 (v br s, 1H), 8.66 (t, 1H), 8.61 (d, 1H), 7.86 (dd, 1H), 7.54 (d, 1H), 7.40 (m, 4H), 7.18 (d, 1H), 7.12 (m, 3H), 6.87 (dd, 1H), 6.70 (dd, 1H), 6.40 ( s, 1H), 6.20 (s, 1H), 3.60 (br s, 2H), 3.50 (m, 4H), 3.35 (br s, 2H), 3.13 (m, 3H), 3.00 (br m, 2H), 2.78,2.77 (both s, 6H in total), 2.70 (br s, 1H), 2.12 (br m, 2H), 1.97 (m, 4H), 1.42 (br t, 2H), 0.97 (s, 6H).</p><p num="0414"> Example 52 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 26C and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.40 (br s, 1H), 11.20 (s, 1H), 9.60 (v br s, 1H), 9.25 (v br s, 1H), 8.70 (t, 1H), 8.62 (d, 1H), 7.86 (dd, 1H), 7.54 (d, 1H), 7.40 (m, 4H), 7.18 (d, 1H), 7.13 (d, 1H), 7.09 (d, 2H), 6.87 (dd, 1H), 6.70 ( dd, 1H), 6.40 (m, 1H), 6.20 (s, 1H), 3.98 (m, 2H), 3.50, 3.40, 3.30 (total m, total 12H), 3.19 (m, 2H), 3.00 (m, m, 4H), 2.75 (br s, 2H), 2.18 (br m, 2H), 2.00 (br m, 4H), 1.43 (br t, 2H), 0.96 (s, 6H).</p><p num="0415"> Example 53 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (Dimethylamino) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 55B and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.41 (br s, 1H), 11.20 (s, 1H), 9.35 (v br s, 2H), 8.66 (t, 1H), 8.62 (d, 1H), 7.86 (dd, 1H), 7.54 (d) , 1H), 7.40 (m, 4H), 7.18 (d, 1H), 7.13 (d, 1H), 7.09 (d, 2H), 6.87 (dd, 1H), 6.70 (dd, 1H), 6.40 (m, 1H), 6.20 (s, 1H), 3.50 (m, 4H), 3.35 (br s, 2H), 3.13 (m, 3H), 3.00 (br m, 2H), 2.78, 2.77 (both s, total 6H) , 2.70 (br s, 1H), 2.20 (br m, 2H), 2.00 (m, 2H), 1.93 (m, 2H), 1.42 (br t, 2H), 0.97 (s, 6H).</p><p num="0416"> Example 54 4- (4-{[2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 54A Methyl 2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 34A of Example 45B with Example 19D.</p><p num="0417"> Example 54B 2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 54A.</p><p num="0418"> Example 54C 4- (4-{[2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 54B and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.50 (br s, 1H), 11.27 (s, 1H), 9.60 (v br s, 1H), 9.20 (v br s, 1H), 8.65 (t, 1H), 8.55 (d, 1H), 7.80 (dd, 1H), 7.57 (d, 1H), 7.40 (d, 2H), 7.30 (dd, 1H), 7.12 (d, 2H), 7.10 (d, 2H), 7.00 (dd, 1H), 6.73 ( dd, 1H), 6.46 (d, 1H), 6.30 (s, 1H), 6.23 (m, 1H), 3.98 (m, 2H), 3.60,3.50,3.40 (total m, total 12H), 3.19 (m, 2H), 3.00 (m, 4H), 2.75 (br s, 2H), 2.23 (br m, 2H), 1.97 (br m, 4H), 1.43 (br t, 2H), 0.98 (s, 6H).</p><p num="0419"> Example 55 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 55A Methyl 2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by replacing the phenol of Example 18F with Example 45A. Here, prior to purification, the crude material by ether formation was desilylated with tetrabutylammonium fluoride in tetrahydrofuran / water 95/5.</p><p num="0420"> Example 55B 2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 55A.</p><p num="0421"> Example 55C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 55B and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.50 (br s, 1H), 11.25 (s, 1H), 9.60 (v br s, 1H), 9.20 (v br s, 1H), 8.65 (t, 1H), 8.55 (d, 1H), 7.80 (dd, 1H), 7.57 (d, 1H), 7.40 (d, 2H), 7.30 (dd, 1H), 7.20 (d, 1H), 7.10 (m, 3H), 7.00 (dd, 1H), 6.73 ( dd, 1H), 6.46 (d, 1H), 6.30 (s, 1H), 6.23 (m, 1H), 3.98 (m, 2H), 3.60,3.50,3.40 (total m, total 12H), 3.19 (m, 2H), 3.00 (m, 4H), 2.75 (br s, 2H), 2.20 (br m, 2H), 2.00 (br m, 4H), 1.43 (br t, 2H), 0.98 (s, 6H).</p><p num="0422"> Example 56 4- (4-{[2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (Dimethylamino) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 54B and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.55 (br s, 1H), 11.27 (s, 1H), 9.40 (v br s, 1H), 9.35 (v br s, 1H), 8.65 (t, 1H), 8.55 (d, 1H), 7.79 (dd, 1H), 7.57 (d, 1H), 7.40 (d, 2H), 7.30 (dd, 1H), 7.20 (d, 1H), 7.10 (m, 3H), 7.00 (dd, 1H), 6.73 ( dd, 1H), 6.46 (d, 1H), 6.30 (s, 1H), 6.23 (m, 1H), 3.50 (m, 4H), 3.35 (br s, 2H), 3.13 (m, 3H), 3.00 ( br m, 2H), 2.78, 2.77 (both s, 6H in total), 2.70 (br s, 1H), 2.22 (br m, 2H), 1.97 (m, 2H), 1.93 (m, 2H), 1.42 (br t, 2H), 0.97 (s, 6H).</p><p num="0423"> Example 57 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (Dimethylamino) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 55B and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.50 (br s, 1H), 11.25 (s, 1H), 9.60 (v br s, 1H), 9.20 (v br s, 1H), 8.65 (t, 1H), 8.55 (d, 1H), 7.79 (dd, 1H), 7.57 (d, 1H), 7.40 (d, 2H), 7.30 (dd, 1H), 7.20 (d, 1H), 7.10 (m, 3H), 7.00 (dd, 1H), 6.73 ( dd, 1H), 6.46 (d, 1H), 6.30 (s, 1H), 6.23 (m, 1H), 3.50 (m, 4H), 3.35 (br s, 2H), 3.13 (m, 3H), 3.00 ( br m, 2H), 2.78, 2.77 (both s, 6H in total), 2.70 (br s, 1H), 2.20 (br m, 2H), 2.00 (m, 2H), 1.93 (m, 2H), 1.42 (br t, 2H), 0.97 (s, 6H).</p><p num="0424"> Example 58 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({4- [(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 45C and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.50 (br s, 1H), 11.24 (s, 1H), 9.50 (v br s, 1H), 8.67 (t, 1H), 8.52 (d, 1H), 7.78 (dd, 1H), 7.70 (br s, 1H), 7.55 (d, 1H), 7.50 (m, 4H), 7.38 (d, 2H), 7.30 (dd, 2H), 7.18 (d, 1H), 7.08 (d, 1H), 6.96 (dd) , 1H), 6.75 (dd, 1H), 6.40 (d, 1H), 6.33 (s, 1H), 6.23 (s, 1H), 4.38 (br s, 1H), 4.00 (m, 2H), 3.80 (br s, 1H), 3.40 (m, 4H), 3.30-2.80 (envelope, 10H), 3.20 (m, 4H), 1.95 (m, 2H).</p><p num="0425"> Example 59 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy) -N-({4- [(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 40C and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.40 (br s, 1H), 11.19 (s, 1H), 9.60 (v br s, 1H), 8.69 (t, 1H), 8.60 (d, 1H), 7.83 (dd, 1H), 7.65 (br s, 1H), 7.50 (m, 5H), 7.38 (m, 5H), 7.12 (m, 2H), 6.83 (dd, 1H), 6.69 (dd, 1H), 6.39 (m, 1H), 6.20 (d , 1H), 4.38 (br s, 1H), 4.00 (m, 2H), 3.80 (br s, 1H), 3.40 (m, 4H), 3.30-2.80 (envelope, 10H), 3.20 (m, 4H), 1.96 (m, 2H).</p><p num="0426"> Example 60 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-methoxyphenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 1E and Example 1F with 4-methoxybenzenesulfonamide.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.57 (s, 1H), 7.74 (d, 2H), 7.50 (m, 5H), 7.35 (m, 6H), 7.10 (t, 1H), 7.02 (m, 2H), 6.87 (d, 2H) , 6.75 (dd, 1H), 6.41 (s, 1H), 4.36 (m, 2H), 3.83 (s, 3H), 3.76 (m, 2H), 3.23 (m, 2H), 3.01 (m, 2H), 2.84 (m, 2H).</p><p num="0427"> Example 61 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-methylphenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 1E and Example 1F with 4-methylbenzenesulfonamide.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.64 (s, 1H), 7.68 (d, 2H), 7.50 (m, 5H), 7.38 (m, 2H), 7.32 (m, 6H), 7.11 (t, 1H), 6.87 (d, 2H) , 6.75 (dd, 1H), 6.41 (s, 1H), 4.36 (m, 2H), 3.76 (m, 2H), 3.23 (m, 2H), 3.01 (m, 2H), 2.84 (m, 2H), 2.37 (s, 3H).</p><p num="0428"> Example 62 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy) -N-({4- [(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 40C and Example 1F with Example 163A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.46 (s, 1H), 11.16 (s, 1H), 8.17 (d, 1H), 7.88 (dd, 1H), 7.68 (br s, 1H), 7.50 (m, 5H), 7.36 (m, 6H) ), 7.13 (s, 1H), 7.03 (d, 1H), 6.84 (dd, 1H), 6.68 (dd, 1H), 6.39 (m, 1H), 6.21 (br s, 1H), 4.32 (s, 2H) ), 3.84 (dd, 2H), 3.25 (m, 7H), 2.93 (m, 4H), 1.84 (m, 2H), 1.54 (m, 2H), 1.24 (m, 2H).</p><p num="0429"> Example 63 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({4- [(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 45C and Example 1F with Example 163A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.58 (s, 1H), 11.27 (s, 1H), 8.12 (d, 1H), 7.71 (m, 2H), 7.52 (m, 5H), 7.32 (m, 5H), 7.18 (d, 1H) , 6.96 (m, 2H), 6.74 (dd, 1H), 6.36 (m, 2H), 6.26 (m, 1H), 4.32 (s, 2H), 3.84 (dd, 2H), 3.25 (m, 7H), 2.93 (m, 4H), 1.84 (m, 2H), 1.54 (m, 2H), 1.24 (m, 2H).</p><p num="0430"> Example 64 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4- {[3- (dimethylamino) propyl] amino} -3-[(Trifluoromethyl) sulfonyl] phenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 27G and Example 1F of Example 27H with Example 40C and Example 170A, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.46 (br s, 1H), 11.18 (s, 1H), 8.21 (d, 1H), 7.98 (dd, 1H), 7.50 (m, 6H), 7.41 (m, 5H), 7.29 (br s,) 1H), 7.17 (s, 1H), 7.08 (d, 1H), 6.84 (dd, 1H), 6.68 (dd, 1H), 6.40 (m, 1H), 6.18 (br s, 1H), 4.32 (br s) , 2H), 3.59 (m, 4H), 3.25 (m, 2H), 3.05 (m, 4H), 2.90 (m, 2H), 2.77 (d, 6H), 1.88 (m, 2H).</p><p num="0431"> Example 65 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({4- [(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide Example 65A 4- (3-morpholinopropylamino) -3- (trifluoromethylsulfonyl) benzenesulfonamide This Example compound was prepared by replacing 4-fluoro-3-nitrobenzenesulfonamide and (tetrahydropyran-4-yl) methylamine in Example 1F with Example 159C and 3-morpholinopropan-1-amine, respectively.</p><p num="0432"> Example 65B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({4- [(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G and Example 1F of Example 27H with Example 40C and Example 65A, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.46 (br s, 1H), 11.18 (s, 1H), 8.18 (d, 1H), 7.91 (m, 1H), 7.50 (m, 6H), 7.41 (m, 5H), 7.30 (m, 1H) ), 7.19 (d, 1H), 7.08 (m, 1H), 6.99 (m, 1H), 6.72 (dd, 1H), 6.48 (br s, 1H), 6.25 (m, 1H), 4.29 (br s, 2H), 4.01 (m, 2H), 3.59 (m, 2H), 3.41 (m, 4H), 3.05 (m, 10H), 2.58 (m, 2H), 1.91 (m, 2H).</p><p num="0433"> Example 66 N-[(3-{[chloro (difluoro) methyl] sulfonyl} -4-{[3- (dimethylamino) propyl] amino} phenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide Example 66A (Difluoromethyl) (2-fluorophenyl) sulfan Powdered NaOH (31.2 g), tris (2- (2-methoxyethoxy) ethyl) amine (5 mL) and 2-fluorobenzenethiol (33.6 mL) in benzene (400 mL) are saturated with chlorodifluoromethane and 80 ° C. Was stirred for 30 minutes and filtered through diatomaceous earth (Celite®). Saturate filtrate LVDS₃The aqueous layer was extracted with diethyl ether. Combine the extracts and dehydrate (DDL)₄), Filtered and concentrated.</p><p num="0434"> Example 66B 1- (Difluoromethylsulfonyl) -2-fluorobenzene 1: 1: 2 CCl at 25 ° C₄/ CH₃Example 66A (46g) in CN / water (1.2L) NaIO₄(164.6g) and RuCl₃ XH₂It was treated with O (534 mg), stirred for 18 hours, diluted with dichloromethane and filtered through diatomaceous earth (Celite®). Saturate filtrate LVDS₃Wash with and dehydrate (Na₂SO₄), Filtered and concentrated. The concentrate was filtered through silica gel.</p><p num="0435"> Example 66C 1- (Chlorodifluoromethylsulfonyl) -2-fluorobenzene Examples 66B (25 g) and N-chlorosuccinimide (17.55 g) in tetrahydrofuran (690 mL) at -78 ° C were treated with lithium hexamethyldisilazide (178.5 mL) over 1 hour and stirred for 1 hour. , Quenched with ammonium chloride. The mixture is extracted with ethyl acetate, the extract is washed with brine and dehydrated (DDL)₄), Filtered and concentrated. The concentrate was chromatographed on silica gel with 0-5% ethyl acetate / hexane.</p><p num="0436"> Example 66D 3- (Chlorodifluoromethylsulfonyl) -4-fluorobenzene-1-sulfonyl chloride Example 66C (44 g) in chlorosulfonic acid (36.7 mL) at 120 ° C was stirred for 18 hours, cooled to 25 ° C, pipetted on crushed ice and extracted with ethyl acetate. The extract is washed with water and brine and dehydrated (DDL)₄), Filtered and concentrated.</p><p num="0437"> Example 66E 3- (Chlorodifluoromethylsulfonyl) -4-fluorobenzenesulfonamide Example 66D (22 g) in isopropanol (690 mL) at -78 ° C was treated with aqueous ammonia (90 mL) for 1 hour, stirred for an additional hour, quenched with 6M HCl (300 mL) and 25 ° C. Was heated and concentrated. The concentrate was mixed with water and extracted with ethyl acetate. Dehydrate the extract (DDL₄), Filtered and concentrated. The concentrate was recrystallized from hexane / ethyl acetate.</p><p num="0438"> Example 66F 3- (Chlorodifluoromethylsulfonyl) -4- (3- (dimethylamino) propylamino) benzenesulfonamide This Example compound was replaced with Example 66E and N, N-dimethylpropane-1,3-diamine, respectively, of 4-fluoro-3-nitrobenzenesulfonamide and (tetrahydropyran-4-yl) methylamine of Example 1F. Prepared.</p><p num="0439"> Example 66G N-[(3-{[chloro (difluoro) methyl] sulfonyl} -4-{[3- (dimethylamino) propyl] amino} phenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 27G and Example 1F of Example 27H with Example 54B and Example 66F, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.20 (s, 1H), 8.28 (m, 1H), 7.99 (m, 1H), 7.55 (m, 2H), 7.38 (m, 2H), 7.21 (m, 3H), 7.09 (d, 2H) , 6.98 (m, 1H), 6.71 (m, 1H), 6.41 (m, 2H), 6.21 (m, 1H), 3.57 (m, 2H), 3.28 (m, 4H), 2.84 (m, 6H), 2.67 (m, 5H), 2.19 (m, 2H), 2.02 (m, 2H), 1.77 (br s, 2H), 1.61 (m, 2H), 1.46 (m, 2H), 0.94 (s, 6H).</p><p num="0440"> Example 67 N-[(3-{[chloro (difluoro) methyl] sulfonyl} -4-{[3- (dimethylamino) propyl] amino} phenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 27G and Example 1F of Example 27H with Example 26C and Example 66F, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.20 (s, 1H), 8.28 (m, 1H), 8.05 (m, 1H), 7.99 (m, 1H), 7.55 (m, 2H), 7.38 (m, 2H), 7.21 (m, 3H) , 7.09 (d, 2H), 6.98 (m, 1H), 6.71 (m, 1H), 6.41 (m, 2H), 6.21 (m, 1H), 3.57 (m, 2H), 3.28 (m, 4H), 3.05 (m, 2H), 2.96 (m, 2H), 2.88 (s, 3H), 2.78 (m, 2H), 2.68 (m, 3H), 2.19 (m, 2H), 2.01 (br s, 2H), 1.72 (m, 2H), 1.45 (m, 2H), 0.93 (s, 6H).</p><p num="0441"> Example 68 2- (1H-Indol-4-yloxy) -4- (4-{[2- (4-Methoxyphenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide Example 68A (2-Bromo-4,4-Dimethylcyclohex-1-enyl) Methanol N, N-dimethylformamide (18.41 ml) was taken up in chloroform (64 ml) and the resulting solution was cooled in an ice bath. Phosphorus tribromide (20.18 ml) was added dropwise over 15 minutes. The resulting suspension was then heated at 70 ° C. for 30 minutes. A solution of 3,3-dimethylcyclohexanone (10 g) in chloroform (21 ml) was added dropwise over 30 minutes. The mixture was stirred at 70 ° C for an additional 2 hours. The mixture was then cooled to room temperature. The solution was carefully poured into ice. Solid sodium bicarbonate was added to neutralize the acid. The mixture was extracted 3 times with ether and the extract was washed with water and brine and dehydrated (DDL).₄). The solvent was removed under vacuum and the crude material was flushed through a silica filler using ether as an eluent. After concentration, the crude material was dissolved in methanol. Sodium borohydride (1.757 g) was carefully added. The resulting mixture was stirred at room temperature overnight and diluted with ethyl acetate. The mixture was washed with water and brine and dehydrated (DDL)₄). The solvent was removed under vacuum and the residue was purified by flash chromatography, eluting from 20% ethyl acetate in hexanes with 100% ethyl acetate.</p><p num="0442"> Example 68B Methyl 2- (1H-indole-4-yloxy) -4- (piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 1C and Example 1B of Example 1D with Example 24F and piperazine, respectively.</p><p num="0443"> Example 68C Methyl 2- (1H-indole-4-yloxy) -4-(4-((2-bromo-4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 18C and Example 18D of Example 18E with Example 68A and Example 68B, respectively.</p><p num="0444"> Example 68D Methyl 2- (1H-indole-4-yloxy) -4-(4-((2- (4-Methoxyphenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate Example 68C (142 mg), 4-methoxyphenylboronic acid (45.6 mg), bis (triphenylphosphine) palladium (II) dichloride (8.7 mg) and cesium fluoride (114 mg) dimethoxyethane (0.9 mL) and methanol ( Together in 0.4 mL) and heated to 90 ° C for 2 hours. The reaction mixture was diluted with ethyl acetate and poured into water. The organic layer is washed with water and brine and dehydrated (DDL)₄), Filtered and concentrated. The obtained solid was mixed with methanol and filtered.</p><p num="0445"> Example 68E 2- (1H-indole-4-yloxy) -4-(4-((2- (4-methoxyphenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 68D.</p><p num="0446"> Example 68F 3-Nitro-4- (3- (pyrrolidin-1-yl) propylamino) benzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine in Example 1F with 3- (pyrrolidin-1-yl) propan-1-amine.</p><p num="0447"> Example 68G 2- (1H-Indol-4-yloxy) -4- (4-{[2- (4-Methoxyphenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G and Example 1F of Example 27H with Examples 68E and 68F.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.56 (brs, 1H), 11.26 (s, 1H), 8.66 (t, 1H), 8.53 (d, 1H), 7.78 (dd, 1H), 7.56 (d, 1H), 7.29 (t, 1H) , 7.19 (d, 1H), 7.10 (d, 1H), 6.98 (m, 3H), 6.88 (m, 2H), 6.74 (m, 1H), 6.43 (d, 1H), 6.36 (br s, 1H) , 6.23 (m, 1H), 3.73 (s, 3H), 3.62 (m, 2H), 3.52 (m, 4H), 3.22 (m, 4H), 2.99 (m, 4H), 2.18 (m, 2H), 1.99 (m, 6H), 1.84 (m, 2H), 1.45 (m, 2H), 1.23 (m, 2H), 0.94 (s, 6H).</p><p num="0448"> Example 69 4- [4-({4,4-Dimethyl-2- [4- (trifluoromethyl) phenyl] cyclohexa-1-en-1-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide Example 69A Methyl 2- (1H-indole-4-yloxy) -4-(4-((4,4-dimethyl-2- (4- (trifluoromethyl) phenyl) cyclohex-1-enyl) methyl) piperazine-1- Indole) benzoate This Example compound was prepared by replacing 4-methoxyphenylboronic acid in Example 68D with 4- (trifluoromethyl) phenylboronic acid.</p><p num="0449"> Example 69B 2- (1H-indole-4-yloxy) -4-(4-((4,4-dimethyl-2- (4- (trifluoromethyl) phenyl) cyclohex-1-enyl) methyl) piperazine-1-yl )benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 69A.</p><p num="0450"> Example 69C 4- [4-({4,4-Dimethyl-2- [4- (trifluoromethyl) phenyl] cyclohexa-1-en-1-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G and Example 1F of Example 27H with Example 69B and Example 68F, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.55 (br s, 1H), 11.26 (s, 1H), 8.66 (t, 1H), 8.53 (d, 1H), 7.78 (m, 1H), 7.67 (m, 2H), 7.56 (m, 1H) ), 7.29 (m, 3H), 7.19 (d, 1H), 7.10 (d, 1H), 6.98 (m, 1H), 6.72 (m, 1H), 6.46 (m, 1H), 6.36 (br s, 1H) ), 6.23 (m, 1H), 3.62 (m, 4H), 3.52 (m, 4H), 3.18 (m, 4H), 3.02 (m, 4H), 2.19 (m, 2H), 2.02 (m, 6H) , 1.82 (m, 2H), 1.47 (m, 2H), 0.94 (s, 6H).</p><p num="0451"> Example 70 4- [4-({4,4-Dimethyl-2- [4- (trifluoromethoxy) phenyl] cyclohexa-1-en-1-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide Example 70A Methyl 2- (1H-indole-4-yloxy) -4-(4-((4,4-dimethyl-2- (4- (trifluoromethoxy) phenyl) cyclohex-1-enyl) methyl) piperazine-1- Indole) benzoate This Example compound was prepared by replacing 4-methoxyphenylboronic acid in Example 68D with 4- (trifluoromethoxy) phenylboronic acid.</p><p num="0452"> Example 70B 2- (1H-indole-4-yloxy) -4-(4-((4,4-dimethyl-2- (4- (trifluoromethoxy) phenyl) cyclohex-1-enyl) methyl) piperazine-1-yl )benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 70A.</p><p num="0453"> Example 70C 4- [4-({4,4-Dimethyl-2- [4- (trifluoromethoxy) phenyl] cyclohexa-1-en-1-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G and Example 1F of Example 27H with Example 70B and Example 68F, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.56 (br s, 1H), 11.26 (s, 1H), 8.66 (t, 1H), 8.54 (d, 1H), 7.80 (m, 1H), 7.63 (m, 2H), 7.56 (m, 3H) ), 7.29 (m, 2H), 7.19 (m, 2H), 6.98 (m, 1H), 6.72 (m, 1H), 6.46 (m, 1H), 6.23 (m, 1H), 3.62 (m, 4H) , 3.52 (m, 4H), 3.18 (m, 4H), 3.02 (m, 4H), 2.19 (m, 2H), 2.02 (m, 6H), 1.82 (m, 2H), 1.47 (m, 2H), 0.94 (s, 6H).</p><p num="0454"> Example 71 4- [4-({4,4-Dimethyl-2- [3- (trifluoromethyl) phenyl] cyclohexa-1-en-1-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide Example 71A Methyl 2- (1H-indole-4-yloxy) -4-(4-((4,4-dimethyl-2- (3- (trifluoromethyl) phenyl) cyclohex-1-enyl) methyl) piperazine-1- Indole) benzoate This Example compound was prepared by replacing 4-methoxyphenylboronic acid in Example 68D with 3- (trifluoromethyl) phenylboronic acid.</p><p num="0455"> Example 71B 2- (1H-indole-4-yloxy) -4-(4-((4,4-dimethyl-2-(3- (trifluoromethyl) phenyl) cyclohex-1-enyl) methyl) piperazine-1-yl )benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 71A.</p><p num="0456"> Example 71C 4- [4-({4,4-Dimethyl-2- [3- (trifluoromethyl) phenyl] cyclohexa-1-en-1-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G and Example 1F of Example 27H with Example 71B and Example 68F, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.55 (br s, 1H), 11.26 (s, 1H), 8.65 (t, 1H), 8.54 (d, 1H), 7.80 (dd, 1H), 7.63 (m, 2H), 7.56 (m, 3H) ), 7.38 (m, 2H), 7.29 (t, 1H), 7.19 (d, 1H), 7.11 (d, 1H), 6.98 (t, 1H), 6.72 (m, 1H), 6.46 (m, 1H) , 6.31 (m, 1H), 6.23 (m, 1H), 3.58 (m, 7H), 3.18 (m, 4H), 3.02 (m, 4H), 2.19 (m, 3H), 2.02 (m, 6H), 1.82 (m, 2H), 1.47 (m, 2H), 0.96 (s, 6H).</p><p num="0457"> Example 72 4- (4-{[2- (3-Fluorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide Example 72A Methyl 2- (1H-indole-4-yloxy) -4-(4-((2- (3-fluorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by replacing 4-methoxyphenylboronic acid in Example 68D with 3-fluorophenylboronic acid.</p><p num="0458"> Example 72B 2- (1H-indole-4-yloxy) -4-(4-((2- (3-fluorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 72A.</p><p num="0459"> Example 72C 4- (4-{[2- (3-Fluorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G and Example 1F of Example 27H with Example 72B and Example 68F, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.55 (br s, 1H), 11.26 (s, 1H), 8.65 (t, 1H), 8.54 (d, 1H), 7.80 (m, 1H), 7.63 (m, 2H), 7.56 (m, 3H) ), 7.38 (m, 2H), 7.29 (t, 1H), 7.19 (d, 1H), 7.11 (d, 1H), 6.98 (m, 1H), 6.72 (m, 1H), 6.46 (m, 1H) , 6.31 (m, 1H), 6.23 (m, 1H), 3.58 (m, 7H), 3.18 (m, 4H), 3.02 (m, 4H), 2.19 (m, 3H), 2.02 (m, 6H), 1.82 (m, 2H), 1.47 (m, 2H), 0.96 (s, 6H).</p><p num="0460"> Example 73 4- (4-{[2- (4-Fluorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yl) Iloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide Example 73A Methyl 2- (1H-indole-4-yloxy) -4-(4-((2- (4-fluorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by replacing 4-methoxyphenylboronic acid in Example 68D with 4-fluorophenylboronic acid.</p><p num="0461"> Example 73B 2- (1H-indole-4-yloxy) -4-(4-((2- (4-fluorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 73A.</p><p num="0462"> Example 73C 4- (4-{[2- (4-Fluorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yl) Iloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G and Example 1F of Example 27H with Example 73B and Example 68F, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.56 (br s, 1H), 11.26 (s, 1H), 8.66 (t, 1H), 8.54 (d, 1H), 7.80 (m, 1H), 7.63 (m, 2H), 7.56 (m, 3H) ), 7.29 (m, 2H), 7.19 (m, 2H), 6.98 (m, 1H), 6.72 (m, 1H), 6.46 (m, 1H), 6.23 (m, 1H), 3.62 (m, 4H) , 3.52 (m, 4H), 3.18 (m, 4H), 3.02 (m, 4H), 2.19 (m, 2H), 2.02 (m, 6H), 1.82 (m, 2H), 1.47 (m, 2H), 0.94 (s, 6H).</p><p num="0463"> Example 74 N-({3-{[chloro (difluoro) methyl] sulfonyl} -4-[(1-methylpiperidin-4-yl) amino] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) ) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide Example 74A 3- (Chlorodifluoromethylsulfonyl) -4- (1-methylpiperidin-4-ylamino) benzenesulfonamide This Example compound was prepared by replacing 4-fluoro-3-nitrobenzenesulfonamide and (tetrahydropyran-4-yl) methylamine in Example 1F with Example 66E and 1-methylpiperidine-4-amine, respectively.</p><p num="0464"> Example 74B N-({3-{[chloro (difluoro) methyl] sulfonyl} -4-[(1-methylpiperidin-4-yl) amino] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) ) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1E and Example 1F of Example 1G with Example 26C and Example 74A, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.07 (s, 1H), 8.11 (d, 1H), 7.89 (dd, 1H), 7.50 (d, 1H), 7.34 (m, 4H), 7.05 (m, 3H), 6.96 (d, 1H) , 6.78 (dd, 1H), 6.60 (m, 2H), 6.36 (s, 1H), 6.13 (d, 1H), 3.67 (m, 1H), 2.97 (m, 6H), 2.71 (s, 2H), 2.59 (m, 2H), 2.46 (s, 3H), 2.16 (m, 6H), 1.98 (m, 4H), 1.55 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0465"> Example 75 4- (4-{[2- (4-chlorophenyl) cyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-({4 -[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 75A Methyl 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) cyclohex-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide and tert-butylpiperazin-1-carboxylate of Example 1A with Example 149D and Example 150A, respectively.</p><p num="0466"> Example 75B 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) cyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 75A.</p><p num="0467"> Example 75C 4- (4-{[2- (4-chlorophenyl) cyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-({4 -[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E and Example 1F of Example 1G with Example 75B and Example 21A, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.07 (s, 1H), 8.52 (d, 1H), 8.12 (d, 1H), 7.79 (dd, 1H), 7.52 (d, 1H), 7.34 (m, 4H), 7.05 (m, 4H) , 6.79 (dd, 1H), 6.59 (dd, 1H), 6.36 (s, 1H), 6.13 (d, 1H), 3.72 (m, 1H), 2.97 (m, 6H), 2.69 (s, 2H), 2.59 (m, 2H), 2.46 (s, 3H), 2.16 (m, 6H), 2.11 (m, 2H), 1.98 (m, 2H), 1.70 (m, 2H), 1.62 (m, 4H).</p><p num="0468"> Example 76 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide Example 76A 4- (1-Methylpiperidin-4-ylamino) -3- (trifluoromethylsulfonyl) benzenesulfonamide This Example compound was prepared by replacing 4-fluoro-3-nitrobenzenesulfonamide and (tetrahydropyran-4-yl) methylamine in Example 1F with Example 159C and 1-methylpiperidine-4-amine, respectively.</p><p num="0469"> Example 76B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E and Example 1F of Example 1G with Example 26C and Example 76A, respectively.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.08 (s, 1H), 8.11 (d, 1H), 7.89 (dd, 1H), 7.50 (d, 1H), 7.34 (m, 4H), 7.05 (m, 3H), 6.98 (d, 1H) , 6.78 (dd, 1H), 6.60 (m, 2H), 6.36 (t, 1H), 6.13 (d, 1H), 3.67 (br s, 1H), 2.97 (m, 6H), 2.71 (s, 3H) , 2.63 (m, 1H), 2.47 (s, 3H), 2.17 (m, 6H), 1.98 (m, 4H), 1.60 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0470"> Example 77 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (phenoxymethyl) benzamide Example 77A 5- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) isobenzofuran-1 (3H) -one 5-Bromoisobenzofuran-1 (3H) -one (400 mg), Example 1B (646 mg) and tribasic potassium phosphate (558 mg) were added to 1,2-dimethoxyethane (10 mL). The solution was degassed under vacuum and flushed with nitrogen 3 times. Tris (dibenzylideneacetone) dipalladium (0) (51.6 mg) and 2- (di-tert-butylphosphino) biphenyl (67.2 mg) were added and the solution was heated to 80 ° C. for 16 hours. The solution was cooled, filtered, concentrated and purified by flash column chromatography on silica gel with 30% ethyl acetate in hexanes.</p><p num="0471"> Example 77B 4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (hydroxymethyl) benzoic acid Example 77A (256 mg) and lithium hydroxide monohydrate (154 mg) were added to 1,4-dioxane (4 mL) and water (1 mL). The solution was heated to 65 ° C. for 16 hours, cooled, concentrated under vacuum and purified with ethyl acetate by flash column chromatography on silica gel. The solution was then dehydrated with anhydrous sodium sulfate to give a crude product of sufficient purity for subsequent use.</p><p num="0472"> Example 77C Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (hydroxymethyl) benzoate Trimethylsilyldiazomethane (2M solution in diethyl ether, 0.214 mL) was added to Example 77B (170 mg) dissolved in ethyl acetate (2 mL) and methanol (2 mL). The solution was mixed for 5 minutes and then the solvent was removed under vacuum to give a crude product of sufficient purity for subsequent use.</p><p num="0473"> Example 77D Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenoxymethyl) benzoate Triphenylphosphine (93 mg) was added to tetrahydrofuran (3 mL) and cooled to 0 ° C. Diethylazodicarboxylate (40% solution, 0.161 mL) was added and the solution was stirred at 0 ° C for 15 minutes. Phenol (33.3 mg) and Example 77C (145 mg) were added and the solution was warmed to room temperature and mixed for 16 hours. The solution was concentrated under vacuum and purified by flash column chromatography on silica gel, increasing from 30% ethyl acetate (hexane) to 50% ethyl acetate (hexane).</p><p num="0474"> Example 77E 4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (phenoxymethyl) benzoic acid This Example compound was prepared by substituting Example 77A of Example 77B with Example 77D.</p><p num="0475"> Example 77F This Example compound was prepared by substituting Example 1E of Example 1G with Example 77E.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.52 (m, 2H), 7.88 (dd, 1H), 7.84 (d, 1H), 7.50 (m, 2H), 7.48 (s, 3H), 7.37 (m, 2H), 7.26-7.10 (m, 4H), 7.01 (s, 1H), 6.87 (t, 1H), 6.83-6.75 (m, 3H), 5.22 (wide s, 2H), 3.84 (dd, 2H), 3.41-3.10 (m, 10H), 2.39 (wide s, 4H), 1.89 (m, 1H), 1.60 (m, 2H), 1.32-1.18 (m, 2H).</p><p num="0476"> Example 78 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4-[(3-morpholine-4-ylpropyl) amino ] Phenyl} sulfonyl) -2-phenoxybenzamide Example 78A N- (4-Sulfamoylphenyl) acrylamide 4-Aminobenzene sulfonamide (1.00 g) and pyridine (1.41 mL) were added to 1,4-dioxane (30 mL). Acryloyl chloride (0.49 mL) was added dropwise and the solution was stirred at room temperature for 3 hours. 1M HCl was added and the solution was extracted with ethyl acetate. The extract was dehydrated with brine and anhydrous sodium sulfate to remove the solvent to give a crude product of sufficient purity for subsequent use.</p><p num="0477"> Example 78B 3-Morphorino-N- (4-Sulfamoylphenyl) Propanamide Example 78A (359 mg) and morpholine (1.38 mL) were added to acetonitrile (10 mL) and N, N-dimethylformamide (1 mL) and mixed at room temperature for 16 hours. The solution was concentrated under vacuum and purified by flash column chromatography on silica gel with 5% methanol in dichloromethane.</p><p num="0478"> Example 78C 4- (3-morpholinopropylamino) benzenesulfonamide Example 78B (268 mg) was added to tetrahydrofuran (4 mL). Borane (1 M, 4.28 mL in tetrahydrofuran) was added slowly and the solution was mixed at room temperature for 16 hours. The reaction was gradually quenched with methanol. N, N-diisopropylethylamine resin (3.42 mmol amine) was added and the solution was mixed at room temperature for 15 minutes. The solution was filtered, concentrated under vacuum and purified by flash column chromatography on silica gel with 10% methanol in ethyl acetate.</p><p num="0479"> Example 78D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4-[(3-morpholine-4-ylpropyl) amino ] Phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 78C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 10.98 (wide s, 1H), 7.51-7.44 (m, 9H), 7.40-7.31 (m, 3H), 7.26-7.21 (m, 1H), 7.13 (tt, 1H), 6.94 (dd, 2H) , 6.75 (dd, 1H), 6.66 (t, 1H), 6.54 (d, 2H), 6.32 (d, 1H), 3.57 (t, 4H), 3.35 (m, 2H), 3.16-3.04 (m, 6H) ), 2.35 (m, 10H), 1.60 (m, 2H).</p><p num="0480"> Example 79 4- {4-([4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (pyridin-3-yloxy) benzamide Example 79A Methyl 4-bromo-2-fluorobenzoate 4-Bromo-2-fluorobenzoic acid (5.00 g) was added to ethyl acetate (35 mL) and methanol (35 mL). Trimethylsilyldiazomethane (2M solution in diethyl ether, 12.56 mL) was added slowly and the solution was mixed at room temperature for 30 minutes. The solvent was removed under vacuum and the crude material was dissolved in ethyl acetate. The solution was extracted with 0.5 M sodium hydroxide and dehydrated with brine and then anhydrous sodium sulfate. After filtration, the solvent was removed under vacuum to give a crude product of sufficient purity for subsequent use.</p><p num="0481"> Example 79B Methyl 4-bromo-2- (pyridin-3-yloxy) benzoate Example 79A (500 mg), pyridine-3-ol (204 mg) and potassium carbonate (385 mg) were added to N, N-dimethylacetamide (18 mL) and the mixture was heated to 145 ° C for 2 hours and then at 130 ° C. Heated for 16 hours. The solution was cooled, added to water (100 mL), extracted with 70% ethyl acetate in hexanes and dehydrated with anhydrous sodium sulfate. After filtration, the solution was concentrated under vacuum and purified by flash column chromatography on silica gel with 50-70% ethyl acetate in hexanes.</p><p num="0482"> Example 79C Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (pyridin-3-yloxy) benzoate Example 79B (367 mg), Example 1B (410 mg) and tribasic potassium phosphate (379 mg) were added to 1,2-dimethoxyethane (6 mL). The solution was degassed under vacuum and flushed with nitrogen 3 times. Tris (dibenzylideneacetone) dipalladium (0) (32.7 mg) and 2- (di-tert-butylphosphino) biphenyl (42.6 mg) were added and the solution was heated to 80 ° C. for 16 hours. The solution was cooled, filtered, concentrated and purified by flash column chromatography on silica gel with 50-70% ethyl acetate in hexanes.</p><p num="0483"> Example 79D 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (pyridin-3-yloxy) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 79C.</p><p num="0484"> Example 79E 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (pyridin-3-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 79D.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.72 (wide s, 1H), 8.64 (t, 1H), 8.46 (d, 1H), 8.15 (t, 2H), 7.75 (dd, 1H), 7.52-7.44 (m, 6H), 7.37 (m) , 2H), 7.26-7.10 (m, 4H), 6.79 (dd, 1H), 6.50 (d, 1H), 3.87 (dd, 2H), 3.40 (s, 2H), 3.38-3.24 (m, 4H), 3.19 (wide s, 4H), 2.37 (wide s, 4H), 1.92 (m, 1H), 1.65 (d, 2H), 1.28 (m, 2H).</p><p num="0485"> Example 80 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (pyridin-3-yloxy) -N-({4- [( Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 79D and Example 1F with Example 2A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.34 (s, 1H), 8.27 (dd, 2H), 7.51-7.44 (m, 8H), 7.41-7.29 (m, 3H), 7.27-7.19 (m, 2H), 6.78 (dd, 1H), 6.72 (t, 1H), 6.56 (d, 2H), 6.44 (d, 1H), 3.86 (dd, 2H), 3.36 (s, 2H), 3.29-3.22 (m, 2H), 3.16 (m, 4H) , 2.96 (t, 2H), 2.34 (m, 4H), 1.77 (m, 1H), 1.66 (d, 2H), 1.21 (m, 2H).</p><p num="0486"> Example 81 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[4-({(1R) -3- (dimethylamino)) -1-[(Phenylthio) methyl] propyl} amino) -3-nitrophenyl] sulfonyl} -2-phenoxybenzamide Example 81A (R) -tert-Butyl 3-(((9H-fluorene-9-yl) methoxy) carbonylamino) -4-hydroxybutanoate Fmoc-D-Asp (OtBu) -OH (9.0 g) and N, N-diisopropylethylamine (4.6 mL) were added to tetrahydrofuran (100 mL) and cooled to -40 ° C. Isobutyl chloroformate (3.1 mL) was added and the solution was gradually warmed to 0 ° C over 30 minutes. The solution was cooled to -20 ° C and sodium borohydride (1.64 g, 43.6 mmol) and methanol (10 mL) were carefully added to it. The solution is gradually warmed to room temperature over 2 hours, diluted with ethyl acetate (200 mL), washed with water (100 mL) and brine (50 mL), dehydrated with anhydrous magnesium sulfate, filtered and concentrated, followed by A crude product of sufficient purity for use was obtained.</p><p num="0487"> Example 81B (R) -tert-Butyl 3-(((9H-fluorene-9-yl) methoxy) carbonylamino) -4- (phenylthio) butanoate Tri-n-butylphosphine (90 μL) and 1,1'-(azodicarbonyl) dipiperidin (91 mg) were added to tetrahydrofuran (4 mL) and treated with Example 81A (90 mg) and thiophenol (21 mg) at room temperature. Stirred for 18 hours. The solution was concentrated and purified by flash column chromatography on silica gel with 50% ethyl acetate in hexanes.</p><p num="0488"> Example 81C (R) -tert-Butyl 3- (2-nitro-4-sulfamoylphenylamino) -4- (phenylthio) butanoate Example 81B (600 mg), 4-fluoro-3-nitrobenzenesulfonamide (298 mg) and N, N-diisopropylethylamine (3 mL) were added to N, N-dimethylformamide (3 mL) and stirred at 60 ° C for 12 hours. .. The reaction mixture was diluted with ethyl acetate (100 mL), washed with water (45 mL) and brine (10 mL), dehydrated with anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel with 30% ethyl acetate in dichloromethane.</p><p num="0489"> Example 81D (R) -3- (2-nitro-4-sulfamoylphenylamino) -4- (phenylthio) butanoic acid Example 81C (468 mg) and 4M HCl in 1,4-dioxane (10 mL) were stirred at 50 ° C. for 5 hours. The solution was concentrated to give a crude product of sufficient purity for subsequent use.</p><p num="0490"> Example 81E (R) -N, N-dimethyl-3- (2-nitro-4-sulfamoylphenylamino) -4- (phenylthio) butaneamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 81D and substituting Example 1F with dimethylamine (2M in tetrahydrofuran).</p><p num="0491"> Example 81F (R) -4- (4- (dimethylamino) -1- (phenylthio) butane-2-ylamino) -3-nitrobenzenesulfonamide Borane (1M, 20.0 mL in tetrahydrofuran) was added to Example 81E (4.06 g). The solution was stirred at room temperature for 16 hours. The reaction was gradually quenched with methanol (5.0 mL) and concentrated aqueous HCl solution (2.0 mL) was added. The solution is stirred at 80 ° C for 3 hours, cooled to room temperature, carefully basified with 4M sodium carbonate, diluted with ethyl acetate (150 mL), washed with water (50 mL) and brine (10 mL), anhydrous magnesium sulfate. It was dehydrated and filtered. The solution was concentrated and purified by flash column chromatography on silica gel with 20% methanol in dichloromethane.</p><p num="0492"> Example 81G 4- {4- (4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[4-({(lR) -3- (dimethylamino)-) 1-[(phenylthio) methyl] propyl} amino) -3-nitrophenyl] sulfonyl} -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 81F.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.33 (d, 1H), 8.28 (d, 1H), 7.61 (dd, 2H), 7.50-7.43 (m, 4H), 7.37-7.14 (m, HH), 6.90 (t, 1H), 6.84 ( d, 1H), 6.71 (d, 2H), 6.70 (dd, 1H), 6.32 (d, 1H), 4.06 (m, 1H), 3.36 (s, 2H), 3.33-3.30 (m, 2H), 3.08 (t, 4H), 2.86 (m, 2H), 2.53 (s, 6H), 2.35 (t, 4H), 2.04 (m, 2H).</p><p num="0493"> Example 82 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (pyridin-4-yloxy) benzamide Example 82A Methyl 4-bromo-2- (pyridin-4-yloxy) benzoate Example 79A (800 mg), pyridine-4-ol (359 mg) and potassium carbonate (617 mg) were added to N, N-dimethylacetamide (20 mL) and the mixture was heated to 125 ° C for 16 hours. The solution was concentrated under vacuum at 48 ° C. and purified by flash column chromatography on silica gel with 20% methanol in dichloromethane.</p><p num="0494"> Example 82B Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (pyridin-4-yloxy) benzoate This Example compound was prepared by substituting Example 79B of Example 79C with Example 82A.</p><p num="0495"> Example 82C 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (pyridin-4-yloxy) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 82B.</p><p num="0496"> Example 82D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2- (pyridin-4-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 82C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.40 (t, 1H), 8.37 (d, 1H), 7.76 (dd, 1H), 7.65 (d, 1H), 7.54-7.48 (m, 1H), 7.47 (s, 3H), 7.42-7.35 ( m, 5H), 7.27-7.23 (m, 1H), 7.06 (dd, 1H), 6.92 (dd, 1H), 6.88 (d, 1H), 5.91 (d, 2H), 3.85 (dd, 2H), 3.39 (s, 2H), 3.34-3.25 (m, 4H), 3.19 (wide, s, 4H), 2.39 (wide s, 4H), 1.92 (m, 1H), 1.65 (d, 2H), 1.27 (m, 2H).</p><p num="0497"> Example 83 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4-[(3-morpholine-4-ylpropyl) amino ] -3-Nitrophenyl} Sulfonyl) -2- (Pyridine-3-yloxy) Benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 79D and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.73 (t, 1H), 8.43 (d, 1H), 8.12 (t, 2H), 7.73 (dd, 1H), 7.55 (d, 1H), 7.51-7.44 (m, 4H), 7.37 (m, 2H), 7.25-7.17 (m, 3H), 7.07 (d, 2H), 6.78 (dd, 1H), 6.47 (d, 1H), 3.65 (t, 4H), 3.47 (q, 2H), 3.38 (s , 2H), 3.28 (m, 2H), 3.17 (br s, 4H), 2.57 (br s, 4H), 2.36 (br s, 4H), 1.84 (m, 2H).</p><p num="0498"> Example 84 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4-[(3-morpholine-4-ylpropyl) amino ] -3-Nitrophenyl} Sulfonyl) -2- (Pyridine-4-yloxy) Benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 82C and Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.55 (t, 1H), 8.37 (d, 1H), 7.77 (dd, 1H), 7.65 (d, 1H), 7.54-7.43 (m, 5H), 7.42-7.32 (m, 4H), 7.26- 7.22 (m, 1H), 7.01 (d, 1H), 6.91 (dd, 1H), 6.66 (d, 1H), 5.90 (d, 2H), 3.60 (t, 4H), 3.43 (q, 2H), 3.39 (s, 2H), 3.18 (br s, 4H), 2.38 (m, 10H), 1.80 (t, 2H).</p><p num="0499"> Example 85 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[2- (4-methylpiperazine-1-) Il) Ethyl] amino} -3-nitrophenyl) Sulfonyl] -2-phenoxybenzamide Example 85A 4- (2- (4-Methylpiperazin-1-yl) ethylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine in Example 1F with 2- (4-methylpiperazin-1-yl) ethaneamine.</p><p num="0500"> Example 85B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[2- (4-methylpiperazine-1-) Il) Ethyl] amino} -3-nitrophenyl) Sulfonyl] -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 85A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.61 (t, 1H), 8.40 (d, 1H), 7.72 (dd, 1H), 7.57 (d, 1H), 7.51-7.44 (m, 5H), 7.36 (m, 2H), 7.26-7.15 ( m, 3H), 6.95 (t, 2H), 6.75 (dd, 2H), 6.71 (dd, 1H), 6.34 (d, 1H), 3.45 (q, 2H), 3.36 (s, 2H), 3.34 (m , 2H), 3.10 (t, 4H), 2.79 (wide s, 4H), 2.68 (t, 2H), 2.60 (wide s, 2H), 2.49 (s, 3H), 2.35 (t, 4H).</p><p num="0501"> Example 86 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (4-methylpiperazin-1-) Il) propyl] amino} -3-nitrophenyl) sulfonyl] -2-phenoxybenzamide Example 86A 4- (3- (4-Methylpiperazin-1-yl) propylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by substituting the (tetrahydropyran-4-yl) methylamine of Example 1F with 3- (4-methylpiperazin-1-yl) propan-1-amine.</p><p num="0502"> Example 86B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (4-methylpiperazin-1-) Il) propyl] amino} -3-nitrophenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 86A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.57 (t, 1H), 8.38 (d, 1H), 7.71 (dd, 1H), 7.59 (d, 1H), 7.50-7.44 (m, 5H), 7.36 (m, 2H), 7.27-7.15 ( m, 3H), 6.98 (d, 2H), 6.91 (t, 1H), 6.73 (dd, 2H), 6.70 (dd, 2H), 6.33 (d, 1H), 3.43 (q, 2H), 3.36 (s) , 2H), 3.34 (m, 2H), 3.09 (t, 4H), 2.82 (wide s, 4H), 2.56 (wide s, 2H), 2.49 (s, 3H), 2.35 (t, 4H), 1.79 ( t, 2H).</p><p num="0503"> Example 87 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4- [[3- (dimethylamino) propyl]] (methyl) ) Amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide Example 87A 4-((3- (Dimethylamino) Propyl) (Methyl) Amino) -3-Nitrobenzene Sulfonamide This Example compound was supplemented with N of 3- (pyrrolidin-1-yl) propan-1-amine of Example 68F.¹, N¹, N³Prepared by replacing with -trimethylpropane-1,3-diamine.</p><p num="0504"> Example 87B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4- [[3-3-yl) (Dimethylamino) propyl] (methyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 87A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.01 (d, 1H), 7.68 (dd, 1H), 7.63 (d, 1H), 7.51-7.44 (m, 5H), 7.36 (m, 2H), 7.26-7.13 (m, 3H), 6.93 ( t, 1H), 6.83 (m, 1H), 6.74 (dd, 2H), 6.69 (dd, 1H), 6.32 (d, 1H), 3.46 (q, 2H), 3.36 (s, 2H), 3.08 (t) , 4H), 2.83 (t, 2H), 2.77 (s, 3H), 2.60 (s, 6H), 2.36 (t, 4H), 1.86 (m, 2H).</p><p num="0505"> Example 88 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[(1-methylpiperidine-4-yl)) Methyl] amino} -3-nitrophenyl) sulfonyl] -2-phenoxybenzamide Example 88A 4-((1-Methylpiperidin-4-yl) methylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing 3- (pyrrolidin-1-yl) propan-1-amine in Example 68F with (1-methylpiperidin-4-yl) methaneamine.</p><p num="0506"> Example 88B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[(1-methylpiperidine-4-yl)) Methyl] amino} -3-nitrophenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 88A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.44 (t, 1H), 8.35 (d, 1H), 7.79 (dd, 1H), 7.62 (d, 1H), 7.51-7.45 (m, 5H), 7.36 (m, 2H), 7.25-7.14 ( m, 3H), 6.99 (d, 1H), 6.89 (t, 1H), 6.71 (d, 2H), 6.68 (dd, 1H), 6.31 (d, 1H), 3.36 (s, 2H), 3.34 (m) , 4H), 3.07 (t, 4H), 2.73 (m, 2H), 2.62 (s, 3H), 2.36 (t, 4H), 1.90-1.82 (m, 3H), 1.47-1.31 (m, 2H).</p><p num="0507"> Example 89 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4-[(1-methylpiperidine-4-yl) amino) ] -3-Nitrophenyl} Sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.38 (t, 1H), 8.09 (d, 1H), 7.73 (m, 1H), 7.59 (d, 1H), 7.52-7.44 (m, 5H), 7.36 (m, 2H), 7.26-7.22 ( m, 1H), 7.17 (t, 1H), 7.05 (d, 1H), 6.90 (t, 1H), 6.83 (m, 1H), 6.72 (d, 2H), 6.70 (dd, 1H), 6.33 (d) , 1H), 3.36 (q, 2H), 3.36 (s, 2H), 3.24-3.12 (m, 2H), 3.09 (t, 4H), 2.80 (m, 1H), 2.59 (s, 3H), 2.36 ( t, 4H), 2.08 (m, 2H), 1.77 (m, 2H).</p><p num="0508"> Example 90 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-cyano-4-{[3- (dimethylamino)) Propyl] amino} phenyl) sulfonyl] -2-phenoxybenzamide Example 90A 3-Cyano-4-fluorobenzenesulfonamide High concentrations of ammonium hydroxide (28% aqueous solution, 3.17 mL) were cooled to 0 ° C. and 3-cyano-4-fluorobenzene-1-sulfonyl chloride (1.00 g) was added. The solution was mixed at 0 ° C for 4 minutes. 4M HCl (10 mL) was added slowly and the solution was extracted with ethyl acetate. The extract was dehydrated with brine and anhydrous sodium sulfate and the solvent was removed under vacuum.</p><p num="0509"> Example 90B 3-Cyano-4- (3- (dimethylamino) propylamino) benzenesulfonamide This Example compound was replaced with Example 90A for 4-chloro-3-nitrobenzenesulfonamide of Example 68F and N of 3- (pyrrolidin-1-yl) propan-1-amine.¹, N¹-Prepared by replacing with dimethylpropane-1,3-diamine.</p><p num="0510"> Example 90C 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-cyano-4-{[3- (dimethylamino)) Propyl] amino} phenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 90B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 7.67 (s, 1H), 7.66 (dd, 1H), 7.59 (d, 1H), 7.51-7.44 (m, 5H), 7.36 (m, 2H), 7.28-7.20 (m, 3H), 6.98 ( t, 2H), 6.77 (dd, 2H), 6.70 (d, 2H), 6.33 (d, 1H), 3.36 (s, 2H), 3.27 (q, 2H), 3.09 (t, 4H), 2.82 (t) , 2H), 2.54 (s, 6H), 2.35 (t, 4H), 1.82 (m, 2H).</p><p num="0511"> Example 91 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(3-pyrrolidin-1-yl) Ilpropyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 68F.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.49 (t, 1H), 8.37 (d, 1H), 7.72 (dd, 1H), 7.62 (d, 1H), 7.50-7.43 (m, 5H), 7.35 (m, 2H), 7.26-7.14 ( m, 3H), 6.97 (d, 1H), 6.90 (t, 1H), 6.72 (d, 2H), 6.69 (dd, 1H), 6.31 (d, 1H), 3.47 (q, 2H), 3.36 (s) , 2H), 3.20 (m, 2H), 3.07 (wide s, 8H), 2.35 (wide s, 4H), 1.95-1.83 (m, 6H).</p><p num="0512"> Example 92 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[4-{[3- (dimethylamino) propyl] amino} -3- (Trifluoromethyl) phenyl] sulfonyl} -2-phenoxybenzamide Example 92A 4-Fluoro-3- (trifluoromethyl) benzenesulfonamide This Example compound was prepared by replacing 3-cyano-4-fluorobenzene-1-sulfonyl chloride in Example 90A with 4-fluoro-3- (trifluoromethyl) benzene-1-sulfonyl chloride.</p><p num="0513"> Example 92B 4- (3- (Dimethylamino) Propylamino) -3- (Trifluoromethyl) Benzene Sulfonamide This Example compound was replaced with Example 92A for 4-fluoro-3-nitrobenzenesulfonamide in Example 1F, and tetrahydropyran-4-yl) methylamine was replaced with N.¹, N¹-Prepared by replacing with dimethylpropane-1,3-diamine.</p><p num="0514"> Example 92C 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[4-{[3- (dimethylamino) propyl] amino} -3- (Trifluoromethyl) phenyl] sulfonyl} -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 92B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 7.77 (s, 1H), 7.68 (dd, 1H), 7.57 (d, 1H), 7.51-7.45 (m, 5H), 7.36 (m, 2H), 7.29-7.21 (m, 3H), 6.99 ( t, 1H), 6.82-6.68 (m, 5H), 6.32 (d, 1H), 3.36 (s, 2H), 3.28 (q, 2H), 3.09 (t, 4H), 2.73 (m, 2H), 2.48 (s, 6H), 2.35 (t, 4H), 1.79 (m, 2H).</p><p num="0515"> Example 93 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[4-({3- [isopropyl (methyl) amino] propyl } Amino) -3-nitrophenyl] Sulfonyl} -2-phenoxybenzamide Example 93A tert-Butylmethyl (3- (2-nitro-4-sulfamoylphenylamino) propyl) carbamate This Example compound was prepared by replacing 3- (pyrrolidin-1-yl) propan-1-amine of Example 68F with tert-butyl 3-aminopropyl (methyl) carbamate.</p><p num="0516"> Example 93B tert-Butyl 3-(4- (N- (4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoyl) sulfamoyl) -2-nitrophenyl Amino) propyl (methyl) carbamate This Example compound was prepared by substituting Example 1F of Example 1G with Example 93A.</p><p num="0517"> Example 93C 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -N- (4- (3- (methylamino) propylamino) -3-nitrophenylsulfonyl) -2 -Phenoxybenzamide Example 93B (112 mg) and triethylsilane (0.082 mL) were added to dichloromethane (2 mL). Trifluoroacetic acid (0.198 mL) was added, the solution was stirred at room temperature for 1 hour and the solvent was removed under vacuum.</p><p num="0518"> Example 93D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-{[4-({3- [isopropyl (methyl) amino] propyl } Amino) -3-nitrophenyl] Sulfonyl} -2-phenoxybenzamide Example 93C (128 mg), acetone (0.014 mL) and sodium cyanoborohydride resin (2.15 mmol / g, 66 mg) were added to tetrahydrofuran (0.9 mL) and acetic acid (0.3 mL), and the solution was stirred at room temperature for 16 hours. Further, acetone (0.014 mL) and sodium cyanoborohydride resin (66 mg) were added, and the solution was stirred for 24 hours. The solution was purified by flash column chromatography on silica gel with 1% acetic acid and 10% methanol in dichloromethane.¹1 H NMR (300MHz, dimethyl sulfoxide-dg) δ 11.93 (wide s, 3H), 8.53 (wide s, 1H), 8.40 (d, 1H), 7.75 (dd, 1H), 7.60 (d, 1H), 7.51- 7.45 (m, 5H), 7.36 (m, 2H), 7.25-7.16 (m, 3H), 7.02 (d, 1H), 6.92 (t, 1H), 6.74 (d, 2H), 6.70 (dd, 1H) , 6.32 (d, 1H), 3.47 (m, 4H), 3.36 (s, 2H), 3.09 (t, 4H), 3.01 (wide s, 2H), 2.58 (s, 3H), 2.35 (t, 4H) , 1.94 (m, 1H), 1.18-1.14 (m, 6H).</p><p num="0519"> Example 94 4- {4- (4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4- [3- (dimethylamino) propoxy] -3-nitro Phenyl} sulfonyl) -2-phenoxybenzamide Example 94A 4- (3- (Dimethylamino) propoxy) -3-nitrobenzene sulfonamide Triphenylphosphine (1.398 g) was added to tetrahydrofuran (20 mL) and cooled to 0 ° C. Diethylazodicarboxylate (40% solution, 2.428 mL) was added and the solution was stirred at 0 ° C for 15 minutes. 4-Hydroxy-3-nitrobenzenesulfonamide (1.163 g) and 3- (dimethylamine) propan-1-ol (0.567 mL) were added, the solution was warmed to room temperature and stirred for 16 hours. The solvent was removed under vacuum and the material was recrystallized with 20% methanol (dichloromethane). The recrystallized solid was washed with dichloromethane, dissolved in methanol / dichloromethane, treated with triethylamine (0.13 mL, 0.924 mmol) and flash column chromatography on silica gel with 10-20% methanol in dichloromethane. Purified.</p><p num="0520"> Example 94B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4- [3- (dimethylamino) propoxy] -3- Nitrophenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 94A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.06 (d, 1H), 7.84 (dd, 1H), 7.65 (d, 1H), 7.52-7.45 (m, 5H), 7.36 (m, 2H), 7.26-7.22 (m, 2H), 7.18 ( td, 2H), 6.89 (t, 1H), 6.69 (d, 1H), 6.68 (d, 2H), 6.32 (d, 1H), 4.25 (t, 2H), 3.36 (s, 2H), 3.13 (t) , 2H), 3.08 (t, 4H), 2.75 (s, 6H), 2.36 (t, 4H), 2.11 (m, 2H).</p><p num="0521"> Example 95 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[2- (4-Methylpiperazin-1-yl) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 85A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.10 (s, 1H), 8.67 (t, 1H), 8.53 (d, 1H), 7.78 (dd, 1H), 7.52 (d, 1H), 7.39-7.31 (m, 4H), 7.08-7.02 ( m, 3H), 6.94 (d, 1H), 6.80 (dd, 1H), 6.61 (dd, 1H), 6.36 (t, 1H), 6.14 (d, 1H), 3.42 (q, 2H), 2.99 (t) , 4H), 2.71 (s, 2H), 2.70-2.48 (m, 10H), 2.39 (s, 3H), 2.16 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 ( s, 6H).</p><p num="0522"> Example 96 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[3- (4-Methylpiperazin-1-yl) propyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 86A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.09 (s, 1H), 8.62 (t, 1H), 8.51 (d, 1H), 7.76 (dd, 1H), 7.53 (d, 1H), 7.38-7.31 (m, 4H), 7.05 (s, 1H), 7.02 (d, 2H), 6.96 (d, 1H), 6.79 (dd, 1H), 6.60 (dd, 1H), 6.35 (t, 1H), 6.14 (d, 1H), 3.40 (q, 2H) ), 2.98 (t, 4H), 2.71 (s, 2H), 2.67 (wide s, 4H), 2.55-2.40 (m, 6H), 2.39 (s, 3H), 2.16 (m, 6H), 1.95 (s) , 2H), 1.77 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0523"> Example 97 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 68F.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.06 (s, 1H), 8.58 (t, 1H), 8.49 (d, 1H), 7.77 (dd, 1H), 7.54 (d, 1H), 7.36-7.31 (m, 4H), 7.06-7.01 ( m, 3H), 6.95 (d, 1H), 6.76 (dd, 1H), 6.57 (dd, 1H), 6.35 (t, 1H), 6.14 (d, 1H), 3.44 (q, 2H), 2.97 (wide) s, 10H), 2.71 (s, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.90-1.80 (m, 6H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0524"> Example 98 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.08 (s, 1H), 8.51 (d, 1H), 8.13 (d, 1H), 7.78 (dd, 1H), 7.52 (d, 1H), 7.37-7.31 (m, 4H), 7.06-7.00 ( m, 4H), 6.79 (dd, 1H), 6.59 (dd, 1H), 6.35 (t, 1H), 6.14 (d, 1H), 3.73 (m, 1H), 3.05-2.95 (m, 6H), 2.71 (s, 2H), 2.60 (m, 2H), 2.48 (s, 3H), 2.16 (m, 6H), 2.01 (m, 2H), 1.95 (s, 2H), 1.70 (m, 2H), 1.38 ( t, 2H), 0.92 (s, 6H).</p><p num="0525"> Example 99 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[3- (4-Methylpiperazin-1-yl) propyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 86A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 1H), 8.59 (t, 1H), 8.45 (d, 1H), 7.72 (dd, 1H), 7.55 (d, 1H), 7.34 (d, 2H), 7.23 (t, 1H) , 7.12 (d, 1H), 7.02 (d, 2H), 6.95 (d, 1H), 6.94 (t, 1H), 6.64 (dd, 1H), 6.35 (d, 1H), 6.23 (m, 2H), 3.41 (q, 2H), 2.98 (t, 4H), 2.71 (wide s, 6H), 2.52-2.42 (m, 6H), 2.41 (s, 3H), 2.15 (m, 6H), 1.95 (s, 2H) ), 1.77 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0526"> Example 100 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [3- ({4- [3- ( Dimethylamino) propoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 94A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.03 (s, 1H), 8.23 (d, 1H), 7.91 (dd, 1H), 7.56 (d, 1H), 7.36-7.29 (m, 4H), 7.19 (d, 1H), 7.05 (d, 2H), 6.97 (s, 1H), 6.73 (dd, 1H), 6.57 (dd, 1H), 6.33 (t, 1H), 6.15 (d, 1H), 4.23 (t, 2H), 3.04 (m, 2H) ), 2.96 (t, 4H), 2.72 (s, 2H), 2.67 (s, 6H), 2.22-2.02 (m, 8H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0527"> Example 101 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[2- (4-Methylpiperazin-1-yl) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 85A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.18 (s, 1H), 8.64 (t, 1H), 8.47 (d, 1H), 7.73 (dd, 2H), 7.56 (d, 1H), 7.34 (d, 2H), 7.24 (t, 1H) , 7.04 (d, 2H), 6.96 (d, 1H), 6.94 (d, 1H), 6.65 (dd, 1H), 6.37 (d, 1H), 6.23 (m, 2H), 3.43 (q, 2H), 2.99 (t, 4H), 2.71 (s, 2H), 2.65 (m, 6H), 2.56 (m, 4H), 2.42 (s, 3H), 2.15 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0528"> Example 102 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 68F.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 1H), 8.54 (t, 1H), 8.44 (d, 1H), 7.76 (dd, 1H), 7.59 (d, 1H), 7.34 (d, 2H), 7.22 (t, 1H) , 7.10 (d, 1H), 7.05 (d, 2H), 6.98-6.89 (m, 2H), 6.62 (dd, 1H), 6.33 (d, 1H), 6.23 (t, 1H), 6.21 (d, 1H) ), 3.44 (q, 2H), 3.10-2.91 (m, 10H), 2.71 (s, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.92-1.79 (m, 6H), 1.38 ( t, 2H), 0.92 (s, 6H).</p><p num="0529"> Example 103 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 1H), 8.44 (d, 1H), 8.11 (d, 1H), 7.75 (dd, 1H), 7.56 (d, 1H), 7.34 (d, 2H), 7.23 (t, 1H) , 7.11 (d, 1H), 7.04 (d, 2H), 7.03 (d, 1H), 6.93 (t, 1H), 6.64 (dd, 1H), 6.34 (d, 1H), 6.22 (m, 2H), 3.73 (m, 1H), 3.08-2.93 (m, 6H), 2.71 (s, 2H), 2.70-2.56 (m, 2H), 2.48 (s, 3H), 2.16 (m, 6H), 2.02 (m, m, 2H), 1.95 (s, 2H), 1.70 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0530"> Example 104 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1-Methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 88A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 10.99 (s, 1H), 8.39 (d, 1H), 8.32 (t, 1H), 7.65 (dd, 1H), 7.54 (d, 1H), 7.34 (d, 2H), 7.30-7.26 (m, 2H), 7.05 (d, 2H), 6.92 (d, 1H), 6.81 (d, 1H), 6.70 (dd, 1H), 6.53 (dd, 1H), 6.30 (t, 1H), 6.15 (d, 1H) ), 3.28-3.19 (m, 2H), 2.93 (t, 4H), 2.83 (m, 2H), 2.71 (s, 2H), 2.68-2.50 (m, 2H), 2.54 (s, 3H), 2.24- 2.10 (m, 6H), 1.95 (wide s, 2H), 1.68 (d, 2H), 1.59 (m, 1H), 1.38 (t, 2H), 1.32-1.17 (m, 2H), 0.92 (s, 6H) ).</p><p num="0531"> Example 105 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[(1-Methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 88A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.11 (s, 1H), 8.44 (t, 1H), 8.41 (d, 1H), 7.74 (dd, 1H), 7.59 (d, 1H), 7.34 (d, 2H), 7.21 (t, 1H) , 7.11-7.02 (m, 3H), 6.98-6.90 (m, 2H), 6.61 (dd, 1H), 6.31 (d, 1H), 6.23 (t, 1H), 6.20 (d, 1H), 3.20 (m) , 2H), 2.95 (t, 4H), 2.71 (s, 2H), 2.62-2.49 (m, 4H), 2.55 (s, 3H), 2.16 (m, 6H), 1.95 (s, 2H), 1.86- 1.78 (m, 3H), 1.42-1.31 (m, 4H), 0.92 (s, 6H).</p><p num="0532"> Example 106 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [3- ({4- [3- ( Dimethylamino) propoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 94A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.10 (s, 1H), 8.16 (d, 1H), 7.90 (dd, 1H), 7.61 (d, 1H), 7.35 (d, 2H), 7.24-7.19 (m, 2H), 7.10-7.01 ( m, 3H), 6.91 (t, 1H), 6.60 (dd, 1H), 6.28 (d, 1H), 6.23 (t, 1H), 6.20 (d, 1H), 4.23 (t, 2H), 3.03 (t) , 2H), 2.95 (t, 4H), 2.72 (s, 2H), 2.67 (s, 6H), 2.17 (m, 6H), 2.07 (m, 2H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0533"> Example 107 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (4-Methylpiperazin-1-yl) -3-nitrophenyl] sulfonyl} benzamide Example 107A 4- (4-Methylpiperazin-1-yl) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing 3- (pyrrolidin-1-yl) propan-1-amine of Example 68F with 1-methylpiperazine.</p><p num="0534"> Example 107B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (4-Methylpiperazin-1-yl) -3-nitrophenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 107A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.21 (s, 1H), 8.18 (d, 1H), 7.77 (dd, 1H), 7.57 (d, 1H), 7.34 (d, 2H), 7.26 (t, 1H), 7.22 (d, 1H) , 7.16 (d, 1H), 7.07-7.02 (m, 2H), 6.96 (t, 1H), 6.87 (dd, 1H), 6.39 (d, 1H), 6.25 (m, 2H), 3.16 (m, 4H) ), 3.01 (t, 4H), 2.73 (s, 2H), 2.66 (wide s, 4H), 2.39 (s, 3H), 2.18 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H) ), 0.92 (s, 6H).</p><p num="0535"> Example 108 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(3-Nitro-4-{[1- (2,2,2-trifluoroethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide Example 108A 3-Nitro-4- (1- (2,2,2-trifluoroethyl) piperidine-4-ylamino) benzenesulfonamide 4-Chloro-3-nitrobenzenesulfonamide (1.300 g), 1- (2,2,2-trifluoroethyl) piperidine-4-amine hydrochloride (1.201 g) and triethylamine (2.30 mL) 1,4-dioxane It was added to (50 mL) and water (5 mL) and heated at 90 ° C for 16 hours. The solution was concentrated under vacuum and purified using flash column chromatography on silica gel while increasing ethyl acetate to 5% methanol in ethyl acetate.</p><p num="0536"> Example 108B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(3-Nitro-4-{[1- (2,2,2-trifluoroethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 108A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.24 (s, 1H), 8.50 (d, 1H), 8.25 (d, 1H), 7.71 (dd, 1H), 7.52 (d, 1H), 7.34 (d, 2H), 7.27 (t, 1H) , 7.17 (d, 1H), 7.11 (d, 1H), 7.04 (d, 2H), 6.97 (t, 1H), 6.71 (dd, 1H), 6.43 (d, 1H), 6.28 (d, 1H), 6.24 (t, 1H), 3.68 (m, 1H), 3.23 (q, 2H), 3.06 (wide s, 4H), 2.95-2.87 (m, 2H), 2.78-2.71 (m, 2H), 2.58 (t) , 2H), 2.25-2.11 (m, 6H), 1.98-1.85 (m, 4H), 1.64 (m, 2H), 1.39 (t, 2H), 0.92 (s, 6H).</p><p num="0537"> Example 109 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[4 -(Dimethylamino) -1-methylpiperidin-4-yl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide Example 109A 4-((4- (Dimethylamino) -1-methylpiperidin-4-yl) methylamino) -3-nitrobenzenesulfonamide This Example compound was used as the 1- (2,2,2-trifluoroethyl) piperidine-4-amine hydrochloride of Example 108A with 4- (aminomethyl) -N, N, 1-trimethylpiperidine-4-amine. Prepared by replacing with.</p><p num="0538"> Example 109B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[4 -(Dimethylamino) -1-methylpiperidin-4-yl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 109A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.06 (s, 1H), 8.56 (wide s, 1H), 8.50 (d, 1H), 7.81 (dd, 1H), 7.54 (d, 1H), 7.36-7.31 (m, 4H), 7.08-7.02 (m, 4H), 6.77 (dd, 1H), 6.57 (dd, 1H), 6.34 (t, 1H), 6.13 (d, 1H), 3.50 (d, 2H), 3.04 (m, 2H), 2.96 ( t, 4H), 2.87 (m, 2H), 2.71 (s, 2H), 2.58 (s, 3H), 2.28 (s, 6H), 2.16 (m, 6H), 1.98 (m, 2H), 1.95 (s , 2H), 1.65-1.54 (m, 2H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="0539"> Example 110 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (2,3-dihydro-1,4-benzodioxin-5- Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 110A Methyl 4-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (2,3-dihydrobenzo [b] [1,4] dioxin-5-yloxy) Benzoate This Example compound was prepared by replacing Example 18E of Example 18F with Example 34A and replacing phenol with 2,3-dihydrobenzo [b] [1,4] dioxin-5-ol.</p><p num="0540"> Example 110B 4- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2- (2,3-dihydrobenzo [b] [1,4] dioxine-5-yloxy) benzoin acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 110A.</p><p num="0541"> Example 110C 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (2,3-dihydro-1,4-benzodioxin-5- Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 110B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ ppm 11.40 (s, 1H), 8.65 (t, 1H), 8.55 (d, 1H), 7.83 (dd, 1H), 7.46 (m, 6H), 7.36 (m, 2H), 7.23 (m, 2H) ), 6.77 (d, 1H), 6.70 (dd, 1H), 6.42 (m, 2H), 6.27 (d, 1H), 4.20 (s, 4H), 3.85 (dd, 2H), 3.37 (m, 4H) , 3.25 (m, 2H), 3.13 (m, 4H), 2.35 (m, 4H), 1.90 (m, 1H), 1.62 (dd, 2H), 1.27 (m, 2H).</p><p num="0542"> Example 111 5- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -1,1'-biphenyl-2-carboxamide Example 111A Methyl 5-(4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) biphenyl-2-carboxylate Example 34A (100 mg, 0.2 mmol) in tetrahydrofuran (1.5 mL) with phenylboronic acid (36.6 mg, 0.3 mmol), tris (dibenzylideneacetone) dipalladium (0) (9.2 mg, 0.01 mmol), tri-tert -Treatment with butylphosphonium tetrafluoroborate (5.8 mg, 0.02 mmol) and cesium fluoride (91 mg, 0.6 mmol), flushed with nitrogen and stirred overnight at ambient temperature. The reaction mixture is diluted with ethyl acetate, washed with water and brine and dehydrated (DDL).₄), Filtered and concentrated. Concentrate by column chromatography on silica gel, CH₂Cl₂The product was obtained by elution in a gradient of 0 to 3% methanol and purification.</p><p num="0543"> Example 111B 5- (4-((4'-Chlorobiphenyl-2-yl) methyl) piperazine-1-yl) biphenyl-2-carboxylic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 111A.</p><p num="0544"> Example 111C 5- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -1,1'-biphenyl-2-carboxamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 111B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ ppm 12.09 (s, 1H), 8.72 (t, 1H), 8.46 (d, 1H), 7.79 (m, 2H), 7.52 (m, 4H), 7.35 (dd, 5H), 7.16 (m, 1H) ), 7.04 (m, 4H), 6.91 (dd, 1H), 6.78 (m, 1H), 4.39 (m, 1H), 3.88 (m, 3H), 3.42 (m, 4H), 3.27 (m, 4H) , 2.96 (m, 4H), 1.95 (m, 1H), 1.67 (m, 2H), 1.31 (m, 2H).</p><p num="0545"> Example 112 5- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-Nitrophenyl) Sulfonyl] -1,1'-biphenyl-2-carboxamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 111B and Example 1F with Example 154A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ ppm 12.09 (s, 1H), 8.74 (t, 1H), 8.47 (d, 1H), 7.83 (dd, 1H), 7.70 (m, 1H), 7.40 (m, 8H), 7.27 (m, 1H) ), 7.20 (m, 1H), 7.07 (m, 4H), 6.91 (dd, 1H), 6.77 (m, 1H), 4.39 (m, 1H), 3.87 (m, 1H), 3.55 (m, 4H) , 3.26 (m, 2H), 3.16 (m, 4H), 3.03 (m, 2H), 2.80 (m, 6H), 1.98 (m, 2H).</p><p num="0546"> Example 113 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 113A Methyl 2-phenoxy-4- (piperazine-1-yl) benzoate This Example compound was prepared by replacing Example 1B of Example 1D with piperazine.</p><p num="0547"> Example 113B Methyl 4- (4- (2-bromo-5-hydroxybenzyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with 2-bromo-5-hydroxybenzaldehyde and tert-butylpiperazin-1-carboxylate with Example 113A. did.</p><p num="0548"> Example 113C Methyl 4- (4- (2-bromo-5- (2- (dimethylamino) ethoxy) benzyl) piperazine-1-yl) -2-phenoxybenzoate A mixture of Example 113B (170 mg), 2-chloro-N, N-dimethylethaneamine hydrochloride (80 mg) and cesium carbonate (278 mg) was suspended in anhydrous N, N-dimethylformamide (3 mL). The reaction mixture was heated at 50 ° C. overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. Wash the organic phase with water and brine and sodium anhydrous₂SO₄Dehydrated with. The solvent was removed under vacuum to give an oily residue. It was used in the next step without purification.</p><p num="0549"> Example 113D Methyl 4-((4'-chloro-4- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by substituting Example 68C of Example 68D with Example 113C and substituting 4-methoxyphenylboronic acid with 4-chlorophenylboronic acid.</p><p num="0550"> Example 113E 4- (4-((4'-Chloro-4- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 113D.</p><p num="0551"> Example 113F 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 113E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.69 (br s, 1H), 9.87 (br s, 1H), 8.63 (t, 1H), 8.46 (d, 1H), 7.75 (dd, 1H), 7.50 (m, 3H), 7.34-7.23 ( m, 6H), 7.14 (m, 2H), 6.98 (m, 1H), 6.78 (m, 3H), 6.44 (d, 1H), 4.37 (t, 2H), 3.86 (m, 2H), 3.60-3.41 (m, 10H), 3.34 (t, 4H), 3.28 (m, 2H), 2.89 (s, 6H), 1.91 (m, 1H), 1.62 (m, 2H), 1.28 (m, 2H).</p><p num="0552"> Example 114 4- (4-{[4'-Chloro-4- (3-piperidin-1-ylpropoxy) -1,1'-biphenyl-2-yl] methyl} piperazin-1-yl) -N-({3 -Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 114A Methyl 4- (4- (2-Bromo-5- (3- (piperidine-1-yl) propoxy) benzyl) piperazin-1-yl) -2-phenoxybenzoate This Example compound was prepared by replacing the 2-chloro-N, N-dimethylethaneamine hydrochloride salt of Example 113C with a 1- (3-chloropropyl) piperidine hydrochloride salt.</p><p num="0553"> Example 114B Methyl 4-((4'-chloro-4- (3- (piperidine-1-yl) propoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by substituting Example 68C of Example 68D with Example 114A and substituting 4-methoxyphenylboronic acid with 4-chlorophenylboronic acid.</p><p num="0554"> Example 114C 4- (4-((4'-Chloro-4- (3- (piperidine-1-yl) propoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 114B.</p><p num="0555"> Example 114D 4- (4-{[4'-Chloro-4- (3-piperidin-1-ylpropoxy) -1,1'-biphenyl-2-yl] methyl} piperazin-1-yl) -N-({3 -Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 114C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.69 (br s, 1H), 9.18 (br s, 1H), 8.63 (t, 1H), 8.46 (d, 1H), 7.75 (dd, 1H), 7.50 (m, 3H), 7.33-7.21 ( m, 6H), 7.15 (d, 2H), 6.98 (m, 1H), 6.78 (m, 3H), 6.44 (d, 1H), 4.11 (t, 2H), 3.87 (dd, 2H), 3.60-3.38 (m, 10H), 3.34 (m, 4H), 3.25 (m, 4H), 2.92 (m, 2H), 2.17 (m, 2H), 1.85 (m, 3H), 1.64 (m, 6H), 1.29 ( m, 2H).</p><p num="0556"> Example 115 4- (4-{[4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 115A Methyl 4- (4- (2-bromo-5- (2-morpholinoethoxy) benzyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by replacing the 2-chloro-N, N-dimethylethaneamine hydrochloride salt of Example 113C with a 4- (2-chloroethyl) morpholine hydrochloride salt.</p><p num="0557"> Example 115B Methyl 4-(4-((4'-chloro-4- (2-morpholinoethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by replacing Example 68C of Example 68D with Example 115A and replacing 4-methoxyphenylboronic acid with 4-chlorophenylboronic acid.</p><p num="0558"> Example 115C 4- (4-((4'-Chloro-4- (2-morpholinoethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 115B.</p><p num="0559"> Example 115D 4- (4-{[4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 115C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.66 (br s, 1H), 8.63 (t, 1H), 8.46 (d, 1H), 7.75 (dd, 1H), 7.50 (m, 3H), 7.31 (m, 4H), 7.23 (m, 2H) ), 7.15 (m, 2H), 6.98 (m, 1H), 6.78 (m, 3H), 6.44 (d, 1H), 4.41 (m, 2H), 3.87 (m, 6H), 3.60-3.38 (m, 12H), 3.36-3.25 (m, 8H), 1.91 (m, 1H), 1.64 (m, 2H), 1.29 (m, 2H).</p><p num="0560"> Example 116 4- [4-({4'-Chloro-4- [3- (dimethylamino) propoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 116A Methyl 4- (4- (2-bromo-5- (3- (dimethylamino) propoxy) benzyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by replacing the 2-chloro-N, N-dimethylethaneamine hydrochloride salt of Example 113C with a 3-chloro-N, N-dimethylpropan-1-amine hydrochloride salt.</p><p num="0561"> Example 116B Methyl 4-((4'-chloro-4- (3- (dimethylamino) propoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by substituting Example 68C of Example 68D with Example 116A and substituting 4-methoxyphenylboronic acid with 4-chlorophenylboronic acid.</p><p num="0562"> Example 116C 4- (4-((4'-Chloro-4- (3- (dimethylamino) propoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 116B.</p><p num="0563"> Example 116D 4- [4-({4'-Chloro-4- [3- (dimethylamino) propoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 116C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.64 (br s, 1H), 9.52 (br s, 1H), 8.63 (t, 1H), 8.47 (d, 1H), 7.75 (dd, 1H), 7.50 (m, 3H), 7.34 (m, 2H), 7.23 (m, 4H), 7.14 (d, 1H), 6.98 (m, 2H), 6.78 (m, 3H), 6.42 (s, 1H), 4.09 (t, 2H), 3.86 (m, 2H) ), 3.50-3.36 (m, 8H), 3.28 (m, 8H), 2.83 (s, 6H), 2.12 (m, 2H), 1.91 (m, 1H), 1.62 (m, 2H), 1.29 (m, 2H).</p><p num="0564"> Example 117 4- (4-{[4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2-phenoxy-N- ({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 115C and Example 1F with Example 163A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 8.11 (d, 1H), 7.86 (dd, 1H), 7.49 (m, 3H), 7.36-7.26 (m, 7H), 7.10 (m, 3H), 6.84 (d, 2H), 6.77 (dd, dd, 1H), 6.41 (s, 1H), 4.38 (m, 2H), 3.84 (m, 4H), 3.55 (m, 2H), 3.50-3.30 (m, 10H), 3.28 (m, 8H), 3.20 (m) , 2H), 1.86 (m, 1H), 1.55 (m, 2H), 1.26 (m, 2H).</p><p num="0565"> Example 118 4- (4-{[4'-Chloro-4- (3-piperidin-1-ylpropoxy) -1,1'-biphenyl-2-yl] methyl} piperazin-1-yl) -2-phenoxy-N -({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 114C and Example 1F with Example 163A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.65 (br s, 1H), 9.06 (br s, 1H), 8.11 (d, 1H), 7.86 (dd, 1H), 7.49 (m, 3H), 7.36-7.20 (m, 7H), 7.06 ( m, 3H), 6.83 (d, 2H), 6.76 (dd, 1H), 6.41 (s, 1H), 4.10 (t, 2H), 3.85 (dd, 2H), 3.40-3.05 (m, 16H), 2.90 (m, 2H), 2.15 (m, 2H), 1.84 (m, 3H), 1.60 (m, 6H), 1.41 (m, 2H), 1.26 (m, 2H).</p><p num="0566"> Example 119 4- [4-({4'-Chloro-4- [3- (dimethylamino) propoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2-phenoxy-N- ({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 116C and Example 1F with Example 163A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 8.11 (d, 1H), 7.86 (dd, 1H), 7.49 (m, 3H), 7.36-7.26 (m, 7H), 7.06 (m, 3H), 6.84 (d, 2H), 6.76 (dd, dd, 1H), 6.41 (d, 1H), 4.09 (t, 2H), 3.84 (dd, 2H), 3.50-3.24 (m, 14H), 3.10 (m, 2H), 2.83 (s, 6H), 2.12 (m) , 2H), 1.86 (m, 1H), 1.55 (m, 2H), 1.26 (m, 2H).</p><p num="0567"> Example 120 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2-phenoxy-N- ({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 113E and Example 1F with Example 163A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.75 (br s, 1H), 9.90 (br s, 1H), 8.10 (d, 1H), 7.85 (dd, 1H), 7.49 (m, 3H), 7.38-7.25 (m, 7H), 7.11 ( d, 2H), 7.03 (m, 1H), 6.82 (d, 2H), 6.77 (dd, 1H), 6.44 (s, 1H), 4.37 (t, 2H), 3.85 (m, 6H), 3.55 (m) , 2H), 3.29 (m, 8H), 3.10 (m, 2H), 2.89 (s, 6H), 1.86 (m, 1H), 1.55 (m, 2H), 1.24 (m, 2H).</p><p num="0568"> Example 121 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({3- Nitro-4-[(3-pyrrolidine-1-ylpropyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 113E and Example 1F with Example 68F.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.70 (br s, 1H), 9.95 (br s, 1H), 9.73 (br s, 1H), 8.69 (t, 1H), 8.49 (d, 1H), 7.79 (dd, 1H), 7.50 (m) , 3H), 7.34 (m, 2H), 7.23 (m, 3H), 7.16 (d, 1H), 7.09 (m, 1H), 7.00 (m, 1H), 6.82 (d, 2H), 6.77 (dd, dd, 1H), 6.42 (s, 1H), 4.37 (m, 2H), 3.70 (m, 6H), 3.54 (m, 8H), 3.21 (m, 4H), 3.19 (m, 2H), 2.88 (s, 6H) ), 1.97 (m, 4H), 1.85 (m, 2H).</p><p num="0569"> Example 122 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 122A Methyl 4- (4- (2-bromo-6-hydroxybenzyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with 2-bromo-6-hydroxybenzaldehyde and tert-butylpiperazin-1-carboxylate with Example 113A. did.</p><p num="0570"> Example 122B Methyl 4-(4-((4'-chloro-3-hydroxybiphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by substituting Example 68C of Example 68D with Example 122A and substituting 4-methoxyphenylboronic acid with 4-chlorophenylboronic acid.</p><p num="0571"> Example 122C Methyl 4-((4'-chloro-3- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoate Example 122B (100 mg) and 2-chloro-N, N-dimethylethaneamine hydrochloride (30 mg) were dissolved in a mixed solvent of dichloromethane (1.5 mL) and 50% aqueous sodium hydroxide solution (0.5 mL), followed by Tetrabutylammonium iodide (15 mg) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with water and brine. Organic phase Na₂SO₄It was dehydrated and concentrated. Flash column purification was performed with 0-5% methanol / dichloromethane to give the product.</p><p num="0572"> Example 122D 4- (4-((4'-Chloro-3- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 122C.</p><p num="0573"> Example 122E 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 122D.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 10.20 (br s, 1H), 9.46 (br s, 1H), 8.65 (t, 1H), 8.47 (d, 1H), 7.78 (d, 1H), 7.75 (dd, 1H), 7.52 (m, 4H), 7.38 (m, 3H), 7.23 (m, 3H), 7.12 (m, 1H), 6.98 (m, 2H), 6.78 (d, 2H), 6.76 (dd, 1H), 6.43 (s, 1H) ), 4.43 (m, 2H), 3.87 (m, 2H), 3.62 (m, 4H), 3.35-3.15 (m, 12H), 2.90 (s, 6H), 1.90 (m, 1H), 1.62 (m, m, 2H), 1.27 (m, 2H).</p><p num="0574"> Example 123 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({3- Nitro-4-[(3-pyrrolidine-1-ylpropyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 122C and Example 1F with Example 68F.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 10.01 (br s, 1H), 9.63 (br s, 1H), 9.32 (br s, 1H), 8.69 (t, 1H), 8.49 (d, 1H), 7.80 (dd, 1H), 7.52 (m) , 4H), 7.38 (m, 2H), 7.25 (m, 3H), 7.15 (d, 1H), 7.01 (m, 1H), 6.95 (m, 1H), 6.81 (d, 2H), 6.76 (m, 1H), 6.41 (s, 1H), 4.43 (m, 4H), 3.56-3.51 (m, 8H), 3.20 (m, 4H), 3.10 (m, 6H), 2.91 (s, 6H), 1.98 (m) , 4H), 1.85 (m, 2H).</p><p num="0575"> Example 124 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2-phenoxy-N- ({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 122C and Example 1F with Example 163A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.71 (br s, 1H), 9.89 (br s, 1H), 9.14 (br s, 1H), 8.11 (d, 1H), 7.86 (dd, 1H), 7.52 (m, 4H), 7.38 (m) , 2H), 7.29 (m, 3H), 7.20 (m, 1H), 7.11 (d, 1H), 7.05 (m, 1H), 6.95 (m, 1H), 6.83 (d, 2H), 6.76 (dd, dd, 1H), 6.40 (s, 1H), 4.41 (m, 2H), 3.85 (m, 2H), 3.59 (m, 4H), 3.44 (m, 2H), 3.28 (m, 8H), 3.06 (m, 2H) ), 2.91 (s, 6H), 1.84 (m, 1H), 1.55 (m, 2H), 1.26 (m, 2H).</p><p num="0576"> Example 125 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 125A 4'-Chloro-4-hydroxybiphenyl-2-carbaldehyde This Example compound was prepared by substituting Example 68C of Example 68D with 2-bromo-5-hydroxybenzaldehyde and substituting 4-methoxyphenylboronic acid with 4-chlorophenylboronic acid.</p><p num="0577"> Example 125B 4'-Chloro-4- (2- (dimethylamino) ethoxy) biphenyl-2-carbaldehyde This Example compound was prepared by substituting Example 122B of Example 122C with Example 125A.</p><p num="0578"> Example 125C Methyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) Benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 125B and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0579"> Example 125D 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) Benzoin acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 125C.</p><p num="0580"> Example 125E 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 125D.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.46 (br s, 1H), 11.25 (s, 1H), 9.80 (br s, 1H), 8.60 (t, 1H), 8.48 (d, 1H), 7.65 (dd, 1H), 7.55 (d, 1H), 7.46 (d, 2H), 7.28 (m, 5H), 7.15 (d, 1H), 7.10 (m, 1H), 7.04 (d, 1H), 6.94 (m, 1H), 6.73 (dd, 1H) ), 6.36 (m, 2H), 6.26 (m, 1H), 4.35 (t, 2H), 3.85 (m, 6H), 3.54 (m, 4H), 3.31 (m, 6H), 3.06 (m, 2H) , 2.88 (s, 6H), 1.88 (m, 1H), 1.60 (m, 2H), 1.28 (m, 2H).</p><p num="0581"> Example 126 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 126A Methyl 2- (1H-indole-5-yloxy) -4-(4-((4'-chloro-4- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) Benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxardhide of Example 1A with Example 125B and tert-butylpiperazin-1-carboxylate with Example 150A.</p><p num="0582"> Example 126B 2- (1H-indole-5-yloxy) -4-(4-((4'-chloro-4- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) benzoin acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 126A.</p><p num="0583"> Example 126C 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 126B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.35 (br s, 1H), 11.17 (s, 1H), 9.85 (br s, 1H), 8.61 (t, 1H) 8.57 (d, 1H), 7.77 (dd, 1H), 7.54 (d, 1H) ), 7.46 (d, 2H), 7.38 (m, 2H), 7.30 (m, 4H), 7.09 (m, 3H), 6.84 (dd, 1H), 6.69 (dd, 1H), 6.36 (m, 1H) , 6.26 (m, 1H), 4.35 (t, 2H), 3.85 (m, 6H), 3.54 (m, 4H), 3.31 (m, 6H), 3.06 (m, 2H), 2.88 (s, 6H), 1.88 (m, 1H), 1.60 (m, 2H), 1.28 (m, 2H).</p><p num="0584"> Example 127 4- (4-{[4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 127A 4'-Chloro-4- (2-morpholinoethoxy) biphenyl-2-carbaldehyde This Example compound was prepared by replacing Example 122B of Example 122C with Example 125A and replacing the 2-chloro-N, N-dimethylethaneamine hydrochloride salt with a 4- (2-chloroethyl) morpholine hydrochloride salt. did.</p><p num="0585"> Example 127B Methyl 2- (1H-indole-5-yloxy) -4-(4-((4'-chloro-4- (2-morpholinoethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxardhide of Example 1A with Example 127A and tert-butylpiperazin-1-carboxylate with Example 150A.</p><p num="0586"> Example 127C 2- (1H-indole-5-yloxy) -4-(4-((4'-chloro-4- (2-morpholinoethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 127B.</p><p num="0587"> Example 127D 4- (4-{[4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 127C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.35 (br s, 1H), 11.17 (s, 1H), 8.61 (t, 1H), 8.57 (d, 1H), 7.77 (dd, 1H), 7.54 (d, 1H), 7.46 (d, 2H) ), 7.38 (m, 2H), 7.29 (m, 4H), 7.09 (m, 3H), 6.84 (dd, 1H), 6.69 (dd, 1H), 6.36 (m, 1H), 6.26 (d, 1H) , 4.39 (t, 2H), 3.85 (m, 6H), 3.54 (m, 10H), 3.31 (m, 8H), 3.06 (m, 2H), 1.88 (m, 1H), 1.60 (m, 2H), 1.27 (m, 2H).</p><p num="0588"> Example 128 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 128A 4'-Chloro-3-hydroxybiphenyl-2-carbaldehyde This Example compound was prepared by substituting Example 68C of Example 68D with 2-bromo-6-hydroxybenzaldehyde and substituting 4-methoxyphenylboronic acid with 4-chlorophenylboronic acid.</p><p num="0589"> Example 128B 4'-Chloro-3- (2- (dimethylamino) ethoxy) biphenyl-2-carbaldehyde This Example compound was prepared by substituting Example 122B of Example 122C with Example 128A.</p><p num="0590"> Example 128C Methyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-3- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) Benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 128B and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0591"> Example 128D 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-3-(2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) Benzoin acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 128C.</p><p num="0592"> Example 128E 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 128D.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.15 (s, 1H), 8.47 (t, 1H) 8.45 (d, 1H), 7.68 (dd, 1H), 7.57 (d, 1H), 7.50 (d, 2H), 7.42 (d, 2H), 7.32 (m, 1H), 7.24 (m, 1H), 7.12 (d, 1H), 7.05 (d, 1H), 6.94 (m, 2H), 6.84 (d, 1H), 6.66 (dd, 1H), 6.35 (d, 1H), 6.25 (m, 2H), 4.17 (t, 2H), 3.85 (m, 2H), 3.54 (m, 10H), 3.40 (m, 6H), 3.30 (s, 6H), 3.02 ( m, 2H), 2.96 (m, 4H), 2.28 (m, 4H), 1.88 (m, 1H), 1.60 (m, 2H), 1.28 (m, 2H).</p><p num="0593"> Example 129 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 129A Methyl 2- (1H-indole-5-yloxy) -4-(4-((4'-chloro-3- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) Benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxardhide of Example 1A with Example 128B and tert-butylpiperazin-1-carboxylate with Example 150A.</p><p num="0594"> Example 129B 2- (1H-indole-5-yloxy) -4-(4-((4'-chloro-3- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) benzoin acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 129A.</p><p num="0595"> Example 129C 4- [4- ({4'-Chloro-3- [2- ( dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 129B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.38 (br s, 1H), 11.19 (s, 1H), 10.00 (br s, 1H), 8.61 (t, 1H) 8.58 (d, 1H), 7.79 (dd, 1H), 7.53 (m, 4H) ), 7.39 (m, 4H), 7.19 (m, 1H), 7.11 (m, 2H), 6.93 (d, 1H), 6.84 (dd, 1H), 6.69 (dd, 1H), 6.39 (m, 1H) , 6.19 (d, 1H), 4.40 (m, 2H), 3.85 (m, 8H), 3.58 (m, 2H), 3.27 (m, 6H), 3.06 (m, 2H), 2.89 (s, 6H), 1.89 (m, 1H), 1.60 (m, 2H), 1.27 (m, 2H).</p><p num="0596"> Example 130 4- (4-{[4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 130A Methyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4- (2-morpholinoethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxardhide of Example 1A with Example 127A and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0597"> Example 130B 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4- (2-morpholinoethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 130A.</p><p num="0598"> Example 130C 4- (4-{[4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 130B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.47 (br s, 1H), 11.23 (s, 1H), 8.59 (t, 1H) 8.47 (d, 1H), 7.63 (dd, 1H), 7.54 (d, 1H), 7.47 (d, 2H) , 7.27 (m, 6H), 7.13 (m, 2H), 7.03 (m, 1H), 6.93 (m, 1H), 6.74 (dd, 1H), 6.35 (m, 1H), 6.24 (m, 1H), 4.39 (t, 2H), 3.85 (m, 6H), 3.54 (m, 10H), 3.26 (m, 10H), 1.88 (m, 1H), 1.59 (m, 2H), 1.27 (m, 2H).</p><p num="0599"> Example 131 4- (4-{[4'-Chloro-3- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 131A 4'-Chloro-3- (2-morpholinoethoxy) biphenyl-2-carbaldehyde This Example compound was prepared by replacing Example 122B of Example 122C with Example 128A and replacing the 2-chloro-N, N-dimethylethaneamine hydrochloride salt with a 4- (2-chloroethyl) morpholine hydrochloride salt. did.</p><p num="0600"> Example 131B Methyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-3- (2-morpholinoethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 131A and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0601"> Example 131C 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-3- (2-morpholinoethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 131B.</p><p num="0602"> Example 131D 4- (4-{[4'-Chloro-3- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 131C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.49 (br s, 1H), 11.25 (s, 1H), 8.59 (t, 1H), 8.50 (d, 1H), 7.68 (dd, 1H), 7.52 (m, 4H), 7.34 (d, 2H) ), 7.28 (m, 1H), 7.18 (m, 2H), 7.06 (d, 1H), 6.94 (m, 2H), 6.73 (dd, 1H), 6.40 (d, 1H), 6.33 (d, 1H) , 6.24 (m, 1H), 4.43 (t, 2H), 3.85 (m, 10H), 3.61 (m, 6H), 3.27 (m, 8H), 3.02 (m, 2H), 1.88 (m, 1H), 1.60 (m, 2H), 1.28 (m, 2H).</p><p num="0603"> Example 132 4- (4-{[4'-Chloro-3- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 132A Methyl 2- (1H-indole-5-yloxy) -4-(4-((4'-chloro-3- (2-morpholinoethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxardhide of Example 1A with Example 131A and tert-butylpiperazin-1-carboxylate with Example 150A.</p><p num="0604"> Example 132B 2- (1H-indole-5-yloxy) -4-(4-((4'-chloro-3- (2-morpholinoethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 132A.</p><p num="0605"> Example 132C 4- (4-{[4'-Chloro-3- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 132B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.34 (br s, 1H), 11.17 (s, 1H), 8.60 (t, 1H), 8.58 (d, 1H), 7.79 (dd, 1H), 7.50 (m, 4H), 7.39 (m, 4H) ), 7.19 (d, 1H), 7.14 (d, 1H), 7.09 (d, 1H), 6.93 (d, 1H), 6.84 (dd, 1H), 6.69 (dd, 1H), 6.39 (m, 1H) , 6.19 (d, 1H), 4.40 (m, 2H), 3.85 (m, 6H), 3.48 (m, 8H), 3.27 (m, 10H), 3.06 (m, 2H), 1.89 (m, 1H), 1.60 (m, 2H), 1.27 (m, 2H).</p><p num="0606"> Example 133 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({4- [(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 113D and Example 1F with Example 21A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 8.34 (d, 1H), 8.05 (d, 1H), 7.69 (dd, 1H), 7.59 (d, 1H), 7.42 (m, 4H), 7.14 (m, 3H), 7.09 (d, 1H) , 6.98 (d, 1H), 6.92 (dd, 1H), 6.87 (m, 1H), 6.84 (m, 3H), 6.30 (d, 1H), 4.16 (t, 2H), 3.07 (m, 6H), 2.95 (m, 4H), 2.56 (m, 2H), 2.45 (s, 3H), 2.35 (m, 4H), 2.03 (m, 2H), 1.68 (m, 2H).</p><p num="0607"> Example 134 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 129B and substituting Example 1F with Example 68F.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.34 (br s, 1H), 11.17 (s, 1H), 9.65 (br s, 1H), 8.63 (t, 1H), 8.60 (d, 1H), 7.86 (dd, 1H), 7.53 (d, 2H), 7.41 (m, 6H), 7.15 (m, 3H), 6.92 (m, 1H), 6.84 (dd, 1H), 6.66 (dd, 1H), 6.38 (m, 1H), 6.16 (d, 1H) ), 4.37 (m, 2H), 3.50 (m, 12H), 3.17 (m, 4H), 2.97 (m, 4H), 2.88 (s, 6H), 1.95 (m, 4H), 1.85 (m, 2H) ..</p><p num="0608"> Example 135 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 126B and Example 1F with Example 68F.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.29 (br s, 1H), 11.16 (s, 1H), 9.56 (br s, 1H), 8.63 (t, 1H), 8.60 (d, 1H), 7.85 (dd, 1H), 7.53 (d, 1H), 7.41 (m, 4H), 7.32 (m, 3H), 7.24 (m, 1H), 7.12 (m, 3H), 6.84 (dd, 1H), 6.66 (dd, 1H), 6.38 (m, 1H) ), 6.18 (d, 1H), 4.33 (t, 2H), 3.50 (m, 12H), 3.17 (m, 4H), 2.97 (m, 4H), 2.86 (s, 6H), 1.95 (m, 4H) , 1.85 (m, 2H).</p><p num="0609"> Example 136 4- (4-{[4'-Chloro-4- (2-morpholine-4-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(3-pyrrolidin-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 127C and Example 1F with Example 68F.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.29 (br s, 1H), 11.16 (s, 1H), 9.54 (br s, 1H), 8.63 (t, 1H), 8.60 (d, 1H), 7.85 (dd, 1H), 7.53 (d, 1H), 7.45 (d, 2H), 7.38 (m, 2H), 7.31 (d, 2H), 7.23 (m, 2H), 7.12 (m, 3H), 6.84 (dd, 1H), 6.66 (dd, 1H) ), 6.38 (m, 1H), 6.18 (d, 1H), 4.36 (t, 2H), 3.82 (m, 4H), 3.50 (m, 8H), 3.17 (m, 10H), 2.98 (m, 4H) , 1.95 (m, 6H), 1.85 (m, 2H).</p><p num="0610"> Example 137 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-[(3-3-yl) Nitro-4-{[1- (2,2,2-trifluoroethyl) piperidine-4-yl] amino} phenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 113E and Example 1F with Example 108A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.71 (br s, 1H), 9.81 (br s, 1H), 8.46 (d, 1H), 8.29 (d, 1H), 7.75 (dd, 1H), 7.50 (m, 3H), 7.30 (m, 4H), 7.21 (m, 3H), 7.10 (m, 1H), 6.97 (m, 1H), 6.77 (m, 3H), 6.43 (s, 1H), 4.36 (t, 2H), 3.72 (m, 2H) ), 3.58 (m, 4H), 3.23 (m, 6H), 2.95 (m, 4H), 2.89 (s, 6H), 2.60 (m, 2H), 1.92 (m, 2H), 1.68 (m, 2H) ..</p><p num="0611"> Example 138 4- (4-{[4'-Chloro-4- (2-pyrrolidine-1-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 138A Methyl 4-(4-((4'-chloro-4-hydroxybiphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by substituting Example 68C of Example 68D with Example 113B and substituting 4-methoxyphenylboronic acid with 4-chlorophenylboronic acid.</p><p num="0612"> Example 138B Methyl 4-((4'-chloro-4- (2- (pyrrolidin-1-yl) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by replacing Example 113B of Example 113C with Example 138A and replacing the 2-chloro-N, N-dimethylethaneamine hydrochloride salt with a 1- (2-chloroethyl) pyrrolidine HCl salt. ..</p><p num="0613"> Example 138C 4- (4-((4'-Chloro-4- (2- (pyrrolidin-1-yl) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 138B.</p><p num="0614"> Example 138D 4- (4-{[4'-Chloro-4- (2-pyrrolidine-1-ylethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 138C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.64 (br s, 1H), 9.98 (br s, 1H), 8.62 (d, 1H), 8.47 (d, 1H), 7.75 (dd, 1H), 7.50 (m, 3H), 7.26 (m, 6H), 7.14 (m, 2H), 6.99 (m, 1H), 6.81 (d, 2H), 6.77 (dd, 1H), 6.43 (d, 1H), 4.36 (t, 2H), 3.86 (dd, 2H) ), 3.62 (m, 8H), 3.28 (m, 8H), 3.10 (m, 4H), 2.04 (m, 2H), 1.90 (m, 3H), 1.65 (m, 2H), 1.29 (m, 2H) ..</p><p num="0615"> Example 139 4- [4-({4'-Chloro-4- [2- (diisopropylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 139A Methyl 4-((4'-chloro-4- (2- (diisopropylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoate This Example compound was prepared by substituting Example 113B of Example 113C with Example 138A and substituting 2-chloro-N, N-dimethylethaneamine hydrochloride salt with 2-diisopropylaminoethyl chloride hydrochloride salt.</p><p num="0616"> Example 139B 4- (4-((4'-Chloro-4- (2- (diisopropylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 139A.</p><p num="0617"> Example 139C 4- [4-({4'-Chloro-4- [2- (diisopropylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -N-({3- Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 27H with Example 139B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.65 (br s, 1H), 8.75 (br s, 1H), 8.62 (d, 1H), 8.47 (d, 1H), 7.75 (dd, 1H), 7.50 (m, 3H), 7.31 (m, 4H), 7.23 (m, 2H), 7.13 (m, 2H), 6.99 (m, 1H), 6.79 (m, 3H), 6.44 (m, 1H), 4.31 (t, 2H), 3.86 (dd, 2H) ), 3.62 (m, 10H), 3.28 (m, 6H), 1.91 (m, 1H), 1.62 (m, 2H), 1.32 (m, 14H).</p><p num="0618"> Example 140 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (2,3-dihydro-1H-indole-5-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide A suspension of Example 40D (22.57 mg) and sodium cyanoborohydride (25 mg) in acetic acid (5 ml) was stirred at room temperature for 2 hours. The product was partitioned between dichloromethane and water. Separate the organic layer and Na₂SO₄It was dehydrated and concentrated. The crude product was purified by RP HPLC (C8, 30-100 acetonitrile / water / 0.1% trifluoroacetic acid).¹1 H NMR (300MHz, dimethyl sulfoxide-dβ) δ 11.56 (s, 1H), 9.60 (s, 1H), 8.66 (t, 1H), 8.57 (d, 1H), 7.85 (dd, 1H), 7.71 (s, 1H), 7.46-7.60 (m, 5H), 7.29-7.42 (m, 3H), 7.25 (d, 1H), 6.95 (s, 1H), 6.82 (s, 1H), 6.73 (d, 1H), 6.36 (s, 1H), 4.32 (bs, 2H), 3.85 (dd, 4H), 3.59 (t, 4H), 3.35 (t, 2H), 3.27 (t, 2H), 3.02 (t, 4H), 1.80- 1.99 (m, 1H), 1.62 (d, 2H), 1.15-1.36 (m, 2H).</p><p num="0619"> Example 141 4- (4-{[2- (4-chlorophenyl) cyclohepta-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({3 -Nitro-4-[(3-pyrrolidine-1-ylpropyl) amino] phenyl} sulfonyl) benzamide Example 141A (Z) -Methyl 2- (Trifluoromethylsulfonyloxy) Cycloheptane-1-encarboxylate This Example compound was prepared by replacing 5,5-dimethyl-2-methoxycarbonylcyclohexanone in Example 18A with methyl 2-oxocycloheptane carboxylate.</p><p num="0620"> Example 141B (Z) -Methyl 2- (4-chlorophenyl) Cycloheptane-1-encarboxylate This Example compound was prepared by substituting Example 18A of Example 18B with Example 141A.</p><p num="0621"> Example 141C (Z)-(2- (4-chlorophenyl) cyclohepta-1-enyl) methanol This Example compound was prepared by substituting Example 18B of Example 18C with Example 141B.</p><p num="0622"> Example 141D (Z) -2- (4-chlorophenyl) cycloheptane-1-encarbaldehyde This Example compound was prepared by substituting Example 143C of Example 143D with Example 141C.</p><p num="0623"> Example 141E (Z) -Ethyl 2- (1H-Indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) Cyclohept-1-enyl) Methyl) Piperazine-1-yl) Benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 141D and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0624"> Example 141F (Z) -2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) cyclohept-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 143E of Example 143F with Example 141E.</p><p num="0625"> Example 141G 4- (4-{[2- (4-chlorophenyl) cyclohepta-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({3 -Nitro-4-[(3-pyrrolidine-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 141F and Example 1F with Example 68F.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.45 (m, 1H), 10.03 (m, 1H), 8.58 (m, 2H), 8.30 (m, 1H), 7.26 (m, HH), 6.25 (m, 2H), 3.14 (m, 12H) , 2.73 (m, 5H), 1.94 (m, 12H), 1.54 (m, 5H).</p><p num="0626"> Example 142 4- (4-{[2- (4-chlorophenyl) cycloocta-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({3 -Nitro-4-[(3-pyrrolidine-1-ylpropyl) amino] phenyl} sulfonyl) benzamide Example 142A (Z) -Ethyl 2- (Trifluoromethylsulfonyloxy) Cyclooct-1-encarboxylate This Example compound was prepared by replacing 5,5-dimethyl-2-methoxycarbonylcyclohexanone in Example 18A with ethyl 2-oxocyclooctanecarboxylate.</p><p num="0627"> Example 142B (Z) -Ethyl 2- (4-Chlorophenyl) Cycloocta-1-encarboxylate This Example compound was prepared by substituting Example 18A of Example 18B with Example 142A.</p><p num="0628"> Example 142C (Z)-(2- (4-chlorophenyl) cycloocta-1-enyl) methanol This Example compound was prepared by substituting Example 18B of Example 18C with Example 142B.</p><p num="0629"> Example 142D (Z) -2- (4-chlorophenyl) cycloocta-1-encarbaldehyde This Example compound was prepared by substituting Example 143C of Example 143D with Example 142C.</p><p num="0630"> Example 142 E (Z) -Ethyl 2- (1H-Indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) Cycloocta-1-enyl) Methyl) Piperazine-1-yl) Benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 142D and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0631"> Example 142F (Z) -2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) cycloocta-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 143E of Example 143F with Example 142E.</p><p num="0632"> Example 142 G 4- (4-{[2- (4-chlorophenyl) cycloocta-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({3 -Nitro-4-[(3-pyrrolidine-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 142F and Example 1F with Example 68F.¹1 H NMR (300MHz, dimethyl sulfoxide-d6) δ 11.51 (m, 1H), 10.01 (m, 1H), 8.58 (m, 2H), 7.26 (m, 12H), 6.35 (m, 2H), 3.14 (m, m, 13H), 2.73 (m, 5H), 1.88 (m, 7H), 1.45 (m, 10H).</p><p num="0633"> Example 143 4- (4-{[2- (4-chlorophenyl) cyclopenta-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({3 -Nitro-4-[(3-pyrrolidine-1-ylpropyl) amino] phenyl} sulfonyl) benzamide Example 143A Ethyl 2- (trifluoromethylsulfonyloxy) cyclopenta-1-encarboxylate This Example compound was prepared by replacing 5,5-dimethyl-2-methoxycarbonylcyclohexanone in Example 18A with ethyl 2-oxocyclopentanecarboxylate.</p><p num="0634"> Example 143B Ethyl 2- (4-chlorophenyl) cyclopenta-1-encarboxylate This Example compound was prepared by substituting Example 18A of Example 18B with Example 143A.</p><p num="0635"> Example 143C (2- (4-Chlorophenyl) cyclopenta-1-enyl) methanol This Example compound was prepared by substituting Example 18B of Example 18C with Example 143B.</p><p num="0636"> Example 143D 2- (4-Chlorophenyl) Cyclopenta-1-enecarbaldehyde Dimethyl sulfoxide (6.12 ml) was added to a solution of oxalyl chloride (1.1 g) in dichloromethane (30 ml) at -78 ° C. The mixture was stirred at 78 ° C. for 30 minutes, then a solution of Example 143C (1.2 g) in dichloromethane (10 ml) was added. The mixture was stirred at 78 ° C. for 2 hours, then triethylamine (10 ml) was added. The mixture was stirred overnight and the temperature was raised to room temperature. The mixture is diluted with ether (300 ml), washed with water and brine, Na₂SO₄Dehydrated with. The solvent was evaporated and column purification (5% ethyl acetate in hexanes) gave the product.</p><p num="0637"> Example 143E Ethyl 2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) cyclopenta-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 143D and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0638"> Example 143F 2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) cyclopenta-1-enyl) methyl) piperazine-1-yl) benzoic acid Example 143 E (254 mg) in solution in tetrahydrofuran (4 ml), methanol (2 ml) and water (2 ml) LiOH-H₂O (126 mg) was added. The mixture was stirred overnight. The mixture was then neutralized with 5% HCl and diluted with ethyl acetate (200 ml). After washing with brine, this is Na₂SO₄Dehydrated with. The solvent was evaporated to give the product.</p><p num="0639"> Example 143G 4- (4-{[2- (4-chlorophenyl) cyclopenta-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({3 -Nitro-4-[(3-pyrrolidine-1-ylpropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 143F and Example 1F with Example 68F.¹1 H NMR (300MHz, dimethyl sulfoxide-d6) δ ppm 11.41 (m, 1H), 10.19 (m, 1H), 8.58 (m, 2H), 7.26 (m, 14H), 6.33 (m, 2H), 3.80 (m) , 4H), 3.13 (m, 12H), 2.69 (m, 5H), 1.95 (m, 7H).</p><p num="0640"> Example 144 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclopenta-1-ene-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 144A Methyl 4,4-dimethyl-2-oxocyclopentane carboxylate This compound was prepared according to WO 2006/035061 (page 53).</p><p num="0641"> Example 144B Methyl 4,4-dimethyl-2- (trifluoromethylsulfonyloxy) cyclopenta-1-encarboxylate This Example compound was prepared by replacing 5,5-dimethyl-2-methoxycarbonylcyclohexanone in Example 18A with ethyl 2-oxocyclopentanecarboxylate.</p><p num="0642"> Example 144C Ethyl 2- (4-chlorophenyl) -4,4-dimethylcyclopenta-1-encarboxylate This Example compound was prepared by substituting Example 18A of Example 18B with Example 144B.</p><p num="0643"> Example 144D (2- (4-Chlorophenyl) -4,4-dimethylcyclopenta-1-enyl) methanol This Example compound was prepared by substituting Example 18B of Example 18C with Example 144C.</p><p num="0644"> Example 144E 2- (4-Chlorophenyl) -4,4-dimethylcyclopenta-1-encarbaldehyde This Example compound was prepared by substituting Example 143C of Example 143D with Example 144D.</p><p num="0645"> Example 144F Ethyl 2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclopent-1-enyl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 144E and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0646"> Example 144G 2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclopenta-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 143E of Example 143F with Example 144F.</p><p num="0647"> Example 144H 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclopenta-1-ene-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 144G and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d6) δ 11.59 (m, 1H), 11.25 (s, 1H), 9.53 (m, 1H), 8.50 (d, 1H), 8.16 (d, 1H), 8.16 (d, 1H), 7.80 (m, 1H), 7.56 (d, 1H), 7.26 (m, 7H), 6.95 (m, 1H), 6.77 (dd, 1H), 6.41 (m, 2H), 6.23 (s, 1H) ), 2.87 (m, 10H), 2.28 (m, 12H), 1.11 (m, 6H).</p><p num="0648"> Example 145 4- (4-{[4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 145A Methyl 6,6-dimethyl-4-oxotetrahydro-2H-pyran-3-carboxylate A suspension of hexane-washed NaH (0.72 g, 60%) in tetrahydrofuran (30 ml) with a solution of 2,2-dimethyldihydro-2H-pyran-4 (3H) -one (2.0 g) in tetrahydrofuran (20 ml). added. The suspension was stirred for 30 minutes. Dimethyl carbonate (6.31 ml) was added dropwise with a syringe. The mixture was reflux heated for 4 hours. The mixture is acidified with 5% HCl, extracted with dichloromethane (3 x 100 ml), washed with water and brine, Na₂SO₄Dehydrated with. After evaporation, the crude product was loaded onto a column and eluted with 10% ethyl acetate in hexanes to give the product.</p><p num="0649"> Example 145B Methyl 6,6-dimethyl-4- (trifluoromethylsulfonyloxy) -5,6-dihydro-2H-pyran-3-carboxylate This Example compound was prepared by replacing 5,5-dimethyl-2-methoxycarbonylcyclohexanone in Example 18A with Example 145A.</p><p num="0650"> Example 145C Methyl 4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-carboxylate This Example compound was prepared by substituting Example 18A of Example 18B with Example 145B.</p><p num="0651"> Example 145D (4- (4-Chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methanol This Example compound was prepared by substituting Example 18B of Example 18C with Example 145C.</p><p num="0652"> Example 145E 4- (4-Chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-carbaldehyde This Example compound was prepared by substituting Example 143C of Example 143D with Example 145D.</p><p num="0653"> Example 145F Ethyl 2- (1H-indole-4-yloxy) -4-(4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) Piperazine-1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 145E and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0654"> Example 145G 2- (1H-indole-4-yloxy) -4-(4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine -1-yl) Benzoic acid This Example compound was prepared by substituting Example 143E of Example 143F with Example 145F.</p><p num="0655"> Example 145H 4- (4-{[4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indole) -4-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 145G and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d6) δ 11.56 (m, 1H), 11.26 (s, 1H), 9.52 (m, 1H), 8.51 (m, 1H), 8.16 (d, 1H), 7.80 (dd, dd, 1H), 7.55 (d, 1H), 7.41 (d, 2H), 7.28 (t, 1H), 7.17 (m, 4H), 6.96 (m, 2H), 6.74 (d, 1H), 6.39 (m, 2H) ), 6.23 (s, 1H), 4.18 (s, 2H), 3.85 (m, 3H), 2.93 (m, 10H), 2.10 (m, 7H), 1.22 (s, 6H).</p><p num="0656"> Example 146 4- (4-{[2- (4-chlorophenyl) cycloocta-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({4 -[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 142F and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d6) δ 11.59 (s, 1H), 11.25 (s, 1H), 9.36 (m, 2H), 8.50 (d, 1H), 8.16 (d, 1H), 7.79 (dd, dd, 1H), 7.55 (d, 1H), 7.40 (d, 2H), 7.28 (m, 1H), 7.14 (m, 5H), 6.96 (t, 1H), 6.74 (dd, 1H), 6.38 (m, 2H) ), 6.23 (s, 1H), 2.91 (m, 14H), 2.27 (m, 6H), 1.49 (m, 11H).</p><p num="0657"> Example 147 4- (4-{[2- (4-chlorophenyl) cyclohept-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({4 -[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 141F and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d6) δ 11.60 (s, 1H), 11.26 (s, 1H), 9.32 (m, 2H), 8.51 (m, 1H), 8.16 (d, 1H), 7.79 (m, 1H), 7.55 (d, 1H), 7.39 (d, 2H), 7.29 (t, 1H), 7.14 (m, 4H), 6.97 (t, 1H), 6.75 (dd, 1H), 6.40 (m, 2H) ), 6.22 (s, 1H), 2.94 (m, 17H), 2.27 (m, 4H), 1.80 (m, 4H), 1.55 (m, 5H).</p><p num="0658"> Example 148 4- (4-{[2- (4-chlorophenyl) cyclopenta-1-ene-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({4 -[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 143F and substituting Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d6) δ 11.60 (s, 1H), 11.26 (s, 1H), 9.47 (m, 2H), 8.51 (m, 1H), 8.16 (d, 1H), 7.77 (m, 1H), 7.56 (d, 1H), 7.43 (d, 2H), 7.20 (m, 6H), 6.96 (t, 1H), 6.77 (dd, 1H), 6.41 (m, 2H), 6.24 (s, 1H) ), 2.93 (m, 17H), 2.01 (m, 8H).</p><p num="0659"> Example 149 4- (4-{[2- (4-chlorophenyl) cyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({4 -[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 149A Ethyl 2- (trifluoromethylsulfonyloxy) cyclohex-1-encarboxylate This Example compound was prepared by replacing 5,5-dimethyl-2-methoxycarbonylcyclohexanone in Example 18A with ethyl 2-oxocyclohexanecarboxylate.</p><p num="0660"> Example 149B Ethyl 2- (4-chlorophenyl) cyclohex-1-encarboxylate This Example compound was prepared by substituting Example 18A of Example 18B with Example 149A.</p><p num="0661"> Example 149C (2- (4-Chlorophenyl) Cyclohex-1-enyl) Methanol This Example compound was prepared by substituting Example 18B of Example 18C with Example 149B.</p><p num="0662"> Example 149D 2- (4-Chlorophenyl) Cyclohexanone-1-encarbaldehyde This Example compound was prepared by substituting Example 143C of Example 143D with Example 149C.</p><p num="0663"> Example 149E Ethyl 2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) cyclohex-1-enyl) methyl) piperazine-1-yl) benzoate The title compound was prepared by replacing 4'-chlorobiphenyl-2-carboxardhide of Example 1A with Example 149D and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0664"> Example 149F 2- (1H-indole-4-yloxy) -4-(4-((2- (4-chlorophenyl) cyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 143E of Example 143F with Example 149E.</p><p num="0665"> Example 149G 4- (4-{[2- (4-chlorophenyl) cyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-({4 -[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 149F and substituting Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d6) δ 11.14 (s, 1H), 8.44 (d, 1H), 8.10 (d, 1H), 7.74 (dd, 1H), 7.56 (d, 1H), 7.34 (d, 2H), 7.23 (m, 1H), 7.01 (m, 5H), 6.63 (dd, 1H), 6.34 (d, 1H), 6.22 (m, 2H), 3.74 (m, 1H), 3.03 (m, 7H) ), 2.67 (m, 5H), 2.07 (m, 11H), 1.67 (m, 7H).</p><p num="0666"> Example 150 4- (4-{[4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 150A Methyl 2- (1H-indole-5-yloxy) -4- (piperazine-1-yl) benzoate This Example compound was prepared by replacing Example 1C of Example 1D with Example 26A and replacing Example 1B with piperazine.</p><p num="0667"> Example 150B Methyl 2- (1H-indole-5-yloxy) -4-(4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) Piperazine-1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 145E and tert-butylpiperazin-1-carboxylate with Example 150A.</p><p num="0668"> Example 150C 2- (1H-indole-5-yloxy) -4-(4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine -1-yl) Benzoic acid This Example compound was prepared by substituting Example 143E of Example 143F with Example 150B.</p><p num="0669"> Example 150D 4- (4-{[4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 150C and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d6) δ 11.00 (s, 1H), 8.42 (d, 1H), 8.07 (d, 1H), 7.67 (dd, 1H), 7.52 (d, 1H), 7.37 (d, 2H), 7.29 (m, 1H), 7.14 (d, 2H), 6.93 (d, 1H), 6.86 (d, 1H), 6.72 (dd, 1H), 6.55 (dd, 1H), 6.31 (s, 1H) ), 6.15 (d, 1H), 5.85 (m, 3H), 4.11 (s, 2H), 3.00 (m, 8H), 2.82 (s, 2H), 2.73 (m, 3H), 2.23 (m, 8H) , 1.57 (m, 2H), 1.18 (s, 6H).</p><p num="0670"> Example 151 4- (4-{[2- (4-chlorophenyl) cyclohepta-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-({4 -[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 151A (Z) -Methyl 2- (1H-Indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) Cyclohept-1-enyl) Methyl) Piperazine-1-yl) Benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 141D and tert-butylpiperazin-1-carboxylate with Example 150A.</p><p num="0671"> Example 151B (Z) -2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) cyclohept-1-enyl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 143E of Example 143F with Example 151A.</p><p num="0672"> Example 151C 4- (4-{[2- (4-chlorophenyl) cyclohepta-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-({4 -[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 151B and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d6) δ 11.06 (s, 1H), 8.48 (d, 1H), 8.11 (d, 1H), 7.74 (dd, 1H), 7.52 (d, 1H), 7.33 (m, 4H), 7.01 (m, 4H), 6.76 (dd, 1H), 6.58 (dd, 1H), 6.34 (s, 1H), 6.14 (d, 1H), 5.75 (s, 1H), 3.69 (m, 1H) ), 2.96 (m, 6H), 2.71 (m, 2H), 2.36 (m, 8H), 2.21 (s, 5H), 1.98 (m, 2H), 1.63 (m, 8H).</p><p num="0673"> Example 152 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1-1-yl] Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 18G and Example 1F with Example 21A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 8.43 (m, 1H) 8.18 (d, 1H) 7.82 (dd, 1H) 7.52 (d, 1H) 7.40 (m, 2H) 7.22 (m, 3H) 7.11 (m, 2H) 7.01 (t, 1H) 6.79 (m, 3H) 6.45 (d, 1H) 3.06 (m, 14H) 2.20 (m, 4H) 2.04 (s, 3H) 1.85 (m, 2H) 1.47 (m, 2H) 0.96 (s, 6H).</p><p num="0674"> Example 153 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[2- (dimethylamino) ethyl] amino} -3-Nitrophenyl) Sulfonyl] -2-phenoxybenzamide Example 153A 4- (2- (Dimethylamino) Ethylamino) -3-Nitrobenzene Sulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with N, N-dimethylethylenediamine.</p><p num="0675"> Example 153B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[2- (dimethylamino) ethyl] amino} -3-Nitrophenyl) Sulfonyl] -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 27H with Example 153A and substituting Example 27G with Example 1E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.75 (br s, 1H), 9.78 (br s, 1H), 9.44 (br s, 1H), 8.66 (t, 1H), 8.49 (d, 1H), 7.83 (d, 1H), 7.70 (m) , 2H), 7.51 (m, 4H), 7.38 (d, 2H), 7.33 (m, 1H), 7.24 (d, 2H), 7.18 (d, 1H), 7.02 (dd, 1H), 6.81 (d, 2H), 6.76 (d, 1H), 6.44 (s, 1H), 4.30 (m, 1H), 3.83 (m, 4H), 3.31 (m, 6H), 3.15 (m, 2H), 3.04 (m, 2H) ), 2.85 (s, 6H).</p><p num="0676"> Example 154 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-Nitrophenyl) Sulfonyl] -2-phenoxybenzamide Example 154A 4- (3- (Dimethylamino) Propylamino) -3-Nitrobenzene Sulfonamide This Example compound was prepared by substituting the (tetrahydropyran-4-yl) methylamine of Example 1F with N, N-dimethyl-1,3-propanediamine.</p><p num="0677"> Example 154B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-Nitrophenyl) Sulfonyl] -2-phenoxybenzamide This Example compound was prepared by replacing Example 1F of Example 27H with Example 154A and replacing Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.68 (br s, 1H), 9.38 (br s, 1H), 8.66 (t, 1H), 8.49 (d, 1H), 7.80 (d, 1H), 7.68 (m, 2H), 7.51 (m, 4H), 7.38 (d, 1H), 7.33 (m, 2H), 7.24 (d, 2H), 7.16 (d, 1H), 7.02 (dd, 1H), 6.81 (d, 2H), 6.76 (d, 1H) ), 6.43 (s, 1H), 4.25 (m, 1H), 3.50 (m, 4H), 3.30 (m, 4H), 3.12 (m, 6H), 2.78 (s, 6H), 1.95 (m, 2H) ..</p><p num="0678"> Example 155 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({4-[(3-morpholine-4-ylpropyl) amino ] -3-Nitrophenyl} Sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 27H with Example 7A and substituting Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.70 (br s, 1H), 9.72 (br s, 1H), 8.68 (t, 1H), 8.49 (d, 1H), 7.81 (d, 1H), 7.70 (m, 2H), 7.51 (m, 4H), 7.37 (d, 2H), 7.33 (m, 1H), 7.24 (d, 2H), 7.15 (d, 1H), 7.03 (dd, 1H), 6.81 (d, 2H), 6.76 (d, 1H) ), 6.44 (s, 1H), 4.24 (m, 1H), 3.97 (m, 2H), 3.63 (m, 4H), 3.28 (m, 4H), 3.18 (m, 4H), 3.06 (m, 4H) , 2.88 (m, 4H), 1.99 (m, 2H).</p><p num="0679"> Example 156 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[4- (dimethylamino) butyl] amino} -3-Nitrophenyl) Sulfonyl] -2-phenoxybenzamide Example 156A 4- (4- (Dimethylamino) Butylamino) -3-Nitrobenzene Sulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with N, N-dimethyl-1,4-butanediamine.</p><p num="0680"> Example 156B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[4- (dimethylamino) butyl] amino} -3-Nitrophenyl) Sulfonyl] -2-phenoxybenzamide This Example compound was prepared by replacing Example 1F of Example 27H with Example 156A and replacing Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.70 (br s, 1H), 9.34 (br s, 1H), 8.63 (t, 1H), 8.48 (d, 1H), 7.79 (d, 1H), 7.70 (m, 2H), 7.51 (m, 4H), 7.39 (d, 2H), 7.33 (m, 1H), 7.24 (d, 2H), 7.12 (d, 1H), 7.01 (dd, 1H), 6.80 (d, 2H), 6.75 (d, 1H) ), 6.44 (s, 1H), 4.28 (m, 1H), 3.83 (m, 4H), 3.45 (m, 10H), 3.10 (m, 4H), 2.85 (s, 6H), 1.66 (m, 4H) ..</p><p num="0681"> Example 157 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-nitro-4-{[1- (phenylsulfonyl)) Piperidine-4-yl] amino} phenyl) sulfonyl] -2-phenoxybenzamide Example 157A tert-Butyl 4- (2-nitro-4-sulfamoylphenylamino) piperidine-1-carboxylate This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with 1-Boc-4-aminopiperidine.</p><p num="0682"> Example 157B 3-Nitro-4- (piperidine-4-ylamino) benzenesulfonamide This Example compound was prepared by substituting Example 1A of Example 1B with Example 157A.</p><p num="0683"> Example 157C 3-Nitro-4- (1- (Phenylsulfonyl) Piperidine-4-Ilamino) Benzene Sulfonamide CH₂Cl₂A mixture of Example 157B (84 mg), benzenesulfonyl chloride (46 mg) and triethylamine (101 mg) in (2 mL) was stirred for 1 hour. The product was chromatographed on silica gel with 25% ethyl acetate / hexane.</p><p num="0684"> Example 157D 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-nitro-4-{[1- (phenylsulfonyl)) Piperidine-4-yl] amino} phenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 27H with Example 157C and Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.68 (br s, 1H), 9.65 (br s, 1H), 8.42 (s, 1H), 8.19 (d, 1H), 7.78 (m, 2H), 7.70 (m, 4H), 7.51 (m, 5H), 7.37 (m, 3H), 7.19 (m, 3H), 6.94 (dd, 1H), 6.75 (m, 3H), 6.44 (s, 1H), 4.28 (m, 1H), 3.73 (m, 4H) ), 3.50 (m, 4H), 3.17 (m, 2H), 3.03 (m, 2H), 2.86 (m, 2H), 1.99 (m, 2H), 1.74 (m, 2H).</p><p num="0685"> Example 158 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-nitro-4-{[1- (quinoline-8) -Ilsulfonyl) piperidine-4-yl] amino} phenyl) sulfonyl] -2-phenoxybenzamide Example 158A 3-Nitro-4- (1- (quinoline-8-ylsulfonyl) piperidine-4-ylamino) benzenesulfonamide This Example compound was prepared by replacing the benzenesulfonyl chloride of Example 157C with a quinoline-8-sulfonyl chloride.</p><p num="0686"> Example 158B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-nitro-4-{[1- (quinoline-8) -Ilsulfonyl) piperidine-4-yl] amino} phenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by replacing Example 1F of Example 27H with Example 158A and replacing Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.66 (br s, 1H), 9.10 (dd, 1H), 8.55 (s, 1H), 8.41 (m, 2H), 8.32 (d, 1H), 8.20 (d, 1H), 7.78 (dd, 2H) ), 7.72 (d, 2H), 7.48 (m, 4H), 7.39 (dd, 2H), 7.33 (m, 1H), 7.17 (m, 3H), 6.95 (dd, 1H), 6.76 (m, 3H) , 6.42 (s, 1H), 4.35 (m, 1H), 3.90 (d, 2H), 3.77 (m, 2H), 3.34 (m, 6H), 2.99 (m, 4H), 1.97 (m, 2H), 1.65 (m, 2H).</p><p num="0687"> Example 159 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-phenoxy-N-({4- {[1- (phenylsulfonyl)) Piperidine-4-yl] amino} -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide Example 159A (2-Fluorophenyl) (Trifluoromethyl) Sulfane Methylbiologen hydrochloride (1.17 g) in N, N-dimethylformamide (80 mL) at 25 ° C is saturated with trifluoromethyliodide and treated with 2-fluorobenzenethiol (9.7 mL) and triethylamine (20 mL). , Stirred for 24 hours, diluted with water (240 mL) and extracted with diethyl ether. The extract was washed with 1M NaOH, saturated ammonium chloride and brine and concentrated.</p><p num="0688"> Example 159B 1-Fluoro-2- (trifluoromethylsulfonyl) benzene Example 159A (17.346g) in 1: 1: 2 carbon tetrachloride: acetonitrile: water (800mL) at 25 ° C with sodium periodate (56.8g) and ruthenium (III) chloride hydrate (183mg) Treated with, stirred for 18 hours, diluted with dichloromethane (100 mL) and filtered through diatomaceous earth (Celite®). The filtrate was washed with saturated sodium bicarbonate and extracted with dichloromethane. The extract is washed with brine and dehydrated (DDL)₄), Filtered and concentrated. The concentrate was filtered through silica gel.</p><p num="0689"> Example 159C 4-Fluoro-3- (trifluoromethylsulfonyl) benzenesulfonamide Example 159B (37.3 g) in 120 ° C chlorosulfonic acid (32.8 mL) was stirred for 18 hours, cooled to 25 ° C and pipetted onto icebreaker. The mixture is extracted with ethyl acetate, the extract is washed with water and brine and dehydrated (DDL)₄), Filtered and concentrated. The crude product is taken in isopropanol (706 mL) at -78 ° C, treated with ammonium hydroxide (98 mL) for 1 hour, stirred for 1 hour, quenched with 6M HCl (353 mL) and warmed to 25 ° C. And concentrated. The concentrate was mixed with water and extracted with ethyl acetate. Extract the extract₄Dehydrated with, filtered and concentrated. The concentrate was recrystallized from ethyl acetate / hexane.</p><p num="0690"> Example 159D tert-Butyl 4- (4-Sulfamoyl-2- (trifluoromethylsulfonyl) phenylamino) piperidine-1-carboxylate This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with 1-Boc-4-aminopiperidine and replacing 4-fluoro-3-nitrobenzenesulfonamide with Example 159C. ..</p><p num="0691"> Example 159E 4- (Piperidin-4-ylamino) -3- (trifluoromethylsulfonyl) benzenesulfonamide This Example compound was prepared by substituting Example 1A of Example 1B with Example 159D.</p><p num="0692"> Example 159F 4- (1- (Phenylsulfonyl) piperidine-4-ylamino) -3- (trifluoromethylsulfonyl) benzenesulfonamide This Example compound was prepared by substituting Example 157B of Example 157C with Example 159E.</p><p num="0693"> Example 159G 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-phenoxy-N-({4- {[1- (phenylsulfonyl)) Piperidine-4-yl] amino} -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 27H with Example 159F and substituting Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.72 (br s, 1H), 9.70 (br s, 1H), 8.07 (s, 1H), 7.67-7.82 (m, 7H), 7.52 (d, 2H), 7.47 (d, 2H), 7.36 ( m, 3H), 7.24 (dd, 2H), 7.14 (d, 1H), 7.01 (m, 1H), 6.78 (d, 2H), 6.72 (m, 2H), 6.44 (d, 1H), 4.27 (m) , 1H), 3.73 (m, 4H), 3.46 (m, 4H), 3.17 (m, 2H), 3.03 (m, 2H), 2.87 (m, 2H), 1.97 (m, 2H), 1.64 (m, m, 2H).</p><p num="0694"> Example 160 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-phenoxy-N-({4- {[1- (quinoline-8) -Ilsulfonyl) piperidine-4-yl] amino} -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide Example 160A 4- (1- (quinoline-8-ylsulfonyl) piperidine-4-ylamino) -3- (trifluoromethylsulfonyl) benzenesulfonamide This Example compound was prepared by replacing Example 157B of Example 157C with Example 159E and replacing benzenesulfonyl chloride with quinoline-8-sulfonyl chloride.</p><p num="0695"> Example 160B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-phenoxy-N-({4- {[1- (quinoline-8) -Ilsulfonyl) piperidine-4-yl] amino} -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by replacing Example 1F of Example 27H with Example 160A and replacing Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.74 (br s, 1H), 9.50 (br s, 1H), 9.08 (dd, 1H), 8.55 (s, 1H), 8.39 (d, 1H), 8.33 (d, 1H), 8.06 (s, 1H), 7.82 (dd, 2H), 7.70 (m, 1H), 7.50 (m, 3H), 7.40 (dd, 2H), 7.33 (m, 1H), 7.21 (m, 2H), 7.08 (m, 2H) ), 6.99 (dd, 1H), 6.95 (s, 1H), 6.78 (d, 1H), 6.73 (m, 2H), 6.42 (s, 1H), 4.35 (m, 1H), 3.75 (m, 4H) , 3.34 (m, 6H), 3.05 (m, 4H), 1.93 (m, 2H), 1.55 (m, 2H.</p><p num="0696"> Example 161 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[(1S) -3- (dimethylamino)) -1-thien-2-ylpropyl] amino} -3-nitrophenyl) sulfonyl] -2-phenoxybenzamide Example 161A (S) -3- (benzyloxycarbonylamino) -3- (thiophene-2-yl) propanoic acid (S) -3-amino-3- (thiophen-2-yl) propanoic acid (0.894 g) and benzyloxycarbonyl chloride 0.980 g in 2M NaOH (8 mL) and dioxane (26 mL) at 0 ° C 24 Stirred for hours. The reaction mixture is acidified with concentrated aqueous HCl solution and extracted twice with ethyl acetate, and the extract is extracted with DDL.₄Dehydrated with, filtered, concentrated and chromatographed on silica gel with 50% ethyl acetate / hexane.</p><p num="0697"> Example 161B (S) -Benzyl 3- (dimethylamino) -3-oxo-1- (thiophen-2-yl) propyl carbamate This Example compound was prepared by substituting Example 1E of Example 1G with Example 161A and substituting Example 1F with dimethylamine.</p><p num="0698"> Example 161C (S) -N¹, N¹-Dimethyl-3- (thiophen-2-yl) propane-1,3-diamine The solutions of Example 161B (400 mg) and borane in tetrahydrofuran (1 M, 2.5 mL) and tetrahydrofuran (6 mL) were stirred for 24 hours. The reaction was quenched with methanol, taken in pH 7 buffer and extracted 3 times with ethyl acetate. The combined extracts were washed with brine and concentrated. The crude product was taken up in HBr in acetic acid (1.1 mL) and stirred for 2 hours. CH reactant₂Cl₂It was poured into (50 mL) and washed with 1M NaOH solution. Organic layer Na₂SO₄It was dehydrated and concentrated.</p><p num="0699"> Example 161D (S) -4- (3- (dimethylamino) -1- (thiophene-2-yl) propylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with Example 161C.</p><p num="0700"> Example 161E 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[(1S) -3- (dimethylamino)) -1-thien-2-ylpropyl] amino} -3-nitrophenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 27H with Example 161D and substituting Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆/ D₂O) δ 11.72 (br s, 1H), 9.51 (br s, 1H), 8.60 (d, 1H), 8.48 (s, 1H), 7.75 (d, 1H), 7.70 (m, 1H), 7.51 (m) , 4H), 7.38 (d, 2H), 7.32 (m, 1H), 7.25 (d, 1H), 7.16 (m, 3H), 7.06 (d, 1H), 6.92 (m, 1H), 6.75 (d, 3H), 6.44 (d, 1H), 5.31 (m, 1H), 4.30 (m, 1H), 3.54 (m, 8H), 3.20 (m, 2H), 3.07 (m, 2H), 2.80 (s, 6H) ), 2.35 (m, 2H).</p><p num="0701"> Example 162 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(thien-2-ylmethyl)) Amino] Phenyl} Sulfonyl) -2-phenoxybenzamide Example 162A 3-Nitro-4- (thiophene-2-ylmethylamino) benzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine in Example 1F with 2-thiophene methylamine.</p><p num="0702"> Example 162B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(thien-2-ylmethyl)) Amino] Phenyl} Sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 27H with Example 162B and Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆/ D₂O) δ 11.67 (br s, 1H), 9.55 (br s, 1H), 9.11 (t, 1H), 8.47 (s, 1H), 7.70 (m, 2H), 7.51 (m, 4H), 7.38 (d , 2H), 7.33 (m, 1H), 7.15 (m, 4H), 7.02 (d, 1H), 6.94 (m, 1H), 6.74 (d, 3H), 6.44 (d, 1H), 4.87 (m, 2H), 4.37 (m, 1H), 3.34 (m, 8H), 3.03 (m, 2H).</p><p num="0703"> Example 163 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-phenoxy-N-({4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide Example 163A 4-((Tetrahydro-2H-pyran-4-yl) methylamino) -3- (trifluoromethylsulfonyl) benzenesulfonamide This Example compound was prepared by replacing 4-fluoro-3-nitrobenzenesulfonamide of Example 1F with Example 159C.</p><p num="0704"> Example 163B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2-phenoxy-N-({4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 27H with Example 163A and substituting Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.71 (br s, 1H), 8.10 (d, 1H), 7.86 (d, 1H), 7.10 (m, 1H), 7.50 (m, 4H), 7.37 (m, 2H), 7.27 (m, 3H) ), 7.08 (m, 1H), 7.03 (dd, 1H), 6.95 (d, 1H), 6.82 (d, 1H), 6.76 (d, 1H), 6.43 (s, 1H), 4.35 (m, 1H) , 3.84 (dd, 2H), 3.35 (m, 8H), 3.22 (m, 2H), 3.03 (m, 2H), 2.86 (m, 2H), 1.86 (m, 1H), 1.55 (m, 2H), 1.26 (m, 2H).</p><p num="0705"> Example 164 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-Nitro-4-{[2- (1H-1) , 2,3-Triazole-1-yl) ethyl] amino} phenyl) sulfonyl] -2-phenoxybenzamide Example 164A 4- (2-Hydroxyethylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with 2-aminoethanol.</p><p num="0706"> Example 164B 4- (2- (tert-Butyldimethylsilyloxy) Ethylamino) -3-Nitrobenzene Sulfonamide Example 164A (131 mg), t-butyldimethylsilyl chloride (75 mg) and imidazole (68 mg) CH₂Cl₂Stirred in (17 mL) for 24 hours. The reaction mixture was chromatographed on silica gel with 10% ethyl acetate / hexane.</p><p num="0707"> Example 164C N- (4- (2- (tert-butyldimethylsilyloxy) ethylamino) -3-nitrophenylsulfonyl) -4- (4-((4'-chlorobiphenyl-2-yl) methyl) piperazine-1- Il) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 164B.</p><p num="0708"> Example 164D 2- (4- (N- (4- (4- ((4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) -2-phenoxybenzoyl) sulfamoyl) -2-nitrophenylamino) ethyl 4-Methylbenzene sulfonate Example 164C (150 mg) and concentrated aqueous HCl solution (0.020 mL) were stirred in tetrahydrofuran (1 mL) and methanol (1 mL) for 1 hour. The mixture was filtered through a short silica gel column. CH the product₂Cl₂It was taken in (1 mL), triethylamine (0.074 mL) and p-toluenesulfonic acid anhydride (58 mg) were added thereto, and the reaction was stirred for 24 hours. The reaction mixture was chromatographed on silica gel with 10% ethyl acetate / hexane.</p><p num="0709"> Example 164E 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-Nitro-4-{[2- (1H-1) , 2,3-Triazole-1-yl) ethyl] amino} phenyl) sulfonyl] -2-phenoxybenzamide Example 164D (30 mg), 1,2,3-triazole (7 mg) and cesium carbonate (55 mg) were stirred in N, N-dimethylformamide (0.2 mL) for 24 hours. The reaction was quenched with ammonium chloride and extracted twice with ethyl acetate. The organic layer that was put together is PEG₄Dehydrated with, filtered and concentrated. The product is 20-100% CH by preparative HPLC using a C18 column, 250 x 50 mm, 10 μ.₃The product was obtained as a trifluoroacetic acid salt by eluting with a gradient of 0.1% trifluoroacetic acid in CN vs. water and purifying.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.75 (br s, 1H), 9.62 (br s, 1H), 8.66 (dd, 1H), 8.44 (d, 1H), 8.18 (s, 1H), 7.72 (m, 3H), 7.51 (m, 5H), 7.36 (m, 3H), 7.19 (dd, 2H), 7.06 (m, 1H), 6.93 (dd, 1H), 6.75 (d, 2H), 6.45 (s, 1H), 4.70 (t, 2H) ), 3.93 (dt, 2H), 3.61 (m, 4H), 3.22 (m, 2H), 3.01 (m, 2H), 2.84 (m, 2H).</p><p num="0710"> Example 165 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-Nitro-4-{[2- (2H-1) , 2,3-Triazole-2-yl) ethyl] amino} phenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared in the same reaction as in Example 164E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.75 (br s, 1H), 9.70 (br s, 1H), 8.67 (dd, 1H), 8.42 (s, 1H), 7.80 (s, 1H), 7.75 (m, 1H), 7.68 (d, 2H), 7.51 (m, 5H), 7.37 (m, 3H), 7.18 (dd, 2H), 6.97 (m, 1H), 6.92 (dd, 1H), 6.75 (d, 2H), 6.46 (s, 1H) ), 4.76 (t, 2H), 3.93 (dt, 2H), 3.67 (m, 4H), 3.22 (m, 2H), 3.03 (m, 2H), 2.84 (m, 2H).</p><p num="0711"> Example 166 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(4-{[3- (dimethylamino) propyl] amino} -3-Nitrophenyl) Sulfonyl] -2- (2-naphthyloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 35B and Example 1F with Example 154A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.83 (br s, 1H), 9.46 (br s, 1H), 8.53 (t, 1H), 8.40 (s, 1H), 7.81 (d, 2H), 7.71 (m, 1H), 7.63 (m, 2H), 7.51 (m, 5H), 7.37 (m, 4H), 7.17 (d, 1H), 7.03 (s, 1H), 6.82 (d, 2H), 6.57 (d, 1H), 4.27 (m, 1H) ), 3.62 (m, 6H), 3.39 (m, 2H), 3.09 (m, 2H), 2.80-3.25 (m, 6H), 2.79 (s, 6H), 1.91 (m, 2H).</p><p num="0712"> Example 167 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-nitro-4-{[2- (2-oxo) Pyridine-1 (2H) -yl) ethyl] amino} phenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by replacing 1,2,3-triazole in Example 164E with pyridine-2-ol.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.70 (br s, 1H), 9.65 (br s, 1H), 8.75 (t, 1H), 8.44 (d, 1H), 7.72 (d, 2H), 7.64 (d, 1H), 7.51 (m, 5H), 7.37 (m, 3H), 7.20 (m, 3H), 6.95 (t, 1H), 6.77 (d, 3H), 6.46 (s, 1H), 6.41 (d, 1H), 6.21 (t, 1H) ), 4.31 (m, 1H), 4.17 (t, 2H), 3.74 (dt, 2H), 3.60 (m, 6H), 3.20 (m, 2H), 3.03 (m, 2H), 2.87 (m, 2H) ..</p><p num="0713"> Example 168 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-[(3-nitro-4-{[2- (pyridine-2) -Iloxy) ethyl] amino} phenyl) sulfonyl] -2-phenoxybenzamide This Example compound was prepared by replacing 1,2,3-triazole in Example 164E with pyridine-2-ol.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.71 (br s, 1H), 9.65 (br s, 1H), 8.84 (t, 1H), 8.44 (d, 1H), 8.19 (d, 1H), 7.74 (m, 3H), 7.51 (m, 5H), 7.37 (m, 3H), 7.20 (m, 3H), 7.00 (dd, 1H), 6.92 (t, 1H), 6.83 (d, 1H), 6.76 (m, 2H), 6.45 (d, 1H) ), 4.56 (t, 2H), 4.31 (m, 1H), 3.81 (dt, 2H), 3.71 (m, 6H), 3.23 (m, 2H), 3.04 (m, 2H), 2.89 (m, 2H) ..</p><p num="0714"> Example 169 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(2-pyridine-4-yl) Ilethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 169A 3-Nitro-4- (2- (pyridin-4-yl) ethylamino) benzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1E with 2- (pyridin-4-yl) ethaneamine.</p><p num="0715"> Example 169B 4- {4-[(4'-Chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -N-({3-nitro-4-[(2-pyridine-4-yl) Ilethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1F of Example 27H with Example 169A and Example 27G with Example 1E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.71 (br s, 1H), 9.70 (br s, 1H), 8.69 (d, 1H), 8.61 (t, 1H), 8.46 (s, 1H), 7.79 (dd, 1H), 7.72 (d, 3H), 7.51 (m, 5H), 7.37 (d, 2H), 7.32 (d, 1H), 7.21 (m, 3H), 6.95 (t, 1H), 6.78 (d, 2H), 6.75 (d, 1H) ), 6.44 (d, 1H), 4.23 (m, 1H), 3.76 (dt, 2H), 3.63 (m, 4H), 3.13 (t, 2H), 2.76-3.24 (m, 6H).</p><p num="0716"> Example 170 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- {[3- (Dimethylamino) propyl] amino} -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 170A 4- (3- (Dimethylamino) Propylamino) -3- (Trifluoromethylsulfonyl) Benzene Sulfonamide This Example compound was replaced with the (tetrahydropyran-4-yl) methylamine of Example 1F with N, N-dimethyl-1,3-propanediamine and 4-fluoro-3-nitrobenzenesulfonamide in Example 159C. Replaced and prepared.</p><p num="0717"> Example 170B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- {[3- (Dimethylamino) propyl] amino} -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 27H with Example 170A and Example 27G with Example 26C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.42 (br s, 1H), 11.17 (s, 1H), 9.37 (br s, 1H), 8.22 (d, 1H), 7.98 (d, 1H), 7.52 (d, 1H), 7.35-7.45 ( m, 4H), 7.19 (d, 1H), 7.08 (m, 3H), 6.85 (dd, 1H), 6.67 (dd, 1H), 6.40 (d, 1H), 6.19 (d, 1H), 3.55 (m) , 8H), 3.04 (m, 4H), 2.77 (s, 6H), 2.72 (m, 2H), 2.17 (m, 2H), 2.00 (m, 2H), 1.88 (m, 2H), 1.44 (m, 2H), 0.93 (s, 6H).</p><p num="0718"> Example 171 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-{[3- (Dimethylamino) Propyl] Amino} -3- (Trifluoromethyl) Phenyl] Sulfonyl} -2- (1H-Indole-5-Iloxy) Benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 26C and Example 1F with Example 92B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.19 (br s, 1H), 9.33 (br s, 1H), 7.94 (d, 1H), 7.85 (d, 1H), 7.54 (d, 1H), 7.35-7.45 (m, 4H), 7.20 ( d, 1H), 7.07 (d, 2H), 6.88 (dd, 2H), 6.67 (dd, 1H), 6.58 (m, 1H), 6.41 (s, 1H), 6.18 (s, 1H), 3.57 (m) , 6H), 3.33 (m, 2H), 3.09 (m, 2H), 3.04 (m, 2H), 2.77 (s, 6H), 2.74 (m, 2H), 2.17 (m, 2H), 2.00 (m, m, 2H), 1.87 (m, 2H), 1.44 (m, 2H), 0.93 (s, 6H).</p><p num="0719"> Example 172 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(3-cyano-4-yl) {[3- (Dimethylamino) propyl] amino} phenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 26C and Example 1F with Example 90B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.19 (br s, 1H), 9.38 (br s, 1H), 7.98 (s, 1H), 7.81 (d, 1H), 7.55 (d, 1H), 7.35-7.45 (m, 4H), 7.20 ( s, 1H), 7.16 (t, 1H), 7.07 (d, 2H), 6.86 (dd, 2H), 6.68 (dd, 1H), 6.41 (s, 1H), 6.18 (s, 1H), 3.57 (m) , 6H), 3.31 (m, 2H), 3.09 (m, 2H), 3.04 (m, 2H), 2.77 (s, 6H), 2.74 (m, 2H), 2.17 (m, 2H), 2.00 (m, m, 2H), 1.87 (m, 2H), 1.44 (m, 2H), 0.93 (s, 6H).</p><p num="0720"> Example 173 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide Example 173A tert-Butyl 1- (Tetrahydro-2H-Pyran-4-yl) Piperidine-4-yl carbamate A mixture of tert-butylpiperidin-4-ylcarbamate (45 g) and dihydro-2H-pyran-4 (3H) -one (24.74 g) in dichloromethane (1000 mL) was treated with sodium triacetoxyborohydride (61.9 g). , Stirred at room temperature for 16 hours, washed with 1M sodium hydroxide, dehydrated with anhydrous sodium sulfate, filtered and concentrated. The concentrate was flash column chromatographed on silica gel with 10-20% methanol / dichloromethane.</p><p num="0721"> Example 173B 1- (Tetrahydro-2H-pyran-4-yl) piperidine-4-amine A solution of Example 173A (52.57 g) in dichloromethane (900 mL) was treated with 4M HCl (462 mL), mixed vigorously at room temperature for 16 hours and concentrated.</p><p num="0722"> Example 173C 3-Nitro-4- (1- (Tetrahydro-2H-Pyran-4-yl) Piperidine-4-Ilamino) Benzene Sulfonamide A mixture of Example 173B (22.12 g), water (43 mL) and triethylamine (43.6 mL) in 1,4-dioxane (300 mL) was stirred at room temperature until Example 173B was completely dissolved. The solution was then treated with 4-chloro-3-nitrobenzenesulfonamide, heated at 90 ° C for 16 hours, cooled and concentrated. 10% methanol in dichloromethane was added and the solution was vigorously stirred at room temperature until a fine suspension was obtained and the mixture was filtered.</p><p num="0723"> Example 173D 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide Example 26C (3.95g) in dichloromethane (70mL) and acetonitrile (20mL), Example 173C (2.66g), 1-ethyl-3- [3- (dimethylamino) propyl] -carbodiimide hydrochloride (2.66g) ) And 4-dimethylaminopyridine (0.846g) are stirred at 35 ° C for 24 hours, cooled and 0-10% methanol in ethyl acetate, then 10% methanol in 1: 1 ethyl acetate / dichloromethane. Used and chromatographed on silica gel. Concentrate the combined fractions, dissolve in 5% methanol / ethyl acetate (1.5L) and saturate the solution NaH₂PO₄Wash with solution and brine, Na₂SO₄Dehydrated with, filtered, concentrated to 300 mL, cooled and filtered. The remaining solution was concentrated to some extent and filtered again to isolate additional products.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.17 (br s, 1H), 10.70 (br s, 1H), 8.60 (d, 1H), 8.20 (br d, 1H), 7.88 (dd, 1H), 7.50 (d, 1H), 7.39 (m, 2H), 7.33 (d, 2H), 7.16 (m, 2H), 7.03 (d, 2H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (s, 1H) ), 3.97 (m, 4H), 3.44 (m, 4H), 3.04 (m, 6H), 2.75 (m, 2H), 2.14 (m, 8H), 1.95 (m, 6H), 1.66 (m, 2H) , 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0724"> Example 174 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 174A 4- (4-Methylpiperazin-1-ylamino) -3-nitrobenzenesulfonamide 4-Chloro-3-nitrobenzenesulfonamide (1g), 4-methylpiperazin-1-amine dihydrochloride (1g) and N in dioxane (10mL)¹, N¹, N², N²-A mixture of tetramethylethane-1,2-diamine (3 mL) was refluxed for 12 hours, cooled to ambient temperature and filtered. The filtrate was added to a silica gel column (Analogix, SF65-200 g) and eluted with 1-5% methanol / dichloromethane) for purification.</p><p num="0725"> Example 174B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 26C (0.108g) in dichloromethane (3mL), Example 174A (64mg), 1-ethyl-3- [3- (dimethylamino) propyl] -carbodiimide hydrochloride (0.08g) and 4-dimethylaminopyridine The mixture (0.08 g) was stirred at ambient temperature overnight and concentrated. The concentrate was added to a preparative HPLC column and eluted with water containing 20-100% acetonitrile / 0.1% trifluoroacetic acid. Trifluoroacetic acid salt solution LVDS₃Neutralized with dichloromethane and extracted with dichloromethane. Saturate this solution LVDS₃Wash with Na₂SO₄Dehydrated with, filtered and concentrated.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 1H), 9.17 (s, 1H), 8.52 (s, 1H), 7.83 (m, 1H), 7.53 (m, 2H), 7.36 (m, 4H), 7.12 (s, 1H) , 7.03 (d, 2H), 6.83 (m, 1H), 6.62 (m, 1H), 6.38 (s, 1H), 6.13 (m, 1H), 5.76 (s, 2H), 2.85 (m, 12H), 2.35 (m, 4H), 2.14 (m, 6H), 1.94 (m, 2H), 1.38 (m, 2H), 0.92 (s, 6H).</p><p num="0726"> Example 175 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 175A 1- (4'-chlorobiphenyl-2-yl) etanone 1- (2-Bromophenyl) etanone (3.1 g, 15.57 mmol) 4-chlorophenylboronic acid (2.92 g), (Ph) in dimethoxyethane-ethanol-water (7: 2: 3, 50 mL)₃P)₂PdCl₂(Bis (triphenylphosphine) palladium (II) dichloride) (1.202 g) and Na₂CO₃The mixture (3.30 g) was heated at 100 ° C. for 3 hours to concentrate. The concentrate was suspended in dichloromethane (30 mL) and the insoluble material was removed by filtration. The filtrate was loaded onto a silica gel column and eluted with 0% -50% dichloromethane in hexanes to give the title compound.</p><p num="0727"> Example 175B tert-Butyl 4- (1- (4'-chlorobiphenyl-2-yl) ethyl) piperazine-1-carboxylate Example 175A (1.9 g) was dissolved in dichloromethane (3 mL) and titanium chloride (IV) (9.06 mL, 9.06 mmol) was added. The solution was cooled to 0 ° C. and tert-butylpiperazin-1-carboxylate (3.07 g) was added. The resulting mixture was stirred at ambient temperature for 3 hours and NaCNBH in methanol (5 mL).₃(0.828 g) was added. The resulting mixture was stirred at room temperature overnight, neutralized with aqueous NaOH solution and then concentrated. Ethyl acetate was added to this concentrate and the insoluble material was filtered off. The organic layer was washed with water and concentrated. The concentrate was dissolved in a mixture of methanol-trifluoroacetic acid-dimethyl sulfoxide, loaded onto a reverse phase C18 column and eluted with 0-80% acetonitrile in water containing 0.1% trifluoroacetic acid over 70 minutes. ..</p><p num="0728"> Example 175C 1-(1- (4'-chlorobiphenyl-2-yl) ethyl) piperazine Trifluoroacetic acid (6 mL) was added to a solution of Example 175B (650 mg) in dichloromethane (6 mL) at 0 ° C. The reaction mixture was stirred at 0 ° C. for 50 minutes and concentrated. Dissolve the concentrate in dichloromethane and LVDS₃Wash with aqueous solution and remove the organic layer with Na₂SO₄It was dehydrated and concentrated.</p><p num="0729"> Example 175D Ethyl 2- (1H-indole-4-yloxy) -4-(4- (1- (4'-chlorobiphenyl-2-yl) ethyl) piperazine-1-yl) benzoate Examples 175C (193 mg) and ethyl 2- (1H-indole-4-yloxy) -4-fluorobenzoate (211 mg) in dimethyl sulfoxide (15 mL) at 135 ° C with potassium hydrogen phosphate (168 mg). Treated overnight and cooled. The reaction mixture was diluted with dichloromethane and washed with water. The organic layer was concentrated. The concentrate was dissolved in dichloromethane, loaded onto a silica gel column and eluted with 0% -10% 10M ammonia methanol in dichloromethane.</p><p num="0730"> Example 175E 2- (1H-indole-4-yloxy) -4-(4- (1- (4'-chlorobiphenyl-2-yl) ethyl) piperazine-1-yl) benzoic acid Example 175D (200 mg) in tetrahydrofuran (10 mL) and methanol (10 mL) was treated with 10% NaOH (3 mL) overnight at 50 ° C. and neutralized with HCl. The mixture was concentrated, the concentrate was taken in water and extracted with dichloromethane. Organic layer Na₂SO₄It was dehydrated and concentrated.</p><p num="0731"> Example 175F 4- (4- (1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) -N-((( 3-Nitro-4-((tetrahydro-2H-pyran-4-ylmethyl) amino) phenyl) sulfonyl) benzamide Examples 175E (66 mg) in dichloromethane (5 mL), 3-nitro-4-((tetrahydro-2H-pyran-4-yl) methylamino) benzenesulfonamide (75 mg) and 4-dimethylaminopyridine (58.4 mg) 1-Ethyl-3- [3- (dimethylamino) propyl] -carbodiimide hydrochloride (45.8 mg) was added to the mixture of. The mixture was stirred at ambient temperature overnight and concentrated. The concentrate was purified by RP HPLC (10-70% acetonitrile in 0.1% trifluoroacetic acid / 70 minutes). Concentrate the desired fraction to remove acetonitrile, dilute the concentrate with dichloromethane, LVDS₃Neutralized with aqueous solution. Dichloromethane layer Na₂SO₄Was dehydrated and concentrated to give the title compound.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ ppm 11.31 (1H, s), 11.25 (1H, s), 8.62 (1H, t), 8.50 (1H, d), 7.68 (1H, dd), 7.53 (2H, d), 7.46 (2H, d) ), 7.37 (1H, t), 7.24-7.31 (4H, m), 7.17 (1H, d), 7.12 (1H, dd), 7.07 (1H, d), 6.96 (1H, t), 6.69 (1H, 1H, dd), 6.42 (1H, d), 6.26 (2H, s), 3.85 (2H, dd), 3.21-3.33 (5H, m), 3.01 (4H, s), 2.29-2.39 (2H, m), 2.15 -2.22 (2H, m), 1.83-1.94 (1H, m), 1.57-1.68 (2H, m), 1.22-1.31 (2H, m), 1.17 (3H, d).</p><p num="0732"> Example 176 N-[(4-{[(4-Aminotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl)- 4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide Example 176A 4-((4-Aminotetrahydro-2H-pyran-4-yl) methylamino) -3-nitrobenzenesulfonamide A mixture of 4-chloro-3-nitrobenzenesulfonamide, 4- (aminomethyl) tetrahydro-2H-pyran-4-aminebis-hydrochloride and triethylamine in dioxane (10 mL) was heated overnight at 110 ° C. After cooling, the reaction mixture was diluted with water (10 mL) and the solid was filtered to give the title compound.</p><p num="0733"> Example 176B N-((4-((((4-Aminotetrahydro-2H-pyran-4-yl) methyl) amino) -3-nitrophenyl) sulfonyl) -4- (4-((2- (4-chlorophenyl)-) 4,4-Dimethylcyclohex-1-en-1-yl) methyl) piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide This Example compound was replaced with Example 1F of Example 1H with Example 55B and Example 1G was replaced with Example 176A (4-aminotetrahydro-2H-pyran-4-yl) methylamino) -3-nitrobenzenesulfonamide. ) Was replaced and prepared.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.15 (s, 1H), 8.51 (s, 1H), 8.45 (d, J = 2.14Hz, 1H), 7.70 (dd, J = 9.0, 1.98Hz, 1H), 7.59 (d, J = 8.85Hz) , 1H), 7.34 (d, J = 8.24Hz, 2H), 7.22 (t, J = 2.59Hz, 1H), 7.11-7.12 (m, 2H), 7.04 (d, J = 8.54Hz, 2H), 6.93 (t, J = 7.78Hz, 1H), 6.62 (dd, J = 9.0, 1.98Hz, 1H), 6.34 (d, J = 7.63Hz, 1H), 6.20-6.23 (m, 2H), 3.55-3.70 ( m, 6H), 2.96 (m, 3H), 2.71 (s, 2H), 2.16 (m, 6H), 1.95 (m, 2H), 1.70-1.74 (m, 2H), 1.55-1.59 (m, 2H) , 1.37-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0734"> Example 177 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 26C (2.85 g, 10 mmol), Example 1F (1.577 g, 5 mmol), 1-ethyl-3- [3- (dimethylamino) propyl] -carbodiimide hydrochloride (1.917 g, 10 mmol), 4- (dimethyl) CH a mixture of amino) pyridine (1.222 g, 10 mmol) and triethylamine (2.8 mL, 20 mmol)₂Cl₂It was treated with (20 mL) and N, N-dimethylformamide (2 mL). The reaction mixture was stirred overnight. The solvent was removed and the residue was partitioned between water and ethyl acetate. Wash the organic layer twice with 1% HCl, then saturated LVDS₃, Washed with brine, dehydrated, filtered and concentrated. The residue was purified by reverse phase HPLC using a C18 column using a gradient of 0.1% TFA in 40-60% acetonitrile / water to give the title compound as a trifluoroacetate. Dissolve TFA salt in dichloromethane (6 ml) and 50% LVDS₃Washed with aqueous solution. Anhydrous Na in the organic layer₂SO₄Was dehydrated and concentrated to give the title compound.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.18 (s, 2H), 8.59-8.64 (m, 2H), 7.80 (dd, 1H), 7.52 (d, 1H), 7.39-7.42 (m, 2H), 7.33 (d, 2H), 7.16 ( d, 1H), 7.10 (d, 1H), 7.03 (d, 2H), 6.8 (dd, 1H), 6.65 (dd, 1H), 6.40) s, 1H), 6.14 (d, 1H), 3.85 (dd) , 2H), 3.24-3.32 (m, 4H), 3.03 (s, 3H), 2.73 (s, 2H), 2.12-2.17 (m, 5H), 1.68-1.94 (m, 3H), 1.61 (d, 2H) ), 1.37 (t, 2H), 1.24-1.27 (m, 2H), 0.92 (s, 6H).</p><p num="0735"> Example 178 Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 178A Trans-4- (4-morpholinocyclohexylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing 1- (tetrahydropyran-4-yl) methylamine in Example 1F with 4-amino-N-morpholinyl piperidine.</p><p num="0736"> Example 178B Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide The title compound was prepared in the same manner as in Example 177 by substituting Example 1F with Example 178A.¹1 H NMR (500MHz, Pyridine-d₅) δ 12.29 (s, 1H), 9.29 (d, J = 2.1Hz, 1H), 8.37 (d, J = 7.6Hz, 1H), 8.32 (dd, J = 9.3,2.3Hz, 1H), 8.18 (d , J = 8.8Hz, 1H), 7.52-7.57 (m, 2H), 7.39-7.47 (m, 3H), 7.10 (dd, J = 8.7,2.3Hz, 1H), 7.05-7.08 (m, 2H), 6.90 (d, J = 9.5Hz, 1H), 6.74 (dd, J = 9.0, 2.3Hz, 1H), 6.59-6.63 (m, 1H), 6.55 (d, J = 2.4Hz, 1H), 3.72-3.78 (m, 4H), 3.33-3.43 (m, 1H), 2.99-3.09 (m, 4H), 2.76 (s, 2H), 2.46-2.54 (m, 4H), 2.16-2.29 (m, 3H), 2.09 -2.14 (m, 4H), 2.05 (d, J = 11.9Hz, 2H), 1.97 (d, J = 1.8Hz, 2H), 1.87 (d, J = 11.6Hz, 2H), 1.19-1.42 (m, 6H), 0.93 (s, 6H).</p><p num="0737"> Example 179 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 179A 4- (2-Methoxyethylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing 1- (tetrahydropyran-4-yl) methylamine in Example 1F with 2-methoxyethylamine.</p><p num="0738"> Example 179B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-nitrophenyl} sulfonyl) benzamide The title compound was prepared in the same manner as in Example 177 by substituting Example 1F with Example 179A.¹1 H NMR (400MHz, DMSO-d₆) δ 11.20 (br. S, 1H) 11.15 (s, 1H) 8.59 (m, 2H) 7.81 (dd, 1H) 7.50 (d, 1H) 7.36 (m, 4H) 7.08 (m, 4H) 6.85 (dd, dd, 1H) 6.65 (dd, 1H) 6.38 (m, 1H) 6.14 (m, 1H) 3.58 (m, 4H) 3.30 (s, 3H) 3.03 (m, 4H) 2.73 (s, 2H) 2.15 (m, 6H) 1.96 (s, 2H) 1.38 (t, 2H) 0.92 (s, 6H).</p><p num="0739"> Example 180 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(3S) -tetrahydro-2H-pyran-3-ylmethyl] amino} phenyl) sulfonyl] benzamide Example 180A (R) -3-nitro-4-((Tetrahydro-2H-pyran-3-yl) methylamino) benzenesulfonamide and (S) -3-nitro-4-((tetrahydro-2H-pyran-3-yl) methylamino) ) Methylamino) benzenesulfonamide This Example compound was prepared by replacing 1- (tetrahydropyran-4-yl) methylamine in Example 1F with (tetrahydro-2H-pyran-3-yl) methaneamine.</p><p num="0740"> Example 180B (S) -3-Nitro-4-((Tetrahydro-2H-pyran-3-yl) Methylamino) Benzene Sulfonamide The racemic mixture of Example 180A was subjected to CO with a chiral SFC using an AD column (21 mm id × 250 mm length).₂The title compound was obtained by dividing in a gradient of 10-30% 0.1% diethylamine methanol over 15 minutes (oven temperature: 40 ° C; flow rate: 40 mL / min).</p><p num="0741"> Example 180C (R) -3-nitro-4-((tetrahydro-2H-pyran-3-yl) methylamino) benzenesulfonamide The racemic mixture of Example 180A was subjected to CO with a chiral SFC using an AD column (21 mm id × 250 mm length).₂The title compound was obtained by dividing in a gradient of 10-30% 0.1% diethylamine methanol over 15 minutes (oven temperature: 40 ° C; flow rate: 40 mL / min).</p><p num="0742"> Example 180D 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(3S) -tetrahydro-2H-pyran-3-ylmethyl] amino} phenyl) sulfonyl] benzamide The title compound was prepared in the same manner as in Example 177, replacing Example 1F with Example 180B.¹1 H NMR (400MHz, DMSO-d₆) δ 11.17 (s, 2H), 8.53-8.65 (m, 2H), 7.80 (d, 1H), 7.51 (d, 1H), 7.38-7.44 (m, 2H), 7.33 (d, 2H), 7.15 ( s, 1H), 7.02-7.09 (m, 3H), 6.82-6.92 (m, 1H), 6.65 (d, 1H), 6.39 (s, 1H), 6.14 (s, 1H), 3.68-3.82 (m, 2H), 3.22-3.32 (m, 2H), 3.13-3.22 (m, 1H), 3.03 (s, 4H), 2.72 (s, 2H), 2.09-2.23 (m, 6H), 1.78-1.98 (m, 4H), 1.56-1.66 (m, 1H), 1.43-1.51 (m, 1H), 1.37 (t, 2H), 1.22-1.33 (m, 1H), 0.92 (s, 6H).</p><p num="0743"> Example 181 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(3R) -tetrahydro-2H-pyran-3-ylmethyl] amino} phenyl) sulfonyl] benzamide The title compound was prepared in the same manner as in Example 177, replacing Example 1F with Example 180C.¹1 H NMR (400MHz, DMSO-d₆) δ 11.17 (s, 2H), 8.53-8.65 (m, 2H), 7.80 (d, 1H), 7.51 (d, 1H), 7.38-7.44 (m, 2H), 7.33 (d, 2H), 7.15 ( s, 1H), 7.02-7.09 (m, 3H), 6.82-6.92 (m, 1H), 6.65 (d, 1H), 6.39 (s, 1H), 6.14 (s, 1H), 3.68-3.82 (m, 2H), 3.22-3.32 (m, 2H), 3.13-3.22 (m, 1H), 3.03 (s, 4H), 2.72 (s, 2H), 2.09-2.23 (m, 6H), 1.78-1.98 (m, 4H), 1.56-1.66 (m, 1H), 1.43-1.51 (m, 1H), 1.37 (t, 2H), 1.22-1.33 (m, 1H), 0.92 (s, 6H).</p><p num="0744"> Example 182 4- (4-{[4- (4-Chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide The title compound was prepared in the same manner as in Example 177, replacing Example 26C with Example 150C.¹1 H NMR (400MHz, DMSO-d₆) δ 11.20 (br s, 1H), 11.17 (s, 1H), 8.63 (t, 1H), 8.59 (d, 1H), 7.79 (dd, 1H), 7.51 (d, 1H), 7.36 (m, 3H) ), 7.13 (m, 2H), 6.86 (dd, 1H), 6.66 (dd, 1H), 6.39 (s, 1H), 6.15 (d, 1H), 4.10 (s, 2H), 3.85 (m, 3H) , 3.50 (m, 2H), 3.42 (m, 2H), 3.24 (m, 4H), 3.02 (m, 4H), 2.82 (m, 2H), 2.16 (m, 2H), 1.61 (m, 3H), 1.25 (m, 4H), 1.17 (s, 6H).</p><p num="0745"> Example 183 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxy-1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide Example 183A 4-((4-Hydroxy-1-methylpiperidine-4-yl) methylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by substituting the (tetrahydropyran-4-yl) methylamine of Example 1F with 4- (aminomethyl) -1-methylpiperidine-4-ol.</p><p num="0746"> Example 183B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxy-1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 183A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.04 (s, 1H), 8.46-8.48 (m, 2H), 7.92 (s, 1H), 7.74 (d, 1H), 7.54 (d, 1H), 7.32-7.34 (m, 5H), 6.97- 7.05 (m, 5H), 6.74-6.76 (m, 1H), 6.55-6.57 (m, 1H), 6.33 (s, 1H), 6.13 (d, 1H), 5.10 (s, 1H), 3.14-3.17 ( m, 2H), 2.95 (br, 5H), 2.71 (br, 2H), 2.14-2.17 (m, 6H), 1.95 (br s, 2H), 1.70 (br, 4H), 1.36-1.39 (m, 2H) ), 1.24-1.26 (m, 2H), 0.92 (s, 6H).</p><p num="0747"> Example 184 4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -3-fluoro-2- (1H-indole) -5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 184A Ethyl 2- (1H-indole-5-yloxy) -3,4-difluorobenzoate This Example compound was prepared by substituting ethyl 2,4-difluorobenzoate of Example 20A with ethyl 2,3,4-trifluorobenzoate and 5-hydroxyindazole with 5-hydroxyindole.</p><p num="0748"> Example 184B Ethyl 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -3 -Fluorobenzoate This Example compound was prepared by substituting Example 20A of Example 20D with Example 184A.</p><p num="0749"> Example 184C 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -3- Fluorobenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 184B.</p><p num="0750"> Example 184D 4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -3-fluoro-2- (1H-indole) -5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 184C and Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 10.98 (br s, 1H), 8.35 (d, 1H), 7.98 (dd, 1H), 7.59 (dd, 1H), 7.35 (m, 3H), 7.28 (t, 1H), 7.21 (d, 1H) ), 7.06 (d, 2H), 6.78 (m, 2H), 6.67 (m, 2H), 6.22 (s, 1H), 3.74 (dd, 2H), 3.39 (m, 4H), 3.06 (m, 3H) , 2.97 (m, 4H), 2.79 (m, 2H), 2.73 (s, 3H), 2.29 (m, 2H), 2.18 (m, 2H), 2.05 (m, 2H), 1.81 (m, 2H), 1.41 (t, 2H), 0.94 (s, 6H).</p><p num="0751"> Example 185 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -3-fluoro-2- (1H-indole) -5-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 184C and Example 1F with Example 173C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 10.98 (br s, 1H), 8.33 (d, 1H), 8.02 (dd, 1H), 7.50 (dd, 1H), 7.35 (m, 3H), 7.26 (t, 1H), 7.19 (d, 1H) ), 7.06 (d, 2H), 6.77 (dd, 2H), 6.67 (m, 2H), 6.22 (s, 1H), 3.90 (dd, 2H), 3.57 (m, 5H), 3.30 (dd, 2H) , 3.06 (m, 3H), 2.94 (m, 4H), 2.78 (m, 2H), 2.27 (m, 4H), 2.18 (m, 2H), 1.98 (m, 4H), 1.80 (m, 2H), 1.55 (m, 2H), 1.41 (t, 2H), 0.94 (s, 6H).</p><p num="0752"> Example 186 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Hydroxy-1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 183A and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.12 (s, 1H), 8.49 (s, 1H), 8.42 (s, 1H), 7.73-7.75 (m, 1H), 7.58 (d, 1H), 7.34 (d, 2H), 7.22 (s, 1H), 7.09 (d, 1H), 7.01-7.05 (m, 3H), 6.92 (t, 1H), 6.61-6.62 (m, 1H), 6.31 (d, 1H), 6.23 (s, 1H), 6.20 (s, 1H), 5.16 (s, 1H), 4.05 (s, 3H), 2.95 (br s, 6H), 2.71 (br s, 2H), 2.62 (br, 3H), 2.16 (br s, 6H) , 1.95 (br s, 2H), 1.72 (br, 4H), 1.37-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0753"> Example 187 N-[(4-{[(3S, 4R) -1-benzyl-3-hydroxypiperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4- (4-) Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide Example 187A 2- (1H-indole-5-yloxy) -N- (4-chloro-3-nitrophenylsulfonyl) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohexa-1) -Enyl) Methyl) Piperazine-1-yl) Benzamide This Example compound was prepared by substituting Example 1F of Example 1G with 4-chloro-3-nitrobenzenesulfonamide and Example 1E with Example 26C.</p><p num="0754"> Example 187B N-[(4-{[(3S, 4R) -1-benzyl-3-hydroxypiperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4- (4-) Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide Example 187A (0.158g), (3S, 4R) -4-amino-1-benzylpiperidin-3-ol, hydrochloric acid (0.049g) and triethylamine (0.1mL) in a dioxane (2mL) mixture at 100 ° C. Heated overnight. The solvent was removed and the residue was redissolved in 1: 1 methanol: dimethyl sulfoxide (3 mL). This was then purified by reverse phase preparative HPLC. The residue was purified by reverse phase HPLC on a C18 column using a gradient of 0.1% TFA in 20-80% acetonitrile / water. The desired fraction was collected and the organic solvent was partially removed under reduced pressure. Saturate the resulting mixture LVDS₃Treated with an aqueous mixture. It was then extracted 3 times with ethyl acetate. The combined organic layer is washed with brine and dehydrated (DDL).₄), Filtered and concentrated to obtain the desired product.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 1H), 8.69 (d, 1H), 8.14 (d, 1H), 7.77 (dd, 1H), 7.51 (d, 1H), 7.29-7.41 (m, 9H), 7.10-7.13 ( m, 1H), 7.13 (d, 2H), 6.84 (dd, 1H), 6.63 (dd, 1H), 6.38 (s, 1H), 6.13 (d, 1H), 5.21-5.22 (br s, 1H), 3.82 (m, 2H), 3.62 (br s, 2H), 3.01 (br s, 4H), 2.71-2.82 (m, 4H), 2.12-2.15 (m, 7H), 1.94 (br s, 2H), 1.81 (br s, 2H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0755"> Example 188 N-[(4-{[(4-Aminotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl)- 4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidine-3-olhydrochloric acid of Example 187B with 4- (aminomethyl) tetrahydro-2H-pyran-4-amine. ..¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.08 (s, 1H), 8.60 (br s, 1H), 8.51 (d, 1H), 7.80 (dd, 1H), 7.54 (d, 1H), 7.32-7.36 (m, 4H), 7.12 (d) , 1H), 7.03-7.05 (m, 3H), 6.77 (dd, 1H), 6.58 (dd, 1H), 6.35 (s, 1H), 6.13 (d, 1H), 3.61-3.70 (m, 4H), 3.53 (br s, 2H), 2.97 (br, 4H), 2.71 (br, 2H), 2.16 (br s, 6H), 1.94 (br s, 2H), 1.67-1.72 (m, 2H), 1.52-1.57 (m, 2H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0756"> Example 189 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[1- (2-Methoxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 189A 4- [1- (2-Methoxy-ethyl) -piperidine-4-ylamino] -3-nitro-benzenesulfonamide 1- (2-Methoxy-ethyl) -piperidine-4-ylamine (2.01 g) and triethylamine (3.24 mL, 2.35 g) were added to 1,4-dioxane (60 mL). 4-Chloro-3-nitrobenzenesulfonamide (2.50 g) was added and the mixture was heated to 90 ° C for 16 hours. The mixture was cooled and the material was purified by flash column chromatography on silica gel with 10% methanol in dichloromethane.</p><p num="0757"> Example 189B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[1- (2-Methoxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 189A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.12 (br s, 1H), 8.52 (d, 1H), 8.18 (d, 1H), 7.76 (dd, 1H), 7.51 (d, 1H), 7.39-7.31 (m, 4H), 7.08-7.05 (m, 4H), 6.80 (dd, 1H), 6.61 (dd, 1H), 6.36 (t, 1H), 6.14 (d, 1H), 3.70 (m, 1H), 3.50 (t, 2H), 3.27 (s, 3H), 2.99 (m, 6H), 2.71 (br s, 4H), 2.16 (m, 6H), 2.02-1.90 (m, 6H), 1.65 (m, 2H), 1.37 (t, 2H) , 0.92 (s, 6H).</p><p num="0758"> Example 190 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 174A and Example 26C with Example 55B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.21 (br s, 1H), 9.14 (s, 1H), 8.45 (d, 1H), 7.71 (dd, 1H), 7.52 (m, 2H), 7.34 (m, 2H), 7.26 (m, 1H) ), 7.15 (d, 1H), 7.04 (m, 2H), 6.95 (t, 1H), 6.67 (m, 1H), 6.38 (d, 1H), 6.25 (m, 2H), 3.01 (m, 4H) , 2.87 (m, 5H), 2.72 (m, 2H), 2.33 (m, 4H), 2.15 (m, 6H), 1.95 (s, 2H), 1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0759"> Example 191 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2-Hydroxyethyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide Example 191A tert-Butyl 4-(4- (N- (2- (1H-indole-4-yloxy) -4-(-4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1- Enyl) Methyl) Piperazin-1-yl) Benzoyl) Sulfamoyl) -2-Nitrophenylamino) Piperidine-1-carboxylate CH of this Example compound for chromatography₂Cl₂Prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 157A, except that 5-7% methanol in was used.</p><p num="0760"> Example 191B 2- (1H-Indole-4-yloxy) -N- (4- (1- (2- (tert-butyldimethylsilyloxy) ethyl) piperidine-4-ylamino) -3-nitrophenylsulfonyl) -4-( -4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzamide Example 191A (400mg), CH₂Cl₂It was dissolved in 4N HCl in (2.5 mL) and dioxane (2.5 mL) and then stirred at room temperature for 30 minutes. Concentrate the reaction, then CH₂Cl₂And saturated LVDS₃It was partitioned into an aqueous solution. Wash the organic layer with brine and Na₂SO₄Dehydrated with. After filtering and concentrating, the obtained crude amine is CH₂Cl₂It was slurryed to (2.5 mL) and (tert-butyldimethylsilyloxy) acetaldehyde (73 mg) was added. After stirring for 15 minutes, sodium triacetoxyborohydride (400 mg) was added and the reaction was stirred at room temperature overnight. CH reactant₂Cl₂Dilute with and saturated with LVDS₃Washed with aqueous solution. Wash the organic layer with brine and Na₂SO₄Dehydrated with. Product, CH₂Cl₂Purified by column chromatography with 1.0-2.5% methanol in.</p><p num="0761"> Example 191C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2-Hydroxyethyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide Example 191B (46 mg) was dissolved in tetrahydrofuran (0.8 mL) followed by 95/5 tetrahydrofuran / H.₂1.0 M tetrabutylammonium fluoride in O (0.075 mL) was added and the reaction was stirred at room temperature overnight. Concentrate the reaction solution and CH₂Cl₂Purified by column chromatography using 2-6% methanol in the medium.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.15 (br s, 1H), 8.44 (d, 1H), 8.13 (br d, 1H), 7.74 (dd, 1H), 7.55 (d, 1H), 7.33 (d, 2H), 7.23 (s, 1H), 7.11 (d, 1H), 7.03 (m, 3H), 6.93 (dd, 1H), 6.64 (d, 1H), 6.33 (d, 1H), 6.23 (s, 1H), 6.22 (s, 1H) ), 3.75 (br s, 1H), 3.61 (br s, 2H), 3.40 (br s, 2H), 3.10 (br s, 2H), 2.98 br s, 4H), 2.78 (br s, 2H), 2.71 (s, 2H), 2.16 (br m, 6H), 2.00 (br d, 2H), 1.95 (s, 2H), 1.72 (br s, 2H), 1.38 (t, 2H), 0.92 (s, 6H) ..</p><p num="0762"> Example 194 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[1- (2-Methoxyethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 189A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.19 (br s, 1H), 8.46 (d, 1H), 8.17 (d, 1H), 7.72 (dd, 1H), 7.55 (d, 1H), 7.35 (d, 2H), 7.25 (t, 1H) ), 7.12 (d, 1H), 7.07-7.02 (m, 3H), 6.94 (t, 1H), 6.66, (dd, 1H), 6.36 (d, 1H), 6.24 (m, 2H), 3.73 (m) , 1H), 3.52 (t, 2H), 3.27 (s, 3H), 3.00 (m, 6H), 2.79 (m, 2H), 2.72 (br s, 2H), 2.16 (m, 6H), 2.04-1.93 (m, 6H), 1.68 (m, 2H), 1.37 (t, 2H), 0.92 (s, 6H).</p><p num="0763"> Example 195 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Hydroxypropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide Example 195A 4- (1- (3- (tert-butyldimethylsilyloxy) propyl) piperidine-4-ylamino) -3-nitrobenzene sulfonamide A mixture of Example 157B (300 mg), (3-bromopropoxy) (tert-butyl) dimethylsilane (304 mg) and cesium carbonate (967 mg) was suspended in anhydrous N, N-dimethylformamide (5 mL). The reaction mixture was heated at 70 ° C. overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water and brine, dehydrated with anhydrous sodium sulfate and concentrated. The crude material was purified by flash column purification with 3-10% methanol / dichloromethane to give the title compound.</p><p num="0764"> Example 195B 2- (1H-Indole-4-yloxy) -N- (4- (1- (3- (tert-butyldimethylsilyloxy) propyl) piperidine-4-ylamino) -3-nitrophenylsulfonyl) -4-( 4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 195A.</p><p num="0765"> Example 195C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Hydroxypropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide A mixture of Example 195B (180 mg) in anhydrous tetrahydrofuran (1 mL) and tetrabutylammonium fluoride (0.5 mL 1M in tetrahydrofuran) was stirred at room temperature for 2 hours. The solvent was removed under vacuum. The residue was purified by reverse phase HPLC using a C18 column using a gradient of 0.1% trifluoroacetic acid in 40-70% acetonitrile / water to give the title compound as trifluoroacetate. Dissolve trifluoroacetic acid salt in dichloromethane (6 ml) and 50% LVDS₃Washed with aqueous solution. Anhydrous Na in the organic layer₂SO₄Dehydrated with, filtered and concentrated to give the title compound.¹1 H NMR (400MHz, dimethyl sulfoxide-dg) δ 11.16 (s, 1H), 8.43 (d, 1H), 8.10 (m, 1H), 7.74 (dd, 1H), 7.57 (d, 1H), 7.34 (d, 2H), 7.23 (m, 1H), 7.10 (m, 1H), 7.02 (m, 3H), 6.93 (m, 1H), 6.65 (dd, 1H), 6.34 (d, 1H), 6.22 (m, 2H) ), 3.74 (m, 2H), 3.47 (m, 4H), 3.14 (m, 2H), 2.97 (m, 4H), 2.74 (m, 4H), 2.60 (m, 1H), 2.17 (m, 4H) , 1.97 (m, 4H), 1.69 (m, 4H), 1.40 (m, 2H), 0.93 (s, 6H).</p><p num="0766"> Example 196 4- [4-({4'-Chloro-3- [3- (dimethylamino) propyl] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 196A 4'-Chloro-3-hydroxybiphenyl-2-carbaldehyde The title compound was prepared in the same manner as described in Example 175A, replacing 1- (2-bromophenyl) etanone with 2-bromo-6-hydroxybenzaldehyde.</p><p num="0767"> Example 196B tert-Butyl 4-((4'-chloro-3-hydroxybiphenyl-2-yl) methyl) piperazine-1-carboxylate The title compound was prepared in the same manner as described in Example 1A, replacing 4'-chlorobiphenyl-2-carboxaldehide with Example 196A.</p><p num="0768"> Example 196C tert-Butyl 4-((4'-chloro-3- (trifluoromethylsulfonyloxy) biphenyl-2-yl) methyl) piperazine-1-carboxylate Trifluoromethanesulfonic anhydride (0.326 ml) was added dropwise to a mixture of Example 196B (390 mg) in pyridine (5 ml) at 0 ° C. The reaction mixture was stirred in an ice bath for 1 hour and diluted with ethyl acetate. The resulting mixture was thoroughly washed with brine and the organic layer was Na.₂SO₄Dehydrated with, filtered and concentrated to give the title compound.</p><p num="0769"> Example 196D tert-Butyl 4-((4'-chloro-3-(3- (dimethylamino) propa-1-ynyl) biphenyl-2-yl) methyl) piperazine-1-carboxylate Examples 196C (380 mg) in N, N-dimethylformamide (1.5 ml), N, N-dimethylprop-2-in-1-amine (0.227 ml), tetrakis (triphenylphosphine) palladium (0) (123 mg) ) And triethylamine (0.492) in a mixture of copper (I) iodide (27.1 mg) and^tBuNI (394 mg) was added. The reaction mixture was heated at 100 ° C. for 4 hours, cooled and diluted with ethyl acetate. Organic layer Na₂SO₄It was dehydrated and concentrated. The residue was purified by flash chromatography with a mixture of methanol, dichloromethane and triethylamine to give the title compound.</p><p num="0770"> Example 196E tert-Butyl 4-((4'-chloro-3- (3- (dimethylamino) propyl) biphenyl-2-yl) methyl) piperazine-1-carboxylate Example 196D (200 mg) in methanol (8 ml), H₂Under atmosphere, it was treated overnight with platinum oxide (IV) (29.1 mg). The insoluble material was filtered off and the filtrate was concentrated to give the title compound.</p><p num="0771"> Example 196F 3- (4'-Chloro-2- (piperazine-1-ylmethyl) biphenyl-3-yl) -N, N-dimethylpropan-1-amine The title compound was prepared in the same manner as described in Example 175C, replacing Example 175B with Example 196E.</p><p num="0772"> Example 196G Ethyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-3- (3- (dimethylamino) propyl) biphenyl-2-yl) methyl) piperazine-1-yl) Benzoate The title compound was prepared in the same manner as described in Example 175D, replacing Example 175C with Example 196F.</p><p num="0773"> Example 196H 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-3-(3- (dimethylamino) propyl) biphenyl-2-yl) methyl) piperazine-1-yl) benzoin acid The title compound was prepared in the same manner as described in Example 175E, replacing Example 175D with Example 196G.</p><p num="0774"> Example 196I 4- [4-({4'-Chloro-3- [3- (dimethylamino) propyl] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E with Example 196H.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.11 (s, 1H), 8.38-8.44 (m, 2H), 7.68 (dd, 1H), 7.56 (d, 1H), 7.44 (d, 2H), 7.19-7.29 (m, 5H), 7.07 ( d, 1H), 6.99 (dd, 1H), 6.87-6.93 (m, 2H), 6.59 (dd, 1H), 6.26 (d, 1H), 6.23 (s, 1H), 6.19 (d, 1H), 3.84 (dd, 2H), 3.22-3.29 (m, 4H), 2.87 (s, 6H), 2.69-2.75 (m, 2H), 2.59 (s, 5H), 2.14 (s, 4H), 1.83-1.92 (m) , 3H), 1.56-1.65 (m, 2H), 1.19-1.31 (m, 4H), 0.81-0.90 (m, 1H) Example 197 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Hydroxypropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-5-Iloxy) Benzamide Example 197A 2- (1H-indole-5-yloxy) -N-(4- (1- (3- (tert-butyldimethylsilyloxy) propyl) piperidine-4-ylamino) -3-nitrophenylsulfonyl) -4-( 4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 195A.</p><p num="0775"> Example 197B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Hydroxypropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-5-Iloxy) Benzamide This Example compound was prepared by substituting Example 195B of Example 195C with Example 197A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.07 (bs, 1H), 8.50 (d, 1H), 8.14 (d ,, 1H), 7.75 (dd, 1H), 7.52 (d, 1H), 7.34 (m, 4H), 7.02 (m, 4H) ), 6.78 (dd, 1H), 6.59 (dd, 1H), 6.34 (m, 1H), 6.14 (d, 1H), 3.46 (m, 4H), 3.16 (m, 2H), 2.98 (m, 4H) , 2.68 (m, 4H), 2.60 (m, 1H), 2.16 (m, 6H), 1.97 (m, 4H), 1.68 (m, 4H), 1.38 (t, 2H), 0.93 (s, 6H).</p><p num="0776"> Example 198 4- {4-[(4'-Chloro-4-morpholine-4-yl-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 198A tert-Butyl 4-((4'-chloro-4-hydroxybiphenyl-2-yl) methyl) piperazine-1-carboxylate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxardhide of Example 1A with Example 125A.</p><p num="0777"> Example 198B tert-Butyl 4-((4'-chloro-4- (trifluoromethylsulfonyloxy) biphenyl-2-yl) methyl) piperazine-1-carboxylate A mixture of Example 198A (3.0 g) and trifluoromethanesulfonic anhydride (3.14 g) in an anhydrous pyridine (50 mL) mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate. The organic phase was washed with water and brine, dehydrated with anhydrous sodium sulfate and concentrated. The residue was used in the next step without further purification.</p><p num="0778"> Example 198C tert-Butyl 4-((4'-chloro-4-morpholinobiphenyl-2-yl) methyl) piperazine-1-carboxylate Example 198B (500 mg), morpholine (80 mg), palladium (II) acetate (22 mg), biphenyl-2-yldi-tert-butylphosphine (50 mg) and cesium carbonate (427 mg) suspension in anhydrous tetrahydrofuran (6 mL) Was heated at 50 ° C overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water and brine, dehydrated with anhydrous sodium sulfate, filtered and concentrated. The crude material was purified by flash column purification using 30-50% ethyl acetate / hexane to give the title compound.</p><p num="0779"> Example 198D 4- (4'-Chloro-2- (piperazine-1-ylmethyl) biphenyl-4-yl) morpholine This Example compound was prepared by substituting Example 1A of Example 1B with Example 198C.</p><p num="0780"> Example 198E Methyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4-morpholinobiphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 20A of Example 20D with Example 24F and Example 20C with Example 198D.</p><p num="0781"> Example 198F 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4-morpholinobiphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 198E.</p><p num="0782"> Example 198G 4- {4-[(4'-Chloro-4-morpholine-4-yl-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 198F.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.26 (bs, 1H), 8.63 (t, 1H), 8.49 (d, 1H), 7.66 (dd, 1H), 7.54 (d, 1H), 7.40 (m, 4H), 7.29 (m, 1H) , 7.02 (m, 6H), 6.73 (dd, 1H), 6.39 (d, 1H), 6.30 (m, 2H), 3.85 (dd, 2H), 3.74 (m, 4H), 3.24 (m, 6H), 3.10 (m, 8H), 2.29 (m, 4H), 1.89 (m, 1H), 1.63 (m, 2H), 1.28 (m, 2H).</p><p num="0783"> Example 199 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide Example 199A tert-Butyl 4-((4'-chloro-3-hydroxybiphenyl-2-yl) methyl) piperazine-1-carboxylate The title compound was prepared in the same manner as described in Example 1A, replacing Example 27C with Example 196A.</p><p num="0784"> Example 199B tert-Butyl 4-((4'-chloro-3- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-carboxylate 60% sodium hydride (0.596 g) was added to the mixture of Example 199A (1.5 g) in N, N-dimethylformamide (20 ml). The mixture was stirred at room temperature for 30 minutes and dimethylaminoethyl chloride hydrochloride (1.073 g) was added. The resulting mixture was stirred overnight and then 60% sodium hydride (0.596 g) and dimethylaminoethyl chloride hydrochloride (1.073 g) were added. The reaction mixture was further stirred overnight, diluted with ethyl acetate, water, saturated LVDS.₃And washed with brine. Organic layer Na₂SO₄Dehydrated with, filtered and concentrated to give the title compound.</p><p num="0785"> Example 199C 2- (4'-Chloro-2- (piperazine-1-ylmethyl) biphenyl-3-yloxy) -N, N-dimethylethaneamine Trifluoroacetic acid (10 ml) was added to the mixture of Example 199B (2 g) in dichloromethane (10 ml) at 0 ° C. The reaction mixture was stirred at room temperature for 30 minutes and concentrated. The residue was loaded onto a C18 column and eluted with 0-50% 0.1% trifluoroacetic acid / water in acetonitrile. The title compound was obtained as a trifluoroacetate.</p><p num="0786"> Example 199D Ethyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-3- (2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) Benzoate The title compound was prepared in the same manner as described in Example 175D, replacing Example 175C with Example 199C.</p><p num="0787"> Example 199E 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-3-(2- (dimethylamino) ethoxy) biphenyl-2-yl) methyl) piperazine-1-yl) Benzoin acid The title compound was prepared in the same manner as described in Example 175E, replacing Example 175D with Example 199D.</p><p num="0788"> Example 199F 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 199E and Example 173C, respectively.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.13 (s, 1H), 8.41 (d, 1H), 8.12 (d, 1H), 7.70 (dd, 1H), 7.58 (d, 1H), 7.52 (d, 2H), 7.43 (d, 2H) , 7.31 (t, 1H), 7.22 (t, 1H), 7.06 (dd, 2H), 6.89-6.97 (m, 2H), 6.84 (d, 1H), 6.64 (dd, 1H), 6.30 (d, 1H) ), 6.24 (dd, 2H), 4.14 (t, 2H), 3.90 (dd, 2H), 3.53-3.73 (m, 2H), 3.22-3.32 (m, 4H), 2.93 (s, 6H), 2.34- 2.46 (m, 7H), 2.29 (s, 5H), 1.97 (d, 2H), 1.73 (d, 2H), 1.41-1.62 (m, 4H).</p><p num="0789"> Example 201 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Diethylamino) cyclohexyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide Example 201A 4- (4- (diethylamino) cyclohexylamino) -3-nitrobenzenesulfonamide This Example compound was formulated with N 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A.¹, N¹-Prepared by replacing with diethylcyclohexane-1,4-diamine.</p><p num="0790"> Example 201B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Diethylamino) cyclohexyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 201A.¹1 H NMR (500MHz, Pyridine-d₅) δ ppm 12.28 (s, 1H), 9.29 (d, 1H), 8.29-8.38 (m, 2H), 8.19 (d, 1H), 7.52-7.57 (m, 2H), 7.40-7.47 (m, 3H) , 7.10 (dd, 1H), 7.06 (d, 2H), 6.92 (d, 1H), 6.74 (dd, 1H), 6.61 (s, 1H), 6.55 (d, 1H), 3.31-3.42 (m, 1H) ), 3.00-3.08 (m, 4H), 2.76 (s, 2H), 2.54-2.61 (m, 1H), 2.51 (q, 4H), 2.21-2.28 (m, 2H), 2.08-2.15 (m, 4H) ), 2.04 (d, 2H), 1.97 (s, 2H), 1.81 (d, 2H), 1.38 (t, 2H), 1.29-1.36 (m, 2H), 1.17-1.28 (m, 2H), 1.05 ( t, 6H), 0.93 (s, 6H).</p><p num="0791"> Example 202 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Dimethylamino) Cyclohexyl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide Example 202A 4- (4- (Dimethylamino) Cyclohexylamino) -3-nitrobenzenesulfonamide This Example compound was formulated with N 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A.¹, N¹-Prepared by replacing with dimethylcyclohexane-1,4-diamine.</p><p num="0792"> Example 202B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Dimethylamino) Cyclohexyl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-4-yloxy) Benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 202A.¹1 H NMR (500MHz, Pyridine-d₅) δ ppm 12.45 (s, 1H), 9.21 (d, 1H), 8.33 (d, 1H), 8.27 (dd, 1H), 8.18 (d, 1H), 7.48 (t, 1H), 7.45 (d, 2H) ), 7.40 (d, 1H), 7.11 (t, 1H), 7.08 (d, 2H), 6.87 (d, 1H), 6.72-6.81 (m, 3H), 6.67 (d, 1H), 3.31-3.41 ( m, 1H), 3.00-3.06 (m, 4H), 2.77 (s, 2H), 2.31 (s, 6H), 2.25 (t, 2H), 2.20-2.25 (m, 1H), 2.10-2.16 (m, 4H), 2.00-2.07 (d, 2H), 1.97 (s, 2H), 1.88 (d, 2H), 1.39 (t, 3H), 1.34 (d, 2H), 1.15-1.28 (m, 4H), 0.94 (s, 6H).</p><p num="0793"> Example 203 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Diethylamino) cyclohexyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 201A.¹1 H NMR (500MHz, Pyridine-d₅) δ 12.44 (s, 1H), 9.21 (d, 1H), 8.34 (d, 1H), 8.28 (dd, 1H), 8.18 (d, 1H), 7.47-7.50 (m, 1H), 7.45 (d, 2H), 7.40 (d, 1H), 7.11 (t, 1H), 7.08 (d, 2H), 6.90 (d, 1H), 6.73-6.81 (m, 3H), 6.67 (d, 1H), 3.32-3.40 (m, 1H), 2.99-3.06 (m, 4H), 2.76 (s, 2H), 2.52-2.60 (m, 1H), 2.49 (q, 4H), 2.25 (t, 2H), 2.09-2.16 (m) , 4H), 2.04 (d, 2H), 1.97 (s, 2H), 1.79 (d, 2H), 1.29-1.42 (m, 4H), 1.16-1.28 (m, 2H), 1.04 (t, 6H), 0.92-0.95 (m, 6H).</p><p num="0794"> Example 204 Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4) -Iloxy) -N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 204A trans-4- (4- morpholinocyclohexyl) -3- nitro ii benzenesulfonamide This Example compound was prepared by substituting 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with trans-4-morpholinocyclohexaneamine.</p><p num="0795"> Example 204B trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4) -Iloxy) -N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 204A.¹1 H NMR (500MHz, Pyridine-d₅) δ 12.45 (s, 1H), 9.21 (d, 1H), 8.36 (d, 1H), 8.26 (dd, 1H), 8.16 (d, 1H), 7.47-7.51 (m, 1H), 7.45 (d, 1H), 7.40 (d, 1H), 7.12 (t, 1H), 6.87 (d, 1H), 6.73-6.81 (m, 3H), 6.68 (d, 1H), 3.71-3.78 (m, 2H), 3.33 -3.42 (m, 1H), 3.00-3.06 (m, 4H), 2.76 (s, 2H), 2.44-2.52 (m, 4H), 2.25 (t, 2H), 2.16-2.23 (m, 2H), 2.09 -2.16 (m, 4H), 2.06 (d, 2H), 1.97 (s, 2H), 1.86 (s, 2H), 1.39 (t, 2H), 1.17-1.35 (m, 6H), 0.94 (s, 6H) ).</p><p num="0796"> Example 205 4- [4-({4'-Chloro-3- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 177, replacing Example 26C and Example 1F with Example 199E and Example 21A, respectively.¹H NMR (500MHz, dichloromethane-d₂) δ 8.70 (d, 1H), 8.56 (s, 1H), 8.40 (d, 1H), 7.95 (dd, 1H), 7.91 (d, 1H), 7.46 (d, 2H), 7.24-7.35 (m, 5H), 7.15 (t, 1H), 6.90 (dd, 2H), 6.83 (d, 1H), 6.75 (d, 1H), 6.60 (dd, 1H), 6.41 (d, 1H), 6.19 (d, 1H) ), 4.05 (t, 2H), 3.58 (s, 1H), 3.32 (s, 2H), 2.95-3.02 (m, 4H), 2.66-2.80 (m, 4H), 2.30-2.35 (m, 4H), 2.24-2.29 (m, 9H), 2.15-2.23 (m, 2H), 2.05 (d, 2H), 1.63-1.73 (m, 2H) Example 206 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(1-Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 177, replacing Example 26C and Example 1F with Example 175E and Example 21A, respectively.¹H NMR (400MHz, dichloromethane-d₂) δ 8.70 (d, 1H), 8.51 (s, 1H), 8.40 (d, 1H), 7.94 (dd, 1H), 7.90 (d, 1H), 7.54 (d, 1H), 7.33 (t, 4H) , 7.21-7.27 (m, 2H), 7.10-7.19 (m, 4H), 6.91 (d, 1H), 6.73 (d, 1H), 6.55-6.60 (m, 1H), 6.41 (s, 1H), 6.16 (d, 1H), 3.52-3.63 (m, 1H), 3.36 (q, 1H), 2.96-3.07 (m, 4H), 2.72-2.79 (m, 2H), 2.33-2.41 (m, 2H), 2.27 (s, 3H), 2.14-2.27 (m, 4H), 2.00-2.09 (m, 2H), 1.63-1.74 (m, 2H), 1.19 (d, 3H).</p><p num="0797"> Example 207 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[4 -(Dimethylamino) tetrahydro-2H-pyran-4-yl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide This Example compound was used as (3S, 4R) -4-amino-1-benzylpiperidine-3-ol in Example 187B, and 4- (aminomethyl) -N, N-dimethyltetrahydro-2H-pyran-4 as hydrochloric acid. -Prepared by replacing with amine.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.84 (br s, 1H), 8.59 (d, 1H), 7.84 (dd, 1H), 7.51 (d, 1H), 7.39-7.43 (m, 2H), 7.33 (d) , 2H), 7.17-7.21 (m, 2H), 7.03 (d, 2H), 6.89 (dd, Hz, 1H), 6.64 (d, 1H), 6.40 (s, 1H), 6.13 (d, 1H), 3.72-3.75 (m, 2H), 3.34-3.57 (m, 4H), 3.02 (br, 4H), 2.71 (br, 2H), 2.27 (s, 6H), 2.16 (br s, 6H), 1.94 (br s, 2H), 1.78-1.85 (m, 2H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0798"> Example 208 N-({4-[(2-aminocyclohexyl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-ene -1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide Example 208A This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidine-3-ol, hydrochloric acid of Example 187B with tert-butyl 2-aminocyclohexylcarbamate.</p><p num="0799"> Example 208B N-({4-[(2-aminocyclohexyl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-ene -1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide Example 208A (0.1 g) in dimethyl sulfoxide (4 mL) was heated under microwave conditions (200 ° C, 1 hour). The residue was purified by reverse phase HPLC using a C18 column using a gradient of 0.1% TFA in 30-70% acetonitrile / water. The desired fraction was collected and the organic solvent was partially removed under reduced pressure. Saturate the resulting mixture LVDS₃Treated with an aqueous mixture. It was then extracted 3 times with ethyl acetate. The combined organic layer is washed with brine and dehydrated (DDL).₄), Filtered and concentrated to give the title compound.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.02 (s, 1H), 8.45 (s, 1H), 8.05 (d, 1H), 7.79-7.81 (m, 1H), 7.56 (d, 1H), 7.30-7.34 (m, 4H), 6.98- 7.06 (m, 4H), 6.73 (d, 1H), 6.54 (dd, 1H), 6.33 (s, 1H), 6.11 (d, 1H), 3.64-3.70 (m, 1H), 2.93 (br, 4H) , 2.71 (br, 2H), 2.14-2.16 (br s, 6H), 1.95 (br s, 2H), 1.67-1.73 (m, 2H), 1.36-1.39 (m, 2H), 0.92 (s, 6H) ..</p><p num="0800"> Example 209 4- [4-({4'-Chloro-4- [3- (dimethylamino) propa-1-inyl] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole-4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 209A tert-Butyl 4-((4'-chloro-4- (3- (dimethylamino) propa-1-ynyl) biphenyl-2-yl) methyl) piperazine-1-carboxylate Example 198B (800 mg), N, N-dimethylprop-2-in-1-amine (373 mg), copper iodide (I) (57 mg), tetrakis (triphenylphosphine) palladium (0) (259 mg), triethylamine A suspension of (757 mg) and tert-butylammonium iodide (829 mg) in anhydrous N, N-dimethylformamide (5 mL) was heated at 100 ° C. for 5 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water and brine, dehydrated with anhydrous sodium sulfate, filtered and concentrated. The crude material was purified on a flash column with 0-3% methanol / dichloromethane to give the title compound.</p><p num="0801"> Example 209B 3- (4'-Chloro-2- (piperazine-1-ylmethyl) biphenyl-4-yl) -N, N-dimethylpropa-2-in-1-amine This Example compound was prepared by substituting Example 1A of Example 1B with Example 209A.</p><p num="0802"> Example 209C Methyl 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4- (3- (dimethylamino) propa-1-inyl) biphenyl-2-yl) methyl) piperazine- 1-yl) benzoate This Example compound was prepared by substituting Example 20A of Example 20D with Example 24F and Example 20C with Example 209B.</p><p num="0803"> Example 209D 2- (1H-indole-4-yloxy) -4-(4-((4'-chloro-4- (3- (dimethylamino) propa-1-inyl) biphenyl-2-yl) methyl) piperazine-1 -Il) Benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 209C.</p><p num="0804"> Example 209E 4- [4-({4'-Chloro-4- [3- (dimethylamino) propa-1-inyl] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole-4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 209D.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.23 (bs, 1H), 8.57 (t, 1H), 8.47 (d, 1H), 7.67 (dd, 1H), 7.54 (m, 2H), 7.43 (m, 5H), 7.24 (m, 2H) , 7.14 (m, 1H), 7.03 (m, 1H), 6.94 (m, 1H), 6.71 (d, 1H), 6.38 (d, 1H), 6.27 (d, 2H), 3.85 (m, 2H), 3.60 (m, 2H), 3.23 (m, 6H), 3.04 (m, 4H), 2.35 (s, 6H), 2.28 (m, 4H), 1.88 (m, 1H), 1.58 (m, 2H), 1.24 (m, 2H).</p><p num="0805"> Example 210 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(3-Nitro-4-{[1- (4,4,4-trifluorobutyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide Example 210A 3-Nitro-4- (1- (4,4,4-trifluorobutyl) piperidine-4-ylamino) benzenesulfonamide Example 157B (600 mg) was combined with 1,1,1-trifluoro-4-iodobutane (595 mg) and potassium carbonate (829 mg) in acetonitrile (15 mL). The reaction was heated to 70 ° C overnight. The reaction was concentrated, then taken to ether and concentrated again. The product was used in the next step without further purification.</p><p num="0806"> Example 210B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(3-Nitro-4-{[1- (4,4,4-trifluorobutyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 210A and Example 1E with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.20 (s, 1H), 8.47 (d, 1H), 8.20 (d, 1H), 7.72 (dd, 1H), 7.54 (d, 1H), 7.34 (d, 2H), 7.25 (t, 1H) , 7.14 (d, 1H), 7.05 (m, 3H), 6.95 (t, 1H), 6.68 (dd, 1H), 6.38 (d, 1H), 6.25 (s, 2H), 3.71 (m, 1H), 3.01 (m, 4H), 2.92 (m, 2H), 2.72 (s, 2H), 2.40 (m, 2H), 2.30 (m, 2H), 2.16 (m, 6H), 1.95 (m, 4H), 1.68 (m, 4H), 1.38 (t, 2H), 1.24 (br s, 1H), 0.92 (s, 6H).</p><p num="0807"> Example 211 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[2-yl] (4-Hydroxy-1-methylpiperidin-4-yl) ethyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was replaced with (3S, 4R) -4-amino-1-benzylpiperidine-3-ol of Example 187B and hydrochloric acid was replaced with 4- (2-aminoethyl) -1-methylpiperidine-4-ol. Prepared.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.05 (s, 1H), 8.61 (s, 1H), 8.47 (d, 1H), 7.77 (dd, 1H), 7.54 (d, 1H), 7.32-7.34 (m, 4H), 7.04 (d, 2H), 7.01 (s, 1H), 6.90 (d, 2H), 6.76 (dd, 1H), 6.57 (dd, 1H), 6.33 (s, 1H), 6.13 (d, 1H), 4.92 (s, 1H) ), 3.43-3.46 (m, 2H), 2.95-3.01 (br, 8H), 2.71 (br, 2H), 2.65 (s, 3H), 2.12-2.16 (br s, 6H), 1.95 (br s, 2H) ), 1.77-1.80 (m, 2H), 1.67-1.71 (m, 4H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0808"> Example 212 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-2-yl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide This Example compound was replaced with (3S, 4R) -4-amino-1-benzylpiperidine-3-ol of Example 187B and hydrochloric acid was replaced with 4- (2-aminoethyl) -1-methylpiperidine-4-ol. Prepared.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 1H), 8.58 (s, 1H), 8.28 (d, 1H), 7.82 (dd, 1H), 7.51 (d, 1H), 7.39-7.42 (m, 2H), 7.33 (d, 2H), 7.20 (d, 1H), 7.17 (d, 1H), 7.14 (d, 1H), 7.03 (d, 2H), 6.86 (d, 1H), 6.85 (d, 1H), 6.65 (dd, 1H) ), 6.39 (s, 1H), 6.15 (d, 1H), 3.87-3.90 (m, 2H), 3.20-3.24 (m, 2H), 3.04 (br, 4H), 2.73 (br, 2H), 2.1 1 -2.17 (m, 5H), 1.95 (br s, 2H), 1.71-1.75 (m, 2H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0809"> Example 213 4- (4-{[4'-Chloro-4- (2-hydroxyethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 213A 4- (2- (tert-butyldimethylsilyloxy) ethoxy) -4'-chlorobiphenyl-2-carbaldehyde A mixture of Example 125A (0.5 g), (2-bromoethoxy) (tert-butyl) dimethylsilane (0.771 g) and cesium carbonate (1.4 g) was suspended in anhydrous N, N-dimethylformamide (5 mL). The reaction mixture was heated at 70 ° C. overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water and brine, dehydrated with anhydrous sodium sulfate, filtered and concentrated. The crude material was purified by flash column purification with 0-5% ethyl acetate / hexane to give the title compound.</p><p num="0810"> Example 213B Methyl 2- (1H-Indole-4-yloxy) -4-(4-((4- (2- (tert-butyldimethylsilyloxy) ethoxy) -4'-chlorobiphenyl-2-yl) methyl) piperazine- 1-yl) benzoate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 213A and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="0811"> Example 213C 2- (1H-Indole-4-yloxy) -4-(4-((4- (2- (tert-butyldimethylsilyloxy) ethoxy) -4'-chlorobiphenyl-2-yl) methyl) piperazine-1 -Il) Benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 213B.</p><p num="0812"> Example 213D 2- (1H-Indol-4-yloxy) -4-(4-((4- (2- (tert-butyldimethylsilyloxy) ethoxy) -4'-chlorobiphenyl-2-yl) methyl) piperazine-1 -Il) -N- (3-Nitro-4-((Tetrahydro-2H-Pyran-4-yl) Methylamino) Phenylsulfonyl) Benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 213C.</p><p num="0813"> Example 213E 4- (4-{[4'-Chloro-4- (2-hydroxyethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 195B of Example 195C with Example 213D.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.24 (m, 1H), 8.62 (t, 1H), 8.50 (d, 1H), 7.67 (dd, 1H), 7.54 (m, 1H), 7.43 (d, 2H), 7.37 (d, 2H) , 7.28 (m, 1H), 7.15 (m, 2H), 7.05 (m, 2H), 6.96 (m, 1H), 6.90 (dd, 1H), 6.73 (dd, 1H), 6.40 (d, 1H), 6.31 (m, 1H), 6.27 (m, 1H), 4.82 (t, 1H), 3.99 (t, 2H), 3.86 (m, 2H), 3.71 (m, 2H), 3.26 (m, 6H), 2.66 (m, 2H), 2.31 (m, 5H), 1.89 (m, 1H), 1.63 (m, 2H), 1.27 (m, 2H).</p><p num="0814"> Example 214 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (Cyclopropylmethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide Example 214A tert-Butyl 1- (cyclopropylmethyl) piperidine-4-ylcarbamate This Example compound was replaced with cyclopropanecarbaldehyde for 4'-chlorobiphenyl-2-carboxaldehide in Example 1A and tert-butylpiperazine-1-carboxylate with tert-butylpiperidine-4-ylcarbamate. Prepared.</p><p num="0815"> Example 214B 1- (Cyclopropylmethyl) Piperidine-4-Aminbis (2,2,2-Trifluoroacetate) This Example compound was prepared by substituting Example 1A of Example 1B with Example 214A.</p><p num="0816"> Example 214C 4- (1- (Cyclopropylmethyl) piperidine-4-ylamino) -3-nitrobenzene sulfonamide This Example compound was prepared by replacing 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with Example 214B.</p><p num="0817"> Example 214D 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (Cyclopropylmethyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 214C.¹1 H NMR (500MHz, Pyridine-d₅) δ 12.28 (s, 1H), 9.30 (d, 1H), 8.49 (d, 1H), 8.34 (dd, 1H), 8.18 (d, 1H), 7.52-7.56 (m, 2H), 7.41-7.46 ( m, 3H), 7.09 (dd, 1H), 7.06 (d, 2H), 6.91 (d, 1H), 6.73 (dd, 1H), 6.61 (d, 1H), 6.54 (d, 1H), 3.45-3.56 (m, 1H), 3.00-3.08 (m, 4H), 2.87 (d, 2H), 2.76 (s, 2H), 2.25 (t, 2H), 2.19 (d, 4H), 2.09-2.14 (m, 4H) ), 1.97 (s, 4H), 1.63-1.73 (m, 2H), 1.38 (t, 2H), 0.84-0.91 (m, 1H), 0.43-0.50 (m, 2H), 0.11 (q, H).</p><p num="0818"> Example 215 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide Example 215A 4- (4-Methylpiperazin-1-ylamino) -3- (trifluoromethylsulfonyl) benzenesulfonamide This Example compound was prepared by substituting (tetrahydropyran-4-yl) methaneamine in Example 1F with 4-methylpiperazin-1-amine and 4-fluoro-3-nitrobenzenesulfonamide in Example 159C.</p><p num="0819"> Example 215B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 215A and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.21 (br s, 1H), 8.09 (m, 1H), 7.98 (m, 1H), 7.83 (dd, 1H), 7.53 (d, 1H), 7.45 (d, 1H), 7.34 (d, 2H) ), 7.26 (t, 1H), 7.16 (d, 1H), 7.04 (d, 2H), 6.97 (t, 1H), 6.66 (dd, 1H), 6.39 (d, 1H), 6.24 (m, 2H) , 2.87 (m, 13H), 2.38 (s, 3H), 2.17 (m, 6H), 1.95 (s, 2H), 1.39 (t, 2H), 0.93 (s, 6H) Example 216 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (4,4,4-trifluorobutyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 210A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.13 (s, 1H), 10.89 (br s, 1H), 8.55 (d, 1H), 8.22 (d, 1H), 7.79 (dd, 1H), 7.50 (d, 1H), 7.34 (m, 4H) ), 7.07 (m, 4H), 6.83 (dd, 1H), 6.63 (dd, 1H), 6.37 (m, 1H), 6.15 (d, 1H), 3.71 (m, 1H), 3.01 (m, 4H) , 2.92 (m, 2H), 2.72 (s, 2H), 2.40 (m, 2H), 2.30 (m, 2H), 2.16 (m, 6H), 1.95 (m, 4H), 1.68 (m, 4H), 1.38 (t, 2H), 1.24 (br s, 1H), 0.92 (s, 6H).</p><p num="0820"> Example 217 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 177, replacing Example 26C and Example 1F with Example 175E and Example 174A, respectively.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.21 (s, 1H), 9.15 (s, 1H), 8.45 (d, 1H), 7.70 (dd, 1H), 7.43-7.56 (m, 5H), 7.34-7.41 (m, 1H), 7.24- 7.31 (m, 4H), 7.10-7.16 (m, 2H), 6.94 (t, 1H), 6.66 (dd, 1H), 6.37 (d, 1H), 6.24 (dd, 2H), 2.80-3.02 (m, 10H), 2.28-2.39 (m, 5H), 2.14-2.24 (m, 2H), 1.16 (d, 3H).</p><p num="0821"> Example 218 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 218A 2- (4-Chlorophenyl) -4,4-dimethylcyclohexa-1-encarbaldehyde This Example compound was prepared by substituting Example 143C of Example 143D with Example 18C.</p><p num="0822"> Example 218B tert-Butyl 4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) -3- (hydroxymethyl) piperazine-1-carboxylate This Example compound was prepared by replacing Example 27C of Example 1A with Example 218A and replacing tert-butyl piperazine-1-carboxylate with tert-butyl 3- (hydroxymethyl) piperazine-1-carboxylate. ..</p><p num="0823"> Example 218C (1-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-2-yl) methanol This Example compound was prepared by substituting Example 1A of Example 1B with Example 218B.</p><p num="0824"> Example 218D Ethyl 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) -3- (hydroxymethyl) piperazine -1-yl) benzoate This Example compound was prepared by substituting Example 20C of Example 20D with Example 218C and substituting Example 20A with Example 26A.</p><p num="0825"> Example 218E 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) -3- (hydroxymethyl) piperazine- 1-Indole) Benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 218D.</p><p num="0826"> Example 218F 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by replacing Example 26C of Example 177 with Example 218E and replacing Example 1F with Example 21A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.07 (s, 1H), 8.50 (d, 1H), 8.14 (d, 1H), 7.45 (d, J = 9.46Hz, 1H), 7.52 (d, 1H), 7.32-7.35 (m, 4H) , 6.99-7.05 (m, 4H), 6.78 (dd, 1H), 6.58-6.59 (m, 1H), 6.34 (s, 1H), 6.14 (d, 1H), 4.42-4.44 (m, 1H), 3.72 (br s, 1H), 3.10-3.25 (m, 6H), 3.00 (br, 2H), 2.58-2.69 (m, 6H), 1.82-2.01 (m, 6H), 1.70 (br, 2H), 1.36- 1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0827"> Example 219 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 218E and substituting Example 1F with Example 173C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.11 (s, 1H), 8.52 (d, 1H), 8.20 (d, 1H), 7.77 (dd, 1H), 7.52 (d, 1H), 7.32-7.38 (m, 4H), 7.03-7.07 ( m, 4H), 6.81 (dd ,, 1H), 6.58-6.60 (m, 1H), 6.36 (s, 1H), 6.14 (d, 1H), 4.44 (s, 1H), 3.92 (dd, 2H), 3.71 (br s, 1H), 3.41-3.43 (m, 2H), 3.02-3.06 (m, 4H), 2.55-2.72 (m, 6H), 2.18-2.24 (m, 2H), 1.91-2.00 (m, 8H), 1.76-1.80 (m, 2H), 1.63-1.65 (m, 2H), 1.49-1.51 (m, 2H), 1.35-1.38 (m, 2H), 0.92 (s, 6H).</p><p num="0828"> Example 220 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methylpiperazin-1-yl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 215A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 1H), 8.15 (d, 1H), 8.04 (s, 1H), 7.95 (dd, 1H), 7.50 (t, 2H), 7.35 (m, 4H), 7.12 (d, 1H) , 7.04 (d, 2H), 6.83 (dd, 1H), 6.61 (dd, 1H), 6.39 (m, 1H), 6.12 (d, 1H), 2.92 (m, 10H), 2.71 (s, 2H), 2.35 (s, 3H), 2.17 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0829"> Example 221 4- (4-{[4'-Chloro-4- (2-hydroxyethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 221A 2- (1H-indole-4-yloxy) -4-(4-((4- (2- (tert-butyldimethylsilyloxy) ethoxy) -4'-chlorobiphenyl-2-yl) methyl) piperazine-1 -Il) -N- (4- (1-methylpiperidin-4-ylamino) -3-nitrophenylsulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 213C and Example 1F with Example 21A.</p><p num="0830"> Example 221B 4- (4-{[4'-Chloro-4- (2-hydroxyethoxy) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-) Iloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 195B of Example 195 with Example 221A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.12 (s, 1H), 8.42 (d, 1H), 8.10 (d, 1H), 7.74 (dd, 1H), 7.58 (d, 1H), 7.40 (m, 4H), 7.21 (m, 1H) , 7.06 (m, 4H), 6.90 (m, 2H), 6.65 (m, 1H), 6.31 (d, 1H), 6.23 (m, 2H), 4.84 (t, 1H), 4.00 (t, 2H), 3.71 (m, 3H), 3.24 (m, 4H), 3.02 (m, 6H), 2.66 (m, 2H), 2.32 (m, 5H), 2.00 (m, 2H), 1.69 (m, 2H).</p><p num="0831"> Example 222 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[3- (3-oxopiperazine-1-yl) propyl] amino} phenyl) sulfonyl] benzamide Example 222A 3-Nitro-4- [3- (3-oxo-piperazin-1-yl) -propylamino] -benzenesulfonamide 4- (3-Amino-propyl) -piperazine-2-one (3.45 g) and triethylamine (5.18 mL, 3.76 g) were added to 1,4-dioxane (100 mL) and N, N-dimethylacetamide (20 mL). Mixed until dissolved. 4-Chloro-3-nitrobenzenesulfonamide (4.00 g) was added and the mixture was heated to 90 ° C for 16 hours. The mixture was cooled and the solvent was removed under vacuum. The material was recrystallized from 20% methanol in dichloromethane, followed by the recrystallized solid washed with 10% methanol in dichloromethane and then washed with 100% dichloromethane for purification.</p><p num="0832"> Example 222B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[3- (3-oxopiperazine-1-yl) propyl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 222A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.16 (br s, 1H), 8.85 (t, 1H), 8.58 (d, 1H), 7.79 (dd, 1H), 7.74 (br s, 1H), 7.51 (d, 1H), 7.43-7.37 ( m, 2H), 7.34 (d, 2H), 7.16 (d, 1H), 7.07-7.01 (m, 3H), 6.86 (dd, 1H), 6.65, (d, 1H), 6.39 (t, 1H), 6.15 (d, 1H), 3.43 (q, 2H), 3.17 (t, 2H), 3.03 (m, 4H), 2.95 (s, 2H), 2.72 (s, 2H), 2.56 (t, 2H), 2.47 (t, 2H), 2.16 (m, 6H), 1.95 (br s, 2H), 1.79 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0833"> Example 223 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(3-Nitro-4-{[3- (3-oxopiperazin-1-yl) propyl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 222A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.24 (br s, 1H), 8.83 (t, 1H), 8.50 (d, 1H), 7.75 (br s, 1H), 7.68 (dd, 1H), 7.53 (d, 1H), 7.34 (d, 2H), 7.28 (t, 1H), 7.18 (d, 1H), 7.04 (d, 2H), 7.02-6.94 (m, 2H), 6.71 (dd, 1H), 6.42 (d, 1H), 6.29-6.23 (m, 2H), 3.43 (q, 2H), 3.17 (m, 2H), 3.05 (m, 4H), 2.96 (s, 2H), 2.72 (s, 2H), 2.57 (t, 2H), 2.48 ( t, 2H), 2.17 (m, 6H), 1.95 (br s, 2H), 1.79 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0834"> Example 224 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 224A 2-Chloro-5-Hydroxycyclohexa-1-encarbaldehyde Phosphoryl oxychloride (4.08 mL) was added to cooled (-10 ° C) N, N-dimethylformamide (20 mL). The temperature was kept below 0 ° C. Stirring was continued for an additional 30 minutes, then 4- (tert-butyldimethylsilyloxy) cyclohexanone (10 g) was added. The mixture is then stirred at room temperature for 2 hours, followed by diluting it with ethyl acetate (300 mL), washing with water (3x), brine and Na.₂SO₄Dehydrated with. After filtration and concentration, the crude product was used directly in the next reaction without further purification.</p><p num="0835"> Example 224B 2- (4-Chlorophenyl) -5-hydroxycyclohexa-1-encarbaldehyde 4-Chlorophenylboronic acid (6.88 g), Example 224A (4.65 g), palladium (II) acetate (131 mg), K₂CO₃Water (200 mL) was added to the mixture of (18.24 g) and tetrabutylammonium bromide (14.18 g). The mixture is stirred at 50 ° C. for 4 hours, cooled, diluted with ethyl acetate (400 mL), washed with water (3x) and brine, Na₂SO₄Dehydrated with. After filtration and concentration, the residue was loaded onto a column and eluted with 5-20% ethyl acetate in hexanes to give the title compound.</p><p num="0836"> Example 224C Methyl 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -5-hydroxycyclohex-1-enyl) methyl) piperazine-1-yl) benzoate Sodium triacetoxyborohydride (1.2 g) was added to a mixture of Example 224B (0.8 g) and Example 150 A (1.2 g) in dichloromethane (20 mL). The mixture was stirred overnight. The mixture was diluted with ethyl acetate (200 mL) and washed with 2% NaOH, water and brine. Na₂SO₄After dehydration with, the solvent was evaporated under vacuum and the residue was loaded onto a column and eluted with 5-10% methanol in dichloromethane to give the title compound.</p><p num="0837"> Example 224D 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -5-hydroxycyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid LiOH · H in a mixture of Example 224C (1.78 g), methanol (10 mL) and water (10 mL) in tetrahydrofuran (30 mL)₂O (0.262 g) was added. The mixture was stirred overnight. The mixture was then neutralized with 5% aqueous HCl, extracted with ethyl acetate (3x), the combined organic layers washed with brine and Na.₂SO₄Dehydrated with. The solvent was evaporated to give the title compound.</p><p num="0838"> Example 224E 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 224D and substituting Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.08 (s, 1H), 8.50 (d, 1H), 8.13 (d, 1H), 7.77 (dd, 1H), 7.52 (d, 1H), 7.34 (m, 4H), 7.04 (m, 4H) , 6.78 (dd, 1H), 6.59 (dd, 1H), 6.35 (s, 1H), 6.13 (d, 1H), 4.59 (d, 1H), 3.74 (m, 2H), 3.39 (m, 1H), 3.03 (m, 7H), 2.68 (m, 3H), 2.41 (m, 4H), 2.17 (m, 7H), 2.00 (m, 3H), 1.71 (m, 3H).</p><p num="0839"> Example 225 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 224D and Example 1F with Example 173C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.07 (s, 1H), 8.47 (d, 1H), 8.14 (d, 1H), 7.92 (s, 1H), 7.72 (dd, 1H), 7.52 (d, 1H), 7.46 (d, 1H) , 7.33 (m, 4H), 7.07 (d, 2H), 6.98 (d, 1H), 6.77 (m, 1H), 6.58 (dd, 1H), 6.34 (s, 1H), 6.14 (d, 1H), 4.59 (m, 1H), 3.90 (dd, 2H), 3.70 (m, 1H), 3.01 (m, 8H), 2.71 (m, 6H), 2.56 (m, 8H), 2.19 (m, 4H), 1.94 (m, 3H), 1.56 (m, 3H).</p><p num="0840"> Example 226 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 224D and Example 1F with Example 174A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.13 (s, 1H), 9.13 (s, 1H), 8.52 (d, 1H), 7.83 (dd, 1H), 7.53 (t, 2H), 7.36 (m, 4H), 7.09 (m, 3H) , 6.83 (dd, 1H), 6.61 (dd, 1H), 6.38 (s, 1H), 6.12 (d, 1H), 4.59 (d, 1H), 3.75 (m, 1H), 2.81 (m, 12H), 2.27 (m, 12H), 1.79 (m, 4H).</p><p num="0841"> Example 227 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2,3-dihydro-1H-indene-2-yl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide Example 227A 4- (1-Indane-2-yl-piperidine-4-ylamino) -3-nitro-benzenesulfonamide 2-Aminoindane (12.84 g) and triethylamine (15.04 mL, 10.92 g) were added to 1,4-dioxane (150 mL) and the mixture was stirred until the solid dissolved. 4-Chloro-3-nitrobenzenesulfonamide (12.77 g) was added and the mixture was heated to 90 ° C for 16 hours. The mixture was cooled and the precipitate was evacuated, washed with 20% methanol in dichloromethane and washed with 100% dichloromethane.</p><p num="0842"> Example 227B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2,3-dihydro-1H-indene-2-yl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 227A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.20 (br s, 1H), 8.48 (d, 1H), 8.21 (d, 1H), 7.73 (dd, 1H), 7.54 (d, 1H), 7.34 (d, 2H), 7.26-7.21 (m) , 3H), 7.16-7.12 (m, 2H), 7.09-7.02 (m, 3H), 6.95 (t, 2H), 6.68 (dd, 1H), 6.39 (d, 1H), 6.24 (m, 2H), 3.74 (m, 1H), 3.18-2.80 (m, 13H), 2.72 (br s, 2H), 2.16 (m, 6H), 2.03 (m, 2H), 1.95 (br s, 2H), 1.68 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0843"> Example 228 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (2,3-dihydro-1H-indene-2-yl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 227A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.12 (br s, 1H), 8.55 (d, 1H), 8.23 (d, 1H), 7.79 (dd, 1H), 7.51 (d, 1H), 7.41-7.31 (m, 4H), 7.22 (m) , 2H), 7.16-7.09 (m, 3H), 7.07-7.01 (m, 3H), 6.83 (dd, 1H), 6.63 (dd, 1H), 6.37 (t, 1H), 6.15 (d, 1H), 3.73 (m, 1H), 3.16-2.82 (m, 13H), 2.71 (br s, 2H), 2.16 (m, 6H), 2.02 (m, 2H), 1.95 (br s, 2H), 1.67 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0844"> Example 229 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1-Morpholine-4-ylcyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidine-3-ol, hydrochloric acid with (1-morpholinocyclohexyl) methaneamine from Example 187B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.19 (s, 1H), 9.08 (s, 1H), 8.60 (d, 1H), 7.81 (dd, 1H), 7.51 (d, 1H), 7.43 (d, 1H), 7.39 (t, 1H) , 7.33 (d, 2H), 7.16-7.18 (m, 2H), 7.03 (d, 2H), 6.88 (dd, 1H), 6.65 (dd, 1H), 6.40 (s, 1H), 6.13 (d, 1H) ), 3.60 (s, 4H), 3.42-3.43 (m, 2H), 3.01 (br s, 4H), 2.72 (br s, 2H), 2.57 (br s, 4H), 2.12-2.16 (m, 7H) , 1.94 (br s, 2H), 1.46-1.60 (m, 12H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0845"> Example 230 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-2-ylmethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide Example 230A tert-Butyl 1- (thiazole-2-ylmethyl) piperidine-4-ylcarbamate This Example compound was prepared by substituting Example 27C of Example 1A with thiazole-2-carbaldehyde and tert-butylpiperazin-1-carboxylate with tert-butylpiperidine-4-ylcarbamate.</p><p num="0846"> Example 230B 1- (Thiazole-2-ylmethyl) Piperidine-4-amine This Example compound was prepared by substituting Example 1A of Example 1B with Example 230A.</p><p num="0847"> Example 230C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-2-ylmethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidin-3-ol, hydrochloric acid of Example 187B with Example 230B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 1H), 8.23 (d, 1H), 7.76-7.79 (m, 2H), 7.65 (s, 1H), 7.53 (d, 1H), 7.38-7.40 (m, 2H), 7.34 ( d, 2H), 7.17 (d, 1H), 7.11 (s, 1H), 7.04 (d, 2H), 6.82 (dd, 1H), 6.62 (d, 1H), 6.38 (s, 1H), 6.14 (d) , 1H), 4.19 (s, 2H), 3.01 (s, 4H), 2.91-2.96 (m, 2H), 2.72 (s, 2H), 2.12-2.17 (m, 6H), 1.95-1.99 (m, 4H) ), 1.47-1.51 (m, 2H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0848"> Example 231 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-4-ylmethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide Example 231A tert-Butyl 1- (thiazole-4-ylmethyl) piperidine-4-ylcarbamate This Example compound was prepared by substituting Example 27C of Example 1A with thiazole-4-carbaldehyde and tert-butylpiperazin-1-carboxylate with tert-butylpiperidine-4-ylcarbamate.</p><p num="0849"> Example 231B 1- (Thiazole-4-ylmethyl) piperidine-4-amine This Example compound was prepared by substituting Example 1A of Example 1B with Example 231A.</p><p num="0850"> Example 231C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[1- (1,3-thiazole-4-ylmethyl) piperidine-4-yl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidin-3-ol, hydrochloric acid of Example 187B with Example 231B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.11 (s, 1H), 9.06 (s, 1H), 8.21 (d, 1H), 7.98 (s, 1H), 7.77 (dd, 1H), 7.54 (d, 1H), 7.33-7.38 (m, 4H), 7.13 (d, 2H), 7.03-7.07 (m, 3H), 6.79 (dd, 1H), 6.60 (dd, 1H), 6.37 (s, 1H), 6.14 (d, 1H), 4.23 (s) , 2H), 2.99 (s, 4H), 2.89-2.94 (m, 2H), 2.71 (s, 2H), 2.12-2.17 (m, 6H), 1.95-1.99 (m, 4H), 1.47-1.51 (m) , 2H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0851"> Example 232 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[4 -(Hydroxymethyl) tetrahydro-2H-pyran-4-yl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide This Example compound was mixed with (3S, 4R) -4-amino-1-benzylpiperidine-3-ol of Example 187B and hydrochloric acid with (4- (aminomethyl) tetrahydro-2H-pyran-4-yl) methanol. Replaced and prepared.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 9.10 (t, 1H), 8.59 (d, 1H), 7.81 (dd, 1H), 7.51 (d, 1H), 7.42 (d, 1H), 7.39 (t, 1H) , 7.16-7.18 (m, 2H), 7.03 (d, 2H), 6.87 (dd, 1H), 6.65 (d, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 5.22 (t, 1H) ), 3.51-3.62 (m, 6H), 3.19 (d, 2H), 3.03 (s, 4H), 2.72 (s, 2H), 2.12-2.17 (m, 6H), 1.94 (s, 2H), 1.45- 1.49 (m, 4H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0852"> Example 233 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (2-Hydroxyethyl) piperazine-1-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide Example 233A 4- (4- (2-Hydroxyethyl) piperazine-1-ylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methaneamine in Example 1F with 2- (4-aminopiperazine-1-yl) ethanol.</p><p num="0853"> Example 233B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (2-Hydroxyethyl) piperazine-1-yl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 233A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.15 (s, 1H), 9.17 (m, 1H), 8.53 (d, 1H), 7.83 (dd, 1H), 7.56 (d, 1H), 7.51 (d, 1H), 7.36 (m, 4H) , 7.13 (m, 1H), 7.03 (m, 2H), 6.84 (dd, 1H), 6.62 (dd, 1H), 6.38 (m, 1H), 6.12 (m, 1H), 4.57 (m, 1H), 3.54 (m, 2H), 2.95 (m, 10H), 2.71 (s, 2H), 2.57 (m, 2H), 2.15 (m, 6H), 1.94 (s, 2H), 1.38 (t, 2H), 0.93 (s, 6H) Example 234 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(3S) -1-methylpyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 234A (S) -tert-Butyl 1-methylpyrrolidine-3-ylcarbamate A mixture of (S) -tert-butyl 1-methylpyrrolidin-3-ylcarbamate (438 mg) in methanol (10 mL), a 37% formaldehyde mixture in water (0.53 mL) and sodium borohydride (267 mg). Was added. The reaction mixture was stirred at room temperature overnight and then concentrated. Dissolve the residue in chloroform (15 mL), brine and LVDS₃Wash with solution and deli₄Dehydrated with, filtered and concentrated. The title compound was used in the next step without further purification.</p><p num="0854"> Example 234B (S) -1-Methylpyrrolidine-3-amine This Example compound was prepared by substituting Example 1A of Example 1B with Example 234A.</p><p num="0855"> Example 234C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(3S) -1-methylpyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with Example 234B and substituting 4-chloro-3-nitrobenzenesulfonamide with Example 310B. ..¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 10.98 (s, 1H), 8.38 (d, 1H), 8.16 (d, 1H), 7.64 (dd, 1H), 7.53 (d, 1H), 7.34 (d, 2H), 7.28 (m, 2H) , 7.05 (d, 2H), 6.89 (d, 1H), 6.72 (d, 1H), 6.68 (dd, 1H), 6.53 (dd, 1H), 6.29 (t, 1H), 6.15 (d, 1H), 4.14 (br s, 1H), 2.93 (m, 4H), 2.71 (m, 4H), 2.33 (m, 2H), 2.27 (s, 3H), 2.16 (m, 6H), 1.95 (s, 2H), 1.61 (m, 1H), 1.38 (t, 2H), 1.24 (br s, 1H), 0.92 (s, 6H).</p><p num="0856"> Example 235 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Fluoropropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-5-Iloxy) Benzamide Example 235A 4- (1- (3-Fluoropropyl) piperidine-4-ylamino) -3-nitrobenzene sulfonamide This Example compound was prepared by substituting 1,1,1-trifluoro-4-iodobutane of Example 210A with 1-fluoro-3-iodopropane.</p><p num="0857"> Example 235B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[1-yl] (3-Fluoropropyl) Piperidine-4-yl] Amino} -3-Nitrophenyl) Sulfonyl] -2- (1H-Indole-5-Iloxy) Benzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 235A and Example 1E with Example 26C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.12 (s, 1H), 10.89 (br s, 1H), 8.48 (d, 1H), 8.152 (d, 1H), 7.79 (dd, 1H), 7.50 (d, 1H), 7.34 (m, 4H) ), 7.03 (m, 4H), 6.83 (dd, 1H), 6.63 (dd, 1H), 6.37 (m, 1H), 6.15 (d, 1H), 3.71 (br s, 1H), 3.01 (m, 4H) ), 2.92 (m, 2H), 2.72 (m, 2H), 2.56 (m, 1H), 2.30 (m, 2H), 2.16 (m, 6H), 1.95 (m, 5H), 1.83 (m, 1H) , 1.68 (m, 2H), 1.38 (m, 2H), 1.24 (br s, 1H), 0.92 (s, 6H).</p><p num="0858"> Example 236 4- [4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- ( 1H-indole-5-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 218E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 2H), 8.62 (s, 1H), 8.58 (s, 1H), 7.78 (d, 1H), 7.52 (d, 1H), 7.39-7.42 (m, 2H), 7.33 (d, 1H), 7.14 (s, 1H), 7.09 (d, 1H), 7.04 (d, 1H), 6.86 (d, 1H), 6.62 (d, 1H), 6.39 (s, 1H), 6.14 (s, 1H) ), 4.46 (m, 1H), 3.85 (dd, 2H), 3.17-3.25 (m, 8H), 2.76 (br s, 2H), 2.58 (br s.2H), 1.89-2.01 (m, 6H), 1.80 (br, 2H), 1.29-1.38 (m, 2H), 0.91 (s, 6H).</p><p num="0859"> Example 237 N-[(4-{[(4-Aminotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- [4-{[2- (4-chlorophenyl)- 4,4-Dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- (1H-indole-5-yloxy) benzamide Example 237A 4-((4-Aminotetrahydro-2H-pyran-4-yl) methylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine in Example 1F with 4- (aminomethyl) tetrahydro-2H-pyran-4-amine.</p><p num="0860"> Example 237B N-[(4-{[(4-Aminotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- [4-{[2- (4-chlorophenyl)- 4,4-Dimethylcyclohex-1-en-1-yl] methyl} -3- (hydroxymethyl) piperazine-1-yl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 218E and Example 1F with Example 237A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.46 (s, 1H), 11.19 (s, 1H), 8.16 (d, 1H), 8.51-8.55 (m, 1H), 8.11 (s, 2H), 7.88 (d, 1H), 7.53 (d, 1H), 7.32-7.43 (m, 5H), 7.15 (s, 1H), 7.09 (d, 1H), 6.85 (dd, 1H), 6.68 (s, 1H), 6.40 (s, 1H), 6.21 (s) , 1H), 3.81-3.82 (m, 2H), 3.70-3.72 (m, 4H), 3.10 (br s, 2H), 2.02-2.09 (m, 2H), 1.60-1.85 (m, 2H), 1.66- 1.73 (m, 2H), 1.35-1.38 (m, 2H), 0.93 (s, 6H).</p><p num="0861"> Example 238 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) -Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidine-3-ol, hydrochloric acid with 1- (aminomethyl) cyclohexanol of Example 187B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 2H), 8.69 (t, 1H), 8.60 (d, 1H), 7.80 (dd ,, 1H), 7.51 (d, 1H), 7.39-7.43 (m, 2H), 7.33 (d , 2H), 7.17 (d, 2H), 7.14 (d, 1H), 7.03 (d, 2H), 6.87 (dd, 1H), 6.65 (d, 1H), 6.40 (s, 1H), 6.14 (d, 1H), 4.73 (s, 1H), 3.03 (s, 4H), 2.74 (s, 2H), 2.12-2.18 (m, 6H), 1.94 (s, 2H), 1.54-1.58 (m, 4H), 1.36 -1.43 (m, 7H), 0.92 (s, 6H).</p><p num="0862"> Example 239 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 179A and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.25 (s, 2H), 8.57 (m, 1H), 8.50 (d, 1H), 7.70 (dd, 1H), 7.52 (d, 1H), 7.34 (d, 2H), 7.28 (t, 1H) , 7.17 (d, 1H), 7.05 (m, 3H), 6.97 (t, 1H), 6.71 (dd, 1H), 6.42 (d, 1H), 6.26 (m, 2H), 3.58 (m, 4H), 3.31 (s, 3H), 3.05 (m, 4H), 2.73 (s, 2H), 2.17 (m, 6H), 1.96 (s, 2H), 1.38 (t, 2H), 0.93 (s, 6H) Example 240 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Hydroxymethyl) Tetrahydro-2H-pyran-4-yl] amino} -3-nitrophenyl) Sulfonyl] -2- (1H-indole-5-yloxy) benzamide Example 240A 4- (4- (Hydroxymethyl) tetrahydro-2H-pyran-4-ylamino) -3-nitrobenzene sulfonamide In this Example compound, the (tetrahydropyran-4-yl) methylamine of Example 1F was replaced with (4-aminotetrahydro-2H-pyran-4-yl) methanol, and 4-chloro-3-nitrobenzenesulfonamide was replaced with 4 Prepared by replacing with -fluoro-3-nitrobenzenesulfonamide.</p><p num="0863"> Example 240B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Hydroxymethyl) Tetrahydro-2H-pyran-4-yl] amino} -3-nitrophenyl) Sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 240A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 2H), 8.63 (d, 1H), 8.50 (s, 1H), 7.92 (s, 1H), 7.79 (dd, 1H), 7.52 (d, 1H), 7.39-7.43 (m, 2H), 7.33-7.34 (m, 3H), 7.18 (s, 1H), 7.03 (d, 2H), 6.87 (dd, 1H), 6.65 (dd, 1H), 6.40 (s, 1H), 6.13 (d) , 1H), 5.04 (t, 1H), 3.67-3.72 (m, 4H), 3.56 (t, 2H), 3.02 (s, 4H), 2.72 (br, 2H), 2.12-2.16 (m, 6H), 1.94-2.01 (m, 3H), 1.81-1.85 (m, 2H), 1.36-1.39 (m, 2H), 1.24 (m, 6H), 0.92 (s, 6H).</p><p num="0864"> Example 241 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[4-yl] (Hydroxymethyl) Tetrahydro-2H-pyran-4-yl] amino} -3-nitrophenyl) Sulfonyl] -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 240A and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.26 (s, 2H), 8.55 (d, J = 2.14Hz, 1H), 8.48 (s, 1H), 7.66 (dd, 1H), 7.54 (d, 1H), 7.34 (d, 2H), 7.27 -7.29 (m, 2H), 7.19 (d, 2H), 7.03 (d, 2H), 6.99 (t, 1H), 6.70 (dd, 1H), 6.44 (d, 1H), 6.27 (s, 1H), 5.04 (t, 1H), 3.67-3.72 (m, 4H), 3.56 (t, 2H), 3.04 (s, 4H), 2.74 (s, 2H), 2.12-2.17 (m, 6H), 1.95-2.01 ( m, 5H), 1.80-1.85 (m, 2H), 1.38 (t, 2H), 1.24 (m, 4H), 0.92 (s, 6H).</p><p num="0865"> Example 242 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Hydroxy-1-tetrahydro-2H-pyran-4-ylethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was mixed with (3S, 4R) -4-amino-1-benzylpiperidine-3-ol of Example 187B and hydrochloric acid with 2-amino-2- (tetrahydro-2H-pyran-4-yl) ethanol. Replaced and prepared.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.18 (s, 1H), 8.60 (d, 1H), 8.57 (d, 1H), 7.79 (dd, 1H), 7.52 (d, 1H), 7.43 (d, 1H), 7.40 (t, 1H) , 7.33 (d, 2H), 7.23 (d, 1H), 7.19 (d, 1H), 7.03 (d, 2H), 6.88 (dd, 1H), 6.65 (dd, 1H), 6.41 (s, 1H), 6.13 (d, 1H), 5.03 (t, 1H), 3.83-3.87 (m, 2H), 3.56-3.73 (m, 4H), 3.26 (t, 2H), 3.03 (s, 4H), 2.72 (s, 2H), 2.12-2.17 (br s, 4H), 1.58-1.62 (m, 2H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0866"> Example 243 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4-({1- [2- (1H-pyrazol-1-yl) ethyl] piperidine-4-yl} amino) phenyl] sulfonyl} benzamide Example 243A 4- (1- (2- (1H-Pyrazole-1-yl) ethyl) piperidine-4-ylamino) -3-nitrobenzene sulfonamide This Example compound was prepared by replacing 1,1,1-trifluoro-4-iodobutane of Example 210A with 1- (2-bromoethyl) -1H-pyrazole. After concentrating the reaction mixture, the ether slurry was filtered to collect the title compound.</p><p num="0867"> Example 243B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4-({1- [2- (1H-pyrazol-1-yl) ethyl] piperidine-4-yl} amino) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 243A and Example 1E with Example 26C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.25 (br s, 1H), 11.14 (s, 1H), 8.55 (d, 1H), 8.22 (d, 1H), 7.74 (m, 2H), 7.50 (d, 1H), 7.40 (m, 3H) ), 7.33 (d, 2H), 7.10 (m, 1H), 7.03 (d, 2H), 6.83 (dd, 1H), 6.63 (dd, 1H), 6.38 (t, 1H), 6.22 (t, 1H) , 6.15 (d, 1H), 4.24 (t, 2H), 3.65 (br s, 1H), 3.02 (m, 4H), 2.78 (m, 6H), 2.27 (m, 2H), 2.16 (m, 6H) , 1.94 (m, 3H), 1.60 (m, 2H), 1.38 (t, 2H), 1.23 (br s, 1H), 0.92 (s, 6H).</p><p num="0868"> Example 244 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.26 (s, 2H), 8.61 (t, 1H), 8.50 (d, 1H), 7.69 (dd, 1H), 7.28 (t, 1H), 7.18 (d, 2H), 7.07 (d, 1H) , 7.04 (d, 2H), 6.97 (t, 1H), 6.71 (dd, 1H), 6.43 (d, 1H), 6.28 (d, 1H), 6.26 (d, 1H), 5.04 (t, 1H), 3.85 (dd, 2H), 3.25-3.31 (m, 6H), 3.05 (s, 4H), 2.74 (s, 2H), 2.14-2.18 (m, 6H), 1.87-1.90 (m, 2H), 1.61- 1.63 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0869"> Example 245 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Methylamino) -3-nitrophenyl] sulfonyl} benzamide Example 245A 4- (Methylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by substituting (tetrahydro-2H-pyran-4-yl) methaneamine in Example 1F with methaneamine.</p><p num="0870"> Example 245B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Methylamino) -3-nitrophenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 245A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.12 (m, 2H), 8.54 (m, 2H), 7.76 (m, 1H), 7.51 (d, 1H), 7.35 (m, 4H), 7.06 (m, 3H), 6.85 (m, 2H) , 6.63 (d, 1H), 6.37 (m, 1H), 6.15 (d, 1H), 3.01 (m, 4H), 2.96 (d, 3H), 2.71 (s, 2H), 2.15 (m, 6H), 1.94 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H) Example 246 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Methylamino) -3-nitrophenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 245A and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.32 (br s, 1H), 11.20 (br s, 1H), 8.54 (br s, 1H), 8.46 (s, 1H), 7.70 (dd, 1H), 7.53 (d, 1H), 7.34 (d) , 2H), 7.26 (m, 1H), 7.14 (d, 1H), 7.04 (d, 2H), 6.94 (t, 1H), 6.87 (m, 1H), 6.67 (m, 1H), 6.37 (m, 1H), 6.25 (m, 2H), 3.02 (m, 4H), 2.97 (d, 3H), 2.72 (s, 2H), 2.16 (m, 6H), 1.94 (s, 2H), 1.38 (t, 2H) ), 0.93 (s, 6H).</p><p num="0871"> Example 247 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N-({{ 4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 175E and Example 1F with Example 7A.¹1 H NMR (500MHz, Pyridine-d₅) δ ppm 12.45 (s, 1H), 9.24 (d, 1H), 8.96 (t, 1H), 8.26 (dd, 1H), 8.16 (d, 1H), 7.65 (d, 1H), 7.46 (m, 5H) ), 7.35 (t, 1H), 7.30 (d, 2H), 7.24 (d, 1H), 7.15 (t, 1H), 6.86 (d, 1H), 6.79 (d, 1H), 6.74 (m, 2H) , 6.61 (d, 1H), 3.78 (t, 4H), 3.41 (q, 1H), 3.31 (m, 2H), 2.94 (m, 4H), 2.34 (m, 6H), 2.24 (m, 2H), 2.10 (m, 2H), 1.72 (m, 2H), 1.15 (d, 3H).</p><p num="0872"> Example 248 4- (4-{[2- (4-Chlorophenyl) -5-hydroxycyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 224D.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.60 (m, 1H), 7.80 (dd, 1H), 7.52 (d, 1H), 7.38 (m, 4H), 7.11 (m, 4H), 6.87 (dd, 1H) , 6.65 (dd, 1H), 6.40 (s, 1H), 6.13 (d, 1H), 4.59 (d, 1H), 3.85 (m, 2H), 3.28 (m, 6H), 3.03 (m, 2H), 2.72 (m, 2H), 2.18 (m, 3H), 1.87 (m, 3H), 1.53 (m, 5H), 1.26 (m, 7H).</p><p num="0873"> Example 249 4- (4-{[2- (4-chlorophenyl) -5-morpholin-4-ylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 249A 8-Chloro-1,4-dioxaspiro [4.5] Deca-7-en-7-carbaldehyde This Example compound was prepared by replacing 4- (tert-butyldimethylsilyloxy) cyclohexanone in Example 224A with 1,4-dioxaspiro [4.5] decane-8-one.</p><p num="0874"> Example 249B 8- (4-Chlorophenyl) -1,4-dioxaspiro [4.5] Deca-7-en-7-carbaldehyde This Example compound was prepared by substituting Example 224A of Example 224B with Example 249A.</p><p num="0875"> Example 249C Methyl 2- (1H-indole-5-yloxy) -4-(4-((8- (4-chlorophenyl) -1,4-dioxaspiro [4.5] deca-7-ene-7-yl) methyl) piperazine- 1-yl) benzoate This Example compound was prepared by substituting Example 224B of Example 224C with Example 249B.</p><p num="0876"> Example 249D 2- (1H-indole-5-yloxy) -4-(4-((8- (4-chlorophenyl) -1,4-dioxaspiro [4.5] deca-7-ene-7-yl) methyl) piperazine-1 -Il) Benzoic acid The title compound was prepared by substituting Example 224C of Example 224D with Example 249C.</p><p num="0877"> Example 249E 2- (1H-indole-5-yloxy) -4-(4-((8- (4-chlorophenyl) -1,4-dioxaspiro [4.5] deca-7-ene-7-yl) methyl) piperazine-1 -Il) -N- (3-Nitro-4-((Tetrahydro-2H-Pyran-4-yl) Methylamino) Phenylsulfonyl) Benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 249D.</p><p num="0878"> Example 249F 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -5-oxocyclohex-1-enyl) methyl) piperazine-1-yl) -N- (3) -Nitro-4-((Tet) Rahidoro -2H- pyran-4-yl) methylamino) phenyl sulfonyl) benzamide Acetone / H₂A mixture of Example 249E (20 mg) and pyridinium p-toluenesulfonate (16.8 mg) in O (1: 1, 3 mL) was heated to 135 ° C for 8 minutes under microwaves. The mixture is diluted with dichloromethane (100 mL), washed with water and brine, Na₂SO₄Dehydrated with. The product was obtained by filtering and evaporating the solvent.</p><p num="0879"> Example 249G 4- (4-{[2- (4-chlorophenyl) -5-morpholin-4-ylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Morpholine (37 mg) and 2-picoline borane complex (15.04 mg) were added to a mixture of Example 249F (120 mg) in dichloromethane (2 mL) and methanol (0.5 mL). The mixture was stirred overnight. The mixture is then diluted with dichloromethane (200 mL) and LVDS₃Wash with aqueous solution, water and brine, Na₂SO₄Dehydrated with. After evaporating the solvent, the residue was dissolved in dichloromethane and in dichloromethane 0-10% 7N NH in 5% methanol.₃The title compound was obtained by chromatography.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.15 (s, 1H), 8.58 (m, 2H), 7.79 (dd, 1H), 7.53 (m, 1H), 7.35 (m, 4H), 7.17 (m, 1H), 7.07 (m, 2H) , 6.85 (dd, 1H), 6.64 (dd, 1H), 6.39 (s, 1H), 6.13 (d, 1H), 3.84 (m, 2H), 3.58 (m, 5H), 3.01 (m, 5H), 2.63 (m, 6H), 2.10 (m, 14H), 1.61 (m, 3H), 1.26 (m, 3H).</p><p num="0880"> Example 250 N-[(4-{[(1-Aminocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa- 1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidin-3-ol, hydrochloric acid with 1- (aminomethyl) cyclohexaneamine, dihydrochloric acid from Example 187B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.04 (s, 1H), 8.47 (d, 1H), 8.39 (s, 1H), 7.79 (dd, 1H), 7.55 (d, 1H), 7.31-7.34 (m, 4H), 6.99-7.08 ( m, 4H), 6.73 (dd, 1H), 6.65 (dd, 1H), 6.33 (s, 1H), 6.12 (d, 1H), 3.55 (d, 2H), 2.94 (s, 4H), 2.71 (s , 2H), 2.14-2.17 (m, 6H), 1.95 (s, 2H), 1.50-1.64 (m, 8H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0881"> Example 251 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxopyrrolidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidine-3-ol, hydrochloric acid with 1- (2-aminoethyl) pyrrolidine-2-one of Example 187B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.58-8.60 (m, 2H), 7.84 (dd, 1H), 7.51 (d, 1H), 7.39-7.32 (m, 2H), 7.33 (d, 2H), 7.18 ( d, 1H), 7.12 (d, 1H), 7.03 (d, 2H), 6.87 (dd, 1H), 6.65 (dd, 1H), 6.40 (s, 1H), 6.17 (d, 1H), 3.53-3.56 (m, 2H), 3.45 (t, 2H), 3.39 (t, 2H), 3.04 (s, 4H), 2.74 (s, 2H), 2.11-2.18 (m, 8H), 1.94 (s, 2H), 1.83-1.90 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0882"> Example 252 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-5-yloxy) -N-({{ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 252A Methyl 2- (1H-indole-5-yloxy) -4-(4- (1- (4'-chlorobiphenyl-2-yl) ethyl) piperazine-1-yl) benzoate The title compound was prepared in the same manner as described in Example 175D, replacing ethyl 2- (1H-indole-4-yloxy) -4-fluorobenzoate with Example 26A.</p><p num="0883"> Example 252B 2- (1H-indole-5-yloxy) -4-(4- (1- (4'-chlorobiphenyl-2-yl) ethyl) piperazine-1-yl) benzoic acid The title compound was prepared in the same manner as described in Example 175E, replacing Example 175D with v252A.</p><p num="0884"> Example 252C 4- {4- [1- (4'-Chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-5-yloxy) -N-({{ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E with Example 252B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.20 (s, 1H), 11.16 (s, 1H), 8.62 (t, 1H), 8.58 (d, 1H), 7.79 (dd, 1H), 7.48-7.54 (m, 2H), 7.45 (d, 2H), 7.35-7.41 (m, 3H), 7.25-7.29 (m, 3H), 7.15 (d, 1H), 7.08-7.13 (m, 2H), 6.86 (dd, 1H), 6.63 (dd, 1H) , 6.38 (s, 1H), 6.13 (d, 1H), 3.85 (dd, 2H), 3.22-3.32 (m, 4H), 3.00 (s, 4H), 2.33 (s, 2H), 2.18 (s, 2H) ), 1.84-1.95 (m, 1H), 1.56-1.66 (m, 2H), 1.21-1.31 (m, 3H), 1.16 (d, 3H).</p><p num="0885"> Example 253 4- (4- {1- [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 253A 1-(2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) ethanol Methylmagnesium chloride (3M in tetrahydrofuran, 7.08 ml) was gradually added to the mixture of Example 218A (3.52 g) in tetrahydrofuran (30 ml) at -78 ° C. After the addition was complete, the reaction mixture was stirred at 0 ° C. for 30 minutes and ice water was added. The resulting mixture is extracted with dichloromethane and the organic layer is Na₂SO₄It was dehydrated and concentrated. The residue was purified by flash chromatography to elute 0-100% dichloromethane in hexanes to give the title compound.</p><p num="0886"> Example 253B 1-(2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) etanone Dess-Martin peryogenan (2.457 g) was added slowly to the mixture of Example 253A (1.18 g) in dichloromethane (20 ml). The reaction mixture was stirred at room temperature for 3 hours and diluted with ether. The resulting mixture was washed with aqueous NaOH solution and water. Organic layer Na₂SO₄It was dehydrated and concentrated. The residue was purified by flash chromatography with 0-100% dichloromethane in hexanes to give the title compound.</p><p num="0887"> Example 253C tert-Butyl 4- (1- (2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) ethyl) piperazine-1-carboxylate Example 253B (2.06 g) and tert-butylpiperazin-1-carboxylate (2.92 g) were treated with titanium (IV) isopropoxide (4.59 ml) at ambient temperature for 24 hours. Sodium cyanoborohydride (0.493 g) in methanol (10 ml) was added. The reaction mixture was stirred overnight and aqueous NaOH solution was added. The resulting mixture was diluted with ethyl acetate (300 ml). The precipitate was filtered off and washed with ethyl acetate. Separate the organic layer, wash with brine, Na₂SO₄Dehydrated with, filtered and concentrated. The residue was dissolved in dichloromethane, loaded onto a silica gel column and eluted with 0-25% ethyl acetate in dichloromethane to give the title compound.</p><p num="0888"> Example 253D 1-(1- (2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) ethyl) piperazine The title compound was prepared in the same manner as described in Example 175C, replacing Example 175B with Example 253C.</p><p num="0889"> Example 253E Ethyl 2- (1H-indole-5-yloxy) -4- (4- (1- (2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) ethyl) piperazine-1-yl) Benzoate The title compound was prepared as described in Example 175D, replacing ethyl 2- (1H-indole-4-yloxy) -4-fluorobenzoate and Example 175C with Example 26A and Example 253D, respectively. did.</p><p num="0890"> Example 253F 2- (1H-indole-5-yloxy) -4-(4- (1- (2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) ethyl) piperazine-1-yl) Benzoin acid The title compound was prepared in the same manner as described in Example 175E, replacing Example 175D with Example 253E.</p><p num="0891"> Example 253G 4- (4- {1- [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 177, replacing Example 26C with Example 253F.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.18 (s, 2H), 8.62 (t, 1H), 8.59 (d, 1H), 7.81 (dd, 1H), 7.52 (d, 1H), 7.38-7.44 (m, 2H), 7.34 (d, 2H), 7.17 (d, 1H), 7.11 (d, 1H), 7.01 (d, 2H), 6.87 (dd, 1H), 6.65 (dd, 1H), 6.40 (t, 1H), 6.13 (d, 1H) ), 3.85 (dd, 2H), 3.22-3.31 (m, 4H), 3.02 (s, 4H), 2.57-2.73 (m, 1H), 2.23 (s, 4H), 1.78-2.15 (m, 5H), 1.57-1.65 (m, 2H), 1.32-1.42 (m, 2H), 1.19-1.31 (m, 2H), 1.01 (d, 3H), 0.91 (d, 6H).</p><p num="0892"> Example 254 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(4-Methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 253F and Example 174A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.15 (s, 1H), 9.19 (s, 1H), 8.54 (d, 1H), 7.85 (dd, 1H), 7.57 (d, 1H), 7.52 (d, 1H), 7.37-7.41 (m, 2H), 7.34 (d, 2H), 7.14 (d, 1H), 7.01 (d, 2H), 6.84 (dd, 1H), 6.62 (dd, 1H), 6.39 (s, 1H), 6.12 (d, 1H) ), 2.81-3.04 (m, 10H), 2.58-2.67 (m, 1H), 2.29-2.45 (m, 5H), 2.15-2.28 (m, 4H), 1.92-2.13 (m, 3H), 1.82 (d) , 1H), 1.29-1.41 (m, 2H), 1.00 (d, 3H), 0.91 (d, 6H).</p><p num="0893"> Example 255 4- {4-[(1R) -1- (4'-chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide The title compound was obtained by separating the racemic mixture of Example 175F by chiral HPLC.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.31 (1H, s), 11.25 (1H, s), 8.62 (1H, t), 8.50 (1H, d), 7.68 (1H, dd), 7.53 (2H, d), 7.46 (2H, d) , 7.37 (1H, t), 7.24-7.31 (4H, m), 7.17 (1H, d), 7.12 (1H, dd), 7.07 (1H, d), 6.96 (1H, t), 6.69 (1H, dd) ), 6.42 (1H, d), 6.26 (2H, s), 3.85 (2H, dd), 3.21-3.33 (5H, m), 3.01 (4H, s), 2.29-2.39 (2H, m), 2.15 2.22 (2H, m), 1.83-1.94 (1H, m), 1.57-1.68 (2H, m), 1.22-1.31 (2H, m), 1.17 (3H, d).</p><p num="0894"> Example 256 4- {4- (1S) -1- (4'-chloro-1,1'-biphenyl-2-yl) ethyl] piperazine-1-yl} -2- (1H-indole-4-yloxy) -N -({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide The title compound was obtained by separating the racemic mixture of Example 175F by chiral HPLC.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.31 (1H, s), 11.25 (1H, s), 8.62 (1H, t), 8.50 (1H, d), 7.68 (1H, dd), 7.53 (2H, d), 7.46 (2H, d) , 7.37 (1H, t), 7.24-7.31 (4H, m), 7.17 (1H, d), 7.12 (1H, dd), 7.07 (1H, d), 6.96 (1H, t), 6.69 (1H, dd) ), 6.42 (1H, d), 6.26 (2H, s), 3.85 (2H, dd), 3.21-3.33 (5H, m), 3.01 (4H, s), 2.29-2.39 (2H, m), 2.15 2.22 (2H, m), 1.83-1.94 (1H, m), 1.57-1.68 (2H, m), 1.22-1.31 (2H, m), 1.17 (3H, d).</p><p num="0895"> Example 257 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({4-[(3-morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 253F and Example 7A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 8.79 (t, 1H), 8.57 (d, 1H), 7.80 (dd, 1H), 7.51 (d, 1H), 7.37-7.44 (m, 2H), 7.34 (d, 2H), 7.15 (d, 1H), 7.06 (d, 1H), 7.01 (d, 2H), 6.85 (dd, 1H), 6.63 (dd, 1H), 6.39 (s, 1H), 6.13 (d, 1H), 3.60 (t, 4H) ), 3.43 (q, 2H), 3.01 (s, 4H), 2.63 (d, 1H), 2.33-2.47 (m, 6H), 2.22 (d, 4H), 1.94-2.15 (m, 3H), 1.75- 1.86 (m, 3H), 1.32-1.40 (m, 2H), 1.00 (d, 3H), 0.91 (s, 3H), 0.90 (s, 3H).</p><p num="0896"> Example 258 4- (4- {1- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] ethyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 253F and Example 173C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.12 (s, 1H), 8.53 (d, 1H), 8.19 (d, 1H), 7.79 (dd, 1H), 7.52 (d, 1H), 7.32-7.40 (m, 4H), 6.99-7.12 ( m, 4H), 6.81 (dd, 1H), 6.60 (dd, 1H), 6.37 (s, 1H), 6.13 (d, 1H), 3.92 (dd, 2H), 3.72 (s, 1H), 3.26-3.31 (m, 2H), 2.98 (s, 6H), 2.77 (s, 1H), 2.54-2.66 (m, 3H), 2.15-2.30 (m, 4H), 1.94-2.14 (m, 5H), 1.73-1.87 (m, 3H), 1.57-1.68 (m, 2H), 1.44-1.54 (m, 2H), 1.31-1.40 (m, 2H), 1.00 (d, 3H), 0.91 (d, 2H).</p><p num="0897"> Example 259 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(cyclohexylmethylmethyl) ) Amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 259A 4- (Cyclohexylmethylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with cyclohexylmethylamine.</p><p num="0898"> Example 259B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(cyclohexylmethylmethyl) ) Amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 259A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.10 (s, 1H), 8.53 (m, 1H), 8.52 (d, 1H), 7.72 (dd, 1H), 7.44 (d, 1H), 7.32, (d, 1H), 7.31 (dd, 1H) ), 7.26 (d, 2H), 7.08 (d, 1H), 6.99 (d, 1H), 6.96 (d, 2H), 6.80 (dd, 1H), 6.58 (dd, 1H), 6.32 (s, 1H) , 6.07 (d, 1H), 3.18 (t, 2H), 2.96 (br m, 4H), 2.65 (d, 2H), 2.06 (br m, 6H), 1.87 (s, 2H), 1.63 (m, 4H) ), 1.56 (m, 2H), 1.30 (t, 2H), 1.11 (m, 2H), 0.91 (m, 3H), 0.85 (s, 6H).</p><p num="0899"> Example 260 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Morpholine-4-ylamino) -3-nitrophenyl] sulfonyl} benzamide Example 260A 4- (Morpholine Amino) -3-Nitrobenzene Sulfonamide This Example compound was prepared by substituting 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with morpholin-4-amine.</p><p num="0900"> Example 260B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Morpholine-4-ylamino) -3-nitrophenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 260A.¹1 H NMR (500MHz, Pyridine-d5) δ 9.28 (s, 1H), 9.25 (d, 1H), 8.39 (dd, 1H), 8.18 (d, 1H), 7.66 (d, 1H), 7.52-7.56 (m) , 2H), 7.40-7.46 (m, 3H), 7.09 (dd, 1H), 7.06 (d, 2H), 6.73 (dd, 1H), 6.60 (s, 1H), 6.54 (d, 1H), 3.87 ( s, 2H), 3.74 (d, 2H), 3.00-3.08 (m, 4H), 2.89 (d, 4H), 2.76 (s, 2H), 2.24 (t, 2H), 2.08-2.15 (m, 4H) , 1.97 (s, 2H), 1.38 (t, 2H), 0.93 (s, 6H).</p><p num="0901"> Example 261 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-3-ylmethyl) amino] phenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 26C and Example 180A, respectively.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 2H), 8.45-8.70 (m, 2H), 7.80 (dd, 1H), 7.51 (d, 1H), 7.38-7.42 (m, 2H), 7.33 (d, 2H), 7.16 ( d, 1H), 7.07 (d, 1H), 7.03 (d, 2H), 6.86 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 3.79 (dd) , 1H), 3.68-3.75 (m, 1H), 3.23-3.38 (m, 3H), 3.18 (dd, 1H), 3.03 (s, 4H), 2.72 (s, 2H), 2.07-2.21 (m, 6H) ), 1.79-1.96 (m, 4H), 1.57-1.64 (m, 1H), 1.41-1.51 (m, 1H), 1.37 (t, 2H), 1.22-1.33 (m, 1H), 0.92 (s, 6H) ).</p><p num="0902"> Example 262 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Morpholine-4-ylamino) -3-nitrophenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 260A.¹1 H NMR (500MHz, Pyridine-d5) δ 12.45 (s, 1H), 9.26 (s, 1H), 9.17 (d, 1H), 8.27 (dd, 1H), 8.17 (d, 1H), 7.61 (d, 1H) ), 7.48 (t, 1H), 7.45 (d, 2H), 7.39 (d, 1H), 7.05-7.13 (m, 3H), 6.71-6.81 (m, 3H), 6.67 (d, J = 2.1Hz, 1H), 3.87 (s, 2H), 3.61-3.78 (m, 2H), 2.99-3.08 (m, 4H), 2.89 (d, 4H), 2.76 (s, 2H), 2.25 (t, 2H), 2.08 -2.16 (m, 4H), 1.97 (s, 2H), 1.39 (t, 2H), 0.94 (s, 6H).</p><p num="0903"> Example 263 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylamino) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidine-3-ol, hydrochloric acid with tetrahydro-2H-pyran-4-amine, hydrochloric acid of Example 187B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.15 (s, 2H), 8.57 (d, 1H), 8.24 (d, 1H), 7.78 (dd, 1H), 7.49 (d, 1H), 7.37-7.40 (m, 3H), 7.32 (d, 2H), 7.12-7.16 (m, 2H), 7.22 (d, 2H), 6.84 (dd, 1H), 6.64 (dd, 1H), 6.37 (s, 1H), 6.13 (d, 1H), 3.85-3.87 (m, 2H), 3.45 (t, 2H), 3.02 (s, 4H), 2.71 (s, 2H), 2.11-2.16 (m, 7H), 1.87-1.93 (m 4H), 1.58-1.62 (m, 2H), 1.36 (t, 2H), 0.90 (s, 6H).</p><p num="0904"> Example 264 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(3-Methyloxetane-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by replacing (3S, 4R) -4-amino-1-benzylpiperidin-3-ol and hydrochloric acid with (3-methyloxetane-3-yl) methaneamine in Example 187B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 2H), 8.67 (t, 1H), 8.58 (d, 1H), 7.81 (dd, 1H), 7.49 (d, 1H), 7.36-7.39 (m, 2H), 7.32 (d, 2H), 7.12-7.14 (m, 2H), 7.02 (d, 2H), 6.84 (dd, 1H), 6.63 (dd, 1H), 6.37 (s, 1H), 6.13 (d, 1H), 4.44 (d) , 2H), 4.30 (d, 2H), 3.55 (d, 2H), 3.01 (s, 4H), 2.70 (s, 2H), 2.11-2.15 (m, 7H), 1.93 (s 3H), 1.36 (t) , 2H), 0.90 (s, 6H).</p><p num="0905"> Example 265 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methoxycyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by replacing (3S, 4R) -4-amino-1-benzylpiperidin-3-ol and hydrochloric acid of Example 187B with 4-methoxycyclohexaneamine.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 2H), 8.83 (d, 1H), 8.30 (d, 1H), 7.79 (dd, 1H), 7.50 (d, 1H), 7.37-7.41 (m, 2H), 7.33 (d, 2H), 7.10-7.14 (m, 2H), 7.03 (d, 2H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 3.24-3.25 (m, 5H), 3.03 (s, 4H), 2.72 (s, 2H), 2.14-2.17 (m, 8H), 1.92 (m 3H), 1.63-1.65 (m, 2H), 1.38 (t, 2H) , 0.92 (s, 6H).</p><p num="0906"> Example 266 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1,1-dioxide thiomorpholine-4-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was replaced with Example 187A for 4-chloro-3-nitrobenzenesulfonamide of Example 189A and 1- (2-methoxy-ethyl) -piperidine-4-ylamine replaced with 4- (3-aminopropyl). Prepared by replacing with thiomorpholine-1,1-dioxide.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 1H), 8.86 (t, 1H), 8.58 (d, 1H), 7.82 (dd, 1H), 7.50 (t, 1H), 7.40 (m, 2H), 7.33 (d, 2H) , 7.15 (m, 1H), 7.04 (m, 3H), 6.85 (dd, 1H), 6.64 (m, 1H), 6.38 (m, 1H), 6.13 (m, 1H), 3.43 (m, 2H), 3.12 (m, 4H), 3.01 (m, 4H), 2.89 (m, 4H), 2.72 (m, 2H), 2.57 (t, 2H), 2.16 (m, 6H), 1.94 (m, 2H), 1.78 (t, 2H), 1.37 (t, 2H), 0.93 (s, 6H).</p><p num="0907"> Example 267 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxopiperidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide This Example compound was replaced with Example 187A for 4-chloro-3-nitrobenzenesulfonamide of Example 189A and 1- (2-methoxy-ethyl) -piperidine-4-ylamine replaced with 1- (2-aminoethyl). Prepared by replacing with piperidine-2-one.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.12 (s, 1H), 8.61 (m, 1H), 8.52 (m, 1H), 7.78 (d, 1H), 7.51 (d, 1H), 7.37 (m, 2H), 7.33 (d, 2H) , 7.10 (m, 2H), 7.04 (d, 2H), 6.81 (m, 1H), 6.61 (d, 1H), 6.37 (s, 1H), 6.13 (d, 1H), 3.52 (m, 4H), 3.28 (t, 2H), 3.00 (m, 4H), 2.71 (m, 2H), 2.17 (m, 8H), 1.94 (m, 2H), 1.63 (m, 4H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0908"> Example 268 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (2-oxoimidazolidine-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide This Example compound was replaced with Example 187A for 4-chloro-3-nitrobenzenesulfonamide of Example 189A and 1- (2-methoxy-ethyl) -piperidine-4-ylamine replaced with 1- (2-aminoethyl). -2-Prepared by replacing with imidazolidone.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.60 (t, 1H), 8.56 (d, 1H), 7.81 (dd, 1H), 7.50 (m, 1H), 7.39 (m, 2H), 7.33 (d, 2H) , 7.15 (m, 1H), 7.08 (d, 1H), 7.02 (d, 2H), 6.85 (dd, 1H), 6.65 (m, 1H), 6.39 (m, 2H), 6.15 (m, 1H), 3.51 (m, 2H), 3.39 (t, 2H), 3.30 (m, 2H), 3.21 (t, 2H), 3.03 (m, 4H), 2.72 (m, 2H), 2.14 (m, 6H), 1.93 (m, 2H), 1.37 (t, 2H), 0.92 (s, 6H).</p><p num="0909"> Example 269 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(2-Pyridine-4-ylethyl) Amino] Phenyl} Sulfonyl) Benzamide 1- (2-Methoxyethyl) -piperidine-4-ylamine of Example 189A, except that this Example compound was purified by preparative HPLC using a Phenomenex Luna C8 (2) 5um 100Å AXIA column (30mmx75mm). Was replaced with 4- (2-aminoethyl) pyridine and 4-chloro-3-nitrobenzenesulfonamide was replaced with Example 187A. Using a gradient of 0.1% trifluoroacetic acid on acetonitrile and water at a flow rate of 50 mL / min (0-0.5 min 10% acetonitrile, 0.5-6.0 min linear gradient 10-100% acetonitrile, 6.0-7.0 min 100% acetonitrile, 7.0-8.0 min linear gradient 100-10% acetonitrile), the title compound was isolated as bistrifluoroacetate.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.45 (br s, 1H), 11.18 (br s, 1H), 8.77 (d, 2H), 8.61 (t, 1H), 8.60 (d, 1H), 7.86 (dd, 1H), 7.84 (d, 2H), 7.54 (d, 1H), 7.43-7.37 (m, 4H), 7.22 (d, 1H), 7.15 (d, 1H), 7.08 (d, 2H), 6.85 (dd, 1H), 6.70 (dd) , 1H), 6.38 (t, 1H), 6.22 (d, 1H), 3.77 (q, 2H), 3.68-3.54 (m, 4H), 3.27 (m, 2H), 3.16 (t, 2H), 3.00 ( m, 2H), 2.74 (m, 2H), 2.18 (m, 2H), 2.01 (d, 2H), 1.45 (t, 2H), 0.94 (s, 6H).</p><p num="0910"> Example 270 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-Morpholine-4-yl-3-nitrophenyl) sulfonyl] benzamide 20-100% CH of this Example compound by preparative HPLC using a crude material on a C18 column, 250 x 50 mm, 10 μ₃Substituting 4-chloro-3-nitrobenzenesulfonamide of Example 189A with Example 187A, except that the title compound was obtained as a trifluoroacetic acid salt by eluting into CN vs. water with a gradient of 0.1% trifluoroacetic acid, 1 It was prepared by replacing-(2-methoxy-ethyl) -piperidine-4-ylamine with morpholine. This salt is dissolved in dichloromethane (6 mL) and 50% LVDS₃Washed with aqueous solution. Anhydrous Na in the organic layer₂SO₄Dehydrated with, filtered and concentrated to give the title compound.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.31 (d, 1H), 7.87 (dd, 1H), 7.53 (d, 1H), 7.41 (m, 2H), 7.33 (d, 2H), 7.24 (d, 1H) , 7.16 (s, 1H), 7.02 (d, 2H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.40 (s, 1H), 6.14 (s, 1H), 3.69 (t, 4H), 3.13 (t, 4H), 3.03 (br s, 4H), 2.75 (s, 2H), 2.19 (br s, 4H), 2.14 (br t, 2H), 1.95 (s, 2H), 1.38 (t, 2H) ), 0.92 (s, 6H).</p><p num="0911"> Example 271 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (4-Methoxypiperidine-1-yl) -3-nitrophenyl] sulfonyl} benzamide 20-100% CH of this Example compound by preparative HPLC using a crude material on a C18 column, 250 x 50 mm, 10 μ₃The 4-chloro-3-nitrobenzene sulfonamide of Example 189A was replaced with Example 187A, except that the product was obtained as a trifluoroacetic acid salt by eluting into CN vs. water with a gradient of 0.1% trifluoroacetic acid. It was prepared by replacing 1- (2-methoxy-ethyl) -piperidine-4-ylamine with 4-methoxy-piperidine. This salt is dissolved in dichloromethane (6 mL) and 50% LVDS₃Washed with aqueous solution. Anhydrous Na in the organic layer₂SO₄Dehydrated with, filtered and concentrated to give the title compound.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.28 (d, 1H), 7.81 (dd, 1H), 7.53 (d, 1H), 7.41 (m, 2H), 7.33 (d, 2H), 7.22 (d, 1H) , 7.16 (s, 1H), 7.04 (d, 2H), 6.86 (dd, 1H), 6.64 (dd, 1H), 6.40 (s, 1H), 6.14 (s, 1H), 3.42 (m, 1H), 3.27 (s, 3H), 3.25 (m, 2H), 3.00 (m, 6H), 2.73 (s, 2H), 2.18 (br s, 4H), 2.13 (br t, 2H), 1.94 (s, 2H) , 1.91 (m, 2H), 1.56 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0912"> Example 272 4- (4-{[2- (4-chlorophenyl) -5-pyrrolidine-1-ylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by replacing the morpholine of Example 249G with pyrrolidine.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.04 (s, 1H), 8.44 (d, 1H), 8.42 (m, 1H), 7.70 (dd, 1H), 7.55 (d, 1H), 7.37 (d, 2H), 7.32 (m, 2H) , 7.09 (d, 2H), 7.00 (d, 1H), 6.89 (d, 1H), 6.76 (d, 1H), 6.54 (d, 1H), 6.32 (d, 1H), 6.13 (d, 1H), 3.83 (m, 3H), 3.06 (m, 15H), 2.23 (m, 6H), 1.84 (m, 6H), 1.62 (m, 4H), 1.24 (m, 3H).</p><p num="0913"> Example 273 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[2- (3-oxopiperazin-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide Example 273A 3-Nitro-4- [2- (3-oxo-piperazin-1-yl) -ethylamino] -benzenesulfonamide 4- (2-Amino-ethyl) -piperazine-2-one (5.51 g) and triethylamine (9.07 mL, 6.59 g) in 1,4-dioxane (100 mL), N, N-dimethylacetamide (20 mL) and water ( 10 mL) was added and mixed until dissolved. 4-Chloro-3-nitrobenzenesulfonamide (7.00 g) was added and the mixture was heated to 90 ° C for 16 hours. The mixture was cooled and the solvent was removed under vacuum. The crude material was recrystallized from 20% methanol in dichloromethane, followed by the recrystallized solid washed with 10% methanol in dichloromethane and then washed with 100% dichloromethane for purification.</p><p num="0914"> Example 273B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[2- (3-oxopiperazin-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 273A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.15 (br s, 1H), 8.73 (t, 1H), 8.58 (d, 1H), 7.82 (dd, 1H), 7.76 (br s, 1H), 7.51 (d, 1H), 7.42-7.38 ( m, 2H), 7.34 (d, 2H), 7.16 (d, 1H), 7.06-7.01 (m, 3H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.38 (t, 1H), 6.15 (d, 1H), 3.48 (q, 2H), 3.17 (m, 2H), 3.04 (m, 6H), 2.72 (br s, 2H), 2.70-2.62 (m, 2H), 2.16 (m, 8H) , 1.95 (br s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0915"> Example 274 4- [4-({4'-Chloro-4- [2- (dimethylamino) ethoxy] -1,1'-biphenyl-2-yl} methyl) piperazine-1-yl] -2- (1H-indole) -4-yloxy) -N-({4-[(4-methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by replacing Example 26C of Example 177 with Example 125D and replacing Example 1F with Example 174A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.62 (s, 1H), 11.33 (s, 1H), 9.55 (d, 1H), 8.49 (d, 1H), 7.74 (dd, 1H), 7.55 (m, 5H), 7.35 (m, 2H) , 7.30 (m, 1H), 7.19 (dd, 2H), 6.96 (m, 2H), 6.73 (dd, 1H), 6.40 (m, 1H), 6.33 (m, 1H), 6.24 (s, 1H), 4.37 (m, 2H), 3.53 (m, 8H), 3.30 (m, 8H), 3.23 (m, 4H), 2.90 (s, 6H), 2.84 (s, 3H).</p><p num="0916"> Example 275 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-Dioxide tetrahydrothien-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was replaced with Example 187A for 4-chloro-3-nitrobenzenesulfonamide of Example 189A and 1- (2-methoxy-ethyl) -piperidine-4-ylamine replaced with (1,1-dioxide tetrahydro). It was prepared by replacing with thiene-3-yl) methylamine.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.72 (t, 1H), 8.59 (d, 1H), 7.82 (dd, 1H), 7.51 (d, 1H), 7.40 (m, 2H), 7.33 (d, 2H) , 7.16 (m, 2H), 7.03 (d, 2H), 6.86 (dd, 1H), 6.65 (dd, 1H), 6.40 (m, 1H), 6.14 (d, 1H), 3.55 (t, 2H), 3.28 (m, 1H), 3.23 (m, 1H), 3.05 (m, 5H), 2.91 (m, 1H), 2.74 (m, 3H), 2.27 (m, 1H), 2.15 (m, 6H), 1.95 (m, 2H), 1.86 (m, 1H), 1.38 (t, 2H), 0.91 (s, 6H).</p><p num="0917"> Example 276 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 1-Dioxide tetrahydrothien-3-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was replaced with Example 187A for 4-chloro-3-nitrobenzenesulfonamide of Example 189A and 1- (2-methoxy-ethyl) -piperidine-4-ylamine replaced with 1,1-dioxide tetrahydrothien. Prepared by replacing with -3ylamine.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.20 (bs, 1H), 11.15 (s, 1H), 8.59 (d, 1H), 8.50 (d, 1H), 7.86 (dd, 1H), 7.50 (d, 1H), 7.39 (m, 2H) , 7.33 (d, 2H), 7.19 (d, 1H), 7.14 (m, 1H), 7.03 (d, 2H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.39 (m, 1H), 6.15 (d, 1H), 4.63 (m, 1H), 3.64 (m, 1H), 3.37 (m, 2H), 3.20 (m, 1H), 3.03 (m, 4H), 2.73 (m, 2H), 2.57 (m, 1H), 2.28 (m, 1H), 2.15 (m, 6H), 1.95 (m, 2H), 1.38 (t, 2H), 0.91 (s, 6H).</p><p num="0918"> Example 277 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3- (trifluoromethyl) phenyl] sulfonyl} benzamide Example 277A 4-((Tetrahydro-2H-pyran-4-yl) methylamino) -3- (trifluoromethyl) benzenesulfonamide 4-Fluoro-3- (trifluoromethyl) benzenesulfonamide (1.056 g), (tetrahydro-2H-pyran-4-yl) methaneamine (0.5 g) and N, N-diisopropyl in a solution of anhydrous dimethyl sulfoxide (15 mL) A mixture of ethylamine (1.68 g) was heated at 90 ° C overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water and brine, dehydrated with anhydrous sodium sulfate, filtered and concentrated to give the title compound.</p><p num="0919"> Example 277B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3- (trifluoromethyl) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 277A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.22 (s, 1H), 11.20 (s, 1H), 7.91 (d, 1H), 7.76 (dd, 1H), 7.55 (d, 1H), 7.41 (m, 4H), 7.20 (m, 1H) , 7.08 (d, 2H), 6.88 (m, 2H), 6.70 (dd, 1H), 6.58 (m, 1H), 6.42 (m, 1H), 6.19 (m, 1H), 3.83 (m, 2H), 3.56 (m, 4H), 3.25 (m, 4H), 3.15 (m, 2H), 2.99 (m, 2H), 2.74 (m, 2H), 2.18 (m, 2H), 2.02 (m, 2H), 1.84 (m, 1H), 1.57 (m, 2H), 1.44 (m, 2H), 1.19 (m, 2H), 0.93 (s, 6H).</p><p num="0920"> Example 278 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [2- ({4- [2- ( 1,3-Dioxolane-2-yl) ethyl] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide A mixture of Example 187A (0.079 g), dicyclohexyl (2', 6'-dimethoxybiphenyl-2-yl) phosphine (0.016 g) and palladium acetate (0.0045 g) in tetrahydrofuran (1 mL) was stirred at room temperature for 5 minutes. .. To this mixture was added (2- (1,3-dioxolane-2-yl) ethyl) zinc (II) bromide (0.6 mL). The reaction mixture was stirred overnight. The solvent was removed and the residue was purified by reverse phase preparative HPLC. The desired fractions were combined and the organic solvent was partially removed. Saturate the resulting mixture LVDS₃Treated with aqueous solution, extracted with ethyl acetate, DDL₄Dehydrated with, filtered and concentrated to give the title compound.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 1H), 8.37 (s, 1H), 8.00 (s, 1H), 7.55 (br s., 1H), 7.52 (d, 1H), 7.33-7.39 (m, 4H), 7.08 ( br s, 1H), 7.04 (d, 2H), 6.83 (dd, 1H), 6.62 (d, 1H), 6.38 (s, 1H), 6.15 (d, 1H), 4.85 (t, 1H), 3.87- 3.89 (m, 2H), 3.76-3.79 (m, 2H), 3.04 (s, 4H), 2.91-2.94 (m, 2H), 2.11-2.15 (m, 4H), 1.88-1.91 (s, 4H), 1.39 (t, 2H), 0.92 (s, 6H).</p><p num="0921"> Example 279 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide Example 279A 3-Nitro-4-((tetrahydro-2H-pyran-4-yl) methoxy) benzenesulfonamide (Tetrahydro-2H-pyran-4-yl) methanol (2.0 g) in tetrahydrofuran (20 mL) was treated with 60% NaH (1.377 g). The mixture was stirred at room temperature for 20 minutes. 4-Fluoro-3-nitrobenzenesulfonamide (2.84 g) was added in portions to this mixture. The reaction was stirred for an additional 2 hours. The mixture was poured into water, neutralized with 10% HCl and extracted 3 times with ethyl acetate. Wash the combined organic layer with brine and deli₄Dehydrated with, filtered and concentrated. The residue was purified by flash column chromatography on silica gel by eluting with 20% -60% ethyl acetate in hexanes.</p><p num="0922"> Example 279B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 279A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 1H), 8.38 (d, 1H), 8.05 (dd, 1H), 7.51 (d, 1H), 7.38-7.41 (m, 3H), 7.34 (d, 1H), 7.15 (d, 1H), 7.04 (d, 2H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.15 (d, 1H), 4.08 (d, 2H), 3.88 (dd, 2H) ), 3.04 (s, 4H), 2.77 (s, 2H), 2.12-2.22 (m, 4H), 1.95 (br s, 2H), 1.64 (dd, 2H), 1.36-1.39 (m, 2H), 0.92 (s, 6H).</p><p num="0923"> Example 280 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(3-Nitro-4-{[2- (3-oxopiperazin-1-yl) ethyl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 273A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.24 (br s, 1H), 8.72 (t, 1H), 8.51 (d, 1H), 7.76 (br s, 1H), 7.72 (dd, 1H), 7.53 (d, 1H), 7.34 (d, 2H), 7.28 (t, 1H), 7.18 (d, 1H), 7.04 (d, 2H), 6.97 (t, 2H), 6.70 (dd, 1H), 6.43 (d, 1H), 6.28-6.23 (m) , 2H), 3.48 (q, 2H), 3.17 (m, 2H), 3.04 (m, 6H), 2.70 (br s, 2H), 2.68-2.63 (m, 2H), 2.16 (m, 8H), 1.95 (br s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0924"> Example 281 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methyl-5-oxopyrrolidine-3-yl) amino] -3-nitrophenyl} sulfonyl) benzamide 20-100% CH of this Example compound by preparative HPLC using a crude product on a C18 column, 250 x 50 mm, 10 μ.₃4-Chloro-3-nitrobenzenesulfonamide of Example 189A was used in Example 187A, except that it was purified by eluting it in CN vs. water with a gradient of 0.1% trifluoroacetic acid to give the product as a trifluoroacetic acid salt. It was prepared by replacing 1- (2-methoxy-ethyl) -piperidine-4-ylamine with 4-amino-1-methylpyrrolidine-2-one hydrochloride. This salt is dissolved in dichloromethane (6 mL) and 50% LVDS₃Washed with aqueous solution. Anhydrous Na in the organic layer₂SO₄Dehydrated with, filtered and concentrated to give the title compound.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 1H), 8.56 (d, 1H), 8.34 (br d, 1H), 7.82 (dd, 1H), 7.53 (d, 1H), 7.39 (m, 2H), 7.33 (d, 2H) ), 7.11 (s, 1H), 7.04 (m, 3H), 6.83 (dd, 1H), 6.64 (dd, 1H), 6.38 (s, 1H), 6.15 (s, 1H), 4.45 (m, 1H) , 3.80 (dd, 1H), 3.35 (m, 1H), 3.02 (br s, 4H), 2.81 (dd, 1H), 2.75 (s, 3H), 2.71 (s, 2H), 2.40 (dd, 1H) , 2.15 (m, 6H), 1.94 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0925"> Example 282 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methyl-6-oxopiperidine-3-yl) amino] -3-nitrophenyl} sulfonyl) benzamide 20-100% CH of this Example compound by preparative HPLC using a crude product on a C18 column, 250 x 50 mm, 10 μ.₃4-Chloro-3-nitrobenzenesulfonamide of Example 189A was used in Example 187A, except that the product was obtained as a trifluoroacetic acid salt by eluting into CN vs. water with a gradient of 0.1% trifluoroacetic acid and purifying. It was prepared by replacing 1- (2-methoxy-ethyl) -piperidine-4-ylamine with 5-amino-1-methylpiperidine-2-one hydrochloride. This salt is dissolved in dichloromethane (6 mL) and 50% LVDS₃Washed with aqueous solution. Anhydrous Na in the organic layer₂SO₄Was dehydrated and concentrated to give the title compound.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 1H), 8.58 (d, 1H), 8.31 (br d, 1H), 7.85 (dd, 1H), 7.53 (d, 1H), 7.39 (m, 2H), 7.33 (d, 2H) ), 7.25 (d, 1H), 7.14 (s, 1H), 7.03 (d, 2H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.39 (s, 1H), 6.14 (s, 1H) , 4.22 (m, 1H), 3.57 (dd, 1H), 3.02 (br s, 4H), 2.84 (m, 1H), 2.83 (s, 3H), 2.72 (s, 2H), 2.36 (m, 2H) , 2.16 (m, 6H), 2.05 (m, 2H), 1.94 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0926"> Example 283 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (piperidine-1-ylamino) phenyl] sulfonyl} benzamide Example 283A 3-Nitro-4- (piperidine-1-ylamino) benzenesulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methaneamine in Example 1F with piperidine-1-amine.</p><p num="0927"> Example 283B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (piperidine-1-ylamino) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 283A and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.27 (brs, 1H), 11.33 (s, 1H), 9.14 (s, 1H), 8.48 (d, 1H), 7.66 (dd, 1H), 7.52 (t, 2H), 7.34 (d, 2H) , 7.29 (t, 1H), 7.19 (d, 1H), 7.04 (d, 2H), 6.97 (t, 1H), 6.71 (dd, 1H), 6.41 (d, 1H), 6.28 (m, 2H), 3.05 (m, 4H), 2.78 (m, 6H), 2.17 (m, 6H), 1.95 (s, 2H), 1.67 (m, 6H), 1.38 (t, 2H), 0.93 (s, 6H).</p><p num="0928"> Example 284 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (piperidine-1-ylamino) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 283A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.28 (s, 1H), 11.11 (s, 1H), 9.02 (s, 1H), 8.50 (s, 1H), 7.79 (dd, 1H), 7.52 (m, 2H), 7.35 (m, 4H) , 7.07 (m, 3H), 6.82 (m, 1H), 6.60 (m, 1H), 6.36 (m, 1H), 6.14 (m, 1H), 2.99 (m, 4H), 2.75 (m, 6H), 2.16 (m, 6H), 1.99 (m, 2H), 1.94 (m, 2H), 1.64 (m, 4H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0929"> Example 285 4- (4-{[4- (4-Chlorophenyl) -1-methyl-1H-pyrazole-5-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N- ({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 285A 4- (4-Chlorophenyl) -1-methyl-1H-pyrazole-5-carbaldehyde 4-Bromo-1-methyl-1H-pyrazole-5-carbaldehyde (0.500g), 4-chlorophenylboronic acid (0.455g), tetrabutylammonium bromide (0.853g), potassium carbonate (0.914g) and palladium acetate (0.914g) 0.030 g) was stirred together in 5 mL of water and heated to 45 ° C. After stirring for 2.5 hours, the reaction was diluted with ethyl acetate (75 mL), washed with water (25 mL) and brine (50 mL), dehydrated with magnesium sulfate, filtered and concentrated to give a crude substance. The solid was chromatographed on silica gel (SF40-80) and eluted over 30 minutes with a gradient of 5% to 25% ethyl acetate / hexane.</p><p num="0930"> Example 285B Methyl 2- (1H-indole-5-yloxy) -4-(4-((4- (4-chlorophenyl) -1-methyl-1H-pyrazole-5-yl) methyl) piperazine-1-yl) benzoate This Example compound was replaced with 4'-chlorobiphenyl-2 carboxaldehyde of Example 1A with Example 285A and tert-butylpiperazin-1-carboxylate was replaced with methyl 2- (1H-indole-5-yloxy)-. Prepared by replacing with 4- (piperazine-1-yl) benzoate.</p><p num="0931"> Example 285C 2- (1H-indole-5-yloxy) -4-(4-((4- (4-chlorophenyl) -1-methyl-1H-pyrazole-5-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 285B.</p><p num="0932"> Example 285D 2- (1H-indole-5-yloxy) -4-(4-((4- (4-chlorophenyl) -1-methyl-1H-pyrazole-5-yl) methyl) piperazine-1-yl) -N- (3-Nitro-4-((Tetrahydro-2H-pyran-4-yl) methylamino) Phenylsulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 285C.¹1 H NMR (300MHz, CDCL3) δ 10.30 (s, 1H), 8.85 (d, 1H), 8.50 (s, 1H), 8.30 (s, 1H), 8.12 (dd, 1H), 7.95 (d, 1H), 7.49 (s, 1H), 7.43 (d, 1H), 7.36-7.22 (m, 6H), 6.97 (dd, 1H), 6.87 (d, 1H), 6.53 (d, 2H), 6.08 (s, 1H) , 4.08-3.98 (m, 2H), 3.92 (s, 3H), 3.55 (s, 2H), 3.42 (s, 2H), 3.33-3.19 (m, 2H), 3.08 (s, 4H), 2.38 (s) , 4H), 1.98 (d, 1H), 1.72 (s, 2H), 1.52-1.33 (m, 2H).</p><p num="0933"> Example 286 4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Methyloxetane-3-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide Example 286A 4-((3-Methyloxetane-3-yl) methoxy) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methanol of Example 279A with (3-methyloxetane-3-yl) methanol.</p><p num="0934"> Example 286B 4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Methyloxetane-3-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 286A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.08 (s, 1H), 8.26 (d, 1H), 8.18 (d, 1H), 7.92 (m, 1H), 7.53 (m, 1H), 7.34 (m, 3H), 7.25 (m, 1H) , 7.04 (m, 3H), 6.91 (m, 1H), 6.76 (m, 1H), 6.59 (m, 1H), 6.35 (m, 1H), 6.15 (d, 1H), 4.47 (d, 1H), 4.29 (d, 1H), 3.40 (m, 2H), 3.13 (m, 2H), 2.98 (m, 4H), 2.72 (m, 2H), 2.16 (m, 6H), 1.94 (m, 2H), 1.36 (m, 5H), 0.93 (s, 6H).</p><p num="0935"> Example 287 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(1-oxide tetrahydro-2H-thiopyran-4-yl) methyl] amino} phenyl) sulfonyl] benzamide Example 287A 3-Nitro-4-((tetrahydro-2H-thiopyran-4-yl) methylamino) benzenesulfonamide This Example compound was prepared by substituting (tetrahydropyran-4-yl) methylamine of Example 1F with (tetrahydro-2H-thiopyran-4-yl) methaneamine, hydrochloride.</p><p num="0936"> Example 287B 3-Nitro-4-((1-oxide tetrahydro-2H-thiopyran-4-yl) methylamino) benzenesulfonamide Example 287A (150 mg) was suspended in methanol (5 mL). The reaction mixture was cooled to 0 ° C., then OXONE® (220 mg) in water (3 mL) was added. The reaction mixture was stirred at room temperature for 2 hours. Filter the precipitate and Na₂S₂O₃Washed with solution and water. The solid was dried overnight in a vacuum oven and used in the next step without further purification.</p><p num="0937"> Example 287C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(1-oxide tetrahydro-2H-thiopyran-4-yl) methyl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 287B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.69 (t, 1H), 8.58 (d, 1H), 7.81 (dd, 1H), 7.51 (d, 1H), 7.40 (m, 2H), 7.33 (d, 2H) , 7.15 (m, 2H), 7.03 (d, 2H), 6.86 (dd, 1H), 6.65 (dd, 1H), 6.40 (m, 1H), 6.13 (m, 1H), 3.38 (m, 4H), 3.05 (m, 6H), 2.73 (m, 2H), 2.11 (m, 8H), 1.95 (m, 3H), 1.67 (m, 2H), 1.38 (t, 2H), 0.90 (s, 6H).</p><p num="0938"> Example 288 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1,3-thiazole-5-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidine-3-ol, hydrochloric acid with thiazole-5-ylmethaneamine, hydrochloric acid of Example 187B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.18 (s, 2H), 9.13 (t, 1H), 8.99 (s, 1H), 8.60 (d, 1H), 7.95 (s, 1H), 7.82 (dd, 1H), 7.50 (d, 1H) , 7.39-7.42 (, 2H), 7.33 (d, 2H), 7.17 (d, 1H), 7.14 (d, 1H), 7.03 (d, 2H), 6.85 (dd, 1H), 6.64 (dd, 1H) , 6.40 (s, 1H), 6.13 (d, 1H), 4.91 (d, 2H), 3.03 (s, 4H), 2.73 (s, 2H), 2.12-2.18 (m, 6H), 1.94 (s, 2H) ), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0939"> Example 289 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 279A and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.25 (s, 1H), 8.21 (d, J = 2.14Hz, 1H), 7.95 (dd, 1H), 7.54 (d, 1H), 7.33-7.38 (m, 3H), 7.28 (t, 1H) , 7.17 (d, 1H), 7.04 (d, 2H), 6.97 (t, 1H), 6.70 (dd, 1H), 6.41 (d, 1H), 6.27-6.29 (m, 2H), 4.08 (d, 2H) ), 3.88 (dd, 2H), 3.07 (s, 4H), 2.80 (s, 2H), 2.24 (br s, 2H), 2.12-2.16 (m, 2H), 1.96 (s, 2H), 1.65 (dd) , 2H), 1.37-1.40 (m, 2H), 0.92 (s, 6H).</p><p num="0940"> Example 290 4- (4-{[2- (4-Chlorophenyl) -5,5-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 290A 2- (4-Chlorophenyl) -5,5-dimethylcyclohexa-1-encarbaldehyde The title compound was prepared in the same manner as described in Example 253B, replacing Example 253A with Example 19C.</p><p num="0941"> Example 290B tert-Butyl 4-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-carboxylate The title compound was prepared in the same manner as described in Example 1A, replacing Example 27C with Example 290A.</p><p num="0942"> Example 290C 1-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine The title compound was prepared in the same manner as described in Example 1B, replacing Example 1A with Example 290B.</p><p num="0943"> Example 290D Ethyl 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoate The title compound was prepared in the same manner as described in Example 20D, replacing Example 20A and Example 20C with Example 26A and Example 290C, respectively.</p><p num="0944"> Example 290E 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) benzoic acid The title compound was prepared in the same manner as described in Example 1E, replacing Example 1D with Example 290D.</p><p num="0945"> Example 290F 2- (1H-indole-5-yloxy) -4-(4-((2- (4-chlorophenyl) -5,5-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -N- (3-Nitro-4-((Tetrahydro-2H-Pyran-4-yl) Methylamino) Phenylsulfonyl) Benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E with Example 290E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 2H), 8.62 (t, 1H), 8.58 (d, 1H), 7.80 (dd, 1H), 7.51 (d, 1H), 7.38-7.43 (m, 2H), 7.33 (d, 2H), 7.16 (d, 1H), 7.10 (d, 1H), 7.07 (d, 3H), 6.86 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H) ), 3.85 (dd, 2H), 3.23-3.31 (m, 4H), 3.02 (s, 4H), 2.68 (s, 2H), 2.17 (d, 6H), 1.85-1.95 (m, 3H), 1.61 ( d, 2H), 1.39 (t, 2H), 1.20-1.30 (m, 2H), 0.92 (s, 6H).</p><p num="0946"> Example 291 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(2-tetrahydro-2H-pyran-4-ylethyl) amino] phenyl} sulfonyl) benzamide Example 291A 3-Nitro-4- (2- (tetrahydro-2H-pyran-4-yl) ethylamino) benzenesulfonamide The title compound was prepared in the same manner as described in Example 1F, replacing (tetrahydropyran-4-yl) methylamine with 2- (tetrahydro-2H-pyran-4-yl) ethaneamine.</p><p num="0947"> Example 291B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(2-tetrahydro-2H-pyran-4-ylethyl) amino] phenyl} sulfonyl) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 26C and Example 291A, respectively.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 2H), 8.57 (d, 1H), 8.53 (t, 1H), 7.80 (dd, 1H), 7.51 (d, 1H), 7.37-7.42 (m, 2H), 7.33 (d, 2H), 7.14 (d, 1H), 7.01-7.05 (m, 3H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 3.83 (dd) , 2H), 3.41 (q, 2H), 3.23-3.30 (m, 2H), 3.02 (s, 4H), 2.71 (s, 2H), 2.08-2.21 (m, 6H), 1.94 (s, 2H), 1.52-1.67 (m, 5H), 1.37 (t, 2H), 1.14-1.25 (m, 2H), 0.92 (s, 6H).</p><p num="0948"> Example 292 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(3-Nitro-4-{[2- (trifluoromethoxy) ethyl] amino} phenyl) sulfonyl] benzamide Example 292A 3-Nitro-4- (2- (trifluoromethoxy) ethylamino) benzenesulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methaneamine in Example 1F with piperidine-1-amine.</p><p num="0949"> Example 292B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) ) -N-[(3-Nitro-4-{[2- (trifluoromethoxy) ethyl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 292A and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.07 (s, 1H), 8.36 (m, 2H), 7.72 (dd, 1H), 7.58 (d, 1H), 7.34 (d, 2H), 7.19 (m, 1H), 7.05 (m, 3H) , 6.91 (m, 2H), 6.59 (d, 1H), 6.21 (m, 3H), 4.28 (t, 2H), 3.72 (q, 2H), 2.94 (m, 4H), 2.71 (s, 2H), 2.15 (m, 6H), 1.95 (s, 2H), 1.39 (t, 2H), 0.93 (s, 6H).</p><p num="0950"> Example 293 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[2- (2-Methoxyethoxy) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 293A 4- (2- (2-Methoxyethoxy) ethylamino) -3-nitrobenzene sulfonamide This Example compound was prepared by substituting the (tetrahydro-2H-pyran-4-yl) methaneamine of Example 1F with 2- (2-methoxyethoxy) ethaneamine.</p><p num="0951"> Example 293B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[2- (2-Methoxyethoxy) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by replacing Example 1F of Example 177 with Example 293A and replacing Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.28 (s, 1H), 11.23 (s, 1H), 8.59 (m, 1H), 8.50 (d, 1H), 7.70 (dd, 1H), 7.52 (d, 1H), 7.34 (d, 2H) , 7.28 (t, 1H), 7.17 (d, 1H), 7.05 (m, 3H), 6.96 (t, 1H), 6.71 (dd, 1H), 6.42 (d, 1H), 6.26 (m, 2H), 3.67 (t, 2H), 3.56 (m, 4H), 3.45 (m, 2H), 3.22 (s, 3H), 3.04 (m, 4H), 2.74 (s, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.93 (s, 6H).</p><p num="0952"> Example 294 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[3- (Methylsulfonyl) propyl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 294A 4- (3- (Methylthio) propylamino) -3-nitrobenzene sulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine in Example 1F with 3- (methylthio) propan-1-amine.</p><p num="0953"> Example 294B 4- (3- (Methylsulfonyl) propylamino) -3-nitrobenzenesulfonamide Example 294A (150 mg) was suspended in anhydrous dichloromethane (5 mL) and meta-chloroperoxybenzoic acid (848 mg) was added at 0 ° C. The reaction mixture was stirred at room temperature overnight. The turbid suspension was filtered. Solid Na₂S₂O₃Aqueous solution, saturated LVDS₃Washed with aqueous solution and water. The solid was dried and used in the next step without further purification.</p><p num="0954"> Example 294C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[3- (Methylsulfonyl) propyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and substituting Example 1F with Example 294B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.25 (m, 1H), 8.65 (t, 1H), 8.51 (d, 1H), 7.69 (dd, 1H), 7.52 (d, 1H), 7.34 (d, 2H), 7.28 (m, 1H) , 7.18 (m, 1H), 7.05 (m, 3H), 6.97 (m, 1H), 6.70 (dd, 1H), 6.42 (d, 1H), 6.26 (m, 2H), 3.55 (m, 2H), 3.23 (t, 2H), 3.05 (t, 4H), 2.98 (s, 3H), 2.76 (m, 2H), 2.18 (m, 6H), 2.02 (m, 2H), 1.96 (m, 2H), 1.38 (t, 2H), 0.93 (s, 6H).</p><p num="0955"> Example 295 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1,1-dioxide thiomorpholine-4-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide This Example compound was replaced with Example 337A for 4-chloro-3-nitrobenzenesulfonamide of Example 189A and 1- (2-methoxy-ethyl) -piperidine-4-ylamine replaced with 4- (3-aminopropyl). Prepared by replacing with thiomorpholine-1,1-dioxide.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.23 (s, 1H), 8.79 (s, 1H), 8.48 (d, 1H), 7.72 (dd, 1H), 7.54 (d, 1H), 7.34 (d, 2H), 7.26 (t, 1H) , 7.15 (d, 1H), 6.99 (m, 4H), 6.67 (dd, 1H), 6.40 (d, 1H), 6.24 (m, 2H), 3.42 (q, 2H), 3.11 (m, 4H), 3.01 (m, 4H), 2.90 (m, 4H), 2.72 (m, 2H), 2.56 (t, 2H), 2.16 (m, 6H), 1.95 (m, 2H), 1.78 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0956"> Example 296 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (2-tetrahydro-2H-pyran-4-ylethyl) phenyl] sulfonyl} benzamide Example 296A (2- (Tetrahydro-2H-pyran-4-yl) ethyl) Zinc (II) bromide The 25 mL round bottom flask was dried at 120 ° C. for 6 hours. Dry this N₂Cooled with a stream. The flask was charged with zinc (0.508 g). The flask was heated under high vacuum at 70 ° C. for 30 minutes. N₂After filling with iodine (0.033 g) and N, N-dimethylacetamide (5.2 mL), the resulting mixture was stirred until the red color of iodine faded. 4- (2-Bromoethyl) tetrahydro-2H-pyran (1.0 g) was then added to the mixture with a syringe. The reaction mixture was stirred at 70 ° C. for 12 hours. After cooling , the reaction mixture was used directly in the next step.</p><p num="0957"> Example 296B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (2-tetrahydro-2H-pyran-4-ylethyl) phenyl] sulfonyl} benzamide This Example compound was prepared by replacing the (2- (1,3-dioxolane-2-yl) ethyl) zinc (II) bromide of Example 278 with Example 296A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.15 (s, 2H), 8.38 (d, 1H), 8.01 (d, 1H), 7.57 (d, 1H), 7.51 (d, 1H), 7.38-7.40 (m, 2H), 7.34 (d, 2H), 7.12 (d, 1H), 7.04 (d, 2H), 6.82 (dd, 1H), 6.64 (dd, 1H), 6.38 (s, 1H), 6.16 (d, 1H), 3.83 (dd, 2H) ), 3.24-3.29 (m, 4H), 3.06 (s, 4H), 2.83-2.86 (m, 3H), 2.27 (br s, 2H), 2.12-2.14 (m, 4H), 1.96 (s, 2H) , 1.95 (s, 2H), 1.46-1.62 (m, 6H), 1.37-1.40 (m, 2H), 0.92 (s, 6H).</p><p num="0958"> Example 297 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4- (1,4) -Dioxane-2-ylmethoxy) -3-nitrophenyl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide Example 297A 4-((1,4-dioxane-2-yl) methoxy) -3-nitrobenzenesulfonamide Methanol (380 mg) in tetrahydrofuran (30 ml) was treated with sodium hydride (60%) (245 mg) at room temperature for 30 minutes. The reaction mixture was cooled in an ice bath and 4-fluoro-3-nitrobenzenesulfonamide (675 mg) was added. The resulting mixture was stirred at room temperature for 2 hours and additional sodium hydride (60%, 245 mg) was added. The reaction mixture was stirred overnight and quenched with ice water (3 ml). The turbid mixture was filtered and the filtrate was concentrated. The residue was mixed with methanol to give the title compound.</p><p num="0959"> Example 297B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4- (1,4) -Dioxane-2-ylmethoxy) -3-nitrophenyl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 26C and Example 297A, respectively.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 2H), 8.39 (d, 1H), 8.06 (dd, 1H), 7.51 (d, 1H), 7.38-7.43 (m, 3H), 7.34 (d, 2H), 7.15 (d, 1H), 7.04 (d, 2H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.39 (s, 1H), 6.15 (d, 1H), 4.20-4.28 (m, 2H), 3.85-3.91 (m, 1H), 3.82 (dd, 1H), 3.74-3.78 (m, 1H), 3.59-3.69 (m, 2H), 3.40-3.51 (m, 2H), 3.05 (s, 4H), 2.78 (s , 2H), 2.23 (s, 4H), 2.14 (s, 2H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0960"> Example 298 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[2- (2-Methoxyethoxy) ethyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 293A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 11.15 (s, 1H), 8.59 (m, 2H), 7.80 (dd, 1H), 7.50 (d, 1H), 7.36 (m, 4H), 7.15 (d, 1H) , 7.09 (d, 1H), 7.03 (d, 2H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.39 (m, 1H), 6.14 (d, 1H), 3.67 (t, 2H), 3.56 (m, 4H), 3.44 (m, 2H), 3.22 (s, 3H), 3.03 (m, 4H), 2.72 (s, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0961"> Example 299 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 1-Dioxide tetrahydrothien-3-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide This Example compound was replaced with the 4-chloro-3-nitrobenzenesulfonamide of Example 189A with Example 337A and 1- (2-methoxy-ethyl) -piperidine-4-ylamine replaced with 1,1-dioxide tetrahydrothien. Prepared by replacing with -3ylamine.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.35 (s, 1H), 11.23 (s, 1H), 8.49 (m, 2H), 7.78 (dd, 1H), 7.52 (d, 1H), 7.34 (d, 2H), 7.27 (m, 1H) , 7.16 (m, 2H), 7.04 (d, 1H), 6.97 (m, 1H), 6.70 (dd, 1H), 6.42 (d, 1H), 6.26 (m, 2H), 4.63 (m, 1H), 3.64 (dd, 1H), 3.37 (m, 2H), 3.20 (m, 1H), 3.05 (m, 4H), 2.74 (m, 2H), 2.58 (m, 1H), 2.28 (m, 1H), 2.16 (m, 6H), 1.95 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0962"> Example 300 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[2- (trifluoromethoxy) ethyl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 292A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (m, 2H), 8.64 (t, 1H), 8.59 (d, 1H), 7.84 (dd, 1H), 7.51 (d, 1H), 7.40 (m, 2H), 7.33 (d, 2H) , 7.16 (m, 2H), 7.04 (d, 2H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.39 (m, 1H), 6.14 (d, 1H), 4.31 (t, 2H), 3.78 (q, 2H), 3.04 (m, 4H), 2.74 (s, 2H), 2.17 (m, 6H), 1.94 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0963"> Example 301 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-Dioxide tetrahydro-2H-thiopyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide Example 301A 3-Nitro-4-((1-dioxide tetrahydro-2H-thiopyran-4-yl) methylamino) benzenesulfonamide This Example compound was prepared by substituting Example 294A of Example 294B with Example 287A.</p><p num="0964"> Example 301B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-Dioxide tetrahydro-2H-thiopyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 301A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.26 (s, 1H), 8.68 (t, 1H), 8.51 (d, 1H), 7.73 (dd, 1H), 7.53 (d, 1H), 7.34 (d, 2H), 7.29 (m, 1H) , 7.19 (d, 1H), 7.12 (d, 1H), 7.04 (d, 2H), 6.99 (m, 1H), 6.70 (dd, 1H), 6.46 (d, 1H), 6.26 (m, 2H), 3.38 (t, 2H), 3.09 (m, 8H), 2.75 (m, 2H), 2.16 (m, 6H), 2.07 (m, 2H), 1.95 (m, 3H), 1.70 (m, 2H), 1.38 (t, 2H), 0.91 (s, 6H).</p><p num="0965"> Example 302 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(2,,, 2-Difluoroethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 302A 4- (2,2-difluoroethylamino) -3-nitrobenzene sulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methaneamine in Example 1F with 2,2-difluoroethaneamine.</p><p num="0966"> Example 302B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(2,,, 2-Difluoroethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 302A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.22 (s, 1H), 11.05 (s, 1H), 8.46 (m, 2H), 7.76 (m, 1H), 7.53 (d, 1H), 7.33 (m, 4H), 7.05 (m, 4H) , 6.76 (m, 1H), 6.57 (d, 1H), 6.34 (m, 1H), 6.14 (m, 1H), 3.89 (m, 2H), 2.97 (m, 4H), 2.71 (s, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0967"> Example 303 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 163A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.28 (m, 1H), 8.13 (d, 1H), 7.78 (dd, 1H), 7.52 (d, 1H), 7.34 (d, 2H), 7.29 (m, 2H), 7.20 (d, 1H) , 7.01 (m, 4H), 6.70 (dd, 1H), 6.45 (d, 1H), 6.27 (m, 2H), 3.85 (dd, 2H), 3.26 (t, 4H), 3.05 (m, 4H), 2.75 (m, 2H), 2.16 (m, 6H), 1.95 (m, 2H), 1.84 (m, 1H), 1.55 (m, 2H), 1.38 (t, 2H), 1.23 (m, 2H), 0.92 (s, 6H).</p><p num="0968"> Example 304 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 163A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.46 (s, 1H), 11.20 (s, 1H), 9.23 (s, 1H), 8.19 (d, 1H), 7.90 (dd, 1H), 7.53 (d, 1H), 7.41 (m, 4H) , 7.33 (m, 1H), 7.17 (d, 1H), 6.86 (dd, 1H), 6.70 (dd, 1H), 6.41 (m, 1H), 6.21 (d, 1H), 3.84 (dd, 2H), 3.57 (m, 4H), 3.26 (m, 6H), 3.00 (m, 2H), 2.74 (s, 2H), 2.18 (s, 2H), 2.01 (s, 2H), 1.83 (m, 1H), 1.54 (m, 2H), 1.45 (t, 2H), 1.23 (m, 2H), 0.94 (s, 6H).</p><p num="0969"> Example 305 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(4,,, 4-Difluorocyclohexyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by replacing (3S, 4R) -4-amino-1-benzylpiperidine-3-ol, hydrochloric acid with 4,4-difluorocyclohexaneamine, hydrochloric acid of Example 187B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 2H), 8.59 (d, 1H), 8.25 (d, 1H), 7.84 (dd, 1H), 7.50 (d, 2H), 7.39-7.41 (m, 2H), 7.33 (d, 2H), 7.15-7.18 (m, 2H), 7.03 (d, 2H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 3.86 (d) , 1H), 3.04 (s, 4H), 2.74 (s, 2H), 1.95-2.18 (m, 14H), 1.69-1.73 (m, 2H), 1.38 (d, 2H), 0.92 (s, 6H).</p><p num="0970"> Example 306 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide Example 306A 1,6-Dioxaspiro [2.5] Octane-2-Carbonitrile A mixture of dihydro-2H-pyran-4 (3H) -one (10.0 g) and 2-chloroacetonitrile (7.55 g) in tert-butanol (10 mL) was sprinkled with 1.0 N potassium tert-butoxide (100 mL) for 20 minutes. Was dropped and processed. The reaction mixture was stirred at room temperature for 16 hours. This was diluted with water (10 mL) and 10% HCl (20 mL). The reaction mixture was concentrated to one-third of its original volume and extracted 4 times with diethyl ether. Wash the combined organic layer with brine and deli₄Dehydrated with, filtered and concentrated. The residue was purified by flash column chromatography using silica gel by eluting with 20-40% ethyl acetate in hexane to give the title compound.</p><p num="0971"> Example 306B 2- (4-Fluorotetrahydro-2H-pyran-4-yl) -2-hydroxyacetonitrile Example 306A (11.5 g) was dissolved in dichloromethane (40 mL) in a polypropylene bottle. The bottle was cooled to 0 ° C. 70% Hydrogen Fluoride-Pyridine (10.31 mL) was added slowly to this mixture. The mixture was warmed to room temperature over 3 hours and stirred for 24 hours. The reaction mixture is diluted with ethyl acetate (200 mL) and saturated with LVDS.₃It was poured into an aqueous solution. Additional solid LVDS₃Was used to carefully neutralize the mixture until foaming stopped. The organic layer was isolated and the aqueous layer was extracted 3 times with additional ethyl acetate (150 mL each). The combined organic layer was washed with 1% HCl, brine and dehydrated (DDL).₄), Filtered and concentrated to obtain the desired compound. This was used directly in the next reaction.</p><p num="0972"> Example 306C (4-Fluorotetrahydro-2H-pyran-4-yl) methanol Example 306B (11.78 g) in 2-propanol (150 mL) and water (37.5 mL) was cooled to 0 ° C. Sodium borohydride (4.2 g) was added to this mixture. The mixture was stirred and warmed to room temperature over 3 hours. The reaction was quenched with acetone and stirred for an additional hour. The clear liquid was decanted and separated from the solid. Solids were washed and decanted with additional ethyl acetate. The combined organic solutions were concentrated. The residue was purified by flash column chromatography using silica gel by eluting with 20-40% ethyl acetate in hexane to give the title compound.</p><p num="0973"> Example 306D 4-((4-Fluorotetrahydro-2H-pyran-4-yl) methoxy) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methanol of Example 279A with Example 306C.</p><p num="0974"> Example 306E 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 306D and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.24 (s, 1H), 8.28 (d, 1H), 7.98 (dd, 1H), 7.54 (d, 1H), 7.42 (d, 1H), 7.34 (d, 2H), 7.28 (t, 1H) , 7.17 (d, 1H), 7.04 (d, 2H), 6.97 (t, 1H), 6.70 (dd, 1H), 6.41 (d, 1H), 6.26-6.28 (m, 2H), 4.38 (d, 2H) ), 3.76-3.80 (m, 2H), 3.57-3.62 (m, 2H), 3.06 (s, 4H), 2.80 (s, 2H), 2.24 (br s, 2H), 2.15-2.25 (m, 2H) , 1.96 (s, 2H), 1.82-1.89 (m, 4H), 1.39 (t, 2H), 0.93 (s, 6H).</p><p num="0975"> Example 307 4- (4-{[4- (4-Chlorophenyl) -1-isopropyl-6-oxo-1,6-dihydropyridine-3-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 307A 4- (4-Chlorophenyl) -2-fluoro-5-methylpyridine 2-Fluoro-4-iodo-5-methylpyridine (1.9 g), 4-chlorophenylboronic acid (1.504 g), tetrakis (triphenylphosphine) in ethanol (20 mL), water (10 mL) and toluene (10 mL) A mixture of palladium (0) (0.463 g) and sodium carbonate (2.55 g) was heated under reflux for 6 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated and the aqueous layer was extracted 3 times with additional ethyl acetate. Wash the combined organic layer with brine and deli₄Dehydrated with, filtered and concentrated. The residue was purified by flash column chromatography on silica gel with 5% ethyl acetate in hexanes to give the title compound.</p><p num="0976"> Example 307B 5- (Bromomethyl) -4- (4-chlorophenyl) -2-fluoropyridine CCl₄A mixture of Example 307A (1.2 g), N-Bromosuccinimide (1.06 g) and AIBN (azobisisobutyronitrile) (0.178 g) in (30 mL) was heated under reflux for 6 hours. After cooling, the solid was filtered off. The filtrate was concentrated, loaded onto a silica gel column and eluted with 3% ethyl acetate in hexanes to give the title compound.</p><p num="0977"> Example 307C tert-Butyl 4-((4- (4-chlorophenyl) -6-fluoropyridin-3-yl) methyl) piperazine-1-carboxylate A mixture of Example 307B (1.24 g), tert-butylpiperazin-1-carboxylate (0.768 g) and potassium carbonate (0.570) in N, N-dimethylformamide (20 mL) was stirred at room temperature for 2 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated and the aqueous layer was extracted 3 times with additional ethyl acetate. Wash the combined organic layer with brine and deli₄Dehydrated with, filtered and concentrated. The residue was purified by flash column chromatography on silica gel with 10% ethyl acetate in hexanes to give the title compound.</p><p num="0978"> Example 307D tert-Butyl 4-((4- (4-chlorophenyl) -6-oxo-1,6-dihydropyridine-3-yl) methyl) piperazine-1-carboxylate A mixture of Example 307C (1.6g) and 5% HCl (20mL) in tetrahydrofuran (20mL) was heated at 80 ° C. overnight. The solvent was removed and dried. The solid was redissolved and added to tetrahydrofuran (50 mL). To this mixture, BOC₂O (di-t-butyl-dicarbonate) (1.118 g), triethylamine (0.72 mL) and 4-dimethylaminopyridine (1.4 g) were added. The solvent was removed and the residue was partitioned between water and ethyl acetate. The reaction mixture was stirred overnight. Dehydrate the organic layer (DDL₄), Filtered and concentrated. The residue was purified by preparative HPLC in water containing 20-100% acetonitrile / 0.1% trifluoroacetic acid to give the title compound.</p><p num="0979"> Example 307E tert-Butyl 4-((4- (4-chlorophenyl) -1-isopropyl-6-oxo-1,6-dihydropyridine-3-yl) methyl) piperazine-1-carboxylate Example 307D (0.404 g) in N, N-dimethylformamide (5 mL) was treated with 60% sodium hydride (0.24 g) at room temperature. 2-Iodine propane (0.204 g) was added to this mixture. The mixture was stirred overnight. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated and the aqueous layer was extracted 3 times with additional ethyl acetate. Wash the combined organic layer with brine and deli₄Dehydrated with, filtered and concentrated. The residue was purified by flash column chromatography on silica gel with 10% ethyl acetate in hexanes to give Example 307E and Example 307F.</p><p num="0980"> Example 307F tert-Butyl 4-((4- (4-chlorophenyl) -6-isopropoxypyridin-3-yl) methyl) piperazine-1-carboxylate This compound was isolated as a by-product during the preparation of Example 307E.</p><p num="0981"> Example 307G 4- (4-Chlorophenyl) -1-isopropyl-5- (piperazine-1-ylmethyl) pyridin-2 (1H) -one This Example compound was prepared by substituting Example 1A of Example 1B with Example 307E.</p><p num="0982"> Example 307H Ethyl 2- (1H-indole-5-yloxy) -4-(4-((4- (4-chlorophenyl) -1-isopropyl-6-oxo-1,6-dihydropyridine-3-yl) methyl) piperazine- 1-yl) benzoate This Example compound was prepared by substituting Example 20C of Example 20D with Example 307G and substituting Example 20A with Example 26A.</p><p num="0983"> Example 307I 2- (1H-indole-5-yloxy) -4-(4-((4- (4-chlorophenyl) -1-isopropyl-6-oxo-1,6-dihydropyridine-3-yl) methyl) piperazine-1 -Il) Benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 307H.</p><p num="0984"> Example 307J 4- (4-{[4- (4-Chlorophenyl) -1-isopropyl-6-oxo-1,6-dihydropyridine-3-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 307I.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.07 (s, 1H), 8.62 (t, 1H), 8.59 (d, 1H), 7.79 (dd, 1H), 7.59 (s, 1H), 7.52-7.53 (m, J 3H), 7.38-7.45 (m, 4H), 7.15 (d, 1H), 7.10 (d, 1H), 6.87 (dd, 1H), 6.68 (dd, 1H), 6.39 (s, 1H), 6.22 (s, 1H), 6.17 ( d, 1H), 5.01-5.06 (m, 1H), 3.85 (dd, 2H), 3.24-3.31 (m, 6H), 3.09 (s, 2H), 3.00 (s, 4H), 2.26 (m, 4H) , 2.09 (m, 2H), 1.60-1.63 (m, 2H), 1.30 (d, 6H).</p><p num="0985"> Example 308 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(Tetrahydro-2H-pyran-4-ylmethyl) amino] carbonyl} phenyl) sulfonyl] benzamide Example 308A 4-Sulfamoyl-N-((tetrahydro-2H-pyran-4-yl) methyl) benzamide 4-Sulfamoylbenzoic acid (201 mg), (tetrahydro-2H-pyran-4-yl) methaneamine (144 mg), 1-hydroxybenzotriazole hydrate (230 mg) and 1-ethyl-3- [3- (dimethylamino)) Propyl] -carbodiimide hydrochloride (288 mg) was combined in acetonitrile. The mixture was stirred at room temperature overnight. The solid was filtered off and the reaction mixture was concentrated. The crude material was purified by flash chromatography by eluting from 2% methanol / dichloromethane with a gradient of 10% methanol / dichloromethane.</p><p num="0986"> Example 308B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(Tetrahydro-2H-pyran-4-ylmethyl) amino] carbonyl} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 308A and Example 1E with Example 26C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.19 (s, 1H), 8.57 (t, 1H), 7.94 (m, 4H), 7.48 (d, 1H), 7.43 (d, 1H), 7.40 (t, 1H), 7.33 (d, 2H) , 7.21 (d, 1H), 7.03 (d, 2H), 6.88 (dd, 1H), 6.63 (dd, 1H), 6.42 (t, 1H), 6.13 (d, 1H), 3.84 (dd, 2H), 3.26 (m, 2H), 3.16 (t, 2H), 3.03 (br s, 4H), 2.74 (br s, 2H), 2.15 (m, 6H), 1.95 (s, 2H), 1.79 (m, 1H) , 1.59 (d, 2H), 1.38 (t, 2H), 1.19 (m, 2H), 0.92 (s, 6H).</p><p num="0987"> Example 309 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide Example 309A 4- (2-Methoxyethylamino) -3- (trifluoromethylsulfonyl) benzenesulfonamide This Example compound was prepared by replacing 4-fluoro-3-nitrobenzenesulfonamide of Example 1F with Example 159C and replacing (tetrahydropyran-4-yl) methylamine with 2-methoxyethylamine.</p><p num="0988"> Example 309B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 309A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.26 (s, 1H), 8.13 (d, 1H), 7.79 (dd, 1H), 7.51 (d, 1H), 7.34 (d, 2H), 7.29 (t, 1H), 7.24 (m, 1H) , 7.19 (d, 1H), 7.04 (d, 2H), 6.99 (m, 3H), 6.70 (dd, 1H), 6.44 (d ,, 1H), 6.27 (m, 2H), 3.52 (m, 4H) , 3.28 (s, 3H), 3.05 (m, 4H), 2.75 (s, 2H), 2.17 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="0989"> Example 310 Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[ (4-Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide Example 310A 4- (Aminomethyl) cyclohexanol The title compound was prepared in the same manner as described in Example 311A, replacing (4-methoxyphenyl) methaneamine with (4-hydroxyphenyl) methaneamine.</p><p num="0990"> Example 310B 2- (1H-indole-5-yloxy) -N- (4-chloro-3-nitrophenylsulfonyl) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohexa-1) -Enyl) Methyl) Piperazine-1-yl) Benzamide The title compound was prepared in the same manner as described in Example 1G, replacing Example 1E and Example 1F with Example 26C and 4-chloro-3-nitrobenzenesulfonamide.</p><p num="0991"> Example 310C Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[ (4-Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide A mixture of Example 310B (100 mg), triethylamine (0.2 ml) and Example 310A (35 mg) in dioxane (5 ml) was heated at 100 ° C. for 20 hours and concentrated. The residue was purified by RP-HPLC (10-70% acetonitrile in 0.1% trifluoroacetic acid water / 70 minutes) to give the title compound as trifluoroacetate.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.40 (s, 1H), 11.18 (s, 1H), 9.20 (s, 1H), 8.60 (t, 1H), 8.58 (d, 1H), 7.77 (dd, 1H), 7.54 (d, 1H) , 7.42 (s, 1H), 7.37-7.41 (m, 3H), 7.14 (d, 1H), 7.04-7.09 (m, 3H), 6.86 (dd, 1H), 6.69 (dd, 1H), 6.39 (s) , 1H), 6.21 (s, 1H), 3.50-3.68 (m, 3H), 3.20-3.27 (m, 3H), 2.93-3.07 (m, 2H), 2.66-2.82 (m, 2H), 2.13-2.22 (m, 2H), 2.01 (s, 2H), 1.83 (d, 2H), 1.67-1.77 (m, 3H), 1.50-1.60 (m, 1H), 1.44 (s, 2H), 0.96-1.17 (m) , 4H), 0.94 (s, 6H).</p><p num="0992"> Example 311 Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 311A (4-Methoxycyclohexyl) methaneamine 5% dry Rh-Al of (4-methoxyphenyl) methaneamine (1 g) in ethanol (10 ml)₂O₃At (0.5g), H₂Under (500 psi), treatment was performed at 60 ° C for 6 hours and then at 125 ° C for 26 hours. The insoluble material was filtered off and the filtrate was concentrated to give the title compound.</p><p num="0993"> Example 311B 4-(((Trans-4-methoxycyclohexyl) methylamino) -3-nitrobenzenesulfonamide 4-Fluoro-3-nitrobenzenesulfonamide (15 g) in tetrahydrofuran (200 ml) and Example 311A (11.71 g) were treated overnight with triethylamine (28.5 ml). The reaction was concentrated, the residue was loaded onto a C18 column and eluted with 40-55% acetonitrile in water to give the title compound.</p><p num="0994"> Example 311C 4-(((Sith-4-methoxycyclohexyl) methylamino) -3-nitrobenzenesulfonamide This compound was prepared in the same procedure as in Example 311B.</p><p num="0995"> Example 311D Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 26C and Example 311B, respectively.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 2H), 8.55-8.62 (m, 2H), 7.78 (dd, 1H), 7.51 (d, 1H), 7.37-7.43 (m, 2H), 7.33 (d, 2H), 7.15 ( d, 1H), 7.01-7.08 (m, 3H), 6.86 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 3.25 (t, 2H), 3.22 (s, 3H), 3.00-3.10 (m, 5H), 2.72 (s, 2H), 2.15 (d, 6H), 2.00 (d, 2H), 1.94 (s, 2H), 1.78 (d, 2H), 1.53-1.65 (m, 1H), 1.38 (t, 2H), 0.96-1.12 (m, 4H), 0.92 (s, 6H).</p><p num="0996"> Example 312 Sith-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[ (4-Hydroxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide The title compound (trifluoroacetic acid salt) was obtained during the purification of Example 310C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.39 (s, 1H), 11.18 (s, 1H), 9.17 (s, 1H), 8.61 (t, 1H), 8.58 (d, 1H), 7.78 (dd, 1H), 7.54 (d, 1H) , 7.34-7.43 (m, 5H), 7.14 (d, 1H), 7.07 (t, 3H), 6.85 (dd, 1H), 6.69 (d, 1H), 6.39 (s, 1H), 6.21 (s, 1H) ), 3.77 (s, 1H), 3.58 (s, 2H), 3.24-3.29 (m, 2H), 2.91-3.07 (m, 2H), 2.60-2.81 (m, 2H), 2.17 (s, 2H), 2.00 (s, 2H), 1.57-1.72 (m, 4H), 1.43 (t, 7H), 0.94 (s, 6H).</p><p num="0997"> Example 313 Sith-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5) -Iloxy) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 26C and Example 311C, respectively.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 2H), 8.60 (t, 1H), 8.58 (d, 1H), 7.78 (dd, 1H), 7.51 (d, 1H), 7.37-7.44 (m, 2H), 7.33 (d, 2H), 7.16 (d, 1H), 7.07 (d, 1H), 7.03 (d, 2H), 6.86 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H) ), 3.36-3.39 (m, 1H), 3.26 (t, 2H), 3.20 (s, 3H), 3.03 (s, 4H), 2.72 (s, 2H), 2.15 (d, 6H), 1.94 (s, 2H), 1.81 (dd, 2H), 1.63-1.73 (m, 1H), 1.48 (dd, 2H), 1.23-1.41 (m, 6H), 0.92 (s, 6H).</p><p num="0998"> Example 314 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (2-tetrahydro-2H-pyran-4-ylethoxy) phenyl] sulfonyl} benzamide Example 314A 3-Nitro-4- (2- (tetrahydro-2H-pyran-4-yl) ethoxy) benzenesulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methanol of Example 279A with 2- (tetrahydro-2H-pyran-4-yl) ethanol.</p><p num="0999"> Example 314B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[3-Nitro-4- (2-tetrahydro-2H-pyran-4-ylethoxy) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 314A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.25 (s, 1H), 8.25 (d, 1H), 7.95 (dd, 1H), 7.54 (d, 1H), 7.39 (d, 1H), 7.34 (d, 2H), 7.29 (m, 1H) , 7.17 (m, 1H), 7.04 (d, 2H), 6.97 (m, 1H), 6.70 (dd, 1H), 6.41 (d, 1H), 6.28 (m, 2H), 4.26 (t, 2H), 3.83 (m, 2H), 3.27 (m, 2H), 3.07 (m, 4H), 2.80 (m, 2H), 2.15 (m, 6H), 1.96 (s, 2H), 1.70 (m, 3H), 1.60 (m, 2H), 1.39 (t, 2H), 1.22 (m, 2H), 0.93 (s, 6H).</p><p num="1000"> Example 315 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Methoxyethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 309A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.18 (d, 1H), 7.92 (dd, 1H), 7.49 (d, 1H), 7.40 (m, 2H), 7.33 (d, 2H), 7.26 (m, 1H) , 7.17 (d, 1H), 7.04 (m, 3H), 6.86 (dd, 1H), 6.65 (dd, 1H), 6.40 (m, 1H), 6.14 (d, 1H), 3.51 (m, 4H), 3.28 (s, 3H), 3.03 (s, 4H), 2.74 (m, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1001"> Example 316 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4- [3- (Methylsulfonyl) propoxy] -3-nitrophenyl} sulfonyl) benzamide Example 316A 4- (3- (Methylthio) propoxy) -3-nitrobenzene sulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methanol of Example 279A with 3- (methylthio) propan-1-ol.</p><p num="1002"> Example 316B 4- (3- (Methylsulfonyl) propoxy) -3-nitrobenzenesulfonamide This Example compound was prepared by substituting Example 294A of Example 294B with Example 316A.</p><p num="1003"> Example 316C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4- [3- (Methylsulfonyl) propoxy] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 316B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.24 (s, 1H), 8.28 (d, 1H), 7.96 (dd, 1H), 7.54 (d, 1H), 7.35 (m, 3H), 7.29 (t, 1H), 7.17 (d, 1H) , 7.04 (d, 2H), 6.96 (m, 1H), 6.71 (dd, 1H), 6.39 (d, 1H), 6.29 (m, 2H), 4.34 (t, 2H), 3.27 (m, 4H), 3.07 (m, 4H), 3.03 (s, 3H), 2.81 (s, 2H), 2.21 (m, 6H), 1.96 (s, 2H), 1.39 (t, 2H), 0.93 (s, 6H).</p><p num="1004"> Example 317 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Methoxypropyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 317A 4- (3-Methoxypropylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by substituting the (tetrahydropyran-4-yl) methylamine of Example 1F with 3-methoxypropan-1-amine.</p><p num="1005"> Example 317B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Methoxypropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 317A.¹1 H NMR (500MHz, Pyridine-d5) δ 12.24 (s, 1H), 9.30 (d, 1H), 8.88 (t, 1H), 8.28 (dd, 1H), 8.19 (d, 1H), 7.51-7.56 (m) , 2H), 7.41-7.46 (m, 3H), 7.04-7.12 (m, 3H), 6.78 (d, 1H), 6.73 (dd, 1H), 6.60 (s, 1H), 6.55 (d, 1H), 3.40 (t, 2H), 3.29-3.36 (m, 2H), 3.27 (s, 3H), 3.01-3.08 (m, 4H), 2.76 (s, 2H), 2.25 (t, 2H), 2.06-2.15 ( m, 4H), 1.97 (s, 2H), 1.78-1.86 (m, 2H), 1.38 (t, 2H), 0.93 (s, 6H).</p><p num="1006"> Example 318 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Methoxypropyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 317A.¹1 H NMR (500MHz, Pyridine-d₅) δ 12.39 (s, 1H), 9.21 (d, 1H), 8.86 (t, 1H), 8.15-8.24 (m, 2H), 7.42-7.50 (m, 3H), 7.38 (d, 1H), 7.04- 7.13 (m, 3H), 6.73-6.81 (m, 4H), 6.67 (d, 1H), 3.39 (t, 2H), 3.32 (q, 2H), 3.27 (s, 3H), 2.96-3.07 (m, 4H), 2.76 (s, 2H), 2.25 (t, 2H), 2.07-2.16 (m, 4H), 1.97 (s, 2H), 1.77-1.87 (m, 2H), 1.39 (t, 2H), 0.94 (s, 6H).</p><p num="1007"> Example 319 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Cyanoethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 319A 4- (2-Cyanoethylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with 3-aminopropanenitrile.</p><p num="1008"> Example 319B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Cyanoethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 319A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.26 (d, 1H), 9.06 (t, 1H), 8.34 (dd, 1H), 8.18 (d, 1H), 7.51-7.57 (m, 2H), 7.39-7.47 (m, 3H), 7.04- 7.11 (m, 3H), 7.00 (d, 1H), 6.74 (dd, 1H), 6.60 (s, 1H), 6.54 (d, 1H), 3.83 (q, J = 6.7Hz, 2H), 3.01-3.08 (m, 4H), 2.98 (t, 2H), 2.76 (s, 2H), 2.25 (t, 2H), 2.07-2.15 (m, 4H), 1.97 (s, 2H), 1.38 (t, 2H), 0.93 (s, 6H).</p><p num="1009"> Example 320 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2-2-yl] Cyanoethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 55B and Example 1F with Example 319A.¹1 H NMR (500MHz, Pyridine-d₅) δ 12.41 (s, 1H), 9.16 (d, 1H), 9.05 (t, 1H), 8.31 (dd, 1H), 8.17 (d, 1H), 7.39 (d, 1H), 7.05-7.13 (m, 3H), 6.99 (d, 1H), 6.78 (dd, 1H), 6.72-6.76 (m, 2H), 6.66 (d, 1H), 3.83 (q, 2H), 3.01-3.07 (m, 4H), 2.98 (t, 2H), 2.76 (s, 2H), 2.25 (t, 2H), 2.08-2.16 (m, 4H), 1.97 (s, 2H), 1.39 (t, 2H), 0.94 (s, 6H).</p><p num="1010"> Example 321 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[(( 3R) -4-hydroxy-1-adamantyl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide The title compound was prepared in the same manner as described in Example 310C, replacing Example 310A with 5-aminomethyl-admantan-2-ol.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 2H), 8.57 (d, 1H), 8.51 (t, 1H), 7.76 (dd, 1H), 7.50 (d, 1H), 7.38-7.42 (m, 2H), 7.33 (d, 2H), 7.11-7.16 (m, 2H), 7.03 (d, 2H), 6.86 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 4.61 (d) , 1H), 3.63 (d, 1H), 3.13 (d, 2H), 3.03 (s, 4H), 2.73 (s, 2H), 2.11-2.21 (m, 6H), 2.04 (d, 2H), 1.95 ( s, 2H), 1.78-1.86 (m, 3H), 1.49-1.60 (m, 6H), 1.38 (t, 2H), 1.29 (d, 2H), 0.92 (s, 6H).</p><p num="1011"> Example 322 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({[Cis -4-Hydroxy-1-adamantyl] methyl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indole-5-yloxy) benzamide The title compound was prepared in the same manner as described in Example 310C, replacing Example 310A with 5-aminomethyl-admantan-2-ol.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 2H), 8.57 (d, 1H), 8.52 (t, 1H), 7.71-7.80 (m, 1H), 7.51 (d, 1H), 7.37-7.42 (m, 2H), 7.33 ( d, 2H), 7.09-7.17 (m, 2H), 7.03 (d, 2H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 4.61 (d, 1H), 3.61 (d, 1H), 3.08 (d, 2H), 3.03 (s, 4H), 2.72 (s, 2H), 2.09-2.21 (m, 6H), 1.82-1.96 (m, 7H) ), 1.55-1.69 (m, 4H), 1.49 (s, 2H), 1.38 (t, 2H), 1.19-1.27 (m, 3H), 0.92 (s, 6H).</p><p num="1012"> Example 323 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(3,3,3-trifluoropropyl) amino] phenyl} sulfonyl) benzamide Example 323A 3-Nitro-4- (3,3,3-trifluoropropylamino) Benzene Sulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methaneamine in Example 1F with 3,3,3-trifluoropropan-1-amine.</p><p num="1013"> Example 323B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(3,3,3-trifluoropropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by replacing Example 1F of Example 177 with Example 323A and replacing Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.34 (s, 1H), 11.19 (s, 1H), 8.53 (m, 1H), 8.47 (s, 1H), 7.74 (dd, 1H), 7.54 (d, 1H), 7.34 (d, 2H) , 7.25 (m, 1H), 7.13 (d, 1H), 6.99 (m, 4H), 6.67 (d, 1H), 6.36 (d, 1H), 6.24 (m, 2H), 3.65 (q, 2H), 3.01 (m, 4H), 2.68 (m, 4H), 2.16 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.93 (s, 6H).</p><p num="1014"> Example 324 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(3,3,3-trifluoropropyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 323A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.06 (s, 1H), 8.44 (m, 2H), 7.75 (dd, 1H), 7.54 (d, 1H), 7.33 (m, 4H), 7.02 (m, 3H), 6.90 (d, 1H) , 6.76 (dd, 1H), 6.58 (dd, 1H), 6.33 (m, 1H), 6.15 (d, 1H), 3.63 (q, 2H), 2.97 (m, 4H), 2.68 (m, 4H), 2.16 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1015"> Example 325 N-({5-bromo-6-[(tetrahydro-2H-pyran-4-ylmethyl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide Example 325A 5-Bromo-6-((Tetrahydro-2H-pyran-4-yl) methylamino) Pyridine-3-sulfonamide A mixture of Example 329A (93 mg), (tetrahydro-2H-pyran-4-yl) methaneamine (40 mg) and triethylamine (0.144 mL) in anhydrous dioxane (4 mL) was heated overnight at 110 ° C. The organic solvent was removed under vacuum. The residue was suspended in dichloromethane. The solid was filtered and dried to give the title compound.</p><p num="1016"> Example 325B N-({5-bromo-6-[(tetrahydro-2H-pyran-4-ylmethyl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 325A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.28 (s, 1H), 11.10 (s, 1H), 8.38 (d, 1H), 7.93 (d, 1H), 7.57 (d, 1H), 7.32 (m, 4H), 7.22 (d, 1H) , 7.02 (m, 3H), 6.71 (dd, 1H), 6.51 (d, 1H), 6.27 (m, 2H), 3.82 (dd, 2H), 3.31 (m, 2H), 3.23 (m, 2H), 3.05 (m, 4H), 2.74 (s, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.88 (m, 1H), 1.55 (m, 2H), 1.37 (m, 2H), 1.18 (m, 2H), 0.92 (s, 6H).</p><p num="1017"> Example 326 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1) , 1-Dioxide tetrahydrothien-3-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-4-yloxy) benzamide This Example compound was replaced with the 4-chloro-3-nitrobenzenesulfonamide of Example 189A with Example 337A and 1- (2-methoxy-ethyl) -piperidine-4-ylamine replaced with (1,1-dioxide tetrahydro). It was prepared by replacing it with thiene-3-yl) methylamine hydrochloride.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.25 (s, 1H), 8.71 (m, 1H), 8.51 (d, 1H), 7.72 (dd, 1H), 7.53 (d, 1H), 7.34 (d, 2H), 7.29 (m, 1H) , 7.18 (d, 1H), 7.12 (d, 1H), 7.04 (d, 2H), 6.98 (m, 1H), 6.70 (dd, 1H), 6.44 (d, 1H), 6.26 (dd, 2H), 3.55 (t, 2H), 3.27 (m, 2H), 3.04 (m, 5H), 2.91 (m, 1H), 2.74 (s, 3H), 2.28 (m, 1H), 2.16 (m, 6H), 1.95 (s, 2H), 1.85 (m, 1H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1018"> Example 327 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 306D.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 2H), 8.41 (d, 1H), 8.10 (dd, 1H), 7.51 (d, 1H), 7.39-7.46 (m, 3H), 7.34 (d, 2H), 7.16 (s, 1H), 7.04 (d2H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.40 (d, 1H), 6.15 (d, 1H), 4.38 (d, 2H), 3.76-3.80 (m, 2H) ), 3.56-3.61 (m, 2H), 3.05 (s, 4H), 2.78 (s, 2H), 2.12-2.23 (m, 6H), 1.95 (s, 2H), 1.80-1.89 (m, 4H), 1.38 ( t, 2H), 0.92 (s, 6H).</p><p num="1019"> Example 328 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4- (Methylamino) -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide Example 328A 4- (Methylamino) -3- (Trifluoromethylsulfonyl) Benzene Sulfonamide This Example compound was prepared by replacing 4-fluoro-3-nitrobenzenesulfonamide of Example 1F with Example 159C and replacing (tetrahydropyran-4-yl) methylamine with methylamine.</p><p num="1020"> Example 328B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4- (Methylamino) -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 328A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.17 (d, 1H), 7.91 (dd, 1H), 7.49 (d, 1H), 7.40 (m, 3H), 7.33 (d, 2H), 7.16 (m, 1H) , 7.04 (d, 2H), 6.87 (m, 2H), 6.65 (dd, 1H), 6.40 (m, 1H), 6.14 (d, 1H), 3.03 (m, 4H), 2.91 (d, 3H), 2.73 (s, 2H), 2.15 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1021"> Example 329 N-{[5-bromo-6- (tetrahydro-2H-pyran-4-ylmethoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide Example 329A 5-Bromo-6-chloropyridin-3-sulfonamide 5-Bromo-6-chloropyridin-3-sulfonyl chloride (8.2 g) in methanol (20 mL) was cooled to 0 ° C. 7N NH in methanol (80 mL) to this mixture₃Was added. The reaction mixture was stirred overnight. The solvent was removed at low temperature and the residue was partitioned between ethyl acetate and water. The aqueous layer was extracted 3 times with ethyl acetate. The combined organic layer is washed with brine and dehydrated (DDL).₄), Filtered and concentrated. The solid was purified by flash column chromatography on silica gel with 10-50% ethyl acetate in hexanes to give the title compound.</p><p num="1022"> Example 329B 5-Bromo-6-((Tetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-sulfonamide Methanol (0.65 g) in tetrahydrofuran (20 mL) was treated with 60% sodium hydride (0.895 g). The reaction mixture was stirred for 10 minutes. Example 329A (1.519 g) was added to this mixture. The reaction mixture was stirred overnight. This was poured into water, neutralized with a 10% aqueous HCl solution, and extracted 3 times with ethyl acetate. Wash the combined organic layer with brine and deli₄Dehydrated with, filtered and concentrated. The residue was purified by flash column chromatography using silica gel by eluting 20% -60% ethyl acetate in hexane to give the title compound.</p><p num="1023"> Example 329C N-{[5-bromo-6- (tetrahydro-2H-pyran-4-ylmethoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 329B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.15 (s, 1H), 8.60 s, 1H), 8.38 (d, 1H), 7.54 (d, 1H), 7.38-7.42 (m, 2H), 7.34 (d, 2H), 7.17 (s, 1H) ), 7.04 (d, 2H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 4.25 (d, 2H), 3.87 (dd, 2H) , 3.05 (s, 4H), 2.80 (s, 2H), 2.25 (s, 4H), 2.12-2.14 (m, 4H), 1.95 (s, 2H), 1.63-1.66 (m, 2H), 1.37-1.40 (m, 2H), 0.92 (s, 6H).</p><p num="1024"> Example 330 4- (4-{[4- (4-Chlorophenyl) -6-isopropoxypyridine-3-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-({ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 330A 1-((4- (4-Chlorophenyl) -6-isopropoxypyridine-3-yl) methyl) piperazine This Example compound was prepared by substituting Example 1A of Example 1B with Example 307F.</p><p num="1025"> Example 330B Ethyl 2- (1H-indole-5-yloxy) -4-(4-((4- (4-chlorophenyl) -6-isopropoxypyridine-3-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by substituting Example 20C of Example 20D with Example 330A and substituting Example 20A with Example 26A.</p><p num="1026"> Example 330C 2- (1H-indole-5-yloxy) -4-(4-((4- (4-chlorophenyl) -6-isopropoxypyridine-3-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 330B.</p><p num="1027"> Example 330D 4- (4-{[4- (4-Chlorophenyl) -6-isopropoxypyridine-3-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) -N-({ 3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 330C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.21, (s, 1H), 11.17 (s, 1H), 8.63 (t, 1H), 8.59 (d, 1H), 8.08 (s, 1H), 7.79 (dd1H), 7.54-7.56 (m, 3H) ), 7.47 (d, 2H), 7.38-7.42 (m, 2H), 7.15 (d, 1H), 7.10 (d, 1H), 6.87 (dd, 1H), 6.68 (dd, 1H), 6.59 (s, 1H), 6.39 (s, 1H), 6.17 (d, 1H), 5.23-5.28 (m, 1H), 3.85 (dd, 2H), 3.24-3.31 (m, 4H), 3.02 (s, 4H), 2.29 (s, 4H), 1.86-1.91 (m, 1H), 1.61-1.63 (m, 2H), 1.28 (d, 6H).</p><p num="1028"> Example 331 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[6- (Tetrahydro-2H-pyran-4-ylmethoxy) -5- (1,3-thiazole-2-yl) pyridin-3-yl] sulfonyl} benzamide Example 331A 6-((Tetrahydro-2H-pyran-4-yl) methoxy) -5- (thiazole-2-yl) Pyridine-3-sulfonamide A mixture of Example 329B (0.070 g), 2- (tributylstannyl) thiazole (0.090 g) and tetrakis (triphenylphosphine) palladium (0) (0.069 g) in dioxane (2 mL) at 90 ° C for 4 hours. It was heated. After cooling, the mixture was loaded onto a silica gel column and eluted with 1: 3 ethyl acetate: hexane to give the title compound.</p><p num="1029"> Example 331B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[6- (Tetrahydro-2H-pyran-4-ylmethoxy) -5- (1,3-thiazole-2-yl) pyridin-3-yl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 331A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.14 (s, 1H), 9.09 (s, 1H), 8.73 (s, 1H), 8.06 (d, 1H), 7.98 (d, 1H), 7.50 (d, 1H), 7.37-7.38 (m, 2H), 7.33 (d, 2H), 7.17 (d, 1H), 7.03 (d, 2H), 6.84 (dd, 1H), 6.62 (dd, 1H), 6.37 (s, 1H), 6.11 (d, 1H) ), 4.46 (d, 2H), 3.91 (dd, 2H), 3.36-3.39 (m, 4H), 3.02 (s, 4H), 2.76 (s, 2H), 2.12-2.20 (s, 8H), 1.94 ( s, 2H), 1.45-1.47 (m, 2H), 1.37 (t, 2H), 0.91 (s, 6H).</p><p num="1030"> Example 332 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(2-Methoxyethyl) amino] carbonyl} phenyl) sulfonyl] benzamide Example 332A N- (2-Methoxyethyl) -4-sulfamoylbenzamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methaneamine of Example 308A with 2-methoxyethaneamine.</p><p num="1031"> Example 332B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(2-Methoxyethyl) amino] carbonyl} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 332A and Example 1E with Example 26C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.28 (br s, 1H), 11.17 (s, 1H), 8.71 (m, 1H), 7.94 (m, 4H), 7.48 (d, 1H), 7.41 (m, 2H), 7.33 (d, 2H) ), 7.21 (d, 1H), 7.03 (d, 2H), 6.88 (dd, 1H), 6.63 (dd, 1H), 6.42 (t, 1H), 6.13 (d, 1H), 3.45 (m, 4H) , 3.27 (s, 3H), 3.03 (m, 4H), 2.73 (br s, 2H), 2.16 (m, 6H), 1.95 (br s, 2H), 1.38 (m, 2H), 0.92 (s, 6H) ).</p><p num="1032"> Example 333 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide Example 333A 5-Cyano-6-((Tetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-sulfonamide A mixture of Example 329B (0.702 g), zinc dicyanozinc (0.129 g) and tetrakis (triphenylphosphine) palladium (0) (0.231 g) in N, N-dimethylformamide (2 mL), vacuum / nitrogen cycle. It was applied 3 times and degassed. The reaction mixture was heated at 120 ° C. for 3 hours. After cooling, it was poured into water and extracted 3 times with ethyl acetate. Wash the combined organic layer with brine and deli₄Dehydrated with, filtered and concentrated. The residue was purified by flash column chromatography using silica gel by eluting with 20% -60% ethyl acetate in hexane to give the title compound.</p><p num="1033"> Example 333B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 333A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.84 (d, 1H), 8.64 (d, 1H), 7.57 (d, 1H), 7.38-7.41 (m, 4H), 7.12 (d, 1H), 7.08 (d, 2H), 6.87 (dd, 1H), 6.71 (dd, 1H), 6.38 (s, 1H), 6.23 (d, 1H), 4.31 (d, 2H), 3.88 (dd, 2H), 3.54 (br s, 2H), 3.02 (br s, 4H), 2.76 (br s, 2H), 2.18 (s, 4H), 2.01 (s, 2H), 1.63-1.66 (m, 2H), 1.49 (t, 2H), 0.94 (s, 6H).</p><p num="1034"> Example 334 N-({4-[(1-Acetylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was replaced with 1- (2-methoxy-ethyl) -piperidine-4-ylamine in Example 189A with 1-acetylpiperidine-4-amine and 4-chloro-3-nitrobenzenesulfonamide in Example 310B. Prepared by replacing with.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.16 (br s, 1H), 8.58 (d, 1H), 8.25 (d, 1H), 7.81 (dd, 1H), 7.51 (d, 1H), 7.43-7.37 (m, 2H), 7.34 (d , 2H), 7.19 (d, 1H), 7.15 (d, 1H), 7.04 (d, 2H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.39 (t, 1H), 6.15 (d, 1H), 4.32-4.23 (m, 1H), 3.96-3.77 (m, 2H), 3.21 (m, 2H), 3.03 (m, 4H), 2.80 (m, 2H), 2.73 (br s, 2H), 2.16 (m, 6H), 2.02 (s, 3H), 1.95 (br s, 2H), 1.65-1.44 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1035"> Example 335 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[1- (Methylsulfonyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was replaced with 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with 1- (methylsulfonyl) piperidine-4-amine to replace 4-chloro-3-nitrobenzenesulfonamide. Prepared by replacing with Example 187A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.15 (br s, 1H), 8.59 (d, 1H), 8.25 (d, 1H), 7.82 (dd, 1H), 7.51 (d, 1H), 7.43-7.38 (m, 2H), 7.34 (d , 2H), 7.14 (m, 2H), 7.04 (d, 2H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.39 (t, 1H), 6.15 (d, 1H), 3.80 (m, 1H), 3.57 (m, 2H), 3.04 (m, 4H), 2.95 (m, 2H), 2.92 (br s, 3H), 2.73 (m, 2H), 2.15 (m, 6H), 2.06-1.98 ( m, 2H), 1.95 (br s, 2H), 1.70 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1036"> Example 336 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 4-dioxane-2-ylmethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 336A 4-((1,4-dioxane-2-yl) methylamino) -3-nitrobenzenesulfonamide The title compound was prepared in the same manner as described in Example 1F, replacing (tetrahydro-2H-pyran-4-yl) methaneamine with (1,4-dioxane-2-yl) methaneamine.</p><p num="1037"> Example 336B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 4-dioxane-2-ylmethyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 26C and Example 336A, respectively.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 2H), 8.54-8.63 (m, 2H), 7.82 (dd, 1H), 7.50 (d, 1H), 7.38-7.42 (m, 2H), 7.33 (d, 2H), 7.16 ( d, 1H), 7.10 (d, 1H), 7.03 (d, 2H), 6.86 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 3.76-3.82 (m, 3H), 3.57-3.68 (m, 2H), 3.45-3.52 (m, 2H), 3.36-3.42 (m, 1H), 3.03 (s, 4H), 2.73 (d, 2H), 2.10-2.22 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1038"> Example 337 N-({4-[(1-Acetylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide Example 337A This Example compound was prepared by replacing Example 1E of Example 1G with Example 55B and Example 1F with 4-chloro-3-nitrobenzenesulfonamide.</p><p num="1039"> Example 337B N-({4-[(1-Acetylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-En-1-yl] Methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with 1-acetylpiperidine and substituting 4-chloro-3-nitrobenzenesulfonamide with Example 337A. did.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.24 (br s, 1H), 8.50 (d, 1H), 8.24 (d, 1H), 7.73 (dd, 1H), 7.52 (d, 1H), 7.34 (d, 2H), 7.27 (t, 1H) ), 7.19-7.13 (m, 2H), 7.04 (t, 2H), 6.97 (t, 1H), 6.70 (dd, 1H), 6.42 (d, 1H), 6.27 (dd, 1H), 6.24 (t, 1H), 4.29 (m, 1H), 3.97-3.78 (m, 2H), 3.22 (m, 2H), 3.05 (m, 4H), 2.81 (m, 2H), 2.72 (br s, 2H), 2.15 ( m, 6H), 2.03 (s, 3H), 1.95 (br s, 2H), 1.66-1.44 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1040"> Example 338 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[1- (Methylsulfonyl) piperidine-4-yl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was replaced with 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with 1- (methylsulfonyl) piperidine-4-amine to replace 4-chloro-3-nitrobenzenesulfonamide. Prepared by replacing with Example 337A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.24 (br s, 1H), 8.50 (d, 1H), 8.25 (d, 1H), 7.74 (dd, 1H), 7.52 (d, 1H), 7.34 (d, 2H), 7.27 (t, 1H) ), 7.17 (d, 1H), 7.12 (d, 1H), 7.04 (d, 2H), 6.97 (t, 1H), 6.70 (dd, 1H), 6.42 (d, 1H), 6.27 (d, 1H) , 6.24 (t, 1H), 3.81 (m, 1H), 3.58 (m, 2H), 3.05 (m, 4H), 2.96 (m, 2H), 2.92 (s, 3H), 2.74 (m, 2H), 2.16 (m, 6H), 2.06-1.98 (m, 2H), 1.95 (br s, 2H), 1.70 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1041"> Example 339 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 339A Methyl 2- (1H-indole-5-yloxy) -4- (4- (2-bromo-4- (trifluoromethyl) benzyl) pi Perazine-1-yl) benzoate This Example compound was prepared by substituting Example 27C of Example 1A with 4-trifluoromethyl-2-bromobenzaldehyde and substituting tert-butylpiperazin-1-carbochelate with Example 150A.</p><p num="1042"> Example 339B Methyl 2- (1H-indole-5-yloxy) -4-(4-((4'-chloro-5- (trifluoromethyl) biphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by replacing 2-fluoro-4-iodo-5-methylpyridine of Example 307A with Example 339A.</p><p num="1043"> Example 339C 2- (1H-indole-5-yloxy) -4-(4-((4'-chloro-5- (trifluoromethyl) biphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 339B.</p><p num="1044"> Example 339D 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 339C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.24, (s, 1H), 11.17 (s, 1H), 8.63 (t, 1H), 7.79 (dd, 1H), 7.72 (m, 2H), 7.38-7.53 (m, 8H), 7.15 (d) , 1H), 7.10 (d, 1H), 6.87 (dd, 1H), 6.67 (dd, 1H), 6.39 (s, 1H), 6.16 (d, 1H), 3.85 (dd, 2H), 3.41 (s, 2H), 3.24-3.31 (m, 6H), 3.04 (s, 4H), 2.29 (s, 4H), 1.60-1.63 (m, 2H), 1.24-1.28 (m, 2H).</p><p num="1045"> Example 340 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[3-Nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 339C and Example 1F with Example 279A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.40, (s, 1H), 11.17 (s, 1H), 8.41 (d, 1H), 8.07 (dd, 1H), 7.70-7.74 (m, 2H), 7.38-7.53 (m, 8H), 7.16 (d, 1H), 6.87 (dd, 1H), 6.67 (dd, 1H), 6.40 (s, 1H), 6.17 (d, 1H), 4.09 (d, 2H), 3.88 (dd, 2H), 3.42 ( s, 2H), 3.05 (s, 4H), 2.30 (s, 4H), 2.00-2.05 (m, 1H), 1.63-1.66 (m, 2H), 1.31-1.37 (m, 2H).</p><p num="1046"> Example 341 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 341A Methyl 2- (1H-indole-5-yloxy) -4- (4- (2-bromo-4-tert-butylbenzyl) piperazin-1-yl) benzoate This Example compound was prepared by substituting Example 27C of Example 1A with 4-tert-butyl-2-bromobenzaldehyde and tert-butylpiperazin-1-carbochelate with Example 150A.</p><p num="1047"> Example 341B Methyl 2- (1H-indole-5-yloxy) -4-(4-((5-tert-butyl-4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoate This Example compound was prepared by replacing 2-fluoro-4-iodo-5-methylpyridine of Example 307A with Example 341A.</p><p num="1048"> Example 341C 2- (1H-indole-5-yloxy) -4-(4-((5-tert-butyl-4'-chlorobiphenyl-2-yl) methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 341B.</p><p num="1049"> Example 341D 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 341C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.22, (s, 1H), 11.16 (s, 1H), 8.62 (t, 1H), 8.58 (d, 1H), 7.79 (dd, 1H), 7.53 (d, 1H), 7.34-7.44 (m) , 8H), 7.18 (s, 1H), 7.14 (d, 1H), 7.09 (d, 1H), 6.86 (dd, 1H), 6.67 (dd, 1H), 6.39 (s, 1H), 6.17 (d, 1H), 3.85 (dd, 2H), 3.24-3.30 (m, 6H), 3.04 (s, 4H), 2.29 (s, 4H), 1.86-1.91 (m, 1H), 1.60-1.63 (m, 2H) , 1.28 (s, 9H).</p><p num="1050"> Example 342 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-{[3-nitro-4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 341C and substituting Example 1F with Example 279A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.25, (br s, 1H), 11.16 (s, 1H), 8.40 (d, 1H), 8.06 (dd, 1H), 7.52 (d, 1H), 7.35-7.46 (m, 8H), 7.19 ( s, 1H), 7.15 (d, 1H), 6.85 (dd, 1H), 6.66 (dd, 1H), 6.39 (s, 1H), 6.17 (d, 1H), 4.08 (d, 2H), 3.88 (dd) , 2H), 3.05 (s, 4H), 2.32 (s, 4H), 1.64 (dd, 2H), 1.32-1.37 (m, 2H), 1.28 (s, 9H).</p><p num="1051"> Example 343 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(2,2,2-trifluoroethyl) amino] phenyl} sulfonyl) benzamide Example 343A 3-Nitro-4- (2,2,2-trifluoroethylamino) benzenesulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methaneamine in Example 1F with 2,2,2-trifluoroethaneamine.</p><p num="1052"> Example 343B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({3-Nitro-4-[(2,2,2-trifluoroethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 343A and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 10.98 (s, 1H), 8.41 (m, 2H), 7.75 (dd, 1H), 7.54 (d, 1H), 7.34 (d, 2H), 7.28 (m, 2H), 7.06 (m, 3H) , 6.93 (m, 1H), 6.70 (dd, 1H), 6.53 (dd, 1H), 6.30 (m, 1H), 6.14 (d, 1H), 4.32 (m, 2H), 2.93 (m, 4H), 2.71 (s, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1053"> Example 344 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(2,2,2-trifluoroethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 343A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.05 (s, 1H), 8.40 (m, 2H), 7.77 (dd, 1H), 7.60 (d, 1H), 7.34 (d, 2H), 7.18 (m, 1H), 7.12 (d, 1H) , 7.04 (m, 3H), 6.88 (t, 1H), 6.58 (dd, 1H), 6.22 (m, 3H), 4.33 (m, 2H), 2.93 (m, 4H), 2.71 (s, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.93 (s, 6H).</p><p num="1054"> Example 345 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-{[(Tetrahydro-2H-pyran-4-ylmethyl) amino] carbonyl} phenyl) sulfonyl] benzamide Example 345A 3-Sulfamoyl-N-((tetrahydro-2H-pyran-4-yl) methyl) benzamide This Example compound was prepared by replacing 4-sulfamoylbenzoic acid in Example 308A with 3-sulfamoylbenzoic acid.</p><p num="1055"> Example 345B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-{[(Tetrahydro-2H-pyran-4-ylmethyl) amino] carbonyl} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1F of Example 1G with Example 345A and Example 1E with Example 26C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.28 (br s, 1H), 11.18 (s, 1H), 8.75 (t, 1H), 8.41 (m, 1H), 8.10 (d, 1H), 8.01 (d, 1H), 7.60 (t, 1H) ), 7.48 (d, 1H), 7.41 (m, 2H), 7.33 (d, 2H), 7.23 (d, 1H), 7.03 (d, 2H), 6.88 (dd, 1H), 6.83 (dd, 1H) , 6.42 (t, 1H), 6.11 (d, 1H), 3.83 (dd, 2H), 3.19 (m, 4H), 3.02 (m, 4H), 2.73 (m, 2H), 2.16 (m, 6H), 1.94 (br s, 2H), 1.80 (m, 1H), 1.58 (dd, 2H), 1.37 (t, 2H), 1.24 (m, 2H), 0.92 (s, 6H).</p><p num="1056"> Example 346 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2R)) -1,4-dioxane-2-ylmethoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 346A (R) -4-((1,4-dioxane-2-yl) methoxy) -3-nitrobenzenesulfonamide The racemic mixture of Example 297A was divided by an SFC chiral AD column to give the title compound.</p><p num="1057"> Example 346B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2R)) -1,4-dioxane-2-ylmethoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 26C and Example 346A, respectively.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 2H), 8.39 (d, 1H), 8.06 (dd, 1H), 7.51 (d, 1H), 7.38-7.43 (m, 3H), 7.34 (d, 2H), 7.15 (d, 1H), 7.04 (d, 2H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.39 (s, 1H), 6.15 (d, 1H), 4.20-4.28 (m, 2H), 3.85-3.91 (m, 1H), 3.82 (dd, 1H), 3.74-3.78 (m, 1H), 3.59-3.69 (m, 2H), 3.40-3.51 (m, 2H), 3.05 (s, 4H), 2.78 (s , 2H), 2.23 (s, 4H), 2.14 (s, 2H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1058"> Example 347 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2S)) -1,4-dioxane-2-ylmethoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 347A (S) -4-((1,4-dioxane-2-yl) methoxy) -3-nitrobenzenesulfonamide The racemic mixture of Example 297A was divided by an SFC chiral AD column to give the title compound.</p><p num="1059"> Example 347B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(2S)) -1,4-dioxane-2-ylmethoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 26C and Example 347A, respectively.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.16 (s, 2H), 8.39 (d, 1H), 8.06 (dd, 1H), 7.51 (d, 1H), 7.38-7.43 (m, 3H), 7.34 (d, 2H), 7.15 (d, 1H), 7.04 (d, 2H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.39 (s, 1H), 6.15 (d, 1H), 4.20-4.28 (m, 2H), 3.85-3.91 (m, 1H), 3.82 (dd, 1H), 3.74-3.78 (m, 1H), 3.59-3.69 (m, 2H), 3.40-3.51 (m, 2H), 3.05 (s, 4H), 2.78 (s , 2H), 2.23 (s, 4H), 2.14 (s, 2H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1060"> Example 348 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide Example 348A 4- (3-morpholinopropylamino) -3- (trifluoromethylsulfonyl) benzenesulfonamide This Example compound was prepared by replacing 4-fluoro-3-nitrobenzenesulfonamide of Example 1F with Example 159C and replacing (tetrahydropyran-4-yl) methylamine with 3-morpholinopropan-1-amine. ..</p><p num="1061"> Example 348B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide 5-Iloxy) -N-({4- (methylamino) -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 348A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.17 (d, 1H), 7.91 (dd, 1H), 7.49 (d, 1H), 7.40 (m, 3H), 7.33 (d, 2H), 7.15 (d, 1H) , 7.03 (m, 3H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.40 (s, 1H), 6.13 (d, 1H), 3.59 (m, 4H), 3.38 (m, 4H), 3.02 (m, 4H), 2.72 (s, 2H), 2.40 (m, 6H), 2.15 (m, 6H), 1.95 (s, 2H), 1.73 (m, 2H), 0.92 (s, 6H).</p><p num="1062"> Example 349 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 348A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.25 (s, 1H), 11.08 (m, 1H), 8.12 (d, 1H), 7.81 (dd, 1H), 7.52 (d, 1H), 7.36 (m, 3H), 7.28 (m, 1H) , 7.19 (d, 1H), 7.04 (d, 2H), 6.98 (m, 2H), 6.69 (dd, 1H), 6.44 (d, 1H), 6.25 (m, 2H), 3.60 (m, 4H), 3.38 (m, 2H), 3.03 (m, 4H), 2.73 (s, 2H), 2.43 (m, 6H), 2.16 (m, 6H), 1.95 (s, 2H), 1.73 (m, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1063"> Example 350 N-({5-bromo-6-[(tetrahydro-2H-pyran-4-ylmethyl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 325A of Example 177 with Example 1F.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.19 (s, 1H), 11.02 (s, 1H), 8.47 (d, 1H), 8.07 (d, 1H), 7.55 (d, 1H), 7.39 (m, 5H), 7.25 (d, 1H) , 7.03 (d, 2H), 6.89 (dd, 1H), 6.65 (dd, 1H), 6.42 (s, 1H), 6.11 (d, 1H), 3.82 (dd, 2H), 3.31 (m, 2H), 3.24 (m, 2H), 3.03 (m, 4H), 2.72 (s, 2H), 2.15 (m, 6H), 1.94 (s, 2H), 1.89 (m, 1H), 1.54 (m, 2H), 1.38 (t, 2H), 1.17 (m, 2H), 0.92 (s, 6H).</p><p num="1064"> Example 351 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Morpholine-4-ylethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide Example 351A 4- (2-morpholinoethylamino) -3- (trifluoromethylsulfonyl) benzenesulfonamide This Example compound was prepared by replacing 4-fluoro-3-nitrobenzenesulfonamide of Example 1F with Example 159C and replacing (tetrahydropyran-4-yl) methylamine with 2-morpholinoetanamine.</p><p num="1065"> Example 351B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(2-Morpholine-4-ylethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 351A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.22 (s, 1H), 11.17 (s, 1H), 8.17 (d, 1H), 7.92 (dd, 1H), 7.61 (s, 1H), 7.48 (d, 1H), 7.40 (m, 2H) , 7.33 (d, 2H), 7.15 (d, 1H), 7.03 (d, 2H), 6.93 (d, 1H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.40 (s, 1H), 6.13 (m, 1H), 3.57 (m, 4H), 3.35 (m, 2H), 3.02 (m, 4H), 2.72 (s, 2H), 2.58 (t, 2H), 2.42 (m, 4H), 2.15 (m, 6H), 1.95 (s, 2H), 1.37 (m, 2H), 0.92 (s, 6H).</p><p num="1066"> Example 352 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N- ({5-cyano-6-) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] pyridine-3-yl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 352A 5-Cyano-6-((Tetrahydro-2H-pyran-4-yl) methylamino) Pyridine-3-sulfonamide This Example compound was prepared by substituting Example 329B of Example 333A with Example 325A.</p><p num="1067"> Example 352B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N- ({5-cyano-6-) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] pyridine-3-yl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 352A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.18 (s, 1H), 8.65 (d, 1H), 8.27 (d, 1H), 8.15 (s, 1H), 7.56 (d, 1H), 7.41 (m, 2H), 7.34 (d, 2H) , 7.22 (d, 1H), 7.04 (d, 2H), 6.88 (dd, 1H), 6.65 (dd, 1H), 6.41 (m, 1H), 6.12 (d, 1H), 3.82 (dd, 2H), 3.33 (m, 2H), 3.24 (t, 2H), 3.04 (m, 4H), 2.75 (s, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.89 (m, 1H), 1.55 (m, 2H), 1.38 (t, 2H), 1.19 (m, 2H), 0.91 (s, 6H).</p><p num="1068"> Example 353 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) oxy] -3-nitrophenyl} sulfonyl) benzamide Example 353A 4- (1-Methylpiperidin-4-yloxy) -3-nitrobenzenesulfonamide NaH (60% in mineral oil) (0.753 g) was added to a mixture of 1-methylpiperidine-4-ol (0.542 g) in tetrahydrofuran (10 mL) at 0 ° C. After stirring for 15 minutes, 4-fluoro-3-nitrobenzenesulfonamide (1.036 g) was added as a solution in tetrahydrofuran (10 mL). The reaction solution was removed from the ice bath and heated to room temperature. After 1 hour, the reaction was poured into water and the pH was adjusted to about 7 with 1N aqueous HCl. The reaction was extracted with dichloromethane (3 x 100 mL), washed with brine, dehydrated with magnesium sulfate, filtered and concentrated. The product was suspended in dichloromethane (mL), sonicated and then filtered to give the title compound.</p><p num="1069"> Example 353B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) oxy] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 353A.¹1 H NMR (300MHz, dimethyl sulfoxide) δ 11.03 (s, 1H), 8.21 (d, 1H), 7.87 (dd, 1H), 7.55 (d, 1H), 7.33 (dd, 4H), 7.25 (d, 1H) , 7.04 (d, 2H), 6.98 (d, 1H), 6.73 (dd, 1H), 6.56 (d, 1H), 6.33 (s, 1H), 6.14 (d, 1H), 4.79 (s, 1H), 2.96 (s, 6H), 2.72 (s, 2H), 2.57 (s, 3H), 2.18 (s, 6H), 1.94 (m, 6H), 1.39 (m, 2H), 0.92 (s, 6H).</p><p num="1070"> Example 354 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide Example 354A 4-((1-Methylpiperidin-4-yl) methoxy) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing 1-methylpiperidine-4-ol of Example 353A with (1-methylpiperidine-4-yl) methanol.</p><p num="1071"> Example 354B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(1-Methylpiperidin-4-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 354A.¹1 H NMR (300MHz, dimethyl sulfoxide) δ 11.01 (s, 1H), 8.19 (d, 1H), 7.87 (dd, 1H), 7.55 (d, 1H), 7.39-7.26 (m, 4H), 7.16 (d, 1H), 7.08-7.01 (m, 2H), 6.96 (d, 1H), 6.72 (dd, 1H), 6.54 (d, 1H), 6.32 (s, 1H), 6.14 (d, 1H), 4.05 (d) , 2H), 2.95 (s, 4H), 2.89-2.59 (m, 7H), 2.17 (s, 6H), 2.00-1.78 (m, 5H), 1.53 (s, 2H), 1.37 (m, 2H), 0.92 (s, 6H).</p><p num="1072"> Example 355 4- (4-{[4- (4-Chlorophenyl) -1- (3-hydroxypropyl) -1,2,5,6-tetrahydropyridin-3-yl] methyl} piperazine-1-yl) -2- (1H-indol-4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 355A tert-Butyl 4-chloro-3-formyl-5,6-dihydropyridine-1 (2H) -carboxylate Phosphoryl oxychloride (3.73 mL) was added dropwise to N, N-dimethylformamide (3.87 mL) at 0 ° C to keep the temperature below 5 ° C. The resulting mixture was diluted with dichloromethane (15 mL) and stirred at room temperature for 1.5 hours. The reaction was then cooled in an ice bath. tert-Butyl 4-oxopiperidine-1-carboxylate (4.98 g) was added as a solution in dichloromethane (20 mL) and the reaction was stirred at room temperature for 1 hour. The reaction mixture was poured into ice and solid sodium acetate, stirred for 15 minutes and extracted with dichloromethane. Thoroughly wash the extract with water and brine and deli₄Dehydrated with, filtered and concentrated to give the title compound.</p><p num="1073"> Example 355B tert-Butyl 4- (4-chlorophenyl) -3-formyl-5,6-dihydropyridine-1 (2H) -carboxylate Example 355A (6.14g), 4-chlorophenylboronic acid (4.10g) and palladium (II) acetate (0.112g) were combined in water to give a suspension. Potassium carbonate (8.98 g) and tetrabutylammonium bromide (4.03 g) were added. The resulting mixture is stirred at 45 ° C. overnight, cooled and the reaction mixture is diluted with ethyl acetate (200 mL) to dissolve any insoluble material, then thoroughly washed with water and EDTA.₄Dehydrated with, filtered and concentrated. The crude material was purified by flash chromatography by eluting from 10% ethyl acetate / hexane with a gradient of 40% ethyl acetate / hexane.</p><p num="1074"> Example 355C tert-Butyl 3-((4- (3- (1H-indole-4-yloxy) -4- (methoxycarbonyl) phenyl) piperazin-1-yl) methyl) -4- (4-chlorophenyl) -5,6 -Dihydropyridine-1 (2H) -carboxylate This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 355B and tert-butylpiperazin-1-carboxylate with Example 68B.</p><p num="1075"> Example 355D Methyl 2- (1H-indole-4-yloxy) -4-(4-((4- (4-chlorophenyl) -1,2,5,6-tetrahydropyridin-3-yl) methyl) piperazine-1-yl ) Benzoate This Example compound was prepared by substituting Example 1A of Example 1B with Example 355C.</p><p num="1076"> Example 355E Methyl 2- (1H-indole-4-yloxy) -4-(4-((4- (4-chlorophenyl) -1- (3-hydroxypropyl) -1,2,5,6-tetrahydropyridine-3-" Indole) methyl) piperazine-1-yl) benzoate Example 355D (539 mg), 3-bromopropane-1-ol (83 mg) and triethylamine (0.42 mL) were combined in acetonitrile. The mixture was heated at 60 ° C. overnight, concentrated, then mixed with ether and filtered to give the title compound.</p><p num="1077"> Example 355F 2- (1H-indole-4-yloxy) -4-(4-((4- (4-chlorophenyl) -1- (3-hydroxypropyl) -1,2,5,6-tetrahydropyridin-3-yl) ) Methyl) piperazine-1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 355E.</p><p num="1078"> Example 355G 4- (4-{[4- (4-Chlorophenyl) -1- (3-hydroxypropyl) -1,2,5,6-tetrahydropyridin-3-yl] methyl} piperazine-1-yl) -2- (1H-indol-4-yloxy) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 355F.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.49 (br s, 1H), 8.44 (s, 1H), 7.69 (dd, 1H), 7.56 (d, 1H), 7.40 (d, 1H), 7.24 (m, 1H) ), 7.13 (m, 3H), 6.98 (m, 1H), 6.94 (t, 1H), 6.86 (dd, 1H), 6.36 (m, 1H), 6.24 (m, 2H), 3.84 (dd, 2H) , 3.47 (t, 2H), 3.26 (m, 4H), 2.99 (br s, 4H), 2.80 (m, 3H), 2.44 (m, 2H), 2.21 (m, 4H), 1.86 (m, 1H) , 1.73 (m, 2H), 1.62 (m, 2H), 1.26 (m, 5H), 1.17 (m, 2H).</p><p num="1079"> Example 356 Benzyl4-({[4-({[4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl)) -2- (1H-indole-5-yloxy) benzoyl] amino} sulfonyl) -2-nitrophenyl] amino} methyl) piperidine-1-carboxylate Example 356A Benzyl4-((2-nitro-4-sulfamoylphenylamino) methyl) piperidine-1-carboxylate The title compound was prepared in the same manner as described in Example 1F, replacing (tetrahydro-2H-pyran-4-yl) methaneamine with benzyl4- (aminomethyl) piperidine-1-carboxylate.</p><p num="1080"> Example 356B Benzyl4-({[4-({[4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl)) -2- (1H-indole-5-yloxy) benzoyl] amino} sulfonyl) -2-nitrophenyl] amino} methyl) piperidine-1-carboxylate The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 26C and Example 356A, respectively.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 2H), 8.63 (t, 1H), 8.58 (d, 1H), 7.79 (dd, 1H), 7.51 (d, 1H), 7.30-7.42 (m, 8H), 7.16 (d, 1H), 7.10 (d, 1H), 7.03 (d, 2H), 6.86 (dd, 1H), 6.65 (dd, 1H), 6.39 (s, 1H), 6.14 (d, 1H), 5.07 (s, 2H) ), 4.02 (d, 2H), 3.29-3.34 (m, 2H), 3.03 (s, 4H), 2.70-2.88 (m, 4H), 2.08-2.23 (m, 6H), 1.94 (s, 2H), 1.81-1.89 (m, 1H), 1.71 (d, 2H), 1.37 (t, 2H), 1.07-1.16 (m, 2H), 0.92 (s, 6H).</p><p num="1081"> Example 357 N-{[3- (aminocarbonyl) -4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexi Sa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide Example 357A 3-Cyano-4-((tetrahydro-2H-pyran-4-yl) methoxy) benzenesulfonamide Sodium hydride (0.284 g) was added to (tetrahydro-2H-pyran-4-yl) methanol (0.206 g) in tetrahydrofuran (5 mL) and the reaction was stirred at room temperature for 20 minutes. The reaction was cooled to 0 ° C., 3-cyano-4-fluorobenzenesulfonamide (0.355 g) in tetrahydrofuran (2 mL) was added dropwise and the reaction was warmed to room temperature. After 3 hours, the reaction was poured into water, acidified with 1N HCl (pH = 1) and extracted with dichloromethane (2 x 75 mL). The organics were combined, washed with brine (50 mL), dehydrated with magnesium sulfate, filtered and concentrated to give the title compound.</p><p num="1082"> Example 357B 5-Sulfamoyl-2-((tetrahydro-2H-pyran-4-yl) methoxy) benzamide A mixture of Example 357A (0.455g) in ethanol (3mL) and tetrahydrofuran (1mL) was added to hydrogen peroxide (30%, 2mL), then NaOH (1.024ml) was added and heated to 35 ° C for 3 hours. did. The mixture was poured into dichloromethane (50 mL) and aqueous 1N HCl (25 mL) to form a precipitate. The title compound was extracted with dichloromethane (3 x 50 mL). The organic layer contained a solid. This was collected by filtration and dried to obtain the title compound.</p><p num="1083"> Example 357C N-{[3- (aminocarbonyl) -4- (tetrahydro-2H-pyran-4-ylmethoxy) phenyl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohexi Sa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 357B.¹1 H NMR (300MHz, CDCL3) δ 10.35 (s, 1H), 8.80 (d, 1H), 8.35 (dd, 2H), 7.91 (d, 1H), 7.44 (d, 2H), 7.39 (d, 1H), 7.34-7.29 (m, 1H), 7.22 (d, 2H), 7.07 (d, 1H), 6.99 (dd, 1H), 6.93-6.87 (m, 2H), 6.58 (s, 1H), 6.48 (dd, dd, 1H), 6.06 (d, 1H), 5.80 (s, 1H), 4.05 (dd, 4H), 3.46 (dd, 2H), 3.03 (s, 4H), 2.73 (s, 2H), 2.19 (m, 7H) ), 1.96 (s, 2H), 1.74 (m, 2H), 1.43 (m, 4H), 0.93 (s, 6H).</p><p num="1084"> Example 358 4- (4-{[4'-Chloro-5- (trifluoromethyl) -1,1'-biphenyl-2-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 339C and Example 1F with Example 173C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.11 (s, 1H), 8.54 (d, 1H), 8.19 (d, 1H), 7.78 (dd, 1H), 7.71-7.74 (m, 2H), 7.44-7.54 (m, 7H), 7.36 7.38 (m, 2H), 7.04-7.07 (m, 2H), 6.87 (dd, 1H), 6.63 (dd, J = 8.7, 1.68Hz, 1H), 6.36 (s, 1H), 6.16 (d, 1H) , 3.93 (dd, 2H), 3.75 (br s, 2H), 3.41 (s, 2H), 3.01-3.07 (m, 6H), 2.66-2.68 (m, 2H), 2.30 (s, 4H), 1.77- 1.80 (m, 2H), 1.47-1.53 (m, 2H).</p><p num="1085"> Example 359 4- {4-[(5-tert-Butyl-4'-chloro-1,1'-biphenyl-2-yl) methyl] piperazine-1-yl} -2- (1H-indole-5-yloxy)- N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 341C and substituting Example 1F with Example 173C.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.11, (s, 1H), 8.53 (t, 1H), 8.19 (d, 1H), 7.76 (dd, 1H), 7.53 (d, 1H), 7.36-7.44 (m, 8H), 7.19 (s , 1H), 7.04-7.07 (m, 2H), 6.81 (dd, 1H), 6.63 (dd, 1H), 6.36 (s, 1H), 6.17 (d, 1H), 3.93 (dd, 2H), 3.74- 3.75 (m, 2H), 3.01-3.07 (m, 6H), 2.64-2.67 (m, 2H), 2.29 (s, 4H), 1.99-2.03 (m, 4H), 1.77-1.80 (m, 2H), 1.65-1.67 (m, 2H), 1.28 (s, 9H).</p><p num="1086"> Example 360 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1-Methyl-1H-imidazol-5-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting (3S, 4R) -4-amino-1-benzylpiperidine-3-ol, hydrochloric acid with (1-methyl-1H-imidazol-5-yl) methaneamine from Example 187B. ..¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.81 (t, 1H), 8.59 (d, 1H), 7.83 (dd, 1H), 7.64 (s, 1H), 7.50 (d, 1H), 7.39-7.42 (m, 2H), 7.33 (d, 2H), 7.16-7.17 (m, 2H), 7.03 (d, 2H), 6.98 (s, 1H), 6.85 (dd, 1H), 6.63 (dd, 1H), 6.40 (s) , 1H), 6.13 (d, 1H), 4.66 (d, 2H), 3.64 (s, 3H), 3.02 (s, 4H), 2.72 (s, 2H), 2.12-2.16 (m, 6H), 1.94 ( s, 2H), 1.37 (t, 2H), 0.92 (s, 6H).</p><p num="1087"> Example 361 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Morpholine-4-ylsulfonyl) phenyl] sulfonyl} benzamide Example 361A 4- (Morpholine Sulfonyl) Benzene Sulfonamide This Example compound was prepared by substituting Example 66D of Example 66E with 4- (morpholinosulfonyl) benzene-1-sulfonyl chloride.</p><p num="1088"> Example 361B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Morpholine-4-ylsulfonyl) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 361A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 10.99 (s, 1H), 7.76 (d, 2H), 7.57 (d, 1H), 7.46 (d, 2H), 7.35 (d, 2H), 7.28 (m, 2H), 7.05 (d, 2H) , 6.89 (d, 1H), 6.70 (dd, 1H), 6.57 (dd, 1H), 6.31 (m, 1H), 6.21 (m, 1H), 3.60 (m, 4H), 2.97 (m, 4H), 2.79 (m, 4H), 2.72 (s, 2H), 2.18 (m, 6H), 1.96 (s, 2H), 1.39 (t, 2H), 0.93 (s, 6H).</p><p num="1089"> Example 362 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 1-Dioxide thiomorpholine-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 362A 4-[(1,1-dioxide thiomorpholine-4-yl) amino] -3-nitrophenyl} sulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with 4-aminothiomorpholine-1,1-dioxide.</p><p num="1090"> Example 362B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1,1, 1-Dioxide thiomorpholine-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 362A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.19 (s, 1H), 11.17 (s, 1H), 9.64 (s, 1H), 8.55 (d, 1H), 7.86 (m, 1H), 7.78 (m, 1H), 7.51 (d, 1H) , 7.40 (m, 2H), 7.33 (d, 2H), 7.16 (s, 1H), 7.03 (d, 2H), 6.86 (dd, 1H), 6.64 (dd, 1H), 6.39 (s, 1H), 6.13 (d, 1H), 3.50 (m, 4H), 3.17 (m, 4H), 3.02 (m, 4H), 2.72 (s, 2H), 2.15 (m, 6H), 1.94 (s, 2H), 1.37 (t, 2H), 0.91 (s, 6H).</p><p num="1091"> Example 363 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 363A tert-Butylsis-4-morpholinocyclohexylcarbamate Methanol (10 ml) was added to a mixture of morpholine (4.08 ml) and tert-butyl 4-oxocyclohexylcarbamate (10 g) stirred at room temperature for 24 hours in titanium (IV) isopropoxide (27.5 ml), followed by borohydride. Sodium borohydride (3.55 g) was carefully added. The reaction mixture was quenched with water, extracted with ether (2 x 100 mL), dehydrated with magnesium sulfate, filtered and concentrated. The crude product was purified with FC (silica gel 200 g, 30% -100% acetone / hexane) to give two products, the title compound and trans 4-morpholinocyclohexylcarbamate.</p><p num="1092"> Example 363B cis-4-morpholinocyclohexaneaminebis (2,2,2-trifluoroacetic acid) This Example compound was prepared by substituting Example 1A of Example 1B with Example 363A.</p><p num="1093"> Example 363C 4- (cis-4-morpholinocyclohexylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with Example 363B.</p><p num="1094"> Example 363D 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4- [cis- (4-morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 363C.¹1 H NMR (500MHz, Pyridine-d₅) δ 12.28 (s, 1H), 9.31 (d, 1H), 8.65 (d, 1H), 8.34 (dd, 1H), 8.17 (d, 1H), 7.53-7.57 (m, 2H), 7.40-7.47 ( m, 3H), 7.03-7.12 (m, 3H), 6.89 (d, 1H), 6.72 (dd, 1H), 6.62 (s, 1H), 6.54 (d, 1H), 3.69-3.75 (m, 4H) , 3.67 (s, 1H), 3.00-3.07 (m, 4H), 2.75 (s, 2H), 2.41-2.47 (m, 4H), 2.24 (t, 2H), 2.07-2.16 (m, 5H), 1.97 (s, 2H), 1.76-1.85 (m, 2H), 1.54-1.65 (m, 6H), 1.38 (t, 2H), 0.93 (s, 6H).</p><p num="1095"> Example 364 N-{[5-bromo-6- (tetrahydro-2H-pyran-4-ylmethoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 329B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.65 (d, 1H), 8.33 (s, 1H), 7.58 (d, 1H), 7.35 (d, 2H), 7.24 (t, 1H), 7.07 (m, 3H) , 6.89 (m, 1H), 6.67 (dd, 1H), 6.27 (m, 3H), 4.29 (d, 2H), 3.88 (dd, 2H), 3.35 (m, 4H), 3.09 (m, 4H), 2.88 (m, 2H), 2.34 (m, 2H), 2.17 (s, 2H), 2.06 (m, 1H), 1.98 (m, 2H), 1.65 (m, 2H), 1.36 (m, 4H), 0.93 (s, 6H).</p><p num="1096"> Example 365 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[6-[(Tetrahydro-2H-pyran-4-ylmethyl) amino] -5- (1,3-thiazole-2-yl) pyridin-3-yl] sulfonyl} benzamide This Example compound was prepared by substituting Example 329B of Example 331A with Example 325B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.22 (s, 1H), 9.76 (t, 1H), 9.12 (m, 1H), 8.50 (d, 1H), 8.26 (d, 1H), 8.02 (d, 1H), 7.87 (d, 1H) , 7.58 (d, 1H), 7.38 (d, 2H), 7.23 (t, 1H), 7.15 (d, 1H), 7.08 (d, 2H), 6.96 (m, 1H), 6.74 (dd, 1H), 6.47 (d, 1H), 6.33 (s, 1H), 6.22 (s, 1H), 3.86 (dd, 2H), 3.52 (t, 6H), 3.29 (m, 4H), 2.99 (m, 2H), 2.74 (m, 2H), 2.18 (s, 2H), 2.01 (s, 2H), 1.88 (m, 1H), 1.62 (m, 2H), 1.45 (t, 2H), 1.28 (m, 2H), 0.94 ( s, 6H).</p><p num="1097"> Example 366 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-cyano-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide Example 366A 3-Cyano-4-((tetrahydro-2H-pyran-4-yl) methylamino) benzenesulfonamide 3-Cyano-4-fluorobenzenesulfonamide (500 mg), (tetrahydropyran-4-yl) methylamine (288 mg) and N, N-diisopropylethylamine (1.3 mL) in tetrahydrofuran (15 mL) overnight at 80 ° C. Heated. The mixture is diluted with ethyl acetate and LVDS₃Wash with solution and brine and dehydrate (Na₂SO₄), Filtered and concentrated. The product was mixed with ethyl acetate.</p><p num="1098"> Example 366B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-cyano-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 366A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.30 (s, 1H), 11.08 (m, 1H), 7.81 (d, 1H), 7.63 (dd, 1H), 7.55 (d, 1H), 7.32 (m, 3H), 7.22 (d, 1H) , 7.17 (m, 1H), 7.02 (m, 3H), 6.79 (d, 1H), 6.71 (dd, 1H), 6.47 (d, 1H), 6.28 (m, 2H), 3.84 (dd, 2H), 3.25 (t, 2H), 3.13 (t, 2H), 3.05 (m, 4H), 2.73 (s, 2H), 2.15 (m, 6H), 1.95 (s, 2H), 1.82 (m, 1H), 1.59 (m, 2H), 1.38 (t, 2H), 1.20 (m, 2H), 0.92 (s, 6H).</p><p num="1099"> Example 367 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-cyano-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 366A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.20 (s, 1H), 10.99 (s, 1H), 7.94 (d, 1H), 7.74 (dd, 1H), 7.53 (d, 1H), 7.44 (d, 1H), 7.41 (m, 1H) , 7.33 (d, 2H), 7.21 (m, 2H), 7.04 (d, 2H), 6.89 (dd, 1H), 6.82 (d, 1H), 6.66 (dd, 1H), 6.42 (s, 1H), 3.83 (dd, 2H), 3.25 (t, 2H), 3.13 (t, 2H), 3.03 (m, 4H), 2.72 (s, 2H), 2.14 (m, 6H), 1.94 (s, 2H), 1.83 (m, 1H), 1.57 (m, 2H), 1.37 (m, 2H), 1.21 (m, 2H), 0.92 (s, 6H).</p><p num="1100"> Example 368 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3,,, 3-Dimethylbutyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was replaced with Example 189A 1- (2-methoxy-ethyl) -piperidine-4-ylamine with 3,3-dimethylbutylamine and 4-chloro-3-nitrobenzenesulfonamide with Example 187A. Prepared.</p><p num="1101"> Example 369 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1S) ) -1- (Hydroxymethyl) -3-methylbutyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with L-leucinol and substituting 4-chloro-3-nitrobenzenesulfonamide with Example 187A. ..</p><p num="1102"> Example 370 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(3-Nitro-4-{[(2R) -tetrahydrofuran-ylmethyl] amino} phenyl) sulfonyl] benzamide This Example compound was replaced with 4-(2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with (R)-(-)-tetrahydrofurfurylamine to replace 4-chloro-3-nitrobenzenesulfonamide. Prepared by replacing with Example 187A.</p><p num="1103"> Example 371 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(1R) ) -1- (Hydroxymethyl) -2-methylpropyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with D-valinol and substituting 4-chloro-3-nitrobenzenesulfonamide with Example 187A. ..</p><p num="1104"> Example 372 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Methoxyphenyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by replacing 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with 4-anisidine and replacing 4-chloro-3-nitrobenzenesulfonamide with Example 187A. ..</p><p num="1105"> Example 373 N-[(4-{[2- (1,3-benzodioxole-5-yl) ethyl] amino} -3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl) ethyl] ) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was replaced with 2-benzo [1,3] dioxol-5-yl-ethylamine in 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A to replace 4-chloro-3-. It was prepared by replacing the nitrobenzene sulfonamide with Example 187A.</p><p num="1106"> Example 374 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[3- (2-oxopyrrolidine-1-yl) propyl] amino} phenyl) sulfonyl] benzamide This Example compound was replaced with 1- (3-amino-propyl) -pyrrolidin-2-one in 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A to replace 4-chloro-3-one. It was prepared by replacing the nitrobenzene sulfonamide with Example 187A.</p><p num="1107"> Example 375 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(4-4-yl] Hydroxyphenyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by replacing 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with 4-aminophenol and replacing 4-chloro-3-nitrobenzenesulfonamide with Example 187A. did.</p><p num="1108"> Example 376 N-{[4-({2- [4- (aminosulfonyl) phenyl] ethyl} amino) -3-nitrophenyl] sulfonyl} -4- (4-{[2- (4-chlorophenyl) -4,4 -Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was replaced with 4- (2-aminoethyl) benzenesulfonamide in Example 189A to replace 1- (2-methoxy-ethyl) -piperidine-4-ylamine with 4-chloro-3-nitrobenzenesulfonamide. Prepared by replacing with Example 187A.</p><p num="1109"> Example 377 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[3-] (1H-imidazol-1-yl) propyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indole-5-yloxy) benzamide This Example compound was replaced with 1- (3-aminopropyl) imidazole in 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A to give 4-chloro-3-nitrobenzenesulfonamide. Prepared by replacing with 187A.</p><p num="1110"> Example 378 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) ) -N-[(3-Nitro-4-{[(1S) -1-phenylethyl] amino} phenyl) sulfonyl] benzamide This Example compound was replaced with (S)-(-)-1-phenylethylamine in 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A to replace 4-chloro-3-nitrobenzenesulfonamide. Was replaced with Example 187A.</p><p num="1111"> Example 379 N-({2-chloro-5-fluoro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide Example 379A 2-Chloro-5-fluoro-4-((tetrahydro-2H-pyran-4-yl) methylamino) benzenesulfonamide 2-Chloro-4,5-difluorobenzenesulfonamide (0.683g), (tetrahydro-2H-pyran-4-yl) methaneamine (0.346g), N, N-diisopropylethylamine (0.681ml) and dioxane (10ml) Heated at 65 ° C for 2.5 days. Additional (tetrahydro-2H-pyran-4-yl) methaneamine (0.346 g) and N, N-diisopropylethylamine (0.681 ml) were added and heating was continued at 70 ° C for 1.5 days. The reaction mixture was concentrated and column chromatographed on silica gel with 0-3% methanol in dichloromethane as the eluent. The obtained solid was mixed with dichloromethane to give the title compound.</p><p num="1112"> Example 379B N-({2-chloro-5-fluoro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 379A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ ppm 11.23 (s, 1H), 11.02 (s, 1H), 7.61 (m, 2H), 7.44 (m, 2H), 7.33 (d, 2H), 7.30 (m, 1H), 7.03 (d, 2H) ), 6.95 (m, 1H), 6.88 (m, 2H), 6.67 (dd, 1H), 6.44 (m, 1H), 6.09 (d, 1H), 3.82 (dd, 2H), 3.22 (m, 2H) , 3.03 (m, 6H), 2.72 (m, 2H), 2.14 (m, 6H), 1.94 (m, 2H), 1.81 (m, 1H), 1.61 (m, 2H), 1.37 (t, 2H), 1.18 (m, 2H), 0.91 (s, 6H).</p><p num="1113"> Example 380 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[2- (2-Methoxyethoxy) ethyl] thio} -3-nitrophenyl) sulfonyl] benzamide Example 380A 4- (2- (2-Methoxyethoxy) ethylthio) -3-nitrobenzene sulfonamide Sodium hydride (0.6 g) in tetrahydrofuran (10 ml) was added to a 100 mL round bottom flask to obtain a suspension. 2- (2-Methoxyethoxy) ethanethiol (1 g) was added slowly. After stirring the mixture for 30 minutes, 4-fluoro-3-nitrobenzenesulfonamide (1.616 g) in 10 ml tetrahydrofuran was added slowly. After stirring the mixture overnight, water was added slowly and the product was extracted with ethyl acetate (20 ml x 3). Na the organic layer together₂SO₄Dehydrated with. After filtering and concentrating the mixture, the crude product was added to a silica gel column and purified by eluting 0-10% methanol in dichloromethane.</p><p num="1114"> Example 380B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[2- (2-Methoxyethoxy) ethyl] thio} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 380A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 10.99 (s, 1H), 8.42 (s, 1H), 7.75 (d, 1H), 7.56 (d, 1H), 7.34 (m, 5H), 7.05 (d, 2H), 6.90 (d, 1H) , 6.69 (dd, 1H), 6.55 (dd, 1H), 6.30 (m, 1H), 6.17 (d, 1H), 3.67 (t, 2H), 3.54 (m, 2H), 3.43 (m, 2H), 3.21 (m, 5H), 2.95 (m, 4H), 2.71 (s, 2H), 2.17 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1115"> Example 381 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-[(4-{[2- (2-Methoxyethoxy) ethyl] thio} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by replacing Example 1F of Example 177 with Example 380A and replacing Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.06 (s, 1H), 8.37 (d, 1H), 7.80 (dd, 1H), 7.61 (d, 1H), 7.45 (d, 1H), 7.34 (d, 2H), 7.18 (t, 1H) , 7.04 (m, 3H), 6.87 (t, 1H), 6.60 (dd, 1H), 6.22 (m, 3H), 3.68 (t, 2H), 3.55 (m, 2H), 3.43 (m, 2H), 3.22 (m, 5H), 2.94 (m, 4H), 2.72 (s, 2H), 2.16 (m, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1116"> Example 382 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-{[4- (Methylsulfonyl) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with 4- (methylamino) -3-nitrobenzenesulfonamide.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.05 (m, 4H), 7.51 (d, 1H), 7.38 (m, 4H), 7.14 (m, 1H), 7.04 (d, 2H), 6.85 (d, 1H) , 6.64 (dd, 1H), 6.40 (m, 1H), 6.17 (d, 1H), 3.27 (s, 3H), 3.05 (m, 4H), 2.79 (m, 2H), 2.21 (m, 6H), 1.96 (s, 2H), 1.39 (t, 2H), 0.92 (s, 6H).</p><p num="1117"> Example 383 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) )-N-{[4- (Methylsulfonyl) phenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 1F of Example 177 with 4- (methylamino) -3-nitrobenzenesulfonamide and Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.26 (s, 1H), 7.96 (m, 4H), 7.54 (d, 1H), 7.35 (d, 2H), 7.30 (m, 1H), 7.18 (d, 1H), 7.05 (d, 2H) , 6.97 (t, 1H), 6.70 (dd, 1H), 6.37 (d, 1H), 6.30 (m, 2H), 3.25 (s, 3H), 3.08 (m, 4H), 2.84 (m, 2H), 2.26 (m, 6H), 1.97 (s, 2H), 1.40 (t, 2H), 0.93 (s, 6H).</p><p num="1118"> Example 384 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(2,,, 2-Dimethyltetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 384A The title compound was prepared as described in Example 297A by substituting (1,4-dioxane-2-yl) methanol with (2,2-dimethyltetrahydro-2H-pyran-4-yl) methanol. did.</p><p num="1119"> Example 384B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4- [(2,,, 2-Dimethyltetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide The title compound was prepared in the same manner as described in Example 175F, replacing Example 175E and Example 1F with Example 26C and Example 384A, respectively.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 2H), 8.38 (d, 1H), 8.05 (dd, 1H), 7.51 (d, 1H), 7.31-7.43 (m, 5H), 7.15 (d, 1H), 7.04 (d, 2H), 6.85 (dd, 1H), 6.65 (dd, 1H), 6.40 (s, 1H), 6.15 (d, 1H), 3.98-4.07 (m, 2H), 3.54-3.67 (m, 2H), 3.05 (s, 4H), 2.78 (s, 2H), 2.09-2.31 (m, 7H), 1.95 (s, 2H), 1.56-1.68 (m, 2H), 1.38 (t, 2H), 1.08-1.27 (m) , 8H), 0.92 (s, 6H).</p><p num="1120"> Example 385 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide Example 385A 5-Bromo-6-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-sulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methanol of Example 329B with Example 306C.</p><p num="1121"> Example 385B 5-Cyano-6-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-sulfonamide This Example compound was prepared by substituting Example 329B of Example 333A with Example 385A.</p><p num="1122"> Example 385C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 385B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.10 (s, 1H), 8.79 (s, 1H), 8.59 (s, 1H), 7.54 (d, 1H), 7.34-7.38 (m, 4H), 7.04-7.06 (m, 3H), 6.79 ( dd, 1H), 6.62 (dd, 1H), 6.35 (s, 1H), 6.17 (d, 1H), 4.28 (d, 2H), 3.76-3.79 (m, 2H), 3.56-3.62 (m, 2H) , 3.07 (br s, 4H), 2.12-2.17 (m, 4H), 1.96 (s, 2H), 1.80-1.84 (m, 2H), 1.40 (t, 2H), 0.94 (s, 6H).</p><p num="1123"> Example 386 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 335A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.20 (s, 1H), 8.67 (d, 1H), 8.35 (d, 1H), 7.57 (d, 1H), 7.36 (d, 2H), 7.26 (t, 1H), 7.11 (d, 1H) , 7.05 (d, 2H), 6.90 (t, 1H), 6.70 (dd, 1H), 6.31 (d, 1H), 6.30 (d, 1H), 6.27 (s, 1H), 4.30 (d, 2H), 3.88 (dd, 2H), 3.35 (m, 2H), 3.12 (br s, 4H), 2.96 (br s, 2H), 2.40 (br s, 4H), 2.16 (br m, 2H), 2.06 (m, 1H), 1.98 (s, 2H), 1.65 (d, 2H), 1.41 (t, 2H), 1.36 (m, 2H), 0.93 (s, 6H).</p><p num="1124"> Example 387 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide Example 387A 5,6-dichloropyridin-3-sulfonamide This Example compound was prepared by replacing 5-bromo-6-chloropyridin-3-sulfonyl chloride in Example 329A with 5,6-dichloropyridine-3-sulfonyl chloride.</p><p num="1125"> Example 387B 5-Chloro-6-((Tetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-sulfonamide This Example compound was prepared by substituting Example 329A of Example 329B with Example 387A.</p><p num="1126"> Example 387C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 387B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.24 (s, 1H), 8.45 (d, 1H), 8.05 (d, 1H), 7.56 (d, 1H), 7.36 (d, 2H), 7.28 (t, 1H), 7.15 (d, 1H) , 7.05 (d, 2H), 6.95 (t, 1H), 6.71 (dd, 1H), 6.39 (d, 1H), 6.30 (d, 1H), 6.27 (s, 1H), 4.26 (d, 2H), 3.88 (dd, 2H), 3.35 (m, 2H), 3.09 (br s, 4H), 2.85 (br s, 2H), 2.30 (br s, 4H), 2.15 (br m, 2H), 2.07 (m, 1H), 1.96 (s, 2H), 1.65 (d, 2H), 1.41 (t, 2H), 1.35 (m, 2H), 0.93 (s, 6H).</p><p num="1127"> Example 388 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Morpholine-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide Example 388A 5-Bromo-6- (2-morpholinoethoxy) Pyridine-3-sulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methanol of Example 329B with 2-morpholinoethanol.</p><p num="1128"> Example 388B 5-Cyano-6- (2-morpholinoethoxy) pyridine-3-sulfonamide This Example compound was prepared by substituting Example 329B of Example 335A with Example 388A.</p><p num="1129"> Example 388C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Morpholine-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-5-yloxy) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 388B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.09 (s, 1H), 8.77 (s, 1H), 8.55 (s, 1H), 7.55 (d, 1H), 7.34-7.36 (m, 4H), 7.04-7.06 (m, 3H), 6.78 ( dd, 1H), 6.63 (d, 1H), 6.35 (s, 1H), 6.16 (s, 1H), 4.61 (t, 2H), 3.58 (m, 4H), 3.05 (br s, 4H), 2.89 ( br s, 4H), 2.65 (br s, 4H), 2.32-2 (br s, 2H), 2.15 (br s, 2H), 1.96 (s, 2H), 1.39 (t, 2H), 0.92 (s, 6H).</p><p num="1130"> Example 389 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) oxy] phenyl} sulfonyl) benzamide Example 389A 1- (Tetrahydro-2H-Pyran-4-yl) Piperidine-4-ol Piperidine-4-ol (7.8 g) and dihydro-2H-pyran-4 (3H) -one (5.0 g) were dissolved in titanium (IV) isopropoxide (30 mL) and the reaction was stirred at room temperature overnight. Methanol (40 mL) was added and the reaction was cooled to 0 ° C. NaBH₄(3.8 g) was added in several portions over 1 hour. After 2 hours, 1N aqueous NaOH solution was added, followed by ethyl acetate. After filtering with Celite, the layers are separated, the aqueous layer is extracted with ethyl acetate, and the combined organic layer is Na.₂SO₄Dehydrated with. Crude material in methanol, 5-10% 7N NH₃CH including₂Cl₂Was purified by column chromatography using.</p><p num="1131"> Example 389B 3-Nitro-4- (1- (Tetrahydro-2H-Pyran-4-yl) Piperidine-4-Iloxy) Benzene Sulfonamide Example 389A (370 mg) was dissolved in tetrahydrofuran (10 mL) and 95% NaH (200 mg) was added. After stirring for 10 minutes, 4-fluoro-3-nitrobenzenesulfonamide (420 mg) was added and the reaction was stirred at room temperature overnight. Reactant in methanol, 6-10% 7N NH₃CH including₂Cl₂Purified by column chromatography using, followed by slurry in diethyl ether, and the solid product was filtered off.</p><p num="1132"> Example 389C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) oxy] phenyl} sulfonyl) benzamide This Example compound is now CH for chromatography₂Cl₂It was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 389B, except that 5-7% methanol was used.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.07 (br s, 1H), 8.27 (s, 1H), 7.92 (d, 1H), 7.55 (d, 1H), 7.33 (m, 5H), 7.04 (m, 3H), 6.77 (dd, 1H) ), 6.58 (d, 1H), 6.35 (s, 1H), 6.14 (s, 1H), 4.85 (s, 1H), 3.93 (dd, 2H), 3.27 (m, 4H), 2.98 (br m, 7H) ), 2.72 (s, 2H), 2.16 (m, 6H), 2.04 (m, 2H), 1.95 (s, 2H), 1.84 (m, 4H), 1.55 (m, 2H), 1.38 (t, 2H) , 0.92 (s, 6H).</p><p num="1133"> Example 390 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Morpholine-4-ylbut-2-inyl) oxy] -3-nitrophenyl} sulfonyl) benzamide Example 390A 4-Morpholine Nobuta-2-in-1-ol To a mixture of morpholine (4.36 g) in toluene (15 mL) was added 4-chlorobut-2-in-1-ol (2.09 g) in toluene (5 mL). The mixture was stirred at 85 ° C for 3 hours. After cooling, the solid was filtered off. The filtrate was vacuum distilled to give the title compound.</p><p num="1134"> Example 390B 4- (4-Morpholine nobuta-2-inyloxy) -3-nitrobenzene sulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methanol of Example 279A with Example 390A.</p><p num="1135"> Example 390C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-({4-[(4-Morpholine-4-ylbut-2-inyl) oxy] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1F of Example 177 with Example 390B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.40 (d, 1H), 8.11 (dd, 1H), 7.49-7.53 (m, 2H), 7.39-7.42 (m, 4H), 7.34 (d, 2H), 7.17 ( d, 1H), 7.04 (d, J = 8.54Hz, 2H), 6.85 (dd, 1H), 6.64 (dd, 1H), 6.40 (s, 1H), 6.14 (d, 1H), 5.15 (s, 2H) ), 3.52-3.54 (m, 4H), 3.04 (br s, 4H), 2.78 (br s, 2H), 2.37-2.39 (m, 4H), 2.12-2.20 (br s, 6H), 1.95 (s, 2H), 1.38 (t, 2H), 0.92 (s, 6H).</p><p num="1136"> Example 391 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-ethynyl-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide Example 391A 6-((Tetrahydro-2H-pyran-4-yl) methoxy) -5-((Triisopropylsilyl) ethynyl) Pyridine-3-sulfonamide Example 329B (0.176 g), bis (triphenylphosphine) palladium (II) chloride (0.176 g), copper (I) iodide (0.010 g), dimethylacetamide (2.5 ml) and triethylamine (0.105 ml) are combined. , Flushed with nitrogen and stirred for 2 minutes. Add (triisopropyl) acetylene (0.135 ml), flush the reaction mixture again with nitrogen, heat overnight at 60 ° C, dilute with ethyl acetate, wash with water and brine, and dehydrate (DDL).₄), Filtered and concentrated, chromatographed on silica gel with 10-30% ethyl acetate in hexanes as eluent to give the title compound.</p><p num="1137"> Example 391B 5-ethynyl-6-((tetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-sulfonamide Example 391A (0.205 g) in tetrahydrofuran (3 ml) at ambient temperature was treated with tetrabutylammonium fluoride (1 M in tetrahydrofuran) (0.906 ml) and stirred at ambient temperature for 4 hours. Additional tetrabutylammonium fluoride (1 M in tetrahydrofuran) (1.8 mL) was added and the mixture was heated at 40 ° C. for 45 minutes. Solid tetrabutylammonium fluoride (0.253 g) was added and heating was continued for 30 minutes. The reaction mixture was concentrated and then chromatographed on silica gel with 0-2% methanol in dichloromethane as eluent to give the title compound.</p><p num="1138"> Example 391C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-ethynyl-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 391B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ ppm 11.23 (s, 1H), 8.50 (d, 1H), 8.09 (d, 1H), 7.56 (d, 1H), 7.34 (m, 2H), 7.28 (m, 1H), 7.18 (d, 1H) ), 7.04 (m, 2H), 6.98 (t, 1H), 6.70 (dd, 1H), 6.44 (d, 1H), 6.27 (m, 2H), 4.55 (s, 1H), 4.25 (d, 2H) , 3.87 (dd, 2H), 3.34 (m, 2H), 3.06 (m, 4H), 2.81 (m, 1H), 2.20 (m, 6H), 2.04 (m, 1H), 1.96 (m, 2H), 1.65 (dd, 2H), 1.35 (m, 5H), 0.92 (m, 6H).</p><p num="1139"> Example 392 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Morpholine-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 388B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.15 (s, 1H), 10.99 (s, 1H), 8.64 (d, 1H), 8.33 (d, 1H), 7.58 (d, 1H), 7.35 (d, 2H), 7.24 (m, 1H) , 7.07 (m, 3H), 6.89 (m, 1H), 6.66 (dd, 1H), 6.26 (m, 3H), 4.59 (t, 2H), 3.58 (m, 4H), 3.05 (m, 4H), 2.87 (m, 4H), 2.62 (m, 4H), 2.24 (m, 6H), 1.98 (m, 2H), 1.40 (t, 2H), 0.93 (s, 6H).</p><p num="1140"> Example 393 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indole-4-yloxy) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 55B and Example 1F with Example 385B.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.17 (s, 1H), 8.66 (s, 1H), 8.36 (s, 1H), 7.58 (d, 1H), 7.36 (d, 2H), 7.25 (s, 1H), 7.07 (m, 3H) , 6.89 (m, 1H), 6.68 (m, 1H), 6.27 (m, 3H), 4.60 (s, 1H), 4.54 (s, 1H), 3.78 (m, 2H), 3.60 (m, 2H), 3.33 (m, 2H), 3.09 (m, 4H), 2.92 (m, 2H), 2.36 (m, 2H), 2.16 (m, 2H), 1.97 (s, 2H), 1.87 (m, 4H), 1.40 (t, 2H), 0.93 (s, 6H).</p><p num="1141"> Example 394 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(3-3-yl] Hydroxy-4-methoxyphenyl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indole-5-yloxy) benzamide This Example compound was replaced with 5-amino-2-methoxyphenol in 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A and 4-chloro-3-nitrobenzenesulfonamide in Example 187A. Prepared by replacing with.</p><p num="1142"> Example 395 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (2,3-dihydro-1H) -Indole-4-yloxy) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 103 (676 mg) and NaCNBH₃(49 mg) were combined in acetic acid (10 mL) and stirred overnight at room temperature. Dilute the reaction with water, 95/5 CH₂Cl₂/ Extracted with methanol. Concentrate the organic layer and remove the crude material by 20-100% CH by preparative HPLC using a C18 column, 250 x 50 mm, 10 μ.₃The title compound was obtained as bistrifluoroacetate by eluting with a gradient of 0.1% trifluoroacetic acid in CN vs. water and purifying.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.57 (br s, 1H), 9.70, 9.50 (both v br s, total 2H), 8.57 (d, 1H), 8.20 (br d, 1H), 7.85 (dd, 1H), 7.50 (d, 1H) ), 7.40 (d, 2H), 7.26 (d, 1H), 7.10 (d, 2H), 6.82 (dd, 1H), 6.75 (dd, 1H), 6.40 (d, 1H), 6.27 (d, 1H) , 5.94 (d, 1H), 4.00, 3.70 (both v br m, total 8H), 3.55 (v br m, 3H), 3.42 (t, 2H), 3.37 (v br m, 1H), 3.10 (br m) , 2H), 2.80 (m, 6H), 2.20 (br m, 4H), 2.03 (s, 2H), 1.82 (br m, 2H), 1.46 (t, 2H), 0.96 (s, 6H).</p><p num="1143"> Example 396 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1-1-yl] Methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (pyridin-3-ylamino) benzamide Example 396A Methyl 4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -2- (pyridin-3-ylamino) benzoate Example 18E (500 mg), cesium carbonate (429 mg), palladium (II) acetate (21 mg), rac-2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (58.5 mg) and toluene (6.4 mg). mL) solution of N₂Degassed at. The mixture was stirred at 115 ° C for 5 minutes. After cooling to room temperature, add pyridine-3-amine (106 mg) and mix the reaction mixture with N.₂It was degassed again and stirred at 115 ° C for 45 minutes. The mixture is cooled to room temperature, diluted with ethyl acetate and H₂O, wash with brine and dehydrate (DDL₄), Filtered and concentrated. The crude product is CH by flash chromatography on silica gel.₂Cl₂It was eluted with / 1% methanol and purified to give the title compound.</p><p num="1144"> Example 396B 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -2- (pyridin-3-ylamino) benzoic acid, dihydrochloric acid This Example compound was prepared by substituting Example 224C of Example 224D with Example 396A.</p><p num="1145"> Example 396C 4- (4-((2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazin-1-yl) -N- (4- (1-methylpiperidin-4-ylamino) ) -3-Nitrophenylsulfonyl) -2- (pyridin-3-ylamino) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 396B and substituting Example 1F with Example 21A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.32-11.40 (br s, 1H), 9.21-9.39 (br s, 1H), 8.51 (d, 1H), 8.33 (d, 1H), 8.09 (dd, 1H), 7.98-8.07 (m, 1H) ), 7.94 (dd, 1H), 7.81 (d, 1H), 7.52-7.58 (m, 1H), 7.36 (d, 2H), 7.24-7.30 (m, 1H), 7.15 (d, 1H), 7.08 ( d, 2H), 6.53 (d, 1H), 6.33 (dd, 1H), 3.81-3.96 (br s, 2H), 3.02-3.12 (br s, 6H), 2.67-2.80 (m, 5H), 2.07- 2.32 (m, 8H), 1.98 (s, 3H), 1.70-1.85 (br s, 1H), 1.41 (t, 3H), 0.95 (s, 6H).</p><p num="1146"> Example 397 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(1-Tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) -2- (pyridin-3-ylamino) benzamide This Example compound was prepared by substituting Example 26C of Example 177 with Example 396B and substituting Example 1F with Example 173C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 9.10-9.33 (br s, 1H), 8.53 (d, 1H), 8.36 (d, 1H), 8.12 (dd, 1H), 8.00-8.07 (m, 1H), 7.96 (dd, 1H), 7.80 (d, 1H), 7.53-7.59 (m, 1H), 7.38 (d, 2H), 7.25-7.31 (m, 1H), 7.20 (d, 1H), 7.09 (d, 2H), 6.53 (s, 1H) ), 6.36 (m, 1H), 4.28-4.75 (br s, 1H), 3.90-4.09 (m, 8H), 3.51-3.61 (m, 2H), 3.35 (m, 8H), 3.01-3.18 (br s) , 4H), 2.15-2.26 (m, 1H), 1.88-2.09 (m, 5H), 1.56-1.86 (m, 4H), 1.44 (t, 2H), 0.96 (s, 6H).</p><p num="1147"> Example 398 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(1-Tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) -2- (pyridin-3-yloxy) benzamide Example 398A 4-Fluoro-2- (Pyridine-3-yloxy) -Methyl benzoate This Example compound was prepared by substituting ethyl 2,4-difluorobenzoate of Example 20A with methyl 2,4-difluorobenzoate and 5-hydroxyindazole with 3-hydroxypyridine.</p><p num="1148"> Example 398B 4- {4- [2- (4-Chloro-phenyl) -4,4-dimethyl-cyclohex-1-enylmethyl] -piperazine-1-yl} -2- (pyridin-3-yloxy) -methyl benzoate This Example compound was prepared by substituting Example 20A of Example 20D with Example 398A.</p><p num="1149"> Example 398C 4- {4- [2- (4-Chloro-phenyl) -4,4-dimethyl-cyclohex-1-enylmethyl] -piperazine-1-yl} -2- (pyridin-3-yloxy) -benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 398B.</p><p num="1150"> Example 398D 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (pyridin-3-yloxy)- N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 398C and Example 1F with Example 173C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.36 (d, 1H), 8.11 (t, 1H), 8.08 (t, 2H), 7.70 (dd, 1H), 7.60 (d, 1H), 7.37 (d, 2H), 7.15 (dd, 1H) , 7.10-7.03 (m, 3H), 7.00 (dd, 1H), 6.73 (dd, 1H), 6.43 (d, 1H), 3.99-3.93 (m, 3H), 3.86 (m, 1H), 3.13 (m) , 6H), 2.78 (br s, 2H), 2.30-2.05 (m, 10H), 1.98 (br s, 2H), 1.92-1.67 (m, 6H), 1.57 (m, 2H), 1.41 (t, 2H) ), 0.94 (s, 6H).</p><p num="1151"> Example 399 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1,2,3,4-tetrahydroisoquinoline-5-yloxy) benzamide Example 399A tert-Butyl 5-hydroxy-3,4-dihydroisoquinoline-2 (1H) -carboxylate A mixture of 1,2,3,4-tetrahydroisoquinoline-5-ol hydrochloric acid (1.0 g), di-tert-butyl dicarbonate (1.27 g) and 1.0N NaOH (14.5 mL) in dioxane (20 mL) at room temperature The mixture was stirred for 16 hours. The reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was neutralized with 5% HCl. The combined organic layer is washed with brine and dehydrated (DDL).₄), Filtered and concentrated. The residue was purified by flash chromatography on silica gel to give the title compound.</p><p num="1152"> Example 399B tert-Butyl 5- (2- (ethoxycarbonyl) -5-fluorophenoxy) -3,4-dihydroisoquinoline-2 (1H) -carboxylate This Example compound was prepared by replacing 5-hydroxyindazole of Example 20A with Example 399A.</p><p num="1153"> Example 399C tert-Butyl 5- (5-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enyl) methyl) piperazine-1-yl) -2- (ethoxycarbonyl) phenoxy) -3,4-dihydroisoquinoline-2 (1H) -carboxylate This Example compound was prepared by substituting Example 20A of Example 20D with Example 399B.</p><p num="1154"> Example 399D 2- (2- (tert-Butyloxycarbonyl) -1,2,3,4-tetrahydroisoquinoline-5-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-enyl) Methyl) Piperazine-1-yl) Benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 399C.</p><p num="1155"> Example 399E 2- (2- (tert-butoxycarbonyl) -1,2,3,4-tetrahydroisoquinoline-5-yloxy) -4-(4-((2- (4-chlorophenyl) -4,4-dimethylcyclohexa -1-Anyl) Methyl) Piperazine-1-yl) Benzoic Acid 3-Nitro-4-((Tetrahydro-2H-Pyran-4-yl) Methylamino) Benzenesulfonic Anhydrous This Example compound was prepared by substituting Example 26C of Example 177 with Example 399D.</p><p num="1156"> Example 399F 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2- (1,2,3,4-tetrahydroisoquinoline-5-yloxy) benzamide A mixture of Example 399E (0.058 g) and trifluoroacetic acid (1 mL) in dichloromethane (10 mL) was stirred for 2 hours. The solvent was removed and the residue was taken up in ethyl acetate. Then saturate this₃, Brine wash and DDL₄Dehydrated with, filtered and concentrated to give the title compound.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 8.36 (t, 1H), 8.27 (d, 1H), 7.65 (d, 1H), 7.36 (d, 2H), 7.07 (d, 2H) 6.93-6.97 (m, 2H), 6.73 (d 1H) , 6.69 (dd, 1H), 6.33 (d, 1H), 6.26 (d, 1H), 4.19 (s, 2H), 3.85 (dd, 2H), 3.05-3.09 (m, 6H), 2.77 (s, 2H) ), 2.17-2.24 (m, 6H), 1.98-1.99 (m, 2H), 1.60-1.63 (m, 2H0,1.41 (t, 2H), 0.94 (s, 6H).</p><p num="1157"> Example 400 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 400A 4-Hydroxy-indazole-1-carboxylic acid tert-butyl ester and 4-hydroxy-indazole-2-carboxylic acid tert-butyl ester 4-Hydroxyindazole (3.94 g) was added to tetrahydrofuran (250 mL) and cooled to 0 ° C. using an ice bath. Sodium hydride (60% dispersion in mineral oil, 1.23 g) was added and the mixture was stirred at 0 ° C for 5 minutes. The mixture was warmed to room temperature and stirred for an additional 20 minutes. The mixture was cooled again to 0 ° C. using an ice bath and tert-butyldimethylchlorosilane (4.65 g) was added. The mixture was warmed to room temperature and stirred for 16 hours. The solvent volume was reduced under vacuum and the residue was vacuum filtered through a silica gel filler, washed with ethyl acetate and the solvent removed under vacuum. Acetonitrile (200 mL), di-tert-butyl dicarbonate (7.06 g) and 4- (dimethylamino) pyridine (0.359 g) were added to the residue. The mixture was stirred at room temperature for 3 hours and the solvent was removed under vacuum. Tetrahydrofuran (200 mL) and tetrabutylammonium fluoride (1 M in tetrahydrofuran, 82 mL) were added to the residue. The mixture was stirred at room temperature for 4 days, the solvent was removed under vacuum and the residue was taken up in ethyl acetate. The mixture was extracted with saturated aqueous ammonium chloride solution, extracted with brine and dehydrated with anhydrous sodium sulfate. The mixture was vacuum filtered through silica gel and the solvent was removed under vacuum to give a mixture of the two products. It was used in the next step without purification.</p><p num="1158"> Example 400B 4-Fluoro-2- (1H-indazole-4-yloxy) -benzoic acid methyl ester Example 400A (5.56g) was added to diglyme (200mL) and potassium tert-butoxide (1M in tetrahydrofuran, 30.8mL) was added. The mixture was mixed at room temperature for 15 minutes, methyl 2,4-difluorobenzoate was added and the mixture was heated at 115 ° C. for 16 hours. The mixture was cooled, the solvent was removed under vacuum, the residue was taken up in dichloromethane (100 mL) and trifluoroacetic acid (22.6 mL) was added. The mixture was stirred at room temperature for 16 hours, the solvent was removed under vacuum, the residue was taken up in ethyl acetate, washed with a saturated aqueous sodium bicarbonate mixture and the organic layer was dehydrated over anhydrous sodium sulfate. This material was purified by flash column chromatography on silica gel, increasing 30% ethyl acetate (in hexane) to 40% ethyl acetate (in hexane).</p><p num="1159"> Example 400C 2- (1H-indazole-4-yloxy) -4-piperazin-1-yl-benzoic acid methyl ester Example 400B (2.00 g) and piperazine (2.71 g) were added to dimethyl sulfoxide (60 mL) and heated to 100 ° C. for 1 hour. The mixture was cooled, added to dichloromethane, washed twice with water, washed with saturated aqueous sodium bicarbonate mixture and dehydrated with anhydrous sodium sulfate. After filtration, the solvent was removed under vacuum.</p><p num="1160"> Example 400D 4- {4- [2- (4-Chloro-phenyl) -4,4-dimethyl-cyclohex-1-enylmethyl] -piperazine-1-yl} -2- (1H-indazole-4-yloxy) -benzoic acid Methyl ester This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxardhide of Example 1A with Example 218A and tert-butylpiperazin-1-carboxylate with Example 400C.</p><p num="1161"> Example 400E 4- {4- [2- (4-Chloro-phenyl) -4,4-dimethyl-cyclohex-1-enylmethyl] -piperazine-1-yl} -2- (1H-indazole-4-yloxy) -benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 400D.</p><p num="1162"> Example 400F 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) )-N-({3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 400E.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.09 (s, 1H), 8.56 (t, 1H), 8.38 (d, 1H), 7.80 (s, 1H), 7.56 (dd, 1H), 7.53 (d, 1H), 7.36 (d, 2H) , 7.16-7.05 (m, 4H), 6.99 (d, 1H), 6.80 (dd, 1H), 6.52 (d, 1H), 6.19 (dd, 1H), 3.87 (dd, 2H), 3.25-3.12 (m) , 6H), 2.78 (m, 2H), 2.30-2.16 (m, 6H), 1.97 (br s, 2H), 1.90 (m, 1H), 1.63 (m, 2H), 1.53 (m, 1H), 1.40 (t, 2H), 1.29 (m, 3H), 0.94 (s, 6H).</p><p num="1163"> Example 401 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide Example 401A N-[(4-Chloro-3-nitrophenyl) sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine -1-yl) -2- (1H-indazole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 400E and substituting Example 1F with 4-chloro-3-nitrobenzenesulfonamide.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.04 (s, 1H), 8.17 (br s, 1H), 7.75 (s, 1H), 7.73 (d, 1H), 7.66-7.61 (m, 2H), 7.38 (d, 2H), 7.11-7.01 (m, 4H), 6.79 (dd, 1H), 6.54 (d, 1H), 6.10 (dd, 1H), 3.38-3.05 (m, 8H), 2.73 (br s, 2H), 2.19 (m, 2H) , 2.00 (br s, 2H), 1.44 (t, 2H), 0.95 (s, 6H).</p><p num="1164"> Example 401B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) )-N-({3-Nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with Example 173B and substituting 4-chloro-3-nitrobenzenesulfonamide with Example 401A. ..¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.05 (br s, 1H), 8.35 (d, 1H), 8.13 (d, 1H), 7.78 (s, 1H), 7.61-7.52 (m, 2H), 7.35 (d, 2H), 7.11-7.03 (m, 4H), 6.98 (d, 1H), 6.77 (dd, 1H), 6.48 (d, 1H), 6.18 (m, 1H), 3.69-3.52 (m, 4H), 3.12 (m, 6H), 2.76 (br s, 2H), 2.67 (m, 4H), 2.28-2.16 (m, 6H), 2.09-2.01 (m, 2H), 1.97 (br s, 2H), 1.95 (m, 2H), 1.50- 1.38 (m, 6H), 0.93 (s, 6H).</p><p num="1165"> Example 402 Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4) -Iloxy) -N-({4-[(4-Morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was replaced with trans-4-morpholine-4-yl-cyclohexylamine in 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A to replace 4-chloro-3-nitrobenzenesulfonamide. Was replaced with Example 401A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.02 (br s, 1H), 8.35 (d, 1H), 8.12 (m, 1H), 7.75 (s, 1H), 7.65-7.55 (m, 2H), 7.35 (d, 2H), 7.10-7.03 (m, 4H), 6.97 (m, 1H), 6.76 (dd, 1H), 6.44 (m, 1H), 6.17 (t, 1H), 3.95 (m, 2H), 3.77 (m, 1H), 3.62 ( m, 1H), 3.10 (m, 6H), 2.75 (br s, 2H), 2.28-2.14 (m, 8H), 2.06 (m, 2H), 1.97 (br s, 2H), 1.85 (m, 2H) , 1.71 (m, 2H), 1.55 (m, 4H), 1.40 (t, 2H), 0.93 (s, 6H).</p><p num="1166"> Example 403 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 403A Methyl 4-fluoro-2- (3-fluoro-2-nitrophenoxy) benzoate Potassium t-butoxide (1.979 g) was added in portions to a solution of methyl 4-fluoro-2-hydroxybenzoate (3.0 g) in tetrahydrofuran (65 mL). The resulting solution was stirred at ambient temperature for 30 minutes and a solution of 1,3-difluoro-2-nitrobenzene (2.338 g) in tetrahydrofuran (15 mL) was added dropwise. After 1 hour, the reaction was heated under reflux for 18 hours. The reaction was quenched with water (10 mL), diluted with brine (75 mL) and extracted with methylene chloride (2 x 75 mL). The crude product was isolated by concentration, purified on silica gel and eluted with a gradient of 10, 20, 50% ethyl acetate in hexanes to give the title compound.</p><p num="1167"> Example 403B Methyl 2 (3- (bis (4-methoxyphenyl) methylamino) -2-nitrophenoxy) -4-fluorobenzoate Example 403A (3.82 g) and bis (4-methoxyphenyl) methaneamine (4.51 g) in a solution of N-methyl-2-pyrrolidinone (65 mL) in N-ethyl-N-isopropylpropan-2-amine (4.30 mL) Was added and the mixture was heated at 100 ° C. for 24 hours. The crude product isolated by concentration was purified on silica gel and eluted with a gradient of 10, 25 and 65% ethyl acetate in hexanes to give the title compound.</p><p num="1168"> Example 403C Methyl 2- (2-amino-3- (bis (4-methoxyphenyl) methylamino) phenoxy) -4-fluorobenzoate A nickel catalyst (2.76 g) was added to a solution of Example 403B (2.76 g) in a stainless steel pressure resistant bottle in tetrahydrofuran (125 mL). The mixture was stirred under 30 psi hydrogen at ambient temperature for 1 hour. The mixture was filtered through a nylon membrane to remove the catalyst and concentrated to give the product.</p><p num="1169"> Example 403D Methyl 2- (1- (bis (4-methoxyphenyl) methyl) -1H-benzo [d] imidazol-4-yloxy) -4-fluorobenzoate Concentrated hydrochloric acid (0.75 mL) was added to a solution of Example 403C (1.25 g) in triethyl orthoformate (30 mL). The mixture was stirred for 18 hours, quenched by the gradual addition of 50% saturated aqueous sodium carbonate solution (100 mL) and extracted with ethyl acetate (2 x 100 mL). The crude product was isolated by concentration, purified on silica gel and eluted with a gradient of 25, 50 and 70% ethyl acetate in hexanes to give the title compound.</p><p num="1170"> Example 403E Methyl 2- (1- (bis (4-methoxyphenyl) methyl) -1H-benzo [d] imidazol-4-yloxy) -4- (piperazine-1-yl) benzoate A solution of Example 403D (500 mg) and piperazine (420 mg) in dimethyl sulfoxide (9 mL) was heated at 100 ° C. for 3 hours. The crude product was isolated by concentration and subsequently post-treated in an aqueous system, which was purified on silica gel and eluted with a gradient of 5 and 10% methanol in methylene chloride to give the title compound.</p><p num="1171"> Example 403F Methyl 2- (1- (bis (4-methoxyphenyl) methyl) -1H-benzo [d] imidazol-4-yloxy) -4- (4-((2- (4-chlorophenyl) -4,4-dimethyl) Cyclohexa-1-enyl) methyl) piperazine-1-yl) benzoate Sodium triacetoxyborohydride (323 mg) was added in portions to a solution of Example 403E (430 mg) and Example 218A (259 mg) in dichloromethane (13 mL). After stirring for 42 hours, the reaction was gradually quenched with saturated aqueous sodium bicarbonate solution (80 mL) and extracted with methylene chloride (2 x 70 mL). The crude product was isolated by concentration, purified on silica gel and eluted with a gradient of 0, 2, 10% methanol in methylene chloride to give the title compound.</p><p num="1172"> Example 403G 2- (1- (bis (4-methoxyphenyl) methyl) -1H-benzo [d] imidazole-4-yloxy) -4- (4-((2- (4-chlorophenyl) -4,4-dimethylcyclohexi) Sa-1-enyl) Methyl) Piperazine-1-yl) Benzoic acid An aqueous solution (3.0 mL) of sodium hydroxide (269 mg) was added to a solution of Example 403F (545 mg) in a mixed solution of methanol (7.50 mL) and tetrahydrofuran (7.50 mL). The reaction mixture was heated at 50 ° C. for 18 hours and then concentrated. The residue was mixed with water (100 mL) and the pH was adjusted to about 7 with 1 M aqueous hydrochloric acid solution. The mixture was extracted with 10% methanol in methylene chloride (10 x 50 mL) and the combined organic layers were concentrated to give the title compound.</p><p num="1173"> Example 403H 2- (1- (bis (4-methoxyphenyl) methyl) -1H-benzo [d] imidazole-4-yloxy) -4- (4-((2- (4-chlorophenyl) -4,4-dimethylcyclohexi) Sa-1-enyl) methyl) piperazin-1-yl) -N- (3-nitro-4-((tetrahydro-2H-pyran-4-yl) methylamino) phenylsulfonyl) benzamide Example 403G (200mg), Example 1F (99mg), Triethylamine (0.122mL), N, N-Dimethylpyridin-4-amine (77mg) Mixing of dichloromethane (8mL) and N, N-dimethylformamide (1mL) In the solution in liquid, N¹-((Ethylimino) methylene)-N³, N³-Dimethylpropane-1,3-diamine hydrochloric acid (96 mg) was added. The reaction mixture was stirred for 18 hours and then concentrated. The crude product was purified on silica gel and eluted with a gradient of 80 and 100% ethyl acetate in hexanes to give the title compound.</p><p num="1174"> Example 403I 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) benzamide The solution of Example 403H (174 mg) and dichloromethane (25 mL) was cooled in an ice bath and 2,2,2-trifluoroacetic acid (25 mL) was gradually added dropwise. The reaction mixture was stirred under nitrogen for 30 minutes and the ice bath was removed. The reaction was stirred for 18 hours and then concentrated. The crude product was purified by reverse phase chromatography with ammonium acetate buffer in acetonitrile to give the title compound.¹1 H NMR (400MHz, Pyridine-d₅) δ 9.30 (d, 1H), 8.69 (t, 1H), 8.59 (s, 1H), 8.42 (dd, 1H), 7.99 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H) , 7.26 (m, 1H), 7.18 (m, 1H), 7.06 (d, 2H), 6.94 (d, 1H), 6.72-6.66 (m, 2H), 5.53 (m, 2H), 3.98 (m, 2H) ), 3.32 (m, 2H), 3.18 (t, 2H), 2.03 (m, 4H), 2.76 (s, 2H), 2.25 (m, 2H), 2.13 (m, 4H), 1.97 (s, 2H) , 1.83 (m, 1H), 1.60 (m, 2H), 1.40-1.29 (m, 4H), 0.94 (s, 6H).</p><p num="1175"> Example 404 N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 404A 5-Chloro-6-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-sulfonamide The title compound was prepared by replacing Example 329A of Example 329B with Example 387A and replacing methanol (tetrahydro-2H-pyran-4-yl) with Example 306C.</p><p num="1176"> Example 404B N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 1F of Example 177 with Example 404A and Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.09 (s, 1H), 8.27 (d, 1H), 7.88 (d, 1H), 7.80 (s, 1H), 7.60 (d, 1H), 7.37 (d, 2H), 7.03-7.10 (m, 4H), 6.79 (dd, 1H), 6.53 (d, 1H), 6.13 (d, 1H), 4.50 (d, 2H), 3.76-3.81 (m, 2H), 3.57-3.63 (m, 2H), 3.04 (br s, 4H), 2.84 (br s, 2H), 2.18 (m, 2H), 1.82-1.92 (m, 4H), 1.42 (t, 2H), 0.94 (s, 6H).</p><p num="1177"> Example 405 N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl)) -4,4-Dimethylcyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-4-yloxy) benzamide The title compound was prepared by replacing Example 1F of Example 177 with Example 404A and replacing Example 26C with Example 55B.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.21 (s, 1H), 8.43 (d, 1H), 8.06 (d, 1H), 7.55 (d, 1H), 7.34 (d, 2H), 7.27 (t, 1H), 7.13 (d, 1H) , 7.04 (d, 2H), 6.93 (t, 1H), 6.69 (dd, 1H), 6.36 (d, 1H), 6.28 (d, 1H), 6.26 (d, 1H), 4.51 (d, 2H), 3.73-3.79 (m, 2H), 3.55-3.61 (m, 2H), 3.08 (br s, 4H), 2.86 (br s, 2H), 2.31 (br s, 2H), 2.18 (m, 2H), 1.95 (s, 2H), 1.79-1.90 (m, 4H), 1.36 (t, 2H), 0.92 (s, 6H).</p><p num="1178"> Example 406 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({5-cyano-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 1F of Example 177 with Example 385B and Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.03 (s, 1H), 8.48 (d, 1H), 8.17 (s, 1H), 7.74 (s, 1H), 7.63 (d, 1H), 7.37 (d, 2H), 7.00-7.08 (m, 4H), 6.77 (dd, 1H), 6.51 (s, 1H), 6.07 (d, 1H), 4.55 (d, 2H), 3.77-3.81 (m, 2H), 3.58-3.63 (m, 2H), 3.20 (br s, 4H), 2.19 (br s, 2H), 1.99 (s, 2H), 1.85-1.92 (m, 4H), 1.42 (t, 2H), 0.94 (s, 6H).</p><p num="1179"> Example 407 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 407A (R) -tert-Butyl 1- (2,2-difluoroethyl) pyrrolidine-3-ylcarbamate N-Ethyl-N-isopropylpropane in a solution of (R) -tert-butylpyrrolidine-3-ylcarbamate (500 mg), 1,1-difluoro-2-iodoethane (618 mg) in N, N-dimethylformamide (6 mL). -2-Amine (1.403 mL) was added and the reaction was stirred at 70 ° C. for 72 hours. The reaction mixture was concentrated and the crude product was purified on silica gel and eluted with a gradient of 0, 2 and 5% methanol in methylene chloride to give the title compound.</p><p num="1180"> Example 407B (R) -1- (2,2-difluoroethyl) pyrrolidine-3-amine Hydrogen chloride in dioxane (5.24 mL), 4M, was added to a solution of Example 407A (525 mg) in a mixed solution of dichloromethane (3 mL) and methanol (2.0 mL). The reaction was stirred for 3 hours and concentrated to give the title compound.</p><p num="1181"> Example 407C (R) -4- (1- (2,2-difluoroethyl) pyrrolidine-3-ylamino) -3-nitrobenzenesulfonamide 4-Fluoro-3-nitrobenzene in a solution of Example 407B (468 mg) in tetrahydrofuran (20 mL), N-ethyl-N-isopropylpropan-2-amine (2.193 mL) and N, N-dimethylformamide (2 mL). Sulfonamide (473 mg) was added and the reaction mixture was stirred for 72 hours. The crude product was isolated by concentration, purified on silica gel and eluted with a gradient of 0.5, 2.5 and 5% methanol in methylene chloride to give the title compound.</p><p num="1182"> Example 407D (R) -2- (1- (bis (4-methoxyphenyl) methyl) -1H-benzo [d] imidazole-4-yloxy) -4- (4-((2- (4-chlorophenyl) -4, 4-Dimethylcyclohexa-1-enyl) methyl) piperazine-1-nitrophenylsulfonyl) benzamide The title compound was prepared by substituting Example 1F of Example 403H with Example 407C.</p><p num="1183"> Example 407E 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide The title compound was prepared by substituting Example 403H of Example 403I with Example 407D.¹1 H NMR (400MHz, Pyridine-d₅) δ 9.26 (d, 1H), 8.60-8.55 (m, 2H), 8.39 (m, 1H), 7.99 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H), 7.25 (m, 1H), 7.17 (m, 1H), 7.06 (d, 2H), 6.86 (d, 1H), 6.72-6.69 (m, 2H), 6.00-6.33 (m, 1H), 5.27 (m, 2H), 4.09 (m, 1H), 3.03 (m, 4H), 2.96-2.86 (m, 4H), 2.81-2.74 (m, 3H), 2.48 (m, 1H), 2.26 (m, 3H), 2.13 (m, 4H) ), 1.97 (s, 2H), 1.67 (m, 1H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1184"> Example 408 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide Example 408A 2- (1- (bis (4-methoxyphenyl) methyl) -1H-benzo [d] imidazol-4-yloxy) -4- (4-((2- (4-chlorophenyl) -4,4-dimethylcyclohexi) Sa-1-enyl) methyl) piperazin-1-yl) -N-(4-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) -3-nitrophenylsulfonyl) benzamide The title compound was prepared by substituting Example 1F of Example 403H with Example 306D.</p><p num="1185"> Example 408B 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] -3-nitrophenyl} sulfonyl) benzamide The title compound was prepared by substituting Example 403H of Example 403I with Example 408A.¹1 H NMR (400MHz, Pyridine-d₅) δ 9.01 (d, 1H), 8.57 (m, 2H), 7.99 (d, 1H), 7.53 (d, 1H), 7.44 (d, 2H), 7.25 (m, 1H), 7.21 (m, 1H) , 7.12 (d, 1H), 7.07 (d, 2H), 6.73-6.70 (m, 2H), 5.35 (m, 2H), 4.36 (s, 1H), 4.31 (s, 1H), 3.88 (m, 2H) ), 3.78 (m, 2H), 3.05 (m, 4H), 2.77 (s, 2H), 2.26 (m, 2H), 2.15 (m, 4H), 2.07-192 (m, 6H), 1.39 (t, 2H), 0.94 (s, 6H).</p><p num="1186"> Example 409 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Fluorotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide Example 409A (4-Fluorotetrahydro-2H-pyran-4-yl) Methylmethane sulfonate CH₂Cl₂A mixture of Example 306C (1.4 g), methanesulfonyl chloride (1.054 mL), triethylamine (2.99 mL) and 4- (dimethylamino) pyridine (0.051 g) in (20 mL) was stirred at 0 ° C for 2 hours. It was concentrated and chromatographed on silica gel with 30% ethyl acetate in hexanes as eluent to give the product.</p><p num="1187"> Example 409B 2-((4-Fluorotetrahydro-2H-pyran-4-yl) methyl) isoindoline-1,3-dione A mixture of Example 409A (1.8 g) and potassium phthalimide (2.356 g) in N, N-dimethylformamide (30 mL) was heated overnight at 150 ° C., diluted with ethyl acetate, washed with water and brine and dehydrated. Dehydration₄), Filtered and concentrated, chromatographed on silica gel using 30% ethyl acetate in hexanes as eluent to give the product.</p><p num="1188"> Example 409C (4-Fluorotetrahydro-2H-pyran-4-yl) methaneamine A mixture of Example 409B (1.4 g) and hydrazine (1.548 mL) in ethanol (40 mL) was heated overnight at 70 ° C. to cool to room temperature and CH.₂Cl₂It was slurried with (200 mL) and the solid was removed by filtration. Concentrate the filtrate and use as eluent 100: 5: 1 ethyl acetate / methanol / NH₄The product was obtained by chromatography on silica gel using OH.</p><p num="1189"> Example 409D 4-((4-Fluorotetrahydro-2H-pyran-4-yl) methylamino) -3-nitrobenzenesulfonamide A mixture of 4-fluoro-3-nitrobenzenesulfonamide (0.44 g) in tetrahydrofuran (10 mL), Example 409 C (0.266 g) and triethylamine (1.11 mL) was heated overnight at 70 ° C. and diluted with ethyl acetate. Rinse with water and brine and dehydrate (EDTA)₄), Filtered and concentrated, chromatographed on silica gel using 50% ethyl acetate in hexanes as eluent to give the product.</p><p num="1190"> Example 409E 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Fluorotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 1F of Example 177 with Example 409D and Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.09 (s, 1H), 8.59 (t, 1H), 8.37 (d, 1H), 7.80 (s, 1H), 7.59 (dd, 1H), 7.37 (d, 2H), 7.04-7.13 (m, 5H), 6.79 (dd, 1H), 6.51 (d, 1H), 6.18 (d, 1H), 3.70-3.79 (m, 4H), 3.50-3.56 (m, 2H), 3.15 (br s, 4H), 2.78 (br s, 2H), 2.32 (br s, 4H), 2.17 (br s, 2H), 1.97 (s, 2H), 1.75-1.83 (m, 4H), 1.40 (t, 2H), 0.93 (s) , 6H).</p><p num="1191"> Example 410 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[6-[(4-4-yl) Fluorotetrahydro-2H-pyran-4-yl) methoxy] -5- (trifluoromethyl) pyridin-3-yl] sulfonyl} -2- (1H-indazole-4-yloxy) benzamide Example 410A 5-Nitro-3- (trifluoromethyl) Pyridine-2-ol 3- (Trifluoromethyl) pyridine-2-ol (2.3 g) was added to concentrated sulfuric acid (15 mL) at 0 ° C. The mixture was stirred at 0 ° C for 5 minutes. Nitric acid (fuming) (6 mL) was added dropwise to this solution over 5 minutes. The reaction mixture was stirred at room temperature for 2 hours and heated at 50 ° C. for 3 hours. After cooling, the reaction mixture was poured onto ice (200 g) and the mixture was extracted 3 times with ethyl acetate. Wash the combined organic layer with brine and deli₄Was dehydrated, filtered, and concentrated under reduced pressure to give the title compound.</p><p num="1192"> Example 410B 2-Chloro-5-nitro-3- (trifluoromethyl) pyridine A mixture of Example 410A (1.69 g), phosphorus pentachloride (2.03 g) and phosphoryl trichloride (0.97 mL) was heated at 90 ° C for 3 hours. After cooling, the reaction mixture was poured into ice and extracted 3 times with ethyl acetate. The extract is washed with brine and EDTA₄Dehydrated with, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel with 1: 9 ethyl acetate / hexane to give the title compound.</p><p num="1193"> Example 410C A mixture of iron (1.5 g) and ammonium chloride (2.38 g) in water (40 mL) was stirred at room temperature for 5 minutes. Example 410B in methanol (40 mL) was added to this suspension. The reaction mixture was stirred at room temperature for 1 hour. Additional iron (1.8 g) was added to the reaction mixture and this was stirred for an additional 3 hours. The solid from the reaction mixture was filtered off and the filtrate was partitioned between water and ethyl acetate. Wash the combined organic layer with brine and deli₄Dehydrated with, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using silica gel by eluting 1: 4 ethyl acetate / hexane to give the title compound.</p><p num="1194"> Example 410D 6-Chloro-5- (trifluoromethyl) Pyridine-3-sulfonyl chloride Under ice cooling, thionyl chloride (4 mL) was added dropwise to water (27 mL) over 20 minutes. Stir the mixture overnight for 12 hours to SO₂The containing solution was obtained. Separately, Example 410 C (1.14 g) in dioxane (5 mL) was added to concentrated HCl (20 mL) at 0 ° C. The solution was stirred for 5 minutes. Sodium nitrite (0.44 g) in water (6 mL) was added dropwise to this mixture at 0 ° C. The solution was stirred at 0 ° C for 3 hours. The solid produced during this period was crushed with a glass rod to ensure that Example 410C reacted completely. This SO₂Copper (I) chloride (0.115 g) was added to the containing solution. The diazotized Example 410C was then added to this solution at 0 ° C. The solution was stirred for 30 minutes. The reaction mixture was extracted with ethyl acetate. Wash the combined organic layer with brine and deli₄Dehydrated with, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel with 1:20 ethyl acetate / hexane to give the title compound.</p><p num="1195"> Example 410E 6-Chloro-5- (trifluoromethyl) Pyridine-3-sulfonamide The title compound was prepared by replacing 5-bromo-6-chloropyridin-3-sulfonyl chloride of Example 329A with Example 410D.</p><p num="1196"> Example 410F The title compound was prepared by replacing Example 329A of Example 329B with Example 410E and replacing methanol (tetrahydro-2H-pyran-4-yl) with Example 306C.</p><p num="1197"> Example 410G 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[6-[(4-4-yl) Fluorotetrahydro-2H-pyran-4-yl) methoxy] -5- (trifluoromethyl) pyridin-3-yl] sulfonyl} -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by replacing Example 1F of Example 177 with Example 410F and replacing Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.05 (s, 1H), 8.59 (s, 1H), 8.17 (d, 1H), 7.76 (s, 1H), 7.62 (d, 1H), 7.37 (d, 2H), 7.00-7.08 (m, 4H), 6.78 (dd, 1H), 6.51 (s, 1H), 6.11 (d, 1H), 4.56 (d, 2H), 3.77-3.80 (m, 2H), 3.57-3.62 (m, 2H), 3.18 (br s, 2H), 2.32 (br s, 4H), 2.18 (br s, 2H), 1.99 (s, 2H), 1.81-1.90 (m, 4H), 1.42 (t, 2H), 0.94 (s, 6H).</p><p num="1198"> Example 411 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) -Cyclopropylmorpholin-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 1E of Example 1G with Example 400E and Example 1F with Example 432A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.09 (s, 1H), 8.57 (m, 1H), 8.37 (d, 1H), 7.81 (s, 1H), 7.56 (dd, 1H), 7.52 (d, 1H), 7.38-7.31 (m, 3H), 7.11-7.07 (m, 3H), 6.97 (d, 1H), 6.80 (dd, 1H), 6.52 (d, 1H), 6.17 (d, 1H), 3.84 (d, 1H), 3.24-3.10 (m, 6H), 2.93 (d, 2H), 2.76 (m, 2H), 2.73 (s, 2H), 2.34-2.10 (m, 8H), 1.97 (bs, 2H), 1.67 (m, 1H), 1.40 (t, 2H), 0.93 (s, 6H), 0.47-0.26 (m, 4H).</p><p num="1199"> Example 412 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) , 4-difluorocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide Example 412A tert-Butyl (4,4-difluorocyclohexyl) methylcarbamate tert-Butyl (4-oxocyclohexyl) methylcarbamate (5 g) and diethylaminosulfatrifluoride (7.45 g) were stirred in dichloromethane (100 mL) for 24 hours. The mixture was quenched with pH 7 buffer (100 mL) and poured into ether (400 mL). The resulting solution was separated and the organic layer was washed twice with water and once with brine and then concentrated to give the crude product and fluoroolefin in a ratio of 3: 2. The crude product is taken in tetrahydrofuran (70 mL) and water (30 mL), N-methylmorpholine-N-oxide (1.75 g) and OsO.₄(2.5 wt% solution in t-butanol) was added and the mixture was stirred for 24 hours. Then Na₂S₂O₃(10 g) was added and the mixture was stirred for 30 minutes. The mixture was then diluted with ether (300 mL) and the resulting solution was separated and rinsed twice with water and once with brine for concentration. The crude product was chromatographed on silica gel with 5-10% ethyl acetate in hexanes to give the title compound.</p><p num="1200"> Example 412B (4,4-difluorocyclohexyl) methaneamine The solution of Example 412A (3 g) in dichloromethane (35 mL), trifluoroacetic acid (15 mL) and triethylsilane (1 mL) was stirred for 2 hours. The solution was concentrated, then concentrated from toluene and placed in high vacuum for 24 hours. The semi-solid was taken up in ether / hexane and filtered to give the product as its trifluoroacetate.</p><p num="1201"> Example 412C 4-((4,4-difluorocyclohexyl) methylamino) -3-nitrobenzenesulfonamide The title compound was prepared by replacing 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with Example 412B.</p><p num="1202"> Example 412D 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-[(4-{[(4) , 4-difluorocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 1E of Example 1G with Example 400E and Example 1F with Example 412C.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.16 (s, 1H), 11.70 (br s, 1H), 8.65 (m, 1H), 8.44 (d, 1H), 7.87 (d, 1H), 7.61 (dd, 2H), 7.41 (d, 2H) ), 7.02-7.20 (m, 4H), 6.88 (dd, 1H), 6.58 (d, 1H), 6.26 (dd, 1H), 3.22 (m, 4H), 2.86 (m, 2H), 2.20-2.35 ( m, 7H), 2.14 (s, 2H), 2.10 (m, 2H), 2.03 (m, 2H), 1.91 (m, 2H), 1.87 (m, 2H), 1.46 (m, 2H), 1.27-1.39 (m, 3H), 1.00 (s, 6H).</p><p num="1203"> Example 413 N-[(5-Chloro-6-{[(4-fluorotetrahydro-2H-pyran-4-yl) methyl] amino} pyridin-3-yl) sulfonyl] -4- (4-{[2- (4) -Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 413A The title compound was prepared by replacing 4-fluoro-3-nitrobenzenesulfonamide of Example 1F with Example 387A and replacing (tetrahydropyran-4-yl) methylamine with Example 409C.</p><p num="1204"> Example 413B N-[(5-Chloro-6-{[(4-fluorotetrahydro-2H-pyran-4-yl) methyl] amino} pyridin-3-yl) sulfonyl] -4- (4-{[2- (4) -Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 1F of Example 177 with Example 413A and Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.14 (s, 1H), 8.19 (d, 1H), 7.87 (s, 1H), 7.60 (d, 1H), 7.56 (d, 1H), 7.36 (d, 2H), 7.31 (br s, 1H) ), 7.08-7.17 (m, 2H), 7.06 (d, 2H), 6.80 (dd, 1H), 6.53 (d, 1H), 6.20 (d, 1H), 3.70-3.78 (m, 4H), 3.43- 3.54 (m, 2H), 3.18 (br s, 4H), 2.81 (s, 2H), 2.26 (br s, 4H), 2.17 (br s, 2H), 1.97 (s, 2H), 1.64-1.80 (m) , 4H), 1.40 (t, 2H), 0.94 (s, 6H).</p><p num="1205"> Example 414 Trans-N-({5-chloro-6-[(4-Methoxycyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 414A Sith- (4-methoxycyclohexyl) methanol and trans- (4-methoxycyclohexyl) methanol Ethyl 4-methoxycyclohexanecarboxylate (1 g) in tetrahydrofuran (10 mL) 1.0 N LiAlH in THF (2 mL)₄Processed at 0 ° C. The mixture was stirred for 2 hours. The reaction was quenched with water (0.6 mL) followed by aqueous 2.0N NaOH solution (0.2 mL). The mixture was stirred for an additional 20 minutes and the solid was filtered off. Take the filtrate in ethyl acetate, wash with brine and deli₄Dehydrated with, filtered and concentrated to give the title compound as a mixture of cis and trans isomers.</p><p num="1206"> Example 414B 5-Chloro-6-((trans-4-methoxycyclohexyl) methoxy) Pyridine-3-sulfonamide The title compound was prepared by replacing Example 329A of Example 329B with Example 387A and replacing methanol (tetrahydro-2H-pyran-4-yl) with Example 414A. Trans isomers were isolated by flash column chromatography on silica gel.</p><p num="1207"> Example 414C Trans-N-({5-chloro-6-[(4-methoxycyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohexa-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 1F of Example 177 with Example 414B and Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.10 (s, 1H), 8.27 (d, 1H), 7.85 (d, 1H), 7.80 (s, 1H), 7.59 (d, 1H), 7.36 (d, 2H), 7.03-7.10 (m, 4H), 6.79 (dd, 1H), 6.53 (d, 1H), 6.14 (d, 1H), 4.19 (d, 2H), 3.24 (s, 3H), 3.20 (m, 4H), 3.07-3.10 (m) , 2H), 2.93 (br s, 2H), 2.39 (s, 4H), 2.18 (s, 2H), 1.98-2.02 (m, 4H), 1.70-1.86 (m, 3H), 1.42 (t, 2H) , 1.08-1.17 (m, 4H), 0.94 (s, 6H).</p><p num="1208"> Example 415 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[4- (2,2-difluoroethyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide Example 415A tert-Butyl 2-((2-nitro-4-sulfamoylphenylamino) methyl) morpholine-4-carboxylate This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with tert-butyl 2- (aminomethyl) morpholine-4-carboxylate.</p><p num="1209"> Example 415B 4- (Morpholine-2-ylmethylamino) -3-nitrobenzenesulfonamide The solution of Example 415A (0.8 g) in methylene chloride (10 mL) and trifluoroacetic acid (10 mL) was stirred at room temperature for 2 hours. The solvent was evaporated and the residue was mixed with diethyl ether. The obtained solid was dissolved in a 5% aqueous sodium carbonate solution (20 mL). The solution was evaporated to dryness and the resulting solid was mixed several times with a solution of 10% methanol in dichloromethane. The organic solution was evaporated to give the title compound.</p><p num="1210"> Example 415C 4-((4- (2,2-difluoroethyl) morpholine-2-yl) methylamino) -3-nitrobenzenesulfonamide Sodium carbonate (254 mg) and 2,2-difluoroethyl iodide (422 mg) were added to a solution of Example 415B (633 mg) in anhydrous N, N-dimethylformamide (10 mL). After stirring at 110 ° C. for 48 hours, the mixture was concentrated. The residue was mixed with water (20 mL) and extracted with ethyl acetate. The crude product was eluted with 10% methanol in methylene chloride and purified on a silica gel column to give the title compound.</p><p num="1211"> Example 415D 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[4- (2,2-difluoroethyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 415C.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.26 (d, 1H), 8.87 (t, 1H), 8.57 (s, 1H), 8.37 (dd, 1H), 7.99 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H) , 7.25 (m, 2H), 7.17 (d, 1H), 7.06 (d, 2H), 6.96 (d, 1H), 6.72-6.69 (m, 2H), 6.31,6.20,6.09 (tt, 1H), 3.90 (m, 1H), 3.86 (d, 1H), 3.68 (dt, 1H), 3.54-3.41 (m, 2H), 3.03 (m, 4H), 2.97 (d, 1H), 2.83-2.75 (m, 4H) ), 2.69 (d, 1H), 2.35 (dt, 1H), 2.27-2.23 (m, 3H), 2.14 (m, 4H), 1.97 (s, 2H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1212"> Example 416 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N- ({5-fluoro-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide Example 416A 5-Bromo-3-fluoro-2-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) pyridine The title compound was replaced with (tetrahydro-2H-pyran-4-yl) methanol of Example 219A with Example 306C and 4-fluoro-3-nitrobenzenesulfonamide with 5-bromo-2,3-difluoropyridine. Prepared.</p><p num="1213"> Example 416B tert-Butyl 5-fluoro-6-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-ylcarbamate Examples 416A (0.658g), tert-butylcarbamate (0.300g), palladium (II) acetate (0.024g), 4,5-bis (diphenylphosphino)-9,9-dimethylxanthene (0.093g) and carbonate. Cesium (1.044 g) was combined with dioxane (10.7 ml) in a 20 mL vial. Vials were flushed with nitrogen, capped and stirred at 100 ° C overnight. The reaction mixture is diluted with ethyl acetate, washed with water and brine and dehydrated (DDL).₄), Filtered and concentrated, and chromatographed on silica gel using 20% ethyl acetate in hexane as eluent.</p><p num="1214"> Example 416C 5-Fluoro-6-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-sulfonyl chloride Thionyl chloride (1.563 mL) was added dropwise to water (9 mL) over 20 minutes under ice-cooling. Stir the mixture for 12 hours to SO₂The containing solution was obtained. Separately, Example 416B (0.295 g) was added to a mixture of dioxane (3.2 mL) and concentrated HCl (8 ml) at 0 ° C. The solution was stirred for 15 minutes, the solution of sodium nitrite (0.065 g) in water (2 mL) was added dropwise at 0 ° C for treatment and stirred at 0 ° C for 3 hours. SO₂The containing solution was cooled to 0 ° C., treated sequentially with copper (I) chloride (0.042 g) and a diazotized mixture and stirred for 30 minutes. The reaction mixture is then extracted with ethyl acetate and the organic layer is dehydrated (DDL).₄), Filtered and concentrated. The concentrate was chromatographed on silica gel using 5-10% ethyl acetate in hexanes as the eluent.</p><p num="1215"> Example 416D 5-Fluoro-6-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-sulfonamide Example 416C (0.08 g) in isopropanol (2 mL) at 0 ° C. was treated with ammonium hydroxide (1.70 mL) and stirred overnight. The reaction mixture was concentrated to dryness, slurried in water, filtered, rinsed with water and dehydrated under vacuum to give the title compound.</p><p num="1216"> Example 416E 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N- ({5-fluoro-6-) [(4-Fluorotetrahydro-2H-pyran-4-yl) methoxy] Pyridine-3-yl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 26C of Example 177 with Example 400E and Example 1F with Example 416D.¹1 H NMR (400MHz, Pyridine-ds) δ 14.67 (s, 1H), 8.84 (d, 1H), 8.38 (d, 1H), 8.06 (d, 1H), 8.00 (dd, 1H), 7.46 (m, 2H) ), 7.35 (d, 1H), 7.12 (m, 3H), 6.87 (m, 2H), 6.47 (d, 1H), 4.56 (d, 2H), 3.80 (m, 4H), 3.18 (m, 4H) , 2.83 (s, 2H), 2.31 (t, 2H), 2.24 (m, 4H), 1.99 (s, 2H), 1.86 (m, 4H), 1.41 (t, 2H), 0.96 (s, 6H).</p><p num="1217"> Example 417 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide Example 417A 2- (1- (bis (4-methoxyphenyl) methyl) -1H-benzo [d] imidazole-4-yloxy) -4- (4-((2- (4-chlorophenyl) -4,4-dimethylcyclohexi) Sa-1-enyl) Methyl) Piperazin-1-yl) -N- (3-Nitro-4- (1- (Tetrahydro-2H-Pyran-4-yl) Piperidine-4-ylamino) Phenylsulfonyl) Benzamide The title compound was prepared by substituting Example 1F of Example 403H with Example 173C.</p><p num="1218"> Example 417B 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(1-tetrahydro-2H-pyran-4-ylpiperidin-4-yl) amino] phenyl} sulfonyl) benzamide The title compound was prepared by substituting Example 403H of Example 403I with Example 417A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.27 (m, 1H), 8.59 (s, 1H), 8.47 (d, 1H), 8.43 (d, 1H), 8.01 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H) , 7.24 (m, 1H), 7.18 (m, 1H), 7.07 (d, 2H), 6.96 (d, 1H), 6.70 (m, 2H), 5.34 (m, 2H), 4.03 (m, 2H), 3.53 (m, 1H), 3.31 (m, 2H), 3.03 (m, 4H), 2.82 (m, 2H), 2.76 (s, 2H), 2.42 (m, 1H), 2.32 (m, 2H), 2.26 -2.19 (m, 2H), 2.14 (m, 4H), 1.98 (m, 4H), 1.67-1.52 (m, 6H), 1.38 (m, 2H), 0.94 (s, 6H).</p><p num="1219"> Example 418 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 418A 2- (1- (bis (4-methoxyphenyl) methyl) -1H-benzo [d] imidazole-4-yloxy) -4- (4-((2- (4-chlorophenyl) -4,4-dimethylcyclohexi) Sa-1-enyl) methyl) piperazin-1-yl) -N-(4- (1-methylpiperidin-4-ylamino) -3-nitrophenylsulfonyl) benzamide The title compound was prepared by substituting Example 1F of Example 403H with Example 21A.</p><p num="1220"> Example 418B 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(1-methylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide The title compound was prepared by substituting Example 403H of Example 403I with Example 418A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.25 (m, 1H), 8.58 (s, 1H), 8.42 (m, 2H), 8.02 (d, 1H), 7.52 (d, 1H), 7.43 (d, 2H), 7.23 (m, 1H) , 7.14 (d, 1H), 7.07 (d, 2H), 6.92 (d, 1H), 6.70 (m, 2H), 5.52 (m, 2H), 3.50 (m, 1H), 3.03 (m, 4H), 2.77 (s, 2H), 2.68 (m, 2H), 2.25 (m, 2H), 2.20 (s, 3H), 2.14 (m, 6H), 1.97-1.90 (m, 4H), 1.67 (m, 2H) , 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1221"> Example 419 N-[(5-Chloro-6-{[1- (cyanomethyl) -4-fluoropiperidine-4-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4-{[2- (4-) Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 419A tert-Butyl 4-fluoro-4- (hydroxymethyl) piperidine-1-carboxylate LiAlH 1-tert-butyl 4-ethyl 4-fluoropiperidine-1,4-dicarboxylate (1.0 g) in tetrahydrofuran (10 mL) at 0 ° C₄The mixture was treated with a 1N solution in tetrahydrofuran (2.54 mL), stirred at room temperature for 2 hours, and a 2N aqueous solution of water (0.2 mL) and NaOH (0.6 mL) was sequentially added dropwise to the mixture, and the mixture was stirred for 1 hour. The solid was filtered off with a diatomaceous earth filler and rinsed with ethyl acetate. The filtrate is washed with water and brine and dehydrated (DDL).₄), Filtered and concentrated to give the title compound.</p><p num="1222"> Example 419B tert-Butyl 4-((3-chloro-5-sulfamoylpyridin-2-yloxy) methyl) -4-fluoropiperidine-1-carboxylate The title compound was prepared by substituting (tetrahydro-2H-pyran-4-yl) methanol of Example 279A with Example 419A and substituting 4-fluoro-3-nitrobenzenesulfonamide with Example 387A.</p><p num="1223"> Example 419C 5-Chloro-6-((4-fluoropiperidine-4-yl) methoxy) Pyridine-3-sulfonamide, 2-trifluoroacetic acid The title compound was prepared by substituting Example 1A of Example 1B with Example 419B.</p><p num="1224"> Example 419D 5-Chloro-6-((1- (cyanomethyl) -4-fluoropiperidine-4-yl) methoxy) Pyridine-3-sulfonamide Example 419C (0.166 g) in acetonitrile (3.00 mL) was treated with 2-chloroacetonitrile (0.027 g) and sodium carbonate (0.064 g), heated overnight at 60 ° C, cooled to room temperature and used as an eluent. CH₂Cl₂Chromatographed on silica gel with 0 to 3% methanol in. The resulting solid was slurried in water, filtered, rinsed with water and diethyl ether and dried in a vacuum oven at 80 ° C. to give the title compound.</p><p num="1225"> Example 419E N-[(5-Chloro-6-{[1- (cyanomethyl) -4-fluoropiperidine-4-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4-{[2- (4-) Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 26C of Example 177 with Example 400E and Example 1F with Example 419D.¹1 H NMR (400MHz, Pyridine-d₅) δ 14.70 (s, 1H), 8.91 (d, 1H), 8.39 (d, 2H), 8.10 (d, 1H), 7.46 (m, 2H), 7.35 (d, 1H), 7.11 (m, 3H) , 6.87 (m, 2H), 6.50 (d, 1H), 4.49 (d, 2H), 3.72 (s, 2H), 3.17 (m, 4H), 2.82 (s, 2H), 2.72 (m, 4H), 2.31 (m, 2H), 2.23 (m, 4H), 2.06 (m, 2H), 1.99 (s, 2H), 1.89 (m, 2H), 1.41 (t, 2H), 0.96 (s, 6H).</p><p num="1226"> Example 420 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydrofuran-3-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide Example 420A 5-Chloro-6-((tetrahydrofuran-3-yl) methoxy) Pyridine-3-sulfonamide The title compound was prepared by replacing Example 329A of Example 329B with Example 387A and replacing (tetrahydro-2H-pyran-4-yl) methanol with (tetrahydro-3-yl) methanol.</p><p num="1227"> Example 420B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydrofuran-3-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 1F of Example 177 with Example 420B and Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.07 (s, 1H), 8.25 (d, 1H), 7.85 (d, 1H), 7.79 (s, 1H), 7.60 (d, 1H), 7.36 (d, 2H), 7.03-7.09 (m, 4H), 6.78 (dd, 1H), 6.51 (d, 1H), 6.13 (dd, 1H), 4.25-4.37 (m, 2H), 3.77-3.81 (m, 2H), 3.64-3.70 (m, 2H) , 3.54-3.57 (m, 2H), 3.17 (br s, 4H), 2.89 (br s, 2H), 2.68-2.71 (m, 1H), 2.33 (m, 3H), 2.16-2.18 (m, 2H) , 1.98-2.01 (m, 3H), 1.66-1.71 (m, 1H), 1.41 (t, 2H), 0.94 (s, 6H).</p><p num="1228"> Example 421 Trans-N-({5-chloro-6-[(4-hydroxycyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 421A 6-((trans-4- (tert-butyldimethylsilyloxy) cyclohexyl) methoxy) -5-chloropyridin-3-sulfonamide The title compound was replaced by Example 329A of Example 329B with Example 387A, and (tetrahydro-2H-pyran-4-yl) methanol was synthesized by the method described in WO2008 / 124878 (page 100). Prepared by replacing with (tert-butyldimethylsilyloxy) cyclohexylmethanol.</p><p num="1229"> Example 421B Trans-N-({5-chloro-6-[(4-hydroxycyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethyl Cyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by removing the tert-butyldimethylsilyl group with trifluoroacetic acid, then replacing Example 1F of Example 177 with Example 421A and replacing Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.12 (s, 1H), 8.29 (d, 1H), 7.88 (d, 1H), 7.84 (s, 1H), 7.40 (d, 2H), 7.07-7.13 (m, 4H), 6.83 (dd, dd, 1H), 6.56 (s, 1H), 6.17 (d, 1H), 4.58 (d, 1H), 4.21 (d, 2H), 3.22 (br s, 4H), 2.36-2.40 (m, 3H), 2.20- 2.24 (m, 2H), 2.02-2.03 (m, 2H), 1.75-1.89 (m, 5H), 1.45 (t, 2H), 1.11-1.21 (m, 4H), 0.98 (s, 6H).</p><p num="1230"> Example 422 N-[(5-Chloro-6-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] oxy} pyridin-3-yl) sulfonyl] -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 422A (R) -tert-Butyl 3- (3-chloro-5-sulfamoylpyridin-2-yloxy) pyrrolidine-1-carboxylate The title compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methanol of Example 387B with (R) -tert-butyl 3-hydroxypyrrolidine-1-carboxylate.</p><p num="1231"> Example 422B (R) -5-chloro-6- (pyrrolidine-3-yloxy) Pyridine-3-sulfonamide hydrochloride Example 422A (480 mg) was dissolved in anhydrous tetrahydrofuran (10 mL), followed by hydrogen chloride in a dioxane solution (4M, 2.5 mL). The reaction mixture was stirred at room temperature overnight. The solvent was removed under vacuum to give the title compound.</p><p num="1232"> Example 422C (R) -5-chloro-6- (1- (2,2-difluoroethyl) pyrrolidine-3-yloxy) Pyridine-3-sulfonamide Examples 422B (353 mg), 1,1-difluoro-2-iodoethane (268 mg) and Na in N, N-dimethylformamide (10 mL)₂CO₃The reaction mixture (283 mg) was heated at 80 ° C. overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water and brine, dehydrated over anhydrous sodium sulfate and concentrated. The crude material was purified with 2.5-3% methanol / dichloromethane to give the title compound.</p><p num="1233"> Example 422D N-[(5-Chloro-6-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] oxy} pyridin-3-yl) sulfonyl] -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 26C of Example 177 with Example 400E and substituting Example 1F with Example 422C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 12.98 (s, 1H), 8.17 (d, 1H), 7.80 (d, 1H), 7.73 (s, 1H), 7.66 (d, 1H), 7.35 (d, 2H), 7.05 (m, 4H) , 6.73 (m, 1H), 6.41 (d, 1H), 6.10 (m, 2H), 5.37 (m, 1H), 2.92 (m, 11H), 2.56 (m, 2H), 2.24 (m, 7H), 1.99 (m, 2H), 1.82 (m, 1H), 1.39 (m, 2H), 0.93 (s, 6H).</p><p num="1234"> Example 423 2- (1H-benzimidazol-4-yloxy) -N-[(5-chloro-6-{[(2S) -4- (N, N-dimethylglycyl) morpholin-2-yl] methoxy} pyridine- 3-Il) Sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide Example 423A (S) -tert-Butyl 2-((3-chloro-5-sulfamoylpyridin-2-yloxy) methyl) morpholine-4-carboxylate This Example compound was prepared by replacing 4-hydroxymethyl-tetrahydropyran in Example 387B with (S) -tert-butyl 2- (hydroxymethyl) morpholine-4-carboxylate.</p><p num="1235"> Example 423B (S) -5-Chloro-6- (Morpholine-2-ylmethoxy) Pyridine-3-Sulfonamide This Example compound was prepared by substituting Example 415A of Example 415B with Example 423A.</p><p num="1236"> Example 423C (5) -5-Chloro-6-((4- (2- (dimethylamino) acetyl) morpholine-2-yl) methoxy) Pyridine-3-sulfonamide Sodium carbonate (0.165 g) and 2- (dimethylamino) acetylchloride hydrochloride (0.40 g) were added to a solution of Example 423B (0.32 g) in anhydrous N, N-dimethylformamide (10 mL). After stirring overnight at ambient temperature, the mixture was concentrated to dryness. Residue 5% Na₂CO₃It was mixed with aqueous solution (20 mL) and extracted with ethyl acetate. The crude product was eluted with 10% methanol in dichloromethane saturated with ammonia and purified on a silica gel column to give the title compound.</p><p num="1237"> Example 423D 2- (1H-benzimidazol-4-yloxy) -N-[(5-chloro-6-{[(2S) -4- (N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridine- 3-Il) Sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 423C.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.08 (d, 1H), 8.60 (t, 1H), 8.57 (s, 1H), 8.01 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H), 7.25 (m, 2H) , 7.15 (m, 1H), 7.07 (d, 2H), 6.73-6.69 (m, 2H), 4.86-4.36 (m, 4H), 4.05-3.90 (m, 1H), 3.88 (d, 1H), 3.62 -3.18 (m, 4H), 3.04 (m, 4H), 2.87 (t, 1H), 2.77 (s, 2H), 2.33 (m, 6H), 2.26 (m, 2H), 2.15 (m, 4H), 1.97 (s, 2H), 1.39 (t, 2H), 0.94 (s, 6H).</p><p num="1238"> Example 424 2- (1H-benzimidazol-4-yloxy) -N-[(5-chloro-6-{[(2R) -4- (N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridine- 3-Il) Sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide Example 424A (R) -tert-Butyl 2-((3-chloro-5-sulfamoylpyridin-2-yloxy) methyl) morpholine-4-carboxylate This Example compound was prepared by replacing 4-hydroxymethyl-tetrahydropyran in Example 387B with (R) -tert-butyl 2- (hydroxymethyl) morpholine-4-carboxylate.</p><p num="1239"> Example 424B (R) -5-Chloro-6- (Morpholine-2-ylmethoxy) Pyridine-3-Sulfonamide This Example compound was prepared by substituting Example 415A of Example 415B with Example 424A.</p><p num="1240"> Example 424C (R) -5-chloro-6-((4- (2- (dimethylamino) acetyl) morpholine-2-yl) methoxy) Pyridine-3-sulfonamide This Example compound was prepared by substituting Example 423B of Example 423C with Example 424B.</p><p num="1241"> Example 424D 2- (1H-benzimidazol-4-yloxy) -N-[(5-chloro-6-{[(2R) -4- (N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridine- 3-Il) Sulfonyl] -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 424C.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.08 (d, 1H), 8.60 (t, 1H), 8.57 (s, 1H), 8.01 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H), 7.25 (m, 2H) , 7.15 (m, 1H), 7.07 (d, 2H), 6.73-6.69 (m, 2H), 4.86-4.36 (m, 4H), 4.05-3.90 (m, 1H), 3.88 (d, 1H), 3.62 -3.18 (m, 4H), 3.04 (m, 4H), 2.87 (t, 1H), 2.77 (s, 2H), 2.33 (m, 6H), 2.26 (m, 2H), 2.15 (m, 4H), 1.97 (s, 2H), 1.39 (t, 2H), 0.94 (s, 6H).</p><p num="1242"> Example 425 N-[(5-chloro-6-{[(2S) -4-(N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 400E and Example 1F with Example 423C and reverse phase using a Waters preparative LC4000 apparatus equipped with a Phenomenex Luna C18 column. Purified by HPLC using a water-acetonitrile mobile phase buffered with ammonium acetate.¹1 H NMR (500MHz, Pyridine-d₅) δ 8.87 (dd, 1H), 8.40 (t, 2H), 8.13 (dd, 1H), 7.46 (d, 2H), 7.35 (d, 1H), 7.15-7.10 (m, 3H), 6.87 (d, 1H), 6.85 (s, 1H), 6.50 (dd, 1H), 4.84-4.46 (m, 4H), 4.02-3.90 (m, 1H), 3.88 (m, 1H), 3.60-3.33 (m, 2H) , 3.25-3.15 (m, 6H), 2.89-2.84 (m, 1H), 2.83 (s, 2H), 2.32-2.23 (m, 12H), 1.99 (s, 2H), 1.41 (t, 2H), 0.96 (s, 6H). 1250969 Example 426 Gary Wang N-[(5-chloro-6-{[(2R) -4-(N, N-dimethylglycyl) morpholine-2-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 400E and Example 1F with Example 424C and reverse phase using a Waters preparative LC4000 apparatus equipped with a Phenomenex Luna C18 column. Purified by HPLC using a water-acetonitrile mobile phase buffered with ammonium acetate.¹1 H NMR (500MHz, Pyridine-d₅) δ 8.87 (dd, 1H), 8.40 (t, 2H), 8.13 (dd, 1H), 7.46 (d, 2H), 7.35 (d, 1H), 7.15-7.10 (m, 3H), 6.87 (d, 1H), 6.85 (s, 1H), 6.50 (dd, 1H), 4.84-4.46 (m, 4H), 4.02-3.90 (m, 1H), 3.88 (m, 1H), 3.60-3.33 (m, 2H) , 3.25-3.15 (m, 6H), 2.89-2.84 (m, 1H), 2.83 (s, 2H), 2.32-2.23 (m, 12H), 1.99 (s, 2H), 1.41 (t, 2H), 0.96 (s, 6H).</p><p num="1243"> Example 427 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (Tetrahydro-2H-pyran-4-ylmethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 1F of Example 177 with Example 387B and Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.09 (s, 1H), 8.27 (d, 1H), 7.85 (d, 1H), 7.80 (s, 1H), 7.59 (d, 1H), 7.36 (d, 2H), 7.03-7.10 (m, 4H), 6.79 (dd, 1H), 6.52 (d, 1H), 6.13 (d, 1H), 4.27 (d, 2H), 3.88 (dd, 2H), 3.19 (br s, 4H), 2.91 (br s) , 2H), 2.36-2.40 (br, 3H), 2.18 (m, 2H), 2.05 (m, 1H), 1.98 (s, 2H), 1.64-1.68 (m, 2H), 1.34-1.43 (m, 4H) ), 1.11-1.21 (m, 4H), 0.94 (s, 6H).</p><p num="1244"> Example 428 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(3R) -1- (cyanomethyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 428A 8- {4- [2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-enylmethyl] piperazine-1-yl} -6-oxa-2,11a-diazazibenzo [c, d, g] azulene -11-on A solution of Example 403 G (4.5 g) in anhydrous dichloromethane (100 mL) was cooled in an ice bath and N, N-dimethylformamide as a catalyst was added. Subsequently, a solution of oxalyl dichloride (1.231 mL) in anhydrous methylene chloride (5 mL) was added dropwise. The ice bath was removed and the reaction was stirred for 1 hour while warming to ambient temperature. The reaction was quenched by adding ice (150 mL) and saturated sodium bicarbonate solution (100 mL). The mixture was further diluted with saturated sodium bicarbonate solution (200 mL) and methylene chloride (200 mL). The organic layer was purified on silica gel and eluted with a gradient of 0, 10, 25 and 100% ethyl acetate in methylene chloride to give the title compound.</p><p num="1245"> Example 428B (R) -tert-Butyl 3- (2-nitro-4-sulfamoylphenylamino) pyrrolidine-1-carboxylate (R) -tert-Butyl 3-aminopyrrolidine-1-carboxylate (1.0 g), tetrahydrofuran (50 ml), N-ethyl-N-isopropylpropan-2-amine (5.61 mL) and N, N-dimethylformamide (R) To a solution of 10 mL) was added 4-fluoro-3-nitrobenzenesulfonamide (1.212 g) and the mixture was stirred for 18 hours. The crude product was isolated by concentration, this material, silica gel and purified by Le, to give the title compound eluted with a gradient of stages of 30, 50 and 75% ethyl acetate in hexane.</p><p num="1246"> Example 428C (R) -3-nitro-4- (pyrrolidin-3-ylamino) benzenesulfonamide A suspension of Example 428B (2.018 g) in anhydrous dichloromethane (25 mL) was cooled in an ice bath and 2,2,2-trifluoroacetic acid (20 mL) was added. After stirring for 15 minutes, the ice bath was removed and the reaction was warmed to ambient temperature over 2 hours. The reaction mixture was concentrated, the residue was dissolved in water and made basic with aqueous sodium carbonate solution. The mixture was repeatedly extracted with 10% methanol in methylene chloride and the organics were concentrated to give the title compound.</p><p num="1247"> Example 428D (R) -4- (1- (cyanomethyl) pyrrolidine-3-ylamino) -3-nitrobenzene sulfonamide Sodium carbonate (132 mg) was added to a solution of Example 428C (440 mg) in anhydrous N, N-dimethylformamide (10 mL). 2-Bromoacetonitrile (0.077 mL) was added to the resulting suspension and the mixture was heated at 60 ° C. for 18 hours. The crude material was isolated by concentration, purified on silica gel and eluted with a gradient of 0.5, 2.5 and 5% methanol in methylene chloride to give the title compound.</p><p num="1248"> Example 428E 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(3R) -1- (cyanomethyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 428D (82.6 mg) in tetrahydrofuran (7 mL) was supplemented with 2,3,4,6,7,8,9,10-octahydropyrimid [1,2-a] azepine (0.063 mL). .. The mixture was stirred at ambient temperature for 45 minutes and a solution of Example 428A (117 mg) in tetrahydrofuran (3 mL) was added. After stirring for 18 hours, the crude product was isolated by concentration and purified by reverse phase chromatography using ammonium acetate buffer in acetonitrile to give the title compound.¹1 H NMR (400MHz, Pyridine-ds) δ 9.27 (d, 1H), 8.59 (s, 1H), 8.55 (d, 1H), 8.40 (dd, 1H), 7.99 (d, 1H), 7.54 (m, 1H) ), 7.43 (d, 2H), 7.25 (m, 1H), 7.16 (m, 1H), 7.07 (d, 2H), 6.86 (d, 1H), 6.69 (m, 2H), 5.73 (m, 2H) , 4.15 (m, 1H), 3.90 (s, 2H), 3.03 (m, 4H), 2.96-287. (M, 2H), 2.81-2.76 (m, 3H), 2.58 (m, 1H), 2.32- 2.23 (m, 3H), 2.14 (m, 4H), 1.97 (s, 2H), 1.73 (m, 1H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1249"> Example 429 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({(3R) -1- [2- (2-methoxyethoxy) ethyl] pyrrolidine-3-yl} amino) -3-nitrophenyl] sulfonyl} benzamide Example 429A (R) -4- (1- (2- (2-Methoxyethoxy) ethyl) pyrrolidine-3-ylamino) -3-nitrobenzenesulfonamide The title compound was prepared by replacing 2-bromoacetonitrile in Example 428D with 1-bromo-2- (2-methoxyethoxy) ethane.</p><p num="1250"> Example 429B 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({(3R) -1- [2- (2-methoxyethoxy) ethyl] pyrrolidine-3-yl} amino) -3-nitrophenyl] sulfonyl} benzamide The title compound was prepared by substituting Example 428D of Example 428E with Example 429A.¹1 H NMR (400MHz, Pyridine-d₅) δ 9.26 (d, 1H), 8.58 (m, 2H), 8.38 (dd, 1H), 8.01 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H), 7.25 (d, 1H) , 7.16 (d, 1H), 7.07 (d, 2H), 6.85 (d, 1H), 6.71-6.69 (m, 2H), 5.33 (m, 2H), 4.05 (m, 1H), 3.63 (m, 4H) ), 3.54 (m, 2H), 3.29 (s, 3H), 3.03 (m, 4H), 2.86 (m, 1H), 2.77 (m, 4H), 2.70 (t, 2H), 2.38 (m, 1H) , 2.27-2.18 (m, 3H), 2.14 (m, 4H), 1.97 (s, 2H), 1.64 (m, 1H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1251"> Example 430 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(3R) -1- (N, N-dimethylglycyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 430A R) -4- (1- (2- (dimethylamino) acetyl) pyrrolidine-3-ylamino) -3-nitrobenzenesulfonamide The title compound was prepared by replacing 2-bromoacetonitrile in Example 428D with 2- (dimethylamino) acetyl chloride.</p><p num="1252"> Example 430B 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(3R) -1- (N, N-dimethylglycyl) pyrrolidine-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide The title compound was prepared by substituting Example 428D of Example 428E with Example 430A.¹1 H NMR (400MHz, Pyridine-d₅) δ 9.25 (m, 1H), 8.59 (d, 1H), 8.47-8.35 (m, 2H), 8.01 (d, 1H), 7.54 (d, 1H), 7.44 (d, 2H), 7.25-7.20 ( m, 2H), 7.16-6.92 (m, 4H), 6.71 (m, 2H), 5.55 (m, 1H), 4.34-4.18 (m, 1H), 4.03 (m, 1H), 3.84-3.63 (m, 3H), 3.44-3.34 (m, 2H), 3.03 (m, 4H), 2.77 (s, 2H), 2.43 (m, 6H), 2.25 (m, 3H), 2.14 (m, 4H), 2.03-1.83 (m, 3H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1253"> Example 431 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[4- (cyanomethyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide Example 431A 4-((4- (Cyanomethyl) Morpholine-2-yl) Methylamino) -3-Nitrobenzene Sulfonamide This Example compound was prepared at ambient temperature by replacing 2,2-difluoroethyl iodide in Example 415C with 2-bromo-acetonitrile.</p><p num="1254"> Example 431B 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[4- (cyanomethyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 431A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.25 (d, 1H), 8.87 (t, 1H), 8.58 (s, 1H), 8.38 (dd, 1H), 8.00 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H) , 7.25 (m, 2H), 7.16 (d, 1H), 7.07 (d, 2H), 6.97 (d, 1H), 6.73-6.68 (m, 2H), 3.96-3.85 (m, 2H), 3.78 (s) , 2H), 3.66 (dt, 1H), 3.53-3.42 (m, 2H), 3.03 (m, 4H), 2.90 (d, 1H), 2.76 (s, 2H), 2.61 (d, 1H), 2.51 ( dt, 1H), 2.40 (t, 1H), 2.25 (m, 2H), 2.14 (m, 4H), 1.97 (s, 2H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1255"> Example 432 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(4-Cyclopropylmorpholine-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 432A 4-((4-Cyclopropyl Morpholine-2-yl) Methylamino) -3-Nitrobenzene Sulfonamide A solution of Example 415B (0.633 g) and (1-ethoxycyclopropoxy) trimethylsilane (1.601 ml) in anhydrous methanol (15 mL) and acetic acid (1.7 ml) was refluxed for 30 minutes and cooled to room temperature. Sodium cyanoborohydride (0.377 g) was then added and the mixture was stirred at ambient temperature overnight. The reaction mixture was concentrated to dryness. Residue 5% Na₂CO₃It was mixed with aqueous solution (25 mL) and extracted with ethyl acetate. The crude product was eluted with 5% and 10% methanol in dichloromethane and purified on a silica gel column to give the title compound.</p><p num="1256"> Example 432B 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(4-Cyclopropylmorpholine-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 432A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.25 (d, 1H), 8.89 (t, 1H), 8.57 (s, 1H), 8.38 (dd, 1H), 8.00 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H) , 7.25 (m, 2H), 7.16 (d, 1H), 7.07 (d, 2H), 6.98 (d, 1H), 6.73-6.68 (m, 2H), 3.90-3.83 (m, 2H), 3.60 (dt , 1H), 3.55-3.41 (m, 2H), 3.03 (m, 4H), 2.96 (d, 1H), 2.76 (s, 2H), 2.69 (d, 1H), 2.35 (dt, 1H), 2.26- 2.20 (m, 3H), 2.14 (m, 4H), 1.97 (s, 2H), 1.59 (m, 1H), 1.38 (t, 2H), 0.94 (s, 6H), 0.47-0.37 (m, 4H) ..</p><p num="1257"> Example 433 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(3-nitro-4-{[(4-oxetane-3-ylmorpholine-2-yl) methyl] amino} phenyl) sulfonyl] benzamide Example 433A 3-Nitro-4-((4- (oxetane-3-yl) morpholine-2-yl) methylamino) benzenesulfonamide This Example compound was prepared by replacing (1-ethoxycyclopropoxy) -trimethylsilane in Example 432A with oxetane-3-one.</p><p num="1258"> Example 433B 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(3-nitro-4-{[(4-oxetane-3-ylmorpholine-2-yl) methyl] amino} phenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 433A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.25 (d, 1H), 8.87 (t, 1H), 8.57 (s, 1H), 8.38 (dd, 1H), 8.02 (d, 1H), 7.53 (d, 1H), 7.44 (d, 2H) , 7.24 (m, 2H), 7.13 (d, 1H), 7.07 (d, 2H), 6.98 (d, 1H), 6.73-6.68 (m, 2H), 4.69-4.62 (m, 4H), 3.98-3.88 (m, 2H), 3.69 (dt, 1H), 3.55-3.35 (m, 3H), 3.03 (m, 4H), 2.77 (s, 2H), 2.74 (d, 1H), 2.44 (d, 1H), 2.25 (m, 2H), 2.14 (m, 4H), 1.97 (s, 2H), 1.94 (m, 1H), 1.87 (t, 1H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1259"> Example 434 N-{[5-chloro-6-(((3R) -1- [2-fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} oxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 434A (R) -5-chloro-6- (1- (1,3-difluoropropan-2-yl) pyrrolidine-3-yloxy) Pyridine-3-sulfonamide Example 422B (278 mg) and 1,3-difluoropropan-2-one (94 mg) were suspended in dichloroethane (10 ml). N, N-Dimethylformamide (1.5 mL) was added dropwise until a white emulsion suspension was formed. The reaction mixture was stirred at room temperature for 15 minutes, followed by the addition of sodium triacetoxyborohydride (424 mg). The reaction mixture was stirred at room temperature overnight. The solvent was removed under vacuum and the crude material was purified with 2.5-5% methanol / dichloromethane to give the title compound.</p><p num="1260"> Example 434B N-{[5-chloro-6-({(3R) -1- [2-fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} oxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide The title compound was prepared by substituting Example 26C of Example 177 with Example 400E and Example 1F with Example 434A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 12.96 (s, 1H), 8.16 (d, 1H), 7.79 (m, 1H), 7.69 (m, 2H), 7.35 (d, 2H), 7.05 (m, 4H), 6.72 (m, 1H) , 6.39 (d, 1H), 6.09 (dd, 3.05Hz, 1H), 5.37 (m, 1H), 4.66 (t, 2H), 4.54 (t, 2H), 2.91 (m, 12H), 2.23 (m, m, 7H), 1.97 (s, 2H), 1.82 (m, 1H), 1.40 (t, 2H), 0.93 (s, 6H).</p><p num="1261"> Example 435 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({(3R) ) -1- [2-Fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indazole-4-yloxy) benzamide Example 435A (R) -1- (1,3-difluoropropan-2-yl) pyrrolidine-3-amine Sodium triacetoxyborohydride (0.853 g) in a solution of (R) -tert-butylpyrrolidine-3-ylcarbamate (0.500 g) and 1,3-difluoropropan-2-one (0.278 g) in dichloromethane (5 mL). added. After stirring for 1 hour, saturate the reactants LVDS₃Quenched with aqueous solution (5 mL). The mixture was extracted with dichloromethane (25 mL) and the organic layer was dehydrated with anhydrous magnesium sulfate, filtered and concentrated. The resulting residue was treated with HCl (4.0 M, 4 mL in 1,4-dioxane) and methanol (1 mL) and stirred for 1 hour. The mixture was concentrated to give the title compound.</p><p num="1262"> Example 435B (R) -4- (1- (1,3-difluoropropan-2-yl) pyrrolidine-3-ylamino) -3-nitrobenzenesulfonamide N-Ethyl-N-isopropylpropan-2-amine (0.512 mL) was added to 4-fluoro-3-nitrobenzenesulfonamide (0.272 g) in tetrahydrofuran (3.0 mL) and Example 435A (0.195 g), and the reaction product was obtained. Was stirred at room temperature. After stirring for 6 hours, the reaction was concentrated, loaded onto silica gel (Reveleris 40 g) and the product was eluted with a gradient of 25-100% ethyl acetate / hexane over 30 minutes to give the title compound.</p><p num="1263"> Example 435C 4- {4- [2- (4-Chloro-phenyl) -4,4-dimethyl-cyclohex-1-enylmethyl] -piperazine-1-yl} -2- [1- (2-trimethylsilanyl-ethoxymethyl] ) -1H-Indazole-4-yloxy] -Methyl benzoate Example 400D (1000 mg) was dissolved in N, N-dimethylformamide (12 mL) and sodium hydride (60% in mineral oil, 45 mg) was added. The solution was stirred at room temperature for 15 minutes, 2- (trimethylsilyl) ethoxymethyl chloride (299 mg) was added and the solution was stirred at room temperature for 45 minutes. The solution was added to water and extracted with ethyl acetate. The extract was washed with brine, dehydrated over anhydrous sodium sulfate, filtered, concentrated and purified by flash column chromatography on silica gel with 30-50% ethyl acetate in hexanes.</p><p num="1264"> Example 435D 4- {4- [2- (4-Chloro-phenyl) -4,4-dimethyl-cyclohex-1-enylmethyl] -piperazine-1-yl} -2- [1- (2-trimethylsilanyl-ethoxymethyl] ) -1H-Indazole-4-yloxy] -Benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 435C.</p><p num="1265"> Example 435E N- {4- {4- [2- (4-Chloro-phenyl) -4,4-dimethyl-cyclohexa-1-enylmethyl] -piperazine-1-yl} -2- [1- (2-trimethylsilanyl) -Ethoxymethyl) -1H-indazole-4-yloxy] -benzoyl} -4-[(R) -1- (2-fluoro-1-fluoromethyl-ethyl) -pyrrolidine-3-ylamino] -3-nitro- Benzene sulfonamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 435D and Example 1F with Example 435B.</p><p num="1266"> Example 435F 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4-({(3R) ) -1- [2-Fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} amino) -3-nitrophenyl] sulfonyl} -2- (1H-indazole-4-yloxy) benzamide Example 435E (103 mg) was dissolved in trifluoroacetic acid (1.8 mL) and water (0.2 mL) and stirred at room temperature for 90 minutes. The solvent was removed under vacuum, the residue was dissolved in 1,4-dioxane (2 mL), treated with 1 M sodium hydroxide (1 mL) and the solution was stirred at room temperature for 30 minutes. The solution was added to saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The extract was washed with brine, dehydrated with anhydrous sodium sulfate, filtered and the solvent removed under vacuum.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.09 (bs, 1H), 8.37 (m, 2H), 7.84 (d, 1H), 7.58-7.45 (m, 2H), 7.36 (d, 2H), 7.17-7.03 (m, 4H), 6.95 ( dd, 1H), 6.84-6.76 (m, 1H), 6.53 (dd, 1H), 6.17 (t, 1H), 4.72 (d, 2H), 4.56 (d, 2H), 4.23 (m, 1H), 3.17 (m, 4H), 3.12-3.03 (m, 2H), 3.02-2.91 (m, 2H), 2.86-2.73 (m, 4H), 2.40-2.14 (m, 6H), 1.97 (bs, 2H), 1.70 (m, 1H), 1.40 (t, 2H), 0.94 (s, 6H).</p><p num="1267"> Example 436 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1-1-yl] Cyclopropylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide Example 436A 4- (1-Cyclopropyl-piperidine-4-ylamino) -3-nitro-benzenesulfonamide This Example compound was prepared by substituting 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with 1-cyclopropyl-piperidine-4-ylamine.</p><p num="1268"> Example 436B N- {4- {4- [2- (4-chlorophenyl) -4,4-dimethyl-cyclohexa-1-enylmethyl] -piperazine-1-yl} -2- [1- (2-trimethylsilanyl-ethoxy) Methyl) -1H-indazole-4-yloxy] -benzoyl} -4- (1-cyclopropyl-piperidine-4-ylamino) -3-nitro-benzenesulfonamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 435D and Example 1F with Example 436A.</p><p num="1269"> Example 436C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({4-[(1-1-yl] Cyclopropylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) -2- (1H-indazole-4-yloxy) benzamide This Example compound was prepared by substituting Example 435E of Example 435F with Example 436B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.05 (bs, 1H), 8.35 (d, 1H), 8.17 (d, 1H), 7.77 (bs, 1H), 7.57 (td, 2H), 7.35 (d, 2H), 7.09-7.03 (m, 4H), 6.98 (d, 1H), 6.77 (dd, 1H), 6.48 (bs, 1H), 6.17 (m, 1H), 3.66 (m, 1H), 3.12 (bs, 4H), 2.92 (m, 2H) ), 2.76 (bs, 2H), 2.21 (m, 8H), 1.97 (bs, 2H), 1.94 (m, 2H), 1.73 (m, 1H), 1.55 (m, 2H), 1.40 (t, 2H) , 0.93 (s, 6H), 0.46 (d, 2H), 0.35 (bs, 2H).</p><p num="1270"> Example 437 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[(2R) -4- (N, N-dimethylglycyl) morpholin-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide Example 437A (R) -tert-Butyl 2-((2-nitro-4-sulfamoylphenylamino) methyl) morpholine-4-carboxylate This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with (R) -tert-butyl 2- (aminomethyl) morpholine-4-carboxylate.</p><p num="1271"> Example 437B (S) -4- (Morpholine-2-ylmethylamino) -3-Nitrobenzenesulfonamide This Example compound was prepared by substituting Example 415A of Example 415B with Example 437A.</p><p num="1272"> Example 437C (R) -4-((4- (2- (Dimethylamino) Acetyl) Morpholine-2-yl) Methylamino) -3-Nitrobenzene Sulfonamide This Example compound was prepared by substituting Example 423B of Example 423C with Example 437B.</p><p num="1273"> Example 437D 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[(2R) -4- (N, N-dimethylglycyl) morpholin-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 437C.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.25 (s, 1H), 8.86 (t, 1H), 8.57 (s, 1H), 8.38 (t, 1H), 8.02 (d, 1H), 7.53 (d, 1H), 7.44 (d, 2H) , 7.24 (m, 2H), 7.13 (d, 1H), 7.07 (d, 2H), 6.97 (dd, 1H), 6.73-6.68 (m, 2H), 4.75,4.50 (dd, 1H), 4.33,4.02 (dd, 1H), 3.93 (m, 1H), 3.85-3.70 (m, 1H), 3.65-3.40 (m, 3H), 3.33 (dd, 1H), 3.25-3.10 (m, 2H), 3.03 (m) , 4H), 2.90 (m, 1H), 2.77 (s, 2H), 2.27-2.25 (m, 8H), 2.14 (m, 4H), 1.97 (s, 2H), 1.38 (t, 2H), 0.94 ( s, 6H).</p><p num="1274"> Example 438 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[(2S) -4- (N, N-dimethylglycyl) morpholin-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide Example 438A (S) -tert-Butyl 2-((2-nitro-4-sulfamoylphenylamino) methyl) morpholine-4-carboxylate This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with (S) -tert-butyl 2- (aminomethyl) morpholine-4-carboxylate.</p><p num="1275"> Example 438B (R) -4- (Morpholine-2-ylmethylamino) -3-Nitrobenzenesulfonamide This Example compound was prepared by substituting Example 415A of Example 415B with Example 438A.</p><p num="1276"> Example 438C (S) -4-((4- (2- (Dimethylamino) Acetyl) Morpholine-2-yl) Methylamino) -3-Nitrobenzene Sulfonamide This Example compound was prepared by substituting Example 423B of Example 423C with Example 438B.</p><p num="1277"> Example 438D 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[(2S) -4- (N, N-dimethylglycyl) morpholin-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 438C.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.25 (s, 1H), 8.86 (t, 1H), 8.57 (s, 1H), 8.38 (t, 1H), 8.02 (d, 1H), 7.53 (d, 1H), 7.44 (d, 2H) , 7.24 (m, 2H), 7.13 (d, 1H), 7.07 (d, 2H), 6.97 (dd, 1H), 6.73-6.68 (m, 2H), 4.75,4.50 (dd, 1H), 4.33,4.02 (dd, 1H), 3.93 (m, 1H), 3.85-3.70 (m, 1H), 3.65-3.40 (m, 3H), 3.33 (dd, 1H), 3.25-3.10 (m, 2H), 3.03 (m) , 4H), 2.90 (m, 1H), 2.77 (s, 2H), 2.27-2.25 (m, 8H), 2.14 (m, 4H), 1.97 (s, 2H), 1.38 (t, 2H), 0.94 ( s, 6H).</p><p num="1278"> Example 439 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(tetrahydro-3-ylmethyl) amino] phenyl} sulfonyl) benzamide Example 439A 3-Nitro-4-((tetrahydrofuran-3-yl) methylamino) benzenesulfonamide This Example compound was prepared by substituting (tetrahydropyran-4-yl) methylamine in Example 1F with (tetrahydropyran-4-yl) methylamine.</p><p num="1279"> Example 439B 2- (1H-benzimidazol-4-yloxy) -4-(4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({3-nitro-4-[(tetrahydro-3-ylmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 439A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.26 (d, 1H), 8.70 (t, 1H), 8.57 (s, 1H), 8.40 (dd, 1H), 8.01 (d, 1H), 7.51 (d, 1H), 7.44 (d, 2H) , 7.24 (m, 2H), 7.14 (d, 1H), 7.07 (d, 2H), 6.89 (d, 1H), 6.73-6.68 (m, 2H), 3.93-3.89 (m, 1H), 3.83 (dd) , 1H), 3.83-3.68 (m, 2H), 3.33-3.23 (m, 2H), 3.03 (m, 4H), 2.77 (s, 2H), 2.55-2.50 (m, 1H), 2.25 (m, 2H) ), 2.14 (m, 4H), 2.00-1.93 (m, 3H), 1.65-1.58 (m, 1H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1280"> Example 440 Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 311B.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.29 (d, 1H), 8.67 (t, 1H), 8.59 (s, 1H), 8.41 (dd, 1H), 7.99 (d, 1H), 7.52 (d, 1H), 7.43 (d, 2H) , 7.24 (m, 1H), 7.17 (m, 1H), 7.07 (d, 2H), 6.90 (d, 1H), 6.72-6.68 (m, 2H), 5.97 (m, 2H), 3.29 (s, 3H) ), 3.14 (t, 2H), 3.02 (m, 5H), 2.76 (s, 2H), 2.25 (m, 2H), 2.13 (m, 4H), 2.07 (m, 2H), 1.97 (s, 2H) , 1.82 (m, 2H), 1.57 (m, 1H), 1.38 (t, 2H), 1.22 (m, 2H), 1.01 (m, 2H), 0.94 (s, 6H).</p><p num="1281"> Example 441 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 409D.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.27 (d, 1H), 8.84 (t, 1H), 8.57 (s, 1H), 8.41 (dd, 1H), 7.99 (d, 1H), 7.52 (d, 1H), 7.43 (d, 2H) , 7.23 (m, 1H), 7.15 (m, 1H), 7.14-7.02 (m, 3H), 6.70 (m, 2H), 6.49 (m, 2H), 3.86 (m, 2H), 3.76-3.69 (m) , 3H), 3.65 (d, 1H), 3.03 (m, 4H), 2.76 (s, 2H), 2.25 (m, 2H), 2.14 (m, 4H), 1.97 (s, 2H), 1.92-1.76 ( m, 4H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1282"> Example 442 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({5-fluoro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 416D.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.02 (d, 1H), 8.59 (s, 1H), 8.35 (m, 1H), 8.01 (d, 1H), 7.51 (d, 1H), 7.44 (d, 2H), 7.22 (m, 2H) , 7.12 (d, 1H), 7.07 (d, 2H), 6.84 (m, 1H), 6.73 (m, 2H), 4.59 (s, 1H), 4.54 (s, 1H), 3.89-3.74 (m, 4H) ), 3.05 (m, 4H), 2.78 (s, 2H), 2.26 (m, 2H), 2.16 (m, 4H), 2.02-1.81 (m, 6H), 1.39 (t, 2H), 0.94 (s, 6H).</p><p num="1283"> Example 443 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4 -(4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 404A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.12 (d, 1H), 8.68 (d, 1H), 8.59 (s, 1H), 7.99 (d, 1H), 7.52 (d, 1H), 7.44 (d, 2H), 7.24 (d, 1H) , 7.15 (d, 1H), 7.07 (d, 2H), 6.73-6.69 (m, 3H), 6.56 (m, 1H), 4.56 (s, 1H), 4.51 (s, 1H), 3.91-3.76 (m) , 4H), 3.04 (m, 4H), 2.77 (s, 2H), 2.26 (m, 2H), 2.15 (m, 4H), 1.99-1.85 (m, 6H), 1.39 (t, 2H), 0.94 ( s, 6H).</p><p num="1284"> Example 444 N-{[5-chloro-6-({(3R) -1- [2-fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} methoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 444A (R) -5-chloro-6-((1- (1,3-difluoropropan-2-yl) pyrrolidine-3-yl) methoxy) Pyridine-3-sulfonamide This Example compound was prepared by substituting Example 422B of Example 434A with Example 445B.</p><p num="1285"> Example 444B N-{[5-chloro-6-({(3R) -1- [2-fluoro-1- (fluoromethyl) ethyl] pyrrolidine-3-yl} methoxy) pyridin-3-yl] sulfonyl} -4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide This Example compound was prepared by replacing Example 26C of Example 177 with Example 400E and replacing Example 1F with Example 444A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 12.98 (s, 1H), 8.19 (d, 1H), 7.81 (d, 1H), 7.73 (s, 1H), 7.66 (d, 1H), 7.35 (d, 2H), 7.05 (m, 4H) , 6.73 (dd, 1H), 6.42 (d, 1H), 6.10 (m, 1H), 4.64 (s, 2H), 4.54 (d, 2H), 4.24 (m, 2H), 3.07 (s, 4H), 2.89 (s, 2H), 2.74 (m, 4H), 2.56 (m, 2H), 2.20 (m, 6H), 1.98 (m, 4H), 1.54 (m, 1H), 1.40 (t, 2H), 0.91 (s, 6H).</p><p num="1286"> Example 445 N-[(5-Chloro-6-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 445A (R) -tert-Butyl 3-((3-chloro-5-sulfamoylpyridin-2-yloxy) methyl) pyrrolidine-1-carboxylate This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methanol of Example 387B with (R) -tert-butyl 3- (hydroxymethyl) pyrrolidine-1-carboxylate.</p><p num="1287"> Example 445B (R) -5-chloro-6- (pyrrolidine-3-ylmethoxy) Pyridine-3-sulfonamide This Example compound was prepared by substituting Example 422A of Example 422B with Example 445A.</p><p num="1288"> Example 445C (R) -5-chloro-6-((1- (2,2-difluoroethyl) pyrrolidine-3-yl) methoxy) Pyridine-3-sulfonamide This Example compound was prepared by substituting Example 422B of Example 422C with Example 445B.</p><p num="1289"> Example 445D N-[(5-Chloro-6-{[(3R) -1- (2,2-difluoroethyl) pyrrolidine-3-yl] methoxy} pyridin-3-yl) sulfonyl] -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide This Example compound was prepared by replacing Example 26C of Example 177 with Example 400E and replacing Example 1F with Example 445C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 12.98 (s, 1H), 8.19 (d, 1H), 7.81 (d, 1H), 7.73 (s, 1H), 7.66 (d, 1H), 7.35 (d, 2H), 7.05 (m, 4H) , 6.72 (dd, 1H), 6.41 (d, 1H), 6.10 (m, 2H), 4.23 (m, 2H), 3.07 (s, 4H), 2.82 (m, 5H), 2.62 (m, 3H), 2.24 (s, 4H), 2.17 (s, 2H), 1.94 (m, 3H), 1.53 (m, 1H), 1.40 (t, 2H), 0.93 (s, 6H).</p><p num="1290"> Example 446 Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4) -Iloxy) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 446A 2- [1- (2-trimethylsilanyl-ethoxymethyl) -1H-indazole-4-yloxy] -4- (4-((2- (4-chlorophenyl) -4,4-dimethylcyclohexa-1-) Enyl) Methyl) Piperazine-1-yl) -N-(4-((trans-4-methoxycyclohexyl) methylamino) -3-nitrophenylsulfonyl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 435D and Example 1F with Example 311B.</p><p num="1291"> Example 446B Trans-4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4) -Iloxy) -N-[(4-{[(4-Methoxycyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 435E of Example 435F with Example 446A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.08 (bs, 1H), 8.53 (t, 1H), 8.37 (d, 1H), 7.84 (d, 1H), 7.53 (m, 2H), 7.35 (d, 2H), 7.09 (d, 2H) , 7.05 (d, 2H), 6.94 (d, 1H), 6.79 (m, 1H), 6.51 (dd, 1H), 6.18 (m, 1H), 3.23 (s, 3H), 3.17-3.00 (m, 5H) ), 2.78 (bs, 2H), 2.30-2.13 (m, 8H), 2.02 (m, 2H), 1.97, (bs, 2H), 1.80 (m, 2H), 1.60 (m, 1H), 1.40 (t) , 2H), 1.07 (m, 4H), 0.93 (s, 6H).</p><p num="1292"> Example 447 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4- (1,4) -Dioxane-2-ylmethoxy) -3-nitrophenyl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide Example 447A N- {4- {4- [2- (4-Chloro-phenyl) -4,4-dimethyl-cyclohexa-1-enylmethyl] -piperazine-1-yl} -2- [1- (2-trimethylsilanyl) -Ethoxymethyl) -1H-indazole-4-yloxy] -benzoyl} -4-([1,4] dioxane-2-ylmethoxy) -3-nitrobenzenesulfonamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 435D and Example 1F with Example 297A.</p><p num="1293"> Example 447B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[4- (1,4) -Dioxane-2-ylmethoxy) -3-nitrophenyl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide This Example compound was prepared by substituting Example 435E of Example 435F with Example 447A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.04 (bs, 1H), 8.07 (bs, 1H), 7.78 (t, 2H), 7.59 (d, 1H), 7.36 (d, 2H), 7.25 (d, 1H), 7.08 (d, 2H) , 7.06 (d, 2H), 6.77 (d, 1H), 6.48 (bs, 1H), 6.15 (m, 1H), 4.20 (t, 2H), 3.92-3.76 (m, 3H), 3.65 (m, 2H) ), 3.48 (td, 2H), 3.14 (bs, 4H), 2.80 (m, 2H), 2.38-2.13 (m, 6H), 1.97 (bs, 2H), 1.40 (t, 2H), 0.94 (s, 6H).</p><p num="1294"> Example 448 N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 448A 5-Chloro-6- (1-cyclopropyl-piperidine-4-ylamino) -pyridin-3-sulfonic acid amide This Example compound was replaced with 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A with 1-cyclopropyl-piperidine-4-ylamine to carry out 4-chloro-3-nitrobenzenesulfonamide. Prepared by replacing with Example 387A.</p><p num="1295"> Example 448B 5-Chloro-6- (1-cyclopropyl-piperidine-4-ylamino) -pyridin-3-sulfonic acid 4- {4- [2- (4-chloro-phenyl) -4,4-dimethyl-cyclohexa-1 -Enylmethyl] -Piperazine-1-yl} -2- [1- (2-trimethylsilanyl-ethoxymethyl) -1H-indazole-4-yloxy] -benzoylamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 435D and Example 1F with Example 448A.</p><p num="1296"> Example 448C N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4, 4-Dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide This Example compound was prepared by substituting Example 435E of Example 435F with Example 448B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.03 (bs, 1H), 8.18 (d, 1H), 7.79 (bs, 1H), 7.65-7.58 (m, 2H), 7.36 (d, 2H), 7.33 (m, 1H), 7.10 (d, 2H), 7.06 (d, 2H), 6.74 (dd, 1H), 6.43 (bs, 1H), 6.19 (m, 1H), 3.95 (m, 1H), 3.08 (m, 4H), 2.96 (m, 2H) ), 2.75 (bs, 2H), 2.37-2.10 (m, 9H), 1.97 (bs, 2H), 1.78 (m, 2H), 1.56 (m, 2H), 1.40 (t, 2H), 0.93 (s, 6H), 0.42 (d, 2H), 0.33 (bs, 2H).</p><p num="1297"> Example 449 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4 -{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide Example 449A 5-Chloro-6- (1-cyclopropylpiperidin-4-ylamino) Pyridine-3-sulfonamide A mixture of Example 387A (0.4 g), 1-cyclopropylpiperidin-4-amine (0.3 g) and N, N-diisopropylethylamine (0.37 mL) in dioxane (3 mL) was heated at 100 ° C. for 18 hours. The crude product was isolated by concentration, purified on silica gel and eluted with ethyl acetate to give the title compound.</p><p num="1298"> Example 449B 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(1-cyclopropylpiperidin-4-yl) amino] pyridin-3-yl} sulfonyl) -4- (4 -{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 449A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.22 (m, 1H), 8.55 (s, 1H), 8.47 (s, 1H), 8.00 (d, 1H), 7.54 (d, 1H), 7.44 (d, 2H), 7.25 (m, 1H) , 7.19 (m, 1H), 7.07 (d, 2H), 7.01 (m, 1H), 6.68 (m, 2H), 5.35 (m, 2H), 4.22 (m, 1H), 3.04-2.95 (m, 6H) ), 2.77 (s, 2H), 2.29-2.24 (m, 4H), 2.14 (m, 4H), 2.03 (m, 2H), 1.97 (s, 2H), 1.70 (m, 2H), 1.52 (m, 1H), 1.38 (t, 2H), 0.94 (s, 6H), 0.35 (m, 4H).</p><p num="1299"> Example 450 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[(1,4-dioxane-2-ylmethyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 336A.¹1 H NMR (500MHz, Pyridine-d₅5) δ 9.24 (m, 1H), 8.81 (m, 1H), 8.56 (s, 1H), 8.37 (dd, 1H), 8.03 (d, 1H), 7.52 (d, 1H), 7.44 (d, 2H) ), 7.21 (m, 1H), 7.11 (m, 1H), 7.07 (d, 2H), 6.92 (d, 1H), 6.71 (m, 2H), 5.33 (m, 2H), 3.94 (m, 2H) , 3.78 (m, 1H), 3.73-3.66 (m, 2H), 3.58 (m, 1H), 3.51-3.36 (m, 3H), 3.03 (m, 4H), 2.77 (s, 2H), 2.26 (m) , 2H), 2.15 (m, 4H), 1.97 (s, 2H), 1.39 (t, 2H), 0.94 (s, 6H).</p><p num="1300"> Example 451 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(1-cyclopropylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 451A 4- (1-Cyclopropylpiperidine-4-ylamino) -3-nitrobenzenesulfonamide N, N-diisopropylethylamine (2.22 g) and 4-dimethyl in a solution of 4-fluoro-3-nitrobenzenesulfonamide (1.26 g) and 1-cyclopropylpiperidin-4-amine (0.802 g) in tetrahydrofuran (20 mL). Aminopyridine (35 mg) was added. Reflux the mixture for 18 hours, cool and then ethyl acetate (200 mL) and LVDS.₃Diluted with aqueous solution. The organic layer was concentrated to isolate the crude product, purified on silica gel and eluted with 5% methanolic ammonia in methylene chloride to give the title compound.</p><p num="1301"> Example 451B 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(1-cyclopropylpiperidin-4-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 451A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.26 (m, 1H), 8.59 (s, 1H), 8.46 (d, 1H), 8.42 (dd, 1H), 8.01 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H) , 7.25 (d, 1H), 7.17 (d, 1H), 7.07 (d, 2H), 6.96 (d, 1H), 6.72-6.67 (m, 2H), 5.48 (m, 2H), 3.54 (m, 1H) ), 3.03 (m, 4H), 2.90 (m, 2H), 2.76 (s, 2H), 2.37 (m, 2H), 2.25 (m, 2H), 2.14 (m, 4H), 1.98-1.91 (m, 4H), 1.56 (m, 3H), 1.38 (t, 2H), 0.94 (s, 6H), 0.42 (m, 4H).</p><p num="1302"> Example 452 Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-({4-[(4-morpholine-4-ylcyclohexyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 204A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.27 (m, 1H), 8.59 (s, 1H), 8.42 (dd, 1H), 8.36 (d, 1H), 8.01 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H) , 7.25 (m, 1H), 7.17 (m, 1H), 7.07 (d, 2H), 6.95 (d, 1H), 6.71 (d, 2H), 6.33 (m, 2H), 3.76 (m, 4H), 3.40 (m, 1H), 3.03 (m, 4H), 2.76 (s, 2H), 2.52 (m, 4H), 2.25 (m, 3H), 2.14 (m, 4H), 2.07 (m, 2H), 1.97 (m, 2H), 1.89 (m, 2H), 1.42-1.21 (m, 6H), 0.94 (s, 6H).</p><p num="1303"> Example 453 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Ill) -N-({4-[(4-methylpiperazin-1-yl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 174A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.25 (m, 2H), 8.59 (s, 1H), 8.44 (m, 1H), 8.00 (d, 1H), 7.68 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H) , 7.25 (m, 1H), 7.17 (m, 1H), 7.06 (d, 2H), 6.72-6.67 (m, 2H), 6.36 (m, 1H), 2.02 (m, 4H), 2.93 (m, 4H) ), 2.76 (s, 2H), 2.74-2.61 (m, 2H), 2.35-2.22 (m, 5H), 2.19 (s, 3H), 2.16-2.10 (m, 4H), 1.97 (m, 2H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1304"> Example 454 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(1-methylpiperidin-4-yl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 88A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.28 (m, 1H), 8.66 (m, 1H), 8.58 (s, 1H), 8.40 (dd, 1H), 8.02 (d, 1H), 7.53 (d, 1H), 7.44 (d, 2H) , 7.24 (m, 1H), 7.15 (m, 1H), 7.07 (d, 2H), 6.89 (d, 1H), 6.73-6.69 (m, 2H), 5.86 (m, 2H), 3.17 (t, 2H) ), 3.01-3.04 (m, 4H), 2.86 (m, 2H), 2.77 (s, 2H), 2.25 (m, 5H), 2.14 (m, 4H), 1.96-1.97 (s, 2H), 1.92 ( m, 2H), 1.70 (m, 2H), 1.60 (m, 1H), 1.48-1.37 (m, 4H), 0.94 (s, 6H).</p><p num="1305"> Example 455 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[({(2R) -4- [2- (2-methoxyethoxy) ethyl] morpholine-2-yl} methyl) amino] -3-nitrophenyl} sulfonyl) benzamide Example 455A (R) -4-((4- (2- (2-Methoxyethoxy) ethyl) morpholine-2-yl) methylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by substituting Example 415B of Example 415C with Example 437B and substituting 2,2-difluoroethyl iodide with 2- (2-methoxyethoxy) ethyl bromide.</p><p num="1306"> Example 455B 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-({4-[({(2R) -4- [2- (2-methoxyethoxy) ethyl] morpholine-2-yl} methyl) amino] -3-nitrophenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 455A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.24 (d, 1H), 8.85 (t, 1H), 8.56 (s, 1H), 8.36 (dd, 1H), 8.03 (d, 1H), 7.51 (d, 1H), 7.44 (d, 2H) , 7.24 (m, 2H), 7.12 (d, 1H), 7.07 (d, 2H), 6.91 (d, 1H), 6.73-6.68 (m, 2H), 3.93-3.86 (m, 2H), 3.72-3.61 (m, 5H), 3.53 (m, 2H), 3.48-3.40 (m, 2H), 3.28 (s, 3H), 3.03 (m, 4H), 2.95 (d, 1H), 2.77 (s, 2H), 2.70 (d, 1H), 2.69 (t, 2H), 2.27-2.10 (m, 8H), 1.97 (s, 2H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1307"> Example 456 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-[(4-{[(4,4-difluorocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 412C.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.29 (d, 1H), 8.73 (t, 1H), 8.58 (s, 1H), 8.42 (dd, 1H), 7.99 (d, 1H), 7.52 (d, 1H), 7.43 (d, 2H) , 7.24 (m, 2H), 7.17 (d, 1H), 7.07 (d, 2H), 6.94 (d, 1H), 6.72 (d, 1H), 6.69 (dd, 1H), 3.22 (t, 2H), 3.03 (m, 4H), 2.76 (s, 2H), 2.25 (m, 2H), 2.13 (m, 6H), 1.97 (s, 2H), 1.85-1.70 (m, 5H), 1.38 (t, 2H) , 1.36-1.33 (m, 2H), 0.94 (s, 6H).</p><p num="1308"> Example 457 N-[(4-{[(4-Acetylmorpholine-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-benzimidazol-4-yloxy) -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide Example 457A 4-((4-Acetyl Morpholine-2-yl) Methylamino) -3-Nitrobenzene Sulfonamide Examples 415B (145 mg) and N-ethyl-N-isopropylpropan-2-amine (120 μl) in anhydrous dichloromethane (5 mL) and N, N-dimethylformamide (2 mL) are cooled in an ice bath and anhydrous. Acetic anhydride (56 μl) was added dropwise. The mixture was stirred at room temperature for 3 hours and concentrated to dryness. The residue was mixed with water. The obtained solid was dried under vacuum to give the title compound.</p><p num="1309"> Example 457B N-[(4-{[(4-Acetylmorpholine-2-yl) methyl] amino} -3-nitrophenyl) sulfonyl] -2- (1H-benzimidazol-4-yloxy) -4- (4- { [2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 457A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.24 (d, 1H), 8.83 (t, 1H), 8.56 (s, 1H), 8.38 (dd, 1H), 8.03 (d, 1H), 7.51 (d, 1H), 7.43 (d, 2H) , 7.24 (m, 2H), 7.09 (d, 1H), 7.07 (d, 2H), 6.91 (dd, 1H), 6.72 (m, 2H), 3.89 (m, 1H), 3.80-3.70 (m, 1H) ), 3.60-3.40 (m, 4H), 3.06 (m, 1H), 3.03 (m, 4H), 2.77 (s, 2H), 2.70 (m, 1H), 2.26 (m, 2H), 2.18-2.13 ( m, 5H), 2.09 (s, 3H), 1.97 (s, 2H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1310"> Example 458 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[4- (methylsulfonyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide Example 458A 4-((4- (Methylsulfonyl) morpholine-2-yl) methylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing acetic anhydride of Example 457A with methanesulfonyl chloride.</p><p num="1311"> Example 458B 2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1- Il) -N-{[4-({[4- (methylsulfonyl) morpholine-2-yl] methyl} amino) -3-nitrophenyl] sulfonyl} benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 458A.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.23 (d, 1H), 8.85 (t, 1H), 8.57 (s, 1H), 8.37 (dd, 1H), 8.01 (d, 1H), 7.52 (d, 1H), 7.43 (d, 2H) , 7.24 (m, 2H), 7.15 (d, 1H), 7.07 (d, 2H), 6.97 (d, 1H), 6.72 (m, 2H), 4.00-3.90 (m, 3H), 3.68-3.59 (m) , 3H), 3.58-3.48 (m, 1H), 3.06-3.02 (m, 7H), 2.98-2.89 (m, 2H), 2.77 (s, 2H), 2.25 (m, 2H), 2.14 (m, 4H) ), 1.97 (s, 2H), 1.38 (t, 2H), 0.94 (s, 6H).</p><p num="1312"> Example 459 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[6-({4- Fluoro-1- [2-fluoro-1- (fluoromethyl) ethyl] piperidine-4-yl} methoxy) -5- (trifluoromethyl) pyridine-3-yl] sulfonyl} -2- (1H-indazole-4) -Iloxy) benzamide Example 459A tert-Butyl 4-fluoro-4-((5-sulfamoyl-3- (trifluoromethyl) pyridin-2-yloxy) methyl) piperidine-1-carboxylate This Example compound was prepared by replacing Example 329A of Example 329B with Example 410E and replacing methanol (tetrahydro-2H-pyran-4-yl) with Example 419A.</p><p num="1313"> Example 459B 6-((4-Fluoropiperidin-4-yl) methoxy) -5- (trifluoromethyl) Pyridine-3-sulfonamide This Example compound was prepared by substituting Example 422A of Example 422B with Example 459A.</p><p num="1314"> Example 459C 6-((1- (1,3-Difluoropropan-2-yl) -4-fluoropiperidin-4-yl) methoxy) -5- (trifluoromethyl) Pyridine-3-sulfonamide This Example compound was prepared by substituting Example 422B of Example 434A with Example 459B.</p><p num="1315"> Example 459D 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[6-({4- Fluoro-1- [2-fluoro-1- (fluoromethyl) ethyl] piperidine-4-yl} methoxy) -5- (trifluoromethyl) pyridine-3-yl] sulfonyl} -2- (1H-indazole-4) -Iloxy) benzamide This Example compound was prepared by replacing Example 26C of Example 177 with Example 400E and replacing Example 1F with Example 459C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 12.94 (d, 1H), 8.40 (d, 1H), 8.11 (d, 1H), 7.68 (m, 2H), 7.35 (d, 2H), 7.06 (d, 2H), 6.99 (d, 2H) , 6.71 (dd, 1H), 6.39 (d, 1H), 6.06 (t, 1H), 4.67 (d, 2H), 4.55 (d, 2H), 4.47 (d, 2H), 3.07 (m, 5H), 2.74 (m, 6H), 2.19 (m, 6H), 1.90 (m, 6H), 1.40 (t, 2H), 0.93 (s, 6H).</p><p num="1316"> Example 460 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-({3-nitro-4-yl) [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide The title compound was prepared in the same manner as described in Example 177, replacing Example 26C with Example 18G.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 12.87 (s, 1H), 11.60 (s, 1H), 8.58 (s, 1H), 8.47 (d, 1H), 8.11 (s, 1H), 7.81-7.91 (m, 1H), 7.76 (dd, dd, 1H), 7.59-7.66 (m, 1H), 7.48 (d, 1H), 7.34 (d, 2H), 7.00-7.11 (m, 5H), 6.73 (dd, 1H), 6.67 (dd, 1H), 6.08 (d, 1H), 3.85 (dd, 2H), 3.20-3.30 (m, 4H), 3.04 (s, 4H), 2.77 (s, 2H), 2.17 (d, 6H), 1.96 (s, 2H), 1.81-1.92 (m, 1H), 1.55-1.66 (m, 2H), 1.39 (t, 2H), 1.17-1.32 (m, 2H), 0.93 (s, 6H).</p><p num="1317"> Example 461 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (2-tetra-2-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide Example 461A 5-Chloro-6- (2- (tetrahydro-2-yl) ethoxy) Pyridine-3-sulfonamide This Example compound was prepared by replacing Example 329A of Example 329B with Example 387A and replacing (tetrahydro-2H-pyran-4-yl) methanol with 2- (tetrahydro-2-yl) ethanol.</p><p num="1318"> Example 461B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-chloro-6- (2-tetra-2-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-indazole-4-yloxy) benzamide This Example compound was prepared by replacing Example 1F of Example 177C with Example 461A and replacing Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.08 (s, 1H), 8.27 (d, J = 2.17Hz, 1H), 7.83 (d, J = 1.83Hz, 1H), 7.80 (s, 1H), 7.58 (d, J = 8.85Hz, 1H) ), 7.36 (d, J = 8.54Hz, 2H), 7.03-7.10 (m, 4H), 6.79 (dd, J = 9,2.29Hz, 1H), 6.54 (d, J = 1.53Hz, 1H), 6.13 (d, J = 7.02Hz, 1H), 4.41-4.47 (m, 2H), 3.91-3.94 (m, 1H), 3.71-3.80 (m, 1H), 3.56-3.63 (m, 2H), 3.25 (br s, 2H), 2.33 (br s, 2H), 2.16-2.18 (m, 2H), 1.92-2.01 (m, 5H), 1.80-1.86 (m, 2H), 1.47-1.53 (m, 1H), 1.42 (t, J-6.26Hz, 2H), 0.94 (s, 6H).</p><p num="1319"> Example 462 Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-[(4-{[(4-cyanocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 462A 2- (Trans-4- (aminomethyl) cyclohexyl) acetonitrile Trifluoroacetic acid (3 mL) was added slowly at 0 ° C to a solution of tert-butyl (trans-4- (cyanomethyl) cyclohexyl) methylcarbamate (500 mg) in dichloromethane (5 mL). The mixture was warmed to room temperature and stirred for 1 hour. The title compound was obtained by concentration.</p><p num="1320"> Example 462B 4-((Trans-4-cyanocyclohexyl) methylamino) -3-nitrobenzenesulfonamide This Example compound was prepared by replacing the (tetrahydropyran-4-yl) methylamine of Example 1F with Example 462A.</p><p num="1321"> Example 462C Trans-2- (1H-benzimidazol-4-yloxy) -4- (4-{[2- (4-chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine- 1-yl) -N-[(4-{[(4-cyanocyclohexyl) methyl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 462B.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.29 (d, 1H), 8.67 (t, 1H), 8.59 (s, 1H), 8.41 (dd, 1H), 7.98 (d, 1H), 7.53 (d, 1H), 7.43 (d, 2H) , 7.25 (m, 1H), 7.19 (m, 1H), 7.07 (d, 2H), 6.91 (d, 1H), 6.73-6.68 (m, 2H), 5.24 (m, 2H), 3.13 (t, 2H) ), 3.03 (m, 4H), 2.76 (s, 2H), 2.43 (m, 1H), 2.25 (m, 2H), 2.13 (m, 4H), 1.99-1.94 (m, 4H), 1.77 (m, m, H), 1.59 (m, 1H), 1.46 (m, 2H), 1.38 (t, 2H), 0.99-0.90 (m, 8H).</p><p num="1322"> Example 463 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(4,4-difluorocyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide Example 463A (4,4-difluorocyclohexylmethanol) methanol Ethyl 4,4-difluorocyclohexanecarboxylate (1.0 g) in diethyl ether (2 mL) was added dropwise to a slurry of lithium aluminum hydride (0.24 g) in diethyl ether (15 mL). The reaction was reflux heated under nitrogen for 4 hours. The reaction was cooled to 0 ° C., followed by careful addition of water (0.24 mL), aqueous 4N NaOH solution (0.24 mL) and water (0.72 mL). The reaction was diluted with diethyl ether (40 mL) and stirred with sodium sulfate for 30 minutes. The mixture was filtered through diatomaceous earth and the filtrate was concentrated to give the title compound.</p><p num="1323"> Example 463B 5-Chloro-6-((4,4-difluorocyclohexyl) methoxy) Pyridine-3-sulfonamide This Example compound was prepared by substituting (tetrahydro-2H-pyran-4-yl) methanol of Example 329B with Example 463A and substituting Example 329A with Example 387A.</p><p num="1324"> Example 463C 2- (1H-benzimidazol-4-yloxy) -N-({5-chloro-6-[(4,4-difluorocyclohexyl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[ 2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) benzamide This Example compound was prepared by substituting Example 428D of Example 428E with Example 463B.¹1 H NMR (500MHz, Pyridine-d₅) δ 9.15 (d, 1H), 8.69 (m, 1H), 8.59 (s, 1H), 7.99 (d, 1H), 7.53 (d, 1H), 7.44 (d, 2H), 7.24 (m, 1H) , 7.16 (m, 1H), 7.07 (d, 2H), 6.70 (m, 2H), 5.45 (m, 2H), 4.22 (d, 2H), 3.04 (m, 4H), 2.77 (s, 2H), 2.26 (m, 2H), 2.16-2.08 (m, 6H), 1.97 (s, 2H), 1.86-1.68 (m, 5H), 1.47-1.36 (m, 4H), 0.94 (m, 6H).</p><p num="1325"> Example 464 N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4 -Dimethylcyclohex-1-en-1-yl] Methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 464A 3-Chloro-4-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) benzenesulfonamide This Example compound was prepared by substituting Example 329A of Example 329B with 3,4-dichlorobenzenesulfonamide and methanol (tetrahydro-2H-pyran-4-yl) with Example 306C.</p><p num="1326"> Example 464B N- (3-Chloro-4-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) phenylsulfonyl) -4- (4-((2- (4-chlorophenyl) -4,4-dimethyl) Cyclohexa-1-enyl) methyl) piperazine-1-yl) -2-(1-((2- (trimethylsilyl) ethoxy) methyl) -1H-indazole-4-yloxy) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 435D and Example 1F with Example 464A.</p><p num="1327"> Example 464C N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] phenyl} sulfonyl) -4- (4-{[2- (4-chlorophenyl) -4,4 -Dimethylcyclohex-1-en-1-yl] Methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide This Example compound was prepared by substituting Example 435E of Example 435F with Example 464B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 13.15 (s, 1H), 11.74-11.31 (m, 1H), 7.85 (s, 1H), 7.67 (d, 1H), 7.62-7.49 (m, 2H), 7.35 (d, 2H), 7.22- 7.09 (m, 3H), 7.05 (d, 2H), 6.80 (d, 1H), 6.53 (s, 1H), 6.23 (d, 1H), 4.26 (d, 2H), 3.79 (d, 2H), 3.62 (dd, 2H), 3.17 (s, 4H), 2.77 (d, 2H), 2.22 (d, 6H), 1.88 (dd, 6H), 1.40 (t, 2H), 0.94 (s, 6H).</p><p num="1328"> Example 465 N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[4- (4-chlorophenyl)) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide Example 465A Methyl 2- (1H-indazole-4-yloxy) -4-(4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) Piperazine-1-yl) benzoate This Example compound was prepared by replacing tert-butylpiperazin-1-carboxylate of Example 1A with Example 400C and replacing Example 27C with Example 145E.</p><p num="1329"> Example 465B Methyl 4-(4-((4- (4-chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine-1-yl) -2- (1-) ((2- (Trimethylsilyl) ethoxy) methyl) -1H-indazole-4-yloxy) benzoate This Example compound was prepared by substituting Example 400D of Example 435C with Example 465A.</p><p num="1330"> Example 465C 4- (4-((4- (4-Chlorophenyl) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine-1-yl) -2- (1-( (2- (Trimethylsilyl) ethoxy) methyl) -1H-indazole-4-yloxy) Benzoic acid This Example compound was prepared by substituting Example 175D of Example 175E with Example 465B.</p><p num="1331"> Example 465D N- (5-Chloro-6-((4-fluorotetrahydro-2H-pyran-4-yl) methoxy) Pyridine-3-ylsulfonyl) -4- (4-((4- (4-chlorophenyl) -6) , 6-Dimethyl-5,6-dihydro-2H-pyran-3-yl) methyl) piperazine-1-yl) -2-(1-((2- (trimethylsilyl) ethoxy) methyl) -1H-indazole-4 -Iloxy) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 465C and Example 1F with Example 404A.</p><p num="1332"> Example 465E N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl) methoxy] pyridin-3-yl} sulfonyl) -4- (4-{[4- (4-chlorophenyl)) -6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl] methyl} piperazine-1-yl) -2- (1H-indazole-4-yloxy) benzamide 20-100% CH of this example compound by preparative HPLC using the final compound, here C18 column, 250 x 50 mm, 10 μ.₃Example 435E of Example 435F was replaced with Example 465D, except that it was eluted in CN vs. water with a gradient of 0.1% trifluoroacetic acid, followed by eluting with 98/2 dichloromethane / methanol and purified by column chromatography. Prepared.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 13.13 (s, 1H), 8.28 (d, 1H), 7.90 (d, 1H), 7.83 (s, 1H), 7.58 (d, 1H), 7.39 (d, 2H), 7.17 (d, 2H) , 7.08 (m, 2H), 6.82 (dd, 1H), 6.57 (d, 1H), 6.14 (d, 1H), 4.52 (d, 2H), 4.15 (s, 2H), 3.80 (m, 2H), 3.60 (m, 2H), 3.20 (v br m, 4H), 2.98 (v br s, 2H), 2.35 (v br m, 4H), 2.18 (s, 2H), 1.87 (m, 4H), 1.20 ( s, 6H).</p><p num="1333"> Example 466 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Tetrahydro-2H-Pyran-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-Indazole-4-yloxy) Benzamide Example 466A 5-Bromo-6- (2- (Tetrahydro-2H-pyran-4-yl) ethoxy) Pyridine-3-sulfonamide This Example compound was prepared by replacing the (tetrahydro-2H-pyran-4-yl) methanol of Example 329B with 2- (tetrahydro-2H-pyran-4-yl) ethanol.</p><p num="1334"> Example 466B 5-Cyano-6- (2- (Tetrahydro-2H-pyran-4-yl) ethoxy) Pyridine-3-sulfonamide This Example compound was prepared by substituting Example 329A of Example 333A with Example 466A.</p><p num="1335"> Example 466C 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -N-{[5-cyano-6- (2-Tetrahydro-2H-Pyran-4-ylethoxy) Pyridine-3-yl] Sulfonyl} -2- (1H-Indazole-4-yloxy) Benzamide This Example compound was prepared by substituting Example 1F of Example 177C with Example 466B and Example 26C with Example 400E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 13.04 (s, 1H), 8.48 (d, 1H), 8.13 (s, 1H), 7.75 (s, 1H), 7.62 (d, 1H), 7.37 (d, 2H), 7.01-7.08 (m, 4H), 6.76 (dd, 1H), 6.51 (d, 1H), 6.08 (d, 1H), 4.47 (t, 2H), 3.81-3.85 (m, 2H), 3.71-3.80 (m, 1H), 2.18 (m, 2H), 1.99 (m, 2H), 1.62-1.72 (m, 5H), 1.42 (t, 2H), 1.23 (m, 2H), 0.94 (s, 6H).</p><p num="1336"> Example 467 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide Example 467A 4-((1R, 3R, 5S) -8-methyl-8-azabicyclo [3.2.1] octane-3-ylamino) -3-nitrobenzene sulfonamide This Example compound, 1- (2-methoxy-ethyl) -piperidine-4-ylamine of Example 189A (1R, 3R, 5S) -8-methyl-8-azabicyclo [3,2,1] octane- Prepared by replacing with 3-amine.</p><p num="1337"> Example 467B 4- (4-{[2- (4-Chlorophenyl) -4,4-dimethylcyclohex-1-en-1-yl] methyl} piperazine-1-yl) -2- (1H-indole-5-yloxy) )-N-[(4-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} -3-nitrophenyl) sulfonyl] benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 26C and Example 1F with Example 467A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.47 (br s, 1H), 11.17 (s, 1H), 9.43 (br s, 1H), 8.69 (d, 1H), 8.62 (d, 1H), 7.90 (dd, 1H), 7.52 (d, 1H), 7.40 (m, 3H), 7.15 (d, 1H), 7.06 (m, 3H), 6.85 (dd, 1H), 6.68 (m, 1H), 6.39 (t, 1H), 6.19 (br s, 1H), 4.01 (m, 1H), 3.91 (m, 2H), 3.58 (m, 3H), 3.01 (m, 3H), 2.73 (m, 5H), 2.32 (m, 6H), 2.16 (m, 6H) ), 2.0 (m, 2H), 1.45 (m, 2H), 0.94 (s, 6H).</p><p num="1338"> Example 468 N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropanoid)] [(1S,, 2S, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide Example 468A Methyl 2-phenoxy-4- (1,4-dioxa-8-azaspiro [4.5] decane-8-yl) benzoate 1,4-Dioxa-8-azaspiro [4.5] decane (1.18 g), methyl 4-fluoro-2-phenoxybenzoate (1.85 g) and K₂CO₃(1.14 g) was stirred in dimethyl sulfoxide (25 mL) at 125 ° C for 24 hours. The mixture was cooled, poured into 300 mL of water, extracted 3 times with ether, the ether extracts were combined and rinsed 3 times with water and brine to concentrate. The residue was chromatographed on silica gel using 10-30% ethyl acetate in hexanes as the eluent to give the title compound.</p><p num="1339"> Example 468B Methyl 4- (4-oxopiperidine-1-yl) -2-phenoxybenzoate Example 468A (23.7 g) was heated to 80 ° C. for 24 hours in a mixture of acetic acid (30 mL), tetrahydrofuran (40 mL) and water (30 mL). The mixture was cooled and concentrated. The crude product was chromatographed on silica gel using 25% ethyl acetate in hexanes as the eluent to give the title compound.</p><p num="1340"> Example 468C Methyl 2-phenoxy-4-(4-((1S, 2S, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] heptane-3-ylamino) piperidine-1-yl) benzoate Examples 468B (0.99 g) and (1S, 2S, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] heptane-3-amine (0.51 mL), 200 mL using Dean-Stark trap. Refluxed in methanol for 24 hours. The solvent was evaporated to a volume of 75 mL and the mixture was cooled to room temperature. NaBH₄(0.115 g) was added and the mixture was stirred for 30 minutes. The reaction was quenched with 10 mL water, partially concentrated and chromatographed on silica gel with 1% triethylamine in ethyl acetate as the eluent to give the title compound.</p><p num="1341"> Example 468D Methyl 2-phenoxy-4- (4- (3-phenyl-N-((1S, 2S, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] heptane-3-yl) propanamide) Piperidine-1-yl) benzoate Example 468C (320 mg), 3-phenylpropanoyl chloride (0.113 mL) and triethylamine (0.116 mL) were stirred in dichloromethane (15 mL) for 24 hours. The reaction mixture was partially concentrated and the residue was chromatographed on silica gel with 20% ethyl acetate in hexanes as eluent to give the title compound.</p><p num="1342"> Example 468E 2-Phenoxy-4- (4- (3-Phenyl-N-((1S, 2S, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] heptane-3-yl) propanamide) piperidine -1-yl) benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 468D.</p><p num="1343"> Example 468F N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropanoid)] [(1S,, 2S, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 468E.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.32 (m, 2H), 7.64 (m, 2H), 7.11-7.29 (m, 6H), 6.95 (dd, 1H), 6.89 (dd, 1H), 6.70 (m, 3H), 6.32 (m, m, 1H), 3.85 (m, 3H), 3.70 (m, 3H), 2.91 (m, 6H), 2.65-2.80 (m, 6H), 1.91 (s, 6H), 1.61 (m, 4H), 1.16-1.36 (m, 4H), 1.11 (m, 6H), 0.95 (m, 4H), 0.87 (d, 2H).</p><p num="1344"> Example 469 N-({4-[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropanoid)] [(1 S, 2S, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 468E and substituting Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.72 (m, 1H), 8.44 (d, 1H), 7.73 (dd, 1H), 7.54 (m, 1H), 7.12-7.28 (m, 6H), 7.05 (dd, 1H), 6.95 (dd, dd, 1H), 6.82 (d, 1H), 6.74 (m, 2H), 6.34 (m, 1H), 3.77 (m, 2H), 3.63 (m, 4H), 3.10 (m, 4H), 3.05 (m, 4H) ), 2.78 (m, 6H), 1.75-2.10 (m, 8H), 1.55 (m, 2H), 1.40 (m, 2H), 1.19 (m, 6H), 1.01 (m, 2H), 0.95 (m, m, 2H), 0.88 (d, 2H).</p><p num="1345"> Example 470 N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropyl)] [(1S, 2S) , 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide Example 470A Methyl 2-phenoxy-4-(4-((3-phenylpropyl) ((1S, 2S, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] heptane-3-yl) amino) piperidine -1-yl) benzoate Examples 468C (320 mg), 3-Phenylpropanal (111 mg) and NaBH (OAc)₃(205 mg) was stirred in dichloromethane (15 mL) for 24 hours. The reaction mixture was chromatographed on silica gel using 20% ethyl acetate in hexanes as the eluent to give the title compound.</p><p num="1346"> Example 470B 2-Phenoxy-4-(4-((3-phenylpropyl) ((1S, 2S, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] heptane-3-yl) amino) piperidine- 1-Il) Benzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 470A.</p><p num="1347"> Example 470C N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropyl)] [(1S, 2S) , 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 470B.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.57 (m, 1H), 8.47 (d, 1H), 7.50 (m, 1H), 7.32 (m, 1H), 7.12-7.31 (m, 7H), 6.99 (dd, 1H), 6.81 (m, 3H), 6.37 (d, 1H), 4.44 (t, 1H), 3.84 (m, 4H), 3.37 (m, 2H), 3.25 (m, 2H), 3.06 (m, 2H), 2.70 (m, 4H) ), 2.57 (m, 4H), 1.82 (m, 2H), 1.77 (m, 4H), 1.52-1.71 (m, 8H), 1.25 (m, 3H), 1.15 (s, 3H), 0.95 (d, 2H), 0.93 (s, 3H), 0.74 (d, 2H).</p><p num="1348"> Example 471 N-({4-[(3-morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxy-4- (4-{(3-phenylpropyl)] [(1S, 2S,, 3S, 5R) -2,6,6-trimethylbicyclo [3.1.1] hepta-3-yl] amino} piperidine-1-yl) benzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 470B and substituting Example 1F with Example 7A.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 8.68 (m, 1H), 8.40 (d, 1H), 7.70 (dd, 1H), 7.55 (d, 1H), 7.11-7.29 (m, 7H), 7.01 (dd, 1H), 6.95 (dd, dd, 1H), 6.76 (d, 2H), 6.34 (m, 1H), 3.75 (m, 2H), 3.61 (m, 4H), 3.43 (m, 4H), 3.05 (m, 6H), 2.75 (m, 2H) ), 2.60 (m, 2H), 2.41 (m, 4H), 2.15 (m, 1H), 1.82 (m, 4H), 1.69 (m, 2H), 1.51 (m, 1H), 1.18 (m, 8H) , 0.96 (m, 1H), 0.94 (s, 3H).</p><p num="1349"> Example 472 4- [4-(2-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} benzyl) piperazine-1-yl] -N-({4 -[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide Example 472A Ethyl 4-fluoro-2-phenoxybenzoate (600 mg) and piperazine (596 mg) were dissolved in anhydrous dimethyl sulfoxide and heated at 130 ° C. overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water and brine, dehydrated with anhydrous sodium sulfate, filtered and concentrated to give the title compound.</p><p num="1350"> Example 472B Example 472A (400 mg), 1- (bromomethyl) -2-nitrobenzene (277 mg) and sodium carbonate (408 mg) were suspended in anhydrous N, N-dimethylformamide (20 mL). The reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was diluted with ethyl acetate. The organic phase was washed with water and brine, dehydrated with anhydrous sodium sulfate, filtered and concentrated. Flash column purification with 10-40% ethyl acetate / hexane gave the title compound.</p><p num="1351"> Example 472C A solution of Example 472B (0.6 g) in methanol (20 ml) was added to Ra-Ni (solvent wash) (0.480 g) in a 250 mL pressure resistant bottle and stirred at 30 psi at room temperature for 3 hours. The mixture was filtered through a nylon membrane and concentrated to give the product.</p><p num="1352"> Example 472D This Example compound was replaced with (1R, 5S) -8-methyl-8-azabicyclo [3,2,1] octane-3-one of 4'-cyclobiphenyl-2-carboxardehide in Example 1A. It was prepared by replacing tert-butylpiperazin-1-carboxylate with Example 472C.</p><p num="1353"> Example 472E This Example compound was prepared by substituting Example 175D of Example 175E with Example 472D.</p><p num="1354"> Example 472F 4- [4-(2-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} benzyl) piperazine-1-yl] -N-({4 -[(3-Morpholine-4-ylpropyl) amino] -3-nitrophenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 472E and substituting Example 1F with Example 7A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.66 (bs, 1H), 9.90 (bs, 1H), 9.56 (s, 1H), 8.69 (t, 1H), 8.50 (d, 1H), 7.81 (dd, 1H), 7.54 (d, 1H) , 7.22 (m, 5H), 7.01 (m, 1H), 6.83 (m, 3H), 6.47 (s, 1H), 3.84 (m, 4H), 3.65 (d, 6H), 3.54 (m, 4H), 3.43 (m, 2H), 3.19 (m, 8H), 2.68 (d, 3H), 2.34 (m, 2H), 2.25 (m, 4H), 1.99 (m, 4H).</p><p num="1355"> Example 473 4- [4-(2-{[(1R, 5S) -8-methyl-8-azabicyclo [3.2.1] octa-3-yl] amino} benzyl) piperazin-1-yl] -N-({3 -Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 472E.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.61 (bs, 1H), 9.38 (bs, 1H), 8.64 (s, 1H), 8.47 (d, 1H), 7.75 (dd, 1H), 7.55 (d, 1H), 7.23 (t, 3H) , 7.15 (d, 2H), 6.98 (t, 1H), 6.82 (d, 3H), 6.47 (s, 2H), 3.85 (m, 6H), 3.31 (m, 12H), 2.68 (d, 3H), 2.06 (m, 9H), 1.62 (m, 2H), 1.29 (m, 2H).</p><p num="1356"> Example 474 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 474A 2-Fluorobenzaldehyde (264 mg), (1S, 5S) -3-azabicyclo [3.2.2] nonane (500 mg) and sodium carbonate (846 mg) were suspended in anhydrous dimethyl sulfoxide (3 mL). The reaction mixture was heated at 135 ° C. overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water and brine, dehydrated with anhydrous sodium sulfate, filtered and concentrated. Flash column purification with 0-10% ethyl acetate / hexane gave the title compound.</p><p num="1357"> Example 474B This Example compound was prepared by substituting 4'-chlorobiphenyl-2-carboxaldehide of Example 1A with Example 474A and tert-butylpiperazin-1-carboxylate with Example 113A.</p><p num="1358"> Example 474C This Example compound was prepared by substituting Example 175D of Example 175E with Example 474B.</p><p num="1359"> Example 474D 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -N-({3-nitro-4-[(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 474C.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.74 (bs, 1H), 8.64 (t, 1H), 8.47 (d, 1H), 7.76 (dd, 1H), 7.54 (m, 2H), 7.43 (d, 2H), 7.23 (m, 3H) , 7.15 (d, 1H), 6.98 (t, 1H), 6.83 (m, 3H), 6.53 (d, 1H), 4.45 (bs, 2H), 3.87 (m, 4H), 3.30 (m, 6H), 3.06 (m, 8H), 1.89 (m, 7H), 1.64 (m, 6H), 1.29 (m, 2H).</p><p num="1360"> Example 475 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -2-phenoxy-N-({4- [(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] -3-[(trifluoromethyl) sulfonyl] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 474C and Example 1F with Example 163A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.78 (bs, 1H), 8.11 (d, 1H), 7.86 (dd, 1H), 7.54 (d, 2H), 7.44 (d, 2H), 7.28 (m, 4H), 7.11 (d, 1H) , 7.04 (m, 1H), 6.85 (m, 3H), 6.53 (d, 1H), 4.46 (m, 2H), 3.86 (m, 4H), 3.28 (m, 6H), 3.10 (m, 4H), 2.98 (d, 4H), 1.97 (s, 2H), 1.84 (m, 5H), 1.64 (m, 6H), 1.26 (m, 2H).</p><p num="1361"> Example 476 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -2-phenoxy-N-({4- [(tetrahydro-2H-pyran-) 4-Ilmethyl) amino] phenyl} sulfonyl) benzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 474C and Example 1F with Example 2A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.19 (bs, 1H), 9.83 (bs, 1H), 7.52 (m, 6H), 7.33 (m, 3H), 7.12 (t, 1H), 6.93 (d, 2H), 6.83 (m, 1H) , 6.56 (d, 2H), 6.47 (d, 1H), 4.47 (s, 2H), 3.85 (m, 4H), 3.26 (m, 2H), 3.11 (m, 4H), 2.96 (m, 6H), 1.97 (s, 2H), 1.81 (m, 6H), 1.64 (m, 7H), 1.22 (m, 2H).</p><p num="1362"> Example 477 4- {4- [2- (3-Azabicyclo [3.2.2] nona-3-yl) benzyl] piperazine-1-yl} -N-({4- [(3-morpholine-4-ylpropyl) amino ] -3-Nitrophenyl} Sulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 27G of Example 27H with Example 474C and Example 1F with Example 7A.¹1 H NMR (400MHz, dimethyl sulfoxide-d₆) δ 11.77 (bs, 1H), 10.04 (bs, 1H), 8.69 (t, 1H), 8.50 (d, 1H), 7.81 (dd, 1H), 7.55 (d, 2H), 7.43 (d, 2H) , 7.24 (m, 3H), 7.15 (d, 1H), 7.01 (t, 1H), 6.84 (m, 3H), 6.52 (d, 1H), 4.44 (s, 2H), 3.97 (s, 2H), 3.54 (m, 6H), 3.39 (m, 4H), 3.19 (m, 8H), 2.97 (d, 4H), 1.99 (m, 4H), 1.83 (m, 4H), 1.64 (m, 4H).</p><p num="1363"> Example 478 4- (4- {2-[(4R, 7S) -2,3,3a, 4,7,7a-hexahydro-1H-4,7-methanoinden-5-yl] benzyl} piperazine-1-yl)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 478A 4- (4-Methoxycarbonyl-3-phenoxy-phenyl) -piperazin-1-carboxylic acid tert-butyl ester This Example compound was prepared by substituting Example 1B of Example 1D with piperazine-1-carboxylic acid tert-butyl ester.</p><p num="1364"> Example 478B 4- (4-carboxy-3-phenoxy-phenyl) -piperazin-1-carboxylic acid tert-butyl ester This Example compound was prepared by substituting Example 1D of Example 1E with Example 478A.</p><p num="1365"> Example 478C 4- (4- {3-Nitro-4-[(tetrahydro-pyran-4-ylmethyl) -amino] -benzenesulfonylaminocarbonyl} -3-phenoxy-phenyl) -piperazin-1-carboxylic acid tert-butyl ester This Example compound was prepared by substituting Example 1E of Example 1G with Example 478B.</p><p num="1366"> Example 478D 3-Nitro-N- (2-phenoxy-4-piperazin-1-yl-benzoyl) -4-[(tetrahydro-pyran-4-ylmethyl) -amino] -benzenesulfonamide This Example compound was prepared by replacing Example 1A of Example 1B with Example 478C, and the title compound was isolated as a monotrifluoroacetic acid salt.</p><p num="1367"> Example 478E Trifluoromethanesulfonic acid (4R, 7S)-(2,3,3a, 4,7,7a-hexahydro-1H-4,7-methano-inden-5-yl) ester (4R, 7R) -octahydro-4,7-methano-indene-5-one (2.00 g) was dissolved in tetrahydrofuran (25 mL) and cooled to -78 ° C using an isopropyl alcohol / dry ice bath. Sodium bis (trimethylsilyl) -amide (1M in tetrahydrofuran, 14.65 mL) was added slowly. The solution was warmed to room temperature, stirred for 1 hour, cooled to -78 ° C using an isopropyl alcohol / dry ice bath, and N-phenyltrifluoromethanesulfonimide (5.23 g) was added. The solution was warmed to room temperature and stirred for 16 hours. Hexane was added, the solution was stirred at room temperature for 1 hour, filtered and the solvent removed under vacuum.</p><p num="1368"> Example 478F (4R, 7S) -2- (2,3,3a, 4,7,7a-hexahydro-1H-4,7-methano-indene-5-yl) -benzaldehyde Example 478E (941 mg), 2-formylphenylboronic acid (600 mg) and tribasic potassium phosphate (1416 mg) were added to tetrahydrofuran (20 mL). The solution was degassed and flushed with nitrogen 3 times. Tetrakis (triphenylphosphine) palladium (0) (244 mg) was added and the solution was heated at 60 ° C. for 16 hours. The solution was cooled, added to water and extracted with 50% ethyl acetate (hexane). The extract was washed with brine, dehydrated over anhydrous sodium sulfate, concentrated and purified by flash column chromatography on silica gel with 10% ethyl acetate (hexane).</p><p num="1369"> Example 478G 4- (4- {2-[(4R, 7S) -2,3,3a, 4,7,7a-hexahydro-1H-4,7-methanoinden-5-yl] benzyl} piperazine-1-yl)- N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 478D (200 mg), Example 478F (74 mg) and sodium cyanoborohydride resin (2.15 mmol / g, 144 mg) were added to tetrahydrofuran (3 mL) and acetic acid (0.7 mL) and stirred at room temperature for 16 hours. The solution was concentrated under vacuum and purified by flash column chromatography on silica gel with 5% methanol (dichloromethane) to give the title compound as monoacetate.¹1 H NMR (300MHz, dimethyl sulfoxide-d₆) δ 11.94 (bs, 1H), 8.64 (t, 1H), 8.48 (d, 1H), 7.76 (dd, 1H), 7.51 (d, 1H), 7.40 (m, 1H), 7.27-7.18 (m, 5H), 7.16 (d, 1H), 6.99 (tt, 1H), 6.83 (dt, 2H), 6.78 (dd, 1H), 6.41 (d, 1H), 6.23 (d, 1H), 3.87 (dd, 2H) ), 3.50 (m, 2H), 3.34 (t, 2H), 3.21 (bs, 4H), 2.73 (bs, 1H), 2.63 (bs, 1H), 2.46 (m, 4H), 2.11 (m, 2H) , 1.95-1.75 (m, 4H), 1.91 (s, 3H), 1.66-1.52 (m, 6H), 1.28 (m, 2H), 1.02 (m, 2H), 0.85 (m, 1H).</p><p num="1370"> Example 479 4- [4- (2- {5-[(1R, 5S) -8-azabicyclo [3.2.1] octa-8-ylmethyl] thien-2-yl} benzyl) piperazine-1-yl] -N-( {3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 479A tert-Butyl 4- (4- (methoxycarbonyl) -3-phenoxyphenyl) piperazin-1-carboxylate This Example compound was prepared by substituting Example 1B of Example 1D with tert-butylpiperazin-1-carboxylate.</p><p num="1371"> Example 479B 4- (4- (tert-Butyloxycarbonyl) piperazine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 1D of Example 1E with Example 479A.</p><p num="1372"> Example 479C tert-Butyl 4-(4- (3-nitro-4-((tetrahydro-2H-pyran-4-yl) methylamino) phenylsulfonylcarbamoyl) -3-phenoxyphenyl) piperazin-1-carboxylate This Example compound was prepared by substituting Example 1E of Example 1G with Example 479B.</p><p num="1373"> Example 479D N- (3-Nitro-4-((Tetrahydro-2H-pyran-4-yl) methylamino) Phenylsulfonyl) -2-phenoxy-4- (piperazin-1-yl) benzamide This Example compound was prepared by substituting Example 1A of Example 1B with Example 479C.</p><p num="1374"> Example 479E 2-((4- (4- (3-Nitro-4-((tetrahydro-2H-pyran-4-yl) methylamino) phenylsulfonylcarbamoyl) -3-phenoxyphenyl) piperazin-1-yl) methyl) phenyl Boronic acid Example 479D (213 mg), 2-formylphenylboronic acid (54 mg) and sodium cyanoborohydride resin (2.38 mmol / g, 252 mg) are added to tetrahydrofuran (3.5 mL) and acetic acid (1.1 mL) and the solution is added at room temperature 16 Stirred for hours. The solution was purified by flash column chromatography on silica gel with 1% acetic acid and 10% methanol in dichloromethane.</p><p num="1375"> Example 479F 8-((5-Bromothiophene-2-yl) methyl) -8-azabicyclo [3.2.1] octane hydrochloride This Example compound was replaced with 5-bromothiophene-2-carbaldehyde in Example 1A 4'-chlorobiphenyl-2-carboxaldehide and tert-butylpiperazin-1-carboxylate replaced with 8-azabicyclo [3.2. 1] Prepared by replacing with octane hydrochloride.</p><p num="1376"> Example 479G 4- (4- (2- (5- (8-Azabicyclo [3.2.1] octane-8-ylmethyl) thiophen-2-yl) benzyl) piperazin-1-yl) -N- (3-nitro-4-yl) ((Tetrahydro-2H-pyran-4-yl) methylamino) Phenylsulfonyl) -2-phenoxybenzamide Example 479E (80 mg), Example 479F (42.5 mg), bis (triphenylphosphine) palladium (II) dichloride (7.7 mg) and lithium hydroxide (10.5 mg) in a microwave vial with dimethoxyethane (1.6 mL). ), Methanol (0.5 mL) and water (0.7 mL) were combined. The reaction mixture was heated in a CEM Discover microwave reactor at 150 ° C. for 15 minutes. The crude material was eluted with a gradient of 5% methanol / dichloromethane from 1% methanol / dichloromethane and purified by flash chromatography.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 8.33 (m, 2H), 7.64 (m, 2H), 7.44 (m, 1H), 7.39 (m, 1H), 7.32 (m, 2H), 7.12 (m, 3H), 6.90 (m, 2H) , 6.85 (t, 1H), 6.68 (m, 3H), 6.30 (d, 1H), 3.83 (dd, 2H), 3.65 (s, 2H), 3.51 (s, 2H), 3.17 (m, 4H), 3.08 (m, 4H), 2.45 (m, 6H), 1.92 (m, 2H), 1.62 (m, 4H), 1.54 (m, 3H), 1.28 (m, 6H).</p><p num="1377"> Example 480 4- [4- (2- {5-[(1R, 5S) -8-azabicyclo [3.2.1] octa-8-ylmethyl] thien-2-yl} benzylidene) piperidine-1-yl] -N-( {3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 480A Methyl 2-phenoxy-4- (1,4-dioxa-8-azaspiro [4.5] decane-8-yl) benzoate Methyl 4-fluoro-2-phenoxybenzoate (2 g) and 1,4-dioxa-8-azaspiro [4.5] decane (1.279 g) were combined with dimethyl sulfoxide O (12 mL) in a 250 mL round bottom flask. Sodium carbonate (1.291 g) was added. The reaction flask was sealed and heated to 130 ° C overnight. The reaction mixture is diluted with ethyl acetate, washed thoroughly with water and brine, and deli₄Dehydrated with, filtered and concentrated to give the desired product.</p><p num="1378"> Example 480B Methyl 4- (4-oxopiperidine-1-yl) -2-phenoxybenzoate Example 480A was taken in acetic acid (30%, 20 mL) and tetrahydrofuran (10 mL). The reaction mixture was heated to 75 ° C overnight. The volume was reduced under vacuum and the residue was neutralized with sodium hydroxide solution and extracted with ethyl acetate. Rinse the extract with water and brine and deli₄Dehydrated with, filtered and concentrated under vacuum to give the desired product.</p><p num="1379"> Example 480C Methyl 4- (4- (2-bromobenzylidene) piperidine-1-yl) -2-phenoxybenzoate Dimethyl sulfoxide (22.88 mL) and sodium hydride (0.332 g) were heated to 70 ° C for 1 hour, then cooled to room temperature, and (2-bromobenzyl) triphenylphosphonium bromide (3.40 g) was divided into several portions. And then stirred at room temperature for 1 hour. A solution of methyl 4- (4-oxopiperidine-1-yl) -2-phenoxybenzoate (1.8 g) in dimethyl sulfoxide (5.20 mL) was then added and the reaction was heated to 70 ° C. over the weekend. The reaction was acidified with 1M aqueous HCl and extracted with ether. Thoroughly wash the combined extracts with water and brine and deli₄Dehydrated with, filtered and concentrated under vacuum. The residue was purified by flash chromatography by eluting 0-20% ethyl acetate in hexanes.</p><p num="1380"> Example 480D Methyl 2-phenoxy-4- (4- (2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzylidene) piperidine-1-yl) benzoate Example 480C (259 mg), bis (pinacolato) diboron (206 mg), [1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium (II) dichloromethane (22 mg) and potassium acetate (159 mg) in dimethyl sulfoxide (2.7 mg) We put together in mL). The reaction was heated to 90 ° C for 36 hours. The reaction mixture is diluted with ethyl acetate, washed thoroughly with water and brine, and deli₄Dehydrated with, filtered and concentrated under vacuum. The crude solid was washed with hexane and hexane / ether (2: 1) to give the desired product.</p><p num="1381"> Example 480E 4- (4- (2- (5- (8-azabicyclo [3.2.1] octane-8-ylmethyl) thiophen-2-yl) benzylidene) piperidine-1-yl) -2-phenoxybenzoic acid This Example compound was prepared by substituting Example 479E of Example 479G with Example 480D.</p><p num="1382"> Example 480F 4- (4- (2- (5- (8-azabicyclo [3.2.1] octane-8-ylmethyl) thiophen-2-yl) benzylidene) piperidine-1-yl) -N- (3-nitro-4-yl) ((Tetrahydro-2H-pyran-4-yl) methylamino) Phenylsulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 1E of Example 1G with Example 480E.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.54 (s, 1H), 9.36 (br s, 1H), 8.48 (d, 1H), 7.76 (dd, 1H), 7.53 (m, 2H), 7.34 (m, 3H), 7.25 (m, 4H) ), 7.16 (d, 1H), 7.00 (t, 1H), 6.84 (d, 2H), 6.81 (dd, 1H), 6.44 (d, 1H), 6.37 (br s, 1H), 4.36 (d, 2H) ), 3.85 (m, 3H), 3.44 (m, 2H), 3.28 (m, 6H), 2.36 (m, 3H), 2.23 (m, 4H), 1.90 (m, 3H), 1.81 (m, 2H) , 1.62 (m, 5H), 1.47 (m, 1H), 1.29 (m, 2H).</p><p num="1383"> Example 481 4- [4- (3- {5-[(1R, 5S) -8-azabicyclo [3.2.1] octa-8-ylmethyl] thien-2-yl} benzyl) piperazine-1-yl] -N-( {3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl} sulfonyl) -2-phenoxybenzamide Example 481A 3-((4- (4- (3-Nitro-4-((tetrahydro-2H-pyran-4-yl) methylamino) phenylsulfonylcarbamoyl) -3-phenoxyphenyl) piperazin-1-yl) methyl) phenyl Boronic acid This Example compound was prepared by replacing 2-formylphenylboronic acid in Example 479E with 3-formylphenylboronic acid.</p><p num="1384"> Example 481B 4- (4- (3- (5- (8-Azabicyclo [3.2.1] octane-8-ylmethyl) thiophen-2-yl) benzyl) piperazin-1-yl) -N- (3-nitro-4-yl) ((Tetrahydro-2H-pyran-4-yl) methylamino) Phenylsulfonyl) -2-phenoxybenzamide This Example compound was prepared by substituting Example 479E of Example 479G with Example 481A.¹1 H NMR (500MHz, dimethyl sulfoxide-d₆) δ 11.76 (br s, 1H), 9.55 (br s, 1H), 8.55 (t, 1H), 8.46 (d, 1H), 7.75 (m, 2H), 7.54 (m, 2H), 7.40 (m, 1H), 7.20 (m, 4H), 6.97 (m, 1H), 6.86 (m, 1H), 6.82 (m, 3H), 6.55 (m, 1H), 4.41 (d, 2H), 3.88 (m, 6H) ), 3.43 (m, 3H), 3.30 (m, 6H), 3.06 (m, 6H), 1.90 (m, 4H), 1.65 (m, 5H), 1.30 (m, 3H).</p>