Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases

FIELD OF THE INVENTION

This invention pertains to compounds which inhibit the activity of Bcl-2 anti-apoptotic proteins, compositions containing the compounds, and methods of treating diseases during which anti-apoptotic Bcl-2 proteins are expressed.

BACKGROUND OF THE INVENTION

Anti-apoptotic Bcl-2 proteins are associated with a number of diseases. There is therefore an existing need in the therapeutic arts for compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins.

Overexpression of Bcl-2 proteins correlates with resistance to chemotherapy, clinical outcome, disease progression, overall prognosis or a combination thereof in various cancers and disorders of the immune system.

Involvement of Bcl-2 proteins in bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer, spleen cancer, and the like is described in commonly-owned PCT US 2004/36770, published as WO 2005/049593, and PCT US 2004/37911, published as WO 2005/024636.

Involvement of Bcl-2 proteins 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), 1283-92; and New England Journal of Medicine 2004, 351(14), 1409-1418. Involvement of Bcl-2 proteins in arthritis is disclosed in commonlyowned United States Provisional Patent Application Serial No. 60/988,479. Involvement of Bcl-2 proteins in bone marrow transplant rejection is disclosed in commonly-owned United States Patent Application Serial No. 11/941,196.

SUMMARY OF THE INVENTION

89929.1

In a first aspect, the present invention relates to a compound or a therapeutically acceptable salt thereof, wherein the compound is chosen from:

N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[2-(4chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-[(6-fluoro-1H-indol-5yl)oxy]benzamide;

N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{[4-(4chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-1-yl)-2-[(6-fluoro1H-indol-5-yl)oxy]benzamide;

N-({5-chloro-6-[(trans-4-hydroxycyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-[(6-fluoro-1H-indazol4-yl)oxy]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}piperazin-1-yl)-2-[(6-fluoro-1Hindazol-4-yl)oxy]benzamide;

tert-butyl 5-[(4-{4-[({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3yl}sulfonyl)carbamoyl]-3-[(6-fluoro-1H-indol-5-yl)oxy]phenyl}piperazin-1-yl)methyl]-4-(4chlorophenyl)-3,6-dihydropyridine-1(2H)-carboxylate;

N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[4(4-chlorophenyl)-1-(1,3-difluoropropan-2-yl)-1,2,5,6-tetrahydropyridin-3-yl]methyl}piperazin1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-[(6-fluoro1H-indazol-4-yl)oxy]-N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

N-({5-chloro-6-[(trans-4-hydroxycyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-[(7-fluoro-1H-indazol4-yl)oxy]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}piperazin-1-yl)-2-[(7-fluoro-1Hindazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-{[3-nitro-4-({[4-(oxetan-3-yl)morpholin-2yl]methyl}amino)phenyl]sulfonyl}benzamide;

1a

AH26(8494627_1):CCG

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-[(6-fluoro1H-indol-5-yl)oxy]-N-{[3-nitro-4-({[4-(oxetan-3-yl)morpholin-2yl]methyl}amino)phenyl]sulfonyl}benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-[(7-fluoro1H-indazol-4-yl)oxy]-N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

N-({5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-[(6-fluoro-1Hindazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-{[5chloro-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(3-methyl-2-oxo-2,3dihydro-1H-benzimidazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-[(4fluorotetrahydro-2H-pyran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(3-methyl-2-oxo-2,3dihydro-1H-benzimidazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(4{[(trans-4-methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo-2,3dihydro-1H-benzimidazol-4-yl)oxy]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl}sulfonyl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-[(4-{[4-fluoro-1-(oxetan-3-yl)piperidin-4-yl]methoxy}-3nitrophenyl)sulfonyl]benzamide;

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AH26(8494627_1):CCG

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-2-[(6-fluoro1H-indazol-4-yl)oxy]-N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-[(4-{[(trans-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-[(4-{[(trans-4-methoxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-({4-[(cis-4-hydroxy-4-methylcyclohexyl)methoxy]-3nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-[(4-{[(cis-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-{[3chloro-4-(tetrahydro-2H-pyran-4-ylmethoxy)phenyl]sulfonyl}-2-[(3-methyl-2-oxo-2,3-dihydro1H-benzimidazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(4-{[(4cyclopropylmorpholin-2-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo-2,3dihydro-1H-benzimidazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-{[3-nitro-4-(2-oxaspiro[3.5]non-7ylmethoxy)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-({4-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]-3nitrophenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-{[4-({[(2S)-4-cyclopropylmorpholin-2-yl]methyl}amino)-3nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(trans-1-fluoro-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)benzamide;

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AH26(8494627_1):CCG

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(cis-1-fluoro-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)benzamide;

2-[(3-amino-1H-indazol-4-yl)oxy]-N-({5-chloro-6-[(trans-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)benzamide;

N-({5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-2-[(3chloro-1H-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-[(4-{[(cis-4-ethyl-4-hydroxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-{[3-nitro-4-({[(2S)-4-(oxetan-3-yl)morpholin-2yl]methyl}amino)phenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-({5-nitro-6-[(tetrahydro-2H-pyran-4-ylmethyl)amino]pyridin-3yl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(2-oxaspiro[3.5]non-7ylmethyl)amino]phenyl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-{[4-({[trans-4-(morpholin-4-yl)cyclohexyl]methyl}amino)-3nitrophenyl]sulfonyl}benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-[(4-{[cis-4-(morpholin-4-yl)cyclohexyl]amino}-3nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({5cyano-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-2-[(6-fluoro1H-indazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-{[4-({[4-({[4-(methoxymethyl)cyclohexyl]methyl}amino)-3nitrophenyl]sulfonyl}amino)-3-nitrophenyl]sulfonyl}benzamide;

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AH26(8494627_1):CCG

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-[(3-nitro-4-{[(3R)-1-(oxetan-3-yl)pyrrolidin-3yl]amino}phenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1-yl)-N-[(3-nitro-4-{[(3S)-1-(oxetan-3-yl)pyrrolidin-3yl]amino}phenyl)sulfonyl]benzamide;

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)benzoyl}sulfamoyl)-2nitrophenyl]morpholine-4-carboxamide; and

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)benzoyl}sulfamoyl)-2-nitrophenyl]-4cyanopiperidine-1-carboxamide.

In a second aspect, the present invention relates to a pharmaceutical composition comprising the compound or therapeutically acceptable salt according to the first aspect, and a pharmaceutically acceptable excipient.

In a third aspect, the present invention relates to use of the compound or therapeutically acceptable salt according to the first aspect for the manufacture of a medicament for treating bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, a lymphoid malignancy of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer in a patient..

In a fourth aspect, the present invention relates to use of the compound or therapeutically acceptable salt according to the first aspect, and one additional therapeutic agent or more than one additional therapeutic agent, for the manufacture of a medicament for treating bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, a lymphoid malignancy of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer in a patient.

1e

AH26(8494627_1):CCG

WO 2011/068560

PCT/US2010/036844

One embodiment of this invention, therefore, pertains to compounds or therapeutically acceptable salts, prodrugs or salts of prodrugs thereof, which are useful as inhibitors of anti-apoptotic Bcl-2 proteins, the compounds having Formula I

<img file="NZ600084A_D0001.tif" />

(I), wherein

A¹ is N or C(A²);

A² is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ COOR¹, OC(O)R¹, NHR¹, Ν(^)2, C(O)NHR¹, CCOJNiR’h, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSO2N(R¹)2, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C^NHSOzR¹, C(NH)NH2, (XNII)NIIR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

B¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C^OR¹, OC^R¹, NHR¹, N(R^J)2, C(O)NHR\ CONCRbz, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, SO₂NH₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR¹)^ NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

D¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ COOR¹, OC(O)R¹, NHR¹, Ν(^)2, C(O)NHR¹, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSO2N(R¹)2, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C^NHSOzR¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

E¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C^OR¹, OC^R¹, NHR¹, Ν(^)2, C(O)NHR\ CONCRbz, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, SO₂NH₂,

89929.1

WO 2011/068560

PCT/US2010/036844

SOzNHR¹, SOzNCR¹^, NHSOzR¹, NR^OzR¹, NIISO2NIIR¹, NHSO2N(R¹)₂, NR^OzNHR¹,

NR¹SO2N(R¹)2, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, ccn^nhr¹,

C(NH)N(R^j)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,

N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; and

Y¹ is H, CN, NO2, C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R¹⁷, OR¹⁷, C(O)R¹⁷, C(O)OR¹⁷, SR¹⁷, SO2R¹⁷, NH2, NHR¹⁷, N(R¹⁷)2, NHC(O)R¹⁷, C(O)NH2, C(O)NHR¹⁷, C(O)N(R¹⁷)2, NHS(O)R¹⁷ or NHSO₂R¹⁷; or

E¹ and Y¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

A², B¹, and D¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R^j, C(O)R\ C(O)OR\ OC(O)R’, NHR¹, Ν(^)2, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QlW’h, SO₂NH₂, SOzNHR¹, SOzNCR¹)^ NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

Y¹ and B¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

A², D¹, and E¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R^j, C(O)R\ C(O)OR¹, OC(O)R’, NHR¹, Ν(^)2, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QOW’E SO2NH2, SOzNHR¹, SOzNCR¹^, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSO2N(R¹)₂, NR^OzNHR¹, NR¹SO2N(R¹)2, C(O)NHNOH, C(O)NHNOR¹, CiWNHSOzR¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

A² and B¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

D¹, E¹, and Y¹ are independently selected H, R¹, OR¹, SR¹, S(O)R¹, SO2R\ C(O)R\ C(O)OR¹, OC(O)R’, NHR¹, Ν(^)2, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹,

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NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, SO2NH2, SOzNHR¹, SO2N(R¹)2, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSO2N(R¹)2, NR^OzNHR¹, NR¹SO2N(R¹)2, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, C(NH)NHR¹, C(NH)N(R¹)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

A² and D¹, together with the atoms to which they are attached, are benzene, naphthalene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

B¹, E¹, and Y¹ are independently selected H, R¹, OR¹, SR¹, S(O)R¹, SO2R\ C(O)R¹, C(O)OR¹, OC(O)R’, NHR¹, N(R^j)2, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, ΝΚ’Ο^ΝΟί’Ε SO₂NH₂, SOzNHR¹, SOzN^h, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

R¹ is R², R³, R⁴ or R⁵;

R^1A is cycloalkyl, cycloalkenyl or cycloalkynyl;

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane or heterocycloalkane;

R³ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^3A; R^3A is cycloalkane or heterocycloalkane;

R⁴ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^4A; R^4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶, NC(R^6A)(R^6B), R⁷, OR⁷, SR⁷, S(O)R⁷, SO2R⁷, NHR⁷, N(R⁷)2, C(O)R⁷, C(O)NH2, C(O)NHR⁷, C(O)N(R⁷)2, NHC(O)R⁷, NR⁷C(O)R⁷, NHSO2R⁷, NHC(O)OR⁷, SO2NH₂, SO₂NHR⁷, SO2N(R⁷)2, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)CH(CH3)NHC(O)CH(CH3)NH2, NHC(O)CH(CH3)NHC(O)CH(CH3)NHR¹, OH, (O), C(O)OH, N3, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I;

R⁶ is C₂-C5-spiroalkyl, each of which is unsubstituted or substituted with OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH(CH₃) or N(CH₃)₂;

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R^6a and R^6b are independently selected alkyl or, together with the N to which they are attached, R^6C;

R^6c is aziridin-l-yl, azetidin-l-yl, pyrrolidin-l-yl or piperidin-l-yl, each having one

CH2 moiety unreplaced or replaced with O, C(O), CNOH, CNOCH3, S, S(O), SO2 or NH;

R⁷ is R⁸, R⁹, R¹⁰or Rⁿ;

Ο Ο Λ Ο Λ

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^9A; R^9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R^10A; R^10A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

Rⁿ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R¹², OR¹², SR¹², S(O)R¹², SO2R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH2, NHR¹², N(R¹²)2, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)2R¹², NR¹²S(O)2R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH2, NHC(O)NHR¹², NHC(O)N(R¹²)2, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)2, C(O)NH2, C(O)NHR¹², C(O)N(R¹²)2, C(O)NHOH, C(O)NHOR¹², C(O)NHSO2R¹², C(O)NR¹²SO2R¹², SO2NH2, SO2NHR¹², SO2N(R¹²)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR¹², C(N)N(R¹²)2, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF₃, CF2CF3, OCF₃, OCF2CF3, F, Cl, Br or I;

R¹² is R¹³,R¹⁴, R¹⁵ or R¹⁶;

R¹³ is phenyl, which is unfused or fused with benzene, heteroarene or R^13A; R^13A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁴ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^14A; R^14A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁵ is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene, each of which is unfused or fused with benzene, heteroarene or R^15A; R^15A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁶ is alkyl, alkenyl or alkynyl;

R¹⁷ is R¹⁸, R¹⁹, R²⁰orR²¹;

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^19A; R^19A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

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R is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R^20A; R^20A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²¹ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R²², OR²², SR²², S(O)R²², SO2R²², C(O)R²², CO(O)R²², OC(O)R²², OC(O)OR²², NH2, NHR²², N(R²²)2, NHC(O)R²², NR²²C(O)R²², NHS(O)2R²², NR²²S(O)2R²², NHC(O)OR²², NR²²C(O)OR²², NHC(O)NH2, NHC(O)NHR²², NHC(O)N(R²²)2, NR²²C(O)NHR²², NR²²C(O)N(R²²)2, C(O)NH2, C(O)NHR²², C(O)N(R²²)2, C(O)NHOH, C(O)NHOR²², C(O)NHSO2R²², C(O)NR²²SO2R²², SO2NH2, SO2NHR²², SO2N(R²²)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR²², C(N)N(R²²)2, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R²² is R²³, R²⁴ or R²⁵;

23 A 23 A

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁴ is heteroarene, which is unfused or fused with benzene, heteroarene or R^24A; R^24Ais cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁵ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

Z¹ is R²⁶ or R²⁷;

Z² is R²⁸, R²⁹ or R³⁰;

Z^1A and Z^2A are both absent or are taken together to form CH₂, CH₂CH₂ or Z^12A;

Z is C₂-C6-alkylene having one or two CH₂ moieties replaced by NH, N(CH₃), S, S(O) or SO₂;

L¹ is a R³⁷, OR³⁷, SR³⁷, S(O)R³⁷, SO2R³⁷, C(O)R³⁷, CO(O)R³⁷, OC(O)R³⁷, OC(O)OR³⁷, NHR³⁷, C(O)NH, C(O)NR³⁷, C(O)NHOR³⁷, C(O)NHSO2R³⁷, SO₂NH, SO₂NHR³⁷, C(N)NH, C(N)NHR³⁷;

R is phenylene, which is unfused or fused with benzene or heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁷ is heteroarylene, which is unfused or fused with benzene or heteroarene or R^27A;

R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

2S 2SA 2SA

R is phenylene, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

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R²⁹ is heteroarylene, which is unfused or fused with benzene or heteroarene or R^29A;

R^29A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene ;

R is cycloalkylene, cycloalkenylene, heterocycloalkylene or heterocycloalkenylene, each of which is unfused or fused with benzene, heteroarene or R^30A; R^30A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R³⁷ is a bond or R^37A;

R^37Ais alkylene, alkenylene, or alkynylene, each of which is unsubstituted or substituted with one or two or three independently selected R^37B, OR^37B, SR³™, S(O)R³™, SO2R³™, C(O)R^37B, CO(O)R³™, OC(O)R^37B, OC(O)OR^37B, NH2, NHR³™, N(R^37B)2, NHC(O)R³™, NR^37BC(O)R^37B, NHS(O)2R^37B, NR^37BS(O)2R^37B, NHC(O)OR^37B, NR^37BC(O)OR^37B, NHC(O)NH2, NHC(O)NHR^37B, NHC(O)N(R^37B)2, NR^37BC(O)NHR^37B, NR^37BC(O)N(R^37B)2, C(O)NH₂, C(O)NHR^37B, C(O)N(R^37B)2, C(O)NHOH, C(O)NHOR^37B, C(O)NHSO2R^37B, C(O)NR^37BSO2R^37B, SO2NH₂, SO₂NHR^37B, SO2N(R^37B)2, C(O)H,

C(O)OH, C(N)NH₂, C(N)NHR^37B, C(N)N(R^37B)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF3, OCF3, OCF₂CF3, F, Cl, Br and I substituents;

R is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;

Z³ is R³⁸, R³⁹ or R⁴⁰;

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R³⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^39A; R^39A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^40A; R^40A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

27 1.A 2A wherein the moieties represented by R andR are substituted (i.e., if Z andZ are absent) or further substituted (i.e., if Z^1A and Z^2A are present) with one or two or three or four of independently selected R⁴¹, OR⁴¹, SR⁴¹, S(O)R⁴¹, SO2R⁴¹, C(O)R⁴¹, CO(O)R⁴¹, OC(O)R⁴¹, OC(O)OR⁴¹, NH2, NHR⁴¹, N(R⁴¹)2, NHC(O)R⁴¹, NR⁴¹C(O)R⁴¹, NHS(O)2R⁴¹, NR⁴¹S(O)2R⁴¹, NHC(O)OR⁴¹, NR⁴¹C(O)OR⁴¹, NHC(O)NH2, NHC(O)NHR⁴¹,

NHC(O)N(R⁴¹)2, NR⁴¹C(O)NHR⁴¹, NR⁴¹C(O)N(R⁴¹)2, C(O)NH₂, C(O)NHR⁴¹, C(O)N(R⁴¹)2, C(O)NHOH, C(O)NHOR⁴¹, C(O)NHSO2R⁴¹, C(O)NR⁴¹SO2R⁴¹, SO2NH₂, SO₂NHR⁴¹, SO2N(R⁴¹)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴¹, C(N)N(R⁴¹)₂, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

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R⁴¹ is R⁴², R⁴³, R⁴⁴ or R⁴⁵;

R⁴² is phenyl, which is unfused or fused with benzene, heteroarene or R^42A; R^42A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴³ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^43A; R^43A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁴ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^44A; R^44A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁵ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁴⁶, OR⁴⁶, SR⁴⁶, S(O)R⁴⁶, SO2R⁴⁶, C(O)R⁴⁶, CO(O)R⁴⁶, OC(O)R⁴⁶, OC(O)OR⁴⁶, NH2, NHR⁴⁶, N(R⁴⁶)2, NHC(O)R⁴⁶, NR⁴⁶C(O)R⁴⁶, NHS(O)2R⁴⁶, NR⁴⁶S(O)2R⁴⁶, NHC(O)OR⁴⁶, NR⁴⁶C(O)OR⁴⁶, NHC(O)NH2, NHC(O)NHR⁴⁶, NHC(O)N(R⁴⁶)2, NR⁴⁶C(O)NHR⁴⁶, NR⁴⁶C(O)N(R⁴⁶)2, C(O)NH₂, C(O)NHR⁴⁶, C(O)N(R⁴⁶)2, C(O)NHOH, C(O)NHOR⁴⁶, C(O)NHSO2R⁴⁶, C(O)NR⁴⁶SO2R⁴⁶, SO2NH₂, SO₂NHR⁴⁶, SO2N(R⁴⁶)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴⁶, C(N)N(R⁴⁶)₂, cnoh, cnoch₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁴⁶ is alkyl, alkenyl, alkynyl, R⁴⁷, R⁴⁸ or R⁴⁹;

R⁴⁷ is phenyl, which is unfused or fused with benzene, heteroarene or R^47A; R^47A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁸ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^48A; R^48A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁹ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^49A; R^49A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

wherein the moieties represented by R⁴², R^42A, R⁴³, R^43A, R⁴⁴, R⁴⁴^ R⁴⁷, R^47A, R⁴⁸, R^48A, R⁴⁹, and R^49A are independently substituted with one or two or three or four of independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S(O)R⁵⁰, SO2R⁵⁰, C(O)R⁵⁰, CO(O)R⁵⁰, OC(O)R⁵⁰, OC(O)OR⁵⁰, NH2, NHR⁵⁰, N(R⁵⁰)2, NHC(O)R⁵⁰, NR⁵⁰C(O)R⁵⁰, NHS(O)2R⁵⁰, NR⁵⁰S(O)2R⁵⁰, NHC(O)OR⁵⁰, NR⁵⁰C(O)OR⁵⁰, NHC(O)NH2, NHC(O)NHR⁵⁰, NHC(O)N(R⁵⁰)2, NR⁵⁰C(O)NHR⁵⁰, NR⁵⁰C(O)N(R⁵⁰)2, C(O)NH₂, C(O)NHR⁵⁰, C(O)N(R⁵⁰)2, C(O)NHOH, C(O)NHOR⁵⁰, C(O)NHSO2R⁵⁰, C(O)NR⁵⁰SO2R⁵⁰, SO2NH₂, SO₂NHR⁵⁰, SO2N(R⁵⁰)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵⁰, C(N)N(R^5o)₂, CNOH, CNOCH₃, OH, (O), CN, n₃, no₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁵⁰ is R⁵¹,R⁵², R⁵³ or R⁵⁴;

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R⁵¹ is phenyl, which is unfused or fused with benzene, heteroarene or R^51A; R^51A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R is heteroaryl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵³ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^53A; R^53A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵⁴ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁵⁵, OR⁵⁵, SR⁵⁵, S(O)R⁵⁵, SO2R⁵⁵, C(O)R⁵⁵, CO(O)R⁵⁵, OC(O)R⁵⁵, OC(O)OR⁵⁵, NH2, NHR⁵⁵, N(R⁵⁵)2, NHC(O)R⁵⁵, NR⁵⁵C(O)R⁵⁵, NHS(O)2R⁵⁵, NR⁵⁵S(O)2R⁵⁵, NHC(O)OR⁵⁵, NR⁵⁵C(O)OR⁵⁵, NHC(O)NH2, NHC(O)NHR⁵⁵, NHC(O)N(R⁵⁵)2, NR⁵⁵C(O)NHR⁵⁵, NR⁵⁵C(O)N(R⁵⁵)2, C(O)NH2, C(O)NHR⁵⁵, C(O)N(R⁵⁵)2, C(O)NHOH, C(O)NHOR⁵⁵, C(O)NHSO2R⁵⁵, C(O)NR⁵⁵SO2R⁵⁵, SO2NH2, SO2NHR⁵⁵, SO2N(R⁵⁵)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR⁵⁵, C(N)N(R⁵⁵)2, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁵⁵ is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl; and wherein each foregoing cyclic moiety is independently unsubstituted, further unsubstituted, substituted or further substituted with one or two or three or four or five of independently selected R^57A, R⁵⁷, OR⁵⁷, SR⁵⁷, S(O)R⁵⁷, SO2R⁵⁷, C(O)R⁵⁷, CO(O)R⁵⁷, OC(O)R⁵⁷, OC(O)OR⁵⁷, NH2, NHR⁵⁷, N(R⁵⁷)2, NHC(O)R⁵⁷, NR⁵⁷C(O)R⁵⁷, NHS(O)2R⁵⁷, NR⁵⁷S(O)2R⁵⁷, NHC(O)OR⁵⁷, NR⁵⁷C(O)OR⁵⁷, NHC(O)NH2, NHC(O)NHR⁵⁷, NHC(O)N(R⁵⁷)2, NR⁵⁷C(O)NHR⁵⁷, NR⁵⁷C(O)N(R⁵⁷)2, C(O)NH₂, C(O)NHR⁵⁷, C(O)N(R⁵⁷)2, C(O)NHOH, C(O)NHOR⁵⁷, C(O)NHSO2R⁵⁷, C(O)NR⁵⁷SO2R⁵⁷, SO2NH₂, SO₂NHR⁵⁷, SO2N(R⁵⁷)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵⁷, C(N)N(R⁵⁷)₂, CNOH, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R^57A is spirocyclyl;

R⁵⁷ is R⁵⁸, R⁵⁹, R⁶⁰or R⁶¹;

R⁵⁸ is phenyl, which is unfused or fused with benzene, heteroarene or R^58A; R^58A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^59A; R^59A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

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R⁶⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^60A; R^60A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶¹ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶², OR⁶², SR⁶², S(O)R⁶², SO2R⁶², C(O)R⁶², CO(O)R⁶², OC(O)R⁶², OC(O)OR⁶², NH2, NHR⁶², N(R⁶²)2, NHC(O)R⁶², NR⁶²C(O)R⁶², NHS(O)2R⁶², NR⁶²S(O)2R⁶², NHC(O)OR⁶², NR⁶²C(O)OR⁶², NHC(O)NH2, NHC(O)NHR⁶², NHC(O)N(R⁶²)2, NR⁶²C(O)NHR⁶², NR⁶²C(O)N(R⁶²)2, C(O)NH₂, C(O)NHR⁶², C(O)N(R⁶²)2, C(O)NHOH, C(O)NHOR⁶², C(O)NHSO2R⁶², C(O)NR⁶²SO2R⁶², SO2NH₂, SO₂NHR⁶², SO2N(R⁶²)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶², C(N)N(R⁶²)₂, cnoh, cnoch₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁶² is R⁶³, R⁶⁴, R⁶⁵ or R⁶⁶;

R⁶³ is phenyl, which is unfused or fused with benzene, heteroarene or R^63A; R^63A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁴ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^64A; R^64A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁵ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^65A; R^65A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁶ is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶⁷, OR⁶⁷, SR⁶⁷, S(O)R⁶⁷, SO2R⁶⁷, C(O)R⁶⁷, CO(O)R⁶⁷, OC(O)R⁶⁷, OC(O)OR⁶⁷, NH2, NHR⁶⁷, N(R⁶⁷)2, NHC(O)R⁶⁷, NR⁶⁷C(O)R⁶⁷, NHS(O)2R⁶⁷, NR⁶⁷S(O)2R⁶⁷, NHC(O)OR⁶⁷, NR⁶⁷C(O)OR⁶⁷, NHC(O)NH2, NHC(O)NHR⁶⁷, NHC(O)N(R⁶⁷)2, NR⁶⁷C(O)NHR⁶⁷, NR⁶⁷C(O)N(R⁶⁷)2, C(O)NH₂, C(O)NHR⁶⁷, C(O)N(R⁶⁷)2, C(O)NHOH, C(O)NHOR⁶⁷, C(O)NHSO2R⁶⁷, C(O)NR⁶⁷SO2R⁶⁷, SO2NH₂, SO₂NHR⁶⁷, SO2N(R⁶⁷)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶⁷, C(N)N(R⁶⁷)₂, cnoh, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituents;

R⁶⁷ is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;

wherein the moieties represented by R^57A, R⁵⁸, R⁵⁹, R⁶⁰, R⁶³, R⁶⁴, R⁶⁵, and R⁶⁷ are unsubstituted or substituted with one or two or three or four of independently selected R⁶⁸, OR⁶⁸, SR⁶⁸, S(O)R⁶⁸, SO2R⁶⁸, C(O)R⁶⁸, CO(O)R⁶⁸, OC(O)R⁶⁸, OC(O)OR⁶⁸, NH2, NHR⁶⁸, N(R⁶⁸)2, NHC(O)R⁶⁸, NR⁶⁸C(O)R⁶⁸, NHS(O)2R⁶⁸, NR⁶⁸S(O)2R⁶⁸, NHC(O)OR⁶⁸, NR⁶⁸C(O)OR⁶⁸, NHC(0)NH2, NHC(O)NHR⁶⁸, NHC(O)N(R⁶⁸)₂, NR⁶⁸C(O)NHR⁶⁸,

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NR⁶⁸C(O)N(R⁶⁸)2, C(O)NH2, C(O)NHR⁶⁸, C(O)N(R⁶⁸)2, C(O)NHOH, C(O)NHOR⁶⁸,

C(O)NHSO₂R⁶⁸, C(O)NR⁶⁸SO2R⁶⁸, SO2NH₂, SO₂NHR⁶⁸, SO2N(R⁶⁸)2, C(O)H, C(O)OH,

C(N)NH₂, C(N)NHR⁶⁸, C(N)N(R⁶⁸)₂, CNOH, CNOCH3, OH, (O), CN, n₃, no₂, cf₃,

CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁶⁸ is R⁶⁹, R™, R⁷¹ or R⁷²;

R⁶⁹ is phenyl, which is unfused or fused with benzene, heteroarene or R^69A; R^69A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷⁰ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^70A; R^70A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷¹ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^71A; R^71A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷² is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁷³, OR⁷³, SR⁷³, S(O)R⁷³, SO2R⁷³, C(O)R⁷³, CO(O)R⁷³, OC(O)R⁷³, OC(O)OR⁷³, NH2, NHR⁷³, N(R⁷³)2, NHC(O)R⁷³, NR⁷³C(O)R⁷³, NHS(O)2R⁷³, NR⁷³S(O)2R⁷³, NHC(O)OR⁷³, NR⁷³C(O)OR⁷³, NHC(O)NH2, NHC(O)NHR⁷³, NHC(O)N(R⁷³)2, NR⁷³C(O)NHR⁷³, NR⁷³C(O)N(R⁷³)2, C(O)NH₂, C(O)NHR⁷³, C(O)N(R⁷³)2, C(O)NHOH, C(O)NHOR⁷³, C(O)NHSO2R⁷³, C(O)NR⁷³SO2R⁷³, SO2NH₂, SO₂NHR⁷³, SO2N(R⁷³)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷³, C(N)N(R⁷³)₂, CNOH, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁷³ is alkyl, alkenyl, alkenyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl; and the moieties represented by R , R , and R are unsubstituted or substituted with one or two or three or four of independently selected NH₂, C(O)NH₂, C(0)NH0H, SO₂NH₂, CF₃, CF₂CF₃, C(O)H, C(O)OH, C(N)NH₂, OH, (O), CN, N₃, no₂, cf₃, cf₂cf₃, ocf₃, OCF₂CF₃, F, Cl, Br or I.

Another embodiment pertains to a compound having Formula (II)

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Y¹

<img file="NZ600084A_D0002.tif" />

z³ (Π), or a therapeutically acceptable salt thereof, wherein R¹⁰⁰ is as described for substituents on R²⁶; n is 0, 1, 2, or 3;

R¹⁰¹ is as described for substituents on R⁴²; m is 1, 2, 3, 4, or 5;

A¹ is N or C(A²);

A² is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C(O)OR\ OC(O)R¹, NHR¹, Ν(^)2,

C(O)NHR¹, CCOJNiR’h, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSO2N(R¹)2, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, (XNII)NIIR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

B¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C^OR¹, OC^R¹, NHR¹, Ν(^)2,

C(O)NHR¹, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR¹)^ NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

D¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ COOR¹, OC(O)R¹, NHR¹, Ν(^)2,

C(O)NHR¹, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

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NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so2nh₂,

SOzNHR¹, SOzNCR¹^, NHSO₂R\ NR^OzR¹, NHSOzNHR¹, NHSOzNCR¹)^ NR^OzNHR¹,

NR¹SO2N(R¹)2, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, ccn^nhr¹,

C(NH)N(R^j)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,

N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

E¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C^OR¹, OC^R¹, NHR¹, Ν(^)2, C(O)NHR’, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, QN^NHR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH₃)R¹,.N(CH₃)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; and

Y¹ is H, CN, NO2, C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R¹⁷, OR¹⁷, C(O)R¹⁷, C(O)OR¹⁷, SR¹⁷, SO2R¹⁷, NH2, NHR¹⁷, N(R¹⁷)2, NHC(O)R¹⁷, C(O)NH2, C(O)NHR¹⁷, C(O)N(R¹⁷)2, NHS(O)R¹⁷ or NHSO₂R¹⁷; or

E¹ and Y¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

A², B¹, and D¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C(O)OR\ OC(O)R’, NHR¹, Ν(^)2, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QOW’E SO₂NH₂, SOzNHR¹, SOzNCR¹^, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, CCN^NHR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

Y¹ and B¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

A², D¹, and E¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R^j, C(O)R\ C(O)OR¹, OC(O)R’, NHR¹, Ν(^)2, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QlW’h, SO₂NH₂, SOzNHR¹, SOzNCR¹)^ NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSO2N(R¹)2, NR^OzNHR¹, NR¹SO2N(R¹)2, C(O)NHNOH, C(O)NHNOR¹,

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C(O)NHSO₂R¹, C(NH)NH2, CCN^NHR¹, C(NH)N(R¹)2 NHSOzNHR¹, NHSO2N(CH₃)R¹,

N(CH₃)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃,

C(O)OH, C(O)NH₂ or C(O)OR^1A; or

A² and B¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

D¹, E¹, and Y¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R^j, C(O)R\ C(O)OR¹, OC(O)R’, NHR¹, NCR¹^, C(O)NHR’, Ο(Ο)Ν(^)2, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QlW’h, SO₂NH₂, SOzNHR¹, SOzNCR¹)^ NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, (’(NII)NIIR¹, ϋ(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

A² and D¹, together with the atoms to which they are attached, are benzene, naphthalene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

B¹, E¹, and Y¹ are independently selected H, R¹, OR¹, SR¹, S(O)R¹, SO2R\ C(O)R¹, C(O)OR¹, OC(O)R’, NHR¹, Ν(^)2, C(O)NHR’, ϋ(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QlW’h, SO2NH2, SOzNHR¹, SOzNCR¹)^ NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR¹)^ C(O)NHNOH, C(O)NHNOR¹, CONHSCkR¹, C(NH)NH2, C(NI I)NI IR¹, ϋ(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

R¹ is R², R³, R⁴ or R⁵;

R^1A is cycloalkyl, cycloalkenyl or cycloalkynyl;

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane or heterocycloalkane;

R³ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^3A; R^3A is cycloalkane or heterocycloalkane;

R⁴ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^4A; R^4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

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R⁵ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶, NC(R^6A)(R^6B), R⁷, OR⁷, SR⁷, S(O)R⁷, SO2R⁷, NHR⁷, N(R⁷)₂, C(O)R⁷, C(O)NH2, C(O)NHR⁷, C(O)N(R⁷)2, NHC(O)R⁷, NR⁷C(O)R⁷, NHSO2R⁷, NHC(O)OR⁷, SO2NH₂, SOzNHR⁷, SO2N(R⁷)2, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)CH(CH3)NHC(O)CH(CH3)NH2, NHC(O)CH(CH3)NHC(O)CH(CH3)NHR¹, OH, (O), C(O)OH, N3, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I;

R⁶ is C₂-C5-spiroalkyl, each of which is unsubstituted or substituted with OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH(CH₃) or N(CH₃)₂;

R^6a and R^6b are independently selected alkyl or, together with the N to which they are attached, R^6C;

R^6c is aziridin-l-yl, azetidin-l-yl, pyrrolidin-l-yl or piperidin-l-yl, each having one CH₂ moiety unreplaced or replaced with O, C(O), CNOH, CNOCH₃, S, S(O), SO₂ or NH;

R⁷ is R⁸, R⁹, R¹⁰or Rⁿ;

Ο Ο Λ Ο Λ

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^9A; R^9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R^10A; R^10A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

Rⁿ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R¹², OR¹², SR¹², S(O)R¹², SO2R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH2, NHR¹², N(R¹²)₂, NHC(0)R¹², NR¹²C(O)R¹², NHS(O)2R¹², NR¹²S(O)2R¹², NHC(0)0R¹², NR¹²C(O)OR¹², NHC(0)NH₂, NHC(0)NHR¹², NHC(O)N(R¹²)2, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)2, C(0)NH₂, C(0)NHR¹², C(O)N(R¹²)₂, C(0)NH0H, C(0)NH0R¹², C(O)NHSO2R¹², C(O)NR¹²SO2R¹², SO2NH2, SO2NHR¹², SO2N(R¹²)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR¹², C(N)N(R¹²)2, CNOH, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R¹²is R¹³, R¹⁴, R¹⁵ or R¹⁶;

R¹³ is phenyl, which is unfused or fused with benzene, heteroarene or R^13A; R^13A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁴ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^14A; R^14A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

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R¹⁵ is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene, each of which is unfused or fused with benzene, heteroarene or R^15A; R^15A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁶ is alkyl, alkenyl or alkynyl;

R¹⁷ is R¹⁸, R¹⁹, R²⁰ or R²¹;

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^19A; R^19A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R^20A; R^20A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²¹ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R²², OR²², SR²², S(O)R²², SO2R²², C(O)R²², CO(O)R²², OC(O)R²², OC(O)OR²², NH2, NHR²², N(R²²)2, NHC(O)R²², NR²²C(O)R²², NHS(O)2R²², NR²²S(O)2R²², NHC(O)OR²², NR²²C(O)OR²², NHC(O)NH2, NHC(O)NHR²², NHC(O)N(R²²)2, NR²²C(O)NHR²², NR²²C(O)N(R²²)2, C(O)NH2, C(O)NHR²², C(O)N(R²²)2, C(O)NHOH, C(O)NHOR²², C(O)NHSO2R²², C(O)NR²²SO2R²², SO2NH2, SO2NHR²², SO2N(R²²)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR²², C(N)N(R²²)2, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R²² is R²³, R²⁴ or R²⁵;

R²³ is phenyl, which is unfused or fused with benzene, heteroarene or R^23A; R^23A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁴ is heteroarene, which is unfused or fused with benzene, heteroarene or R^24A; R^24Ais cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁵ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

Z² is R²⁸, R²⁹ or R³⁰;

Z^1A and Z^2A are both absent or are taken together to form CH₂, CH₂CH₂ or Z^12A;

Z is C₂-C6-alkylene having one or two CH₂ moieties replaced by NH, N(CH₃), S, S(O) or SO₂;

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L¹ is a R³⁷, OR³⁷, SR³⁷, S(O)R³⁷, SO₂R³⁷, C(O)R³⁷, CO(O)R³⁷, OC(O)R³⁷,

OC(O)OR³⁷, NHR³⁷, C(O)NH, C(O)NR³⁷, C(O)NHOR³⁷, C(O)NHSO2R³⁷, SO2NH,

SO₂NHR³⁷, C(N)NH, C(N)NHR³⁷;

R is phenylene, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁹ is heteroarylene, which is unfused or fused with benzene or heteroarene or R^29A; R^29A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene ;

R³⁰ is cycloalkylene, cycloalkenylene, heterocycloalkylene or heterocycloalkenylene, each of which is unfused or fused with benzene, heteroarene or R^30A; R^30A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R³⁷ is a bond or R^37A;

R^37Ais alkylene, alkenylene, or alkynylene, each of which is unsubstituted or substituted with one or two or three independently selected R^37B, OR^37B, SR³™, S(O)R³™, SO2R^37B, C(O)R^37B, CO(O)R³™, OC(O)R^37B, OC(O)OR^37B, NH2, NHR³™, N(R^37B)2, NHC(O)R³™, NR^37BC(O)R^37B, NHS(O)2R^37B, NR^37BS(O)2R^37B, NHC(O)OR^37B, NR^37BC(O)OR^37B, NHC(O)NH2, NHC(O)NHR^37B, NHC(O)N(R^37B)2, NR^37BC(O)NHR^37B, NR^37BC(O)N(R^37B)2, C(O)NH₂, C(O)NHR^37B, C(O)N(R^37B)2, C(O)NHOH, C(O)NHOR^37B, C(O)NHSO2R^37B, C(O)NR^37BSO2R^37B, SO2NH₂, SO₂NHR^37B, SO2N(R^37B)2, C(O)H,

C(O)OH, C(N)NH₂, C(N)NHR^37B, C(N)N(R^37B)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF3, OCF3, OCF₂CF3, F, Cl, Br and I substituents;

R is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;

Z³ is R³⁸, R³⁹ or R⁴⁰;

R³⁸ is phenyl, which is unfused or fused with benzene, heteroarene or R^38A; R^38A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R³⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^39A; R^39A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

r40 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^40A; R^40A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

wherein the moieties represented by R are independently substituted with one or two or three or four of independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S(O)R⁵⁰, SO2R⁵⁰, C(O)R⁵⁰, CO(O)R⁵⁰, OC(O)R⁵⁰, OC(O)OR⁵⁰, NH2, NHR⁵⁰, N(R⁵⁰)2, NHC(O)R⁵⁰, NR⁵⁰C(O)R⁵⁰, NHS(O)2R⁵⁰, NR⁵⁰S(O)2R⁵⁰, NHC(O)OR⁵⁰, NR⁵⁰C(O)OR⁵⁰, NHC(O)NH2, NHC(O)NHR⁵⁰,

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NHC(O)N(R⁵⁰)2, NR⁵⁰C(O)NHR⁵⁰, NR⁵⁰C(O)N(R⁵⁰)2, C(O)NH₂, C(O)NHR⁵⁰, C(O)N(R⁵⁰)₂,

C(O)NHOH, C(O)NHOR⁵⁰, C(O)NHSO₂R⁵⁰, C(O)NR⁵⁰SO2R⁵⁰, SO2NH₂, SO₂NHR⁵⁰,

SO₂N(R⁵⁰)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR⁵⁰, C(N)N(R^5o)2, cnoh, cnoch₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁵⁰ is R⁵¹,R⁵², R⁵³ or R⁵⁴;

R⁵¹ is phenyl, which is unfused or fused with benzene, heteroarene or R^51A; R^51A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵² is heteroaryl, which is unfused or fused with benzene, heteroarene or R^52A; R^52A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵³ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^53A; R^53A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵⁴ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁵⁵, OR⁵⁵, SR⁵⁵, S(O)R⁵⁵, SO2R⁵⁵, C(O)R⁵⁵, CO(O)R⁵⁵, OC(O)R⁵⁵, OC(O)OR⁵⁵, NH2, NHR⁵⁵, N(R⁵⁵)₂, NHC(O)R⁵⁵, NR⁵⁵C(O)R⁵⁵, NHS(O)2R⁵⁵, NR⁵⁵S(O)2R⁵⁵, NHC(O)OR⁵⁵, NR⁵⁵C(O)OR⁵⁵, NHC(O)NH2, NHC(O)NHR⁵⁵, NHC(O)N(R⁵⁵)2, NR⁵⁵C(O)NHR⁵⁵, NR⁵⁵C(O)N(R⁵⁵)2, C(O)NH2, C(O)NHR⁵⁵, C(O)N(R⁵⁵)2, C(O)NHOH, C(O)NHOR⁵⁵, C(O)NHSO2R⁵⁵, C(O)NR⁵⁵SO2R⁵⁵, SO2NH2, SO2NHR⁵⁵, SO2N(R⁵⁵)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR⁵⁵, C(N)N(R⁵⁵)2, cnoh, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁵⁵ is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl; and wherein R²⁶ is further unsubstituted or further substituted and each foregoing cyclic moiety are independently unsubstituted, further unsubstituted, substituted or further substituted with one or two or three or four or five of independently selected R^57A, R⁵⁷, OR⁵⁷, SR⁵⁷, S(O)R⁵⁷, SO2R⁵⁷, C(O)R⁵⁷, CO(O)R⁵⁷, OC(O)R⁵⁷, OC(O)OR⁵⁷, NH2, NHR⁵⁷, N(R⁵⁷)2, NHC(O)R⁵⁷, NR⁵⁷C(O)R⁵⁷, NHS(O)2R⁵⁷, NR⁵⁷S(O)2R⁵⁷, NHC(O)OR⁵⁷, NR⁵⁷C(O)OR⁵⁷, NHC(0)NH2, NHC(O)NHR⁵⁷, NHC(O)N(R⁵⁷)2, NR⁵⁷C(O)NHR⁵⁷, NR⁵⁷C(O)N(R⁵⁷)2, C(O)NH₂, C(O)NHR⁵⁷, C(O)N(R⁵⁷)2, C(0)NH0H, C(O)NHOR⁵⁷, C(O)NHSO2R⁵⁷, C(O)NR⁵⁷SO2R⁵⁷, SO2NH₂, SO₂NHR⁵⁷, SO2N(R⁵⁷)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵⁷, C(N)N(R⁵⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R^57A is spirocyclyl;

R⁵⁷ is R⁵⁸, R⁵⁹, R⁶⁰or R⁶¹;

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5S 5SA 5SA

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^59A; R^59A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^60A; R^60A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶¹ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶², OR⁶², SR⁶², S(O)R⁶², SO2R⁶², C(O)R⁶², CO(O)R⁶², OC(O)R⁶², OC(O)OR⁶², NH2, NHR⁶², N(R⁶²)2, NHC(O)R⁶², NR⁶²C(O)R⁶², NHS(O)2R⁶², NR⁶²S(O)2R⁶², NHC(O)OR⁶², NR⁶²C(O)OR⁶², NHC(O)NH2, NHC(O)NHR⁶², NHC(O)N(R⁶²)2, NR⁶²C(O)NHR⁶², NR⁶²C(O)N(R⁶²)2, C(O)NH₂, C(O)NHR⁶², C(O)N(R⁶²)2, C(O)NHOH, C(O)NHOR⁶², C(O)NHSO2R⁶², C(O)NR⁶²SO2R⁶², SO2NH₂, SO₂NHR⁶², SO2N(R⁶²)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶², C(N)N(R⁶²)₂, cnoh, cnoch₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁶² is R⁶³, R⁶⁴, R⁶⁵ or R⁶⁶;

R⁶³ is phenyl, which is unfused or fused with benzene, heteroarene or R^63A; R^63A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁴ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^64A; R^64A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁵ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^65A; R^65A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁶ is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶⁷, OR⁶⁷, SR⁶⁷, S(O)R⁶⁷, SO2R⁶⁷, C(O)R⁶⁷, CO(O)R⁶⁷, OC(O)R⁶⁷, OC(O)OR⁶⁷, NH2, NHR⁶⁷, N(R⁶⁷)2, NHC(O)R⁶⁷, NR⁶⁷C(O)R⁶⁷, NHS(O)2R⁶⁷, NR⁶⁷S(O)2R⁶⁷, NHC(O)OR⁶⁷, NR⁶⁷C(O)OR⁶⁷, NHC(O)NH2, NHC(O)NHR⁶⁷, NHC(O)N(R⁶⁷)2, NR⁶⁷C(O)NHR⁶⁷, NR⁶⁷C(O)N(R⁶⁷)2, C(O)NH₂, C(O)NHR⁶⁷, C(O)N(R⁶⁷)2, C(O)NHOH, C(O)NHOR⁶⁷, C(O)NHSO2R⁶⁷, C(O)NR⁶⁷SO2R⁶⁷, SO2NH₂, SO₂NHR⁶⁷, SO2N(R⁶⁷)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶⁷, C(N)N(R⁶⁷)₂, cnoh, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituents;

R⁶⁷ is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;

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PCT/US2010/036844 wherein the moieties represented by R^57A, R⁵⁸, R⁵⁹, R⁶⁰, R⁶³, R⁶⁴, R⁶⁵, and R⁶⁷ are unsubstituted or substituted with one or two or three or four of independently selected R⁶⁸, OR⁶⁸, SR⁶⁸, S(O)R⁶⁸, SO2R⁶⁸, C(O)R⁶⁸, CO(O)R⁶⁸, OC(O)R⁶⁸, OC(O)OR⁶⁸, NH2, NHR⁶⁸, N(R⁶⁸)2, NHC(O)R⁶⁸, NR⁶⁸C(O)R⁶⁸, NHS(O)2R⁶⁸, NR⁶⁸S(O)2R⁶⁸, NHC(O)OR⁶⁸, NR⁶⁸C(O)OR⁶⁸, NHC(O)NH2, NHC(O)NHR⁶⁸, NHC(O)N(R⁶⁸)₂, NR⁶⁸C(O)NHR⁶⁸, NR⁶⁸C(O)N(R⁶⁸)2, C(O)NH2, C(O)NHR⁶⁸, C(O)N(R⁶⁸)2, C(O)NHOH, C(O)NHOR⁶⁸, C(O)NHSO₂R⁶⁸, C(O)NR⁶⁸SO2R⁶⁸, SO2NH₂, SO₂NHR⁶⁸, SO2N(R⁶⁸)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶⁸, C(N)N(R⁶⁸)₂, CNOH, CNOCH3, OH, (O), CN, n₃, no₂, cf₃,

CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁶⁸ is R⁶⁹, R™, R⁷¹ or R⁷²;

R⁶⁹ is phenyl, which is unfused or fused with benzene, heteroarene or R^69A; R^69A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷⁰ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^70A; R^70A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷¹ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^71A; R^71A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷² is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁷³, OR⁷³, SR⁷³, S(O)R⁷³, SO2R⁷³, C(O)R⁷³, CO(O)R⁷³, OC(O)R⁷³, OC(O)OR⁷³, NH2, NHR⁷³, N(R⁷³)2, NHC(O)R⁷³, NR⁷³C(O)R⁷³, NHS(O)2R⁷³, NR⁷³S(O)2R⁷³, NHC(O)OR⁷³, NR⁷³C(O)OR⁷³, NHC(O)NH2, NHC(O)NHR⁷³, NHC(O)N(R⁷³)2, NR⁷³C(O)NHR⁷³, NR⁷³C(O)N(R⁷³)2, C(O)NH₂, C(O)NHR⁷³, C(O)N(R⁷³)2, C(O)NHOH, C(O)NHOR⁷³, C(O)NHSO2R⁷³, C(O)NR⁷³SO2R⁷³, SO2NH₂, SO₂NHR⁷³, SO2N(R⁷³)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷³, C(N)N(R⁷³)₂, CNOH, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁷³ is alkyl, alkenyl, alkenyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl; and the moieties represented by R , R , and R are unsubstituted or substituted with one or two or three or four of independently selected NH₂, C(O)NH₂, C(O)NHOH, SO₂NH₂, CF₃, CF₂CF₃, C(O)H, C(O)OH, C(N)NH₂, OH, (O), CN, N₃, no₂, cf₃, cf₂cf₃, ocf₃, OCF₂CF₃, F, Cl, Br or I.

Still another embodiment pertains to a compound of Formula I or Formula II, wherein A¹ is C(A²); and A² is H.

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Still another embodiment pertains to a compound of Formula I or Formula II, wherein

A¹ is C(A²) or N; A² is H; and B¹ is NHR¹.

Still another embodiment pertains to a compound of Formula I or Formula II, wherein

A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; and D¹ is H.

Still another embodiment pertains to a compound of Formula I or Formula II, wherein A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H.

Still another embodiment pertains to a compound of Formula I or Formula II, wherein A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO₂.

Still another embodiment pertains to compounds having Formula I, which are 4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(methylamino)phenoxy)-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)piperazin-1 -yl)-2-((2methyl-lH-indol-5-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl)methyl)piperazin-1 -yl)-2-((2methyl-lH-indol-5-yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-chlorophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-nitrophenoxy)-N-((3-nitro-4((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(hydroxymethyl)phenoxy)-N((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-((4-((3morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-((4-((3(dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-chlorophenoxy)-N-((4-((3morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((4-((3morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-chlorophenoxy)-N-((4-((3(dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((4-((3(dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((l-methyl-lH-indol-4yl)oxy)benzamide;

2-(3-(acetylamino)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-aminophenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(3-aminophenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-methoxyphenoxy)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(dimethylamino)phenoxy)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-cyanophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((2-methyl-l,3-benzothiazol-6yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((2-methyl-l,3-benzothiazol-5yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1, l'-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((2-methyl-l,3-benzothiazol-5yl)oxy)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(3-(dimethylamino)-3oxopropyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(2-(dimethylamino)-2oxoethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(3(dimethylamino)propyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(2(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-nitro-4-((tetrahydro-2H-pyran4-yl)methylamino)phenylsulfonylcarbamoyl)phenoxy)-N,N-dimethylbenzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-morpholin-4ylphenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(2,4-dimethyl-l,3-thiazol-5yl)phenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(3,5dichlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nittophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-4-(2-(dimethylamino)ethoxy)-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2(3-chlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3yl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(2(dimethylamino)ethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-isopropylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohex-l-en-l-yl)methyl)piperazin-l-yl)-N((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indazol-4-yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3difluorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-ethylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((3-nitro-4-((l,2,2,6,6-pentamethylpiperidin-4yl) amino)phenyl) sulfony l)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3difluorophenoxy)-N-((3-nitro-4-((l-tetrahydro-2H-pyran-4-ylpiperidin-4yl) amino)phenyl) sulfony l)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((7fluoro-lH-indol-5-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

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4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3difluorophenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((4'-chloro-4-(2-pyrrolidin-l-ylethyl)-l,r-biphenyl-2yl)methyl)piperazin-l-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3dichlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indazol-4-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohept-1 -en- l-yl)methyl)piperazin-1 -yl)N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide; 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl)methyl)piperazin-1 -yl)-N-((4-(( 1methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)-2-(3(trifluoromethyl)phenoxy)benzamide;

4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetrahydroquinolin5 -yl)oxy )benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,5dichlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chloro-4-fluorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclopent-1 -en-1 yl)methyl)piperazin-1 -yl) -N- ((4- ((1 -methylpiperidin-4-yl) amino) -3 nitrophenyl)sulfonyl)benzamide;

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4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indol-4-yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2chloro-3-(trifluoromethyl)phenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-cyclopropylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indol-4-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,5dichlorophenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((l-methyl-lH-indol-4-yl)oxy)N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-morpholin-4-ylphenoxy)-N((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((3-(3-morpholin-4-yl-3oxopropyl) -1 H-indol- 5 -y l)oxy)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-cyanophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((3-(3-morpholin-4-yl-3oxopropyl)-lH-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((3-(3-morpholin-4-ylpropyl)lH-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(lH-imidazol-l-yl)phenoxy)N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-nitrophenoxy)-N-((4((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)benzyl(ethyl)carbamate; tert-butyl 3-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)benzyl(ethyl)carbamate;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(acetylamino)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; tert-butyl 4-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)phenylcarbamate;

2-(1, r-biphenyl-2-yloxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; tert-butyl 3-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)phenylcarbamate;

2-(1, r-biphenyl-3-yloxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(2(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

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2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-morpholin-4-ylphenoxy)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((2-methyl-l,3-benzothiazol-5yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(3-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-l-carboxylate;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4((3-(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(2-morpholin-4ylethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3-nitro-4-((tetrahydro-2Hpyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetr ahydroquinolin-5yl)oxy)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

tert-butyl 4-(4-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((4-((3morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-l-carboxylate;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4ylpropyl) amino)- 3 -nitrophenyl) sulfonyl) -2-(3 -pyridin-4-ylphenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-4-ylphenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-3-ylphenoxy)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(2-(dimethylamino)-2oxoethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-1 -yl)-2-(( 1 -methyl-1 H-benzimidazol-5 yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(methylcarbamoyl)phenoxy)-N-(4(3-morpholinopropylamino)-3-nitrophenylsulfonyl)benzamide;

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazin-l-yl)-N-(4-(3-(dimethylamino)propylamino)3 -nitrophenylsulfonyl) -2-(3- (methylcarbamoyl)phenoxy)benzamide; 4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(2-(dimethylamino)-2oxoethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((3-(3-(dimethylamino)propyl)lH-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1, l'-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3(hydroxymethyl)phenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((4-methoxybenzyl)oxy)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

N-(4-((4-aminotetrahydro-2H-pyran-4-yl)methylamino)-3-nitrophenylsulfonyl)-2-(3chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enyl)methyl)piperazin-lyl)benzamide;

4-(4-(l-(4'-chlorobiphenyl-2-yl)ethyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-(3-nitro-4((tetrahydro-2H-pyran-4-yl)methylamino)phenylsulfonyl)benzamide;

N- {[4-{4- [(4'-chloro-1,1 '-biphenyl-2-yl)methyl]piperazin-1 -yl} -2-(3,5 dichlorophenoxy)phenyl]sulfonyl}-4-[(l-methylpiperidin-4-yl)amino]-3-nitrobenzamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; 4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-2-(3fluorophenoxy)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 - y 1) - 2-(3 fluorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl]sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

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2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l5 yl]methyl}piperazin-l-yl)-N-({4-[(l-cyclopentylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(4fluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l10 yl]methyl}piperazin-l-yl)-N-({4-[(l-cyclopropylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-4-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin- l-yl)-N-({ 4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2,3difluorophenoxy)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin- l-yl)-2-(2fluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin-l-yl)-N-({ 4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2fluorophenoxy)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin-1 -yl)-2-(2fluorophenoxy)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-425 yl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin-1 -yl)-2-(2fluorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide; 4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin- l-yl)-2-(2fluorophenoxy)-N-({4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

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2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(35 fluorophenoxy)-N-((4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-cyclopentylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l10 yl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-N-({4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(3fluorophenoxy)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin-1 -yl)-N-( {4[(1 -cyclopentylpiperidin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2-(2,3 difluorophenoxy (benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -y 11 methyl} piperazin-1 -yl)-N-( {4[(1 -cyclopentylpiperidin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2-(220 fluorophenoxy)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(2,3difluorophenoxy)-N-((4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide; 4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-2-(2,3difluorophenoxy)-N-[(3-nitro-4-([l-(thien-3-ylmethyl)piperidin-425 yl] amino} phenyl) sulfonyl] benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(2-fluorophenoxy (benzamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(3-fluorophenoxy (benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(4-fluorophenoxy (benzamide; 4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin-l-yl)-2-(2,3difluorophenoxy)-N-[(4-{[l-(2-fluoroethyl)piperidin-4-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

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2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(2-morpholin-4-ylethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl ] methyl }piperazin- l-yl)-N- [(4- {[3-(4-methylpiperazin-1 -yl)propyl] amino} -3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-[[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3yl]methyl}piperazin-l-yl)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-(2,3-difluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

N-([4-[(l-allylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -y 1)-2-(2,3-difluorophenoxy)benzamide; 2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-([4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl] methyl} piperazin-1 -yl) -N- ({3 -nitro-4- [(3 -pyrrolidin-1 ylpropyl)amino]phenyl} sulfonyl)benzamide;

2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-([4-[(2-morpholin-4-ylethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-6-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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2-(2-chloro-6-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl ] methyl }piperazin- l-yl)-N- [(4- {[(1 -methylpiperidin-4-yl)methyl] amino} -3nitrophenyl)sulfonyl]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(2,3difluorophenoxy)-N-[(4- {[(l-methylpiperidin-4-yl)methyl] amino} -3nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(4fluoro-lH-indol-5-yl)oxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[3(methoxymethoxy)-2-methylphenoxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(3hydroxy-2-methylphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3yl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-(3-iodophenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N- [(4- {[ 1 -(2-hydroxyethyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(3-nitro-4-([l-(2-phenylethyl)piperidin-4yl] amino} phenyl) sulfonyl] benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3,4dichlorophenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3,5-difluorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(3methoxyphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[3(hydroxymethyl)phenoxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l,4-dimethylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l,4-dimethylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([4-({l-[2-(2-methoxyethoxy)ethyl]piperidin-4-yl}amino)-3nitrophenyl] sulfonyl} benzamide;

2-(2-chloro-3-hydroxyphenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(3-nitro-4-([l-(3-phenylpropyl)piperidin-4yl] amino} phenyl) sulfonyl] benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([l-(2-methoxyethyl)piperidin-4-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N-( {4- [(1 -ethylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

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2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-isopropylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3hydroxyphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; 2-(2-chloro-3-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-3-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3nitrophenyl)sulfonyl]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(2methoxyphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(2methylphenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3methylphenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4- {[6-(4-chlorophenyl)-1,3-benzodioxol-5-yl]methyl}piperazin-1yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-ly 11 methyl} piperazin-1 -yl)-N-( {4- [(4-methylpiperazin-1 -yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3y 11 methyl} piperazin-1 -yl)-N-( {4- [(4-methylpiperazin-1 -yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-(2,3-difluorophenoxy)-N-((4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-ly 1 ] methyl} piperazin-1 - y 1)-N- [ (4 - {[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-ly 1 ] methyl} piperazin-1 - y 1)-N- [ (4 - {[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-{[4-({l-[2-(dimethylamino)-2-oxoethyl]piperidin-4-yl}amino)3 -nitrophenyl] sulfonyl} benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([l-(2-morpholin-4-ylethyl)piperidin-4-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

N-[(4-([(4-aminotetrahydro-2H-pyran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(2chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl] methyl} piperazin-1 -yl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N- [(4- {[(4-hydroxy-1 -methylpiperidin-4-yl)methyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 - y 1) - 2- [ (6 fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([(3S)-l-methylpyrrolidin-3-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([(3R)-l-methylpyrrolidin-3-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- l-en-l-yl]methyl}piperazin- l-yl)-N-({4[(1 -methylpiperidin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2- [3-(1 H-pyrrol-2yl)phenoxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N- [(4- {[(4-hydroxy-1 -methylpiperidin-4-yl)methyl]amino} -3nitrophenyl)sulfonyl]benzamide;

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2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6,7difluoro-lH-indol-5-yl)oxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6,7difluoro-1 H-indol-5-yl)oxy] -N-( {3 -nitro-4- [(1 -tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

tert-butyl 4-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-([((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)amino]carbonyl (phenoxy)- ΙΗ-indole-1 -carboxylate;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[4-(dimethylamino)cyclohexyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[4-(diethylamino)cyclohexyl]amino}-3nitrophenyl)sulfonyl]benzamide;

Trans-2-(3-chlorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-((4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-{4-[l-(4'-chloro-l,r-biphenyl-2-yl)ethyl]piperazin-l-yl}-2-(2-chlorophenoxy)-N-((4-[(lmethylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-lyl]methyl}piperazin-l-yl)-N-((4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-4-yl)oxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-4-yl)oxy]-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(4-methylpiperazin-l-yl)amino]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

2-((1,3 -bis [(4-methylpiperazin-1 -yl)methyl] -1 H-indol-4-yl} oxy)-4-(4- {[2-(4-chlorophenyl)4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-[(4-{[3(dimethylamino)propyl] amino} - 3 -nitrophenyl) sulfonyl] benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[3-(dimethylamino)propyl] amino} -3-nitrophenyl)sulfonyl] -2-((3- [(4-methylpiperazin-1 yl)methyl]- lH-indol-4-yl }oxy (benzamide;

2-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enyl)methyl)piperazin-l-yl)-2-(4-(lmethylpiperidin-4-ylamino)-3-nitrophenylsulfonylcarbamoyl)phenoxy)-N,Ndimethylbenzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-N-( {3nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]phenyl}sulfonyl)-2-{[2(trifluoromethyl) -1 H-indol-4-yl] oxy} benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-N-( {4[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-([6-(trifluoromethyl)-lH-indol-5yl]oxy} benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({3nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]phenyl}sulfonyl)-2-{[6(trifluoromethyl) -1 H-indol- 5 -yl] oxy} benzamide;

2-[(2-amino-l,3-thiazol-4-yl)methoxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6,7difluoro-lH-indol-5-yl)oxy]-N-((4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin- l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

tert-butyl 4-[(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-lyl)-2-{[({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)amino]carbonyl }phenoxy)methyl]-1,3-thiazol-2-ylcarbamate; 2-[(2-amino-l,3-thiazol-4-yl)methoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -y 1 ] methyl} piperazin-1 -yl)-N-( {4- [(1 -methylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(2-chlorophenyl)amino]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6methoxy-lH-indol-5-yl)oxy]-N-([3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(2-amino-l,3-benzothiazol-6-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -y 11 methyl} piperazin-1 -yl)-N-( {4- [(1 -methylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[(2-chlorophenyl)amino]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

tert-butyl 5-[5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en- l-yl]methyl (piperazin-1yl)-2-({ [(4-{ [3-(dimethylamino)propyl]amino}-3nitrophenyl)sulfonyl] amino} carbonyl)phenoxy] -1 H-indole-1 -carboxylate;

2-[(2-amino-l,3-benzothiazol-6-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(1 -tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5 -yl)oxy ] -N- [(3 -nitro-4- {[3 -(3 -oxopiperazin-1 yl)propyl] amino} phenyl) sulfonyl] benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-((4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6,7-difluoro-lH-indol-5-yl)oxy]-N-((4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-N- [(4{[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 -nitrophenyl)sulfonyl] -2- [(6-fluoro-1Hindol-5-yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-N-[(4{[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 -nitrophenyl)sulfonyl] -2- [(6,7-difluoro-1Hindol-5-yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6,7difluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([3-(3-oxopiperazin-lyl)propyl] amino} phenyl) sulfonyl] benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 - y 1) - 2- [ (6 fluoro- lH-indol-5-yl)oxy]-N-({4-[(2-hydroxy- l-tetrahydro-2H-pyran-4-ylethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-([4-(([4-(hydroxymethyl)tetrahydro-2H-pyran-4yl] methyl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6,7difluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-({4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5 -yl)oxy ] -N- [(3 -nitro-4- {[1-(1,3 -thiazol-4-ylmethyl)piperidin-4yl] amino} phenyl) sulfonyl] benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)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-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-[(4-{ [(3S, 4R)-3-hydroxy-l-(l, 3-thiazol-4-ylmethyl)piperidin-4yl] amino} -3 -nitrophenyl) sulfonyl] benzamide;

2-(2-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl }piperazin- l-yl)-N- {[4-( {[4-(hydroxymethyl)tetrahydro-2H-pyran-4yl]methyl]amino)-3-nitrophenyl]sulfonyl]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl]piperazin- l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N- {[3-nitro-4-(tetrahydro-2H-pyran-4ylamino)phenyl] sulfonyl} benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-[[4-(morpholin-4-ylamino)-3-nitrophenyl]sulfonyl}benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-{[4-(morpholin-4-ylamino)-3-nitrophenyl]sulfonyl]benzamide;

2-(2-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-[(3-nitro-4-{[3-(3-oxopiperazin-lyl)propyl] amino} phenyl) sulfonyl] benzamide;

2-(6-aminopyridin-3-yl)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

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4-(4-( l-[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]ethyl]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-4-yl)oxy]-N-[(3-nitro-4-{[3-(3-oxopiperazin-lyl)propyl] amino} phenyl) sulfonyl] benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([(3S)-tetrahydro-2H-pyran-3ylmethyl] amino} phenyl) sulfonyl] benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([(3R)-tetrahydro-2H-pyran-3ylmethyl] amino} phenyl) sulfonyl] benzamide;

tert-butyl 5-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)-3,4-dihydroisoquinoline-2( 1H)carboxylate;

2-[(6-aminopyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-5,5 -dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro- lH-indol-5 -yl)oxy] -N-( {4- [(2-methoxyethyl)amino] -3 nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-([3-nitro-4-(tetrahydro-2H-pyran-4ylmethoxy)phenyl] sulfonyl} benzamide;

2-[(3-chloro-lH-indol-5-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(3-chloro-lH-indol-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({3nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[(2-oxo-2,3-dihydrolH-indol-5 -yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({3nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[(2-oxo-2,3-dihydrolH-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-4-yl)oxy]-N-((4-[(2-methoxyethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

tert-butyl 5-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -y 1 ]methyl}piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate; tert-butyl 4-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -y 1 ]methyl}piperazin-1 yl)-2-([({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate;

2-[(6-aminopyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(2-aminopyridin-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2- [(5 -bromopyridin-3 -yl)oxy] -4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2Hpyran-3-yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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PCT/US2010/036844 tert-butyl 5-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-3-ylcarbamate;

2-[(5-aminopyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

tert-butyl 4-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -y 1 ]methyl}piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate;

2- [(3 -chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(2-aminopyridin-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6hydroxypyridin-3-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-{[6-(benzyloxy)pyridin-3-yl]oxy}-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[4(l,4-dioxan-2-ylmethoxy)-3-nitrophenyl]sulfonyl}-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

2-[(3-chloro-lH-indol-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -y 11 methyl} piperazin-1 -yl)-N-( {4[(4-methylpiperazin-l-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-lH-indol-4yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -y 11 methyl} piperazin-1 -yl)-N-( {4[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-lH-indol-4yl)oxy]benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({3nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]phenyl}sulfonyl)-2-[(2-oxo-2,3dihydro-lH-indol-4-yl)oxy]benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl] methyl} piperazin- l-yl)-N-{ [4-(1,4-dioxan-2-ylmethoxy)-3nitrophenyl] sulfonyl} benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-({4-[(l,4-dioxan-2-ylmethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-N-({4[(1,4-dioxan-2-ylmethyl)amino] -3 -nitrophenyl} sulfony 1)-2- [(6-fluoro-1 H-indol-5 yl)oxy]benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-((4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro2H-pyran-3-yl]methyl}piperazin-l-yl)-N-((4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-1-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-((4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-1-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)N-([5-cyano-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

2-{[3-(2-aminoethyl)-lH-indol-5-yl]oxy}-4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohexl-en-l-yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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2-{[3-(2-aminoethyl)-lH-indol-5-yl]oxy]-4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex1- en-1 -yl ] methyl (piperazin- l-yl)-N-( {4- [(4-methylpiperazin-1 -yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[5cyano-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

2- [(6-amino-5-fluoropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-{[5chloro-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-N((4- [(4-morpholin-4-ylcyclohexyl)amino] -3 -nitrophenyl} sulfony 1)-2- [(1 -oxo-1,2,3,4tetrahydroisoquinolin-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-{[5cyano-6-( 1,4-dioxan-2-ylmethoxy)pyridin-3 -yl] sulfonyl} -2- [(6-fluoro-1 H-indol-5 yl)oxy]benzamide;

N-([5-bromo-6-(l,4-dioxan-2-ylmethoxy)pyridin-3-yl]sulfonyl]-4-(4-{[2-(4-chlorophenyl)4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

Trans-N-((5-bromo-6-[(4-morpholin-4-ylcyclohexyl)amino]pyridin-3-yl]sulfonyl)-4-(4-{[2(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-1Hindol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({5cyano-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl} sulfonyl)-2-[(6-fluoro1 H-indol-5 -yl)oxy]benzamide;

2-(3-amino-5-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-lyl]methyl]piperazin-l-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1-yl] methyl] piperazin- l-yl)-N- {[5cyano-6-(2-morpholin-4-ylethoxy)pyridin-3-yl]sulfonyl]-2-[(6-fluoro-lH-indol-5yl)oxy ]benzamide;

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Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-1 H-indol-5-yl)oxy] -N-( {4- [(4-morpholin-4-ylcyclohexyl)oxy] -3 nitrophenyl} sulfonyl)benzamide;

N-([5-bromo-6-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]pyridin-3-yl]sulfonyl)-4(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 - y 1)-2 - [ (6fluoro-lH-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3-nitrophenyl]sulfonyl)-2-[(2-oxo-2,3dihydro-lH-indol-4-yl)oxy]benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-[[5-(4-chlorophenyl)-2,3,6,7-tetrahydrooxepin4-yl]methyl]piperazin-l-yl)-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-[[5-(4-chlorophenyl)-2,3,6,7-tetrahydrooxepin4-yl]methyl]piperazin-l-yl)-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl]piperazin-l-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-([4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-([4-[(4-morpholin-4-ylbut-2-ynyl)oxy]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2- [(6fluoro- lH-indol-5 -yl)oxy ] -N- [(4- {[ 1 -(methylsulfonyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-N({4-[(4-morpholin-4-ylcyclohexyl)amino]-3-nitrophenyl]sulfonyl)-2-[(2-oxo-2,3-dihydrolH-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({4[(2-methoxyethyl)amino]-3-nitrophenyl]sulfonyl)-2-[(2-oxo-2,3-dihydro-lH-indol-4yl)oxy]benzamide;

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4- (4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[5ethynyl-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lH-indol5- yl)oxy]benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)N-([5-ethynyl-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N-( (4-[(4-morpholin-4ylcyclohexy l)amino] - 3 -nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({5cyano-6-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)oxy]pyridin-3-yl}sulfonyl)-2-[(6-fluoro1 H-indol-5 -yl)oxy]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} piperazin-1 -yl)-2- [(6-fluoro1 H-indol-5 -yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-N-( {4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin- 1 -yl)-N-( {4[(4-ethylmorpholin-3 -yl)methoxy] -3 -nitrophenyl} sulfony 1)-2- [(6-fluoro- lH-indol-5 yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([(3S)-l-tetrahydro-2H-pyran-4-ylpiperidin-3yl] amino} phenyl) sulfony 1 ] ben/am i de;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-((4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N-( {4[(1,1 -dioxidothiomorpholin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2- [(6-fluoro-1 H-indol-5yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydrofuran-3ylmethyl)amino]phenyl} sulfonyl)benzamide;

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Trans-N-({5-bromo-6-[(4-morpholin-4-ylcyclohexyl)oxy]pyridin-3-yl}sulfonyl)-4-(4-{ [2-(4chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl Jpiperazin-1-yl)-2-[(6-fluoro-1Hindol-5-yl)oxy]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-N[(4-([4-(dicyclopropylamino)cyclohexyl] amino} -3-nitrophenyl)sulfonyl] -2- [(6-fluoro-1Hindol-5-yl)oxy]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([4-(tetrahydro-2H-pyran-4ylamino)cyclohexyl]amino}phenyl)sulfonyl]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([4-(4-tetrahydro-2H-pyran-4-ylpiperazin-lyl)cyclohexyl] amino} phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-[(4-{ [(4-fluorotetrahydro-2H-pyran-4-yl)methyl] amino]-3nitrophenyl)sulfonyl]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-[(4-([(4-hydroxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-({3-[3(dimethylamino)propyl]-lH-indol-4-yl]oxy)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl]piperazin- l-yl)-2-({3-[3(dimethylamino)propyl] - lH-indol-4-yl} oxy)-N-( {4- [(4-methylpiperazin-1 -yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-N-( {4[(l-cyclopropyl-4-fluoropiperidin-4-yl)methoxy]-3-nitrophenyl]sulfonyl)-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-{ [1-(4methoxybenzyl)-1H-1,2,3-benzotriazol-4-yl]oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl] methyl} piperazin-1 -yl)-N-( {4- [(4-methylpiperazin-1 -yl) amino] -3 nitrophenyl} sulfonyl)benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl | methyl} pi pcrazi η-1 -yl )-N- {[4-(1,4-dioxan-2-ylmethoxy)-3nitrophenyl] sulfonyl} benzamide;

Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[(4methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-([4-[(l,4-dioxan-2-ylmethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {4- [(3 -morpholin-4-ylpropyl)amino] -3 [(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-([4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl] methyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-amino-5-(5-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-lyl)-2-[[([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)nicotinamide;

2-[(6-amino-5-cyanopyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-[(4-[[(3R)-l-(2,2-difluoroethyl)pyrrolidin-3-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {4- [(1 -methylpiperidin-4-yl)amino] -3 [(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

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2- {[6-(acetylamino)pyridin-3-yl]oxy} -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en1- yl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 - y 1) - 2-({6 [(methylsulfonyl)amino]pyridin-3-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin- l-yl)-N- {[4({(3R)-1 - [2-fluoro-1 -(fluoromethyl)ethyl]pyrrolidin-3 -yl} amino)-3 -nitrophenyl] sulfonyl} -2[(6-fluoro-lH-indol-5-yl)oxy]benzamide;

2- [(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {4- [(1 -cyclopropylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( [4- [(4-methylpiperazin-1 -yl) amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-([4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-({4-[(l,4-dioxan-2-ylmethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-methylpyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[(4-fluorotetrahydro-2H-pyran-4-yl)methyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(1 -oxetan-3 -ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-isopropylpyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexl-en-l-yl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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2-[(6-amino-5-cyclopropylpyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N-({ 3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

Trans-2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N - [(4- {[(4methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(3methyl-2-oxo-2,3-dihydro-lH-benzimidazol-4-yl)oxy]-N-([3-nitro-4-[(tetrahydro-2H-pyran4-ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl]methyl} piperazin-1 -yl)-N - [(4- {[(4-cyclopropylmorpholin-2-yl)methyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl]methyl} piperazin-1 -yl)-N - [ (4- {[ (3 R) -1 -cyclopropylpyrrolidin-3 -yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl] methyl} piperazin-1 -yl)-N- {[4-( {4-fluoro-1 - [2-fluoro-1 (fluoromethyl)ethyl]piperidin-4-yl}methoxy)-3-nitrophenyl]sulfonyl}benzamide; tert-butyl 6-bromo-4-(5-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-2-[[([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate; tert-butyl 4-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enyl)methyl)piperazin-l-yl)2-(3-nitro-4-((tetrahydro-2H-pyran-4yl)methylamino)phenylsulfonylcarbamoyl)phenoxy)pyridine-2,6-diyldicarbamate;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-{ [6(cyclopropylamino)pyridin-3-yl]oxy} -N-( {3-nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-2({6-[(2,2-difluoroethyl)amino]pyridin-3-yl]oxy)-N-[(4-{[(4methoxycyclohexyl)methyl]amino]-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-({6[(2,2-difluoroethyl)amino]pyridin-3-yl]oxy)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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2-{[5-chloro-6-(methylamino)pyridin-3-yl]oxy}-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N-({ 3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -y 1 ] methyl} piperazin-1 -yl)-N-( {4- [({4- [2-fluoro-1 -(fluoromethyl)ethyl]morpholin-2yl} methyl)amino]-3-nitrophenyl} sulfonyl)benzamide;

2-[(2-amino-6-bromopyridin-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(2,6diaminopyridin-4-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-([3-nitro-4-(tetrahydro-2H-pyran-4ylmethoxy)phenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl} piperazin-1 -yl)-N- {[4-( {(3R)-1 - [2-fluoro-1 -(fluoromethyl)ethyl]piperidin-3 yl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

tert-butyl 5-bromo-4-(5-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(4chloro-lH-pyrrolo[2,3-b]pyridin-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({ 3nitro-4- [(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl} sulfony 1)-2-( {6-((2,2,2trifluoroethyl)amino]pyridin-3-yl} oxy)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-[(4-([(4-hydroxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro2H-pyran-3-yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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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}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydrofuran-3ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2Hpyran-3-yl]methyl}piperazin-l-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-({9-(4-chlorophenyl)-3-[2-fluoro-l(fluoromethyl)ethyl]-3-azaspiro[5.5]undec-8-en-8-yl}methyl)piperazin-l-yl]-N-({3-nitro-4[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[9-(4-chlorophenyl)-3-isopropyl-3azaspiro[5.5]undec-8-en-8-yl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[l-(N,N-dimethylglycyl)-4fluoropiperidin-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl} piperazin-1 -yl)-N- {[4-( {(3R)-1 - [2-fluoro-1 -(fluoromethyl)ethyl]pyrrolidin-3 yl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

2-[(2-amino-5-bromopyridin-4-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len- 1-yl] methyl] piperazin- l-yl)-N-[(4- {[(4,4-difluorocyclohexyl)methyl]amino} -3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-({4'-chloro-3-[2-(dimethylamino)ethoxy]-l,l·biphenyl-2-yl} methyl)piperazin-1 -yl] -N-( {3-nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[[5-chloro-6-({(3R)-l-[2-fluoro-l(fluoromethyl)ethyl]pyrrolidin-3 -yl} methoxy )pyridin-3 -yl] sulfonyl} -4-(4- {[2-(4chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl }piperazin-1 -yl)benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[(3R)-1-(2,2difluoroethyl)pyrrolidin-3-yl] methoxy }pyridin-3-yl)sulfonyl]-4-(4- {[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] methyl }piperazin-1 -yl)benzamide; Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[(4cyanocyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-({5-fluoro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-[[l-(2,2-difluoroethyl)-4fluoropiperidin-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]phenyl} sulfonyl)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl] methyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N- {[6-( {4-fluoro-1 - [2-fluoro-1 (fluoromethyl)ethyl]piperidin-4-yl]methoxy)-5-(trifluoromethyl)pyridin-3yl] sulfonyl} benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({ 3nitro-4- [(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl} sulfony 1)-2- [2-( lH-pyrazol-4yl)phenoxy]benzamide;

2-[2-(2-aminopyridin-3-yl)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en1- yl]methyl]piperazin-l-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({3nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl]sulfonyl)-2-[2-(lH-pyrazol-5yl)phenoxy]benzamide;

2- [(6-amino-5-chloropyridin-3-yl)oxy]-N-([5-chloro-6-[(4,4difluorocyclohexyl)methoxy]pyridin-3-yl] sulfony 1)-4-(4- {[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide; N-([5-chloro-6-[(4,4-difluorocyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{ [4-(4chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl]piperazin-l-yl)-2-[(6-fluoro1 H-indol-5 -yl)oxy]benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[(4,4-difluorocyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{ [2-(4chlorophenyl )-4,4-di methylcyclohex-1-en-1-yl ]methyl [piperazin-1-yl)-2-| (6-fluoro-111indol-5-yl)oxy]benzamide;

N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{ [4-(4chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)-2-[(6-fluorolH-indol-5 -yl)oxy]benzamide;

N-( {5 -chloro-6- [(trans-4-hydroxycyclohexyl)methoxy]pyridin-3 -yl} sulfonyl)-4-(4- {[2-(4chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6-fluoro-lHindazol-4-yl)oxy]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} piperazin-1 -yl)-2- [(6-fluorolH-indazol-4-yl)oxy]benzamide;

tert-butyl 5-[(4-{4-[({5-chloro-6- [(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3yl} sulfonyl)carbamoyl] -3 - [(6-fluoro- lH-indol-5 -yl)oxy]phenyl} piperazin-1 -yl)methyl] -4-(4chlorophenyl)-3,6-dihydropyridine-1 (2H)-carboxylate;

N-([5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl}sulfonyl)-4-(4{[4-(4-chlorophenyl)-1-(1,3-difluoropropan-2-yl)-1,2,5,6-tetr ahydropyridin-3yl]methyl}piperazin-l-yl)-2-[(6-fluoro-lH-indol-5-yl)oxy]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 - y 1) - 2- [ (6 fluoro- lH-indazol-4-yl)oxy]-N-[(4-{ [(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino }-3nitrophenyl)sulfonyl]benzamide;

N-( {5 -chloro-6- [(trans-4-hydroxycyclohexyl)methoxy]pyridin-3 -yl} sulfonyl)-4-(4- {[2-(4chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl }piperazin-1 -yl)-2- [(7-fluoro- 1Hindazol-4-yl)oxy]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} piperazin-1 -yl)-2- [(7-fluorolH-indazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-{[3-nitro-4-([[4-(oxetan-3-yl)morpholin-2yl] methyl} amino)phenyl] sulfonyl} benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5 -yl)oxy ] -N- {[3 -nitro-4-( {[4-(oxetan-3 -yl)morpholin-2yl] methyl} amino)phenyl] sulfonyl} benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 - y 1) - 2- [ (7 fluoro- lH-indazol-4-yl)oxy]-N-[(4-{ [(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino }-3nitrophenyl)sulfonyl]benzamide;

N-([5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-2- [(6-fluorolH-indazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[5chloro-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(3-methyl-2-oxo-2,3dihydro-lH-benzimidazol-4-yl)oxy]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 11 methyl} piperazin-1 -yl)-N-( {4[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(3-methyl-2-oxo2,3-dihydro-lH-benzimidazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[(trans-4-methoxycyclohexyl)methyl]amino} -3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo2,3-dihydro-lH-benzimidazol-4-yl)oxy]benzamide;

2- [(3-amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-[(4-[[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2- [(3-amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 y 1 ] methyl} piperazin- l-yl)-N-({ 4- [(4-fluorotetrahydro-2H-pyran-4-yl)methoxy] -3 nitrophenyl} sulfonyl)benzamide;

2-[(3-amino-lH-indazol-4-yl)oxy]-N-([5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-lyl] methyl} piperazin-1 -yl)benzamide;

2- [(3 -amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-l-yl]methyl}piperazin-l-yl)-N-[(4-[[4-fluoro-l-(oxetan-3-yl)piperidin-4-yl]methoxy}-3nitrophenyl)sulfonyl]benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indazol-4-yl)oxy]-N-([4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl]methyl} piperazin-1 -yl)-N - [(4- {[(trans-4-hydroxy-4methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2- [(3 -amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-[(4-[[(trans-4-methoxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-l-yl]methyl}piperazin-l-yl)-N-([4-[(cis-4-hydroxy-4-methylcyclohexyl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2- [(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -y 11 methyl} piperazin-1 -yl)-N - [(4- {[(cis-4-hydroxy-4-methylcyclohexyl)methyl] amino} 3- nitrophenyl)sulfonyl]benzamide;

4- (4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[3chloro-4-(tetrahydro-2H-pyran-4-ylmethoxy)phenyl]sulfonyl}-2-[(3-methyl-2-oxo-2,3dihydro-lH-benzimidazol-4-yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-N-[(4{[(4-cyclopropylmorpholin-2-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo2,3-dihydro-lH-benzimidazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-l-yl]methyl}piperazin-l-yl)-N-[[3-nitro-4-(2-oxaspiro[3.5]non-7ylmethoxy)phenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-l-yl]methyl}piperazin-l-yl)-N-([4-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl]methyl (piperazin- l-yl)-N- {[4-( {[(2S)-4-cyclopropylmorpholin-2-yl]methyl} amino)3 -nitrophenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([5-chloro-6-[(trans-l-fluoro-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([5-chloro-6-[(cis-l-fluoro-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] methyl }piperazin-1 -yl)benzamide;

2-[(3-amino-lH-indazol-4-yl)oxy]-N-([5-chloro-6-[(trans-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] methyl }piperazin-1 -yl)benzamide;

N-([5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-2-[(3chloro-lH-indazol-4-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl] methyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-[(4-[[(cis-4-ethyl-4-hydroxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-{[3-nitro-4-({[(2S)-4-(oxetan-3-yl)morpholin-2yl] methyl} amino)phenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {5 -nitro-6- [(tetrahydro-2H-pyran-4ylmethyl)amino]pyridin-3-yl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(2-oxaspiro[3.5]non-7ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-{[4-({[trans-4-(morpholin-4yl)cyclohexyl] methyl} amino) - 3 -nitrophenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[cis-4-(morpholin-4-yl)cyclohexyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({5cyano-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-2-[(6-fluorolH-indazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl }piperazin- l-yl)-N- {[4-( {[4-( {[4-(methoxymethyl)cyclohexyl]methyl} amino)3 -nitrophenyl] sulfonyl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-[(3-nitro-4-{[(3R)-l-(oxetan-3-yl)pyrrolidin-3yl] amino} phenyl) sulfonyl] benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-[(3-nitro-4-{[(3S)-l-(oxetan-3-yl)pyrrolidin-3yl] amino} phenyl) sulfonyl] benzamide;

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)benzoyl} sulfamoyl)-2nitrophenyl] morpholine-4-c arboxamide;

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)benzoyl} sulfamoyl)-2-nitrophenyl] -4cyanopiperidine-1 -carboxamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({3-nitro-4[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl} sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({4-[(4morpholin-4-ylcyclohexy 1) amino] - 3 -nitrophenyl} sulfonyl)benzamide; and therapeutic ally acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-[(3-nitro-4{[(3R)-l-(oxetan-3-yl)pyrrolidin-3-yl]amino]phenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to Trans-4-(4- {[2-(4-chlorophenyl)-4,4dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lH-indol-5-yl)oxy]-N-[(3nitro-4-{[4-(tetrahydro-2H-pyran-4-ylamino)cyclohexyl]amino]phenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lH-indol-5-yl)oxy]-N-[(3nitro-4-{[(3S)-tetrahydro-2H-pyran-3-ylmethyl]amino]phenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

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Still another embodiment pertains to 4-(4- {[2-(4-chloropheny 1)-4,4dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6-fluoro- lH-indol-4-yl)oxy] -N- [(3 nitro-4-[[3-(3-oxopiperazin-l-yl)propyl]amino}phenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 2-(2-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)4.4- dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-[(4-{[3(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-{[2-(4-chloropheny 1)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -y 1)-2-(3,4-dichlorophenoxy)-N-( {4 - [ (1 methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)4.4- dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-N-((4-((l-isopropylpiperidin-4yl)amino)-3-nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-((4'-chloro-l,l'-biphenyl-2yl)methyl)piperazin-l-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-((4'-chloro-l,l'-biphenyl-2yl)methyl)piperazin-l-yl)-2-((2-methyl-l,3-benzothiazol-6-yl)oxy)-N-((3-nitro-4((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-((4'-chloro-l,l'-biphenyl-2yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex1 -en-1 -yl)methyl)piperazin-1 -yl)-2-((2-methyl- lH-indol-5-yl)oxy)-N-((4-(( 1 methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Another embodiment pertains to a composition for treating bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia,

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PCT/US2010/036844 colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small cell lung cancer or spleen cancer, said composition comprising an excipient and a therapeutically effective amount of the compound of Formula (I).

Another embodiment pertains to a method of treating bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small cell lung cancer or spleen cancer in a patient, said method comprising administering to the patient a therapeutically effective amount of Formula (I).

Another embodiment pertains to a method of treating bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small cell lung cancer or spleen cancer in a patient, said method comprising administering to the patient therapeutically effective amount of the compound of Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.

DETAILED DESCRIPTION OF THE INVENTION

Variable moieties herein are represented by identifiers (capital letters with numerical and/or alphabetical superscripts) and may be specifically embodied.

It is meant to be understood that proper valences are maintained for all moieties and combinations thereof, that monovalent moieties having more than one atom are drawn from left to right and are attached through their left ends, and that divalent moieties are also drawn from left to right.

It is also meant to be understood that a specific embodiment of a variable moiety herein may be the same or different as another specific embodiment having the same identifier.

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The term alkenyl as used herein, means a straight or branched hydrocarbon chain containing from 2 to 10 carbons and containing at least one carbon-carbon double bond. The term “C_x-C_y alkyl” means a straight or branched hydrocarbon chain containing at least one carbon-carbon double bond containing x to y carbon atoms. The term “C2-C4 alkenyl” means an alkenyl group containing 2-4 carbon atoms. Representative examples of alkenyl include, but are not limited to buta-2,3-dienyl, ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4pentenyl, 5-hexenyl, 2-heptenyl, 2-methyl-l-heptenyl, and 3-decenyl.

The term alkenylene means a divalent group derived from a straight or branched chain hydrocarbon of 2 to 4 carbon atoms and contains at least one carbon-carbon double bond. The term “C_x-C_y alkylene” means a a divalent group derived from a straight or branched hydrocarbon chain containing at least one carbon-carbon double bond and containing x to y carbon atoms. Representative examples of alkenylene include, but are not limited to, -CH=CH- and -CH₂CH=CH-.

The term alkyl as used herein, means a straight or branched, saturated hydrocarbon chain containing from 1 to 10 carbon atoms. The term “Cx-C_y alkyl” means a straight or branched chain, saturated hydrocarbon containing x to y carbon atoms. For example “C2-C10 alkyl” means a straight or branched chain, saturated hydrocarbon containing 2 to 10 carbon atoms. Examples of alkyl include, 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, 3methylhexyl, 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 straight or branched, saturated hydrocarbon chain of 1 to 10 carbon atoms, for example, of 1 to 4 carbon atoms.

The term “Cx-C_y alkylene” means a divalent group derived from a straight or branched chain, saturated hydrocarbon containing x to y carbon atoms. For example “C2-C6 alkylene” means a straight or branched chain, saturated hydrocarbon containing 2 to 6 carbon atoms.

Examples of alkylene include, but are not limited to, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, and -CH₂CH(CH₃)CH₂-.

The term alkynyl as used herein, means a straight or branched chain hydrocarbon group containing from 2 to 10 carbon atoms and containing at least one carbon-carbon triple bond. The term “C_x-C_y alkynyl” means a straight or branched chain hydrocarbon group containing from x to y carbon atoms. Representative examples of alkynyl include, but are not limited, to acetylenyl, 1-propynyl, 2-propynyl, 3-butynyl, 2-pentynyl, and 1-butynyl.

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The term alkynylene, as used herein, means a divalent radical derived from a straight or branched chain hydrocarbon group containing from 2 to 10 carbon atoms and containing at least one carbon-carbon triple bond.

The term aryl as used herein, means phenyl.

The term cyclic moiety, as used herein, means benzene, phenyl, phenylene, cycloalkane, cycloalkyl, cycloalkylene, cycloalkene, cycloalkenyl, cycloalkenylene, cycloalkyne, cycloalkynyl, cycloalkynylene, heteroarene, heteroaryl, heterocycloalkane, heterocycloalkyl, heterocycloalkene, heterocycloalkenyl and spiroalkyl.

The term cycloalkylene or cycloalkyl or “cycloalkane” as used herein, means a monocyclic or bridged hydrocarbon ring system. The monocyclic cycloalkyl is a carbocyclic ring system containing three to eight carbon atoms, zero heteroatoms and zero double bonds. Examples of monocyclic ring systems include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. The monocyclic ring may contain one or two alkylene bridges, each consisting of one, two, or three carbon atoms, each linking two nonadjacent carbon atoms of the ring system. Non-limiting examples of such bridged cycloalkyl ring systems include bicyclo[3.1.1]heptane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]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 noradamantane), and tricyclo[3.3.1.1^3,7]decane (adamantane). The monocyclic and bridged cycloalkyl can be attached to the parent molecular moiety through any substitutable atom contained within the ring system.

The term cycloalkenylene, or cycloalkenyl or “cycloalkene” as used herein, means a monocyclic or a bridged hydrocarbon ring system. The monocyclic cycloalkenyl has four-, five-, six-, seven- or eight carbon atoms and zero heteroatoms. The four-membered ring systems have one double bond, the five-or six-membered ring systems have one or two double bonds, and the seven- or eight-membered ring systems have one, two, or three double bonds. Representative examples of monocyclic cycloalkenyl groups include, but are not limited to, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. The monocyclic cycloalkenyl ring may contain one or two alkylene bridges, each consisting of one, two, or three carbon atoms, each linking two non-adjacent carbon atoms of the ring system. Representative examples of the bicyclic cycloalkenyl groups include, but are not limited to, 4,5,6,7-tetrahydro-3aH-indene, octahydronaphthalenyl, and 1,6-dihydro-pentalene. The monocyclic and bicyclic cycloalkenyl can be attached to the parent molecular moiety through any substitutable atom contained within the ring systems.

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The term cycloalkyne, or cycloalkynyl, or cycloalkynylene, as used herein, means a monocyclic or a bridged hydrocarbon ring system. The monocyclic cycloalkynyl has eight or more carbon atoms, zero heteroatoms, and one or more triple bonds. The monocyclic cycloalkynyl ring may contain one or two alkylene bridges, each consisting of one, two, or three carbon atoms, each linking two non-adjacent carbon atoms of the ring system. The monocyclic and bridged cycloalkynyl can be attached to the parent molecular moiety through any substitutable atom contained within the ring systems.

The term heteroarene, or heteroaryl, or heteroarylene, as used herein, means a five-membered or six-membered aromatic ring having at least one carbon atom and one or more than one independently selected nitrogen, oxygen or sulfur atom. The heteroarenes of this invention are connected through any adjacent atoms in the ring, provided that proper valences are maintained. Representative examples of heteroaryl include, but are not limited to, furanyl (including, but not limited thereto, furan-2-yl), imidazolyl (including, but not limited thereto, lH-imidazol-l-yl), isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyridinyl (e.g. pyridin-4-yl, pyridin-2-yl, pyridin-3-yl), pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl (including, but not limited thereto, thien-2yl, thien-3-yl), triazolyl, and triazinyl.

The term heterocycloalkane, or heterocycloalkyl, or heterocycloalkylene, as used herein, means monocyclic or bridged three-, four-, five-, six-, seven-, or eightmembered ring containing at least one heteroatom independently selected from the group consisting of Ο, N, and S and zero double bonds. The monocyclic and bridged heterocycloalkane are connected to the parent molecular moiety through any substitutable carbon atom or any substitutable nitrogen atom contained within the rings. The nitrogen and sulfur heteroatoms in the heterocycle rings may optionally be oxidized and the nitrogen atoms may optionally be quartemized. Representative examples of heterocycloalkane groups include, but are not limited to, Representative examples of heterocycloalkane groups include, but are not limited to, morpholinyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, dioxolanyl, tetrahydrofuranyl, thiomorpholinyl, dioxanyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxetanyl, piperazinyl, imidazolidinyl, azetidine, azepanyl, aziridinyl, diazepanyl, dithiolanyl, dithianyl, isoxazolidinyl, isothiazolidinyl, oxadiazolidinyl, oxazolidinyl, pyrazolidinyl, tetrahydrothienyl, thiadiazolidinyl, thiazolidinyl, thiomorpholinyl, trithianyl, and trithianyl.

The term heterocycloalkene, or heterocycloalkenyl, or heterocycloalkenylene, as used herein, means monocyclic or bridged three-, four-, five-, six-, seven-, or eightmembered ring containing at least one heteroatom independently selected from the group

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PCT/US2010/036844 consisting of Ο, N, and S and one or more double bonds. The monocyclic and bridged heterocycloalkene are connected to the parent molecular moiety through any substitutable carbon atom or any substitutable nitrogen atom contained within the rings. The nitrogen and sulfur heteroatoms in the heterocycle rings may optionally be oxidized and the nitrogen atoms may optionally be quartemized. Representative examples of heterocycloalkene groups include, but are not limited to, tetrahydrooxocinyl, 1,4,5,6-tetrahydropyridazinyl, 1,2,3,6tetrahydropyridinyl, dihydropyranyl, imidazolinyl, isothiazolinyl, oxadiazolinyl, isoxazolinyl, oxazolinyl, pyranyl, pyrazolinyl, pyrrolinyl, thiadiazolinyl, thiazolinyl, and thiopyranyl.

The term phenylene, as used herein, means a divalent radical formed by removal of a hydrogen atom from phenyl.

The term spiroalkyl, as used herein, means alkylene, both ends of which are attached to the same carbon atom and is exemplified by C2-spiroalkyl, C3-spiroalkyl, C4-spiroalkyl, Cs-spiroalkyl, C6-spiroalkyl, C7-spiroalkyl, Cs-spiroalkyl, C9-spiroalkyl and the like.

The term spiroheteroalkyl, as used herein, means spiroalkyl having one or two CH2 moieties replaced with independently selected O, C(O), CNOH, CNOCH3, S, S(O), SO2 or NH and one or two CH moieties unreplaced or replaced with N.

The term spiroheteroalkenyl, as used herein, means spiroalkenyl having one or two CH2 moieties replaced with independently selected O, C(O), CNOH, CNOCH3, S, S(O), SO2 or NH and one or two CH moieties unreplaced or replaced with N and also means spiroalkenyl having one or two CH2 moieties unreplaced or replaced with independently selected O, C(O), CNOH, CNOCH3, S, S(O), SO2 or NH and one or two CH moieties replaced with N.

The term, spirocyclo, as used herein, means two substituents on the same carbon atom, that, together with the carbon atom to which they are attached, form a cycloalkane, heterocycloalkane, cycloalkene, or heterocycloalkene ring.

The term C2-C5-spiroalkyl, as used herein, means C2-spiroalkyl, C3-spiroalkyl, C4-spiroalkyl, and Cs-spiroalkyl.

The term C2-spiroalkyl,” as used herein, means eth-l,2-ylene, both ends of which replace hydrogen atoms of the same CH2 moiety.

The term C3-spiroalkyl,” as used herein, means prop-1,3-ylene, both ends of which replace hydrogen atoms of the same CH2 moiety.

The term C4-spiroalkyl,” as used herein, means but-l,4-ylene, both ends of which replace hydrogen atoms of the same CH2 moiety.

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The term Cs-spiroalkyl,” as used herein, means pent-l,5-ylene, both ends of which replace hydrogen atoms of the same CH2 moiety.

The term C6-spiroalkyl,” as used herein, means hex-l,6-ylene, both ends of which replace hydrogen atoms of the same CH2 moiety.

The term NH protecting group, as used herein, means trichloroethoxycarbonyl, tribromoethoxycarbonyl, benzyloxycarbonyl, para-nitrobenzylcarbonyl, ortho-bromobenzyloxycarbonyl, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, phenylacetyl, formyl, acetyl, benzoyl, tert-amyloxycarbonyl, tert-butoxycarbonyl, para-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyl-oxycarbonyl, 4-(phenylazo)benzyloxycarbonyl, 2-furfuryl-oxycarbonyl, diphenylmethoxycarbonyl, 1,1dimethylpropoxy-carbonyl, isopropoxycarbonyl, phthaloyl, succinyl, alanyl, leucyl, 1adamantyloxycarbonyl, 8-quinolyloxycarbonyl, benzyl, diphenylmethyl, triphenylmethyl, 2nitrophenylthio, methanesulfonyl, para-toluenesulfonyl, N,N-dimethylaminomethylene, benzylidene, 2-hydroxybenzylidene, 2-hydroxy-5-chlorobenzylidene, 2-hydroxy-l-naphthylmethylene, 3-hydroxy-4-pyridylmethylene, cyclohexylidene, 2-ethoxycarbonylcyclohexylidene, 2-ethoxycarbonylcyclopentylidene,

2- acetylcyclohexylidene, 3,3-dimethyl-5-oxycyclo-hexylidene, diphenylphosphoryl, dibenzylphosphoryl, 5-methyl-2-oxo-2H-l,3-dioxol-4-yl-methyl, trimethylsilyl, triethylsilyl, and triphenylsilyl.

The term C(O)OH protecting group, as used herein, means methyl, ethyl, n-propyl, isopropyl, 1,1-dimethylpropyl, n-butyl, tert-butyl, phenyl, naphthyl, benzyl, diphenylmethyl, triphenylmethyl, para-nitrobenzyl, para-methoxybenzyl, bis(para-methoxyphenyl)methyl, acetylmethyl, benzoylmethyl, para-nitrobenzoylmethyl, para-bromobenzoylmethyl, paramethanesulfonylbenzoylmethyl, 2-tetrahydropyranyl 2-tetrahydrofuranyl, 2,2,2-trichloroethyl, 2-(trimethylsilyl)ethyl, acetoxymethyl, propionyloxymethyl, pivaloyloxymethyl, phthalimidomethyl, succinimidomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxymethyl, methoxyethoxymethyl, 2-(trimethylsilyl)ethoxymethyl, benzyloxymethyl, methyl thiomethyl, 2-methylthioethyl, phenylthiomethyl, l,l-dimethyl-2-propenyl, 3-methyl3- butenyl, allyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, diethylisopropylsilyl, tertbutyldimethylsilyl, tert-butyldiphenylsilyl, diphenylmethylsilyl, and tert-butylmethoxyphenylsilyl.

The term OH or SH protecting group, as used herein, means benzyloxycarbonyl, 4nitrobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl,

3,4-dimethoxybenzyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl,

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1,1 -dimethylpropoxycarbonyl, isopropoxycarbonyl, isobutyloxycarbonyl, diphenylmethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2,2,2-tribromoethoxycarbonyl, 2(trimethylsilyl)ethoxycarbonyl, 2-(phenylsulfonyl)ethoxycarbonyl, 2(triphenylphosphonio)ethoxycarbonyl, 2-furfuryloxycarbonyl, 1-adamantyloxycarbonyl, vinyloxycarbonyl, allyloxycarbonyl, S-benzylthiocarbonyl, 4-ethoxy-l-naphthyloxycarbonyl, 8-quinolyloxycarbonyl, acetyl, formyl, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, methoxyacetyl, phenoxyacetyl, pivaloyl, benzoyl, methyl, tert-butyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, l,l-dimethyl-2-propenyl, 3-methyl-3-butenyl, allyl, benzyl (phenylmethyl), para-methoxybenzyl, 3,4-dimethoxybenzyl, diphenylmethyl, triphenylmethyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiopyranyl, methoxymethyl, methyl thiomethyl, benzyloxymethyl, 2-methoxyethoxymethyl, 2,2,2-trichloro-ethoxymethyl, 2-(trimethylsilyl)ethoxymethyl, 1-ethoxyethyl, methanesulfonyl, para-toluenesulfonyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, diethylisopropylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, diphenylmethylsilyl, and tert-butylmethoxyphenylsilyl.

Compounds

Geometric isomers may exist in the present compounds. Compounds of this invention may contain carbon-carbon double bonds or carbon-nitrogen double bonds in the E or Z configuration, wherein the term “E” represents higher order substituents on opposite sides of the carbon-carbon or carbon-nitrogen double bond and the term “Z” represents higher order substituents on the same side of the carbon-carbon or carbon-nitrogen double bond as determined by the Cahn-Ingold-Prelog Priority Rules. The compounds of this invention may also exist as a mixture of “E” and “Z” isomers. Substituents around a cycloalkyl or heterocycloalkyl are designated as being of cis or trans configuration. Furthermore, the invention contemplates the various isomers and mixtures thereof resulting from the disposal of substituents around an adamantane ring system. Two substituents around a single ring within an adamantane ring system are designated as being of Z or E relative configuation.

For examples, see C. D. Jones, M. Kaselj, R. N. Salvatore, W. J. le Noble J. Org. Chem.

1998, 63, 2758-2760 and E. L. Eliel, and S.H. Wilen. (1994) Stereochemistry of Organic Compounds. New York, NY: John Wiley &amp; Sons, Inc.

Compounds of this invention may contain asymmetrically substituted carbon atoms in the R or S configuration, in which the terms R and S are as defined by the IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, 13-10. Compounds having asymmetrically substituted carbon atoms with equal amounts of R and S configurations are racemic at those carbon atoms. Atoms with an excess of one

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PCT/US2010/036844 configuration over the other are assigned the configuration present in the higher amount, preferably an excess of about 85%-90%, more preferably an excess of about 95%-99%, and still more preferably an excess greater than about 99%. Accordingly, this invention includes racemic mixtures, relative and absolute stereoisomers, and mixtures of relative and absolute stereoisomers.

Compounds of this invention containing NH, C(O)OH, OH or SH moieties may have attached thereto prodrug-forming moieties. The prodrug-forming moieties are removed by metabolic processes and release the compounds having the freed hydroxyl, amino or carboxylic acid in vivo. Prodrugs are useful for adjusting such pharmacokinetic properties of the compounds as solubility and/or hydrophobicity, absorption in the gastrointestinal tract, bioavailability, tissue penetration, and rate of clearance. An example of a compound with a prodrug-forming moiety is [3-chloro-5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yljmethyl} piperazin-1 - y 1)-2 - {[({3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)-2-iminopyridin-l(2H)-yl]methyl dihydrogen phosphate (EXAMPLE 397), which is a prodrug of 2-[(6-amino-5-chloropyridin3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide (EXAMPLE 318).

Isotope Enriched or Labeled Compounds

Compounds of the invention can exist in isotope-labeled or isotope-enriched form containing one or more atoms having an atomic mass or mass number different from the atomic mass or mass number most abundantly found in nature. Isotopes can be radioactive or non-radioactive isotopes. Isotopes of atoms such as hydrogen, carbon, phosphorous, sulfur, fluorine, chlorine, and iodine include, but are not limited to, Η, H, C, C, N, Ο, P, ³⁵S, ¹⁸F, ³⁶C1, and ¹²⁵I. Compounds that contain other isotopes of these and/or other atoms are within the scope of this invention.

In another embodiment, the isotope-labeled compounds contain deuterium (²H), tritium (³H) or ¹⁴C isotopes. Isotope-labeled compounds of this invention can be prepared by the general methods well known to persons having ordinary skill in the art. Such isotopelabeled compounds can be conveniently prepared by carrying out the procedures disclosed in the Examples disclosed herein and Schemes by substituting a readily available isotopelabeled reagent for a non-labeled reagent. In some instances, compounds may be treated with isotope-labeled reagents to exchange a normal atom with its isotope, for example, hydrogen for deuterium can be exchanged by the action of a deuteric acid such as D2SO4/D2O. In

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PCT/US2010/036844 addition to the above, relevant procedures and intermediates are disclosed, for instance, in

Lizondo, J et al., Drugs Fut, 21(11), 1116 (1996); Brickner, S J et al., J Med Chem, 39(3),

673 (1996); Mallesham, B et al., Org Lett, 5(7), 963 (2003); PCT publications WO1997010223, W02005099353, WO1995007271, W02006008754; US Patent Nos. 7538189; 7534814; 7531685; 7528131; 7521421;7514068;7511013;and US Patent Application Publication Nos. 20090137457; 20090131485; 20090131363; 20090118238; 20090111840;20090105338;20090105307;20090105147; 20090093422; 20090088416; and

20090082471, the methods are hereby incorporated by reference.

The isotope-labeled compounds of the invention may be used as standards to determine the effectiveness of Bcl-2 inhibitors in binding assays. Isotope containing compounds have been used in pharmaceutical research to investigate the in vivo metabolic fate of the compounds by evaluation of the mechanism of action and metabolic pathway of the nonisotope-labeled parent compound (Blake et al. J. Pharm. Sci. 64, 3, 367-391 (1975)). Such metabolic studies are important in the design of safe, effective therapeutic drugs, either because the in vivo active compound administered to the patient or because the metabolites produced from the parent compound prove 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 (1999).

In addition, non-radio active isotope containing drugs, such as deuterated drugs called “heavy drugs,” can be used for the treatment of diseases and conditions related to Bcl-2 activity. Increasing the amount of an isotope present in a compound above its natural abundance is called enrichment. Examples of the amount of enrichment include from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79,

84, 88, 92, 96, to about 100 mol %. Replacement of up to about 15% of normal atom with a heavy isotope has been effected and maintained for a period of days to weeks in mammals, including rodents and dogs, with minimal observed adverse effects (Czajka D M and Finkel A J, Ann. N.Y. Acad. Sci. 1960 84: 770; Thomson J F, Ann. New York Acad. Sci 1960 84: 736; Czakja D M et al., Am. J. Physiol. 1961 201: 357). Acute replacement of as high as 15%-23% in human fluids with deuterium was found not to cause toxicity (Blagojevic N et al. in 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)).

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Stable isotope labeling of a drug can alter its physico-chemical properties such as pKa and lipid solubility. These effects and alterations can affect the pharmacodynamic response of the drug molecule if the isotopic substitution affects a region involved in a ligand-receptor interaction. While some of the physical properties of a stable isotope-labeled molecule are different from those of the unlabeled one, the chemical and biological properties are the same, with one important exception: because of the increased mass of the heavy isotope, any bond involving the heavy isotope and another atom will be stronger than the same bond between the light isotope and that atom. Accordingly, the incorporation of an isotope at a site of metabolism or enzymatic transformation will slow said reactions potentially altering the pharmacokinetic profile or efficacy relative to the non-isotopic compound.

Amides, Esters and Prodrugs

Prodrugs are derivatives of an active drug designed to ameliorate some identified, undesirable physical or biological property. The physical properties are usually solubility (too much or not enough lipid or aqueous solubility) or stability related, while problematic biological properties include too rapid metabolism or poor bioavailability which itself may be related to a physicochemical property.

Prodrugs are usually prepared by: a) formation of ester, hemi esters, carbonate esters, nitrate esters, amides, hydroxamic acids, carbamates, imines, Mannich bases, phosphates, phosphate esters, and enamines of the active drug, b) functionalizing the drug with azo, glycoside, peptide, and ether functional groups, c) use of aminals, hemi-aminals, polymers, salts, complexes, phosphoramides, acetals, hemiacetals, and ketal forms of the drug. For example, see Andrejus Korolkovas's, Essentials of Medicinal Chemistry, John WileyInterscience Publications, John Wiley and Sons, New York (1988), pp. 97-118, which is incorporated in its entirety by reference herein.

Esters can be prepared from substrates of formula (I) containing either a hydroxyl group or a carboxy group by general methods known to persons skilled in the art. The typical reactions of these compounds are substitutions replacing one of the heteroatoms by another atom, for example:

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Scheme 1

O

X

II-C CI

OCH₂CH₃

O

Λ + Cl® h₃c och₂ch₃

Acyl Chloride Alkoxide

Ester

Amides can be prepared from substrates of formula (I) containing either an amino group or a carboxy group in similar fashion. Esters can also react with amines or ammonia to form amides.

Scheme 2 ro

X

R'5' OR'

O®

R—|—O-R' © nh₃

O®H ^r-R-^r’ nh₂

Ji + H-O-R' R NH₃ :NH,

Another way to make amides from compounds of formula (I) is to heat carboxylic acids and amines together.

Scheme 3

O heat 9

R—U—OH ⁺ HN(R')₂ R—U—N(R')₂

In Schemes 2 and 3 above, R and R' are independently substrates of formula (I), alkyl or hydrogen.

Suitable groups for for A¹, B¹, D¹, E¹, Y¹, L¹, Z^1A, Z^2A, Z¹, Z², and Z³ in compounds of Formula (I) are independently selected. The described embodiments of the present invention may be combined. Such combination is contemplated and within the scope of the present invention. For example, it is contemplated that embodiments for any of A¹, B¹, D¹, E¹, Y¹, L¹, Z^1A, Z^2A, Z¹, Z², and Z³ can be combined with embodiments defined for any other of A¹, B¹, D¹, E¹, Y¹, L¹, Z^1A, Z^2A, Z¹, Z², and Z³.

One embodiment of this invention, therefore, pertains to compounds or therapeutically acceptable salts, prodrugs or salts of prodrugs thereof, which are useful as inhibitors of anti-apoptotic Bcl-2 proteins, the compounds having Formula (I)

<img file="NZ600084A_D0003.tif" />

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A¹ is N or C(A²);

A² is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C(O)OR\ OC(O)R¹, NHR¹, Ν(^)2, C(O)NHR¹, CCOJNiR’h, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR¹^, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR¹^, NR^OzNHR¹, NR^OzNCRbz, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, QN^NHR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

B¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C^OR¹, OC^R¹, NHR¹, Ν(^)2, C(O)NHR¹, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSO2N(R¹)2, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, QN^NHR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

D¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ COOR¹, OC(O)R¹, NHR¹, Ν(^)2, C(O)NHR¹, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSO2N(R¹)2, NR^OzNHR¹, NR^OzNCRbz, C(O)NHNOH, C(O)NHNOR¹, C^NHSOzR¹, C(NH)NH2, QN^NHR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

E¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C^OR¹, OC^R¹, NHR¹, N(R^J)2, C(O)NHR’, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSO2N(R¹)2, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C^NHSOzR¹, C(NH)NH₂, QN^NHR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH₃)R¹,.N(CH₃)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; and

Y¹ is H, CN, NO2, C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R¹⁷, OR¹⁷, C(O)R¹⁷, C(O)OR¹⁷, SR¹⁷, SO2R¹⁷, NH2, NHR¹⁷, N(R¹⁷)2, NHC(O)R¹⁷, C(O)NH2, C(O)NHR¹⁷, C(O)N(R¹⁷)2, NHS(O)R¹⁷ or NHSO₂R¹⁷; or

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E¹ and Y¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

and

A², B¹, and D¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R¹, C(O)R¹, C(O)OR\ OC(O)R\ NHR¹, NCRbz, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QOW’E SO₂NH₂, SOzNHR¹, SOzNCR¹^, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR¹^, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

Y¹ and B¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

A², D¹, and E¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C(O)OR¹, OC(O)R\ NHR¹, Ν(^)2, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QlW’h, SO2NH2, SOzNHR¹, δΟ2Ν(^)₂, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, Ν^δΟ₂Ν(^)₂, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

A² and B¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

D¹, E¹, and Y¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R¹, C(O)R\ C(O)OR¹, OC(O)R\ NHR¹, Ν(^)₂, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QlW’h, SO₂NH₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, CONHSOzR¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

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A² and D¹, together with the atoms to which they are attached, are benzene, naphthalene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

and

B¹, E¹, and Y¹ are independently selected H, R¹, OR¹, SR¹, S(O)R¹, SO2R¹, C(O)R¹, C(O)OR¹, OC(O)R\ NHR¹, N(R^j)₂, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, ΝΚ’Ο^ΝΟί’Ε SO₂NH₂, SOzNHR¹, 8Ο₂Ν(^)₂, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzN^h, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

R¹ is R², R³, R⁴ or R⁵;

R^1A is cycloalkyl, cycloalkenyl or cycloalkynyl;

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane or heterocycloalkane;

R³ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^3A; R^3A is cycloalkane or heterocycloalkane;

R⁴ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^4A; R^4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶, NC(R^6A)(R^6B), R⁷, OR⁷, SR⁷, S(O)R⁷, SO2R⁷, NHR⁷, N(R⁷)2, C(O)R⁷, C(O)NH2, C(O)NHR⁷, C(O)N(R⁷)2, NHC(O)R⁷, NR⁷C(O)R⁷, NHSO2R⁷, NHC(O)OR⁷, SO2NH₂, SOzNHR⁷, SO2N(R⁷)2, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)CH(CH3)NHC(O)CH(CH3)NH2, NHC(O)CH(CH3)NHC(O)CH(CH3)NHR¹, OH, (O), C(O)OH, N3, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I;

R⁶ is C₂-C5-spiroalkyl, each of which is unsubstituted or substituted with OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH(CH₃) or N(CH₃)₂;

R^6a and R^6b are independently selected alkyl or, together with the N to which they are attached, R^6C;

R^6c is aziridin-l-yl, azetidin-l-yl, pyrrolidin-l-yl or piperidin-l-yl, each having one CH₂ moiety unreplaced or replaced with O, C(O), CNOH, CNOCH₃, S, S(O), SO₂ or NH;

R⁷ is R⁸, R⁹, R¹⁰or R¹¹;

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Ο Ο Λ Ο Λ

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^9A; R^9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R^10A; R^10A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

Rⁿ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R¹², OR¹², SR¹², S(O)R¹², SO2R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH2, NHR¹², N(R¹²)2, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)2R¹², NR¹²S(O)2R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH2, NHC(O)NHR¹², NHC(O)N(R¹²)2, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)2, C(O)NH2, C(O)NHR¹², C(O)N(R¹²)2, C(O)NHOH, C(O)NHOR¹², C(O)NHSO2R¹², C(O)NR¹²SO2R¹², SO2NH2, SO2NHR¹², SO2N(R¹²)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR¹², C(N)N(R¹²)2, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R¹²is R¹³, R¹⁴, R¹⁵ or R¹⁶;

R¹³ is phenyl, which is unfused or fused with benzene, heteroarene or R^13A; R^13A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁴ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^14A; R^14A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁵ is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene, each of which is unfused or fused with benzene, heteroarene or R^15A; R^15A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁶ is alkyl, alkenyl or alkynyl;

R¹⁷ is R¹⁸, R¹⁹, R²⁰orR²¹;

R¹⁸ is phenyl, which is unfused or fused with benzene, heteroarene or R^18A; R^18A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^19A; R^19A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R^20A; R^20A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²¹ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R²², OR²², SR²², S(O)R²², SO₂R²², C(O)R²²,

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CO(O)R²², OC(O)R²², OC(O)OR²², NH2, NHR²², N(R²²)2, NHC(O)R²², NR²²C(O)R²², NHS(O)2R²², NR²²S(O)2R²², NHC(O)OR²², NR²²C(O)OR²², NHC(O)NH2, NHC(O)NHR²², NHC(O)N(R²²)2, NR²²C(O)NHR²², NR²²C(O)N(R²²)2, C(O)NH2, C(O)NHR²², C(O)N(R²²)2, C(O)NHOH, C(O)NHOR²², C(O)NHSO2R²², C(O)NR²²SO2R²², SO2NH2, SO2NHR²², SO2N(R²²)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR²², C(N)N(R²²)2, cnoh, cnoch₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R²² is R²³, R²⁴ or R²⁵;

R²³ is phenyl, which is unfused or fused with benzene, heteroarene or R^23A; R^23A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁴ is heteroarene, which is unfused or fused with benzene, heteroarene or R^24A; R^24Ais cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁵ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

Z¹ is R²⁶ or R²⁷;

Z² is R²⁸, R²⁹ or R³⁰;

Z^1A and Z^2A are both absent or are taken together to form CH₂, CH₂CH₂ or Z^12A;

Z is C₂-C6-alkylene having one or two CH₂ moieties replaced by NH, N(CH₃), S, S(O) or SO₂;

L¹ is a R³⁷, OR³⁷, SR³⁷, S(O)R³⁷, SO2R³⁷, C(O)R³⁷, CO(O)R³⁷, OC(O)R³⁷, OC(O)OR³⁷, NHR³⁷, C(O)NH, C(O)NR³⁷, C(O)NHOR³⁷, C(O)NHSO2R³⁷, SO₂NH, SO₂NHR³⁷, C(N)NH, C(N)NHR³⁷;

R is phenylene, which is unfused or fused with benzene or heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁷ is heteroarylene, which is unfused or fused with benzene or heteroarene or R^27A; R^27A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R is phenylene, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁹ is heteroarylene, which is unfused or fused with benzene or heteroarene or R^29A; R^29A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene ;

R is cycloalkylene, cycloalkenylene, heterocycloalkylene or heterocycloalkenylene, each of which is unfused or fused with benzene, heteroarene or R^30A; R^30A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R³⁷ is a bond or R^37A;

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R is alkylene, alkenylene, or alkynylene, each of which is unsubstituted or substituted with one or two or three independently selected R^37B, OR³™, SR³™, S(O)R³™, SO2R³™, C(O)R³™, CO(O)R³™, OC(O)R³™, OC(O)OR³™, NH2, NHR³™, N(R³™)2, NHC(O)R³™, NR³™C(O)R³™, NHS(O)2R³™, NR³™S(O)2R³™, NHC(O)OR³™, NR³™C(O)OR³™, NHC(O)NH2, NHC(O)NHR³™, NHC(O)N(R³™)2, NR³™C(O)NHR³™, NR³™C(O)N(R³™)2, C(O)NH₂, C(O)NHR³™, C(O)N(R³™)2, C(O)NHOH, C(O)NHOR³™, C(O)NHSO2R³™, C(O)NR³™SO2R³™, SO2NH₂, SO₂NHR³™, SO2N(R³™)2, C(O)H,

C(O)OH, C(N)NH₂, C(N)NHR³™, C(N)N(R³™)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF3, OCF₂CF₃, F, Cl, Br and I substituents;

R³™ is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;

Z³ is R³⁸, R³⁹ or R⁴⁰;

R³⁸ is phenyl, which is unfused or fused with benzene, heteroarene or R^38A; R^38A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R³⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^39A; R^39A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^40A; R^40A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

27 1.A 2A wherein the moieties represented by R andR are substituted (i.e., if Z andZ are absent) or further substituted (i.e., if Z^1A and Z^2A are present) with one or two or three or four of independently selected R⁴¹, OR⁴¹, SR⁴¹, S(O)R⁴¹, SO2R⁴¹, C(O)R⁴¹, CO(O)R⁴¹, OC(O)R⁴¹, OC(O)OR⁴¹, NH2, NHR⁴¹, N(R⁴¹)2, NHC(O)R⁴¹, NR⁴¹C(O)R⁴¹, NHS(O)2R⁴¹, NR⁴¹S(O)2R⁴¹, NHC(O)OR⁴¹, NR⁴¹C(O)OR⁴¹, NHC(O)NH2, NHC(O)NHR⁴¹,

NHC(O)N(R⁴¹)2, NR⁴¹C(O)NHR⁴¹, NR⁴¹C(O)N(R⁴¹)2, C(O)NH₂, C(O)NHR⁴¹, C(O)N(R⁴¹)2, C(O)NHOH, C(O)NHOR⁴¹, C(O)NHSO2R⁴¹, C(O)NR⁴¹SO2R⁴¹, SO2NH₂, SO₂NHR⁴¹, SO2N(R⁴¹)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴¹, C(N)N(R⁴¹)₂, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁴¹ is R⁴², R⁴³, R⁴⁴ or R⁴⁵;

R⁴² is phenyl, which is unfused or fused with benzene, heteroarene or R^42A; R^42A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴³ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^43A; R^43A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

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R⁴⁴ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^44A; R^44A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁵ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁴⁶, OR⁴⁶, SR⁴⁶, S(O)R⁴⁶, SO2R⁴⁶, C(O)R⁴⁶, CO(O)R⁴⁶, OC(O)R⁴⁶, OC(O)OR⁴⁶, NH2, NHR⁴⁶, N(R⁴⁶)2, NHC(O)R⁴⁶, NR⁴⁶C(O)R⁴⁶, NHS(O)2R⁴⁶, NR⁴⁶S(O)2R⁴⁶, NHC(O)OR⁴⁶, NR⁴⁶C(O)OR⁴⁶, NHC(O)NH2, NHC(O)NHR⁴⁶, NHC(O)N(R⁴⁶)2, NR⁴⁶C(O)NHR⁴⁶, NR⁴⁶C(O)N(R⁴⁶)2, C(O)NH₂, C(O)NHR⁴⁶, C(O)N(R⁴⁶)2, C(O)NHOH, C(O)NHOR⁴⁶, C(O)NHSO2R⁴⁶, C(O)NR⁴⁶SO2R⁴⁶, SO2NH₂, SO₂NHR⁴⁶, SO2N(R⁴⁶)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴⁶, C(N)N(R⁴⁶)₂, cnoh, cnoch₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁴⁶ is alkyl, alkenyl, alkynyl, R⁴⁷, R⁴⁸ or R⁴⁹;

R⁴⁷ is phenyl, which is unfused or fused with benzene, heteroarene or R^47A; R^47A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁸ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^48A; R^48A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁹ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^49A; R^49A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

wherein the moieties represented by R⁴², R^42A, R⁴³, R^43A, R⁴⁴, R⁴⁴^ R⁴⁷, R^47A, R⁴⁸, R^48A, R⁴⁹, and R^49A are independently substituted with one or two or three or four of independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S(O)R⁵⁰, SO2R⁵⁰, C(O)R⁵⁰, CO(O)R⁵⁰, OC(O)R⁵⁰, OC(O)OR⁵⁰, NH2, NHR⁵⁰, N(R⁵⁰)2, NHC(O)R⁵⁰, NR⁵⁰C(O)R⁵⁰, NHS(O)2R⁵⁰, NR⁵⁰S(O)2R⁵⁰, NHC(O)OR⁵⁰, NR⁵⁰C(O)OR⁵⁰, NHC(O)NH2, NHC(O)NHR⁵⁰, NHC(O)N(R⁵⁰)2, NR⁵⁰C(O)NHR⁵⁰, NR⁵⁰C(O)N(R⁵⁰)2, C(O)NH₂, C(O)NHR⁵⁰, C(O)N(R⁵⁰)2, C(O)NHOH, C(O)NHOR⁵⁰, C(O)NHSO2R⁵⁰, C(O)NR⁵⁰SO2R⁵⁰, SO2NH₂, SO₂NHR⁵⁰, SO2N(R⁵⁰)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵⁰, C(N)N(R^5o)₂, CNOH, CNOCH₃, OH, (O), CN, n₃, no₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁵⁰ is R⁵¹,R⁵², R⁵³ or R⁵⁴;

R⁵¹ is phenyl, which is unfused or fused with benzene, heteroarene or R^51A; R^51A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R is heteroaryl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

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R⁵³ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^53A; R^53A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵⁴ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁵⁵, OR⁵⁵, SR⁵⁵, S(O)R⁵⁵, SO2R⁵⁵, C(O)R⁵⁵, CO(O)R⁵⁵, OC(O)R⁵⁵, OC(O)OR⁵⁵, NH2, NHR⁵⁵, N(R⁵⁵)2, NHC(O)R⁵⁵, NR⁵⁵C(O)R⁵⁵, NHS(O)2R⁵⁵, NR⁵⁵S(O)2R⁵⁵, NHC(O)OR⁵⁵, NR⁵⁵C(O)OR⁵⁵, NHC(O)NH2, NHC(O)NHR⁵⁵, NHC(O)N(R⁵⁵)2, NR⁵⁵C(O)NHR⁵⁵, NR⁵⁵C(O)N(R⁵⁵)2, C(O)NH2, C(O)NHR⁵⁵, C(O)N(R⁵⁵)2, C(O)NHOH, C(O)NHOR⁵⁵, C(O)NHSO2R⁵⁵, C(O)NR⁵⁵SO2R⁵⁵, SO2NH2, SO2NHR⁵⁵, SO2N(R⁵⁵)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR⁵⁵, C(N)N(R⁵⁵)2, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁵⁵ is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl; and wherein each foregoing cyclic moiety is independently unsubstituted, further unsubstituted, substituted or further substituted with one or two or three or four or five of independently selected R^57A, R⁵⁷, OR⁵⁷, SR⁵⁷, S(O)R⁵⁷, SO2R⁵⁷, C(O)R⁵⁷, CO(O)R⁵⁷, OC(O)R⁵⁷, OC(O)OR⁵⁷, NH2, NHR⁵⁷, N(R⁵⁷)2, NHC(O)R⁵⁷, NR⁵⁷C(O)R⁵⁷, NHS(O)2R⁵⁷, NR⁵⁷S(O)2R⁵⁷, NHC(O)OR⁵⁷, NR⁵⁷C(O)OR⁵⁷, NHC(O)NH2, NHC(O)NHR⁵⁷, NHC(O)N(R⁵⁷)2, NR⁵⁷C(O)NHR⁵⁷, NR⁵⁷C(O)N(R⁵⁷)2, C(O)NH₂, C(O)NHR⁵⁷, C(O)N(R⁵⁷)2, C(O)NHOH, C(O)NHOR⁵⁷, C(O)NHSO2R⁵⁷, C(O)NR⁵⁷SO2R⁵⁷, SO2NH₂, SO₂NHR⁵⁷, SO2N(R⁵⁷)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵⁷, C(N)N(R⁵⁷)₂, CNOH, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R^57A is spirocyclyl;

R⁵⁷ is R⁵⁸, R⁵⁹, R⁶⁰or R⁶¹;

R⁵⁸ is phenyl, which is unfused or fused with benzene, heteroarene or R^58A; R^58A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^59A; R^59A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^60A; R^60A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶¹ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶², OR⁶², SR⁶², S(O)R⁶², SO2R⁶², C(O)R⁶², CO(O)R⁶², OC(O)R⁶², OC(O)OR⁶², NH2, NHR⁶², N(R⁶²)₂, NHC(O)R⁶², NR⁶²C(O)R⁶²,

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NHS(O)₂R⁶², NR⁶²S(O)2R⁶², NHC(O)OR⁶², NR⁶²C(O)OR⁶², NHC(O)NH2, NHC(O)NHR⁶²,

NHC(O)N(R⁶²)2, NR⁶²C(O)NHR⁶², NR⁶²C(O)N(R⁶²)2, C(O)NH₂, C(O)NHR⁶², C(O)N(R⁶²)₂,

C(O)NHOH, C(O)NHOR⁶², C(O)NHSO₂R⁶², C(O)NR⁶²SO2R⁶², SO2NH₂, SO₂NHR⁶²,

SO₂N(R⁶²)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR⁶², C(N)N(R⁶²)2, cnoh, cnoch₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁶² is R⁶³, R⁶⁴, R⁶⁵ or R⁶⁶;

R⁶³ is phenyl, which is unfused or fused with benzene, heteroarene or R^63A; R^63A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁴ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^64A; R^64A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁵ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^65A; R^65A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁶ is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶⁷, OR⁶⁷, SR⁶⁷, S(O)R⁶⁷, SO2R⁶⁷, C(O)R⁶⁷, CO(O)R⁶⁷, OC(O)R⁶⁷, OC(O)OR⁶⁷, NH2, NHR⁶⁷, N(R⁶⁷)2, NHC(O)R⁶⁷, NR⁶⁷C(O)R⁶⁷, NHS(O)2R⁶⁷, NR⁶⁷S(O)2R⁶⁷, NHC(O)OR⁶⁷, NR⁶⁷C(O)OR⁶⁷, NHC(O)NH2, NHC(O)NHR⁶⁷, NHC(O)N(R⁶⁷)2, NR⁶⁷C(O)NHR⁶⁷, NR⁶⁷C(O)N(R⁶⁷)2, C(O)NH₂, C(O)NHR⁶⁷, C(O)N(R⁶⁷)2, C(O)NHOH, C(O)NHOR⁶⁷, C(O)NHSO2R⁶⁷, C(O)NR⁶⁷SO2R⁶⁷, SO2NH₂, SO₂NHR⁶⁷, SO2N(R⁶⁷)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶⁷, C(N)N(R⁶⁷)₂, cnoh, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituents;

R⁶⁷ is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;

wherein the moieties represented by R^57A, R⁵⁸, R⁵⁹, R⁶⁰, R⁶³, R⁶⁴, R⁶⁵, and R⁶⁷ are unsubstituted or substituted with one or two or three or four of independently selected R⁶⁸, OR⁶⁸, SR⁶⁸, S(O)R⁶⁸, SO2R⁶⁸, C(O)R⁶⁸, CO(O)R⁶⁸, OC(O)R⁶⁸, OC(O)OR⁶⁸, NH2, NHR⁶⁸, N(R⁶⁸)2, NHC(O)R⁶⁸, NR⁶⁸C(O)R⁶⁸, NHS(O)2R⁶⁸, NR⁶⁸S(O)2R⁶⁸, NHC(O)OR⁶⁸, NR⁶⁸C(O)OR⁶⁸, NHC(0)NH2, NHC(O)NHR⁶⁸, NHC(O)N(R⁶⁸)₂, NR⁶⁸C(O)NHR⁶⁸, NR⁶⁸C(O)N(R⁶⁸)2, C(O)NH2, C(O)NHR⁶⁸, C(O)N(R⁶⁸)2, C(0)NH0H, C(O)NHOR⁶⁸, C(O)NHSO₂R⁶⁸, C(O)NR⁶⁸SO2R⁶⁸, SO2NH₂, SO₂NHR⁶⁸, SO2N(R⁶⁸)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶⁸, C(N)N(R⁶⁸)₂, CNOH, CNOCH₃, OH, (O), CN, n₃, no₂, cf₃,

CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁶⁸ is R⁶⁹, R™, R⁷¹ or R⁷²;

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R⁶⁹ is phenyl, which is unfused or fused with benzene, heteroarene or R^69A; R^69A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷⁰ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^70A; R^70A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷¹ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^71A; R^71A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷² is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁷³, OR⁷³, SR⁷³, S(O)R⁷³, SO2R⁷³, C(O)R⁷³, CO(O)R⁷³, OC(O)R⁷³, OC(O)OR⁷³, NH₂, NHR⁷³, N(R⁷³)2, NHC(O)R⁷³, NR⁷³C(O)R⁷³, NHS(O)2R⁷³, NR⁷³S(O)2R⁷³, NHC(O)OR⁷³, NR⁷³C(O)OR⁷³, NHC(O)NH2, NHC(O)NHR⁷³, NHC(O)N(R⁷³)2, NR⁷³C(O)NHR⁷³, NR⁷³C(O)N(R⁷³)2, C(O)NH₂, C(O)NHR⁷³, C(O)N(R⁷³)2, C(O)NHOH, C(O)NHOR⁷³, C(O)NHSO2R⁷³, C(O)NR⁷³SO2R⁷³, SO2NH₂, SO₂NHR⁷³, SO2N(R⁷³)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷³, C(N)N(R⁷³)₂, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁷³ is alkyl, alkenyl, alkenyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl; and the moieties represented by R , R , and R are unsubstituted or substituted with one or two or three or four of independently selected NH₂, C(O)NH₂, C(O)NHOH, SO₂NH₂, CF₃, CF₂CF₃, C(O)H, C(O)OH, C(N)NH₂, OH, (O), CN, N₃, no₂, cf₃, cf₂cf₃, ocf₃, OCF₂CF₃, F, Cl, Br or I.

Another embodiment of this invention pertains to compounds of Formula (I), wherein

A¹ is N or C(A²);

A² is H, R¹, OR¹, SR¹, S(O)R\ SOzR¹, C(O)R\ COOR¹, OC(O)R¹, NHR¹, Ν(^)₂, C(O)NHR¹, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C^NHSOzR¹, C(NH)NH2, ( (NI I)NI IR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

B¹ is H, R¹, OR¹, SR¹, S(O)R\ SOzR¹, C(O)R\ C^OR¹, OC^R¹, NHR¹, Ν(^)₂, C(O)NHR¹, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹,

NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹,

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NI^SOzNCR¹^, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, QNH^HR¹,

C(NH)N(R¹)2 NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,

N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

D¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ COOR¹, OC(O)R¹, NHR¹, Ν(^)2, C(O)NHR¹, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR¹^, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR¹^, NR^OzNHR¹, NR^OzNCRbz, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, QN^NHR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

E¹ is H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C^OR¹, OC^R¹, NHR¹, Ν(^)2, C(O)NHR’, CONCR^z, NHC(O)R¹, NR^OR¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH₂, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR¹C(O)N(R¹)2, so₂nh₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, QN^NHR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH₃)R¹,.N(CH₃)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; and

Y¹ is H, CN, NO2, C(O)OH, F, Cl, Br, I, CF3, OCF3, CF2CF3, OCF2CF3, R¹⁷, OR¹⁷, C(O)R¹⁷, C(O)OR¹⁷, SR¹⁷, SO2R¹⁷, NH2, NHR¹⁷, N(R¹⁷)2, NHC(O)R¹⁷, C(O)NH2, C(O)NHR¹⁷, C(O)N(R¹⁷)2, NHS(O)R¹⁷ or NHSO₂R¹⁷; or

E¹ and Y¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

A², B¹, and D¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C(O)OR\ OC(O)R’, NHR¹, N(R^J)2, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QlW’h, SO₂NH₂, SOzNHR¹, SOzNCR¹)^ NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSO2N(R¹)2, NR^OzNHR¹, NR¹SO2N(R¹)2, C(O)NHNOH, C(O)NHNOR¹, CiWNHSOzR¹, C(NH)NH2, CCN^NHR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

Y¹ and B¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

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A², D¹, and E¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R¹, (Z(O)R¹, C(O)OR¹, OC(O)R’, NHR¹, NCRbz, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QlW’h, SO₂NH₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

A² and B¹, together with the atoms to which they are attached, are benzene, naphthylene, heteroarene cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

D¹, E¹, and Y¹ are independently selected H, R¹, OR¹, SR¹, S(O)R\ SO2R\ C(O)R\ C(O)OR¹, OC(O)R’, NHR¹, Ν(^)2, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QlW’h, SO₂NH₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, C(O)NHSO2R¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)₂ NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂, N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A; or

A² and D¹, together with the atoms to which they are attached, are benzene, naphthalene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; and

B¹, E¹, and Y¹ are independently selected H, R¹, OR¹, SR¹, S(O)R¹, SO2R¹, C(O)R¹, C(O)OR¹, OC(O)R’, NHR¹, Ν(^)₂, C(O)NHR’, Ο(Ο)Ν(^)₂, NHC(O)R¹, NR¹C(O)R¹, NHC(O)OR¹, NR¹C(O)OR¹, NHC(O)NH2, NHC(O)NHR¹, NHC(O)N(R¹)2, NR¹C(O)NHR¹, NR’QlW’h, SO₂NH₂, SOzNHR¹, SOzNCR^z, NHSOzR¹, NR^OzR¹, NHSOzNHR¹, NHSOzNCR^z, NR^OzNHR¹, NR^OzNCR^z, C(O)NHNOH, C(O)NHNOR¹, CONHSOzR¹, C(NH)NH2, C(NI I)NI IR¹, 0(ΝΗ)Ν(^)2 NHSOzNHR¹, NHSO2N(CH3)R¹, N(CH3)SO₂N(CH₃)R¹, F, Cl, Br, I, CN, NO₂,N₃, OH, C(O)H, CHNOH, CH(NOCH₃), CF₃, C(O)OH, C(O)NH₂ or C(O)OR^1A;

R¹ is R², R³, R⁴ or R⁵;

R^1A is cycloalkyl, cycloalkenyl or cycloalkynyl;

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane or heterocycloalkane;

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R³ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^3A; R^3A is cycloalkane or heterocycloalkane;

R⁴ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^4A; R^4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶, NC(R^6A)(R^6B), R⁷, OR⁷, SR⁷, S(O)R⁷, SO2R⁷, NHR⁷, N(R⁷)₂, C(O)R⁷, C(O)NH2, C(O)NHR⁷, C(O)N(R⁷)2, NHC(O)R⁷, NR⁷C(O)R⁷, NHSO2R⁷, NHC(O)OR⁷, SO2NH₂, SOzNHR⁷, SO2N(R⁷)2, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)CH(CH3)NHC(O)CH(CH3)NH2, NHC(O)CH(CH3)NHC(O)CH(CH3)NHR¹, OH, (O), C(O)OH, N3, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br or I;

R⁶ is C₂-C5-spiroalkyl, each of which is unsubstituted or substituted with OH, (O), N₃, CN, CF₃, CF₂CF₃, F, Cl, Br, I, NH₂, NH(CH₃) or N(CH₃)₂;

R^6a and R^6b are independently selected alkyl or, together with the N to which they are attached, R^6C;

R^6c is aziridin-l-yl, azetidin-l-yl, pyrrolidin-l-yl or piperidin-l-yl, each having one CH₂ moiety unreplaced or replaced with O, C(O), CNOH, CNOCH₃, S, S(O), SO₂ or NH;

R⁷ is R⁸, R⁹, R¹⁰or Rⁿ;

Ο Ο Λ Ο Λ

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^9A; R^9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R^10A; R^10A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

Rⁿ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R¹², OR¹², SR¹², S(O)R¹², SO2R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH2, NHR¹², N(R¹²)₂, NHC(0)R¹², NR¹²C(O)R¹², NHS(O)2R¹², NR¹²S(O)2R¹², NHC(0)0R¹², NR¹²C(O)OR¹², NHC(0)NH₂, NHC(0)NHR¹², NHC(O)N(R¹²)2, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)2, C(0)NH₂, C(0)NHR¹², C(O)N(R¹²)₂, C(0)NH0H, C(0)NH0R¹², C(O)NHSO2R¹², C(O)NR¹²SO2R¹², SO2NH2, SO2NHR¹², SO2N(R¹²)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR¹², C(N)N(R¹²)2, CNOH, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R¹² is R¹³,R¹⁴, R¹⁵ or R¹⁶;

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R¹³ is phenyl, which is unfused or fused with benzene, heteroarene or R^13A; R^13A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁴ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^14A; R^14A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁵ is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene, each of which is unfused or fused with benzene, heteroarene or R^15A; R^15A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁶ is alkyl, alkenyl or alkynyl;

R¹⁷ is R¹⁸, R¹⁹, R²⁰ or R²¹;

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R¹⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^19A; R^19A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R^20A; R^20A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²¹ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R²², OR²², SR²², S(O)R²², SO2R²², C(O)R²², CO(O)R²², OC(O)R²², OC(O)OR²², NH2, NHR²², N(R²²)2, NHC(O)R²², NR²²C(O)R²², NHS(O)2R²², NR²²S(O)2R²², NHC(O)OR²², NR²²C(O)OR²², NHC(O)NH2, NHC(O)NHR²², NHC(O)N(R²²)2, NR²²C(O)NHR²², NR²²C(O)N(R²²)2, C(O)NH2, C(O)NHR²², C(O)N(R²²)2, C(O)NHOH, C(O)NHOR²², C(O)NHSO2R²², C(O)NR²²SO2R²², SO2NH2, SO2NHR²², SO2N(R²²)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR²², C(N)N(R²²)2, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R²² is R²³, R²⁴ or R²⁵;

R²³ is phenyl, which is unfused or fused with benzene, heteroarene or R^23A; R^23A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁴ is heteroarene, which is unfused or fused with benzene, heteroarene or R^24A; R^24Ais cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁵ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl each of which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

Z¹ is R²⁶ or R²⁷;

Z² is R²⁸, R²⁹ or R³⁰;

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Z^1A and Z^2A are both absent or are taken together to form CH2, CH2CH2 or Z^12A;

Z is C2-C6-alkylene having one or two CH2 moieties replaced by NH, N(CH3), S,

S(O) or SO₂;

L¹ is a R³⁷, OR³⁷, SR³⁷, S(O)R³⁷, SO2R³⁷, C(O)R³⁷, CO(O)R³⁷, OC(O)R³⁷, OC(O)OR³⁷, NHR³⁷, C(O)NH, C(O)NR³⁷, C(O)NHOR³⁷, C(O)NHSO2R³⁷, SO₂NH, SO2NHR³⁷, C(N)NH, C(N)NHR³⁷;

R is phenylene, which is unfused or fused with benzene or heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

27 A

R is heteroarylene, which is unfused or fused with benzene or heteroarene or R ;

R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁸ is phenylene, which is unfused or fused with benzene, heteroarene or R^28A; R^28A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R²⁹ is heteroarylene, which is unfused or fused with benzene or heteroarene or R^29A; R^29A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene ;

R³⁰ is cycloalkylene, cycloalkenylene, heterocycloalkylene or heterocycloalkenylene, each of which is unfused or fused with benzene, heteroarene or R^30A; R^30A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R³⁷ is a bond or R^37A;

37A

R is alkylene, alkenylene, or alkynylene, each of which is unsubstituted or substituted with one or two or three independently selected R^37B, OR^37B, SR³™, S(O)R³™, SO2R³™, C(O)R³™, CO(O)R³™, OC(O)R³™, OC(O)OR³™, NH2, NHR³™, N(R³™)2, NHC(O)R³™, NR^37BC(O)R^37B, NHS(O)2R³™, NR^37BS(O)2R³™, NHC(O)OR^37B, NR^37BC(O)OR^37B, NHC(O)NH2, NHC(O)NHR^37B, NHC(O)N(R³™)2, NR^37BC(O)NHR^37B, NR^37BC(O)N(R³™)2, C(O)NH₂, C(O)NHR^37B, C(O)N(R³™)2, C(O)NHOH, C(O)NHOR^37B, C(O)NHSO2R³™, C(O)NR^37BSO₂R³™, SO2NH2, SO2NHR³™, SO2N(R³™)2, C(O)H,

C(O)OH, C(N)NH₂, C(N)NHR^37B, C(N)N(R³™)₂, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br and I substituents;

R³™ is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;

Z³ is R³⁸, R³⁹ or R⁴⁰;

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R³⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^39A; R^39A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

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R⁴⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^40A; R^40A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

wherein the moieties represented by R²⁶ and R²⁷ are substituted with OR⁴¹;

R⁴¹ is R⁴², R⁴³, R⁴⁴ or R⁴⁵;

R⁴² is phenyl, which is unfused or fused with benzene, heteroarene or R^42A; R^42A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴³ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^43A; R^43A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁴ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^44A; R^44A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁵ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁴⁶, OR⁴⁶, SR⁴⁶, S(O)R⁴⁶, SO2R⁴⁶, C(O)R⁴⁶, CO(O)R⁴⁶, OC(O)R⁴⁶, OC(O)OR⁴⁶, NH2, NHR⁴⁶, N(R⁴⁶)2, NHC(O)R⁴⁶, NR⁴⁶C(O)R⁴⁶, NHS(O)2R⁴⁶, NR⁴⁶S(O)2R⁴⁶, NHC(O)OR⁴⁶, NR⁴⁶C(O)OR⁴⁶, NHC(O)NH2, NHC(O)NHR⁴⁶, NHC(O)N(R⁴⁶)2, NR⁴⁶C(O)NHR⁴⁶, NR⁴⁶C(O)N(R⁴⁶)2, C(O)NH₂, C(O)NHR⁴⁶, C(O)N(R⁴⁶)2, C(O)NHOH, C(O)NHOR⁴⁶, C(O)NHSO2R⁴⁶, C(O)NR⁴⁶SO2R⁴⁶, SO2NH₂, SO₂NHR⁴⁶, SO2N(R⁴⁶)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴⁶, C(N)N(R⁴⁶)₂, cnoh, cnoch₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁴⁶ is alkyl, alkenyl, alkynyl, R⁴⁷, R⁴⁸ or R⁴⁹;

R⁴⁷ is phenyl, which is unfused or fused with benzene, heteroarene or R^47A; R^47A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁸ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^48A; R^48A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁴⁹ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^49A; R^49A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

wherein the moieties represented by R⁴², R^42A, R⁴³, R^43A, R⁴⁴, R⁴⁴^ R⁴⁷, R^47A, R⁴⁸, R^48A, R⁴⁹, and R^49A independently substituted with one or two or three or four of independently selected R⁵⁰, OR⁵⁰, SR⁵⁰, S(O)R⁵⁰, SO2R⁵⁰, C(O)R⁵⁰, CO(O)R⁵⁰, OC(O)R⁵⁰, OC(O)OR⁵⁰, NH2, NHR⁵⁰, N(R⁵⁰)2, NHC(O)R⁵⁰, NR⁵⁰C(O)R⁵⁰, NHS(O)2R⁵⁰, NR⁵⁰S(O)2R⁵⁰, NHC(O)OR⁵⁰, NR⁵⁰C(O)OR⁵⁰, NHC(O)NH2, NHC(O)NHR⁵⁰, NHC(O)N(R⁵⁰)2, NR⁵⁰C(O)NHR⁵⁰, NR⁵⁰C(O)N(R⁵⁰)2, C(O)NH₂, C(O)NHR⁵⁰, C(O)N(R⁵⁰)₂, C(O)NHOH,

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C(O)NHOR⁵⁰, C(O)NHSO₂R⁵⁰, C(O)NR⁵⁰SO2R⁵⁰, SO2NH₂, SO₂NHR⁵⁰, SO2N(R⁵⁰)2, C(O)H,

C(O)OH, C(N)NH₂, C(N)NHR⁵⁰, C(N)N(R^5o)₂, CNOH, CNOCH3, OH, (O), CN, N₃, NO₂,

CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁵⁰ is R⁵¹,R⁵², R⁵³ or R⁵⁴;

R⁵¹ is phenyl, which is unfused or fused with benzene, heteroarene or R^51A; R^51A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵² is heteroaryl, which is unfused or fused with benzene, heteroarene or R^52A; R^52A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵³ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^53A; R^53A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁵⁴ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁵⁵, OR⁵⁵, SR⁵⁵, S(O)R⁵⁵, SO2R⁵⁵, C(O)R⁵⁵, CO(O)R⁵⁵, OC(O)R⁵⁵, OC(O)OR⁵⁵, NH2, NHR⁵⁵, N(R⁵⁵)₂, NHC(O)R⁵⁵, NR⁵⁵C(O)R⁵⁵, NHS(O)2R⁵⁵, NR⁵⁵S(O)2R⁵⁵, NHC(O)OR⁵⁵, NR⁵⁵C(O)OR⁵⁵, NHC(O)NH2, NHC(O)NHR⁵⁵, NHC(O)N(R⁵⁵)2, NR⁵⁵C(O)NHR⁵⁵, NR⁵⁵C(O)N(R⁵⁵)2, C(O)NH2, C(O)NHR⁵⁵, C(O)N(R⁵⁵)2, C(O)NHOH, C(O)NHOR⁵⁵, C(O)NHSO2R⁵⁵, C(O)NR⁵⁵SO2R⁵⁵, SO2NH2, SO2NHR⁵⁵, SO2N(R⁵⁵)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR⁵⁵, C(N)N(R⁵⁵)2, CNOH, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁵⁵ is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl; and wherein each foregoing cyclic moiety is independently unsubstituted, further unsubstituted, substituted or further substituted with one or two or three or four or five of independently selected R^57A, R⁵⁷, OR⁵⁷, SR⁵⁷, S(O)R⁵⁷, SO2R⁵⁷, C(O)R⁵⁷, CO(O)R⁵⁷, OC(O)R⁵⁷, OC(O)OR⁵⁷, NH2, NHR⁵⁷, N(R⁵⁷)2, NHC(O)R⁵⁷, NR⁵⁷C(O)R⁵⁷, NHS(O)2R⁵⁷, NR⁵⁷S(O)2R⁵⁷, NHC(O)OR⁵⁷, NR⁵⁷C(O)OR⁵⁷, NHC(0)NH2, NHC(O)NHR⁵⁷, NHC(O)N(R⁵⁷)2, NR⁵⁷C(O)NHR⁵⁷, NR⁵⁷C(O)N(R⁵⁷)2, C(O)NH₂, C(O)NHR⁵⁷, C(O)N(R⁵⁷)2, C(0)NH0H, C(O)NHOR⁵⁷, C(O)NHSO2R⁵⁷, C(O)NR⁵⁷SO2R⁵⁷, SO2NH₂, SO₂NHR⁵⁷, SO2N(R⁵⁷)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵⁷, C(N)N(R⁵⁷)₂, CNOH, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁵⁷ is R⁵⁸, R⁵⁹, R⁶⁰or R⁶¹;

R^57A is spirocyclyl;

5S 5SA 5SA

R is phenyl, which is unfused or fused with benzene, heteroarene or R ; R is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

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R⁵⁹ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^59A; R^59A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁰ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^60A; R^60A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶¹ is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶², OR⁶², SR⁶², S(O)R⁶², SO2R⁶², C(O)R⁶², CO(O)R⁶², OC(O)R⁶², OC(O)OR⁶², NH2, NHR⁶², N(R⁶²)2, NHC(O)R⁶², NR⁶²C(O)R⁶², NHS(O)2R⁶², NR⁶²S(O)2R⁶², NHC(O)OR⁶², NR⁶²C(O)OR⁶², NHC(O)NH2, NHC(O)NHR⁶², NHC(O)N(R⁶²)2, NR⁶²C(O)NHR⁶², NR⁶²C(O)N(R⁶²)2, C(O)NH₂, C(O)NHR⁶², C(O)N(R⁶²)2, C(O)NHOH, C(O)NHOR⁶², C(O)NHSO2R⁶², C(O)NR⁶²SO2R⁶², SO2NH₂, SO₂NHR⁶², SO2N(R⁶²)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶², C(N)N(R⁶²)₂, cnoh, cnoch₃, OH, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁶² is R⁶³, R⁶⁴, R⁶⁵ or R⁶⁶;

R⁶³ is phenyl, which is unfused or fused with benzene, heteroarene or R^63A; R^63A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁴ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^64A; R^64A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁵ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^65A; R^65A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁶⁶ is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶⁷, OR⁶⁷, SR⁶⁷, S(O)R⁶⁷, SO2R⁶⁷, C(O)R⁶⁷, CO(O)R⁶⁷, OC(O)R⁶⁷, OC(O)OR⁶⁷, NH2, NHR⁶⁷, N(R⁶⁷)2, NHC(O)R⁶⁷, NR⁶⁷C(O)R⁶⁷, NHS(O)2R⁶⁷, NR⁶⁷S(O)2R⁶⁷, NHC(O)OR⁶⁷, NR⁶⁷C(O)OR⁶⁷, NHC(O)NH2, NHC(O)NHR⁶⁷, NHC(O)N(R⁶⁷)2, NR⁶⁷C(O)NHR⁶⁷, NR⁶⁷C(O)N(R⁶⁷)2, C(O)NH₂, C(O)NHR⁶⁷, C(O)N(R⁶⁷)2, C(O)NHOH, C(O)NHOR⁶⁷, C(O)NHSO2R⁶⁷, C(O)NR⁶⁷SO2R⁶⁷, SO2NH₂, SO₂NHR⁶⁷, SO2N(R⁶⁷)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶⁷, C(N)N(R⁶⁷)₂, cnoh, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I substituents;

R⁶⁷ is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;

wherein the moieties represented by R^57A, R⁵⁸, R⁵⁹, R⁶⁰, R⁶³, R⁶⁴, R⁶⁵, and R⁶⁷ are unsubstituted or substituted with one or two or three or four of independently selected R⁶⁸, OR⁶⁸, SR⁶⁸, S(O)R⁶⁸, SO2R⁶⁸, C(O)R⁶⁸, CO(O)R⁶⁸, OC(O)R⁶⁸, OC(O)OR⁶⁸, NH2, NHR⁶⁸,

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N(R⁶⁸)2, NHC(O)R⁶⁸, NR⁶⁸C(O)R⁶⁸, NHS(O)2R⁶⁸, NR⁶⁸S(O)₂R⁶⁸, NHC(O)OR⁶⁸,

NR⁶⁸C(O)OR⁶⁸, NHC(O)NH2, NHC(O)NHR⁶⁸, NHC(O)N(R⁶⁸)2, NR⁶⁸C(O)NHR⁶⁸,

NR⁶⁸C(O)N(R⁶⁸)2, C(O)NH2, C(O)NHR⁶⁸, C(O)N(R⁶⁸)2, C(O)NHOH, C(O)NHOR⁶⁸,

C(O)NHSO₂R⁶⁸, C(O)NR⁶⁸SO2R⁶⁸, SO2NH₂, SO₂NHR⁶⁸, SO2N(R⁶⁸)2, C(O)H, C(O)OH,

C(N)NH₂, C(N)NHR⁶⁸, C(N)N(R⁶⁸)₂, CNOH, CNOCH3, OH, (O), CN, n₃, no₂, cf₃,

CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁶⁸ is R⁶⁹, R™, R⁷¹ or R⁷²;

R⁶⁹ is phenyl, which is unfused or fused with benzene, heteroarene or R^69A; R^69A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷⁰ is heteroaryl, which is unfused or fused with benzene, heteroarene or R^70A; R^70A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷¹ is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R^71A; R^71A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R⁷² is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁷³, OR⁷³, SR⁷³, S(O)R⁷³, SO2R⁷³, C(O)R⁷³, CO(O)R⁷³, OC(O)R⁷³, OC(O)OR⁷³, NH2, NHR⁷³, N(R⁷³)2, NHC(O)R⁷³, NR⁷³C(O)R⁷³, NHS(O)2R⁷³, NR⁷³S(O)2R⁷³, NHC(O)OR⁷³, NR⁷³C(O)OR⁷³, NHC(O)NH2, NHC(O)NHR⁷³, NHC(O)N(R⁷³)2, NR⁷³C(O)NHR⁷³, NR⁷³C(O)N(R⁷³)2, C(O)NH₂, C(O)NHR⁷³, C(O)N(R⁷³)2, C(O)NHOH, C(O)NHOR⁷³, C(O)NHSO2R⁷³, C(O)NR⁷³SO2R⁷³, SO2NH₂, SO₂NHR⁷³, SO2N(R⁷³)2, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷³, C(N)N(R⁷³)₂, CNOH, cnoch₃, oh, (O), CN, N₃, NO₂, CF₃, CF₂CF₃, OCF₃, OCF₂CF₃, F, Cl, Br or I;

R⁷³ is alkyl, alkenyl, alkenyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl; and ztq -7z\ i-j 7 the moieties represented by R , R , and R are unsubstituted or substituted with one or two or three or four of independently selected NH₂, C(O)NH₂, C(0)NH0H, SO₂NH₂, CF₃, CF₂CF₃, C(O)H, C(O)OH, C(N)NH₂, OH, (O), CN, N₃, no₂, cf₃, cf₂cf₃, ocf₃, OCF₂CF₃, F, Cl, Br or I.

In one embodiment of Formula (I), A¹ is N. In another embodiment of Formula (I), A¹is C(A²). In another embodiment of Formula (I), A¹ is C(A²); and A² is H.

In one embodiment of Formula (I), B¹ is NHC(O)R\ NHSO₂R\ OR¹, or NHR¹. In another embodiment of Formula (I), A¹ is C(A²); A² is H; and B¹ is NHR¹. In another embodiment of Formula (I), A¹ is C(A²); A² is H; and B¹ is OR¹. In another embodiment of Formula (I), A¹ is C(A²); A² is H; and B¹ is NI ISO^R¹. In another embodiment of Formula

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PCT/US2010/036844 (I), A¹ is C(A²); A² is H; and B¹ is NHC(O)R¹. In another embodiment of Formula (I), A¹ is

C(A²) or N; A² is H; and B¹ is NHR¹. In another embodiment of Formula (I), A¹ is C(A²) or

N; A² is H; and B¹ is OR¹. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is H;

and B¹ is NHSO2R¹. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is H; and B¹ is NHC(O)R¹.

In one embodiment of Formula (I), D¹ is H. In another embodiment of Formula (I),

A¹ is C(A²); A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (I), A¹ is C(A²); A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (I), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (I), A¹ is C(A²); A²is Η; B¹ is NHC(O)R¹; and D¹ is H. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (I), A¹ is C(A²) or N;

A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (I), A¹ is C(A²) or N; A²is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; and D¹ is H.

In one embodiment of Formula (I), E¹ is H. In another embodiment of Formula (I),

A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (I), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (I), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (I), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R’; D¹ is H; and E¹ is H.

In one embodiment of Formula (I), Y¹ is H, CN, NO2, F, Cl, Br, CF3, R¹⁷, or SO2R¹⁷. In another embodiment of Formula (I), Y¹ is NO2. In another embodiment of Formula (I), Y¹is Cl. In another embodiment of Formula (I), Y¹ is SO2R¹⁷; wherein R¹⁷ is as defined herein. In another embodiment of Formula (I), Y¹ is SO2R¹⁷; wherein R¹⁷ is alkyl. In another embodiment of Formula (I), Y¹ is R¹⁷; wherein R¹⁷ is alkynyl. In another embodiment of Formula (I), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO₂R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (I), A¹ is C(A²); A² is H; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (I), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO₂R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (I), A¹ is C(A²); A² is Η; B¹ is

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OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO2R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is H; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is H; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO₂R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (I), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl.

In one embodiment of Formula (I), R¹ is R², and R² is phenyl. In another embodiment of Formula (I), R¹ is R², and R² is phenyl which is substituted with NO₂, and NHR⁵⁷.

In one embodiment of Formula (I), R¹ is R⁴ or R⁵. In one embodiment of Formula (I), R¹ is R⁴. In one embodiment of Formula (I), R¹ is R⁵. In one embodiment of Formula (I), R¹is R⁴; and R⁴ is cycloalkyl, or heterocycloalkyl. In one embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl. In one embodiment of Formula (I), R¹ is R⁴; and R⁴ is heterocycloalkyl.

In one embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl; wherein R⁴ is unsubstituted or substituted as defined herein. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted as defined herein. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with R⁵⁷, NHR⁵⁷, or N(R⁵⁷)2. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; and R⁵⁷ is R⁶⁰. In another embodiment of Formula (I), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; and R⁶⁰ is heterocycloalkyl. In another embodiment of Formula (I), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl; wherein the heterocycloalkyl ring is morpholinyl or piperazinyl. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with N(R⁵⁷)2. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶¹, and R⁶¹ is alkyl which is unsubstituted. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)₂, R⁵⁷ is R⁶⁰, and R⁶⁰ is cycloalkyl which is unsubstituted. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is

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PCT/US2010/036844 cycloalkyl; wherein the cycloalkyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷, R⁵⁷ is R⁶⁰, and R⁶⁰ is heterocycloalkyl which is unsubstituted.

In one embodiment of Formula (I), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein R⁴ is unsubstituted or substituted as defined herein. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted as defined herein. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted with R⁵⁷. In another embodiment of Formula (I), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the heterocycloalkyl ring is substituted with one or two or three or four or five more R⁵⁷; SC&gt;2R⁵⁷,or OH, and R⁵⁷ is R⁶⁰ or R⁶¹. In another embodiment of Formula (I), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰ or R⁶¹; R⁶⁰ is cycloalkyl or heterocycloalkyl; and R⁶¹ is alkyl. In another embodiment of Formula (I), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl, wherein the heterocycloalkyl is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of Formula (I), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is cycloalkyl, wherein the cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of Formula (I), R¹ is R⁴; R⁴is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl ring is

57 61 61 substituted with one or two or three or four or five R ; R is R^D1;R^D1 is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl. In another embodiment of Formula (I), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl ring is

57 61 61 substituted with one or two or three or four or five R ; R is R^D1;R^D1 is alkyl; and the alkyl

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In one embodiment of Formula (I), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted. In one embodiment of Formula (I), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted with R⁷, OR⁷, N(R⁷)2, or OH.

In one embodiment of Formula (I), R⁷ is R¹⁰ or Rⁿ which are unsubstituted or substituted as defined herein. In another embodiment of Formula (I), R⁷ is R¹⁰ which is unsubstituted or substituted as defined herein. In another embodiment of Formula (I), R⁷ is Rⁿ which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (I), R¹⁰ is cycloalkyl or heterocycloalkyl which are unsubstituted or substituted as defined herein. In another embodiment of Formula (I), R¹⁰ is heterocycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (I), R¹⁰ is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxanyl, piperidinyl, piperizinyl, or pyrrolidinyl, which are unsubstituted or substituted as defined herein. In another embodiment of Formula (I), R¹⁰ is tetrahydropyranyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (I), R¹⁰ is morpholinyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (I), R¹⁰ is cycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (I), R¹⁰ is cyclohexyl which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (I), Rⁿ is alkyl which is unsubstituted. In another embodiment of Formula (I), Rⁿ is methyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (I), Rⁿ is alkyl, which is substituted as defined herein. In another embodiment of Formula (I), Rⁿ is alkyl, which is substituted with OR¹²,

R¹² is R¹⁶, and R¹⁶ is alkyl.

Another embodiment of this invention pertains to compounds of Formula (I), wherein

A¹ is N or C(A²);

A² is H;

B¹ is OR¹, NHC(O)R\ NHR¹, or NHSO2R¹;

D¹ is H;

E¹ is H; and

Y¹ is H, CN, NO2, F, Cl, Br, CF3, R¹⁷, or SO2R¹⁷;

R¹ is R², R⁴ or R⁵;

R² is phenyl;

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R⁴ is cycloalkyl, or heterocycloalkyl;

R⁵ is alkyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁷, OR⁷, N(R⁷)2, OH, F, Cl, Br or I;

R⁷ is R¹⁰or Rⁿ;

R¹⁰ is cycloalkyl or heterocycloalkyl;

Rⁿ is alkyl, each of which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br or I;

R¹⁷ is R²¹;

R²¹ is alkyl, or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br or I;

Z¹ is R²⁶;

Z² is R³⁰;

Z^1A and Z^2A are both absent;

L¹ is a R³⁷;

R²⁶ is phenylene;

R³⁰ is heterocycloalkylene;

R³⁷ is R^37A;

R is alkylene, alkenylene, or alkynylene, each of which is unsubstituted or substituted with one or two or three independently selected F, Cl, Br and I substituents;

Z³ is R³⁸, or R⁴⁰;

3S 38A 3SA

R is phenyl, which is unfused or fused with R ; R is heterocycloalkane;

R⁴⁰ is cycloalkenyl, or heterocycloalkenyl;

wherein the moieties represented by R andR are substituted (i.e., if Z andZ are absent) or further substituted (i.e., if Z^1A and Z^2A are present) with one or two or three or four of independently selected R⁴¹, OR⁴¹, or NHR⁴¹;

R⁴¹ is R⁴², R⁴³, or R⁴⁵;

R⁴² is phenyl, which is unfused or fused with heteroarene or R^42A; R^42A is heterocycloalkane;

R⁴³ is heteroaryl, which is unfused or fused with heteroarene;

R⁴⁵ is alkyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁴⁶, F, Cl, Br or I;

R⁴⁶ is R⁴⁷, or R⁴⁸;

R⁴⁷ is phenyl;

R is heteroaryl;

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PCT/US2010/036844 wherein the moieties represented by R⁴², R^42A, R⁴³, R^43A, R⁴⁴, R⁴⁴^ R⁴⁷, R^47A, R⁴⁸,

R^48A, R⁴⁹, and R^49A are independently substituted with one or two or three or four of independently selected R⁵⁰, OR⁵⁰, CO(O)R⁵⁰, NH2, NHR⁵⁰, N(R⁵⁰)2, NHC(O)R⁵⁰,

NHS(O)₂R⁵⁰, NHC(O)OR⁵⁰,, C(O)NH2, C(O)NHR⁵⁰, C(O)N(R⁵⁰)2, OH, (O), CN, no₂, cf₃,

F, Cl, Br or I;

R⁵⁰ is R⁵¹,R⁵², R⁵³ or R⁵⁴;

R⁵¹ is phenyl;

R⁵² is heteroaryl;

R⁵³ is cycloalkyl or heterocycloalkyl;

R⁵⁴ is alkyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁵⁵, OR⁵⁵, C(O)R⁵⁵, NH2, NHR⁵⁵, N(R⁵⁵)2, NR⁵⁵C(O)OR⁵⁵, C(O)N(R⁵⁵)₂, OH, F, Cl, Br or I;

R⁵⁵ is alkyl, phenyl, or heterocycloalkyl; and wherein each foregoing cyclic moiety is independently unsubstituted, further unsubstituted, substituted or further substituted with one or two or three or four or five of independently selected R^57A, R⁵⁷, OR⁵⁷, SO2R⁵⁷, C(O)R⁵⁷, CO(O)R⁵⁷, NH2, NHR⁵⁷, N(R⁵⁷)₂, OH, (O), CN, NO₂, F, Cl, Br or I;

R^57A is spirocyclyl;

R⁵⁷ is R⁵⁸, R⁶⁰ or R⁶¹;

R⁵⁸ is phenyl;

R⁶⁰ is cycloalkyl, or heterocycloalkyl;

R⁶¹ is alkyl, or alkenyl, each of which is unsubstituted or substituted with one or two or three of independently selected R⁶², OR⁶², N(R⁶²)2, C(O)N(R⁶²)2, OH, F, Cl, Br or I;

R⁶² is R⁶³, R⁶⁴, R⁶⁵ or R⁶⁶;

R⁶³ is phenyl;

R⁶⁴ is heteroaryl;

R⁶⁵ is cycloalkyl, or heterocycloalkyl;

R⁶⁶ is alkyl, each of which is unsubstituted or substituted with one or two or three of independently selected OR⁶⁷, F, Cl, Br or I substituents;

R⁶⁷ is alkyl;

wherein the moieties represented by R^57A, R⁵⁸, R⁶⁰, R⁶³, R⁶⁴, and R⁶⁵ are unsubstituted or substituted with one or two or three or four of independently selected R⁶⁸, F, Cl, Br or I;

R⁶⁸ is R⁷¹ or R⁷²;

R⁷¹ is heterocycloalkyl;

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R⁷² is alkyl which is is unsubstituted or substituted with one or two or three of independently selected OR⁷³, F, Cl, Br or I; and

R⁷³ is alkyl.

Still another embodiment pertains to compounds having Formula (I), which are

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(methylamino)phenoxy)-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)piperazin-1 -yl)-2-((2methyl-lH-indol-5-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl)methyl)piperazin-1 -yl)-2-((2methyl-lH-indol-5-yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-chlorophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-nitrophenoxy)-N-((3-nitro-4((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(hydroxymethyl)phenoxy)-N((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-((4-((3morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-((4-((3(dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-chlorophenoxy)-N-((4-((3morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((4-((3morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-chlorophenoxy)-N-((4-((3(dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide; 4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((4-((3(dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide; 4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((l-methyl-lH-indol-4yl)oxy)benzamide;

2-(3-(acetylamino)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-aminophenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(3-aminophenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-methoxyphenoxy)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(dimethylamino)phenoxy)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-cyanophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((2-methyl-l,3-benzothiazol-6yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((2-methyl-l,3-benzothiazol-5yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1, l'-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((2-methyl-l,3-benzothiazol-5yl)oxy)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(3-(dimethylamino)-3oxopropyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(2-(dimethylamino)-2oxoethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(3(dimethylamino)propyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(2(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-nitro-4-((tetrahydro-2H-pyran4-yl)methylamino)phenylsulfonylcarbamoyl)phenoxy)-N,N-dimethylbenzamide; 4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-morpholin-4ylphenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(2,4-dimethyl-l,3-thiazol-5yl)phenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide; 2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-1 -yl) -N- ((4- ((1 -methylpiperidin-4-yl) amino) -3 nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(3,5dichlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-4-(2-(dimethylamino)ethoxy)-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2(3-chlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3yl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(2(dimethylamino)ethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

100

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2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-isopropylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohex-l-en-l-yl)methyl)piperazin-l-yl)-N((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indazol-4-yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3difluorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-ethylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((3-nitro-4-((l,2,2,6,6-pentamethylpiperidin-4yl) amino)phenyl) sulfony l)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3difluorophenoxy)-N-((3-nitro-4-((l-tetrahydro-2H-pyran-4-ylpiperidin-4yl) amino)phenyl) sulfony l)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((7fluoro-lH-indol-5-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3difluorophenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

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2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((4'-chloro-4-(2-pyrrolidin-l-ylethyl)-l,r-biphenyl-2yl)methyl)piperazin-l-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3dichlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indazol-4-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohept-l-en-l-yl)methyl)piperazin-l-yl)N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-N-((4-((lmethylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)-2-(3(trifluoromethyl)phenoxy)benzamide;

4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetrahydroquinolin5 -yl)oxy )benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,5dichlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nittophenyl)sulfonyl)benzamide;

2-(2-chloro-4-fluorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclopent-1 -en-1 yl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indol-4-yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

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4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2chloro-3-(trifluoromethyl)phenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-cyclopropylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indol-4-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,5dichlorophenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((l-methyl-lH-indol-4-yl)oxy)N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-morpholin-4-ylphenoxy)-N((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((3-(3-morpholin-4-yl-3oxopropyl) -1 H-indol- 5 -y l)oxy)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-cyanophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((3-(3-morpholin-4-yl-3oxopropyl)-lH-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((3-(3-morpholin-4-ylpropyl)lH-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(lH-imidazol-l-yl)phenoxy)N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-nitrophenoxy)-N-((4((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)benzyl(ethyl)carbamate; tert-butyl 3-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)benzyl(ethyl)carbamate;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(acetylamino)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; tert-butyl 4-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)phenylcarbamate;

2-(1, r-biphenyl-2-yloxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; tert-butyl 3-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)phenylcarbamate;

2-(1, r-biphenyl-3-yloxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(2(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-morpholin-4-ylphenoxy)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((2-methyl-l,3-benzothiazol-5yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(3-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-l-carboxylate; 2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4((3- (dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(2-morpholin-4ylethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3-nitro-4-((tetrahydro-2Hpyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-((2-oxo-1,2,3,4-tetr ahydroquinolin-5yl)oxy)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

tert-butyl 4-(4-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((4-((3morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-l-carboxylate;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-pyridin-4-ylphenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-4-ylphenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-3-ylphenoxy)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(2-(dimethylamino)-2oxoethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1, l'-biphenyl-2-yl)methyl)piperazin-1 -yl)-2-(( 1 -methyl-1 H-benzimidazol-5 yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide; 4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(methylcarbamoyl)phenoxy)-N-(4(3-morpholinopropylamino)-3-nitrophenylsulfonyl)benzamide;

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4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazin-l-yl)-N-(4-(3-(dimethylamino)propylamino)3 -nitrophenylsulfonyl) -2-(3- (methylcarbamoyl)phenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(2-(dimethylamino)-2oxoethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((3-(3-(dimethylamino)propyl)lH-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3(hydroxymethyl)phenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((4-methoxybenzyl)oxy)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

N-(4-((4-aminotetrahydro-2H-pyran-4-yl)methylamino)-3-nitrophenylsulfonyl)-2-(3chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enyl)methyl)piperazin-lyl)benzamide;

4-(4-(l-(4'-chlorobiphenyl-2-yl)ethyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-(3-nitro-4((tetrahydro-2H-pyran-4-yl)methylamino)phenylsulfonyl)benzamide;

N- {[4-{4- [(4'-chloro-1,1 '-biphenyl-2-yl)methyl]piperazin-1 -yl} -2-(3,5 dichlorophenoxy)phenyl]sulfonyl}-4-[(l-methylpiperidin-4-yl)amino]-3-nitrobenzainide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

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2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(l-cyclopentylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(45 fluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-cyclopropylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-4-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- ί10 yl]methyl}piperazin-l-yl)-N-((4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2,3difluorophenoxy (benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -y 11 methyl} piperazin- 1 -yl)-2-(2fluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; 4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl | methyl} piperazin-1 -yl)-N-( {4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2fluorophenoxy)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2-(2fluorophenoxy)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2-(2fluorophenoxy)-N-((4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -y 11 methyl} piperazin- 1 -yl)-2-(2fluorophenoxy)-N-((4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide; 2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N-((4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

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2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(l-cyclopentylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l5 yl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-N-({4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl]sulfonyl)-2-(3fluorophenoxy)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-N-({4[(1 -cyclopentylpiperidin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2-(2,3 difluorophenoxy (benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-N-( {4[(1 -cyclopentylpiperidin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2-(215 fluorophenoxy)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(2,3difluorophenoxy)-N-((4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide; 4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-2-(2,3difluorophenoxy)-N-[(3-nitro-4-([l-(thien-3-ylmethyl)piperidin-420 yl] amino} phenyl) sulfonyl] benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(2-fluorophenoxy (benzamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(3-fluorophenoxy (benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(4-fluorophenoxy (benzamide; 4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2-(2,3 difluorophenoxy)-N-[(4-{[l-(2-fluoroethyl)piperidin-4-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(2-morpholin-4-ylethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

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2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl ] methyl }piperazin- l-yl)-N- [(4- {[3-(4-methylpiperazin-1 -yl)propyl] amino} -3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-[[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3yl]methyl}piperazin-l-yl)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-(2,3-difluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

N-([4-[(l-allylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -y 1) -2- (2,3 -difluorophenoxy)benzamide; 2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1y 11 methyl} piperazin-1 -yl)-N-( {4- [(1 -methylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1y 11 methyl} piperazin- l-yl)-N-({ 3 -nitro-4- [(3 -pyrrolidin-1 ylpropyl)amino]phenyl} sulfonyl)benzamide;

2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-([4-[(2-morpholin-4-ylethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-6-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-6-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl ] methyl }piperazin- l-yl)-N- [(4- {[(1 -methylpiperidin-4-yl)methyl] amino} -3nitrophenyl)sulfonyl]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(2,3difluorophenoxy)-N-[(4- {[(l-methylpiperidin-4-yl)methyl] amino} -3nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(4fluoro-lH-indol-5-yl)oxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[3(methoxymethoxy)-2-methylphenoxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-2-(3hydroxy-2-methylphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3yl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-(3-iodophenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N- [(4- {[ 1 -(2-hydroxyethyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(3-nitro-4-([l-(2-phenylethyl)piperidin-4yl] amino} phenyl) sulfonyl] benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(3,4dichlorophenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

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2-(2-chloro-3,5-difluorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3methoxyphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[3(hydroxymethyl)phenoxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l,4-dimethylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l,4-dimethylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([4-({l-[2-(2-methoxyethoxy)ethyl]piperidin-4-yl}amino)-3nitrophenyl] sulfonyl} benzamide;

2-(2-chloro-3-hydroxyphenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(3-nitro-4-([l-(3-phenylpropyl)piperidin-4yl] amino} phenyl) sulfonyl] benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([l-(2-methoxyethyl)piperidin-4-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N-( {4- [(1 -ethylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-isopropylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3hydroxyphenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-3-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3nitrophenyl)sulfonyl]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2-(2methoxyphenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin- l-yl)-2-(2methylphenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; 4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 - y 1) - 2-(3 methylphenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; 2-(2-chlorophenoxy)-4-(4- {[6-(4-chlorophenyl)-1,3-benzodioxol-5-yl]methyl}piperazin-lyl)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin- l-yl)-N-({ 4- [(4-methylpiperazin-1 -yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-[[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3y 11 methyl} piperazin- l-yl)-N-({ 4- [(4-methylpiperazin-1 -yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-(2,3-difluorophenoxy)-N-({4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-ly 11 methyl} piperazin-1 - y 1)-N- [ (4 - {[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

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2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-ly 1 ] methyl} piperazin-1 - y 1)-N- [ (4 - {[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-{[4-({l-[2-(dimethylamino)-2-oxoethyl]piperidin-4-yl}amino)3 -nitrophenyl] sulfonyl} benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([l-(2-morpholin-4-ylethyl)piperidin-4-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

N-[(4-([(4-aminotetrahydro-2H-pyran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(2chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl] methyl} piperazin-1 -yl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 - y 1)-N- [ (4 - {[(4-hydroxy-1 -methylpiperidin-4-yl)methyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 - y 1) - 2- [ (6 fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([(3S)-l-methylpyrrolidin-3-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([(3R)-l-methylpyrrolidin-3-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- l-en-l-yl]methyl}piperazin- l-yl)-N-({4[(1 -methylpiperidin-4-yl)amino] -3 -nitrophenyl} sulfony 1)-2- [3-(1 H-pyrrol-2yl)phenoxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N- [(4- {[(4-hydroxy-1 -methylpiperidin-4-yl)methyl]amino} -3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6,7difluoro-lH-indol-5-yl)oxy]-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6,7difluoro-1 H-indol-5-yl)oxy] -N-( {3 -nitro-4- [(1 -tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

tert-butyl 4-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-{[({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)amino]carbonyl[phenoxy)-ΙΗ-indole-1 -carboxylate;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[4-(dimethylamino)cyclohexyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[4-(diethylamino)cyclohexyl]amino}-3nitrophenyl)sulfonyl]benzamide;

Trans-2-(3-chlorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-([4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-{4-[l-(4'-chloro-l,r-biphenyl-2-yl)ethyl]piperazin-l-yl}-2-(2-chlorophenoxy)-N-({4-[(lmethylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1y I ] methyl} piperazin-1 -yl)-N-( {4- [(1 -methylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1y 11 methyl} piperazin- l-yl)-N-({ 4- [(4-methylpiperazin-1 -yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-4-yl)oxy]-N-([4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-4-yl)oxy]-N-([3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

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2-(2-chloro-4-hydroxyphenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(4-methylpiperazin-l-yl)amino]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

2-((1,3 -bis [(4-methylpiperazin-1 -yl)methyl] -1 H-indol-4-yl} oxy)-4-(4- {[2-(4-chlorophenyl)4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-[(4-{[3(dimethylamino)propyl] amino} - 3 -nitrophenyl) sulfonyl] benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[3 -(dimethylamino)propyl] amino} -3-nitrophenyl)sulfonyl] -2-((3- [(4-methylpiperazin-1 yl)methyl]- lH-indol-4-yl }oxy (benzamide;

2-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enyl)methyl)piperazin-l-yl)-2-(4-(lmethylpiperidin-4-ylamino)-3-nitrophenylsulfonylcarbamoyl)phenoxy)-N,Ndimethylbenzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({3nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]phenyl]sulfonyl)-2-{[2(trifluoromethyl) -1 H-indol-4-yl] oxy} benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-N-( {4[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-([6-(trifluoromethyl)-lH-indol-5yl]oxy} benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({3nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]phenyl]sulfonyl)-2-{[6(trifluoromethyl) -1 H-indol- 5 -yl] oxy} benzamide;

2-[(2-amino-l,3-thiazol-4-yl)methoxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(1 -tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6,7difluoro-lH-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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PCT/US2010/036844 tert-butyl 4-[(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-lyl)-2-{[({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)amino]carbonyl }phenoxy)methyl]-1,3-thiazol-2-ylcarbamate;

2-[(2-amino-l,3-thiazol-4-yl)methoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -y 1 ] methyl} piperazin-1 -yl)-N-( {4- [(1 -methylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(2-chlorophenyl)amino]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 - y 1) - 2- [ (6 methoxy-lH-indol-5-yl)oxy]-N-([3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(2-amino-l,3-benzothiazol-6-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -y 11 methyl} piperazin-1 -yl)-N-( {4- [(1 -methylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[(2-chlorophenyl)amino]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

tert-butyl 5-[5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl ] methyl} piperazi η-1 yl)-2-({ [(4-{ [3-(dimethylamino)propyl]amino}-3nitrophenyl)sulfonyl] amino} carbonyl)phenoxy] -1 H-indole-1 -carboxylate;

2-[(2-amino-l,3-benzothiazol-6-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(1 -tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-2- [(6fluoro- lH-indol-5 -yl)oxy ] -N- [(3 -nitro-4- {[3 -(3 -oxopiperazin-1 yl)propyl] amino} phenyl) sulfonyl] benzamide;

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Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6,7-difluoro-lH-indol-5-yl)oxy]-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 -nitrophenyl)sulfonyl] -2- [(6-fluoro-1Hindol-5-yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 -nitrophenyl)sulfonyl] -2- [(6,7-difluoro-1Hindol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6,7difluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([3-(3-oxopiperazin-lyl)propyl] amino} phenyl) sulfonyl] benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-({4-[(2-hydroxy- l-tetrahydro-2H-pyran-4-ylethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-{ [4-(( [4-(hydroxymethyl)tetrahydro-2H-pyran-4yl]methyl]amino)-3-nitrophenyl]sulfonyl]benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl]piperazin- l-yl)-2-[(6,7difluoro-1 H-indol-5-yl)oxy] -N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl]piperazin-l-yl)-N-({4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5 -yl)oxy ] -N- [(3 -nitro-4- {[1-(1,3 -thiazol-4-ylmethyl)piperidin-4yl] amino} phenyl) sulfonyl] benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)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-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-[(4-[[(3S,4R)-3-hydroxy-l-(l,3-thiazol-4-ylmethyl)piperidin-4yl] amino} -3 -nitrophenyl) sulfonyl] benzamide;

2-(2-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl }piperazin- l-yl)-N- {[4-( {[4-(hydroxymethyl)tetrahydro-2H-pyran-4yl] methyl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N- {[3-nitro-4-(tetrahydro-2H-pyran-4ylamino)phenyl] sulfonyl} benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 - y 1) - 2- [ (6 fluoro-lH-indol-5-yl)oxy]-N-([4-(morpholin-4-ylamino)-3-nitrophenyl]sulfonyl]benzamide; 2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-{[4-(morpholin-4-ylamino)-3-nitrophenyl]sulfonyl}benzamide;

2-(2-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-[(3-nitro-4-{[3-(3-oxopiperazin-lyl)propyl] amino} phenyl) sulfonyl] benzamide;

2-(6-aminopyridin-3-yl)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( l-[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]ethyl]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-4-yl)oxy]-N-[(3-nitro-4-([3-(3-oxopiperazin-lyl)propyl] amino} phenyl) sulfonyl] benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-[(3-nitro-4- {[(3S)-tetr ahydro-2H-pyran-3ylmethyl] amino} phenyl) sulfonyl] benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-[(3-nitro-4- {[(3R)-tetrahydro-2H-pyran-3ylmethyl] amino} phenyl) sulfonyl] benzamide;

tert-butyl 5-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)-3,4-dihydroisoquinoline-2( 1H)carboxylate;

2-[(6-aminopyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-5,5 -dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-((4-[(2-methoxyethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N- {[3-nitro-4-(tetrahydro-2H-pyran-4ylmethoxy)phenyl] sulfonyl} benzamide;

2-((3 -chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-((3 -chloro- lH-indol-4-yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin-1 -yl)-N-( {3nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl]sulfonyl)-2-[(2-oxo-2,3-dihydro1 H-indol-5 -yl)oxy]benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({3nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-[(2-oxo-2,3-dihydrolH-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-4-yl)oxy]-N-((4-[(2-methoxyethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

tert-butyl 5-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -y 1 ]methyl}piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate; tert-butyl 4-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -y 1 ]methyl}piperazin-1 yl)-2-([({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate;

2-[(6-aminopyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(2-aminopyridin-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2- [(5 -bromopyridin-3 -yl)oxy] -4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2Hpyran-3-yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-1-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

tert-butyl 5-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-3-ylcarbamate;

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2-[(5-aminopyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl(piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

tert-butyl 4-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -y 1 ]methyl}piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate;

2- [(3 -chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl(piperazin-l-yl)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(2-aminopyridin-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl(piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6hydroxypyridin-3-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-{[6-(benzyloxy)pyridin-3-yl]oxy (-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl(piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl(piperazin-l-yl)-N-{[4(l,4-dioxan-2-ylmethoxy)-3-nitrophenyl]sulfonyl}-2-[(6-fluoro-lH-indol-5yl)oxy (benzamide;

2-[(3-chloro-lH-indol-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N-( {4- [(4-methylpiperazin-1 -yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-N-( {4[(4-methylpiperazin-l-yl)amino]-3-nitrophenyl(sulfonyl)-2-[(2-oxo-2,3-dihydro-lH-indol-4yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl(piperazin-l-yl)-N-({4[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl(sulfonyl)-2-[(2-oxo-2,3-dihydro-lH-indol-4yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl(piperazin-l-yl)-N-({3nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]phenyl(sulfonyl)-2-[(2-oxo-2,3dihydro-1 H-indol-4-yl)oxy]benzamide;

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2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl] methyl} piperazin- l-yl)-N-{ [4-(1,4-dioxan-2-ylmethoxy)-3nitrophenyl] sulfonyl} benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-({4-[(l,4-dioxan-2-ylmethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-N-({4[(1,4-dioxan-2-ylmethyl)amino] -3 -nitrophenyl} sulfonyl)-2- [(6-fluoro-1 H-indol-5 yl)oxy]benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl(piperazin-l-yl)-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro2H-pyran-3-yl]methyl(piperazin-l-yl)-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl(piperazin-l-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl(piperazin-l-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl(piperazin-l-yl)N-([5-cyano-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl(-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

2-{[3-(2-aminoethyl)-lH-indol-5-yl]oxy(-4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex1 -en-1 -yl]methyl (piperazin- l-yl)-N-( {3-nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-( [3-(2-aminoethyl)-lH-indol-5-yl]oxy}-4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex1 -en-1 -yl]methyl (piperazin- l-yl)-N-( {4- [(4-methylpiperazin-1 -yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[5cyano-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

2-[(6-amino-5-fluoropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl ] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[5chloro-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-N({4- [(4-morpholin-4-ylcyclohexyl)amino] -3 -nitrophenyl} sulfony 1)-2- [(1 -oxo-1,2,3,4tetrahydroisoquinolin-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-{ [5cy ano-6-( 1,4-dioxan-2-ylmethoxy)pyridin-3 -yl] sulfonyl} -2- [(6-fluoro-1 H-indol-5 yl)oxy]benzamide;

N-[[5-bromo-6-(l,4-dioxan-2-ylmethoxy)pyridin-3-yl]sulfonyl]-4-(4-{[2-(4-chlorophenyl)4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

Trans-N-({5-bromo-6-[(4-morpholin-4-ylcyclohexyl)amino]pyridin-3-yl]sulfonyl)-4-(4-{[2(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({5cyano-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl} sulfonyl)-2-[(6-fluoro1 H-indol-5 -yl)oxy]benzamide;

2-(3-amino-5-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-lyl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl]piperazin-l-yl)-N- {[5cyano-6-(2-morpholin-4-ylethoxy)pyridin-3-yl]sulfonyl]-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-({4-[(4-morpholin-4-ylcyclohexyl)oxy]-3nitrophenyl} sulfonyl)benzamide;

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N-([5-bromo-6-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]pyridin-3-yl}sulfonyl)-4(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -y 11 methyl} piperazin-1 - y 1)-2 - [ (6fluoro-lH-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3dihydro-lH-indol-4-yl)oxy]benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-[[5-(4-chlorophenyl)-2,3,6,7-tetrahydrooxepin4-yl]methyl}piperazin-l-yl)-N-([4-[(4-morpholin-4-ylcyclohexyl)amino]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-[[5-(4-chlorophenyl)-2,3,6,7-tetrahydrooxepin4-yl]methyl}piperazin-l-yl)-N-([4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-([4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-([4-[(4-morpholin-4-ylbut-2-ynyl)oxy]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-2- [(6fluoro- lH-indol-5 -yl)oxy ] -N- [(4- {[ 1 -(methylsulfonyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-N({4-[(4-morpholin-4-ylcyclohexyl)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydrolH-indol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(2-methoxyethyl)amino]-3-nitrophenyl}sulfonyl)-2-[(2-oxo-2,3-dihydro-lH-indol-4yl)oxy]benzamide;

4- (4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[5ethynyl-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lH-indol5- yl)oxy]benzamide;

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4-(4-( |4-(4-chlorophenyl )-6,6-dimethyl-5,6-dihydro-2I I-pyran-3-yl|methyl [piperazin- 1-yl)N-([5-ethynyl-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N-( {4-[(4-morpholin-4ylcyclohexy l)amino] - 3 -nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({5cyano-6-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)oxy]pyridin-3-yl}sulfonyl)-2-[(6-fluorolH-indol-5 -yl)oxy]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} piperazin-1 -yl)-2- [(6-fluorolH-indol-5 -yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(4-ethylmorpholin-3 -yl)methoxy] -3 -nitrophenyl} sulfonyl)-2- [(6-fluoro- lH-indol-5 yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([(3S)-l-tetrahydro-2H-pyran-4-ylpiperidin-3yl] amino} phenyl) sulfonyl] benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-((4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- l-en-l-yl]methyl}piperazin- l-yl)-N-({4[(1,1 -dioxidothiomorpholin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2- [(6-fluoro-1 H-indol-5yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydrofuran-3ylmethyl)amino]phenyl} sulfonyl)benzamide;

Trans-N-((5-bromo-6-[(4-morpholin-4-ylcyclohexyl)oxy]pyridin-3-yl}sulfonyl)-4-(4-{ [2-(4chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

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Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-N[(4-([4-(dicyclopropylamino)cyclohexyl] amino} -3-nitrophenyl)sulfonyl] -2- [(6-fluoro-1Hindol-5-yl)oxy]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-{[4-(tetrahydro-2H-pyran-4ylamino)cyclohexyl]amino}phenyl)sulfonyl]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-{[4-(4-tetrahydro-2H-pyran-4-ylpiperazin-lyl)cyclohexyl] amino} phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-[(4-{[(4-hydroxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-({3-[3(dimethylamino)propyl]-lH-indol-4-yl]oxy)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl]piperazin- l-yl)-2-({3-[3(dimethylamino)propyl] - lH-indol-4-yl} oxy)-N-( {4- [(4-methylpiperazin-1 -yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-N-( {4[(l-cyclopropyl-4-fluoropiperidin-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-{ [1-(4methoxybenzyl)-1H-1,2,3-benzotriazol-4-yl]oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl] methyl} piperazin-1 -yl)-N-( {4- [(4-methylpiperazin-1 -yl) amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-l-yl]methyl]piperazin-l-yl)-N-{ [4-(1,4-dioxan-2-ylmethoxy)-3nitrophenyl] sulfonyl} benzamide;

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Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N - [(4- {[(4methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-([4-[(l,4-dioxan-2-ylmethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl} piperazin-1 -yl)-N-( {4- [(3 -morpholin-4-ylpropyl)amino] -3 [(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-([4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl] methyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -y 1 ] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-amino-5-(5-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-lyl)-2-[[([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)nicotinamide;

2-[(6-amino-5-cyanopyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -y 1 ] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-[(4-[[(3R)-l-(2,2-difluoroethyl)pyrrolidin-3-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -y 1 ] methyl} piperazin-1 -yl)-N-( {4- [(1 -methylpiperidin-4-yl)amino] -3 [(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

2- {[6-(acetylamino)pyridin-3-yl]oxy} -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enl-yl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 - y 1) - 2-({6 [(methylsulfonyl)amino]pyridin-3-yl}oxy)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin- l-yl)-N- {[4({(3R)-1 - [2-fluoro-1 -(fluoromethyl)ethyl]pyrrolidin-3 -yl} amino)-3 -nitrophenyl] sulfonyl} -2[(6-fluoro-lH-indol-5-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {4- [(1 -cyclopropylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( [4- [(4-methylpiperazin-1 -yl) amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-([4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-({4-[(l,4-dioxan-2-ylmethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-methylpyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[(4-fluorotetrahydro-2H-pyran-4-yl)methyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(1 -oxetan-3 -ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-isopropylpyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex1- en-l-yl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2- [(6-amino-5-cyclopropylpyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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Trans-2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N - [(4- {[(4methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 - y 1) - 2- [ (3 methyl-2-oxo-2,3-dihydro-lH-benzimidazol-4-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-pyran4-ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl]methyl} piperazin-1 -yl)-N - [(4- {[(4-cyclopropylmorpholin-2-yl)methyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl]methyl} piperazin-1 -yl)-N - [ (4- {[ (3 R) -1 -cyclopropylpyrrolidin-3 -yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl] methyl} piperazin-1 -yl)-N- {[4-( {4-fluoro-1 - [2-fluoro-1 (fluoromethyl)ethyl]piperidin-4-yl}methoxy)-3-nitrophenyl]sulfonyl}benzamide; tert-butyl 6-bromo-4-(5-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-2-[[([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate; tert-butyl 4-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enyl)methyl)piperazin-l-yl)2-(3-nitro-4-((tetrahydro-2H-pyran-4yl)methylamino)phenylsulfonylcarbamoyl)phenoxy)pyridine-2,6-diyldicarbamate;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-{ [6(cyclopropylamino)pyridin-3-yl]oxy} -N-( {3-nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2({6-[(2,2-difluoroethyl)amino]pyridin-3-yl]oxy)-N-[(4-{[(4methoxycyclohexyl)methyl]amino]-3-nitrophenyl)sulfonyl]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 - y 1) - 2-({6 [(2,2-difluoroethyl)amino]pyridin-3-yl]oxy)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-{[5-chloro-6-(methylamino)pyridin-3-yl]oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl ] methyl} piperazin-1 -yl)-N-( {4- [({4- [2-fluoro-1 -(fluoromethyl)ethyl]morpholin-2yl} methyl)amino]-3-nitrophenyl} sulfonyl)benzamide;

2-[(2-amino-6-bromopyridin-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(2,6diaminopyridin-4-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-([3-nitro-4-(tetrahydro-2H-pyran-4ylmethoxy)phenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl} piperazin-1 -yl)-N- {[4-( {(3R)-1 - [2-fluoro-1 -(fluoromethyl)ethyl]piperidin-3 yl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

tert-butyl 5-bromo-4-(5-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-2-([({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(4chloro-lH-pyrrolo[2,3-b]pyridin-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({ 3nitro-4- [(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl} sulfony 1)-2-( {6-((2,2,2trifluoroethyl)amino]pyridin-3-yl} oxy)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-[(4-([(4-hydroxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro2H-pyran-3-yl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)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]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl ] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydrofuran-3ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-[[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2Hpyran-3-yl]methyl}piperazin-l-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-({9-(4-chlorophenyl)-3-[2-fluoro-l(fluoromethyl)ethyl]-3-azaspiro[5.5]undec-8-en-8-yl}methyl)piperazin-l-yl]-N-({3-nitro-4[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[9-(4-chlorophenyl)-3-isopropyl-3azaspiro[5.5]undec-8-en-8-yl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-[[l-(N,N-dimethylglycyl)-4fluoropiperidin-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] me thyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N- {[4-( {(3R)-1 - [2-fluoro-1 -(fluoromethyl)ethyl]pyrrolidin-3 yl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

2-[(2-amino-5-bromopyridin-4-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len- 1-yl] methyl] piperazin- l-yl)-N-[(4- {[(4,4-difluorocyclohexyl)methyl]amino} -3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-({4'-chloro-3-[2-(dimethylamino)ethoxy]-l,l·biphenyl-2-yl} methyl)piperazin-1 -yl] -N-( {3-nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[[5-chloro-6-([(3R)-l-[2-fluoro-l(fluoromethyl)ethyl]pyrrolidin-3 -yl} methoxy )pyridin-3 -yl] sulfonyl} -4-(4- {[2-(4chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl }piperazin-1 -yl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-[[(3R)-1-(2,2difluoroethyl)pyrrolidin-3-yl] methoxy }pyridin-3-yl)sulfonyl]-4-(4- {[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide;

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Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N - [(4- {[(4cyanocyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-([5-fluoro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl}sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-[[l-(2,2-difluoroethyl)-4fluoropiperidin-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]phenyl} sulfonyl)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl] methyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N- {[6-( {4-fluoro-1 - [2-fluoro-1 (fluoromethyl)ethyl]piperidin-4-yl}methoxy)-5-(trifluoromethyl)pyridin-3yl] sulfonyl} benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({ 3nitro-4- [(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl} sulfony 1)-2- [2-( lH-pyrazol-4yl)phenoxy]benzamide;

2-[2-(2-aminopyridin-3-yl)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en1- yl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({3nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl]sulfonyl)-2-[2-(lH-pyrazol-5yl)phenoxy]benzamide;

2- [(6-amino-5-chloropyridin-3-yl)oxy]-N-([5-chloro-6-[(4,4difluorocyclohexyl)methoxy]pyridin-3-yl} sulfony 1)-4-(4- {[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] me thyl} piperazin-1 -yl)benzamide; N-([5-chloro-6-[(4,4-difluorocyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{ [4-(4chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl]piperazin-l-yl)-2-[(6-fluoro1 H-indol-5 -yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-[(4{[(4,4-difluorocyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

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N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{ [2-(4chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl Jpiperazin-1-yl)-2-[(6-fluoro-1Hindol-5-yl)oxy]benzamide;

N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{ [4-(4chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)-2-[(6-fluorolH-indol-5 -yl)oxy]benzamide;

N-({5-chloro-6-[(trans-4-hydroxycyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{ [2-(4chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6-fluoro-lHindazol-4-yl)oxy]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 -y 1 ] methyl} piperazin-1 -yl)-2- [(6-fluorolH-indazol-4-yl)oxy]benzamide;

tert-butyl 5-[(4-{4-[({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3yl} sulfonyl)carbamoyl] -3 - [(6-fluoro- lH-indol-5 -yl)oxy]phenyl} piperazin-1 -yl)methyl] -4-(4chlorophenyl)-3,6-dihydropyridine-1 (2H)-carboxylate;

N-([5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl}sulfonyl)-4-(4{[4-(4-chlorophenyl)-1-(1,3-difluoropropan-2-yl)-1,2,5,6-tetr ahydropyridin-3yl]methyl}piperazin-l-yl)-2-[(6-fluoro-lH-indol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indazol-4-yl)oxy]-N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

N-( {5 -chloro-6- [(trans-4-hydroxycyclohexyl)methoxy]pyridin-3 -yl} sulfonyl)-4-(4- {[2-(4chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl (piperazin-1 -yl)-2- [(7-fluoro- 1Hindazol-4-yl)oxy]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} piperazin-1 -yl)-2- [(7-fluorolH-indazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-{[3-nitro-4-([[4-(oxetan-3-yl)morpholin-2yl] methyl} amino)phenyl] sulfonyl} benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2- [(6fluoro- lH-indol-5 -yl)oxy ] -N- {[3 -nitro-4-( {[4-(oxetan-3 -yl)morpholin-2yl] methyl} amino)phenyl] sulfonyl} benzamide;

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4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 - y 1) - 2- [ (7 fluoro-lH-indazol-4-yl)oxy]-N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

N-({5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6-fluorolH-indazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[5chloro-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(3-methyl-2-oxo-2,3dihydro-lH-benzimidazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(3-methyl-2-oxo2,3-dihydro-lH-benzimidazol-4-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[(trans-4-methoxycyclohexyl)methyl]amino} -3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo2,3-dihydro-lH-benzimidazol-4-yl)oxy]benzamide;

2- [(3-amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-[(4-{[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2- [(3-amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 y 1 ] methyl} piperazin- l-yl)-N-({ 4- [(4-fluorotetrahydro-2H-pyran-4-yl)methoxy] -3 nitrophenyl} sulfonyl)benzamide;

2-[(3-amino-lH-indazol-4-yl)oxy]-N-([5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-ly 11 methyl} piperazin-1 -yl)benzamide;

2- [(3-amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-l-yl]methyl}piperazin-l-yl)-N-[(4-[[4-fluoro-l-(oxetan-3-yl)piperidin-4-yl]methoxy}-3nitrophenyl)sulfonyl]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-2-[(6fluoro-lH-indazol-4-yl)oxy]-N-((4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl ] methyl} piperazin-1 -yl)-N - [(4- {[(trans-4-hydroxy-4methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2- [(3 -amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-[(4-[[(trans-4-methoxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-l-yl]methyl}piperazin-l-yl)-N-([4-[(cis-4-hydroxy-4-methylcyclohexyl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2- [(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[(cis-4-hydroxy-4-methylcyclohexyl)methyl] amino} 3- nitrophenyl)sulfonyl]benzamide;

4- (4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[3chloro-4-(tetrahydro-2H-pyran-4-ylmethoxy)phenyl]sulfonyl]-2-[(3-methyl-2-oxo-2,3dihydro-lH-benzimidazol-4-yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[(4-cyclopropylmorpholin-2-yl)methyl]amino]-3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo2,3-dihydro-lH-benzimidazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-l-yl]methyl}piperazin-l-yl)-N-[[3-nitro-4-(2-oxaspiro[3.5]non-7ylmethoxy)phenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-l-yl]methyl}piperazin-l-yl)-N-([4-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl]methyl }piperazin- l-yl)-N- {[4-( {[(2S)-4-cyclopropylmorpholin-2-yl]methyl} amino)3 -nitrophenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([5-chloro-6-[(trans-l-fluoro-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] me thyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([5-chloro-6-[(cis-l-fluoro-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide;

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2-[(3-amino-lH-indazol-4-yl)oxy]-N-([5-chloro-6-[(trans-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] methyl }piperazin-1 -yl)benzamide;

N-([5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-2-[(3chloro-lH-indazol-4-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-1yl] methyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-[(4-{[(cis-4-ethyl-4-hydroxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-{[3-nitro-4-({[(2S)-4-(oxetan-3-yl)morpholin-2yl] methyl} amino)phenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {5 -nitro-6- [(tetrahydro-2H-pyran-4ylmethyl)amino]pyridin-3-yl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(2-oxaspiro[3.5]non-7ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-{[4-({[trans-4-(morpholin-4yl)cyclohexyl] methyl} amino) - 3 -nitrophenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[cis-4-(morpholin-4-yl)cyclohexyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({5cyano-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-2-[(6-fluoro1 H-indazol-4-yl)oxy]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl }piperazin- l-yl)-N- {[4-( {[4-( {[4-(methoxymethyl)cyclohexyl]methyl} amino)3 -nitrophenyl] sulfonyl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-[(3-nitro-4-[[(3R)-l-(oxetan-3-yl)pyrrolidin-3yl] amino} phenyl) sulfonyl] benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-[(3-nitro-4-{[(3S)-l-(oxetan-3-yl)pyrrolidin-3yl] amino} phenyl) sulfonyl] benzamide;

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)benzoyl} sulfamoy 1)-2nitrophenyl] morpholine-4-c arboxamide;

N-[4-({2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)benzoyl} sulfamoy l)-2-nitrophenyl] -4cyanopiperidine-1 -carboxamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({3-nitro-4[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl} sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4-[(4morpholin-4-ylcyclohexy 1) amino] - 3 -nitrophenyl} sulfonyl)benzamide; and therapeutic ally acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to [3-chloro-5-(5-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- {[({3-nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl]sulfonyl)amino]carbonyl}phenoxy)-2-iminopyridin-l(2H)-yl]methyl dihydrogen phosphate; and therapeutically acceptable salts, and metabolites thereof.

Still another embodiment pertains to 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-[(3-nitro-4{[(3R)-l-(oxetan-3-yl)pyrrolidin-3-yl]amino]phenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to Trans-4-(4- {[2-(4-chlorophenyl)-4,4dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lH-indol-5-yl)oxy]-N-[(3nitro-4-{[4-(tetrahydro-2H-pyran-4-ylamino)cyclohexyl]amino]phenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lH-indol-5-yl)oxy]-N-[(3nitro-4-{[(3S)-tetrahydro-2H-pyran-3-ylmethyl]amino]phenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

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Still another embodiment pertains to 4-(4- {[2-(4-chloropheny 1)-4,4dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6-fluoro- lH-indol-4-yl)oxy] -N- [(3 nitro-4-[[3-(3-oxopiperazin-l-yl)propyl]amino}phenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 2-(2-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)4.4- dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-[(4-{[3(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-{[2-(4-chloropheny 1)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -y 1)-2-(3,4-dichlorophenoxy)-N-( {4 - [ (1 methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)4.4- dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-N-((4-((l-isopropylpiperidin-4yl)amino)-3-nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-((4'-chloro-l,l'-biphenyl-2yl)methyl)piperazin-l-yl)-2-(2-(2-(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-((4'-chloro-l,l'-biphenyl-2yl)methyl)piperazin-l-yl)-2-((2-methyl-l,3-benzothiazol-6-yl)oxy)-N-((3-nitro-4((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-((4'-chloro-l,l'-biphenyl-2yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

Still another embodiment pertains to 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex1 -en-1 -yl)methyl)piperazin-1 -yl)-2-((2-methyl- lH-indol-5-yl)oxy)-N-((4-(( 1 methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

In another aspect, the present invention provides compounds of Formula (II)

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Y¹

<img file="NZ600084A_D0004.tif" />

z³ (Π) and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof, wherein A¹, B¹, D¹, E¹, Y¹, Z², L¹, and Z³ are as described herein for Formula (I), n is 0, 1, 2, or 3; describing the number of additional substituents on R²⁶, and R¹⁰⁰ is as described for substituents on R²⁶, m is 1, 2, 3, 4, or 5; describing the number of substituents on R⁴², and R¹⁰¹ is as described for substituents on R⁴².

In one embodiment of Formula (II), A¹ is N. In another embodiment of Formula (II), A¹ is C(A²). In another embodiment of Formula (II), A¹ is C(A²); and A² is H.

In one embodiment of Formula (II), B¹ is NHQCOR¹, NHSO2R¹, OR¹, or NHR¹. In another embodiment of Formula (II), A¹ is C(A²); A² is H; and B¹ is NHR¹. In another embodiment of Formula (II), A¹ is C(A²); A² is H; and B¹ is OR¹. In another embodiment of Formula (II), A¹ is C(A²); A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (II), A¹ is C(A²); A² is H; and B¹ is NHC(O)R¹. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is H; and B¹ is NHR¹. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is H; and B¹ is OR¹. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is H; and B¹ is NHC(O)R’.

In one embodiment of Formula (II), D¹ is H. In another embodiment of Formula (II), A¹ is C(A²); A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (II), A¹ is C(A²); A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (II), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (II), A¹ is C(A²);

A² is Η; B¹ is NHC(O)R¹; and D¹ is H. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (II), A¹ is C(A²)

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N; A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; and D¹ is H.

In one embodiment of Formula (II), E¹ is H. In another embodiment of Formula (II), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (II), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (II), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (II), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R’; D¹ is H; and E¹ is H.

In one embodiment of Formula (II), Y¹ is H, CN, NO2, F, Cl, Br, CF3, R¹⁷, or SO2R¹⁷. In another embodiment of Formula (II), Y¹ is NO2. In another embodiment of Formula (II),

Y¹ is Cl. In another embodiment of Formula (II), Y¹ is SO2R¹⁷; wherein R¹⁷ is as defined herein. In another embodiment of Formula (II), Y¹ is SO2R¹⁷; wherein R¹⁷ is alkyl. In another embodiment of Formula (II), Y¹ is R¹⁷; wherein R¹⁷ is alkynyl. In another embodiment of Formula (II), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO2R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (II), A¹ is C(A²); A² is H; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (II), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (II), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO₂ or SO₂R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is H; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (II), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl.

In one embodiment of Formula (II), R¹ is R², and R² is phenyl. In another embodiment of Formula (II), R¹ is R², and R² is phenyl which is substituted with NO2, and NHR⁵⁷.

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In one embodiment of Formula (II), R¹ is R⁴ or R⁵. In one embodiment of Formula (II), R¹ is R⁴. In one embodiment of Formula (II), R¹ is R⁵. In one embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl, or heterocycloalkyl. In one embodiment of Formula (II),

R¹ is R⁴; and R⁴ is cycloalkyl. In one embodiment of Formula (II), R¹ is R⁴; and R⁴ is heterocycloalkyl.

In one embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein R⁴ is unsubstituted or substituted as defined herein. In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted as defined herein. In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with R⁵⁷, NHR⁵⁷, or N(R⁵⁷)2. In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; and R⁵⁷ is R⁶⁰. In another embodiment of Formula (II), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; and R⁶⁰ is heterocycloalkyl. In another embodiment of Formula (II), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl; wherein the heterocycloalkyl ring is morpholinyl or piperazinyl. In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with N(R⁵⁷)2- In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2. In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶¹, and R⁶¹ is alkyl which is unsubstituted. In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶⁰, and R⁶⁰ is cycloalkyl which is unsubstituted. In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷, R⁵⁷ is R⁶⁰, and R⁶⁰ is heterocycloalkyl which is unsubstituted.

In one embodiment of Formula (II), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein R⁴is unsubstituted or substituted as defined herein. In another embodiment of Formula (II), R¹ is

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R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted as defined herein. In another embodiment of Formula (II), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted with R⁵⁷. In another embodiment of Formula (II), R¹is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the heterocycloalkyl ring is substituted with one or two or three or four or five more R⁵⁷; SC&gt;2R⁵⁷,or OH, and R⁵⁷ is R⁶⁰ or R⁶¹. In another embodiment of Formula (II), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰ or R⁶¹; R⁶⁰ is cycloalkyl or heterocycloalkyl; and R⁶¹ is alkyl. In another embodiment of Formula (II), R¹is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl, wherein the heterocycloalkyl is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of Formula (II), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is cycloalkyl, wherein the cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of Formula (II), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl, or

57 61 61 piperizinyl ring is substituted with one or two or three or four or five R ; R is R^D1;R^D1 is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl. In another embodiment of Formula (II), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl, or

57 61 61 piperizinyl ring is substituted with one or two or three or four or five R ; R is R^D1;R^D1 is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl; wherein the Ci-alkyl, C2-alkyl, or C3alkyl are unsubstituted or substituted.

In one embodiment of Formula (II), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted. In one embodiment of Formula (II), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted with R⁷, OR⁷, N(R⁷)2, or OH.

In one embodiment of Formula (II), R⁷ is R¹⁰ or Rⁿ which are unsubstituted or substituted as defined herein. In another embodiment of Formula (II), R⁷ is R¹⁰ which is unsubstituted or substituted as defined herein. In another embodiment of Formula (II), R⁷ is Rⁿ which is unsubstituted or substituted as defined herein.

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In one embodiment of Formula (II), R¹⁰ is cycloalkyl or heterocycloalkyl which are unsubstituted or substituted as defined herein. In another embodiment of Formula (II), R¹⁰ is heterocycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (II), R¹⁰ is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxanyl, piperidinyl, piperizinyl, or pyrrolidinyl, which are unsubstituted or substituted as defined herein. In another embodiment of Formula (II), R¹⁰ is tetrahydropyranyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (II), R¹⁰ is morpholinyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (II), R¹⁰ is cycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (II), R¹⁰ is cyclohexyl which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (II), Rⁿ is alkyl which is unsubstituted. In another embodiment of Formula (II), Rⁿ is methyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (II), Rⁿ is alkyl, which is substituted as defined herein. In another embodiment of Formula (II), Rⁿ is alkyl, which is substituted with OR¹², R¹² is R¹⁶, and R¹⁶ is alkyl.

In one embodiment of Formula (II), n is 0 and m is 1. In another embodiment of Formula (II), n is 0 and m is 2.

Still another embodiment pertains to compounds having Formula (II), which are 4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(methylamino)phenoxy)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-chlorophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-nitrophenoxy)-N-((3-nitro-4((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(hydroxymethyl)phenoxy)-N((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-((4-((3morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-((4-((3(dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-chlorophenoxy)-N-((4-((3morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((4-((3morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-chlorophenoxy)-N-((4-((3(dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-chlorophenoxy)-N-((4-((3(dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide;

2-(3-(acetylamino)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-aminophenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(3-aminophenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-methoxyphenoxy)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(dimethylamino)phenoxy)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-cyanophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(3-(dimethylamino)-3oxopropyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(2-(dimethylamino)-2oxoethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(3(dimethylamino)propyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2-(2(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(5-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-nitro-4-((tetrahydro-2H-pyran4-yl)methylamino)phenylsulfonylcarbamoyl)phenoxy)-N,N-dimethylbenzamide; 4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(2((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-morpholin-4ylphenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(2,4-dimethyl-l,3-thiazol-5yl)phenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(3,5dichlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-4-(2-(dimethylamino)ethoxy)-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2(3-chlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3yl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(2(dimethylamino)ethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

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2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-isopropylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l5 yl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohex-l-en-l-yl)methyl)piperazin-l-yl)-N((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,310 difluorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide; 2-(3-bromophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l15 yl)methyl)piperazin-l-yl)-N-((4-((l-ethylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((3-nitro-4-((l,2,2,6,6-pentamethylpiperidin-4yl) amino)phenyl) sulfony l)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3difluorophenoxy)-N-((3-nitro-4-((l-tetrahydro-2H-pyran-4-ylpiperidin-4yl) amino)phenyl) sulfony l)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3difluorophenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-((4'-chloro-4-(2-pyrrolidin-l-ylethyl)-l,r-biphenyl-2yl)methyl)piperazin-l-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-430 ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,3dichlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)cyclohept-l-en-l-yl)methyl)piperazin-l-yl)N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

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4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-N-((4-((lmethylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)-2-(3(trifluoromethyl)phenoxy)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,5dichlorophenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(2-chloro-4-fluorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclopent-1 -en-1 yl)methyl)piperazin-l-yl)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2chloro-3-(trifluoromethyl)phenoxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl)methyl)piperazin-l-yl)-N-((4-((l-cyclopropylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-(2,5dichlorophenoxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-morpholin-4-ylphenoxy)-N((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-cyanophenoxy)-N-((3-nitro4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4((dimethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(lH-imidazol-l-yl)phenoxy)N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-nitrophenoxy)-N-((4((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)benzyl(ethyl)carbamate; tert-butyl 3-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)benzyl(ethyl)carbamate;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3((ethylamino)methyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(acetylamino)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; tert-butyl 4-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)phenylcarbamate;

2-(1, r-biphenyl-2-yloxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; tert-butyl 3-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)phenylcarbamate;

2-(1, r-biphenyl-3-yloxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide; 4-(4-((4'-chloro-1, r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(2(dimethylamino)ethyl)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((3nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-morpholin-4-ylphenoxy)-N((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;

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PCT/US2010/036844 tert-butyl 4-(3-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((3-nitro-4((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-l-carboxylate; 2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4((3- (dimethylamino)propyl) amino)- 3 -nitrophenyl) sulfonyl)benzamide;

2-(3-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(2-morpholin-4ylethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

2-(4-(benzyloxy)phenoxy)-4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

tert-butyl 4-(4-(5-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((((4-((3morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)amino)carbonyl)phenoxy)phenyl)piperazine-l-carboxylate;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(3-pyridin-4-ylphenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-4-ylphenoxy)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3-morpholin-4ylpropyl)amino)-3-nitrophenyl)sulfonyl)-2-(4-pyridin-3-ylphenoxy)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(4-(2-(dimethylamino)-2oxoethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(methylcarbamoyl)phenoxy)-N-(4(3-morpholinopropylamino)-3-nitrophenylsulfonyl)benzamide;

4-(4-((4'-chlorobiphenyl-2-yl)methyl)piperazin-l-yl)-N-(4-(3-(dimethylamino)propylamino)3 -nitrophenylsulfonyl) -2-(3- (methylcarbamoyl)phenoxy)benzamide; 4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-(3-(2-(dimethylamino)-2oxoethoxy)phenoxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-(3(hydroxymethyl)phenoxy)benzamide;

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N-(4-((4-aminotetrahydro-2H-pyran-4-yl)methylamino)-3-nitrophenylsulfonyl)-2-(3chlorophenoxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enyl)methyl)piperazin-lyl)benzamide;

4-(4-(l-(4'-chlorobiphenyl-2-yl)ethyl)piperazin-l-yl)-2-(2-chlorophenoxy)-N-(3-nitro-45 ((tetrahydro-2H-pyran-4-yl)methylamino)phenylsulfonyl)benzamide;

N- {[4-{4- [(4'-chloro-1,1 '-biphenyl-2-yl)methyl]piperazin-1 -yl} -2-(3,5 dichlorophenoxy)phenyl]sulfonyl}-4-[(l-methylpiperidin-4-yl)amino]-3-nitrobenzamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-320 nitrophenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl} piperazin-1 -yl)-N-( {4- [(1 -cyclopentylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-2-(425 fluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; 2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(l-cyclopropylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-4-fluorophenoxy)-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-130 yl]methyl}piperazin-l-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(2,3difluorophenoxy)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(2fluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-N-({4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(25 fluorophenoxy)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(2fluorophenoxy)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(210 fluorophenoxy)-N-((4-[(3-morpholin-4-ylpropyl)amino]-3-nitrophenyl}sulfonyl)benzamide; 4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(2fluorophenoxy)-N-({4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide; 2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-415 yl)amino]phenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(320 fluorophenoxy)-N-({4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide; 2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-cyclopentylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l25 yl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-({4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-(3fluorophenoxy)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-({4[(1 -cyclopentylpiperidin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2-(2,3 difluorophenoxy (benzamide;

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4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-N-({4[(1 -cyclopentylpiperidin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2-(2fluorophenoxy)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(2,35 difluorophenoxy)-N-({4-[(2-morpholin-4-ylethyl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-(2,3difluorophenoxy)-N-[(3-nitro-4-([l-(thien-3-ylmethyl)piperidin-4yl] amino} phenyl) sulfonyl] benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(410 {[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(2-fluorophenoxy (benzamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(3-fluorophenoxy (benzamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-[(4{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-(4-fluorophenoxy (benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin-1 -yl)-2-(2,3 difluorophenoxy)-N-[(4-{[l-(2-fluoroethyl)piperidin-4-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(2-morpholin-4-ylethyl)amino]-320 nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([3-(dimethylamino)propyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l25 yl]methyl }piperazin- l-yl)-N- [(4- {[3-(4-methylpiperazin-1 -yl)propyl] amino} -3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3yl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl(2-(2,3-difluorophenoxy)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

N-((4-[(l-allylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-4-(4-([2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)-2-(2,3-difluorophenoxy)benzamide;

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2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-({4-[(3-morpholin-4-ylpropyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl] methyl} piperazin-1 -yl) -N- ({3 -nitro-4- [(3 -pyrrolidin-1 ylpropyl)amino]phenyl} sulfonyl)benzamide;

2-(3-chloro-2-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-((4-[(2-morpholin-4-ylethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-6-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-6-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl (piperazin- l-yl)-N- [(4- {[(1 -methylpiperidin-4-yl)methyl] amino} -3nitrophenyl)sulfonyl]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- l-en-l-yl]methyl}piperazin- l-yl)-2-(2,3difluorophenoxy)-N-[(4- {[(l-methylpiperidin-4-yl)methyl] amino} -3nitrophenyl)sulfonyl]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2- [3(methoxymethoxy)-2-methylphenoxy]-N-([4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-2-(3hydroxy-2-methylphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-bromophenoxy)-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3yl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-(3-iodophenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-ly 1 ] methyl} piperazin-1 -yl)-N- [(4- {[ 1 -(2-hydroxyethyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(3-nitro-4-([l-(2-phenylethyl)piperidin-4yl] amino} phenyl) sulfonyl] benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3,4dichlorophenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-3,5-difluorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3methoxyphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 - y 1) - 2- [ 3 (hydroxymethyl)phenoxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l,4-dimethylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l,4-dimethylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-([4-((l-[2-(2-methoxyethoxy)ethyl]piperidin-4-yl}amino)-3nitrophenyl] sulfonyl} benzamide;

2-(2-chloro-3-hydroxyphenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(3-nitro-4-{[l-(3-phenylpropyl)piperidin-4yl] amino} phenyl) sulfonyl] benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([l-(2-methoxyethyl)piperidin-4-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N-( {4- [(1 -ethylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-isopropylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3hydroxyphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide; 2-(2-chloro-3-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-3-fluorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[3-(dimethylamino)propyl]amino}-3nitrophenyl)sulfonyl]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(2methoxyphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(2methylphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3methylphenoxy)-N-((4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4- {[6-(4-chlorophenyl)-1,3-benzodioxol-5-yl]methyl}piperazin-1yl)-N-((4-[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

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2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-[[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3yl]methyl}piperazin-l-yl)-N-([4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-(2,3-difluorophenoxy)-N-((4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N- [(4- {[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-(2-chlorophenoxy)-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N- [(4- {[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[[4-({l-[2-(dimethylamino)-2-oxoethyl]piperidin-4-yl (amino)3 -nitrophenyl] sulfonyl} benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([l-(2-morpholin-4-ylethyl)piperidin-4-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

N-[(4-[[(4-aminotetrahydro-2H-pyran-4-yl)methyl]amino}-3-nitrophenyl)sulfonyl]-2-(2chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl] methyl} piperazin-1 -yl)benzamide;

2-(2-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N- [(4- {[(4-hydroxy-1 -methylpiperidin-4-yl)methyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([(3S)-l-methylpyrrolidin-3-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-([(3R)-l-methylpyrrolidin-3-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(1 -methylpiperidin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2- [3-(1 H-pyrrol-2yl)phenoxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-(3fluorophenoxy)-N- [(4- {[(4-hydroxy-1 -methylpiperidin-4-yl)methyl]amino} -3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[4-(dimethylamino)cyclohexyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[(4-{[4-(diethylamino)cyclohexyl]amino}-3nitrophenyl)sulfonyl]benzamide;

Trans-2-(3-chlorophenoxy)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1yl]methyl}piperazin-l-yl)-N-([4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-{4-[l-(4'-chloro-l,r-biphenyl-2-yl)ethyl]piperazin-l-yl}-2-(2-chlorophenoxy)-N-([4-[(lmethylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N-( {4- [(1 -methylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-ly 11 methyl} piperazin-1 -yl)-N-( {4- [(4-methylpiperazin-1 -yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-(2-chloro-4-hydroxyphenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl} piperazin-1 -yl)-N-( {4- [(4-methylpiperazin-1 -yl)amino] -3 [(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

2-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enyl)methyl)piperazin-l-yl)-2-(4-(lmethylpiperidin-4-ylamino)-3-nitrophenylsulfonylcarbamoyl)phenoxy)-N,Ndimethylbenzamide;

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2-(2-chloro-4-hydroxyphenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-[3-(acetylamino)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-(3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-(4-amino-3-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-(2-chlorophenoxy)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl }piperazin- l-yl)-N- {[4-( {[4-(hydroxymethyl)tetrahydro-2H-pyran-4yl] methyl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

2-(3-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-[[4-(morpholin-4-ylamino)-3-nitrophenyl]sulfonyl}benzamide;

2-(2-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-[(3-nitro-4-{[3-(3-oxopiperazin-lyl)propyl] amino} phenyl) sulfonyl] benzamide;

2-(3-amino-5-chlorophenoxy)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({ 3nitro-4- [(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl} sulfony 1)-2- [2-( lH-pyrazol-4yl)phenoxy]benzamide;

2-[2-(2-aminopyridin-3-yl)phenoxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enl-yl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-N-( {3nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl]sulfonyl)-2-[2-(lH-pyrazol-5158

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In another aspect, the present invention provides compounds of Formula (III)

<img file="NZ600084A_D0005.tif" />

(III) and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof, wherein A¹, B¹, D¹, E¹, Y¹, Z², L¹, and Z³ are as described herein for Formula (I), n is 0, 1, 2, or 3; describing the number of additional substituents on R²⁶, and R¹⁰⁰ is as described for substituents on R , and at least one R is a substituent as described for substituents on R and R^42A, and the remainder are H.

In one embodiment of Formula (III), A¹ is N. In another embodiment of Formula (III), A¹ is C(A²). In another embodiment of Formula (III), A¹ is C(A²); and A² is H.

In one embodiment of Formula (III), B¹ is NIKXOjR¹, NHSO2R¹, OR¹, or NHR¹. In another embodiment of Formula (III), A¹ is C(A²); A² is H; and B¹ is NHR¹. In another embodiment of Formula (III), A¹ is C(A²); A² is H; and B¹ is OR¹. In another embodiment of Formula (III), A¹ is C(A²); A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (III), A¹ is C(A²); A² is H; and B¹ is NHC(O)R¹. In another embodiment of Formula (III), A¹is C(A²) or N; A² is H; and B¹ is NHR¹. In another embodiment of Formula (III), A¹ is C(A²) or N; A² is H; and B¹ is OR¹. In another embodiment of Formula (III), A¹ is C(A²) or N; A²is H; and B¹ is NHSO2R¹. In another embodiment of Formula (III), A¹ is C(A²) or N; A² is H; and B¹ is NHC(O)R¹.

In one embodiment of Formula (III), D¹ is H. In another embodiment of Formula (III), A¹ is C(A²); A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (III), A¹ is C(A²); A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (III), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (III), A¹ is

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C(A²); A² is Η; B¹ is NHC(O)R¹; and D¹ is H. In another embodiment of Formula (III), A¹ is

C(A²) or N; A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (III), A¹ is

C(A²) or N; A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (III), A¹ is

C(A²) or N; A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (III),

A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; and D¹ is H.

In one embodiment of Formula (III), E¹ is H. In another embodiment of Formula (III), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (III), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (III), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (III), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (III), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is H; and E¹is H. In another embodiment of Formula (III), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (III), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (III), A¹ is C(A²) or N;

A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H.

In one embodiment of Formula (III), Y¹ is H, CN, NO2, F, Cl, Br, CF3, R¹⁷, or SO2R¹⁷. In another embodiment of Formula (III), Y¹ is NO2. In another embodiment of Formula (III), Y¹ is Cl. In another embodiment of Formula (III), Y¹ is SO2R¹⁷; wherein R¹⁷ is as defined herein. In another embodiment of Formula (III), Y¹ is SO2R¹⁷; wherein R¹⁷ is alkyl. In another embodiment of Formula (III), Y¹ is R¹⁷; wherein R¹⁷ is alkynyl. In another embodiment of Formula (III), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO2R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (III), A¹is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NCk.In another embodiment of Formula (III), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (III), A¹ is C(A²); A²is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl. In another embodiment of Formula (III), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO₂ or SO₂R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (III), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (III), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (III), A¹ is C(A²) or N; A² is Η; B¹ is OR¹;

D¹ is Η; E¹ is H; and Y¹ is Cl.

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In one embodiment of Formula (III), R¹ is R², and R² is phenyl. In another embodiment of Formula (III), R¹ is R², and R² is phenyl which is substituted with NO2, and

NHR⁵⁷.

In one embodiment of Formula (III), R¹ is R⁴ or R⁵. In one embodiment of Formula (III), R¹ is R⁴. In one embodiment of Formula (III), R¹ is R⁵. In one embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl, or heterocycloalkyl. In one embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl. In one embodiment of Formula (III), R¹ is R⁴; and R⁴ is heterocycloalkyl.

In one embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl; wherein R⁴ is unsubstituted or substituted as defined herein. In another embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted as defined herein. In another embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with R⁵⁷, NHR⁵⁷, or N(R⁵⁷)2. In another embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; and R⁵⁷ is R⁶⁰. In another embodiment of Formula (III), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; and R⁶⁰ is heterocycloalkyl. In another embodiment of Formula (III), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl; wherein the heterocycloalkyl ring is morpholinyl or piperazinyl. In another embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with N(R⁵⁷)2- In another embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2. In another embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶¹, and R⁶¹ is alkyl which is unsubstituted. In another embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶⁰, and R⁶⁰ is cycloalkyl which is unsubstituted. In another embodiment of Formula (III), R¹ is R⁴; and R⁴is cycloalkyl; wherein the cycloalkyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (III), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and

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In one embodiment of Formula (III), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein R⁴is unsubstituted or substituted as defined herein. In another embodiment of Formula (III), R¹is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted as defined herein. In another embodiment of Formula (III), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted with R⁵⁷. In another embodiment of Formula (III), R¹is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the heterocycloalkyl ring is substituted with one or two or three or four or five more R⁵⁷; SC&gt;2R⁵⁷,or OH, and R⁵⁷ is R⁶⁰ or R⁶¹. In another embodiment of Formula (III), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰ or R⁶¹; R⁶⁰ is cycloalkyl or heterocycloalkyl; and R⁶¹ is alkyl. In another embodiment of Formula (III), R¹is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl, wherein the heterocycloalkyl is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of Formula (III), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is cycloalkyl, wherein the cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of Formula (III), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl, or

57 61 61 piperizinyl ring is substituted with one or two or three or four or five R ; R is R^D1;R^D1 is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl. In another embodiment of Formula (III), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl,

57 61 61 or piperizinyl ring is substituted with one or two or three or four or five R ; R is R^D1;R^D1 is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl; wherein the Ci-alkyl, C2-alkyl, or C3alkyl are unsubstituted or substituted.

In one embodiment of Formula (III), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted. In one embodiment of Formula (III), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted with R⁷, OR⁷, N(R⁷)2, or OH.

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In one embodiment of Formula (III), R⁷ is R¹⁰ or Rⁿ which are unsubstituted or substituted as defined herein. In another embodiment of Formula (III), R is R which is unsubstituted or substituted as defined herein. In another embodiment of Formula (III), R⁷ is

Rⁿ which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (III), R¹⁰ is cycloalkyl or heterocycloalkyl which are unsubstituted or substituted as defined herein. In another embodiment of Formula (III), R¹⁰ is heterocycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (III), R¹⁰ is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxanyl, piperidinyl, piperizinyl, or pyrrolidinyl, which are unsubstituted or substituted as defined herein. In another embodiment of Formula (III), R¹⁰ is tetrahydropyranyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (III), R¹⁰ is morpholinyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (III), R¹⁰ is cycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (III), R¹⁰ is cyclohexyl which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (III), Rⁿ is alkyl which is unsubstituted. In another embodiment of Formula (III), Rⁿ is methyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (III), Rⁿ is alkyl, which is substituted as defined herein. In another embodiment of Formula (III), Rⁿ is alkyl, which is substituted with OR¹², R¹² is R¹⁶, and R¹⁶ is alkyl.

In one embodiment of Formula (III), n is 0.

Still another embodiment pertains to compounds having Formula (III), which are 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((2methyl-lH-indol-5-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((2methyl-lH-indol-5-yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((7fluoro-lH-indol-5-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,l'-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((3-(3-morpholin-4-yl-3oxopropyl) -1 H-indol- 5 -y l)oxy)benzamide;

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((3-(3-morpholin-4-yl-3oxopropyl)-lH-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((3-(3-morpholin-4-ylpropyl)lH-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((3-(3-(dimethylamino)propyl)lH-indol-5-yl)oxy)-N-((3-nitro-4-((tetrahydro-2H-pyran-4ylmethyl)amino)phenyl)sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(4fluoro- lH-indol-5-yl)oxy]-N-({4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6,7difluoro-lH-indol-5-yl)oxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6,7difluoro-1 H-indol-5-yl)oxy] -N-( {3 -nitro-4- [(1 -tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(l-methylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-([6-(trifluoromethyl)-lH-indol-5yl] oxy} benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({3nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]phenyl}sulfonyl)-2-{[6(trifluoromethyl) -1 H-indol- 5 -yl] oxy} benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6,7difluoro-lH-indol-5-yl)oxy]-N-((4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin- l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6methoxy-lH-indol-5-yl)oxy]-N-({3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

tert-butyl 5-[5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en- l-yl]methyl}piperazin-1yl)-2-({ [(4-{ [3-(dimethylamino)propyl]amino}-3nitrophenyl)sulfonyl] amino} carbonyl)phenoxy] -1 H-indole-1 -carboxylate;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5 -yl)oxy ] -N- [(3 -nitro-4- {[3 -(3 -oxopiperazin-1 yl)propyl] amino} phenyl) sulfonyl] benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-([4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl }piperazin-1 -yl)-2[(6,7-difluoro-lH-indol-5-yl)oxy]-N-([4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-N-[(4{[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 -nitrophenyl)sulfonyl] -2- [(6-fluoro-1Hindol- 5 -yl)oxy ]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-N- [(4{[ 1 -(cyclopropylmethyl)piperidin-4-yl] amino} -3 -nitrophenyl)sulfonyl] -2- [(6,7-difluoro-1Hindol- 5 -yl)oxy ]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2- [(6,7difluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-{ [3-(3-oxopiperazin-1yl)propyl] amino} phenyl) sulfonyl] benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 - y 1) - 2- [ (6 fluoro-lH-indol-5-yl)oxy]-N-({4-[(2-hydroxy-l-tetrahydro-2H-pyran-4-ylethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-{ [4-({ [4-(hydroxymethyl)tetrahydro-2H-pyran-4yl] methyl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl]piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6,7difluoro-1 H-indol-5-yl)oxy] -N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl]piperazin-l-yl)-N-((4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro- lH-indol-5 -yl)oxy ] -N- [(3 -nitro-4- {[1-(1,3 -thiazol-4-ylmethyl)piperidin-4yl] 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-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 - y 1) - 2- [ (6 fluoro- lH-indol-5-yl)oxy]-N-[(4-{ [(3S, 4R)-3-hydroxy-l-(l, 3-thiazol-4-ylmethyl)piperidin-4yl] amino} -3 -nitrophenyl) sulfonyl] benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro- lH-indol-5-yl)oxy]-N- {[3-nitro-4-(tetrahydro-2H-pyran-4ylamino)phenyl] sulfonyl} benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 - y 1) - 2- [ (6 fluoro-lH-indol-5-yl)oxy]-N-([4-(morpholin-4-ylamino)-3-nitrophenyl]sulfonyl}benzamide; 4-(4-( l-[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]ethyl]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([(3S)-tetrahydro-2H-pyran-3ylmethyl] amino} phenyl) sulfonyl] benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([(3R)-tetrahydro-2H-pyran-3ylmethyl] amino} phenyl) sulfonyl] benzamide;

4-(4- {[2-(4-chlorophenyl)-5,5 -dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-((4-[(2-methoxyethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N- {[3-nitro-4-(tetrahydro-2H-pyran-4ylmethoxy)phenyl] sulfonyl} benzamide;

2-[(3-chloro-lH-indol-5-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2Hpyran-3-yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(3-chloro-lH-indol-5-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl] piperazin- l-yl)-N- {[4(l,4-dioxan-2-ylmethoxy)-3-nitrophenyl]sulfonyl}-2-[(6-fluoro-lH-indol-5yl)oxy (benzamide;

2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin- l-yl)-N-{ [4-(1,4-dioxan-2-ylmethoxy)-3nitrophenyl] sulfonyl} benzamide;

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2- [(6-chloro- lH-indol-5 -yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-({4-[(l,4-dioxan-2-ylmethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({4[(1,4-dioxan-2-ylmethyl)amino] -3 -nitrophenyl} sulfonyl)-2- [(6-fluoro-1 H-indol-5 yl)oxy]benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro2H-pyran-3-yl]methyl}piperazin-l-yl)-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-({4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-((4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-((4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

4-(4-{[4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)N-([5-cyano-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

2-{[3-(2-aminoethyl)-lH-indol-5-yl]oxy}-4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex1- en-l-yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2- {[3-(2-aminoethyl)-lH-indol-5-yl]oxy}-4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex1 -en- l-yl]methyl (piperazin- l-yl)-N-( {4- [(4-methylpiperazin-1 -yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl} piperazin- l-yl)-N- {[5cyano-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl(-2-[(6-fluoro-lH-indol-5yl)oxy (benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[5chloro-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[5cyano-6-( 1,4-dioxan-2-ylmethoxy)pyridin-3 -yl] sulfonyl} -2- [(6-fluoro-1 H-indol-5 yl)oxy]benzamide;

N-{[5-bromo-6-(l,4-dioxan-2-ylmethoxy)pyridin-3-yl]sulfonyl}-4-(4-( [2-(4-chlorophenyl)4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

Trans-N-((5-bromo-6-[(4-morpholin-4-ylcyclohexyl)amino]pyridin-3-yl]sulfonyl)-4-(4-{[2(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-({5cyano-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl} sulfonyl)-2-[(6-fluorolH-indol-5 -yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-N-{[5cyano-6-(2-morpholin-4-ylethoxy)pyridin-3-yl]sulfonyl]-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2[(6-fluoro-1 H-indol-5-yl)oxy] -N-( (4- [(4-morpholin-4-ylcyclohexyl)oxy] -3 nitrophenyl} sulfonyl)benzamide;

N-((5-bromo-6-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]pyridin-3-yl]sulfonyl)-4(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 - y 1)-2 - [ (6fluoro-lH-indol-5-yl)oxy]benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-([5-(4-chlorophenyl)-2,3,6,7-tetrahydrooxepin4-yl]methyl]piperazin-l-yl)-N-((4-[(4-morpholin-4-ylcyclohexyl)amino]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

Trans-2-[(6-chloro-lH-indol-5-yl)oxy]-4-(4-([5-(4-chlorophenyl)-2,3,6,7-tetrahydrooxepin4-yl]methyl]piperazin-l-yl)-N-((4-[(4-morpholin-4-ylcyclohexyl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl]piperazin-l-yl)2-[(6-fluoro-lH-indol-5-yl)oxy]-N-({4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]-N-((4-[(4-morpholin-4-ylbut-2-ynyl)oxy]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5 -yl)oxy ] -N- [(4- {[ 1 -(methylsulfonyl)piperidin-4-yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

4- (4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-{[5ethynyl-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lH-indol5- yl)oxy]benzamide;

4-(4-( [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)N-([5-ethynyl-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl}-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({5cyano-6-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4-yl)oxy]pyridin-3-yl}sulfonyl)-2-[(6-fluoro1 H-indol-5 -yl)oxy]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 -y 1 ] methyl} piperazin-1 -yl)-2- [(6-fluoro1 H-indol-5 -yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 11 methyl} piperazin-1 -yl)-N-( {4[(l-cyclopropylpiperidin-4-yl)amino]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-N-( {4[(4-ethylmorpholin-3-yl)methoxy]-3-nitrophenyl}sulfonyl)-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([(3S)-l-tetrahydro-2H-pyran-4-ylpiperidin-3yl] amino} phenyl) sulfonyl] benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-N-({4[(1,1 -dioxidothiomorpholin-4-yl)amino] -3 -nitrophenyl} sulfonyl)-2- [(6-fluoro-1 H-indol-5yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro-lH-indol-5-yl)oxy]-N-((3-nitro-4-[(tetrahydrofuran-3ylmethyl)amino]phenyl} sulfonyl)benzamide;

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Trans-N-({5-bromo-6-[(4-morpholin-4-ylcyclohexyl)oxy]pyridin-3-yl}sulfonyl)-4-(4-{ [2-(4chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl Jpiperazin-1-yl)-2-[(6-fluoro-1Hindol-5-yl)oxy]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-N[(4-([4-(dicyclopropylamino)cyclohexyl] amino} -3-nitrophenyl)sulfonyl] -2- [(6-fluoro-1Hindol-5-yl)oxy]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([4-(tetrahydro-2H-pyran-4ylamino)cyclohexyl]amino}phenyl)sulfonyl]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-[(3-nitro-4-([4-(4-tetrahydro-2H-pyran-4-ylpiperazin-lyl)cyclohexyl] amino} phenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(6fluoro- lH-indol-5-yl)oxy]-N-[(4-{ [(4-fluorotetrahydro-2H-pyran-4-yl)methyl] amino]-3nitrophenyl)sulfonyl]benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl }piperazin-1 -yl)-2[(6-fluoro-lH-indol-5-yl)oxy]-N-[(4-([(4-hydroxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-N-( {4[(l-cyclopropyl-4-fluoropiperidin-4-yl)methoxy]-3-nitrophenyl]sulfonyl)-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl]piperazin-l-yl)-N- {[4({(3R)-1- [2-fluoro- l-(fluoromethyl)ethyl]pyrrolidin-3-yl} amino)-3-nitrophenyl]sulfonyl} -2[(6-fluoro-lH-indol-5-yl)oxy]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]piperazin-l-yl)-2-[(6fluoro-lH-indol-5-yl)oxy]benzamide;

N-({5-chloro-6-[(4,4-difluorocyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-{ [4-(4chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl]piperazin-l-yl)-2-[(6-fluoro1 H-indol-5 -yl)oxy]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-N-[(4{[(4,4-difluorocyclohexyl)methyl]amino]-3-nitrophenyl)sulfonyl]-2-[(6-fluoro-lH-indol-5yl)oxy]benzamide;

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N-({3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{ [2-(4chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6-fluoro-lHindol-5-yl)oxy]benzamide;

N-([3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl}sulfonyl)-4-(4-{ [4-(45 chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-l-yl)-2-[(6-fluorolH-indol-5 -yl)oxy]benzamide;

tert-butyl 5-[(4-{4-[({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3yl} sulfonyl)carbamoyl] -3 - [(6-fluoro- lH-indol-5 -yl)oxy]phenyl} piperazin-1 -yl)methyl] -4-(4chlorophenyl)-3,6-dihydropyridine-1 (2H)-carboxylate;

N-([5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl}sulfonyl)-4-(4{[4-(4-chlorophenyl)-1-(1,3-difluoropropan-2-yl)-1,2,5,6-tetr ahydropyridin-3yl]methyl}piperazin-l-yl)-2-[(6-fluoro-lH-indol-5-yl)oxy]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro- lH-indol-5 -yl)oxy ] -N- {[3 -nitro-4-( {[4-(oxetan-3 -yl)morpholin-215 yl]methyl }amino)phenyl] sulfonyl (benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

In another aspect, the present invention provides compounds of Formula (IV)

<img file="NZ600084A_D0006.tif" />

and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof, wherein A¹, B¹, D¹, E¹, Y¹, Z², L¹, and Z³ are as described herein for Formula (I), n is 0, 1, 2, or 3; describing the number of additional substituents on R²⁶, and R¹⁰⁰ is as described for

102 /i o substituents on R , and at least one R is a substituent as described for substituents on R and R^42A, and the remainder are H.

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In one embodiment of Formula (IV), A¹ is N. In another embodiment of Formula (IV), A¹ is C(A²). In another embodiment of Formula (IV), A¹ is C(A²); and A² is H.

In one embodiment of Formula (IV), B¹ is NHCXCOR¹, NHSO2R¹, OR¹, or NHR¹. In another embodiment of Formula (IV), A¹ is C(A²); A² is H; and B¹ is NHR¹. In another embodiment of Formula (IV), A¹ is C(A²); A² is H; and B¹ is OR¹. In another embodiment of Formula (IV), A¹ is C(A²); A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (IV), A¹ is C(A²); A² is H; and B¹ is NHC(O)R¹. In another embodiment of Formula (IV), A¹is C(A²) or N; A² is H; and B¹ is NHR¹. In another embodiment of Formula (IV), A¹ is C(A²) or N; A² is H; and B¹ is OR¹. In another embodiment of Formula (IV), A¹ is C(A²) or N; A²is H; and B¹ is NHSO2R¹. In another embodiment of Formula (IV), A¹ is C(A²) or N; A² is H; andB¹ is NHC(O)R¹.

In one embodiment of Formula (IV), D¹ is H. In another embodiment of Formula (IV), A¹ is C(A²); A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (IV), A¹ is C(A²); A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (IV), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (IV), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; and D¹ is H. In another embodiment of Formula (IV), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (IV), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (IV), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (IV),

A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; and D¹ is H.

In one embodiment of Formula (IV), E¹ is H. In another embodiment of Formula (IV), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (IV), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (IV), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (IV), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (IV), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is H; and E¹is H. In another embodiment of Formula (IV), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (IV), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (IV), A¹ is C(A²) or N;

A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H.

In one embodiment of Formula (IV), Y¹ is H, CN, NO2, F, Cl, Br, CF3, R¹⁷, or SO2R¹⁷. In another embodiment of Formula (IV), Y¹ is NO2. In another embodiment of Formula (IV), Y¹ is Cl. In another embodiment of Formula (IV), Y¹ is SO2R¹⁷; wherein R¹⁷ is as defined herein. In another embodiment of Formula (IV), Y¹ is SO2R¹⁷; wherein R¹⁷ is

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In one embodiment of Formula (IV), R¹ is R², and R² is phenyl. In another embodiment of Formula (IV), R¹ is R², and R² is phenyl which is substituted with NO2, and NHR⁵⁷.

In one embodiment of Formula (IV), R¹ is R⁴ or R⁵. In one embodiment of Formula (IV), R¹ is R⁴. In one embodiment of Formula (IV), R¹ is R⁵. In one embodiment of Formula (IV), R¹ is R⁴; and R⁴ is cycloalkyl, or heterocycloalkyl. In one embodiment of Formula (IV), R¹ is R⁴; and R⁴ is cycloalkyl. In one embodiment of Formula (IV), R¹ is R⁴; and R⁴ is heterocycloalkyl.

In one embodiment of Formula (IV), R¹ is R⁴; and R⁴ is cycloalkyl; wherein R⁴ is unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted as defined herein. In another embodiment of Formula (IV), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with R⁵⁷, NHR⁵⁷, or N(R⁵⁷)2. In another embodiment of Formula (IV), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; and R⁵⁷ is R⁶⁰. In another embodiment of Formula (IV), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; and R⁶⁰ is heterocycloalkyl. In another embodiment of Formula (IV), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl; wherein the heterocycloalkyl ring is morpholinyl or piperazinyl. In another embodiment of Formula (IV), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is

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In one embodiment of Formula (IV), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein R⁴is unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), R¹is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted as defined herein. In another embodiment of Formula (IV), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted with R⁵⁷. In another embodiment of Formula (IV), R¹is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the heterocycloalkyl ring is substituted with one or two or three or four or five more R⁵⁷; SC&gt;2R⁵⁷,or OH, and R⁵⁷ is R⁶⁰ or R⁶¹. In another embodiment of Formula (IV), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰ or R⁶¹; R⁶⁰ is cycloalkyl or heterocycloalkyl; and R⁶¹ is alkyl. In another embodiment of Formula (IV), R¹is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl, wherein the heterocycloalkyl is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of Formula (IV), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is cycloalkyl, wherein the cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of Formula (IV), R¹ is

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R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl, or

57 61 61 piperizinyl ring is substituted with one or two or three or four or five R ; R is R^D1;R^D1 is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl. In another embodiment of Formula (IV), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl,

C-7 C-y Z--1 Z--1 or piperizinyl ring is substituted with one or two or three or four or five R ; R is ROUROl is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl; wherein the Ci-alkyl, C2-alkyl, or C3alkyl are unsubstituted or substituted.

In one embodiment of Formula (IV), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted. In one embodiment of Formula (IV), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted with R⁷, OR⁷, N(R⁷)2, or OH.

In one embodiment of Formula (IV), R⁷ is R¹⁰ or Rⁿ which are unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), R is R which is unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), R⁷ is Rⁿ which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (IV), R¹⁰ is cycloalkyl or heterocycloalkyl which are unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), R¹⁰ is heterocycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), R¹⁰ is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxanyl, piperidinyl, piperizinyl, or pyrrolidinyl, which are unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), R¹⁰ is tetrahydropyranyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), R¹⁰ is morpholinyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), R¹⁰ is cycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), R¹⁰ is cyclohexyl which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (IV), Rⁿ is alkyl which is unsubstituted. In another embodiment of Formula (IV), Rⁿ is methyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (IV), Rⁿ is alkyl, which is substituted as defined herein. In another embodiment of Formula (IV), Rⁿ is alkyl, which is substituted with OR¹², R¹² is R¹⁶, and R¹⁶ is alkyl.

In one embodiment of Formula (IV), n is 0.

Still another embodiment pertains to compounds having Formula (IV), which are

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4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-N-((4-((3(dimethylamino)propyl)amino)-3-nitrophenyl)sulfonyl)-2-((l -methyl- lH-indol-4yl)oxy)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indol-4-yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indol-4-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((4'-chloro-l,r-biphenyl-2-yl)methyl)piperazin-l-yl)-2-((l-methyl-lH-indol-4-yl)oxy)N-((4-((3-morpholin-4-ylpropyl)amino)-3-nitrophenyl)sulfonyl)benzamide;

tert-butyl 4-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-([((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)amino]carbonyl (phenoxy)- ΙΗ-indole-1 -carboxylate;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-4-yl)oxy]-N-((4-[(l-methylpiperidin-4-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -y 11 methyl} piperazin-1 - y 1) - 2- [ (6 fluoro-lH-indol-4-yl)oxy]-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-((1,3 -bis [(4-methylpiperazin-1 -yl)methyl] -1 H-indol-4-yl} oxy)-4-(4- {[2-(4-chlorophenyl)4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-[(4-{[3(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-N- [(4{[3-(dimethylamino)propyl]amino}-3-nitrophenyl)sulfonyl]-2-((3-[(4-methylpiperazin-lyl)methyl]- lH-indol-4-yl }oxy (benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({ 3nitro-4- [(1 -tetrahydro-2H-pyran-4-ylpiperidin-4-yl)amino]phenyl} sulfonyl)-2- {[2(trifluoromethyl) -1 H-indol-4-yl] oxy} benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 -yl)-2- [(6fluoro-1 H-indol-4-yl)oxy ] -N- [(3 -nitro-4- {[3 -(3 -oxopiperazin-1 yl)propyl] amino} phenyl) sulfonyl] benzamide;

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2- [(3 -chloro- lH-indol-4-yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6fluoro-lH-indol-4-yl)oxy]-N-([4-[(2-methoxyethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2- [(3 -chloro- lH-indol-4-yl)oxy] -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-([4-[(4-methylpiperazin-l-yl)amino]-3nitrophenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 - y 1) - 2-({3 - [ 3 (dimethylamino)propyl]-lH-indol-4-yl} oxy)-N-( {3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-2-({3-[3(dimethylamino)propyl] - lH-indol-4-yl} oxy)-N-( {4- [(4-methylpiperazin-1 -yl)amino] -3 nitrophenyl}sulfonyl)benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

In another aspect, the present invention provides compounds of Formula (V)

E¹ Y¹

<img file="NZ600084A_D0007.tif" />

^Z² R¹⁰³

Z³ (V) and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof, wherein A¹, B¹, D¹, E¹, Y¹, Z², L¹, and Z³ are as described herein for Formula (I), n is 0, 1, 2, or 3; describing the number of additional substituents on R²⁶, and R¹⁰⁰ is as described for substituents on R²⁶, and at least one of R¹⁰³ or R¹⁰⁴ is a substituent as described for substituents on R and R and the remainder are H.

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In one embodiment of Formula (V), A¹ is N. In another embodiment of Formula (V),

A¹ is C(A²). In another embodiment of Formula (V), A¹ is C(A²); and A² is H.

In one embodiment of Formula (V), B¹ is NHQCOR¹, NHSO2R¹, OR¹, or NHR¹. In another embodiment of Formula (V), A¹ is C(A²); A² is H; and B¹ is NHR¹. In another embodiment of Formula (V), A¹ is C(A²); A² is H; and B¹ is OR¹. In another embodiment of Formula (V), A¹ is C(A²); A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (V), A¹ is C(A²); A² is H; and B¹ is NHC(O)R¹. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is H; and B¹ is NHR¹. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is H; and B¹ is OR¹. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is H; and B¹ is NHC(O)R¹.

In one embodiment of Formula (V), D¹ is H. In another embodiment of Formula (V), A¹ is C(A²); A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (V), A¹ is C(A²); A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (V), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (V), A¹ is C(A²);

A² is Η; B¹ is NHC(O)R¹; and D¹ is H. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; and D¹ is H.

In one embodiment of Formula (V), E¹ is H. In another embodiment of Formula (V), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (V), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (V), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (V), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H.

In one embodiment of Formula (V), Y¹ is H, CN, NO2, F, Cl, Br, CF3, R¹⁷, or SO2R¹⁷. In another embodiment of Formula (V), Y¹ is NO2. In another embodiment of Formula (V), Y¹ is Cl. In another embodiment of Formula (V), Y¹ is SO2R¹⁷; wherein R¹⁷ is as defined herein. In another embodiment of Formula (V), Y¹ is SO2R¹⁷; wherein R¹⁷ is alkyl. In another

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PCT/US2010/036844 embodiment of Formula (V), Y¹ is R¹⁷; wherein R¹⁷ is alkynyl. In another embodiment of Formula (V), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO2R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (V), A¹ is C(A²); A² is H; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (V), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (V), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO₂R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is H; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (V), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl.

In one embodiment of Formula (V), R¹ is R², and R² is phenyl. In another embodiment of Formula (V), R¹ is R², and R² is phenyl which is substituted with NO₂, and NHR⁵⁷.

In one embodiment of Formula (V), R¹ is R⁴ or R⁵. In one embodiment of Formula (V), R¹ is R⁴. In one embodiment of Formula (V), R¹ is R⁵. In one embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl, or heterocycloalkyl. In one embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl. In one embodiment of Formula (V), R¹ is R⁴; and R⁴ is heterocycloalkyl.

In one embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein R⁴ is unsubstituted or substituted as defined herein. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted as defined herein. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with R⁵⁷, NHR⁵⁷, or N(R⁵⁷)₂. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; and R⁵⁷ is R⁶⁰. In another embodiment of Formula (V), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; and R⁶⁰ is heterocycloalkyl. In another embodiment of Formula (V), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl; wherein the heterocycloalkyl ring is morpholinyl or piperazinyl. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is

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PCT/US2010/036844 substituted with N(R⁵⁷)2- In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶¹, and R⁶¹ is alkyl which is unsubstituted. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶⁰, and R⁶⁰ is cycloalkyl which is unsubstituted. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷, R⁵⁷ is R⁶⁰, and R⁶⁰ is heterocycloalkyl which is unsubstituted.

In one embodiment of Formula (V), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein R⁴is unsubstituted or substituted as defined herein. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted as defined herein. In another embodiment of Formula (V), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted with R⁵⁷. In another embodiment of Formula (V), R¹is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the heterocycloalkyl ring is substituted with one or two or three or four or five more R⁵⁷; SC&gt;2R⁵⁷,or OH, and R⁵⁷ is R⁶⁰ or R⁶¹. In another embodiment of Formula (V), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰ or R⁶¹; R⁶⁰ is cycloalkyl or heterocycloalkyl; and R⁶¹ is alkyl. In another embodiment of Formula (V), R¹is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl, wherein the heterocycloalkyl is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of Formula (V), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is cycloalkyl, wherein the cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of Formula (V), R¹ is

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R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl, or

57 61 61 piperizinyl ring is substituted with one or two or three or four or five R ; R is R^D1;R^D1 is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl. In another embodiment of Formula (V), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl,

C-7 C-y Z--1 Z--1 or piperizinyl ring is substituted with one or two or three or four or five R ; R is ROUROl is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl; wherein the Ci-alkyl, C2-alkyl, or C3alkyl are unsubstituted or substituted.

In one embodiment of Formula (V), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted. In one embodiment of Formula (V), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted with R⁷, OR⁷, N(R⁷)2, or OH.

In one embodiment of Formula (V), R⁷ is R¹⁰ or Rⁿ which are unsubstituted or substituted as defined herein. In another embodiment of Formula (V), R is R which is unsubstituted or substituted as defined herein. In another embodiment of Formula (V), R⁷ is Rⁿ which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (V), R¹⁰ is cycloalkyl or heterocycloalkyl which are unsubstituted or substituted as defined herein. In another embodiment of Formula (V), R¹⁰ is heterocycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (V), R¹⁰ is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxanyl, piperidinyl, piperizinyl, or pyrrolidinyl, which are unsubstituted or substituted as defined herein. In another embodiment of Formula (V), R¹⁰ is tetrahydropyranyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (V), R¹⁰ is morpholinyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (V), R¹⁰ is cycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (V), R¹⁰ is cyclohexyl which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (V), Rⁿ is alkyl which is unsubstituted. In another embodiment of Formula (V), Rⁿ is methyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (V), Rⁿ is alkyl, which is substituted as defined herein. In another embodiment of Formula (V), Rⁿ is alkyl, which is substituted with OR¹², R¹² is R¹⁶, and R¹⁶ is alkyl.

In one embodiment of Formula (V), n is 0. In another embodiment of Formula (V), n is 0, R¹⁰⁴ is NH2, and one R¹⁰³ is Cl or Br, and the remainder are H.

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Still another embodiment pertains to compounds having Formula (V), which are

2-(6-aminopyridin-3-yl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(6-aminopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

tert-butyl 5-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate; tert-butyl 4-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-([((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl}sulfonyl)amino]carbonyl}phenoxy)pyridin-2-ylcarbamate;

2-[(6-aminopyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(2-aminopyridin-4-yl)oxy]-4-(4-{[2-(4-chloropheny 1)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(l-tetrahydro-2H-pyran-4-ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(5-bromopyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

tert-butyl 5-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-3-ylcarbamate; 2-[(5-aminopyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

tert-butyl 4-(5-(4-( [2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 -yl]methyl} piperazin-1 yl)-2-([((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate; 2-[(2-aminopyridin-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(6hydroxypyridin-3-yl)oxy]-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-{[6-(benzyloxy)pyridin-3-yl]oxy )-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-fluoropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl ] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-N-({ 4-[(4-morpholin-4ylcyclohexy l)amino] - 3 -nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( [4- [(4-methylpiperazin-1 -yl) amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl }piperazin- l-yl)-N- {[4-(1,4-dioxan-2-ylmethoxy)-3nitrophenyl] sulfonyl} benzamide;

Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- l-yl]methyl }piperazin-1 -yl)-N- [(4- {[(4methoxycyclohexyl)methyl]amino]-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-([4-[(l,4-dioxan-2-ylmethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {4- [(3 -morpholin-4-ylpropyl)amino] -3 [(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3[(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl] methyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- 1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-amino-5-(5-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-lyl)-2-{[({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)nicotinamide;

2-[(6-amino-5-cyanopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- 1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-[(4-{[(3R)-l-(2,2-difluoroethyl)pyrrolidin-3-yl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {4- [(1 -methylpiperidin-4-yl)amino] -3 [(trifluoromethyl)sulfonyl]phenyl} sulfonyl)benzamide;

2- {[6-(acetylamino)pyridin-3-yl]oxy} -4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en1- yl]methyl]piperazin-l-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 - y 1) - 2-({6 [(methylsulfonyl)amino]pyridin-3-yl]oxy)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2- [(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {4- [(1 -cyclopropylpiperidin-4-yl)amino] -3 nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {4- [(4-methylpiperazin-1 -yl) amino] -3 nitrophenyl} sulfonyl)benzamide;

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2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-({4-[(l,4-dioxan-2-ylmethyl)amino]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-methylpyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl} piperazin-1 -yl)-N - [(4- {[(4-fluorotetrahydro-2H-pyran-4-yl)methyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin- l-yl)-N-( {3 -nitro-4- [(1 -oxetan-3 -ylpiperidin-4yl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-isopropylpyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex1- en-l-yl]methyl]piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2- [(6-amino-5-cyclopropylpyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

Trans-2-[(6-amino-5-bromopyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -y 1 ] methyl} piperazin-1 -yl)-N - [(4- {[(4methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[(4-cyclopropylmorpholin-2-yl)methyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N - [ (4- {[ (3 R) -1 -cyclopropylpyrrolidin-3 -yl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N- {[4-( {4-fluoro-1 - [2-fluoro-1 (fluoromethyl)ethyl]piperidin-4-yl}methoxy)-3-nitrophenyl]sulfonyl}benzamide;

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PCT/US2010/036844 tert-butyl 6-bromo-4-(5-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-2-([({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate; tert-butyl 4-(5-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-enyl)methyl)piperazin-l-yl)2-(3-nitro-4-((tetrahydro-2H-pyran-4yl)methylamino)phenylsulfonylcarbamoyl)phenoxy)pyridine-2,6-diyldicarbamate;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-{ [6(cyclopropylamino)pyridin-3-yl]oxy} -N-( {3-nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

Trans-4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 -yl)-2({6-[(2,2-difluoroethyl)amino]pyridin-3-yl}oxy)-N-[(4-{[(4methoxycyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-({6[(2,2-difluoroethyl)amino]pyridin-3-yl}oxy)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-( [5-chloro-6-(methylamino)pyridin-3-yl]oxy (-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl] methyl} piperazin-1 -yl)-N-( {4- [({4- [2-fluoro-1 -(fluoromethyl)ethyl]morpholin-2yl} methyl)amino]-3-nitrophenyl} sulfonyl)benzamide;

2-[(2-amino-6-bromopyridin-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-l-yl]methyl]piperazin-l-yl)-2-[(2,6diaminopyridin-4-yl)oxy]-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-l-yl]methyl]piperazin-l-yl)-N-([3-nitro-4-(tetrahydro-2H-pyran-4ylmethoxy)phenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1en-1 -yl]methyl} piperazin-1 -yl)-N- {[4-( {(3R)-1 - [2-fluoro-1 -(fluoromethyl)ethyl]piperidin-3 yl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

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PCT/US2010/036844 tert-butyl 5-bromo-4-(5-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-lyl]methyl]piperazin-l-yl)-2-([({3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)amino]carbonyl }phenoxy)pyridin-2-ylcarbamate;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-N-({ 3nitro-4- [(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl} sulfony 1)-2-( {6-((2,2,2trifluoroethyl)amino]pyridin-3-yl} oxy)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-[(4-([(4-hydroxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro2H-pyran-3-yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfony l)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -y 1 ] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydrofuran-3ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-((5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-([4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2Hpyran-3-yl]methyl}piperazin-l-yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-((9-(4-chlorophenyl)-3-[2-fluoro-l(fluoromethyl)ethyl]-3-azaspiro[5.5]undec-8-en-8-yl}methyl)piperazin-l-yl]-N-({3-nitro-4[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([9-(4-chlorophenyl)-3-isopropyl-3azaspiro[5.5]undec-8-en-8-yl]methyl}piperazin-l-yl)-N-((3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-([l-(N,N-dimethylglycyl)-4fluoropiperidin-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1-yl] me thyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N- {[4-( {(3R)-1 - [2-fluoro-1 -(fluoromethyl)ethyl]pyrrolidin-3 yl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

2-[(2-amino-5-bromopyridin-4-yl)oxy]-4-(4-([2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N-( {3 -nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len- 1-yl] methyl} piperazin- l-yl)-N-[(4- {[(4,4-difluorocyclohexyl)methyl]amino} -3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-[4-({4'-chloro-3-[2-(dimethylamino)ethoxy]-l,l·biphenyl-2-yl} methyl)piperazin-1 -yl] -N-( {3-nitro-4- [(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-{[5-chloro-6-({(3R)-l-[2-fluoro-l(fluoromethyl)ethyl]pyrrolidin-3 -yl} methoxy )pyridin-3 -yl] sulfonyl} -4-(4- {[2-(4chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl }piperazin-1 -yl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{[(3R)-1-(2,2difluoroethyl)pyrrolidin-3-yl] methoxy }pyridin-3-yl)sulfonyl]-4-(4- {[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide; Trans-2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[(4cyanocyclohexyl)methyl]amino]-3-nitrophenyl)sulfonyl]benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-([5-fluoro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl]sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-[(5-chloro-6-{ [1-(2,2-difluoroethyl)-4\fluoropiperidin-4-yl]methoxy}pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]phenyl} sulfonyl)-4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 yl] methyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N- {[6-( {4-fluoro-1 - [2-fluoro-1 (fluoromethyl)ethyl]piperidin-4-yl}methoxy)-5-(trifluoromethyl)pyridin-3yl] sulfonyl} benzamide;

2- [(6-amino-5 -chloropyridin-3-yl)oxy] -N-( {5 -chloro-6- [(4,4difluorocyclohexyl)methoxy]pyridin-3-yl}sulfony 1)-4-(4- {[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-{[3-nitro-4-({[4-(oxetan-3-yl)morpholin-2yl] methyl} amino)phenyl] sulfonyl} benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-[(4-{[4-fluoro-l-(oxetan-3-yl)piperidin-4-yl]methoxy}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl ] methyl} piperazin-1 -yl)-N - [(4- {[(trans-4-hydroxy-4methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulfonyl]benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-([4-[(cis-4-hydroxy-4-methylcyclohexyl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2- [(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[(cis-4-hydroxy-4-methylcyclohexyl)methyl] amino} 3- nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-[[3-nitro-4-(2-oxaspiro[3.5]non-7ylmethoxy)phenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-([4-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl }piperazin- l-yl)-N- {[4-( {[(2S)-4-cyclopropylmorpholin-2-yl]methyl} amino)3 -nitrophenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([5-chloro-6-[(trans-l-fluoro-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] me thyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-([5-chloro-6-[(cis-l-fluoro-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl] me thyl} piperazin-1 -yl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-[(4-[[(cis-4-ethyl-4-hydroxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-{[3-nitro-4-([[(2S)-4-(oxetan-3-yl)morpholin-2yl] methyl} amino)phenyl] sulfonyl} benzamide;

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2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl ] methyl} piperazin- l-yl)-N-( {5 -nitro-6- [(tetrahydro-2H-pyran-4ylmethyl)amino]pyridin-3-yl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-({3-nitro-4-[(2-oxaspiro[3.5]non-7ylmethyl)amino]phenyl} sulfonyl)benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl}piperazin-l-yl)-N-{[4-({[trans-4-(morpholin-4yl)cyclohexyl] methyl} amino) - 3 -nitrophenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl] methyl} piperazin-1 -yl)-N - [(4- {[cis-4-(morpholin-4-yl)cyclohexyl] amino} -3 nitrophenyl)sulfonyl]benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-1 -yl]methyl }piperazin- l-yl)-N- {[4-( {[4-( {[4-(methoxymethyl)cyclohexyl]methyl} amino)3 -nitrophenyl] sulfonyl} amino)- 3 -nitrophenyl] sulfonyl} benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-[(3-nitro-4-[[(3R)-l-(oxetan-3-yl)pyrrolidin-3yl] amino} phenyl) sulfonyl] benzamide;

2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-len-l-yl]methyl]piperazin-l-yl)-N-[(3-nitro-4-[[(3S)-l-(oxetan-3-yl)pyrrolidin-3yl] amino} phenyl) sulfonyl] benzamide;

N-[4-([2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)benzoyl} sulfamoy 1)-2nitrophenyl] morpholine-4-c arboxamide;

N-[4-([2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-[[2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)benzoyl} sulfamoy l)-2-nitrophenyl] -4cyanopiperidine-1 -carboxamide;

and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

In another aspect, the present invention provides compounds of Formula (VI)

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<img file="NZ600084A_D0008.tif" />

(VI) and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof, wherein A¹, B¹, D¹, E¹, Y¹, Z², L¹, and Z³ are as described herein for Formula (I), n is 0, 1, 2, or 3; describing the number of additional substituents on R²⁶, and R¹⁰⁰ is as described for

O A 1ΓΙ’) ΛO substituents on R , and at least one R is a substituent as described for substituents on R and R^42A, and the remainder are H.

In one embodiment of Formula (VI), A¹ is N. In another embodiment of Formula (VI), A¹ is C(A²). In another embodiment of Formula (VI), A¹ is C(A²); and A² is H.

In one embodiment of Formula (VI), B¹ is NHCCCOR¹, NHSO2R¹, OR¹, or NHR¹. In another embodiment of Formula (VI), A¹ is C(A²); A² is H; and B¹ is NHR¹. In another embodiment of Formula (VI), A¹ is C(A²); A² is H; and B¹ is OR¹. In another embodiment of Formula (VI), A¹ is C(A²); A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (VI), A¹ is C(A²); A² is H; and B¹ is NHC(O)R¹. In another embodiment of Formula (VI), A¹is C(A²) or N; A² is H; and B¹ is NHR¹. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is H; and B¹ is OR¹. In another embodiment of Formula (VI), A¹ is C(A²) or N; A²is H; and B¹ is NHSO2R¹. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is H; and B¹ is NHC(O)R¹.

In one embodiment of Formula (VI), D¹ is H. In another embodiment of Formula (VI), A¹ is C(A²); A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (VI), A¹ is C(A²); A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (VI), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (VI), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; and D¹ is H. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (VI), A¹ is

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C(A²) or N; A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (VI),

A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; and D¹ is H.

In one embodiment of Formula (VI), E¹ is H. In another embodiment of Formula (VI), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VI), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VI), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VI), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is H; and E¹is H. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VI), A¹ is C(A²) or N;

A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H.

In one embodiment of Formula (VI), Y¹ is H, CN, NO2, F, Cl, Br, CF3, R¹⁷, or SO2R¹⁷. In another embodiment of Formula (VI), Y¹ is NO2. In another embodiment of Formula (VI), Y¹ is Cl. In another embodiment of Formula (VI), Y¹ is SO2R¹⁷; wherein R¹⁷ is as defined herein. In another embodiment of Formula (VI), Y¹ is SO2R¹⁷; wherein R¹⁷ is alkyl. In another embodiment of Formula (VI), Y¹ is R¹⁷; wherein R¹⁷ is alkynyl. In another embodiment of Formula (VI), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO2R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (VI), A¹is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NCk.In another embodiment of Formula (VI), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (VI), A¹ is C(A²); A²is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO₂ or SO₂R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (VI), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl.

In one embodiment of Formula (VI), R¹ is R², and R² is phenyl. In another embodiment of Formula (VI), R¹ is R², and R² is phenyl which is substituted with NO2, and NHR⁵⁷.

In one embodiment of Formula (VI), R¹ is R⁴ or R⁵. In one embodiment of Formula (VI), R¹ is R⁴. In one embodiment of Formula (VI), R¹ is R⁵. In one embodiment of Formula

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PCT/US2010/036844 (VI), R¹ is R⁴; and R⁴ is cycloalkyl, or heterocycloalkyl. In one embodiment of Formula (VI),

R¹ is R⁴; and R⁴ is cycloalkyl. In one embodiment of Formula (VI), R¹ is R⁴; and R⁴ is heterocycloalkyl.

In one embodiment of Formula (VI), R¹ is R⁴; and R⁴ is cycloalkyl; wherein R⁴ is unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted as defined herein. In another embodiment of Formula (VI), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with R⁵⁷, NHR⁵⁷, or N(R⁵⁷)2- In another embodiment of Formula (VI), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; and R⁵⁷ is R⁶⁰. In another embodiment of Formula (VI), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; and R⁶⁰ is heterocycloalkyl. In another embodiment of Formula (VI), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl; wherein the heterocycloalkyl ring is morpholinyl or piperazinyl. In another embodiment of Formula (VI), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with N(R⁵⁷)2- In another embodiment of Formula (VI), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2. In another embodiment of Formula (VI), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶¹, and R⁶¹ is alkyl which is unsubstituted. In another embodiment of Formula (VI), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶⁰, and R⁶⁰ is cycloalkyl which is unsubstituted. In another embodiment of Formula (VI), R¹ is R⁴; and R⁴is cycloalkyl; wherein the cycloalkyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (VI), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (VI), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷, R⁵⁷ is R⁶⁰, and R⁶⁰ is heterocycloalkyl which is unsubstituted.

In one embodiment of Formula (VI), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein R⁴is unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), R¹is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted as defined herein. In another embodiment of Formula (VI), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein

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PCT/US2010/036844 the heterocycloalkyl ring is substituted with R⁵⁷. In another embodiment of Formula (VI), R¹is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the heterocycloalkyl ring is substituted with one or two or three or four or five more R⁵⁷; SC&gt;2R⁵⁷,or OH, and R⁵⁷ is R⁶⁰ or R⁶¹. In another embodiment of Formula (VI), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰ or R⁶¹; R⁶⁰ is cycloalkyl or heterocycloalkyl; and R⁶¹ is alkyl. In another embodiment of Formula (VI), R¹is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl, wherein the heterocycloalkyl is morpholinyl, tetrahydropyranyl or oxetanyl. In another embodiment of Formula (VI), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is cycloalkyl, wherein the cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of Formula (VI), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl, or

57 61 61 piperizinyl ring is substituted with one or two or three or four or five R ; R is R^D1;R^D1 is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl. In another embodiment of Formula (VI), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl,

C-7 C-y Z--1 Z--1 or piperizinyl ring is substituted with one or two or three or four or five R ; R is ROUROl is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl; wherein the Ci-alkyl, C2-alkyl, or C3alkyl are unsubstituted or substituted.

In one embodiment of Formula (VI), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted. In one embodiment of Formula (VI), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted with R⁷, OR⁷, N(R⁷)2, or OH.

In one embodiment of Formula (VI), R⁷ is R¹⁰ or Rⁿ which are unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), R is R which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), R⁷ is Rⁿ which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (VI), R¹⁰ is cycloalkyl or heterocycloalkyl which are unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), R¹⁰ is

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PCT/US2010/036844 heterocycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), R¹⁰ is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxanyl, piperidinyl, piperizinyl, or pyrrolidinyl, which are unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), R¹⁰ is tetrahydropyranyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), R¹⁰ is morpholinyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), R¹⁰ is cycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), R¹⁰ is cyclohexyl which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (VI), Rⁿ is alkyl which is unsubstituted. In another embodiment of Formula (VI), Rⁿ is methyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VI), Rⁿ is alkyl, which is substituted as defined herein. In another embodiment of Formula (VI), Rⁿ is alkyl, which is substituted with OR¹², R¹² is R¹⁶, and R¹⁶ is alkyl.

In one embodiment of Formula (VI), n is 0.

Still another embodiment pertains to compounds having Formula (VI), which are

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl}piperazin-l-yl)-2-[(4chloro-lH-pyrrolo[2,3-b]pyridin-5-yl)oxy]-N-({ 3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

In another aspect, the present invention provides compounds of Formula (VII)

<img file="NZ600084A_D0009.tif" />

z³ (VII) and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof,

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PCT/US2010/036844 wherein A¹, B¹, D¹, E¹, Y¹, Z², L¹, and Z³ are as described herein for Formula (I), n is 0, 1, 2, or 3; describing the number of additional substituents on R²⁶, and R¹⁰⁰ is as described for substituents on R , and at least one R is a substituent as described for substituents on R and R^42A, and the remainder are H.

In one embodiment of Formula (VII), A¹ is N. In another embodiment of Formula (VII), A¹ is C(A²). In another embodiment of Formula (VII), A¹ is C(A²); and A² is H.

In one embodiment of Formula (VII), B¹ is NHQCOR¹, NHSO2R¹, OR¹, or NHR¹. In another embodiment of Formula (VII), A¹ is C(A²); A² is H; and B¹ is NHR¹. In another embodiment of Formula (VII), A¹ is C(A²); A² is H; and B¹ is OR¹. In another embodiment of Formula (VII), A¹ is C(A²); A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (VII), A¹ is C(A²); A² is H; and B¹ is NHC(O)R¹. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is H; and B¹ is NHR¹. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is H; and B¹ is OR¹. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is H; and B¹ is NHC(O)R¹.

In one embodiment of Formula (VII), D¹ is H. In another embodiment of Formula (VII), A¹ is C(A²); A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (VII), A¹ is C(A²); A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (VII), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (VII), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; and D¹ is H. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; and D¹ is H.

In one embodiment of Formula (VII), E¹ is H. In another embodiment of Formula (VII), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VII), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VII), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VII), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H.

In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H.

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In one embodiment of Formula (VII), Y¹ is H, CN, NO2, F, Cl, Br, CF3, R¹⁷, or SO2R¹⁷. In another embodiment of Formula (VII), Y¹ is NO2. In another embodiment of Formula (VII), Y¹ is Cl. In another embodiment of Formula (VII), Y¹ is SO2R¹⁷; wherein R¹⁷is as defined herein. In another embodiment of Formula (VII), Y¹ is SO2R¹⁷; wherein R¹⁷ is alkyl. In another embodiment of Formula (VII), Y¹ is R¹⁷; wherein R¹⁷ is alkynyl. In another embodiment of Formula (VII), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO2R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (VII), A¹is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NC&gt;2.In another embodiment of Formula (VII), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (VII), A¹ is C(A²);

A² is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO2R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is H; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (VII), A¹ is C(A²) or N; A² is H; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl.

In one embodiment of Formula (VII), R¹ is R², and R² is phenyl. In another embodiment of Formula (VII), R¹ is R², and R² is phenyl which is substituted with NO2, and NHR⁵⁷.

In one embodiment of Formula (VII), R¹ is R⁴ or R⁵. In one embodiment of Formula (VII), R¹ is R⁴. In one embodiment of Formula (VII), R¹ is R⁵. In one embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl, or heterocycloalkyl. In one embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl. In one embodiment of Formula (VII), R¹ is R⁴; and R⁴ is heterocycloalkyl.

In one embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein R⁴ is unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted as defined herein. In another embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with R⁵⁷, NHR⁵⁷, or N(R⁵⁷)2. In another embodiment of Formula (VII), R¹is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; and R⁵⁷ is R⁶⁰. In another embodiment of Formula (VII), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; and R⁶⁰ is heterocycloalkyl. In another

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PCT/US2010/036844 embodiment of Formula (VII), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl; wherein the heterocycloalkyl ring is morpholinyl or piperazinyl. In another embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with N(R⁵⁷)2- In another embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2. In another embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶¹, and R⁶¹ is alkyl which is unsubstituted. In another embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶⁰, and R⁶⁰ is cycloalkyl which is unsubstituted. In another embodiment of Formula (VII), R¹ is R⁴; and R⁴is cycloalkyl; wherein the cycloalkyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (VII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷, R⁵⁷ is R⁶⁰, and R⁶⁰ is heterocycloalkyl which is unsubstituted.

In one embodiment of Formula (VII), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein R⁴is unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), R¹is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted as defined herein. In another embodiment of Formula (VII), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is substituted with R⁵⁷. In another embodiment of Formula (VII), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the heterocycloalkyl ring is substituted with one or two or three or four or five more R⁵⁷; SC&gt;2R⁵⁷,or OH, and R⁵⁷ is R⁶⁰ or R⁶¹. In another embodiment of Formula (VII), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰or R⁶¹; R⁶⁰ is cycloalkyl or heterocycloalkyl; and R⁶¹ is alkyl. In another embodiment of Formula (VII), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl, wherein the heterocycloalkyl is morpholinyl, tetrahydropyranyl or oxetanyl. In another

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PCT/US2010/036844 embodiment of Formula (VII), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl; ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is cycloalkyl, wherein the cycloalkyl is cyclopropyl or cyclopentyl. In another embodiment of Formula (VII), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl ring is substituted with one or two or three or four or five R⁵⁷; R⁵⁷is R⁶¹;R⁶¹ is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl. In another embodiment of Formula (VII), R¹ is R⁴; R⁴ is heterocycloalkyl; wherein the heterocycloalkyl ring is piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl, and wherein the piperidinyl, pyrrolinyl, morpholinyl, or piperizinyl ring is substituted with one or two or three or four or five R⁵⁷; R⁵⁷is R⁶¹;R⁶¹ is alkyl; and the alkyl is Ci-alkyl, C2-alkyl, or C3-alkyl; wherein the Ci-alkyl, C2alkyl, or C3-alkyl are unsubstituted or substituted.

In one embodiment of Formula (VII), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted. In one embodiment of Formula (VII), R¹ is R⁵; and R⁵ is alkyl which is unsubstituted or substituted with R⁷, OR⁷, N(R⁷)2, or OH.

In one embodiment of Formula (VII), R⁷ is R¹⁰ or Rⁿ which are unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), R is R which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), R⁷ is Rⁿ which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (VII), R¹⁰ is cycloalkyl or heterocycloalkyl which are unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), R¹⁰is heterocycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), R¹⁰ is tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, dioxanyl, piperidinyl, piperizinyl, or pyrrolidinyl, which are unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), R¹⁰ is tetrahydropyranyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), R¹⁰is morpholinyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), R¹⁰ is cycloalkyl which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), R¹⁰ is cyclohexyl which is unsubstituted or substituted as defined herein.

In one embodiment of Formula (VII), Rⁿ is alkyl which is unsubstituted. In another embodiment of Formula (VII), Rⁿ is methyl, which is unsubstituted or substituted as defined herein. In another embodiment of Formula (VII), Rⁿ is alkyl, which is substituted as defined

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PCT/US2010/036844 herein. In another embodiment of Formula (VII), Rⁿ is alkyl, which is substituted with OR¹²,

R¹² is R¹⁶, and R¹⁶ is alkyl.

In one embodiment of Formula (VII), n is 0.

Still another embodiment pertains to compounds having Formula (VII), which are 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indazol-4-yl)oxy)-N-((4-((3-morpholin-4-ylpropyl)amino)-3nitrophenyl)sulfonyl)benzamide;

4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl)methyl)piperazin-l-yl)-2-((3methyl-lH-indazol-4-yl)oxy)-N-((4-((l-methylpiperidin-4-yl)amino)-3nitrophenyl)sulfonyl)benzamide;

N-( {5-chloro-6- [(trans-4-hydroxycyclohexyl)methoxy]pyridin-3 -yl} sulfonyl)-4-(4- {[2-(4chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl]piperazin-l-yl)-2-[(6-fluoro-lHindazol-4-yl)oxy]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} piperazin-1 -yl)-2- [(6-fluorolH-indazol-4-yl)oxy]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 - y 1) - 2- [ (6 fluoro- lH-indazol-4-yl)oxy]-N-[(4-{ [(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino }-3nitrophenyl)sulfonyl]benzamide;

N-( {5-chloro-6- [(trans-4-hydroxycyclohexyl)methoxy]pyridin-3 -yl} sulfonyl)-4-(4- {[2-(4chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl]methyl }piperazin-1 -yl)-2- [(7-fluoro- 1Hindazol-4-yl)oxy]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} piperazin-1 -yl)-2- [(7-fluorolH-indazol-4-yl)oxy]benzamide;

4-(4- {[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-1 -yl] methyl} piperazin-1 - y 1) - 2- [ (7 fluoro-lH-indazol-4-yl)oxy]-N-[(4-{ [(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino }-3nitrophenyl)sulfonyl]benzamide;

N-([5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl)-4-(4{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en-1 -yl] methyl} piperazin-1 -yl)-2- [(6-fluorolH-indazol-4-yl)oxy]benzamide;

2- [(3 -amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 yl]methyl]piperazin-l-yl)-N-[(4-[[(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

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2- [(3 -amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 y 1 ] methyl} piperazin- l-yl)-N-({ 4- [(4-fluorotetrahydro-2H-pyran-4-yl)methoxy] -3 nitrophenyl} sulfonyl)benzamide;

2-[(3-amino-lH-indazol-4-yl)oxy]-N-([5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4yl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en-lyl] methyl} piperazin-1 -yl)benzamide;

2- [(3 -amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-([3-nitro-4-[(tetrahydro-2H-pyran-4ylmethyl)amino]phenyl} sulfonyl)benzamide;

4-(4-( [2-(4-chlorophenyl)-4,4-dimethylcyclohex- 1-en- l-yl]methyl}piperazin- l-yl)-2-[(6fluoro-lH-indazol-4-yl)oxy]-N-({4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3nitrophenyl} sulfonyl)benzamide;

2- [(3-amino-1 H-indazol-4-yl)oxy] -4-(4- {[2-(4-chloropheny 1)-4,4-dimethylcyclohex-1 -en-1 yl]methyl}piperazin-l-yl)-N-[(4-([(trans-4-methoxycyclohexyl)methyl]amino}-3nitrophenyl)sulfonyl]benzamide;

2-[(3-amino-lH-indazol-4-yl)oxy]-N-((5-chloro-6-[(trans-4-hydroxy-4methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-4-(4-([2-(4-chlorophenyl)-4,4dimethylcyclohex-1 -en- 1-yl]methyl (piperazin-1 -yl)benzamide;

N-((5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl(sulfonyl)-2-[(3chloro-lH-indazol-4-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1y 1 ] methyl} piperazin-1 -yl)benzamide;

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-l-en-l-yl]methyl(piperazin-l-yl)-N-({5cyano-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl}sulfonyl)-2-[(6-fluorolH-indazol-4-yl)oxy]benzamide; and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof.

In another aspect, the present invention provides compounds of Formula (VIII)

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<img file="NZ600084A_D0010.tif" />

(VIII) and therapeutically acceptable salts, prodrugs, salts of prodrugs and metabolites thereof, wherein A¹, B¹, D¹, E¹, Y¹, Z², L¹, and Z³ are as described herein for Formula (I), n is 0, 1, 2, or 3; describing the number of additional substituents on R²⁶, and R¹⁰⁰ is as described for substituents on R , and at least one R is a substituent as described for substituents on R and R^42A, and the remainder are H.

In one embodiment of Formula (VIII), A¹ is N. In another embodiment of Formula (VIII), A¹ is C(A²). In another embodiment of Formula (VIII), A¹ is C(A²); and A² is H.

In one embodiment of Formula (VIII), B¹ is NHCCCOR¹, NHSO2R¹, OR¹, or NHR¹. In another embodiment of Formula (VIII), A¹ is C(A²); A² is H; and B¹ is NHR¹. In another embodiment of Formula (VIII), A¹ is C(A²); A² is H; and B¹ is OR¹. In another embodiment of Formula (VIII), A¹ is C(A²); A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (VIII), A¹ is C(A²); A² is H; and B¹ is NHC(O)R¹. In another embodiment of

Formula (VIII), A¹ is C(A²) or N; A² is H; and B¹ is NHR¹. In another embodiment of

Formula (VIII), A¹ is C(A²) or N; A² is H; and B¹ is OR¹. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is H; and B¹ is NHSO2R¹. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is H; and B¹ is NHC(O)R¹.

In one embodiment of Formula (VIII), D¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; and D¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; and D¹ is H. In another embodiment

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PCT/US2010/036844 of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; and D¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is NHSO2R¹; and D¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; and D¹ is H.

In one embodiment of Formula (VIII), E¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹is NHSO2R¹; D¹ is H; and E¹ is H. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is NHC(O)R¹; D¹ is H; and E¹ is H.

In one embodiment of Formula (VIII), Y¹ is H, CN, NO2, F, Cl, Br, CF3, R¹⁷, or SO2R¹⁷. In another embodiment of Formula (VIII), Y¹ is NO2. In another embodiment of Formula (VIII), Y¹ is Cl. In another embodiment of Formula (VIII), Y¹ is SO2R¹⁷; wherein R¹⁷ is as defined herein. In another embodiment of Formula (VIII), Y¹ is SO2R¹⁷; wherein R¹⁷is alkyl. In another embodiment of Formula (VIII), Y¹ is R¹⁷; wherein R¹⁷ is alkynyl. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO2R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO2R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (VIII), A¹ is C(A²); A² is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2 or SO2R¹⁷; wherein R¹⁷ is alkyl or alkynyl. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is NO2. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is NHR¹; D¹ is Η; E¹ is H; and Y¹ is SO₂R¹⁷, wherein R¹⁷ is alkyl substituted with three F. In another embodiment of Formula (VIII), A¹ is C(A²) or N; A² is Η; B¹ is OR¹; D¹ is Η; E¹ is H; and Y¹ is Cl.

In one embodiment of Formula (VIII), R¹ is R², and R² is phenyl. In another embodiment of Formula (VIII), R¹ is R², and R² is phenyl which is substituted with NO2, and NHR⁵⁷.

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In one embodiment of Formula (VIII), R¹ is R⁴ or R⁵. In one embodiment of Formula (VIII), R¹ is R⁴. In one embodiment of Formula (VIII), R¹ is R⁵. In one embodiment of

Formula (VIII), R¹ is R⁴; and R⁴ is cycloalkyl, or heterocycloalkyl. In one embodiment of

Formula (VIII), R¹ is R⁴; and R⁴ is cycloalkyl. In one embodiment of Formula (VIII), R¹ is

R⁴; and R⁴ is heterocycloalkyl.

In one embodiment of Formula (VIII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein R⁴ is unsubstituted or substituted as defined herein. In another embodiment of Formula (VIII), R¹is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted as defined herein. In another embodiment of Formula (VIII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with R⁵⁷, NHR⁵⁷, or N(R⁵⁷)2. In another embodiment of Formula (VIII), R¹is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; and R⁵⁷ is R⁶⁰. In another embodiment of Formula (VIII), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; and R⁶⁰ is heterocycloalkyl. In another embodiment of Formula (VIII), R¹ is R⁴; R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with R⁵⁷; R⁵⁷ is R⁶⁰; R⁶⁰ is heterocycloalkyl; wherein the heterocycloalkyl ring is morpholinyl or piperazinyl. In another embodiment of Formula (VIII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is substituted with N(R⁵⁷)2- In another embodiment of Formula (VIII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2. In another embodiment of Formula (VIII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶¹, and R⁶¹ is alkyl which is unsubstituted. In another embodiment of Formula (VIII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with N(R⁵⁷)2, R⁵⁷ is R⁶⁰, and R⁶⁰ is cycloalkyl which is unsubstituted. In another embodiment of Formula (VIII), R¹ is R⁴; and R⁴is cycloalkyl; wherein the cycloalkyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (VIII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷. In another embodiment of Formula (VIII), R¹ is R⁴; and R⁴ is cycloalkyl; wherein the cycloalkyl ring is cyclohexyl; and wherein the cyclohexyl ring is substituted with NHR⁵⁷, R⁵⁷ is R⁶⁰, and R⁶⁰ is heterocycloalkyl which is unsubstituted.

In one embodiment of Formula (VIII), R¹ is R⁴; and R⁴ is heterocycloalkyl; wherein R⁴ is unsubstituted or substituted as defined herein. In another embodiment of Formula

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