Glucocorticoid receptor modulators

This invention relates to glucocorticoid receptors, together with their use and pharmaceutical compositions.

This invention also provides non-steroidal compounds which are selective (peas agonist and antagonist) steroid receptors, especially the glucocorticoid receptor. This invention also provides pharmaceutical compositions containing these compounds. Sick-block receptors are useful for the treatment of diseases such as obesity, diabetes, bfilgu and others as described below.

Core receptors are commonly defined as a family of linker transcription factors that are activators in link binding, (RM Evans, 240 Science, 889 (1988)). Members of this family include the following receptors: glucocorticoids, ovarian corticosteroids, androgen, progesterone and estrogen. Naturally occurring compounds for these receptors are molecules of low molecular weight that play an important role in health and in many diseases. Abundance or lack of these links can have severe physiological consequences. For example, an excess of glucocorticoids leads to Cushingsheilkenna, while too many amounts of glucocorticoids lead to Addisonsveiki.

The glucocorticoid receptor (GR) is present in cells that show the response of glucocorticoids as it is present in the cell cycle in an inactivated state until stimulated by agonists. Vifi stimulation moves the glucocorticosteroid over the cellular couple, which interacts specifically with DNA and / or protein and controls the transcription in a glucocorticosteroid manner. Two examples of the proteins that interact with the glucocorticosteroids are the transcription factors API and NFk-B. Antibiotics inhibitory inhibitors of API and NFk-B mifilafir transcription and are considered to be responsible for any of the bipolar blocking activity of glucocorticoids administered intravenously. For fibroids, glucocorticosteroids can also show physiological effects regardless of core enrollment. Biologically potent glucocorticosteroids include hydrocortisone and corticosteroids. There are many arthritis-steroidal anti-inflammatory drugs and paced dexamethasone, prednisin and prednisilone. By definition, glucocorticosteroid antagonists bind the vectors and prevent the presence of glucocorticosteroids, and call for a GR mifilafia event, related to transcripts. RU486 is a drug of the most common glucocorticosteroid antifungal drug.

U.S. Patent No. 3,683,091 discloses phenanthrin compounds, especially certain di-7-hydroxy or methyl-2,3,4,4a, 9,10-hexahydrophenantren-2-one and 4a-alkyl derivatives, hydrogenated derivatives, functional derivatives and potentially active neighborhoods of which are useful as specific antidepressant agents.

Japanese Patent Application, Publication No. 45014056, published on May 20, 1970, discloses a prodrug of 1,2,3,4,9,10,11a, 12-octahydro-7-methoxy-12β-butylphenanephen-2β-ol and certain derived pairs of which are useful as anti-androgen and antiviral drugs.

Japanese Patent Application, Publication No. 6-263688, published on September 20, 1994, discloses certain phenanthene derivatives that are leukocyte-1 (IL-1) inhibitors. It also describes the development of them and certain intermediaries.

International patent application, publication no. WO 95/10266, published April 20, 1995, describes the proliferation and formulation of certain phenanthene derivatives as the nitrogen ecox novel synthesis inhibitor.

Japanese Patent Application, Publication No. 45-36500, published November 20, 1970, describes power sequences for the propagation of certain light-acting phenanthrene derivatives useful as anti-androgenic drugs.

European Patent Application, Publication No. 0 188 396, published July 23, 1986, discloses certain substituted stereotypes, certain methods and intermediates for the propagation thereof, their use and pharmaceutical compositions containing them. It is reported that these compounds have anti-glucocorticosteroid activity, some of which have glucocorticosteroid activity.

CF Bigge et al., J. Med. Chem. 1993, 36, 1977-1995, describe the novel and pharmacological assessment of the octahydrophenantrenamine group and their specific heterocyclic analogues as potential non-competitive antagonists for the N-methyl-D-aspartate receptor complex.

PR Kanjilal et al., J. Org. Chem. 1985, 50, 857-863, describe novel studies related to the proliferation of certain complex diterpenoids.

G. Sinha et al., J. Chem. Soc., Perkin Trans. I (1983), (10), 2519-2528, disclose the reconstitution of the turbine bridging diches cis-3,4,4a, 9,10,10a-hexahydro-1,4a-ethanophenanthrene-2 ​​(1H), 12-dione and trans-3,4,4a, 9,10,10a-hexahydro-3,4a-ethanophenanthrene-2 ​​(1H), 12-dione with highly regional valine molecular weight aldol condensation through spacecraftically defined cis- and trans-2,2-ethylenedioxy-1 , 2,3,4,4a, 9,10,10a-oktahýdrófenantren-4a-ýlaset-aldehyde.

UR Ghatak, M. Sarkarog SK Patra, Tetrahedron Letters no. 32, p. 2929-2931, 1978, discloses a simple, cross-functional pathway to certain multicircular bridal scavenger products useful for the proliferation of several complexed terpathoids.

PN Chakrabortty et al., Indian J. Chem. (1974), 12 (9), 948-55, describe the synthesis of 1α-methyl-1β, 4β-dicarboxyl-1,2,3,4,4a, 9,10,10aβ-octahydrophenanthrene, intermediate intermediate on certain dipteroids and diterp alkaloids and on 1β-4α β-dicarboxyl-1,2,3,4,4a, 9,10,1-Oaa-octahydrophenanthrene.

E. Fujita et al., J. Chem. Soc., Perkin Trans. I (1974), (1), 165-77, describe a derivative of 5-methoxy-2-tetralone on ent-3-p, 2-epoxy-3-methoxy-17-naphthauran-16a-diol.

H. Sdassi et al., Synthetic Communications, 25 (17), 2569-2573 (1995) describe enantiomeric selective synthesis of (R) - (+) - 4a-cyanomethyl-6-methoxy-3,4,9, 10-tetrahydrophenanthrene-2-one, a key ingredient in morphine synthesis.

T. Ibuka et al., Yakugaku Zasshi (1967), 87 (8), 1014-17, describe certain alkaloids of menispermaceous plants.

Japanese Patent No. 09052899, dated February 25, 1997, discloses certain dipter or triterpen derivatives which are leukotriene antagonists as attached to Trypterium wilfordii extract for treatment use.

U.S. Patent No. 5,669,127 describes certain non-steroidal compounds, such as 5H-chromo [3,4-f] quinoline, which are selective for steroid receptors.

U.S. Patent No. 5,767,113 describes certain synthetic steroidal compounds which are useful for the potentiation of activated glucose-induced response and for reducing polyvalent learning.

Published European Patent Application 0 683 172, published November 11, 1995, discloses certain 11,21-bisphenyl-19-norpregna derivatives having anti-glucose activity and which can be used to treat or prevent glucose-dependent diseases.

D. Bonnet-Delpon et al., Tetrahedron (1996), 52 (1), 59-70, describes certain CF₃-set alkenum as a good partner in Diels-Alder reactions with Danishefsky's Dien and in 1,3-bipolar cyclic cycles with certain nitrons and unstable asomethine ions.

International Patent Application Publication No. WO 98/26783, published June 25, 1998, discloses the use of certain steroid compounds with antiglycerin activity, excludes mepepristone, for the propagation of prophylaxis or treatment of psychotic or hypoglycaemia.

International Patent Application Publication No. WO 98/27986, published July 2, 1998, discloses a treatment for insulin-dependent diabetes (NIDDM), enhancing Type II diabetes, by administering a combination of treatment agents that exhibit Type I agonist activity and glucocorticoid receptor agonist activity. Therapeutic agents such as certain steroidal compounds having both type II agonist and glucocorticosteroid type II antagonist activity are also described.

International Patent Application Publication No. WO 98/31702, published July 23, 1998, discloses certain 16-hydroxy-11- (substituted phenyl) -estra-4,9-diene derivatives useful for the treatment or prophylaxis of glucocorticoid diseases or syndromes.

Published European Patent Application 0 903 146, published March 24, 1999, discloses that steroid 21-hydroxy-6,19-oxidopogesterone (21OH-6OP) has been found to be a selective anti-glucocorticosteroid useful for the treatment of high-density diseases of diabetes mellitus, like Cushing's syndrome or depression.

All patents and published patent applications referred to above are hereby incorporated as a whole.

YES Findlay et al., Tetrahedron Letters no. 19, bis. 869-872, 1962, describe decisive intermediates for the reconstitution of diterpine alkaloids.

In spite of the presence of glucocorticosteroid therapies in the subject, there is a continuing need for and continuing the search for selective glucocorticosteroid treatments in the subject. Identification of non-steroidal compounds having specificity for one or more steroid receptors, but which have decreased or no cross-activity for other steroids or intracellular receptors, is highly valuable in this subject.

This invention specifically provides:

a compound of formula I

<img file="IS2743B_D0001.tif" />

a mixture thereof or a pharmaceutically acceptable salt of said compound or hydrogen atom; where m is 1 or 2;

- is a possible interface;

A is selected from the group consisting of

<img file="IS2743B_D0002.tif" />

D θγ CR₇, CR₇R_1s, N, NR₇ promote 0;

E is C, CR₆ promote N;

F is CR₄, CR₄R₅ promote 0;

G, H and I, together with two carbon atoms from the A-ring, promote 2 carbon atoms from the B-ring form a 5-membered heterocyclic ring containing one more more N, power on given power it is all power one and 0 in each cycle;

J, K, L and M together with 2 carbon atoms, the B-ring forms a 6-membered heterocyclic ring containing one further N-atom;

X is a) absent, b) -CH₂-, c) -CH (OH) -phenyl d) -C (O) -;

R is a) -H, b) -Z-CF₃, c) - (C1-C6 alkyl, d) - (C₂-C₆) alkenyl, e) - (C₂-C₆) alkynyl, f) -CHO, g) -CH = N-OR₁₂, h) -ZC (O) OR₁₂, i) -ZC (O) -NR₁₂R₁₃, j) -ZC (O) -NR₁₂-Z-het, k) -Z-NR₁₂R₁₃, I) -Z-NR₁₂het, m) -Z-het, n) -ZO-het, O) -Z-aryl, p) -ZO-aryl, q) -CHOH-aryl, iso) -C (O) ; pair of aryl substituents o) enhancing r) is independently substituted with 0, 1 enhancing 2 of the following: -Z-OH, -Z-NR₁₂R₁₃, -Z-NR₁₂-het, -C (O) NR₁₂R₁₃, -C (O) OC1-4alkyl, -C (O) OH, -C (O) -heth, -NRu-C1-C10C1-6alkyl, -NR₁₂-C (O) - (C₂-C₆) alkenyl, -NR₁₂-C (O) - (C₂-C₆) alkynyl, -NR₁₂-C (O) -Z-het, -CN, -Z-het, -O- (C₁-C₃) Alkyl-C (O) NR_L2R₁₃, -O- (C_rC₃) Alkyl-C (O) O- (C_rC₆) alkyl, -NR2-Z-C1-10 alkyl, -N (ZC (O) O (C₁-C₆) Alkyl)₂, -NR₁₂-ZC (O) NR₁₂R 11, -Z-NR₁₂-SO₂-ri₃, -NR₁₂-SO₂-het, -C (O) H, -Z-NRir2-OC1 -C5 alkyl, -Z-NR₁₂-Z-NR₁₂R_3l -Z-NR₁₂- (C₃-C₆) cycloalkyl, -ZN (Z0 (C 1 -C 6) alkyl)₂, -SO₂R₂₎ -SO₂, -SR-i₂, -SO₂NR₁₂R₁₃, -O-O (O) - (C₄) alkyl, -O-SO₂- (C₁-C₄) alkyl, -halogen or -CF₃;

Z in each case is independent of another) - (C₀-C₅) alkyl, b) - (C₂-C₆) alkenyl or c) - (C₂-C₆) Alkynyl;

R₂ is a) -H, b) -halogen, c) -OH, d) - (C1-C6alkyl substituted with 0 or 1 -OH, e) -NR₁₂R₁₃, f) -ZC (O) O (C, -C₆) alkyl, g) -ZC (O) NR₁₂R_13L h) -O- (C 1 -C 6)₆) alkyl, i) -ZOC (O) - (C 1 -C 6 alkyl, j) -ZO- (C₁-C₃) Alkyl-C (O) NR₁₂R₁₃, k) -ZO-C 1 -C 6 alkyl-C 1-10 cycloalkyl, (I)

-O- (C₂-C₆) alkenyl, m) -O- (C₂-C₆) alkynyl, n) -O2-het, o) -COOH, p) -C (OH) R 1₂R₃ or q) -Z-CN;

R₃ is a) -H, b) - (C1 -C10) alkyl wherein 1 or 2 carbon atoms, apart from a carbon atom, may optionally be substituted by one or two heteroatoms independently selected from S, O and N, and wherein each carbon atom is Seated with 0.1 or 2 R_y, c) - (C₂-C₁₀) alkenyl substituted with 0, 1 or 2 R_y, d) - (C₂-C₁₀) alkynyl wherein one carbon atom, in addition to the carbon-bonded carbon atom, may optionally be substituted by one oxygen atom and a pair of which each carbon atom is substituted with 0, 1 or 2 R_y, e) -CH = C-CH₂, f) -CN, g) - (C₃-C₆) cycloalkyl, h) -Z-aryl, i) -Z-het, j) -C (O) O (C, -C₆) alkyl, k) -O (C_rC_e) alkyl, I) -ZSR₁₂, m) -ZS (O) -R₁₂, n) -ZS (O)₂-R₁₂, o) -CF₃, p) -NR₁₂O- (C1 -C6) alkyl or q) -CH2₂OR_y, provided that another of R₂and r₃ is absent when there is a double link between CR₂R₃ (7th position) and F group (8th position) on the C-ring;

R_y is in each case independently a) -OH, b) halogen, c) -Z-CF₃, d) -Z-CF (C₁-C₃alkyl)₂, e) -CN, f) -NR₁₂R₃, g) - (C₃-C₆) cycloalkyl, h) - (C₃-C₆) cycloalkenyl, i) - (C₀-C₃) alkyl-aryl, j) -het or k) -N₃;

or R₂ and r₃ are summarized to form a) = CHR₁₁, b) = NOR_1b c) = 0, d) = N-NR₁₂, e) = N-NR₁₂C (O) -R₁₂, f) oxiranyl or g) 1,3-dioxolan-4-yl;

R₄ and r₅ are in each case independently a) -H, b) -CN, c) - (C₁-C_B) alkyl substituted with 0 to 3 halogens, d) - (C₂-C₅) alkenyl substituted with 0 to 3 halogens, e) - (C₂-C_s) alkynyl substituted with 0 to 3 halogens, f) -O-C1-C6alkyl substituted with 0 to 3 halogens, g) -O- (C₂-C₆) alkenyl substituted with 0 to 3 halogens, h) -O- (C₂-C₆) alkynyl substituted with 0 to 3 halogens, i) halogen, j) -OH, k) - (C₃-C₅) cycloalkyl or I) - (C₃-C₆) Cycloalkenyl;

or R₄ and r₅ are combined to form = 0;

R₆ is a) -H, b) -CN, c) - (C 1 -C 6)₆) alkyl substituted with 0 to 3 halogens, d) - (C₂-C₆) alkenyl substituted with 0 to 3 halogens, e) - (C₂-C₆) alkynyl which is substituted with 0 to 3 halogens or f) -OH;

R₇ and R6 are each independently, a) -H, b) -halogen, (c) -CN, d) - (C1-6alkyl) substituted with 0 to 3 halogen, e) - (C₂-C₆) alkenyl substituted with 0 to 3 halogens or f) - (C₂-C₆) alkynyl substituted with 0 to 3 halogens; assuming that R₇ is other than -CN or -halogen when D is NR₇;

or R₇ and Ri₆ are combined to form = 0;

R_e, R₉, R₁₄ and r₁₅ are each independently a) -H, b) halogen, c) - (C1 -C6) alkyl substituted with 0 to 3 halogens, d) - (C₂-C₆) alkenyl substituted with 0 to 3 halogens, e)

- (C₂-C₆) alkynyl which is substituted with 0 to 3 halogens, f) -CN, g) - (C₃-C₆) cycloalkyl, h) - (C₃-C₆) -cycloalkenyl, i) -OH, j) -O-C1 -C6 alkyl, k) -O-C1 -C6 alkenyl, (C1 -C6) cycloalkyl, m) -NR₁₂R₁₃, n) -C (O) OR₁₂ or o) -C (O) NR₁₂RI3;

or Rg and R_g are combined on the C-ring to form = 0; with the condition force when m is 2 is only a single set of R₈ and r_g tangible to force image = 0;

promote R.₁₄ and r₁₅ are combined to force the image = 0; with the requirement force when R₁₄ and r₁₅ are compiled to force the image = 0, is D more than CR? and E is annafl a C;

R₁₀ is a) - (C1 -C6) alkyl substituted with 0 to 3 substituents independently selected from -halogen, -OH and -N₃, b) - (C₂-C₁₀) alkenyl which is substituted with 0 to 3 substituents independently selected from -halogen, -OH and -N₃, c) - (C₂-C₁₀) alkynyl which is substituted with 0 to 3 substituents independently selected from halogen, -OH and -N₃, d) -halogen, e) -Z-CN, f) -OH, g) -Z-het, h) -Z-NR₁₂R₁₃, i) -ZC (O) -het, j) -Z-C₁₋₆CrC₆alkyl, k) -ZC (O) -NR₁₂R₁₃, 1) -ZC (O) -NR₁₂-Z-CN, m) -ZC (O) -NR1₂-Z-het, n) -ZC (O) -NR₁₂-Z-aryl, o) -ZC (O) -NR₁₂-Z-NR₁₂R₁₃, p) -ZC (O) -NR₁₂-ZO (C_rC₆) alkyl, q) - (C₀-C₆) alkyl-C (O) OH, R) -Z-C1-10C1C1) alkyl, s) -ZO- (C₀-C₆) alkyl-het, t) -ZO- (C₀-C₆) alkyl-aryl, u) -Z-C 1 -C 6 C 1-6 alkyl substituted with 0 to 2 R_x, v) -ZO- (C_rC₆) alkyl -CH (O), w) -ZO-jCrC1alkyl-NR5 -het, x) -ZO2-het-Z-het, y) -ZO2-het-Z-NR₁₂R₁₃, z) -ZOZ-het-C (O) -het, a1) -ZO2C (O) -het, b1) -ZO2C (O) -het-het, d) -ZO2C (O) - (C_rC₆) alkyl, d 1) -ZO 2 C (S) -NR₁₂R₁₃, e1) -ZO2C (O) -NR₁₂R₁₃, f1) -ZO2- (C1 -C6)₃) Alkyl-C (O) NR₁₂R₁₃, g1) -ZO2C (O) -O (CrC₆) alkyl, hi) -ZO 2 C (O) -OH, (1) -ZO 2 -CO 2 -NR 4 -OCC 1 -C 6 alkyl, j 1) -ZO 2 C (O) -NR₁₂-OH, k 1) -ZO 2 C (O) -NR₁₂-Z-NR₁₂R₁₃, 11) -ZOZC (O) -NR₁₂-Z-het, ml) -ZO2C1 -NR5 -SOHCrC1 alkyl, n1) -ZO2C (= NR₁₂) (NR₁₂R₁₃), o1) -ZOZC (= NOR₁₂) (NR₁₂R₁₃), p1) -Z-NR₁₂-C (O) -O2 -NR12 R13, q1) -ZSC (O) -NR₁₂R₁₃, r 1) -ZO-SO₂- (C, -C₆) alkyl, s1) -ZO-SO₂-aryl, t1) -ZO-SO2₂NR₁₂R₁₃, u1) -ZO-SO₂-CF₃, v1) -Z-NR₁₂-C (O) OR₁₃ promote w1) -Z-NR₁₂C (O) R₃;

promote R._g and r₁₀ are summarized in the formula of formula A-5 for power generation a) = 0 amplification b) = NOR₁₂;

Rn is a) -H, b) - (C1-C6) alkyl, c) - (C₃-C₆) cycloalkyl moiety d) - (C₀-C₃) Alkyl-aryl;

R12 and R₁₃ In each case, independent of (a) -H, b) - (C1-C6)₆) alkyl pairs which promote 2 carbon atoms, in addition to the carbon atoms, may optionally be replaced by one or two heterocycles independently selected from S, O and N and wherein each carbon atom is substituted with 0 to 6 halogen, c ) - (C₂-C₆) alkenyl substituted with 0 to 6 halves, enhancing d) - (C1-6) alkynyl wherein a carbon atom, which is other than a carbon atom, may optionally be replaced by one oxygen atom and wherein each carbon atom is substituted with 0 to 6 halves;

boosting R12 and R13 are combined with N to power generation;

or R₆ and r_M or R1₅ are combined to form 1,3-dioxolanyl;

aryl is a) phenyl substituted with 0 to 3 R_x, b) naphthyl substituted with 0 to 3 R_x or c) biphenyl substituted with 0 to 3 R_x;

it is a 5-, 6- or 7-membered saturated, partially saturated or unsaturated ring containing from one (1) to three (3) heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur; and comprising potentially bicyclic groups wherein any of said heterocyclic rings is condensed with a benzene ring or other heterocyclic group; and the nitrogen can verify in an oxidized state which gives N-oxide the form; and set with 0 to 3 r_x;

R_x is in each case independently a) -halogen, b) -OH, c) - (C 1 -C 6)₆) alkyl, d) - (C₂-C₆) alkenyl, e) - (C₂-C₆) alkynyl, f) -O (C 1 -C 6)₆) alkyl, g) -O (C₂-C₆) alkenyl, h) -O (C₂-C₆) alkynyl, i) - (C₀-C₆) alkyl-NR12R13, j) -C- (O) -NR1₂R₁₃, k) -Z-SO₂R |₂, I) -Z-SOR 1₂&gt; m) -Z-SRi₂, n) -NR1₂-SO₂R-3, O) -NR₁₂-C (O) -R, 3, p) -NR₁₂-OR_13i q) -SO₂NR₁₂R₁₃, r) -CN, s) -CF₃, t) -C (O) (C_rC₅) alkyl, u) = O, V) -Z-SO₂-phenyl or w) -Z-SO₂-was called';

aryl 'is phenyl, naphthyl or biphenyl;

is a 5-, 6- or 7-membered saturated, partially saturated or unsaturated ring containing from one (1) to three (3) heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur; and which includes potentially bicyclic groups wherein any of said heterocyclic rings is a dense benzene ring of another heterocyclic group;

grandfather said:

1) X-Ri is an optionally substituted hydrogen atom;

2) when R₉ and r₁₀ are placed on the A-ring, they are but one-dimensional double-methoxy;

3) when R₂ and r₃ are taken together to form = CHR n efia = O pair where R n is -O (C 1 -C 6) alkyl, then X is -R, but (C 1 -C 6)₄) Alkyl;

4) when R₂ and r₃ are summarized and are = 0 and R₉ is hydrogen on the A-ring; efia when R₂ is hydroxy, is R₃ hydrogen and R₉ is hydrogen on the A-ring, then R is₁₀ annafi and -O (C_rC₆) alkyl of -O-CH₂-phenyl in the 2-position on the A-ring;

5) when X-RI is (C₁-C₄) alkyl, (C₂-C₄) alkenyl efia (C₂-C₄) alkynyl, R₉ and r₁₀ annafi and monohydroxyphosphate = 0, paired with a diolform pair of pairs, when peer is combined; and

6) when X is absent, Rt is a group containing a heteroatom which is independently selected from N, O, S, which is directly linked to the periphery of the B-ring efia C-ring.

This invention specifically provides a compound according to claim 1, wherein a pharmaceutically acceptable salt of said compound or substitution, characterized in that the A-ring is selected from the group consisting of:

<img file="IS2743B_D0003.tif" />

D is CR7, CR₁₆R₇ or 0;

EerC, CR₆ or N;

F is CR₄, CR4R5 or O; and

X is -CH_Z-.

This invention specifically provides:

a compound according to claim 2, or a pharmaceutically acceptable salt of said compound or a hydrogen atom, characterized in that D is CH₂, E is CH; F is CH₂; R₈ is -H; R_g is -H; m is 2; R₁₄ is -H; R15 is -H; and the A-ring is the group of formula A-1a.

Additionally, this invention provides:

a compound of formula II

<img file="IS2743B_D0004.tif" />

a fused pair of or a pharmaceutically acceptable salt of said compound or substitution, characterized in that R₂ is a) -OH or b) -O-CH₂-was called; R₃ is a) - (C1 -C6) alkyl substituted with 0 or 1 of the following: -CF₃, -CN, - (C₃-C₆) cycloalkyl, -phenyl or -N₃, b) -C 2 -C- which is substituted with 1 of the following: - (C 1 -C 6 alkyl, -Cl, -CF₃, - (C₃-C₆) cycloalkyl, -phenyl or -benzyl; c) -CH₂OH, d) -CH 2 OHC 1 -C 4 alkyl group as a carbon atom is optionally substituted by one oxygen atom, e) -CH₂OH (C₂-C₅) alkenyl, f) -CH₂O (C₂-C₅) alkynyl pair as a carbon atom is optionally substituted by 1 oxygen atom, g) -CH₂OR_y, h) -CN or i) -CF₃; R_y is a) - (C_rC₃) Alkyl-CF₃, b) - (C₃-C_s) cycloalkyl, c) -phenyl or d) -benzyl;

or R₂ and r₃ are combined to form a) -1,3-dioxolan-4-yl or b) = NOR₁i; R11 era) -H, b) - (C 1 -C 6 alkyl, c) - (C₃-C₆) cycloalkyl, d) -phenyl or e) -benzyl.

Even more specific, the invention provides:

compounds of formula II

<img file="IS2743B_D0005.tif" />

a vapor thereof or a pharmaceutically acceptable salt of said compound or vapor, characterized in that

R is a) - (C₁-C₄) alkyl, b) - (C₂-C₄) alkenyl, c) -phenyl substituted with 0 or 1 of the following: -OH, -NR₁₂R₁₃, -NR 2 -CFOHC 1 -C 6 alkyl, -CN, -Z-het, -O-fCrC 2 alkyl-C 2 O 7 -NR 4 R 4, -NR₁₂-ZC (O) NR₁₂R 11, -Z-NR₁₂-SO₂-ri₃, -NR₁₂-SO₂-het, -OC (O) - (C1 -C4)₄) alkyl or -O-SO₂- (C₁-C₄) Alkyl; d) -O-phenyl substituted with 0 or 1 of the following: -Z-NR-i₂R₁₃ or -C (O) NR₁₂Ri3, or e) -CH = CH-phenyl wherein phenyl is substituted with 0 or 1 of the following: -Z-NR₁₂R₁₃ or -C (O) NR 1₂R₁₃;

Z is every case independently - (C₀-C₂) Alkyl;

R10 is a) -CH (OH) (C₁-C₅) alkyl, b) -CN, c) -OH, d) -het, e) -O (O) - (O, -) 3, 1, f) -C (O) -NR₁₂R₁₃, g) -C (O) -NH-Z-het, h) -O- (C₀-C₂) alkyl, i) -O2 C (O) -NR₁₂R₁₃, j) -OZC (O) -NH- (C₀-C₃) alkyl-het or k) -O-ZC (O) -NH- (Co-C₃) Alkyl-NRI₂R₃;

R₂ and r₁₃ are independently another a) -H or b) - (CrC₄) Alkyl;

or R₁₂ and Rn are combined with N to form hot.

This invention specifically provides:

compounds of formula II

<img file="IS2743B_D0006.tif" />

a mixture thereof or a pharmaceutically acceptable salt of said compound or substitution, characterized in that R is a) - (C₂-C₄) alkyl, b) -CH₂CH-CH₂ or c) -phenyl;

R₂ is-OH;

R₃ is a) - (C 1 -C 6 alkyl substituted with 0 or 1 CF₃, b) -C≡C-CH₃, c) -Oct-O-1, d) -C 1 -C-CF₃, e) -CH₂O (C₁-C₃) alkyl substituted with 0 or 1 CF₃, or f) -CF₃;

R₁₀ is -OH or -CN.

In addition, this invention specifically provides: compounds of formula III

<img file="IS2743B_D0007.tif" />

or a pharmaceutically acceptable salt of the aforementioned compound, characterized in that R₃ and r₁₀ are as peer are defined in claim 6.

Particularly gives this invention:

compounds of formula II

<img file="IS2743B_D0008.tif" />

a pair of or a pharmaceutically acceptable salt of said compound or vapor, characterized by

R is a) - (C₂-C₄) alkyl, b) -CH₂-CH = CH₂ or c) -phenyl;

R₂ is -OH;

R₃ is a) - (C 1 -C 6) alkyl substituted with 0 or 1 CF₃, b) -C≡C-CH₃, c) -C≡C-CI, d) -C≡C-CF₃, e) -CH₂O (C_rC₃) alkyl substituted with 0 or 1 CF₃ or f) -CF₃;

R₁₀ is -C (O) -NH-Z pair selected from the group consisting of a) pyridinyl substituted with 0 or 1 methyl, b) pyrimidinyl, c) pyrazinyl, d) morpholinyl and e) oxadiazolyl;

Z is - (C₀-C₂) Alkyl.

In addition, this invention specifically provides:

compounds of formula III

<img file="IS2743B_D0009.tif" />

or a pharmaceutically acceptable salt of said compound, characterized in that R₃ is a) - (CH₂)₂-CF₃, b) - (CH₂)₂-CH₃, c) -CH₃, d) -C≡C-CH₃, e) -C 1 -C-Cl or f) -CF₃;

R₈ is as defined in claim 8.

In addition, this invention specifically provides:

compounds selected from the group consisting of:

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N- (4-pyridinylmethyl) 4bS- (4ba, 7a, 8aft)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N- (2-pyridinylmethyl) 4bS- (4ba, 7a, 8aft)] -;

2-phenanthrenecarboxamide, 4b, 5,67,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N- (3-pyridinylmethyl) -, [4bS- (4ba, 7a, 8ap)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-2-pyridinyl-, [4bS- (4ba, 7a, 8aP)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-pyrazinyl-, [4bS- (4ba , 7a, 8aP)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-3-pyridinyl-, [4bS- (4ba, 7a, 8aP)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4b, 7a, 8a, 3)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- propyl-, [4bS- (4ba, 7a, 8aP)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-N- (2-pyridinylmethyl) -, [4bS- (4ba , 7a, 8ap)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-N- (4-pyridinylmethyl) -, [4bS- (4ba , 7a, 8aP)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octabydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-N- (3-pyridinylmethyl) -, [4bS- (4ba , 7a, 8ap)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-N-2-pyridinyl-, [4bS- (4ba, 7a , 8aP)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-4-pyridinyl-, [4bS- (4ba, 7a , 8a3)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-N-3-pyridinyl-, [4bS- (4ba, 7a , 8ap)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- (3,3,3-trifluoropropyl) -, [4bS, 7S, 8aR] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7-methyl-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -, [4bS, 7R, 8aR] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7-methyl-4b- (phenylmethyl) -N-3-pyridinyl-, (4bS, 7R, 8aR) -; and

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- (trifluoromethyl) -, [4bS, 7R, 8aR] -; or a pharmaceutically acceptable salt of said compound.

In particular, this invention provides compounds selected from the group consisting of:

a compound of formula III wherein R₃ is -C 2 C-CH₃ and r₁₀ is

-C (O) -NH-CH₂- (4-pyridinyl); or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -C 2 C-CH₃ and r₁₀ is

-C (O) -NH-CH₂- (2-pyridinyl); or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -C = C-CH₃ and r₁₀ is

-C (O) -NH-CH₂- (3-pyridinyl); or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -CsC-CH₃ and r₁₀ is

-C (O) -NH- (2-pyrazinyl); or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -C = C-CH₃ and r₁₀ is

-C (O) -NH-CH₂- (2-methyl-3-pyridinyl); or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is - (CH₂)₂-CH₃ and r₁₀ is

-C (O) -NH-CH₂- (2-methyl-3-pyridinyl); or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is - (CH₂)₂-CH₃ and r₁₀ is

-C (O) -NH-CH₂- (2-pyridinyl); or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is - (CH₂) 2-CH₃ and Ri₀ is

-C (O) -NH-CH₂- (2-methyl-3-pyridinyl); or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -CH₃ and R-æ is

-C (O) -NH-CH₂- (2-methyl-3-pyridinyl); or pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -CH₃ and r₁₀ is

-C (O) -NH- (3-pyridinyl); or a pharmaceutically acceptable salt thereof; and a compound of formula III wherein R₃ is -CF₃ and r₁₀ is

-C (O) -NH-CH₂- (2-methyl-3-pyridinyl); or a pharmaceutically acceptable salt thereof.

Additionally, this invention provides:

compounds of formula II

<img file="IS2743B_D0010.tif" />

a mixture thereof or a pharmaceutically acceptable salt of said compound of a hydrogen atom; pair with which FL is a) - (C₂-C₄) alkyl, b) -CH₂-CH = CH₂ or c) -phenyl;

R₂ is -OH;

R₃ is a) - (C1 -C4)₄) alkyl substituted with CFF₃, b) -ΟξΟΟΗ₃, c) -C 1 -C-Cl, d) -CeC-CF_3i e) -CH₂O (C₁-C₃) alkyl substituted with CFF₃, efia f) -CF₃;

R₁₀ is -O- (C₁-C₂) alkyl group selected from the group consisting of a) pyridinyl substituted with methyl, b) pyrimidinyl, c) pyrazinyl, d) morpholinyl and e) oxadiazolyl.

This invention specifically provides a compound

<img file="IS2743B_D0011.tif" />

or a pharmaceutically acceptable salt of said compound, characterized by the presence of R₃ is a) - (CH₂)₂-CF₃, b) - (CH₂)₂-CH₃, c) -CH₃, d) -CeC-CH₃, e) -CaC-CI efia f) -CF₃;

R₁₀ is -O- (C₁-C₂) alkyl-het is selected from the group consisting of a) pyridinyl, b) 3-pyridinyl, c) 4-pyridinyl, d) 2-methyl-3-pyridinyl and e) pyrazinyl.

This invention also provides compounds selected from the group consisting of:

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (3-pyridinylmethoxy) -, [2R- (2a , 4a 10aP)] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (4-pyridinylmethoxy) -, [2R- (2u , 4a 10aP)] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (2-pyridinylmethoxy) -, [2R- (23 , 4aci, 10aP)] -;

2-phenanephrenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2- (1-propynyl) -, [2R- (23,4aa, 10aβ)] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2-propyl-, [2R - (2a, 4a, 10a3)] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (2-pyridinylmethoxy) -, [2R- (2a, 4aα, 10aβ )] -;

2-phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (3-pyridinylmethoxy) -, [2R- (2 R, 4aα, 10aβ )] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-4-pyridinyl) methoxy] -4a- (phenylmethyl) -2-propyl-, [2R - (2o, 4a 1Oap)] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (pyrazinyl-methoxy) - [2R- (23,4aα, 10aβ )] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -2- (3,3,3-trifluoropropyl) 2S- (23,4aa, 10aP) j;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2- 3-trifluoropropyl) -, [2S- (2α, 4aα, 10aβ)] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (2-pyridinylmethoxy) -2- (3,3,3-trifluoropropyl) 2S- (2R, 4a 10aP)] -; and

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2- (trifluoromethyl) (2R, 4aS, 10aR) -; or pharmaceutically acceptable salt of said compound, and from the group consisting of:

a compound of formula III pair as R₃ is -C 2 C-CH₃ and r₁₀ is

-O-CH₂- (4-pyridinyl); or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -C 2 C-CH₃ and r₁₀ is

-O-CH₂- (2-pyridinyl); or pharmaceutically acceptable salt pair;

a compound of formula III wherein R₃ is - (CH₂)₂-CF₃ and r₁₀ is

-O-CH₂- (3-pyridinyl); or pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is - (CH₂)₂-CF₃ and r₁₀ is

-O-CH₂- (2-methyl-3-pyridinyl); or pharmaceutically acceptable salt thereof;

a compound of formula III pair as R₃ is - (CH₂)₂-CF₃ and r₁₀ is

-O-CH₂- (2-pyridinyl); or pharmaceutically acceptable salt pair; and a compound of formula III pair as R₃ is -CF₃ and r₁₀ is

-O-CH₂- (2-methyl-3-pyridinyl); promote a pharmaceutically acceptable salt pair.

In particular, this invention provides a compound according to claim 5 of formula II

<img file="IS2743B_D0012.tif" />

a vapor thereof or a pharmaceutically acceptable salt of said compound or vapor, characterized in that

R is a) - (C₂-C₄) alkyl, b) -CH₂-CH = CH₂ or c) -phenyl;

R₂ is -OH;

R₃ is a) - (C₁-C₄) alkyl substituted with 0 or 1 CF₃, b) -C≡C-CH₃, c) -C≡C-CI, d) -C≡C-CF_3l e) -CH₂O (C₁-C₃) alkyl substituted with 0 or 1 CF₃, or f) -CF₃;

R₁₀ is a) -OZC (O) -NH- (C₀-C₃) Alkyl-N ((C₁-C₂) Alkyl)₂, b) -OZC (O) -NR₁₂R₁₃ or c) -OZC (O) -NH- (C₀-C₃) alkyl selected from the group consisting of 1) pyridinyl substituted with 0 or 1 methyl, 2) pyrimidinyl, 3) pyrazinyl, 4) morpholinyl, 5) pyrrolidinyl, 6) imidazolyl and 7) oxadiazolyl;

R12 09 R13 are independently another a) -H or b) - (C-₂) Alkyl;

or R₁₂ and r₁₃ are combined with N to form pyrrolidinyl;

Z is - (C₀-C₁) Alkyl.

In particular, this invention provides a compound according to claim 15 of formula III

<img file="IS2743B_D0013.tif" />

or a pharmaceutically acceptable salt of the aforementioned compound, characterized in that R₃ era) - (CH₂)₂-CF₃, b) - (CH₂)₂-CH₃, c) -CH₃, d) -C≡C-CH₃, e) -CsC-Cl or f) -CF₃;

R₁₀ is a) -OC (O) -NH- (C₀-C₃) Alkyl-N ((C₁-C₂) Alkyl)₂, b) -OC (O) -N (CH₃)₂, c) -O-O (O) - (1-pyrrolidinyl) or d) -OC (O) -NH- (C₀-C₃) alkyl, wherein it is selected from the group consisting of 1) 2-pyridinyl, 2) 3-pyridinyl, 3) 4-pyridinyl, 4) 2-methyl-3-pyridinyl, 5) pyrazinyl, 6) morpholinyl, 7) pyrrolidinyl and 8) imidazolyl.

This invention specifically provides a compound according to claim 16, characterized in that it is valid from the group consisting of:

carbamic acid, dimethyl-, 7- (chloroethynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -2-phenanthrenyl ester, (4bS, 8aR) -;

1-pyrrolidinecarboxylic acid, 7- (chloroethynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -2-phenanthrenyl ester, (4bS, 8aR) -;

carbamic acid, [2- (1-pyrrolidinyl) ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) 2-phenanthrenyl ester, monohydrochloride, [4bS- (4ba, 7a, 8aP)] -; carbamic acid, [2- (4-morpholinyl) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) 2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] -;

carbamic acid, [3- (1H-imidazol-1-yl) propyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1 -propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aβ)] -;

carbamic acid, [2- (dimethylamino) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl ester , [4bS- (4ba, 7a, 8aP)] -;

carbamic acid, [3- (1-pyrrolidinyl) propyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2 -phenantrenyl ester, [4bS- (4ba, 7a, 8ap)] -;

carbamic acid, [2- (3-pyridinyl) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2 -phenantrenyl ester, [4bS- (4ba, 7a, 8ap)] -;

carbamic acid, (2-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) 7- (1-propynyl) -2-phenanthrenyl ester, [4bS - (4ba, 7a, 8aP)] -;

carbamic acid, [2- (2-pyridinyl) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2 -phenantrenyl ester, [4bS- (4ba, 7a, 8aP)] -;

carbamic acid, (4-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) 7- (1-propynyl) -2-phenanthrenyl ester, [4bS - (4ba, 7a, 8aP)] -;

carbamic acid, (3-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) 7- (1-propynyl) -2-phenanthrenyl ester, [4bS - (4ba, 7a, 8aP)] and carbamic acid, [2- (4-pyridinyl) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl ) -7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] -;

or a pharmaceutically acceptable salt of said compound, and selected from the group consisting of:

a compound of formula III wherein R₃ is -C = C-CH₃ and r₁₀ is

OC (O) -NH- (CH₂)₂- (1-pyrrolidinyl); or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -C 2 C-CH₃ and R10 is

OC (O) -NH- (CH₂)₂-N (CH₃)₂; or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -C 2 C-CH₃ and r₁₀ is

OC (O) -NH- (CH₂) -2-pyridyl; or a pharmaceutically acceptable salt pair;

a compound of formula III pair as R₃ is -C 2 C-CH₃ and Rio is

OC (O) -NH- (CH₂) -4-pyridyl; or a pharmaceutically acceptable salt pair; and a compound of formula III pair as R₃ is -C = C-CH₃ and r₁₀ is

-OC (O) -NH-CH₂-3-pyridyl; or a pharmaceutically acceptable salt thereof.

This invention also provides a compound in accordance with claim 1 of formula IV

<img file="IS2743B_D0014.tif" />

IV hydrogen atom or a pharmaceutically acceptable salt of said compound or a hydrogen atom, characterized in that R_s is -H; R₉ is -H; m is 2; R₇ is -H; R₁₄ is -H; R₁₅ is -H; R_1S is -H; and the A-ring is the group of formula A-1a.

This invention specifically provides a compound combination according to claim 18 with formula V

<img file="IS2743B_D0015.tif" />

or a pharmaceutically acceptable salt of said compound or substitution, characterized in that X is -CH₂-;

R1 is a) - (C_rC₄) alkyl, b) - (C₂-C₄) alkenyl, c) -phenyl substituted with 0 or 1 of the following: -OH, -NR₁₂R₁₃, -NR₁₂-C (O) - (C_rC₄) alkyl, -CN, -Z-het, -O-C1 -C6 -alkyl-C1-10-NR4 R11, -NR5₁₂-ZC (O) NR₁₂R 11, -Z-NR₁₂-SO₂-R, 3, -NR₁₂-SO₂-het, -OC (O) - (C1 -C4)₄) alkyl or -O-SO₂- (C_rC₄) Alkyl; d) -O-phenyl substituted with 0 or 1 of the following: -Z-NR₁₂R₁₃ or -C (O) NR_{) 2}R₁₃; e) -CH = CH-phenyl pair as phenyl is substituted with 0 or 1 of the following: -Z15 NR_L2R₁₃or-C (O) NR₁₂R₁₃;

What happens is the case - (C₀-C₂) Alkyl;

R₄ and r₅ are each hydrogen or are combined to form = 0;

R₁₀ is a) -CH 2 OHC 1 -C 6 alkyl, b) -CN, c) -OH, d) -het, e) -C (O) - (C_rC₄) alkyl, f) -C (O) -NR12 R13, 9) -C (O) -NH-Z-het, h) -O- (C₀-C₃) alkyl-het, i) -OZC (O) -NR₁₂R₁₃, j) -OZC (O) 2 NH- (C₀-C₃) alkyl-het or k) -O- (C₀-C₃) Alkyl-phenyl;

R₁₂ and Ri₃ are in each case independently a) -H or b) - (C1 -C6)₄) Alkyl.

This invention also provides a compound of formula VIII

<img file="IS2743B_D0016.tif" />

or disappearing thereof, characterized by the fact that

D 'is C;

X 'is-CH₂-;

Rb is phenyl substituted with 0 to 2 R '_x;

R '₅, R '_7i R '_b, R '_9i R '₁₅ and R '₁₆ are each independently, a) -H, b) -O-C1-C6alkyl, c) - (C1-C6alkyl or d) halogen;

R '_1O is a) -halogen, b) -CN, c) -OH, d) -C (O) -NR '₁₂R '₁₃, e) -C (O) -NR '₁₂-Z'-hetero which is substituted with 1 R '_x, f) -C (O) -NR '₁₂-Z'-aryl pair wherein aryl is substituted with 1 R '_x, g) -O- (C 1 -C 6)₆) alkyl-heteroaryl substituted with R 1 '_x, h) -O- (C₀-C₆) alkyl-aryl pair wherein aryl is substituted with 1 R '_x;

Z 'a) - (C₀-C₆) alkyl, b) - (C₂-C₆) alkenyl, ester c) - (C₂-C₆) Alkynyl;

R '_x is a) -halogen, b) -OH, c) - (C_rC₆) alkyl, d) -CN, e) -CF₃, f) - (C₀-C₆) Alkyl-NR₁₂R '₁₃, g) -C (O) -NR '₁₂R '₁₃, h) -NR '₁₂-SO₂R '₁₃, i) -NR '₁₂-C (O) -R '₁₃, j) -SO₂R '₁₂ promote k) -SO₂NRR₂R '₁₃; R '₂ and R '₁₃ are (each case independently another) -H inhibit b) - (CrC₆) Alkyl;

aryl erfenyl;

It is a 5-6-membered 7-atom methothoric agent, a major part of a methothorphide enhancing an unsaturated ring containing from one (1) to hetero (3) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur.

In addition, this invention provides a compound of formula 3 of Formula II

<img file="IS2743B_D0017.tif" />

a vapor pair of pharmaceutical promoter has a salt of said compound enhancing a vapor, characterized by the effect of R is -phenyl;

R₂ is-OH;

R₃ is a) - (C1-4alkyl) substituted with 0 or 1 CF₃, b) -C≡C-CH₃, c) -C≡C-CI, d) -C≡C-CF₃, e) -CH₂O (C₁-C₃) alkyl substituted with 0 or 1 CF₃, or f) -CF₃;

R₁₀ is -OH, -CN, -C (O) OH or -O (O) O (O, -C₆) Alkyl.

Particularly, this invention provides a compound combination of claim 21 of formula III

<img file="IS2743B_D0018.tif" />

or a pharmaceutically acceptable salt of said compound, characterized in that R₃ is a) - (CH₂)₂-CF₃, b) - (CH₂)₂-CH₃, c) -CH₃, d) -C≡C-CH₃, e) -C 1 -C-Cl or f) -CF₃;

R₁₀ is as defined in claim 23.

This invention further provides a compound according to claim 22, characterized in that it is valid from the group consisting of:

a compound of formula III wherein R₃ is -CeC-CH₃ and r₁₀ is -OH; or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -C 2 C-CH₃ and r₁₀ is -CN; a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is -C = C-CH₃ and r₁₀ is -COOH; or a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is - (CH₂)₂-CH₃ and r₁₀ is -OH; Such a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is - (CH₂)₂-CH₃ and r₁₀ is -CN; Such a pharmaceutically acceptable salt thereof;

a compound of formula III wherein R₃ is - (CH₂)₂-CH₃ and r₁₀ is -COOH; or a pharmacologically acceptable salt pair;

a compound of formula III pair as R₃ is - (CH₂)₂-CF₃ and Ri₀ is -OH; Your pharmacologically healthy salty pair of;

a compound of formula III pair as R₃ is - (CH₂)₂-CF₃ and r₁₀ is -CN; Your pharmacologically healthy salty pair of;

a compound of formula III pair as R₃ is - (CH₂)₂-CF₃ and r₁₀ is -COOH; Your pharmacologically healthy salty pair of;

a compound of formula III pair as R₃ is -CH₃ and r₁₀ is -OH; Your pharmacologically healthy salty pair of;

a compound of formula III pair as R₃ is -CH₃ and r₁₀ is -CN; Your pharmacologically healthy salty pair of;

a compound of formula III pair as R₃ is -CH₃ and r₁₀ is -COOH; or a pharmaceutically acceptable protein pair;

a compound of formula III pair as R₃ is -CF₃ and r₁₀ is -OH; or a pharmaceutically acceptable salt pair;

a compound of formula III pair as R₃ is -CF₃ and r₁₀ is -CN; or a pharmaceutically acceptable salt pair;

a compound of formula III pair as R₃ is -CF₃ and r₁₀ is -COOH; or a pharmaceutically acceptable salt pair.

This invention also provides the use of a compound according to claim 1, comprising a pair of or pharmaceutically acceptable salt of said compound or substitute for the manufacture of a medicament for the treatment of a condition selected from the group consisting of obesity, diabetes, anxiety, depression, neuropathy or inflammatory disease in a mammal.

This invention also provides use according to claim 31, wherein the glucocorticosteroid agent is a compound according to claim 1, leaving a pair of or pharmaceutically acceptable salt of said compound or substitution.

Furthermore, a disclosed use according to claim 33, wherein the glucocorticosteroid receptor is a compound that is valid from the group consisting of:

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N- (4-pyridinylmethyl) 4bS- (4ba, 7a, 8aP)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N- (2-pyridinylmethyl) 4bS- (4ba, 7a, 8aP)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N- (3-pyridinylmethyl) 4bS- (4ba, 7a, 8aP)] -;

carbamic acid, [2- (dimethylamino) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2- phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-pyrazinyl-, [4bS- (4ba , 7a, 8aP)] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (4-pyridinylmethyl) -, [2R- (2a , 4aa, 10ap)] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (2-pyridinylmethoxy) -, [2R- ( 23.4aa, 1θθβ)] -;

2-phenanthrenecarbonitrile, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a, 8aP )] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a, 8a (3)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) propyl, [4bS- (4ba, 7a, 8aβ)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-N- (2-pyridinylmethyl) -, [4bS- (4ba , 7a, 8aP)] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -2- (3,3,3-trifluoropropyl) 2S- (2a, 4a 10aP)] -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2- 3-trifluoropropyl) -, [2S- (2 R, 4aα, 10aβ)] -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- (3 , 3,3-trifluoropropyl) -, (4bS, 7R, 8aR);

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7-methyl-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -, (4bS, 7R, 8aR) -;

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7-methyl-4b- (phenylmethyl) -N-3-pyridinyl-, (4bS, 7R, 8aR) -;

2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2- (trifluoromethyl) (2R, 4aS, 10aR) -; and

2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- (trifluoromethyl) -, (4bS, 7R, 8aR);

or disappearing thereof or a pharmaceutically acceptable salt of said compound or substitution.

This invention also provides a pharmaceutical composition characterized in that it contains a measurably effective amount of Compound Compound No. 1, comprising a pair of pharmaceutically acceptable salts of said compound enhancing the wicking and pharmaceutically acceptable excipient enhances a prosthetic agent.

Compound of Formula III

<img file="IS2743B_D0019.tif" />

pair as r₃ is a) - (CH₂)₂-CF₃, b) m- (CH₂)₂-CH₃, c) -CH₃, d) -C≡C-CH₃, e) -CsC-C1 inhibitor f) -CF₃; and Rio is -O-CH₂- the pair of which is pyridinyl substituted with 1 methyl; There is a result of the reaction of a compound of formula III-A

<img file="IS2743B_D0020.tif" />

Ill-A where R₃ is as defined above, the base of the base in aprotic solvents at room temperature to 200 ° C; and then a compound of formula R10-X1 wherein R₁₀ is as defined above and X is halogen, mesylate promotes tosylate.

She specifically gives this product where the base is NaH, t-butoxide enhancement Et₃n; and the solvent is DMF enhancing THF.

A compound of formula III

<img file="IS2743B_D0021.tif" />

where R₃ is a) - (CH₂)₂-CF₃, b) - (CH₂)₂-CH₃, c) -CH₃, d) -C≡C-CH₃, e) -C = C-C1 inhibitors f) -CF₃; R₁₀ is -C (O) -NH-Z-wherein it is selected from the group consisting of a) pyridinyl substituted with methyl, b) pyrimidinyl, c) pyrazinyl, d) morpholinyl and e) oxadiazolyl; and Z is - (C 1 -C 6 alkyl) is a forced leaving agent with the reaction of a compound of formula III-B

<img file="IS2743B_D0022.tif" />

Ill-B where R₃ is as defined herein, above the force of a clot reagent and a compound of formula NH₂-Z- is a salt thereof, where -Z and -H are as defined herein, above the aprotic solvents at 0 ° C to 100 ° C. It specifically describes this method wherein the clot reagent is selected from the group consisting of 1- (3-dimethylaminopropyl-3-ethylcarbodiimide (EDC), dicyclohexylcarbodiimide (DCC) and hydroxy-benzotriazole hydrate (HOBt).

A compound of formula III

<img file="IS2743B_D0023.tif" />

pair as r₃ is a) - (CH₂)₂-CF₃, b) - (CH₂)₂-CH₃, c) -CH₃, d) -ΟξΟ-ΟΗ₃, e) -C = C-Cl or f) -CF₃; R₁₀ is -C (O) -NH-Z-wherein it is selected from the group consisting of a) pyridinyl substituted with 0 or 1 methyl, b) pyrimidinyl, c) pyrazinyl, d) morpholinyl and e) oxadiazolyl; and Z is - (C 1 -C 6) alkyl can be prepared by the reaction of a compound of formula III-C

<img file="IS2743B_D0024.tif" />

III-C pair as R₃ is as defined above, by three (C₁-C₄) alkyl-compound and a compound of formula NH₂-Z-the pair -Z and -S are as peer are defined above in solvent at 0 ° C to 40 ° C. She specifically gives this method a pair of tris (C₁-C₄) alkyl-aryl compound is Al (CH₃)₃ and the solvent is methylene chloride.

<img file="IS2743B_D0025.tif" />

pair as r₃ is a) - (CH₂)₂-CF₃, b) - (CH₂)₂-CH₃, c) -CH₃, d) -C≡C-CH₃, e) -C = C-Cl or f) -CF₃; R_w is a) -OC (O) -N (CH₃)₂, b) -O-C (O) - (1-pyrrolidinyl) or c) -OC (O) -NH- (C₀-C₃) -alkyl group selected from the group consisting of 1) 2-pyridinyl, 2) 3-pyridinyl, 3) 4-pyridinyl, 4) 2-methyl-3-pyridinyl, 5) pyrazinyl, 6) morpholinyl , 7) pyrrolidinyl and

8) imidazolyl can be prepared by the reaction of a compound of formula III-A

<img file="IS2743B_D0026.tif" />

pair as r₃ is as defined above, with phosgene or triphosgene in aprotic solvent and preferably with a compound which is valid from the group consisting of NH (CH₃)₂, 1-pyrrolidinyl and NH₂- (C₀-C₃) alkyl-hetero as defined above at 0 ° C to room temperature. The solvent may be toluene.

A compound of formula III

<img file="IS2743B_D0027.tif" />

pair as r₃ is a) - (CH₂)₂-CF₃, b) - (CH₂)₂-CH₃, c) -CH₃, d) -ΟξΟ-ΟΗ₃, e) -ChC-CI and f) -CF₃; and R 10 is -O- (C 1 -C 6)₂) alkyl-substituted pair of pyridinyl substituted with methyl may be prepared by reaction of a compound of formula III-D pair as R₁₀ is as defined above, by R₃metal selected from the group consisting of R₃Li, R₃MgBr and R₃MgCl pair as R₃ is as defined above in aprotic solvent at -78 ° C to room temperature.

A compound of formula III

<img file="IS2743B_D0028.tif" />

pair as r₃ is -CF₃; and r₁₀ is -O- (C₁-C₂) alkyl-substituted pair of pyridinyl substituted with 0 or 1 methyl may be prepared by the reaction of a compound of formula III-D

<img file="IS2743B_D0029.tif" />

III-D pair as R₁₀ is as defined above above, at trimethylsilyl-CF₃ in the presence of tert-butylammonium fluoride in a proteolytic solvent; and b) hydrolysis of the intermediate which is precipitated with tert-butylammonium fluoride or hydrochloric acid.

A compound of formula III

<img file="IS2743B_D0030.tif" />

pair as r₃ is a) - (CH₂)₂-CF₃, b) - (CH₂)₂-CH₃, c) -CH₃, d) -C≡C-CH₃, e) -CeC-Cl eda f) -CF₃; and r₁₀ is -C (O) -NH-Z-het pair selected from the group consisting of a) pyridinyl substituted with 0 or 1 methyl, b) pyrimidinyl, c) pyrazinyl, d) morpholinyl and e) oxadiazolyl; and Z is in each case independently - (C₀-C₂) alkyl can be prepared by the reaction of a compound of formula III-D

<img file="IS2743B_D0031.tif" />

where R₁₀ is as defined above with R₃metal selected from the group consisting of R₃Li, R₃MgBr and R₃MgCl where R₃ is as defined in an aprotic solvent at -78 ° C to room temperature.

A compound of formula III

<img file="IS2743B_D0032.tif" />

where R₃ is a) - (CH₂)₂-CF₃, b) - (CH₂)₂-CH₃, c) -CH₃, d) -C≡C-CH₃, e) -C = C-Cl or f) -CF₃; and r₁₀ is -C (O) -NH-Z-wherein it is selected from the group consisting of a) pyridinyl substituted with 0 or 1 methyl, b) pyrimidinyl, c) pyrazinyl, d) morpholinyl and e) oxadiazolyl; and Z is in each case independently - (C₀-C₂) alkyl can be prepared by a) reacting a compound of formula III-D

<img file="IS2743B_D0033.tif" />

ill-D pair as R₁₀ is as defined above with trimethylsilyl-CF₃ (presence of tert-butylammonium fluoride or seslum fluoride in a proteolytic solvent; and b) hydrolysis of the intermediate resulting from tert-butylammonium fluoride or hydrochloric acid.

The compounds of this invention are given a name in accordance with the IUPAC or CAS nomenclature.

In one of the methods for administering the compounds of this invention, the carbon atoms in the ring can be numbered as shown in the following simplified structure:

<img file="IS2743B_D0034.tif" />

Alternatively, by another means for administering the compounds of this invention, the carbon atoms may be numbered in the ring as shown in the following simple structure:

<img file="IS2743B_D0035.tif" />

The carbon atom content of the different hydrocarbon-containing groups is expressed by a factor giving the minimum and maximum number of carbon atoms in the group, ie coefficient Cj-Cj indicates a group with a number of "i" to the number of "j" of carbon atoms. By this means, for example, (C_rC₃) alkyl to alkyl having one to three carbon atoms, or methyl, ethyl, propyl and isopropyl, and all of the cyclic forms and linear and branched forms thereof.

Examples of alkyl having a single to zero carbon atom are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl and nonyl and all forms of hydrogen and linear and branched.

An example of alkenyl having two to five carbon atoms is ethylene, propenyl, butenyl, pentenyl and all forms of hydrogen and a linear and branched form thereof.

An example of alkynyl having two to five carbon atoms is ethynyl, propynyl, butynyl, pentynyl and all forms of hydrogen and a linear and branched form thereof.

The name of cycloalkyl, cycloalkenyl and cycloalkynyl refers to cyclic forms of alkyl, alkenyl and alkynyl. An example of (C₃-C₈) cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

The term halogen covers chlorine, bromine, iodine and fluorine.

The term aryl refers to a optionally substituted six-membered aromatic ring, including a polyaromatic ring. Examples of aryl include overphenyl, naphthyl and biphenyl.

The term refers to a optionally substituted 5-, 6- or 7-membered saturated, partially saturated or unsaturated heterocyclic ring containing from 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and comprising potentially bicyclic groups wherein any of the above-mentioned heterocyclic rings is condensed on a benzene ring or other heterocyclic ring; and the nitrogen atom may be in an oxidized state which gives the N-oxide form; and substituted with 0 to 3 independent substituents.

The following paragraphs describe typical circles for the general circular information included here.

Examples of five-membered rings are furyl, thienyl, 2H-pyrrolyl, 3H-pyrrolyl, pyrrolyl, 2-pyrrolidinyl, 3-pyrrolidinyl, pyrrolidinyl, 1,3-dioxolanyl, oxazolyl, thiazolyl, imidazolyl, 2H-imidazolyl, 2-imidazolinyl , imidazolidinyl, pyrazolyl, 2-pyrazolinyl, pyrazolinyl, isoxazolyl, isothiazolyl,

1,2-dithiolyl, 1,3-dithiolyl, 3H-1,2-oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-thiadiazolyl, 1,2,3,4-oxatriazolyl, 1,2,3,5-oxatriazolyl, 3H-1,2, 3-dioxazolyl, 1,2,4-dioxazolyl, 1,3,2-dioxazolyl, 1,3,4-dioxazolyl, 5H-1,2,5-oxathiazolyl and 1,3-oxathiolyl.

Examples of six-membered rings are 2H-pyranyl, 4H-pyranyl, pyridinyl, piperidinyl, 1,2-dioxinyl,

1,3-dioxinyl, 1,4-dioxanyl, morpholinyl, 1,4-dithianyl, thiomorpholinyl, pyridazinyl, pyrimidinyl, pyrazinyl, piperazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, 1,2,3- triazinyl, 1,3,5-trithiazyl, 4H-1,2-oxazinyl, 2H-1,3-oxazinyl, 6H-1,3-oxazinyl, 6H-1,2-oxazinyl, 1,4-oxazinyl, 2H- 1,2-oxazinyl, 4H-1,4-oxazinyl, 1,2,5-oxadiazinyl, 1,4-oxazinyl, o-isoxysinyl, p-isoxysinyl, 1,2,5-oxathiazinyl, 1,2,6- oxadiazinyl, 1,4,2-oxadiazinyl and 1,3,5,2-oxadiazinyl.

Examples of seven-membered ring are asepinyl, oxepinyl, thiopinyl and 1,2,4-diazepinyl.

Examples of eight-membered rings are cyclooctyl, cyclooctyl and cyclooctadienyl.

Examples of bicyclic circles consisting of combinations of two fused partially saturated, fully saturated or fully unsaturated five or six membered rings optionally substituted with 1 to 4 heteroatoms selected independently from nitrogen, sulfur and oxygen are indolizinyl, indolyl, isoindolyl, 3H-indolyl, 1H-isoindolyl, indolinyl, cyclopenta (b) pyridinyl, pyrano (3,4-b) pyrrolyl, benzofuryl, isobenzofuryl, benzo (b) thienyl, benzo ) thienyl, 1 H-indazolyl, indoxazinyl, benzoxazolyl, anthranilyl, benzimidazolyl, benzthiazolyl, purinyl, 4H-quinolizinyl, quinolinyl, isoquinolinyl, sinolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, indenyl, isoindenyl, naphthyl, tetralinyl, decalinyl, 2H-1-benzopyranyl, pyrido (3,4-b) pyridinyl, pyrido (3,2-b) pyridinyl, pyrido (4,3-b) pyridinyl, 2H-1,3-benzo xasínýl,

As used herein, the term "mammals" means all mammals, including, for example, primates such as humans and monkeys. Examples of other mammals in this species include rabbits, dogs, cats, cows, goats, sheep and horses .

The term "treating", "treating" or "treating" as used herein includes prophylaxis (for example, prophylaxis) and liner treatment.

By "pharmaceutically acceptable" is meant that the carrier, carrier, diluent, adjuvant and / or salt must be compatible with other substances in the composition, I am not harmful to the recipient.

The compounds of formula I of this invention are prepared as described in the schemes, preparations and examples below, or are prepared by methods analogous to those which are known and readily available to those skilled in the art. (each of the schemes corresponds to the R groups (e.g., R₂ etc. ...) as stated above. In addition, the variable n is defined as 0 to 6. However, it should be understood that those skilled in the art will know that other functionalities described herein at the stated positions of the compounds of formula I also cover potential substituents for analogue positions on the structure within the schedules.

Scheme A-1

<img file="IS2743B_D0036.tif" />

A-3a

Schedule A-1 - continuation

<img file="IS2743B_D0037.tif" />

<img file="IS2743B_D0038.tif" />

<img file="IS2743B_D0039.tif" />

Schedule A-2

<img file="IS2743B_D0040.tif" />

27Í3

Schedule A-2 - continuation

<img file="IS2743B_D0041.tif" />

A-3b

<img file="IS2743B_D0042.tif" />

<img file="IS2743B_D0043.tif" />

<img file="IS2743B_D0044.tif" />

<img file="IS2743B_D0045.tif" />

<img file="IS2743B_D0046.tif" />

A-2b

A-3a or A-3b ''

<img file="IS2743B_D0047.tif" />

<img file="IS2743B_D0048.tif" />

A-5a or A-5b

Scheme A-3

A-3a or A-3b

<img file="IS2743B_D0049.tif" />

<img file="IS2743B_D0050.tif" />

A-5a and A-5b

Schemun A-1, A-2 and A-3

Compounds of Formula A-1 (prepared as described in Org. Syn. 1971, 51, 109-112) (wherein D is methylene, substituted carbon, oxygen, sulfuric acid protecting agent, R₁₀ is halogen, hydrogen, methyl ether, benzyl ether, as described above, and the above parameters are as defined in the above-mentioned supra) is a reactant of a nitrogen-containing base, such as pyrrolidine, piperidine efia morpholine , reflux temperature in aprotic solvents such as toluene, benzene, dichloromethane or dioxane and subsequently reacted with an alkylating agent of formula R₂-C₄) alkyl linear chain or isopropyl, t-butyl or benzyl group is as described in the above summary, and Xt is a leaving group (see Francis A. Carey, in Advanced Organic Chemistry, Section A, Section 5.6 for Example) in dioxane , methanol, ethanol, isopropanol, DMF, DMSO or THF to give a compound of formula A-2. Typical alkylation intermediates are monounsaturated, benzylphenylaluminum halides, and preferably are alkylbromides of alkyl iodides.

Alternatively, the compound of formula A-1 is converted to anion with a strong base such as sodium hydride, sodium methoxide, lithium diisopropylamide, lithium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, potassium t-butoxide or other, in aprotic solvents, such as dimethylformamide (DMF) or tetrahydrofuran (THF). This reaction is carried out at -78 ° C to room temperature with the base of the base. The resulting anion is alkylated with a reactive alkylating agent of formula R1X-X1 as previously verified as defined for the compound of formula A-2.

Alternatively, Compound of Formula A-1 Reactor, and alkali, such as pyrrolidine or acid, such as acetic acid or hydrochloric acid, in solvents such as toluene, benzene, methane sulfane ethanol. The resulting intermediate is a hydrogen atom, the use of palladium on carbon-inducing agents of other reagents such as platinum oxide of rhodium on alumina (see PN Rylander in Hydrogenation Methods, Academic Press, New York, 1985; Herbert O. House of Modern Synthetic Reactions, Chapter 1, bis. 1-45; and John Fried and John A. Edwards in Organic Reactions in Steroid Chemistry, Chapter 3, bis. 111-145) to give a compound of formula A-2. Alternatively, the intermediate is a reactive reducing agent such as alkaline (class IA of the atomic) orphanuclear group (class IIA I atomic system), optionally selected as Li, Na efia Ca, and amine,₃ ethylene diamine, aprotic solvent, such as THF efia dioxane, at -78 ° C to room temperature to give a compound of formula A-2.

Compound of Formula A-2 is the reaction of (R) - (+) - N-methylbenzylamine (as shown in Scheme A-2) of (S) - (-) -ethylethylbenzylamine (as shown in Scheme A-1) and electrical devices of formula A-6 (for the formation of a 6-membered ring) of a device of formula A-7 (to form a 5-membered ring) pair of R₅, R₃ and r₉ are as peer are defined here from above the summary and X₂ is a leaving group represented by halogen atoms such as bromide (see Francis A. Carey, in Advanced Organic Chemistry, Section A, Section 5.6 for Example), in aprotic solvents such as toluene to give C2-S or C2-R substituted intermediates of formula A-2a (which will form a 6-membered ring) and formula A-2b (which will form a 5-membered ring), as shown in Schemes A-1 and A-2. These intermediates of formula A-2a and A-2b can be cyclized or cyclized as shown in the schemes.

Alternatively, the compound of formula A-2 is reacted with an electron of Formula A-6 (to form a 6-membered ring) or with an electron of Formula A-7 (to form a 5-membered ring) and a base, such as sodium methoxide or KOH, in a solvent such as methanol to give a racemic mixture of the intermediates of formula A-2a according to Examples A-1 and A-2 (which will form a 6-membered ring) or to give a racemic mixture of the intermediates of formula A-2b according to Schemes A-1 and A-2 (which will form a five-membered circle). This disappearance can also directly confer a racemic mixture of products A-3a according to Schemes A-1 and A-2 (having a six-membered ring) or directly administered a racemic mixture of products A-3b according to schemes A-1 and A-2 ( which has a five-member ring), where the mixtures can be separated by HPLC or other methods of light material.

Intermediate Formula A-2a or A-2b is reacted with a base such as sodium methoxide or KOH, in a solvent such as methanol, or is reacted with an acid such as p-toluenesulfonic acid in a solvent such as toluene to give the compound with Formula A-3a or A-3b, wherein the variables are as defined in the summary above and in which R₁₀ is halogen, hydrogen, methyl ether or benzyl ether or is as described in the summary above.

Alternatively, the compounds of formula A-3a or A-3b are prepared from the compound of formula A-2a or A-2b, according to other disclosed cyclization methods, some of which are disclosed in Μ. E. Jung, Tetrahedron, 1976, 32, p. 3-31.

The compound of formula A-3a or A-3b wherein R₁₀ For example, methoxy is reacted with BBr₃ or BCI₃ and tetrabutylammonium iodide or dimethylbromomide in aprotic solvents, such as dichloromethane or toluene at -78 ° C to room temperature to give the compound of formula A-3a or A-3b wherein R₁₀ for example hydroxy.

Alternatively, there is a compound of formula A-3a or A-3b wherein R₁₀ for example, methoxy is reacted with sodium methanethiol in DMF or reacted with methionine in methanesulfonic acid to give a compound of formula A-3a or A-3b wherein R₁₀ is, for example, hydroxy.

Compounds of formula A-3a or A-3b wherein R₁₀ For example, hydroxy can be produced by other methods known in the seeds as described in Protecting Groups in Organic Synthesis, Second Edition, TW Greene and PGM Wuts, John Wiley and Sons, Inc. (1991) Efia as shown in Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989), bis. 501-527.

Compounds of formula A-3a or A-3b wherein R₁₀ is halogen, hydrogen, methyl ether or hydroxy or is as described in the summary above, hydrogenated with palladium on carbon catalytic agents such as platinum oxide or rhodium on aluminum oxide (see PN Rylander In Hydrogenation Methods, Academic Press, New York, 1985; Herbert O. House In Modern Synthetic Reactions, Chapter 1, Biz. 1-45; and John Fried and John A. Edwards Organic Reactions in Steroid Chemistry, Chapter 3, Bis. 111-145). In different solvents covering methanol, ethanol and THF to give compounds of formula A-4a, A-4b or A-5a or A-5b wherein the parameters are as described in the summary above and in which the cis compound is the primary products.

Compounds of Formula A-3a, A-3b wherein R₁₀ is hydrogen, methyl ether, hydroxy or is as described in the summary above, the reaction is a reducing agent such as alkali (ΙΑ I atomic system) or alkaline earth metal (class IIA I atomic system), including Li, Na efia Ca , and amln, like NH₃ ethylene diamine, in an aprotic solvent, such as THF efia dioxane, at -78 ° C to room temperature to give compounds of formula A-5a, A-5b or A-4a or A-4b wherein the variables are as described in The summary above and the pairs of the trans compound are the avian products.

Alternatively, as shown in Scheme A-3 is compounded with Formula A-3a of Form A-3b according to Scheme A-1 pair as R₁₀ is halogen, hydrogen, methyl ether, hydroxy, carboxymethyl as described above is treated with an alcohol or diol, such as methanol or ethylene glycol, and a strong acid, such as p-toluenesulfonic acid, in an aprotic solvent such as toluene or benzene, to form a ketal intermediate of formula A-6 pair, m is one or two, R_a is lower alkyl or a pair of R_a taken together with two oxygen atoms forms, for example, 1,3-dioxolane and the pair of the other variables are as defined in the summary above. Alternatively, this Ketal Intermediate Verifier can be produced by other disclosed methods, such as peerri described in Protecting Groups in Organic Synthesis, Second Edition, TW Greene and PGM Wuts, John Wiley and Sons, Inc. (1991). Ketal intermediates are hydrogenated using Pd (OH)₂ on carbon or other reagents, such as platinum oxide or rhodium on alumina (see PN Rylander in Hydrogenation Methods, Academic Press, New York, 1985; Herbert P. House in Modern Synthetic Reactions, Chapter 1, bis. 1-45; and John Fried and John A. Edwards in Organic Reactions in Steroid Chemistry, Chapter 3, Bis. 111-145) In laser imaging such as toluene from 15-2000 psi (which is about 1 to about 14 psi) H₂ vifi room temperature to 100 ° C.

The intermediate product of formula A-7 is therefore an acidic acid such as p-toluic acid in acetone or is reacted using different methods known in the literature, such as those described in Protecting Groups in Organic Synthesis, Second Edition, TW Greene and PGM Wuts, John Wiley and Sons, Inc. (1991), to give a compound of formula A-5a according to Scheme A-1, a compound of formula A-5b according to Scheme A-1 pair as R₁₀ is halogen, hydrogen, methyl ether, hydroxy eda as described in the summary above, and the other variables are as defined in the summary above. The quaternary stereoisomers of these compounds are produced with conductors that are oblique peams as described above.

Alternatively, as shown in Scheme A-3, a compound of formula A-3a is A-3b according to Scheme A-1, a pair of R₁₀ is halogen, hydrogen, methyl ether, hydroxy or as described above, reacted with triethyl orthoformate and p-toluenesulfonic acid ethanol toluene to form a single ether intermediate with the A-8 pair which is one or two, R_aethyl or other unsubstituted or cyclic lower alkyl or acyl, the higher reagent used, and the other variables are as defined in the above-mentioned summary. The Ad Odrum benefits can be produced by other ethnologists with other behaviors that are identified in the seeds such as peim, described in the Protecting Groups in Organic Synthesis, Second Edition, TW Greene and PGM Wuts, John Wiley and Sons, Inc. (1991). The enoleter milliafurdine is hydrogenated with the use of Pd on CaCO₃ or other reagents, such as platinum oxide or aluminum oxide (see PN Rylander In Hydrogenation Methods, Academic Press, New York, 1985; Herbert 0. House in Modern Synthetic Reactions, Chapter 1, bis. 1-45; and John Fried and John A. Edwards Organic Reactions in Steroid Chemistry, Chapter 3, bis. 111-145) in a variety of different solvents, pairs of etanoli, methane and THF at 15-60 psi H₂ pressure. Milliafurdine, which is derived from Formula A-9, is an acylated acidic acid such as HCl In water, in a liquid solvent such as ethanol, which is reacted with other conditions discussed in the literature, as described in Protecting Groups in Organic Synthesis , Onnur edition, TW Greene and PGM Wuts, John Wiley and Sons, Inc. (1991), to give a compound of formula A-5a according to Scheme A-1 (which is a 6-membered ring) of a compound of formula A-5b according to Scheme A-1 (having a 5-membered ring) pair as R₁₀ is halogen, hydrogen, methyl ether, hydroxy eda, as described in the summary above, and the other variables are as defined in the summary above. The tertiary stereomers of these compounds are produced with conductors that are analogous to the peams described above.

The Ad Odrum advantage is the intermediate value that appears according to formula A-3a or A-3b In Scheme A-1 hydrogen using the Pd / BaSO₄ solvent such as ethanol at 15 to 200 psi H₂ pressurized to give a compound of formula A-5a in Scheme A-1 (having a 6-membered ring) of a compound of formula A-5b form A-1 (having a 5-membered ring) pair as R₅ is COOR_a2 and couple as R_a2 is for example Ci-C₆alkyl. Odrum substrates used by the aforementioned hydrogenation reactions are described. Ν. Rylander Hydrogenation Methods, Academic Press, New York, 1985.

Alternatively, in Examples A-1 and A-2, the compounds of formula A-5a or A-5b are prepared from compounds of formula A-3a or A-3b by other disclosed reducing methods, and some are described by P. Jankowski, S. Marczak, J. Wicha, Tetrahedron,

1998, 12071-12150.

Scheme B

<img file="IS2743B_D0051.tif" />

<img file="IS2743B_D0052.tif" />

Schedule B - continuation

<img file="IS2743B_D0053.tif" />

<img file="IS2743B_D0054.tif" />

<img file="IS2743B_D0055.tif" />

Scheme B

A compound of formula B-1, obtained as described in Scheme Α-1 and Scheme H, is reacted with a base, such as NaH, t-butoxycarbonate Et₃N, in aprotic solvent, such as DMF or CH₃CN, a variable temperature between room temperature and 200 ° C depending on the level of the solvent used, and is reacted with an alkylating agent of formula R_b-Xi wherein X 1 is a leaving group, to give a compound of formula B-2 wherein R_b is, for example, an alkyl or allyl-heterocyclic group and is further explained by a number of different groups within the definition of R₁₀ In the summary above. To obtain compounds of formula B-2 which are carbamates where R_b is for example -C (O) NR₁₂R₃ and where R-I2 and R₁₃ are as defined in the above summary, a compound of formula B-1 reactive compound of a compound of formula R₁₂R₁₃-NC (O) Cl. Alternatively, to obtain compounds of formula B-2, which are carbamates wherein R_b is, for example, C (O) NR₁₂Ri3 is a compound of formula B-1 reactant of phosgene or triphosgene in aprotic solvent such as toluene and subsequently with amines of formula R₁₂R₃NH. To obtain compounds of formula B-2 which are thiocarbamates wherein R_b is for example -C (S) NR 1₂R₃ and r_i2 and r₁₃ are as defined in the Summary hereinbelow, a compound of formula B-1 is reactive with a compound of formula R₁₂R₁₃NC (S) Cl. In this chart, the other parameters are as defined in the summary above.

A compound of formula B-3 pair, for example, one to six (prepared according to the methods of formula B-2 compound) is the reaction of a base such as Na₂CO₃Non-aqueous sodium chloride in aprotic solvent such as DMF, a temperature between room temperature and 200 ° C, depending on the level of the solvent used, and is a reactive reaction of an amine of formula R₁₂R₁₃NH to obtain a compound of formula B-4 wherein n is, for example, one to six and R₁₂ and r₁₃ are as defined in the summary above.

A compound of formula B-5, which is, for example, 1 to 6 (produced by the intermediates of formula B-2 compound) is the reaction of the variable OsO₄, N-methylmorpholine-N-oxide enhancer K₂MnO₄ to give the corresponding diol to power. The diol is an oxidation cleavage with NalO₄ boosting Pb (OAc) to give a compound of formula B-6, wherein n is one to six, for example. Alternatively, compounds of formula B-5 reactants of ozone and supported by dimethylsulfite, triphenylphosphine promote another known reagent to give a compound of formula B-6. Generally, compounds of Formula B-6 from the compound of Formula B-5 are obtained from the catalysts shown in Comprehensive Organic Transformation, RC Larock, VCH Publisher, Inc. (1989) p. 595-596, p. 615-616.

Alternatively, the compound of formula B-4 wherein n is, for example, one to six, and R12 and R11 are as defined in the above summary, from the compound of formula B-6 wherein n is one to six , for example with decreasing aminination. Reducing amination is typically carried out with a reducing agent, such as sodium cyanoborohydride or sodium triacetoxyborohydride, preferably at a pH between six and eight. The reaction is usually carried out in a proteolytic solvent such as methanol or ethanol or in a mixture of solvents such as dichloromethane / methanol at a temperature of about -78 ° C to about 40 ° C (see A. Abdel-Magid, C Maryanoff, K. Carson, Tetrahedron Lett. Vol. 34, Issue 41, 5595-98, 1990). Other essays include the use of titanium isopropoxide and sodium cyanoborohydride (RJ Mattson et al., J. Org. Chem., 1990, 55,

The compound of formula B-7 wherein n is, for example, one to six (prepared by the methods of formula B-2 compound) is reacted with its hydroxyamine or HCl salt in a proteolytic solvent such as ethanol or methanol, and a base such as K₂CO₃ at a temperature between room temperature and 150 ° C depending on the nature of the solvent used to give the compound of formula B-8 wherein n is one to six, for example.

To obtain compounds of formula B-9 where, for example, R_b1 is alkyl and n is one to six, the compound of formula B-8 wherein n is one to six, for example, reacted with a base, such as NaH and R_bRCH₂C0₂An aprotic solvent such as THF at a temperature between room temperature and 140 ° C depends on the nature of the solvent used. To obtain compounds of formula B-9 wherein R_b1 is = 0 and n is, for example, one to six is ​​the compound of formula B-8 wherein n is one to six, for example, reacted with a base, such as pyridine and 2-ethylhexyl chloroformate in aprotic solvent, such as DMF. The resulting intermediate is heated to reflux in xylene or other high boiling aromatic solvent to give the compound of formula B-9 wherein R_b1 is = 0. To obtain compounds of formula B-9 wherein R_bi is = S and n is, for example, one to six is ​​the compound of formula B-8 wherein n is one to six, for example, reacted with a base such as DBU in aprotic solvent, such as CH₃CN and TCDI (1,1-thiocarbonyldimidazole).

The compound of formula B-7 wherein n is, for example, one to six is ​​reacted with TMSN₃ and AIMe₃1 aprotic solvent such as toluene at a temperature between 40 ° C and 200 ° C depending upon the nature of the solvent used to give the compound of formula B-10 wherein n is one to six, for example. In addition, there are obtained compounds of formula B-10 by reaction of the aforementioned compound according to formula B-7 with NaN₃ and triethylamine or ammonium chloride in aprotic solvents, such as DMF, at elevated temperatures.

A compound of formula B-7 wherein n is, for example, one to six is ​​reacted with amines and Al (Me)₃ in aprotic solvents such as toluene at a temperature between room temperature and 180 ° C depends on the nature of the solvent used to give the compound of formula B-11 where n is, for example, one to six and R₁₂ and r₁₃ are as defined in the summary above. Alternatively, the compound of formula B-11 is obtained by reaction of the aforementioned compound of Formula B-7 with amines in the presence of Lewis acid, such as AICI₃ or ZnCl₂ at 150 ° C to 200 ° C or in the presence of a metallic organic substrate, such as CuCl, CuBr, or lanthanide (III) triftate. (See Tetrahedron Lett. 1993, Vol. 34, Issue 40, 63956398).

A compound of formula B-12 wherein n is, for example, one to six (produced according to the residues of formula B-2 compound) is reacted with its amine or salt and AI (Me)₃ in an aprotic solvent such as dichloromethane to give a compound of formula B-13 where n is, for example, one to six and R_i2 and r₁₃ are independently hydrogen, alkyl, hydroxy or methoxy, for example or as defined in the summary above. Alternatively, compounds of Formula B-12 are hydrolysed by the effervescent reactions mentioned in Greene and Wuts, Protecting Groups in Organic Synthesis, Wiley, New York (1981), to give the corresponding free acid. The free acid thus obtained is an amine and a clutch reagent, such as DCC or EDCI, to give the aforementioned compound of formula B-13 (as shown in Comprehensive Organic Transformation, RC Larock, VCH Publisher, Inc. (1989) bis. 972-976).

In order to obtain compounds of formula B-14 where for example n is one to six, Z is 0 and R_b2is an alkyl radical of halogen, is a compound of formula B-12 wherein n is one to six, for example, a reaction of a base, such as NaH, in an aprotic solvent such as THF and Na₂C (= N-OH) R_b2 where R. | is alkyl vifl bakfleeflishitastig. For power, compounds of formula B-12 are obtained, for example, n is one to six, Z is n and R_b2 is an alkyl radical of halogen, is a compound of formula B-12 wherein n is one to six, for example, a reaction of a base, such as NaOMe, a proteolytic solvent such as MeOH and an aminoguanidine nitrate.

A compound of formula B-15 wherein R₁₂ and r_i3 are as defined in the Summary hereinbelow (produced by the hydrolysis of Formula B-2 compound) is dissolved in aprotic solvents such as toluene and refluxed to yield a compound of Formula B-16 wherein R₁₂ and r₁₃ are as defined in the summary above.

Scheme C (CRgRgJm fy (CRgRgJm Rj

<img file="IS2743B_D0056.tif" />

C-16

Scheme C

The compound of formula C-1 (which is the same as Compound of Formula B-1, see Scheme B) is treated with an acid scavenger, such as 2,6-lutidine, diisopropylethylamine or potassium carbonate with trifluoromethylsulfonyl reagents such as trifluoromethylsulfonic anhydride, N-phenyltrifluoromethanesulfonamide or 4-nitrophenyl trifluoromethanesulfonate with or without catalyst, such as 4-dimethylaminopyridine (DMAP), in dichloromethane and dichloromethane, DMF or methyl-2-pyrrolidinone (NMP) from -78 ° C to room temperature to give the compound of formula C-2 where R₁₀ is -OS (O)₂CF₃. In this chart, the other parameters are as defined in the summary above. Alternatively, the aforementioned compounds of formula C-2 are prepared from the compound of formula C-1 according to other disclosed fluoroalkylsulfonylation methods, such as lyric K. Ritter. Synthesis, 1993, bis. 735-762.

Compounds of formula C-2 pair as the group in R₁₀ The living room is OS (O)₂CF₃ Elemental halogen is a reaction of a metal cyanide, preferably a cyanide (II) cyanide (Zn (CN)₂), and vifi palladium sprays, such as tetrakis (triphenylphosphine) palladium (0) (Pd (PPh₃)₄), palladium (II) acetate or tris (dibenzylideneacetone) dipalladium (O) in a solvent such as N-methyl-2-pyrrolidinone (NMP), DMF of acetonitrile at room temperature to 120 DEG C. to give a cyanomethyl compound of formula C-3.

For example, a compound of formula C-4 is as hereinbefore defined. It is tetrasolyl is a compound of formula C-3 reactants of dibutyltin oxide (Bu₂SnO) and trimethylsilylide (TMSN₃) in toluene from room temperature! to reflux. The preferred advantages are the compounds of formula C-4, which, for example, are tetrazolyl produced from the compound of formula C-3 in accordance with other disclosed derivatives, and some are described in SJ Wittenberger, Organic Preparations and Procedures Int. 1994, 26 (5), bis. 499-531. The aforementioned advantages of compounds of formula C-4 are as defined in the formula 2-pyridyl or 3-pyridyl by the reaction of the compound of formula C-2 heterocyclic metal, such as bromo-2-pyridinium chloride diethyl- (3- pyridyl) boron, and catalyst such as Pd (PPh₃)₂Cl₂, tetrakis- (triphenylphosphine) palladium (0) (Pd (PPh₃)₄) palladium acetate and 1,1'-bis (diphenylphosphino) ferrocene, in organic solvent such as THF, DMF efia NMP room temperature to 150 ° C, depending on the solvent of the solvent.

A compound of formula C-2 is a reaction of CO 1-3 atm, with catalysts such as palladium acetate (Pd (OAc)₂) and 1,1'-bis (diphenylphosphino) ferrosen (DPPF) or bis (diphenylphosphino) propane (DPPP), tetrakis (triphenylphosphine) palladium (0) (Pd (PPh)₃)₄), dibenzylideneacetone) dipalladium (O) and base, such as triethylamine potassium carbonate, hydrogen alcohol, such as methanol, ethanol or benzyl alcohol, in a solvent such as DMF, NMP, DMSO, room temperature to 150 ° C, subject to the solvent of the solvent, which yields the ester of formula C-5, a pair of R_c is for example alkyl or aryl.

A water-soluble base such as KOH, in solvent, such as THF, is added to a solution of the compound of formula C-5 I solvent, such as THF. The resulting solution is stirred at room temperature to reflux to give the acid of formula C-6.

A solution of the compound of formula C-6, diphenylphosphoryl lithium (DPPA), triethylamine and alcohol of formula R_COH, such as t-butanol, is stirred at room temperature to reflux until carbamate of formula C-7, which is, for example, R_c is t-butyl.

Compound of formula C-6 is treated with a clutch reagent such as 1,3-dimethylaminopropyl-3-ethylcarbodiimide (EDC) eddicyclohexylcarbodiimide (DCC) and hydroxybenzotriazole hydrate (HOBt) with non-catalyst such as 4-dimethylaminopyridine (DMAP) and amine R₁₂R₃NH, in aprotic solvent, such as dichloromethane or DMF, at 0 ° C to room temperature to give amide of formula C-8 pair as R₁₂ and r₁₃ are as peers are defined in the summary above. Compounds of formula C-8 are also derived from the compound of formula C-6 by odor-brightening clutch methods, such as described in Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 972-988.

Alternatively, the esters of Formula C-5 may be added to a mixture of trimethylsilyl (Al (CH₃)₃) and R₁₂R₁₃NH such as 1- (3-aminopropyl) imidazole In solvent, such as dichloromethane, dichloroethane (DCE) ed toluene at 0 ° C to room temperature. The resulting mixture is stirred at room temperature to the reflux temperature to give an amide of formula C-8 pair which, for example, R 1₂ is hydrogen and r₁₃ is propyl-imidazol-1-yl and is further defined in the Summary above,

The ester of formula C-5 is reacted with a reductive amide such as sodium borohydride or diisobutylalumide in an organic solvent, such as methane, THF ed hexane, which is used at -78 ° C to room temperature to give an alcohol of formula C- 9 pairs as R_c1 is H. For example, other compounds of formula C-9 pairs, such as R_c1 is methyl is a compound of formula C-5 reacted at R_c1metal, such as metal magnesium bromide, in an organic solvent, such as THF, toluene, at -78 ° C to room temperature.

Carbamate of Formula C-7, pair as R_c For example, t-butyl is reacted with an acid such as trifluoroacetic acid (TFA) solvent, such as dichloromethane, at -78 ° C to room temperature to give an amine of formula C-10. A compound of formula C-10 can be prepared from the compound of formula C-7, a pair of R_c T-butyl, benzyl or other protecting groups, according to behavioral disclosures, and some are described in Protecting Groups in Organic Synthesis, Second Edition, TW Greene and PGM Wuts, John Wiley and Sons, Inc. (1991).

To obtain the compound of formula C-11 wherein R_c2 is -OSO₂-methyl is the compound of formula C-9 wherein R_chydrogen or alkyl is reacted with methyl sulfonation reagents, such as methanesulfonyl chloride (MsCl) and acid scavengers, such as diisopropylethylamine, in an organic solvent such as THF or toluene at -78 ° C to room temperature. To obtain the compound of formula C-11 wherein R_c2 is Cl is the compound of formula C-9 wherein R_c1 hydrogen or alkyl is reacted with chlorination reagents, such as thionyl chloride, an acid scavenger, such as pyridine, in an organic solvent such as methylene chloride at -78 ° C to room temperature.

The amine of formula C-10 is reacted with an acylation reagent, such as CH₃COCl and acid scavengers, such as triethylamine or pyridine, in a solvent such as methylene chloride or THF at -78 ° C to room temperature to give the amide of formula C-12 wherein R 1₂ is as defined in the summary above.

The compound of formula C-13 (obtained from the compound of formula C-6 by reaction with N, O-dimethylhydroxylamine hydrochloride, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, HOBt and DMAP) is reacted with R_c3metal, such as ethylmagnesium bromide, in a solvent such as THF or toluene at -78 ° C to room temperature to give the compound of formula C-14, wherein R 1 is, for example, ethyl.

The compounds of formula C-11 and amine reagents, such as sodium azide, in solvents such as DMF, NMP or DMSO, are stirred at room temperature to 150 ° C depending on the nature of the solvent used to give the compound of formula C-15 wherein R_c1 is hydrogen or alkyl and R_c4 is N₃. The resulting extract is treated with a reducing reagent, such as triphenylphosphine (PPh₃) in a solvent or a mixture of solvents, such as THF, methanol and water, at -20 ° C to reflux, to give the compound of formula C-15 wherein is NH₂.

The aldehyde of formula C-14 wherein R_c3 is hydrogen or ketone of formula C-14 wherein R_c3 alkyl is treated with a reducing agent such as sodium borohydride or dibisobutylalanide, in an organic solvent such as methanol, THF or hexane depending on the nature of the reducing agent used at -78 ° C to room temperature to give an alcohol of formula C-16 wherein Rc3 is for example ethyl.

The amine of formula C-15 pair as R_c1 is hydrogen or alkyl and R_c4 is -NH₂ is reacted with an alkylation reagent, such as CH₃COCl and acid scavengers, such as triethylamine or pyridine, in a solvent such as methylene chloride or THF at -78 ° C to room temperature to give the amide of formula C-17 pair as R₁₂ and r₁₃ are as peer are defined in the summary above.

Scheme D

<img file="IS2743B_D0057.tif" />

D-13 D-14

Scheme D

A compound of formula D-1 is prepared from cyclohexane-1,3-dione which can be purchased according to known methods described in Chem. Ber., 85, 1061 (1952); Org. Syn., Coll. Vol. V, page 486; and S. Ramachandran and MS Newman, Org. Syn. 41, 38 (1961). The reaction of trifluoroethoformate, p-toluenesulfonic acid and ethanol in toluene yields a diethyl ether of formula D-2. In this chart, the other variables are as defined in the summary above.

Compound of Formula D-2-Ethanol Propylene Methane is hydrogen with the use of 1 atm H₂ on Pd / CaCO₃ boosting strontium carbamate to produce a compound of formula D-3. Compounds of formula D-3 are the reaction of lithium diisopropylamine (prepared from diisopropylamine and n-butyl lithium) and n-bromosuccinimide in THF to obtain a bromo compound of formula D-4. Compound of Formula D-3 is the reaction of ethylformate THF and potassium t-butoxide to produce a carboxyaldehyde of Formula D-5.

Compounds of Formula D-4 are hydrolysis of hydrochloric acid, such as sulfuric acid, to give a compound of Formula D-6. Similarly, when the compounds of Formula D-8 and D-9 solid, as described below, they are hydrolysed with aqueous hydrochloric acid to obtain compounds of Formula D-10 and D-11, as can be expected.

Compound of Formula D-6 is the reaction of the thiourea in acetonitrile and the next heat transferring force to obtain the amine-substituted thiazole compound of Formula D-7. Carboxaldehyde of Formula D-5 is the reaction of hydrazine in ethanol / water to obtain a pyrazole compound of Formula D-8. Carboxaldehyde Compound of Formula D-5 is the reaction of a reflux solution of sodium metal and guanidine sulfate in isopropyl alcohol to obtain an amino-substituted pyrimidine compound of Formula D-9.

Compound of Formula D-7 is a reaction of a metallic compound, R₃metal, like R₃Li, R₃MgBr promote R₃MgCl (e.g., lipo-2-chloroethyl) in aprotic solvents such as THF -78 ° C to room temperature to give a compound of Formula D-12 pair as R₂and r₃ are, for example, hydroxy and chloroethynyl, and are further defined in the summary above. Similarly solid compounds of formula D-13 and D-14 from compounds according to Formula D-10 and D-11 including analogous effervescent agents.

Scheme Ε

<img file="IS2743B_D0058.tif" />

Scheme Ε

The compound of formula E-1 (which is the same as the compound of formula A-3a (see Scheme A) wherein R₁₀ methoxy and other parameters as defined in the summary above) are treated with reducing metal reagents, such as alkaline (class ΙΑ in the atomic system) or alkaline earth metal (class IIA in the atomic system), including Li, Na or Ca , amine like NH₃ or ethylenediamine, and a proton protrusion, such as t-butyl alcohol or ethanol, an aprotic solvent such as THF or dioxane at -78 ° C to room temperature to give the compound of formula E-2, wherein the variables are identical to those is described in the summary above.

The compound of formula E-2 wherein the variables are as described above is reacted with R₃metal, like R₃Li, R₃MgBr or R₃MgCl, where R₃ for example, alkynyl, in aprotic solvent such as THF at low temperature to give the compound of formula E-3 wherein the variables are as described above.

The compound of formula E-3 is reacted with aqueous acid, such as HCl, acetic acid or oxalic acid, in a solvent such as THF or dioxane at -20 ° C to reflux to give compounds of formula E-4 and E-5 therein The variables are as defined in the summary above. In different proportions depending on the nature of the water-soluble acid and solvent used. Compounds of Formula E-4 and E-5 may be prepared by other methods of light as described in Protecting Groups in Organic Synthesis, Second Edition, TW Greene and PGM Wuts, John Wiley and Sons, Inc. (1991).

Scheme F

I (CRJftype ^R2 ^Η° ~ Ί (^CR8^R9) rn,^R2

P ~ η (CR₈R₉)_m fy ° KA / 4-¾ ' ¹³

<img file="IS2743B_D0059.tif" />

r^R r, &lt;t; ° C^R'⁵

F-15 ^rWR₇

F-12

Scheme F

Compounds of formula F-1 (prepared as described in Examples A, B, C and H), the parameters as described above are summarized hereinbelow with oxidizing agent such as osmium tetroxide (t-butanol, methyl ether) promoting a miflil for renewal of the oxidant, such as methylene chloride, such as N-methylmorpholine-N-oxide, without catalyst, such as pyridine, such as methylene chloride, at 0 ° C to room temperature to obtain the intermediate compound of formula F-2 pair The variables are as described in the summary above.

Compounds of Formula F-2 pair of the parameters as described above (the summary above is reaction with a carbonylation reagent, such as carbonyl-dimidazole, diphosphogenic phosgene, solvent such as THF, methylene chloride, vial 0 ° C to reflux to obtain (2-oxo-1,3-dioxolan-4-yl) methyl compound of formula F-3 pair to which all the parameters are as described in the summary above.

Diphenyl compounds of formula F-2 pair as the parameters are as described above in the summary above is oxidation cleavage with oxidation reagents, such as sodium perjiclate (NalO₄), without an acidic acid, such as sodium bicarbonate, in a solvent such as methylene chloride, at 0 ° C to room temperature to obtain the aldehyde of formula F-4 pair as the parameters are as described. In the summary above.

The power of several advantages is a compound of formula F-1 pair whose parameters are as described above. In the Summary, the above-mentioned effect is consistent with antioxidant reagents, such as osmium tetroxide in t-butanol, and oxidative cleavage reagents, such as sodium perjiclate (NalO₄), to enhance the oxidation of the oxidant, such as N-methylmorpholine-N-oxifl, with a catalyst, such as pyridine, in the solvent mixture, such as dioxane-boosted water, at 0 ° C to room temperature to obtain the aldehyde according to Formula F-4 pair whose parameters are as described above in the summary above.

The majority of the advantages are compounds of formula F-1 pair whose parameters are as described above. In the Summary, the control is summarized above the reaction mixture with nonionic solvents, such as THF, at -78 ° C to 0 ° C followed by treatment with a reducing agent, such as dimethylsulfide, vifl -78 ° C to room temperature to give the aldehyde of formula F-4 pair as the parameters are as described in the summary above.

Aldehyde of Formula F-4 pair, as the parameters are as described above, is summarized in the summary above. The reaction mixture with amine (NHR₁₂R₁₃, for example piperidini), for example, a purrkmifil, such as molecular sieve magnesium sulfate, with a reducing agent, such as sodium triacetoxyborohydride (NaBH (OAc)₃) promote sodium cyanoborohydride (NaCNBH₃) in the solvent emulsion, the mixture of solvents, such as acetic acid and / or dichloromethane, at 0 ° C to room temperature, to give a compound of formula F-5, a pair of compounds R₁₂ and r₁₃together, piperidinyl and pairs as the other variables are as described above. In the summary above.

Oxime-containing compound of formula F-6 pair as R₁₂ is hydroxy and alkoxy and the pair of the other variables are as described. In the summary above, is prepared by the reaction of the formula F-4 compound pair with the parameters as described above. In the Summary, above, with hydroxylamine or alkoxyamine and HCl salt, with eda without base, like KHCO₃ pyridine, in solvent, such as methane, ethylene pyridine, at 0 ° C to reflux.

Immunization reagent, such as PO (OR₁)₂CH₂R₁ is treated with a base such as lithium diisopropylamine (LDA) and n-butylipipel and is reacted with aldehyde according to formula F-4 pair as the parameters are as described in the summary above in solvent such as THF at -78 ° C to room temperature to obtain an alkenyl compound of formula F-7 pair whose parameters are as defined in the summary above.

Aldehodide of Formula F-4 pair as the parameters are as described above. In the summary above above, medoxamides such as diisobutylalumhydride (DiBAL) [hexane and sodium borohydride (NaBH₄) in solvent, such as THF methane, at -78 ° C to room temperature to give an alkdihidide of formula F-8 pair as the parameters are as described above. In the summary above.

The alkenyl compound of Formula F-7 pair, as the parameters are as described above, is hydrogenated with the use of hydrogen with palladium on carbon catalysts such as platinum oxide and rhodium on alumina (see PN Rylander In Hydrogenation Methods, Academic Press, New York, 1985; Herbert 0. House! Modern Synthetic Reactions, Chapter 1, bis. 1-45; and John Fried and John A. Edwards in Organic Reactions in Steroid Chemistry, Chapter 3, bis. 111-145) in different solvents paired with methane, ethane and THF to give a compound of formula F-9 pair as the parameters are as described above. In the summary above.

Alkdihidide of Formula F-8 is coupled to RrArylOH, using asdcarboxylate such as diethyl dicarboxylate (DEAD), trialkylphosphine such as triphenylphosphine (PPh₃) In a solvent, such as methylene chloride, to give a compound of formula F-10 pair as R_f is formyl and other ardmatic linkers as described in the summary above and the other parameters are as defined in the summary above. Alternatively, the formula F-10 compound is produced by reaction of the compound of formula F-8 at p2743 toluenesulfonyl chloride. The intermediate obtained in DMF is reacted with an alkali metal salt of RrArylOH to give a compound of formula F-10.

The ester of formula F-11 (produced from aldehyde of formula F-4 according to the unlefination process described above) as a pair of R_t1 is, for example, methyl and the above parameters are as described in the summary above, reacting a water-soluble base, such as KOH, in a solvent similar to THF, and the resulting solution is heated to room temperature for reflux to get the acid of formula F-11 pair as R_f1 is hydrogen and all of the parameters are as described in the summary above.

Compound of formula F-11 pair as R_f1 hydrogen and other parameters are as described above. The above is treated with a clot reagent, such as 1,3-dimethylaminopropyl-3-ethylcarbodiimide (EDC) dicyclohexylcarbodiimide (DCC) and hydroxybenzotriazole hydrate (HOBt), non-catalytic , such as 4-dimethylaminopyridine (DMAP) and amine (NHR₁₂R₁₃, for example pyrrolidine) in aprotic solvents, such as dichloromethane DMF, at 0 ° C to room temperature to give a compound of formula F-12 pair which, for example, R₁₂ and Ri₃ together, pyrrolidinyl, and the other variables are as described in the summary above. Compounds of formula F-12 are prepared from compounds of Formula F-11 according to other disclosed clotting methods, and some of the terms are described Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 972-988.

Compound of formula F-13 pair as R_f2 is COOR_F3, pair as r_F3 is, for example, methyl, and the pairs of the other variables are as defined in the above-mentioned summary (prepared from the aldehyde of formula F-4 according to the olefination method described above) is hydrogenated with a water-soluble base, such as KOH, in solvents, such as THF, and the resulting solution is stirred at room temperature to reflux to give a compound of formula F-13 pair as R_f2 is COOH and the other variables are as described. (Summary of the foregoing.

Compound of formula F-13 pair as R_f2 COOH is treated with a clay substrate such as 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide (EDC) dicyclohexylcarbodiimide (DCC) and hydroxybenzotriazole hydrate (HOBt), non-catalytic agents, such as 4-dimethylaminopyridine (DMAP ) and amini (R₁₂R₁₃NH, such as pyrrolidine) in an aprotic solvent, such as dichloromethane DMF, at 0 ° C to room temperature, to give a compound of formula F-14 pair which, for example, R₁₂ and r₁₃ taken together, pyrrolidinyl, R 'and R' are taken together to form = 0, and the other variables are as described in the summary above. Compounds of Formula F-14 are also prepared from compounds of Formula F-13 according to other disclosed coupling methods, and some are described Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 972-988.

Compounds of formula F-13 pair as R_f2 is CHO and the other variables are as described. In the summary above (produced analogously to the compound of formula F-7) is treated with amine (NHR₁₂R₃, for example piperidine), including non-cellulose compounds, such as magnesium sulfate magnesium sulfate, and a reducing agent such as sodium triacetoxyborohydride (NaBH (OAc)₃) of sodium cyanoborohydride (NaCNBH₃) solvents from solvents, such as acetic acid and / or dichloromethane, at 0 ° C to room temperature to give a compound of formula F-14, a pair such as, for example, R12 and R₁₃ taken together with the nitrogen atom are piperidinyl, each R 'is H, and the pair of the other variables are as described above. In the summary above.

Protective compounds Compound of Formula F-13 pair as R_f2 is for daemis CH₂OTBDMS is prepared from the aldehyde of Formula F-4 by Wittig-clot as described above. This compound is deprotected in the alcohol with the use of tetrabutylammonium fluoride in a solvent, such as tetrahydrofuran. This molecule pair as R_f2 is CH₂OH is reacted with methanesulfonyl chloride, diisopropylethylamine and mono-or dihydric amines, such as morpholine, to give a compound of formula F-14 pair as R_i2 and r₁₃ are taken together, for example, morpholinyl, and each R 'is H and the other variables are as described in the summary above.

Compounds of formula F-10 pairs as R_f is CHO and the other variables are as described in the summary above (which is produced as described above) is treated with amine (NHR₁₂R₁₃, for example piperidine), including non-cellulose compounds, such as magnesium sulfate magnesium sulfate, and a reducing agent such as sodium triacetoxy-borohydride (NaBH (OAc)₃) of sodium cyanoborohydride (NaCNBH₃) In a solvent mixture of solvents, such as acetic acid and / or dichloromethane, at 0 ° C to room temperature, obtain a compound of formula F-15, a pair such as, for example, R₁₂ and r₁₃ taken together with N are piperidinyl, R 'is H and the other variables are as described above in the summary above. Compounds of formula F-15, paired with R &amp; apos; and R &amp; apos; are taken together to form = 0, are derived from the leaving fragments which are the analogous peams described above.

Scheme G

<img file="IS2743B_D0060.tif" />

<img file="IS2743B_D0061.tif" />

<img file="IS2743B_D0062.tif" />

<img file="IS2743B_D0063.tif" />

<img file="IS2743B_D0064.tif" />

<img file="IS2743B_D0065.tif" />

Scheme G

A compound of formula G-1 wherein Z is NH₂ and the other variables are as defined in the summary above (produced according to the chromaticity in Schemes A and H) is a reaction with aldehydes promoting ketone such as R₁₂C (O) R₁₃ and vial of sodium triacetoxyborohydride (Na (OAc)₃BH) or sodium cyanoborohydride (NaCNBH₃) as a reducing agent to produce a reduction amine product of formula G-2 wherein Z (N and the other variables are as defined in the above-mentioned Summary of the Preferences. Compound of the formula is a compound of formula G-2 produced by the compound of formula G-1 according to various reductive amination procedures known in the art, as described for the preparation of the compound of formula B-4, Scheme B above.

Compound of formula G-1 wherein Z is NH₂ enhancing OH is the reaction of a conjugate reagent such as 1,3-dimethylaminopropyl-3-ethylcarbodiimide (EDC) promoting dicyclohexylcarbodiimide (DCC) and hydroxybenzotriazole hydrate (HOBt) and base, such as 4-dimethylamino2743 pyridine (DMAP) or triethylamine, in aprotic solvent, such as methylene chloride, and an acid to give a compound of formula G-3 pair as Z is O or NR_12l R_g is for example alkyl and the other variables are as defined in the summary above. Alternatively, compounds of formula G-3 of the compound of formula G-1 according to standard acylation, such as the metabolism of the compound according to formula G-1 with a base such as pyridine, and acyl halide or anhydride an aprotic solvent can be administered according to the formula Formula G-3.

Compound of formula G-4 wherein is 0 or NR₁₂ and the other variables are as defined in the above summary test of the compound according to formula G-1 according to the methods outlined in Scheme B, such as the preparation of carbamate according to formula B-2 pair as R_b is -C (O) NR₁₂RI3. The aforementioned advantages are compounded according to formula G-4 pair which is NHBoc reactant of a base, such as m-BuLi, aprotic solvent and amine to give a compound of formula G-4 pair as Zt is NH.

Compound of formula G-1 is a reaction compound of formula R_g1SO₂CI and base, such as triethylamine, in aprotic solvents, such as THF to give a compound of formula G-5 pair which is L is 0 to NR₁₂, R_g1 is for alkyl and the other variables are as defined in the summary above.

Compound of formula G-1 pair as 7_y is -NH₂ and the other variables are as the pairs are defined. In the summary above, the reaction is by (Me₂NCH ​​= N)₂ In aprotic solvents such as toluene and vifi acids, such as p-toluenesulfonic acid, may give a compound of formula G-6 pair as the variables are as defined in the above-mentioned summary.

Scheme Η

<img file="IS2743B_D0066.tif" />

Scheme Η

The compound of formula H-1 wherein the variables are as defined in the above summary (prepared by the methods of Scheme A above) is reacted with reagents such as P (Rh 2) 3 CH₂R₁₂ or PO (OR_h2)₂CH₂R₁₂ where R_h2 is lower alkyl or aryl and the other variables are as defined above and bases such as lithium diisopropylamide (LDA) or sodium hydride (NaH) in aprotic solvents, such as THF or DMF, to give the compound of formula H- 2 wherein Z is CH and R₁₂ and the other parameters are as defined in the summary above.

The compound of formula H-1 is reacted with the compound of formula H₂NOR₁₂ or its hydrochloride salt in ethanol or methanol, with or without sodium acetate (NaOAc) at room temperature or at reflux temperature of the solvent, to give the compound of formula H-2 wherein Z is N and R₁₂ and the other variables are as defined in the summary above.

A compound of formula H-1 is reacted at R_hOH pair as R_h is, for example, lower alkyl and ethylene glycol, and an acid such as p-toluenesulfonic acid in aprotic solvent such as toluene at reflux temperature under Dean-Stark trap to remove water to give a compound of formula H-3 pair as R_h is, for example, lower alkyl and a pair of R_h taken together with two oxygen atoms forms for the 1,3-dioxolane, and the other variables are as defined in the above-mentioned summary.

A compound of formula H-2 pair wherein Z is CH, R₁₂ is, for example, alkyl and the other variables are as the pairs are defined as the above-mentioned formula is reacted at H₂, and Pd / C or other reagents as described by PN Rylander Hydrogenation Methods, Academic Press, New York, 1985, solvents, such as methane, to give a compound of formula H-4 pair wherein Z is CH, R₁₂ is, for example, alkyl and the other variables are as defined in the above-mentioned summary.

A compound of formula H-2 pair wherein Z is N, R₁₂ is the case with alkyl and the other variables are as defined. In the summary above, reaction is carried out with hydrochloric acid in methanol and boron trimethylamine complex (Me₃NBH₃) or a further reducing agent to give a compound of formula H-4 pair wherein Z is NH, R₁₂ is alkyl and the other variables are as defined in the above-mentioned summary.

To odor the attached compound of formula H-4 from the compound of formula H-2 with odor hydrogenation behaviors that are known and readily available in the art.

A compound of formula H-1 is reacted with trimethylsulfonium iodide ((CH₃)₃S⁺F) edimethylsulfoxonium iodide ((CH₃)₃S⁺-&gt; OI ') and bases, such as potassium t-butoxide, in aprotic solvents such as DMF to give a compound of formula H-5, pair of variables as defined in the Summary above. Advantageously, a compound of formula H-5 from the compound of formula H-1 analogous to that shown in Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 468-470.

A compound of formula H-1 is reacted at R₃metal, like R₃Li, R₃MgBr eda R₃MgCl, pair as R₃ is, for example, alkynyl or alkyl in aprotic solvents such as THF at low temperature to give a compound of formula H-6 pair as R₃ is alkenyl and alkyl and the other variables are as defined in the present summary above.

A compound of formula H-1 is reacted with TMSCF₃ and TBAF as described in GA Olah et al., J. Am. Chem. Soc. (1989) 111, 393, to give a compound of formula H-6 pair as R₃ is -CF₃ and the other variables are as the pairs are defined in the summary above. Ad odor is a compound of formula H-1 reacted at adra -CF₃ Nuclear devices that are known and obviously disclosed include, but not limited to, those described by J. Russell, N. Roques, Tetrahedron, 1998, 54, 13777-13782.

Alternatively, there is a compound of formula H-5, the pair of which the parameters are as defined in the summary above, the reaction force of R₃metal like r₃Li, R₃MgBr promote R₃MgCl, pair as R₃ for example, alkyl in aprotic solvents such as THF canceling low temperature to give a compound of formula H-6 pair as R₃ is for example -CH₂-alkyl, and the other variables are as defined in the above-mentioned summary. The other advantages are compounds of formula H-5 pairs whose variables are as defined in the present summary above the reaction rate at R₃-X-ore, like R₃ONA, R₃SNA, R₃OK, R₃OL strengthen R₃Match pairs as R₃ is, for example, alkynyl and X is the formula S in aprotic solvents such as THF, with room temperature to the residual flux level of the solvent used as a power source to give a compound of formula H-6 pair as R₃ is, for example, -O-CH₂-alkynyl radical -S-CH₂-alkynyl and the other variables are as defined in the above-mentioned summary. The majority of the compounds are compounds of formula H-5, the variables being as defined herein, above the reaction rate of the amine aprotic solvent such as THF, for room temperature to the residual liquid phase of the solvent used as a power source to give a compound of formula H -6 pairs as R₃ is -CH₂NR₁₂R₁₃ and the other variables are as the pairs are defined in the summary above.

Compound of Formula H-6 pair as R₃ is alkynyl and the other variables are as the pairs are defined in the summary below, the reaction factor of H₂, Pd / C boost PtO₂ to give the corresponding saturated alkyl product. Compound of Formula H-6 pair as R₃ is alkynyl and the other variables are as defined in the summary above, the reaction rate of LiAIH₄ in aprotic solvents such as THF to yield the corresponding trans-alkenyl fluoride. A compound of formula H-6 pair as R₃ is alkynyl and the other variables are as defined by the summary of the force of force above is the reaction force of H₂ and relieves catalytic convergence to give the corresponding cis-alkenyl derivative. Generally, these compounds contain the use of multiple conditions as described in Modern Synthetic Reactions, Herbert 0. House, Ed., Chapters 1 &amp; 2.

Compound of Formula H-6 pair as R₃ is hydroxyalkyl and the other variables are as defined herein, the reaction of acid such as p-toluene sulfonic acid in aprotic solvents such as toluene vial backflow temperature to give a compound of formula H-7 pair which is 1 2 and the other variables are as paer are defined in the summary above. The majority of advantages are compounds of formula H-6 pairs as R₃ contains a leaving group such as halogen, mesylate, tosylate or triflate and the other variables are as defined in the present invention, the reaction of a base such as NaH in aprotic solvents such as THF to give a compound of formula H-7 pair as n is 1 efia 2 and the other variables are as the pairs are defined in the summary above.

Compounds of formula H-6 pairs as the variables are as defined in the above-mentioned summary, the reaction of a base such as Et₃N efia NaH and R_h1X pairs that matter to R_M is methyl and X is halogen and other leaving groups in an aprotic solvent such as THF of methylene chloride to give a compound of formula H-8 pair which, for example, R_h1 methyl and the other variables are as defined in the summary above. The other advantages are compounded according to formula H-6 pairs as the variables are as defined in the summary above above the reaction of V₂CHR_h1, pair of those who like R_h1 is methyl and rh (oac)₃, In aprotic solvents such as methylene chloride to yield a compound of formula H-8 wherein, for example, R_h1 methyl and other variables are as defined in the summary above.

Scheme I

<img file="IS2743B_D0067.tif" />

Scheme I

A compound of formula 1-1 wherein R is, for example, benzyl and a single moiety is produced as described in LM-Fuentes, GL Larson, Tetrahedron Lett. 1982, 23 (3), bis. 271-274. Compounds of formula I-1, wherein R is, for example, benzyl, and a pair of two is produced as described in A. Ijima, K. Takashi, Chem Pharm. Bull. 1973, 21 (1), bis. 215-219. A compound of formula 1-1 and a compound of formula I-2 (which can be purchased by weight) (a salt of the compound of formula I-2, such as hydrobromide hydrochloride salt) is a reaction solvent such as isopropanol between 200 ° C and 300 ° C to yield a compound of formula I-3 pair as R₁₀ is hydroxy and the other variables are as described above in the summary above.

Compound of Formula I-3 pair as R₁₀ hydroxy and the other variables are as described above. In the summary above, which is a solvent such as DMF, the reaction of a base, such as potassium t-butoxide in t-butanol, and electrical appliances, such as benzyl bromide, vifl 0 ° C to 100 ° C to yield a compound of formula I-3 as R₁₀ is, for example, O-benzyl.

Compound of Formula I-3 pair as R₁₀ is, for example, O-benzyl and the other variables are as defined in the above-mentioned summary, which is a solvent, such as THF, is treated with 2 equivalents of strong base, such as lithium diisopropylamide, THF, -78 ° C to 0 ° C, and is then treated with electrical appliances, such as methyl chloroformate (CICOOMe) vifl -78 ° C to 0 ° C. Other electrical devices, such as propyl iodide, are added and the mixture released was between 0 ° C to 55 ° C to give a compound of Formula I-4 pair, such as R₁₀ is -O-benzyl, R₃ is propyl, R, i is methoxy and the other variables are as defined in the summary above.

Compounds of formula I-4, such as Rw is -O-benzyl, R₃ is propyl, Rh is methoxy and the other variables are as defined in the summary below, the hydrogen atom to obtain compounds of formula I-4, such as R₁₀ is hydroxy, R₃ is propyl, Rh is methoxy and the other variables are as defined in the above-mentioned summary above, including the use of ammonium formate (NH / HCOO) methane and palladium on carbon catalytic reflux backflow. Compounds of formula I-5, which are prepared herein, include a pair, for example, R₁₀ is -O-benzyl radical -O-methyl, R₃ is propyl and the other variables are as defined in the Summary of the Invention above, is treated with boron trichloride (BBr₃) methylene chloride vial -78 ° C to room temperature to give the corresponding compound pair as R₁₀ is hydroxy. Likewise, compounds of formula I-6, which are prepared herein, represent a moiety such as R₁₀ is -O-benzyl, R₃ is propyl and the other variables are as defined herein above the cross-linking phenomenon. Other different hydrogenation agents and conditions are known and accessible to the industry, such as the use of H₂ on palladium on carbon catalyst in methanol.

A compound of formula I-4 wherein for example R₁₀ is -O-benzyl, R₃ is propyl, R_t1 methoxy and other parameters are as defined in the summary above, is reacted with reductamidil, such as lithium aluminum hydride (LiAlH₄) solvent, such as THF, at 0 ° C to reflux to give a compound of formula I-5 wherein, for example, R₁₀ is -O-benzyl, R₃ is propyl and the other variables are as defined in the summary above.

A compound of formula I-4 wherein, for example, R₁₀ is -O-benzyl, R₃ is propyl, R 1 is methoxy and the other variables are as defined in the above briefing, reacted with reducing agents such as lithium borohydride (LiBH₄), In a solvent, such as THF, at 0 ° C to room temperature to give a compound of formula I-6 wherein, for example, R₁₀ is -O-benzyl, R₃ is propyl and the other variables are as defined in the summary above. Other different esterification conditions are known and available in the art.

A compound of formula I-7 (which is prepared by the methods described in Scheme A) is reacted with tallium trinitrite.3H₂OI solvent, such as methylene chloride to give the acid of formula I-8 wherein R_i2 is H and where for example R1-X- is benzyl and R10 is CH₃-C (O) -O, and these parameters are further defined in the summary above.

The acid of formula I-8 wherein R_i2 is H and where for example R_rX is benzyl and R₁₀ is CH₃-C (O) -O and wherein these variables are further defined in the summary above, the reaction of alcohol, such as methane and catalyzed acid, such as sulfuric acid, is at 0 DEG C. to reflux to give the ester of formula I- 8 where R_i2 is methyl and, for example, R_rX- is benzyl and Rio is hydroxy, and since these variables are further defined in the summary above.

Scheme J

<img file="IS2743B_D0068.tif" />

<img file="IS2743B_D0069.tif" />

Scheme J

A compound of formula J-1 pair which corresponds to the above-mentioned summary (see Scheme A for Producer Coupling) is reacted at bases such as sodium methoxide, in a proteolytic solvent such as methane and methyl acrylate to give a compound of formula J-2 pair of variables correspond to peim In the summary above. In addition, a compound of formula J-1 is prepared using the conditions described in Scheme A for the preparation of the compound of formula A-2 from the compound of formula A-1.

A compound of formula J-2 pair corresponding to the formula I above is reacted at a base such as sodium carbonate in a liquid solvent, a mixture of solvents such as methanol / water at 90 DEG C. to give a compound of formula J-3 variables correspond to peim In the summary above. Ad odor advantage is a compound of Formula J-2 hydrolysis with the behaviors mentioned in ί Protecting Groups in Organic Synthesis, Second Edition, TW Greene and PGM Wuts, John Wiley and Sons, Inc. (1991) to give the corresponding free acid according to formula J-3 pair, which correspond to the corresponding summary of the above-mentioned above.

Compounds of formula J-3 wherein the variables correspond to the above summary hereinbelow, the reactivity of the reducing agent, such as sodium borohydride in a proteolytic solvent such as ethanol to give a compound of formula J-4 wherein the variables are as defined in the summary here counts above. The power of choice is a compound of formula J-4 prepared from the compound of formula J-3 in accordance with other reduction methods described in Modern Synthetic Reactions, Chapters 2-3, bis. 45-227, Herbert 0. House, Ed., Academic Press, New York (1985).

A compound of formula J-5 wherein the variables are as defined in the summary hereinbelow is prepared from the compound of formula J-4 using the use of BBr₃ promote BCI₃ and tetrabutylammonium iodide promote dimethylborobromide aprotic solvents such as dichloromethane toluene, vifl -78 ° C to room temperature.

A compound of formula J-6 is prepared from the compound according to the use of the conditions described in Scheme H for the preparation of the compound of formula H-6 from the compound of formula H-1.

Scheme K

<img file="IS2743B_D0070.tif" />

(CR₈R₉)_m θ '** (CFUR0U 9'^R1 (CRjRg)_m

O-Rk

<img file="IS2743B_D0071.tif" />

Scheme K

The oil compounds in this scheme may act as intermediates for Schemes A-3, B, C, F, G or H.

A compound of formula K-1 (prepared as described in Scheme A-3), a pair of R₁₀is halogen, hydrogen, carboxylate, methyl ether promoting benzyl ether reinforcement is as described in the summary above, R_k is, for example, lower alkyl moiety as R_h combined lower alkyl, and all of the resulting parameters are as described in the summary above, is treated with hydrogen boron reagent, such as BH₃ In THF in aprotic solvents, such as THF hydrogenated dioxane, from 0 ° C to 60 ° C and preferably treated with oxidizing agents, such as hydrogen peroxide and water-soluble sodium hydroxide, from 0 ° C to 60 ° C to give a compound of formula K-2 . Generally, compounds of formula K-2 are prepared from the compound of formula K-1 copolymers of excipients which are the subject of the invention, such as Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 497-498.

Compound of formula K-2, pair of R₁₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether promoter is as described In the summary above, R_k is, for example, lower alkyl moiety as R_k combined lower alkyl, and all of the resulting parameters are as described in the Summary of the Invention above, is treated with a flurening agent, such as diethylaminoglycerin trifluoride (DAST), in aprotic solvents, such as dichloromethane, from 0 ° C to 60 ° C , depending on the magnitude of the solvent molecule, which is used to yield a compound of Formula K-5. Generally, compounds of formula K-5 are prepared from the compound of Formula K-2 similar to another halogenation method known in the art, as is the case in Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 353-363.

Compound of formula K-2, pair of R₁₀ is halogen, hydrogen, carboxylate, methyl ether promoting benzyl ether reinforcement is as described in the summary above, R_k is, for example, lower alkyl promoting a pair of R_k combined lower alkyl, and all of the resulting variables are as described. In the summary above, there is a significant amount of oxidizing agent, such as (nPr)₃NRuO₄and N-methylmorpholine-N-oxide, such as dichloromethane, from 0 ° C to 60 ° C, dependent on the solvent of the solvent used to yield a compound of Formula K-3. Generally, compounds of Formula K-3 are prepared from the compound of Formula K-2 according to various oxidizing agents which are known as, for example, Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 604-614.

Compound of formula K-3, pair of R₁₀ is halogen, hydrogen, carboxylate, methyl ether promoting benzyl ether reinforcement is as described in the summary above, R_k is for example lower alkyl or where R_k combined lower alkyl, and all other variables are as described in the above summary, is a flame retardant agent such as diethylamino sulfur trifluoride (DAST) in aprotic solvents, such as dichloromethane, from 0 ° C to 60 ° C C, depending on the nature of the solvent used as a bridge, to give a compound of formula K-6. Alternatively, compounds of formula K-6 are prepared from the compound of formula K-3 in accordance with other halogenation methods known in the art, as exemplified by Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 353-363.

A compound of formula K-1, pair of R₁₀ is halogen, hydrogen, carboxylate, methyl ether promoting benzyl ether promoter is as described in the Summary of the Preferences herein above, R_k is, for example, lower alkyl moiety as R_k which are combined are cyclic lower alkyl, and all of the resulting variables are as described in the Summary of the foregoing, is treated with an oxidizing agent capable of alloxification, such as selenium dioxide (SeO₂) and / or t-butyl hydrogen peroxide or chromium trichloride in a solvent such as dichloromethane, from 0 ° C to 60 ° C, depending on the yield of the solvent used as a power source to yield a compound of formula K-4. Alternatively, compounds of formula K-4 are prepared from the compound of formula K-2 according to various oxidizing agents which are known as, for example, Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 592-593.

Compound of formula K-4, pair of R_k is, for example, lower alkyl moiety as R_k which are summarized are cyclic lower alkyl, and the other variables are as described in the summary above, is a reduction in the use of Pd (OH)₂ on carbon enhancing multi-reactive reagents, such as platinum oxide enhancing rhodium on aluminum oxide (see PN Rylander in Hydrogenation Methods, Academic Press, New York, 1985; Herbert O. House In Modern Synthetic Reactions, Chapter 1, Biz. 1-45; and John Fried and John A. Edwards in Organic Reactions in Steroid Chemistry, Chapter 3, bis. 111-145) below 15 to 1000 psi (which is about 1 to about 133 atm) H₂ Protein In a solvent such as toluene, t-butyl methyl ether, promote ethanol, from 0 ° C to 60 ° C, dependent on the solvent of the solvent used to provide a compound of formula K-7.

Compound of Formula K-7, pair of R₁₀ is halogen, hydrogen, carboxylate, methyl ether promoting benzyl ether promoter is as described In the summary above, R_k is, for example, lower alkyl promoting a pair of R_k are combined with lower secondary alkyl, and all of the resulting variables are as described above, as described above, is a reducing agent such as sodium borohydride or lipid aluminum hydride, such as methane sulfate THF, at -78 DEG C. to 60 ° C, dependent on the reduction of the reducing agent and / or enhancing the solvent used to provide a compound of formula K-9, a pair of R₇ is hydrogen. Generally, a compound of formula K-9 is prepared from the compound of formula K-4 in accordance with several of the reducing factors discussed in the art, as examples of Comprehensive Organic Transformation,

RC Larock, VCH Publishers Inc. (1989) p. 527-547. Alternatively, the compound of formula K-7, wherein R₁₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether or is as described in the above summary, R_k is, for example, lower alkyl or wherein R_ktaken together are lower secondary alkyl, and all other variables are as described in the above summary, treated with R₇metal, like R₇Li, R₇MgBr or R₇MgCl, wherein R₇ for example alkyl, in aprotic solvent, such as THF or diethyl ether, from -78 ° C to 60 ° C, depending on the nature of R₇and / or the solvent used to give the compound of formula K-9, wherein R₇ is for example alkyl.

The compound of formula K-3, wherein R₁₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether or is as described in the above summary, R_k is, for example, lower alkyl or wherein R_k taken together with a reducing agent, such as sodium borohydride or lithium aluminum hydride, in a solvent such as methanol or THF, from -78 DEG C. to 60 ° C, depending on the nature of the reducing agent and / or solvent used to give the compound of formula K-8, wherein R₁₅ is hydrogen. Alternatively, a compound of formula K-8 is prepared from the compound of formula K-3 according to other methods of reduction known in the art, as examples of Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) p. 527-547. Alternatively, the compound of formula K-3, wherein R₁₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether or is as described in the above summary, R_k is, for example, lower alkyl or wherein R_k taken together are lower secondary alkyl, and all other variables are as described in the above summary, treated with R₁₅metal, like R₁₅Li, R₁₅MgBr or R₁₅MgCl, where R₁₅ is, for example, alkyl, in an aprotic solvent such as THF or diethyl ether from -78 ° C to 60 ° C, depending on the nature of R1₆and / or the solvent used to give the compound of formula K-8, wherein R₁₅ is for example alkyl.

The compound of formula K-7, wherein R₁₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether or is as described in the above summary, R_k is, for example, lower alkyl or wherein R_k taken together with lower alkyl, and all other variables as described above are reacted in anion with a base such as sodium hydride, sodium methoxide or lithium diisopropylamide, in a solvent such as THF or DMF from -78 ° C to 60 ° C, depending on the nature of the base and solvent used. The reaction mixture is treated with an alkylating agent of formula R₁₄-X, wherein R₁₄ is, for example, alkyl and X is a leaving group (see Francis A. Carey, in Advanced Organic Chemistry, Section A, Section 5.6 for Example) to give the compound of formula K-10, wherein R₁₄ and r₁₅ are, for example, alkyl or hydrogen or mixtures thereof.

The compound of formula K-3, wherein R₁₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether or is as described in the above summary, R_k is, for example, lower alkyl or wherein R_k combined with lower secondary alkyl, and all other variables as described in the above, is reacted in anion with a base such as sodium hydride, sodium methoxide, or lithium diisopropylamide in a solvent such as THF or DMF from -78 ° C to 60 ° C, depending on the nature of the base or solvent used. The reaction mixture is treated with an alkylating agent of formula R₇-X, wherein R₇ is, for example, alkyl and X is a leaving group (see Francis A. Carey, in Advanced Organic Chemistry, Section A, Section 5.6 for Example) to give the compound of formula K-11, a pair of R₇ and r₁₅ are for example alkyl or hydrogen or mixtures of pairs.

The compound of formula K-10, pair of R₁₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether or is as described in the above summary, R_k is, for example, lower alkyl or a pair of R_k taken together with a reducing agent, such as sodium borohydride or lithium aluminum hydride, in a solvent such as methanol or THF, from -78 DEG C. to 60 ° C, depending on the nature of the reducing agent and / or solvent used to give the compound of formula K-12, a pair of R₇ is hydrogen. Alternatively, the compound of formula K-12 is prepared from the compound of formula K-10 by other reducing methods known in the art, as examples of Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 527-547. Alternatively, the compound of formula K-10, pair of R₁₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether or is as described in the above summary, R_k is, for example, lower alkyl or a pair of R_k taken together are lower secondary alkyl, and all other variables are as described in the above summary, be treated with R₇metal, like R₇Li, R₇MgBr or R₇MgCl, pair as R₇ is, for example, alkyl, in an aprotic solvent such as THF or diethyl ether from -78 ° C to 60 ° C, depending on the nature of R₇and / or the solvent used to give the compound of formula K-12, a pair of R₇ is for example alkyl.

The compound of formula K-11, pair of R1₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether or is as described in the above summary, R_k is, for example, lower alkyl or a pair of R_k taken together with a reducing agent, such as sodium borohydride or lithium aluminum hydride, in a solvent such as methanol or THF, from -78 DEG C. to 60 ° C, depending on the nature of the reducing agent and / or solvent used to give the compound of formula K-13, a pair of R₁₅ is hydrogen. Alternatively, a compound of formula K-13 is prepared from the compound of formula K-11 by other reducing methods known in the art, as examples of Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 527-547. Alternatively, the compound of formula K-11, pair of R₁₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether or is as described in the above summary, R_k is, for example, lower alkyl or a pair of R_k combined are lower secondary alkyl, and all other variables are as described. In the above summary, treated with R₁₅metal, like R₁₅Li, R₁₅MgBr, or R₁₅MgCl, where R₁₅ is, for example, alkyl, in aprotic solvents, such as THF of diethyl ether from -78 ° C to 60 ° C, depending on the nature of R₁₅ore and / or solvents which are useful in obtaining a compound of formula K-13, wherein R₁₅ is for Daemis alkyl.

Compounds of formula K-7, pair of R₁₀ is halogen, hydrogen, carboxylate, methyl ether, benzyl ether, is as described in the foregoing, R_k is, for example, a lower alkyl radical as R_k combined with lower secondary alkyl, and all of the above parameters are described in the summary above, is treated with a fluorescent agent, such as diethylamino sulfur dioxide fluoride (DAST), in aprotic solvent, such as dichloromethane, from 0 ° C to 60 ° C, has the substance of the solvent used to provide a compound of formula K-14. The aforementioned advantages are compounds of formula K-14 prepared from the compound of formula K-7 according to other halogenation methods known in the art, as examples of Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 353-363.

Compound of formula K-9, pair of R₁₀ is halogen, hydrogen, carboxylate, methyl ether or benzyl ether or is as described in the summary above, R_k is, for example, lower alkyl and a pair of R_k combined lower alkyl, and all of the above variables are as described above, is treated with fluorescent agent such as diethylamino sulfur trifluoride (DAST) in aprotic solvent, such as dichloromethane, from 0 ° C to 60 ° C, has the substance of the solvent which is useful in obtaining a compound of formula K-15. The aforementioned advantages are compounded according to formula K-15 prepared from the compound of formula K-9 with other halogenation methods known in the art, such as Comprehensive Organic Transformation, RC Larock, VCH Publishers Inc. (1989) bis. 353-363.

Some of the residues which are useful for the preparation of the compounds described herein may require protection of remote activity (for example, primary amine, two-membered amine, carboxyl of Formula I precursors). The need for protective protection will vary depending on the nature of the distant activity and the conditions of the production catalysts. The need for adequate protection can be verified by professionals in this area. The use of such a protection / protection product is also well known. For a general description of protecting groups and their use, see TW Greene, Protective Groups in Organic Synthesis, John Wiley &amp; Sons, New York, 1991.

The compounds given herein may also be verified as an allotype. The case of isotopes capable of verifying the incorporated compounds is comprised of isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, as well as²H, ³H, ¹³C ¹⁴C ¹⁵n, ¹⁸0,¹⁷0,³¹P, ³²P, ³⁵S, ¹⁸F and ³⁶CI. Certain aliphatic compounds of this invention, to a single pair of radioactive isotopes such as³H and ¹⁴C are incorporated, are useful in drug and / or substrate tissue distribution assays. Hydrogen, ie³H and carbon-14, ie ¹⁴C, isotopes are especially preferred because of the ease of producing and analyzing them. Substitution with heavier isotopes, such as dihydrates, ie²H, can provide certain treatment options because of increased metabolic stability, such as increasing the half life of the organism or reducing the dose requirement, and therefore may be preferable in some cases. Co-formulated compounds can generally be produced by performing the methods described in the schemes and / or in the examples below, by substituting readily readily-readable detergent substrates and non-allotransmitted substrates.

Any of the compounds of this invention may be constructed as a pharmaceutically acceptable salt for incorporation into different pharmaceutical compositions. As used herein, pharmacologically acceptable salts include but are not limited to hydrochloric, hydrobromic, hydrochloric, hydrochloric, sulfuric, sulfonic, citric, camphoric, maleic, acetic, lactic, nicotinic, nitric, succinic, phosphoric, malonic maleic acid, salicylic acid, phenylacetic acid, stearic acid, palmitic acid, pyridine, ammonium, piperazine, diethylamine, nicotinamide, formic acid, fumaric acid, urea, sodium, potassium, calcium, magnesium, zinc, lithium, cinnamic acid, methylamino, methanesulfonic acid, picric acid, p-toluenesulfonic acid , naphthalenesulfonic acid, tartaric acid, triethylamino, dimethylamino and tris (hydroxymethyl) aminomethane. In addition, pharmaceutically acceptable salts will be apparent to professionals in this field. When more than one basic group is present, the name refers to polysaccharide (for example, double salts).

Some of the compounds of this invention are acidic and may form a salt with a pharmaceutically acceptable cation. Some of the compounds of this invention are basic and may form a salt with a pharmaceutically acceptable anion. Oil-containing salts, pairs of double-salts, are within the scope of this invention and can be reproduced by conventional methods. They can be simply produced by contacting acid and basic groups with each other, either in water, non-water or in part to a water medium. For example, the mesylate salt is prepared by reaction of the free base form of the compound of formula I with methanesulfonic acid under standard conditions. Likewise, the hydrochloric acid salt is prepared by reaction of the free base form of the compound of formula I with hydrochloric acid by standard conditions.

In addition, when compounds of this invention form hydrates and solvates are also within the scope of this invention.

The compounds of this invention also cover racemates, stereoisomers and mixtures of these compounds, including isotopically-labeled and radiolabelled compounds. Thus, isolation can be resolved according to standard dissolution methods, including particle crystallization and hand column chromatography.

Alternatively, the compounds of this invention have asymmetric carbon atoms and are therefore enantiomers or diastereoisomers. Polymer mixtures can be separated into their individual enantiomers on the basis of physical / chemical differences according to peripheral phage known in the art, for example by chromatography and / or partial crystallization. The enantiomers of the enantiomers may be transformed into conversion of an enantiomeric mixture into a stereoisomeric reaction with a reactive hydrophobic compound (e.g. alcohol), separation of the diastereomers, and conversion (e.g. hydrolysis) of the individual diastereomers to corresponding enantiomers. All flakes disappear, including enantiomers, enantiomers and mixtures thereof are considered as part of this invention.

The following formulations of the compounds of this invention (which are represented by single-phase buildings) are preferred and the first proposition is preferable:

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The compounds of this invention can be verified by more trace forms, pairs of single molecules, ketoforms, and quaternary pairs. Oil spun turbine forms are within the scope of this invention.

The use of GR agonists, antiparasitic agents and antitussive agents of this invention may affect a fundamental, interfering system in the body, related to carbohydrate, protein and lipid metabolism, ionic and water balance, and cardiovascular function, kidney, central nervous system, immune system, skeletal and muscle and other organs and tissues. (in this regard, GR is responsible for the use of polycystic diseases related to high levels of efa lack of glucocorticoids in the body.

The compounds of this invention disappear and pharmaceutically acceptable salts are useful for inducing a decrease in pills. In mammalian pests, wishing to lose weight. As a result of this invention, the present invention has limited activity, the compounds of this invention have disappeared and fused pairs of ability to induce weight loss in different ways, such as suppression of appetite, decreased food intake and stimulation of metabolic rate in external tissues, and thus increased energy consumption. In addition, the compounds of this invention, disappearing and salts thereof may be used to induce better metabolism of nutrients from fat in muscle tissue in mammals. Although it does not necessarily lead to weight loss, this increase in muscle mass may be useful for preventing or treating diseases,

As stated hereinabove, compounds, disappearing and pharmaceutically acceptable salts of this invention may be combined with a pharmaceutically acceptable carrier, a carrier or a pharmaceutical composition useful for the treatment of the biological condition of the disorder given herein in mammals, and more preferred, human subjects. Essentially, the carriers of the promoter used in these pharmaceutical compositions may be present in many different forms of high dose delivery line, for example, in ears, by mouth, on board, in stools or in the uterus. The compounds, salts and salts of this invention may be administered together in a balanced, conventional dosage form, such as by the uterine parenteral end-arm, through the skin.

For oral administration, the pharmaceutical composition may be in the form of solution, suspension, tablet, pill, capsule, powder and similar. Tomatoes containing various excipients such as sodium citrate, calcium carbonate and calcium phosphate are used together with various disintegrating agents such as starch and preferably potato-coated tapioca starch, and complex complexes, together with binders such as polyvinylpyrrolidone, sucrose, gelatin and acacia. Additionally, lubricants such as magnesium stearate, sodium lauryl sulphate and talc can often be useful for forming loaves. Solid-state compositions of a similar nature are also used as fillers in soft and hard filled filled gelatin capsules; and the chosen ingredients in this context also cover lactic soda as well as high molecular weight polyethylene glycols.

Because of simple donations, capsules and capsules are the most favorable dosage form for oral administration of pharmaceutical compositions according to this invention.

For parenteral administration, solutions are used in sesame edible jelly nutrients or water-soluble propylene glycol, together with deodorant aqueous solutions of corresponding water-soluble salts. Thus, aqueous solutions are applied in this case, in case of pea, and first the liquid diluent can be pressurized with sufficient saline or glucose. These aqueous solutions are especially suitable for intravenous, intramuscular, subcutaneous and abdominal injection. In this context, the sterile water medium, which is used according to standard methods well known to professionals in this area, is easy to obtain.

For intravenous administration (for example, on the surface), diluted sterile, water-soluble or partially water-soluble solutions (usually in concentrations of about 0.1% to 5%) are prepared or solutions as mentioned above for administration outside administration.

For administration to the surface, the formulas of the compounds of this invention are contemplated by the use of a microwaved, moisturizing foundation, such as ointment of efa cream. The case of a suitable ointment base is vitreous, vitreous plus flammable silicon compounds, lanolin and water in oil mist.

Disclosures for the dissemination of different pharmaceutical compositions with a certain amount of active ingredients are known, and will become apparent in the light of this disclosure for those skilled in the art. For example, reminders for drug delivery, see Remington's Pharmaceutical Sciences, Mack Publishing Company, Easter, Pa., 15th edition (1975).

Pharmaceutical compositions and compounds disappears and pharmaceutically acceptable soft tissues of this invention will generally be administered in the form of dosage units (for example, tablet, capsule, etc.) in a therapeutically effective amount of a compound of a salt of from about 0.1 kg / kg of body weight to about 500 mg / kg body weight, especially from about 1 pg / kg to about 250 mg / kg, and especially from about 2 pg / kg to about 100 mg / kg . Particularly, a compound of this invention will be administered in an amount of about 0.1 mg / kg to about 500 mg / kg of body weight, ranging from about 0.1 mg / kg to about 50 mg / kg of equilibrium weight. As will be appreciated by those skilled in the art, the magnification of a pharmaceutical composition according to this invention will be appreciated by a patient of a range of subjects,

The following paragraphs describe examples of combinations, doses, etc. which are useful for non-human animals. The compounds of this invention may not be administered by mouth, for example by injection. The amount of a compound of formula I, wherein a pharmaceutically acceptable salt is administered by a pharmacologically effective dose is generally the daily dose administered by oral administration between about 0.01 and 500 mg / kg of equilibrium, Preferably, it is between 0.1 and 50 mg / kg of equilibrium weight. Suitably, if your drinking water is cool, the treatment dose of the medium should be taken into account for daily water consumption. It is advisable to dispense the flour directly to the drinking water, preferably in the form of a liquid, water-soluble concentrate (such as an aqueous solution of water-soluble salt). Conveniently, the active ingredient is also added directly into the feed, as it is, or in the form of animal feed additives, also referred to as compound feed or concentrate. It is useful to use a compound compound or concentrate from the treatment medium in a cage to integrate the multiplier into the feed. Suitable cucumbers are liquids promoting solids, as needed, such as water, different types of flour, such as almond flour, soya bean flour, cottonseed oil, linseed oil, corn flour and rice flour, moles, urea, bone meal and mineral compounds commonly used in bird feed. Particularly effective cucumber is the animal feed itself, peas is a small part of such feed. The carrier material causes equal distribution of the active substance into the synthetic feed to which the feed mixture is mixed. It is important that the compounds are mixed in the feed mixture and then in the feed. In this regard, the mollusc can be scattered, boosting it to dissolve. In the case of foul oily cucumbers such as soybean oil, maize oil, cottonseed oil and whipped cream, promote a volatile organic solvent, and then mix it with a mixture of cocoa. Determine the power ratio of the active substance. The pile has the possibility of high variability because of the power consumed by the control of the magnitude of the mifil. In the synthetic feed, with the mixing of a sufficient proportion of the feed mixture, if the feed to power is given the desired concentration of the desired factor.

Extracts could be used to verify mixed yields of feed containing protein-containing foods such as soybean oil and other flour, as described above, for the production of concentrate supplementary supplements suitable for direct administration to animals. In such cases, the animals can eat normal food. The power of choice may thus accurately detect pancreatic supplements directly into feed for a proliferation of nutrient-equivalent synthetic feed containing a therapeutically effective amount of a compound of the invention. The mixes are carefully assembled according to standard actuators, such as twisted mixers, to ensure uniformity.

Since the dietary supplements are placed on the surface of the feed, the pulp also helps ensure equal distribution of the active substance on the surface of the feed.

This invention has more advantages in the field of veterinary medicine. For a pet owner, promote a veterinarian who oskar after breeding and reduce the unwanted fat of the pet, have a power to catch.

Drinking water and lining that are effective for the production of fat-reduced meat cuts and for potato fat-reduced meat and fat ratios are generally produced by the preparation of a compound according to the invention for a sufficient amount of animal feed to be delivered from a compartment 10 '³to 500 ppm of the compound in a hydrophilic enhancer.

Preferred medication in pig, cow, goat and goat feed contains generally from 1 to 400 g of active ingredient per ton of fibrillation, the pair of which the optimal magnitude for this animal is usually about 50 to 300 g per tonne of florin .

Preferred pet food, such as cats and dogs, generally contains about 1 to 400 g and boils 10 to 400 g of active ingredient per tonne of feed.

For parenteral administration In animals, the compounds of this invention can be prepared in the form of pasta or pellets and administered as transplantation, usually under the skin of the head or ear of the animal in which an increase in the formation of fat-reduced meat is sought and the ratio of between fatty meat and fat. In general, intramuscular administration of the injection into a sufficient amount of a compound of this invention for the animal to receive 0.001 to 50 mg / kg / day of body weight of the active substance.

The optimal dose for birds, pigs, cows, sheep, goats and pets ranges from 0.1 to 50 mg / kg / day of body weight of active ingredient.

Pasta compositions can be prepared by suspending an active compound in a pharmaceutically acceptable oil such as vegetable oil, sesame oil, maize oil or the like. Pellets containing effective amounts of a compound of this invention are contemplated by the combination of a compound of this invention with a decorative agent such as a carbon wax, a karnaubavax and a like; and lubricant, as magnesium stearate calcium ester is added to add (to improve the microspheres).

The pad is obviously adorned. You can give more than one miniature car to the desired dose, which will give rise to fat-lowering meat production and improve the ratio of fat and meat to fat. Furthermore, it has been possible to use transplantations at determined intervals during the animal treatment period to maintain the right amount of medicine in the animal body.

The activity of the compounds according to this invention is demonstrated according to one or more of the assays described below:

The following is a description of the analysis for glucocorticoid receptor antagonist / antagonist assays: HeLa cells containing indigenous human glucocorticosteroids are introduced with 3xGRE-luciferase plasmid, which is generated by supportive behaviors and plasmid! which shows neomycin resistance. New glucose-resistant cell lines are generated and audible. One platelet aggregate that is symbolic of HeLa-GRE9 is used to determine the activity of the compounds for the glucocorticosteroid. The cells are maintained in a wide range of columns and pears crossed into a 96-well tray one day for different concentrations of activity (10 '¹² to 10 '⁵) of the experimental compounds In the dwarf and nausea of ​​known sugar starch agents (peas dexamethasone, hydrocortisone) for 24 hours. The interviews are carried out in three copies. Cell solutions are formed and the luciferase activity is determined using a photometer. The efficacy is evaluated by the comparison of the luciferase activity in cells treated with experimental compounds in cells treated with dexamethasone agonist. The antagonist activity is evaluated by comparing lupiferase activity to the EC50 concentration of dexamethasone in the absence and presence of experimental compounds. EC₅₀ (concentration that produces 50% of maximal response) for dexamethasone is calculated from dose response curves.

The following is a description of the diagnosis to determine the competitive barrier binding of human type II glucocorticosteroid expressed in Sf9 cells: protocol for binding: the compounds are tested in a binding transfer assay using human glucocorticoid receptors expressed in Sf9 cells by ³H-dexamethasone as a link. Human glucocorticoid receptors are expressed in Sf9 cells as described in Mol. Endocrinology 4: 209, 1990. Pellets containing Sf9 cells expressing human GR receptor in 1L containers are digested with 40 μL of 20 mM AEBSF stock solution (Calbiochem, LaJolla, CA) containing 50 mg / mL leupeptin and 40 mL homogenite is added to. The analysis is performed in 96-well polypropylene beads in a final volume of 130 μL containing 200 μg of Sf9 rotary protein, 6.9 nM of³H-dexamethasone (Amersham, Arlington Heights, IL) in the presence of experimental compounds, experimental compounds (for totalization) or overexamination of dexamethasone (7 μm non-radioactive, to determine non-specific binding) in a volatile volume of diagnostic tubes. All compounds are tested in six strengths in two copies (concentration range 0.1-30 nM or 3-1000 nM). The test compounds are diluted from 25 mM stock solution in 100% DMSO with 70% EtOH and added in volume of 2 μL. When all finishes are closed, shake the dishes, close them with a sealing band and grease a 4 ° C overnight.

After overnight crops, free counting with dextran-coated charcoal is removed as follows: 75 pL dextran-coated charcoal (5.0 g of activated charcoal, 0.5 g dextran adjusted to 100 mL by analytical pad) are added to bins Shake and grow for 5 minutes at 4 ° C. The trays are then spun down to a cooled table separator at maximum speed for 15 minutes. 100 μL of the flotation from each well are placed in a 96-well PET tray with 200 pL of sintering coconut and counted on beta beet (1450 MicroBeta Trilux, from Wallac, Turku, Finland).

Data analysis: After non-specific binding has been verified, counting is counted as an integer present. The intensity of amplification of the experimental compound is modulated by the curve of the curve to force determine the IC₅₀ (concentration of compound that accounts for 50% of total counting).

Assay: diagnostic tube: 2.0 mL of 1 M Tris, 0.2 mL of 0.5 mM EDTA, 77.1 mg of DTT, 0.243 g of sodium oligonate in volume of 100 mL of water;

homogenization: 2.0 mL of 0.5 MK₂HPO₄ (pH 7.6), 20 μl of 0.5 M EDTA (pH 8.0), 77.1 mg of DTT, 0.486 g of sodium molybdate in volume of 100 mL of water.

The following is a lysing of the assay for determination of metabolism: TCCD cells from the ATCC containing internal human progesterone and saline transfusions are transiently introduced with 3xGRE luciferase using Lipofectamine Plus (GIBCO-DRL, Gaithersburg, MD). 24 hours after implantation, the cells are maintained in a volumetric fluidized serum and placed in a 96-well tray. After the day, the cells are treated with different strengths (10 '¹² to 10 '⁵) of experimental compounds in the absence and presence of native progesterone receptor (progesterone) and native saltosteroid agonist (aldosterone) for up to 24 hours. The treatment is performed in premium specimens. Cell solutions are formed and luciferase activity is determined using a photometer. Mechanism of action is evaluated by comparison of lupidirase activity in cells treated with a compound of cells treated with either agonist progesterone or aldosterone. The antagonist activity is assessed by comparing luciferase activity to EC₅₀ progesterone or aldosterone concentrations in the absence and presence of the compound. EC₅₀ (concentration of 50% of the peak response) for progesterone and aldosterone is calculated from the dose response curves.

The following is a description of the diagnosis for the determination of antihypertensive and anti-obesity activity: obesity, diabetic ob / ob mouse is used to evaluate the anti-diabetes and anti-obesity activity of the compounds. Six to ten week male ob / ob mice (Jackson Labs, Bar Harbor, Maine) is a valid experimental compound for 2 to 10 days. Glucose levels in fluorescents are determined by the measurements of glucose in samples as fast as midnight haemorrhage. Glucose is a quantitative-intelligent use of Abbott Autoanalyzer (Abbott, Inc., Abbott Park, IL). Monitoring is taken daily with differential detection.

The following is a description of the ability to determine the ability of a compound to inhibit glucocorticoid agonist induction of hepatocellular aminotransferase (TAT) activity In contagious rats: animals: male Sprague Dawley rats (from Charles River, Wilmington MA) (including adrenaline adrenal glands force at least one week before screening) with a body weight of 90 g are used for use. The rats are raised with a standard of flotation for 7-10 days, but pears are used in the screen.

Experimental test report: rats (usually 3 in each treatment group) are given experimental compounds, Peri promotes positive fluctuation (Ru486) by either hemorrhagic ulcer, by mouth, under the head of a hay fever. The dosage bar for the test compounds is representative of one of the following: 100% PEG 400, 0.25% methylcellulose In water, 70% ethanol enhances 0.1 N HCl and the compounds are tested in the range of from 10 to 125 mg / kg. The compounds are given in a volume of 1.0 mL / 100 g of equilibrium (for oral administration) boosting 0.1 mL / 100 g of equal weight for a prolonged release gift. 10 minutes after administration of the test compound, the rats are injected with dexamethasone (0.03 mg / kg in the peritoneal volume in a volume of 0.1 mL / 100 g) or carry. In order to produce dexamethasone short-dose is dexamethasone (from Sigma, St. Louis, MO) dissolve in 100 mL ethanol and dilute with water (end: 10% ethanol: 90% water, volume: volume). Groups treated with carry-bearing, carry-dexamethasone and Ru486-dexamethasone are included in each screening. The compounds are only tested against dexamethasone. Three hours after injection of dexamethasone, the rats are sacrificed by a shackle. Samples of liver (0.3 g) are taken and placed in 2.7 mL of iced dough and homogeneously made with polystyrene. In order to get a cell loop, the liver paw is spun at 105,000 g for 60 minutes. and flotifi is stored at -80 ° C prior to analysis. TAT is detected on 100 pL of 1:20 dilution of 105,000 g flotation using the Granner and Tomkins fracture (Methods in Enzymology 17A: 633-637,1970) and a reaction time of 8-10 minutes. TAT activity is expressed as pmol / product / min / g of liver. volume: volume). Groups treated with carry-bearing, carry-dexamethasone and Ru486-dexamethasone are included in each screening. The compounds are only tested against dexamethasone. Three hours after injection of dexamethasone, the rats are sacrificed by a shackle. Samples of liver (0.3 g) are taken and placed in 2.7 mL of iced dough and homogeneously made with polystyrene. In order to get a cell loop, the liver paw is spun at 105,000 g for 60 minutes. and flotifi is stored at -80 ° C prior to analysis. TAT is detected on 100 pL of 1:20 dilution of 105,000 g flotation using the Granner and Tomkins fracture (Methods in Enzymology 17A: 633-637,1970) and a reaction time of 8-10 minutes. TAT activity is expressed as pmol / product / min / g of liver. volume: volume). Groups treated with carry-bearing, carry-dexamethasone and Ru486-dexamethasone are included in each screening. The compounds are only tested against dexamethasone. Three hours after injection of dexamethasone, the rats are sacrificed by a shackle. Samples of liver (0.3 g) are taken and placed in 2.7 mL of iced dough and homogeneously made with polystyrene. In order to get a cell loop, the liver paw is spun at 105,000 g for 60 minutes. and flotifi is stored at -80 ° C prior to analysis. TAT is detected on 100 pL of 1:20 dilution of 105,000 g flotation using the Granner and Tomkins fracture (Methods in Enzymology 17A: 633-637,1970) and a reaction time of 8-10 minutes. TAT activity is expressed as pmol / product / min / g of liver. Bear-Dexamethasone and Ru486-Dexamethasone are included in each screening. The compounds are only tested against dexamethasone. Three hours after injection of dexamethasone, the rats are sacrificed by a shackle. Samples of liver (0.3 g) are taken and placed in 2.7 mL of iced dough and homogeneously made with polystyrene. In order to get a cell loop, the liver paw is spun at 105,000 g for 60 minutes. and flotifi is stored at -80 ° C prior to analysis. TAT is detected on 100 pL of 1:20 dilution of 105,000 g flotation using the Granner and Tomkins fracture (Methods in Enzymology 17A: 633-637,1970) and a reaction time of 8-10 minutes. TAT activity is expressed as pmol / product / min / g of liver. Bear-Dexamethasone and Ru486-Dexamethasone are included in each screening. The compounds are only tested against dexamethasone. Three hours after injection of dexamethasone, the rats are sacrificed by a shackle. Samples of liver (0.3 g) are taken and placed in 2.7 mL of iced dough and homogeneously made with polystyrene. In order to get a cell loop, the liver paw is spun at 105,000 g for 60 minutes. and flotifi is stored at -80 ° C prior to analysis. TAT is detected on 100 pL of 1:20 dilution of 105,000 g flotation using the Granner and Tomkins fracture (Methods in Enzymology 17A: 633-637,1970) and a reaction time of 8-10 minutes. TAT activity is expressed as pmol / product / min / g of liver. 3 g) take and place 2.7 mL of iced dough and make homogeneous with polystyrene. In order to get a cell loop, the liver paw is spun at 105,000 g for 60 minutes. and flotifi is stored at -80 ° C prior to analysis. TAT is detected on 100 pL of 1:20 dilution of 105,000 g flotation using the Granner and Tomkins fracture (Methods in Enzymology 17A: 633-637,1970) and a reaction time of 8-10 minutes. TAT activity is expressed as pmol / product / min / g of liver. 3 g) take and place 2.7 mL of iced dough and make homogeneous with polystyrene. In order to get a cell loop, the liver paw is spun at 105,000 g for 60 minutes. and flotifi is stored at -80 ° C prior to analysis. TAT is detected on 100 pL of 1:20 dilution of 105,000 g flotation using the Granner and Tomkins fracture (Methods in Enzymology 17A: 633-637,1970) and a reaction time of 8-10 minutes. TAT activity is expressed as pmol / product / min / g of liver.

Interpretation: Treatment data are analyzed using the ANOVA with the least-significant (PLSD) post-experimental analysis. The compounds are considered to be active in this assay pair as the TAT activity in the group treated with the compound for dexametas delivery is significantly reduced (P &lt;0.05) in proportion to the VAT TAT activity in the Bear dexamethasone treated group.

The following is a description of the analysis to determine the effect of a compound on two typical genes that are generated by the inflammatory response. This diagnosis, IL-1 (leukocyte-1) induced MMP-1 (baseline metalloprotein-1) and IL-8 (leukocyte-8) proliferation in human cartilage cells is performed as follows: SW 1353 human breast cell tumors (derived from ATCC ) from corridor 12 through corridor 19 are used in a 96-hole format analysis. The cells are the same in a 96-well tray in DMEM (Dulbeccos modified Eagle Milk) with 10% bovine serum and grown at 37 ° C, 5% CO₂. After 24 hours, serum-containing microfibre is removed and replaced with 200 μg / ml DMEM containing 1 mg / L insulin, 2 g / L lactalbumin hydrolysate and 0.5 mg / L ascorbic acid and resuspended 37 ° C C, 5% CO₂. The next morning, serum-free milk is removed and replaced with 150 pL / hole of fresh serum-free mifil containing +/- 20 ng / mL of IL-1 beta, +/- nM dexamethasone, +/- compound. The conditions are implemented In three sections, use of only the inner 60 holes in the 96-well tray. On the outer side, the surrounding holes in the tray contain 200 pL of serum-free DMEM. The trays are baked at 37 ° C, 5% CO₂. 24 hours post-addition of IL-1, 25 μL of sample from each well removed in vitro infectious conditions for IL-8 production assay. The samples are stored vifi -20 ° C pair to pau are detected. IL-8 residues are evaluated using the Quantikine human IL-8 ELISA R &amp; D Systems (D8050) console on samples thrown 60-times in RD5P Calibrator trimmer, as described in the manufacturer's manufacturer's manual. Percentage of multiple IL-1 inhibitors is determined by the mean of each of the samples. Predictive post-operative bias has verified from the median sign from untreated cells. IC₅₀ is determined on the basis of a logical process of percent parts of the reference against the strength of the inhibitor. 72 hours after IL-1 addition, the remainder of the medium is removed and stored at -20 ° C until diagnosed for MMP-1 production. The MMP-1 production line is measured with the Bio-Trak MMP-1 ELISA Compound from Amersham (RPN2610) on 100 μL of pure sample by following the manufacturer's protocol.

Percentage of mean IL-1 mediamy is determined for median time of each of the samples. In three copies after dregid, the median mark from untreated cells. IC₅₀ is determined based on a logical process of percentage of criterion against the barrier strength. Dexametasdn has been shown to be a good positive antidiabetic agent for induced IL-8 and MMP-1 expression (IC₅₀= 5nm).

EXAMPLE

Preparation 1 1-Benzyl-6-methoxy-3,4-dihydro-1H-naphthalen-2-one

A solution of 51 g (0.289 mol) of 6-methoxy-2-tetralone of formula A-1 wherein D is C, R₁₀ is methoxy; R₁₄, R₁₆ and r₁₆ each H and 24.2 mL (0.289 mdl) pyrididine in 1.5 L of toluene were refluxed over Dean-Stark trap over night. After removal of the static water, the reaction mixture was cooled to room temperature, concentrated and dissolved in 725 mL of dioxane. Out of this solution was added 52 mL (0.434 mdl) benzyl bromide and the resulting solution was refluxed overnight. Water (100 mL) was added to the solution and the resulting solution was refluxed for 2 hours. The mixture was cooled to room temperature and poured into 1 N HCl solution and extracted 3 times with EtOAc. Organic login was washed with H₂O and saturated with NaHCO₃, then dried over Na₂SO₄, and there was a lot of puzzles. Crude product was purified by flash chromatography on SiO₂ using 10% EtOAc to 15% EtOAc. In hexane as a gradient eluent to give 65.2 g of addition afidin in this yellow oil formulation (85%). IR (pure) 2937, 1712, 1500 cm '¹; ¹1H NMR (400 MHz, CDCl3) d2.41-2.59 (m, 3H), 2.76 (dt, 1H, J = 5.4, 15.5), 3.15-3.70 (m, 2H), 3.67 (t, 1H, J = 6.3), 3.77 (s, 3H), 6.67-6.70 (m, 2H), 6.81 (d, 1H, J = 8.1), 6.87-6.89 (m, 2H), 7.13-7.17 (m, 3H); ¹³C NMR (100 MHz, CDCl 3) δ 27.44, 38.19, 39.19, 54.13, 55.14, 112.11, 112.96, 126.30, 128.07, 128.26, 129 , 35, 129.53, 138.05, 138.20, 158.30, 212.41; MS m / z 267 (M + H)⁺.

Preparation 2 1 (R) -Benzyl-6-methoxy-1 (S) - (3-oxo-butyl) -3,4-dihydro-1H-naphthalen-2-dn

A solution of 62 g (0.23 mol) of the title product of Preparation 1 and 28 mL (0.23 mdl) of freshly prepared (S) - (-) - alpha-methyl benzylamine 100 mL of toluene was refluxed over Dean -Stark trap, over night. After removal of the stoichatic water, the imine solution was cooled to 0 ° C and 21 mL (0.26 mol) of freshly-methylvinylketone was added dropwise to the solution. The solution was rapid at 0 ° C for 30 minutes and at a temperature of 40 ° C over night. The reaction mixture was then cooled to 10 ° C and 17 mL of acetic acid and 14 mL of H₂The solution was removed and the resulting solution was heated at room temperature for 2 hours. The solution was poured into H₂Oh and she extracted price tags times with EtOAc. The combined lifeline login was washed with 1 N HCI, H₂O, mettuflu NaHCO₃, then dried over Na₂SO₄, and then evaporated until everything was purred. The crude product was purified by chromatography on SiO₂ Using the 15% EtOAc to 35% EtOAc hexane as a gradient eluent to give 48 g of the resulting product as a yellow solid. ¹1 H NMR (400 MHz, CDCl 3) 51.38 (s, 3H), 1.40-1.51 (m, 2H), 1.64 (ddd, 1H, J = 2.1, 4.5, 14) , 1.97 (br s, 1H), 2.20 (dt, 1H, J = 4.5, 13), 2.59 (d, 1H, J = 6.6), 3.08 (d, 1H , J = 18), 3.16 (d, 1H, J = 16), 3.33 (dd, 1H, J = 6.6, 18), 3.62 (d, 1H, J = 16), 3 , 72 (s, 3H), 6.57 (d, 1H, J = 2.5), 6.67 (dd, 1H, J = 2.5, 8.8), 7.00-7.23 m, 6H); ¹³13 C NMR (100 MHz, CDCl 3 , 09, 125.37, 127.63, 127.69, 130.27, 132.21, 145.45, 138.65, 157.88, 213.49; MS m / z 337 (M + H)⁺, 319 (M-OH)⁺.

Preparation 3 1 (S) -benzyl-6-methoxy-1 (R) - (3-oxo-butyl) -3,4-dihydro-1H-naphthalen-2-one The title compound was prepared by the use of force analogous forces and yields 2 times the use of (R) - (+) - alphamethyl benzylamine the initial imine formation. Power starting with 4.64 g of 1-benzyl-6-methoxy-3,4-dihydro-1H-naphthalen-2-one produced 3.58 g of the title product in this yield as a yellow solid.¹1 H NMR (400 MHz, CDCl 3) δ 1.38 (s, 3H), 1.40-1.51 (m, 2H), 1.64 (ddd, 1H, J = 2.1, 4.5, 13 ), 1.97 (broad, 1H), 2.20 (dt, 1H, J = 4.5, 13), 2.59 (d, 1H, J = 6.6), 3.08 (d, 1H , J = 18), 3.16 (d, 1H, J = 16), 3.33 (dd, 1H, J = 6.6, 18), 3.62 (d, 1H, J = 16), 3 , 72 (s, 3H), 6.57 (d, 1H, J = 2.5), 6.67 (dd, 1H, J = 2.5), 6.67 (dd, 1H, J = 2, 5, 8.8), 7.00-7.23 (m, 6H); ¹³C NMR (100 MHz, CDCl 3) δ 27.90, 32.79, 34.40, 38.43, 41.49, 53.51, 55.12, 58.47, 79.06, 112.05, 113, 09, 125.37, 127.63, 127.69, 130.27, 132.21, 135.45, 138.65, 157.88, 213.49; MS m / z 337 (M + H)⁺, 319 (M-OH)⁺

Preparation 4 2 (3H) -phenantrenone, 4a - [(4-isopropylaminophenyl) methyl] -4,4a, 9,10-tetrahydro-7-hydroxy-, (S)

Into a stirred solution of 200 mg of the title product from the residue was added 18 μL of 0.216 mL of AcOH, 3 mL of acetone flask and 3 mL of dichloromethane under N₂ air was added 373 mg of NaBH (OAc)₃ vifl room temperature. The reaction mixture was stirred at room temperature for 2 hours, then quenched with NaHCO₃ (Mettuflu). The mixture was extracted with EtOAc (X3), washed with brine, purrkufl over Na₂SO₄, siufl and samsflfnufl couple to everything was purred. Purification by flash chromatography on SiO₂ Mean use of 30% EtOAc in hexane as eluent gave 108 g of the resulting product as a white powder (47%). MS m / z 362 (M + H)⁺.

Preparation 5 2 (1H) -phenantrenone, 4a - [[3- (dimethylamino) phenyl] methyl] -3,4,4a, 9,10,10a-hexahydro-7-hydroxy-, (4aS-cis).

A solution of 255 mg of the title product from preparation 19 μl 0.11 mL of formaldehyde (37% v / v), 255 mg of 5% Pd (OH)₂/ C and 10 mL EtOH were shaken under 50 psi (about 3.3 psi) H₂ prince ί two days. The mix was siufl and samsflfnufl couple to everything was purr.

Purification by flash chromatography on SiO₂ using 2% EtOAc in hexane to 40% EtOAc in hexane as a gradient eluent gave 133 mg (48%) of the resultant in this example as a white gaseous powder. MS m / z 450 (M + H)⁺.

Preparation 6 1-Naphthalenepropanoic acid, 1,2,3,4-tetrahydro-6-methoxy-2-oxo-1- (phenylmethyl) methyl ester

To a solution of 3.18 g of the title compound from Preparation 1 in 30 mL of anhydrous MeOH was added 31 mL of 0.5 M NaOMe / MeOH at -15 ° C under a nitrogen atmosphere. This solution was stirred vigorously while 1.5 mL of fresh methyl methacrylate was added dropwise at -15 ° C. The mixture was stirred for 1 hour at 0 ° C and then allowed to settle for 5 minutes. The precipitate was collected by filtration and silica gel was combined with MeOH to give 2 g (52%) of the title product as a white solid. MS m / z 353 (M + H)⁺.

Preparation of 1-Naphthalenepropanoic acid, 1,2,3,4-tetrahydro-6-methoxy-2-oxo-1- (phenylmethyl) A solution of 200 mg of title product from Preparation 6 and 92 mg of Na₂CO₃ in 8 mL of MeOH and 10 mL of water was refluxed for 30 minutes. The mixture was quenched and adjusted to pH 5 with 1N HCl solution. NaCl was asked to form a mettada solution. The solution was extracted with EtOAc (X3), crushed with brine, and purr over Na₂SO₄, silent and cohabiting couple to everything was purred. Additive product In this production, 98% was obtained as a white solid. MS m / z 339 (M + H)⁺.

Preparation 8 3H-Naphtho [2,1-b] pyran-3-one, 1,2,4a, 5,6,10b-hexahydro-8-methoxy-10b- (phenylmethyl) To a solution of 199 mg of the title product from Preparation 7 in 5 mL of ethanol was added 67 mg of sodium borohydride at 0 ° C under N₂ air. The mixture was then allowed to settle overnight at room temperature. The solution was then acidified to pH 1 with 1N HCl solution and extracted with EtOAc (X3), purr quench over Na₂SO₄, filtered and aggregated pairs until everything was purred. Purification with TLC SiO₂ using 35% EtOAc in hexane as eluent afforded 73 mg (37%) of the title product as a white light powder. MS m / z 323 (M + H

Preparation of 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [3- [4- (t-butyldimethylsilyloxymethyl) phenyl] -2- propenyl] - [2R- [2,4] (E), 10β]] Title compound In this preparation, was prepared by methods described hereinbelow.

Preparation of 9a carbamic acid, dimethyl- 4b- [2-acetaldehyde] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1-propynyl) -2-phenanthrenyl ester , [4bS- (4H, 7T, 8L)] To a stirred solution of 4a (2H) -phenanthrenasaldehyde, 2- (1-propynyl) -1,3,4,9,10,10a-hexahydro-2, 7-dihydroxy- [2R- (2,4,4,10)] - (1.5 g) in THF was added radially in 4-dimethyl-2743 aminopyridine (0.12 g), triethylamine (1.8 g) and dimethylcarbamoyl chloride (1.6 g). After 18 hours, the homogeneous mixture was quenched with saturated aqueous ammonium chloride, extracted with ethyl acetate, the organic layer was dried over sodium sulfate and concentrated in vacuo. The resulting oil was purified by flash chromatography on silica gel (30-50% ethyl acetate / hexane) to give the title compound of this residue as a colorless solid, 2.3 g.

Preparation of 10 carbamic acid, dimethyl, 4b- (2-hydroxyethyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1-propynyl) -2-phenanthyl ester, [ 4bS- [4t] [8]] In a cooled (-78 ° C), a rapid solution of the title product of Preparation 9a (2.3 g) in tetrahydrofuran (60 mL) was added 1M solution of diisobutylalanide in cyclohexane (8 mL). 2.5 hours, reaction was stopped with 0.5 M sodium potassium tartrate and the resulting mixture was stirred over room temperature. The two-phase mixture was extracted with ethyl acetate (3x), combined extracts were combined with brine, supernatant sodium sulfate and concentrated Flash chromatography gave a colorless frost. Flash chromatography on silica gel (50-75% ethyl acetate / hexane) gave the title product from this residue as a colorless seed, 1.9 g.

PREPARATION 11 8-R, Sa-Benzyl-6-ethoxy-3,7,8,8a-tetrahydro-2H-naphthalen-1-one A solution of 8-R, Sa-benzyl-3,4,8,8a-tetrahydro -2H, 7H-naphthalene-1,6-dione (5.0 g), triethyl chloroformate (13 mL), p-toluenesulfonic acid (200 mg), ethanol (1.5 mL) in toluene (100 mL) 80 ° C for 1.5 hours. The reaction solution was cooled, diluted with ethyl ether, washed with 1N NaOH, water, brine, dried over sodium sulfate and concentrated in vacuo to give red oil. Filtration (20% ethyl ether / hexane) through one piece of Florisil® gave the title product from this residue as a red solid, 5.7 g.

Frameworks 12 (cis / trans) -8-R, Sa-benzyl-6-ethoxy-3,4,4a, 5,8,8a-hexahydro-2H-naphthalen-1-one

A solution of the title product of Preparation 11 (2 g) in ethanol (56 mL) was hydrogenated at 1 atmospheric hydrogen pressure over 2% strontium carbonate (0.2 g) for 4.5 hours. After removal of the catalyst by filtration and aerosol sampling, the trans and cis atoms of the title product in this reaction were followed by chromatography on silica gel (0-2% ethyl acetate / hexane). The reaction mixture (0.1 g) was first eluted as a trans (1.2 g) transient.

PREPARATION 13 (trans) -8-R, Sa-benzyl-2-bromo-6-ethoxy-3,4,4a, 5,8,8a-hexahydro-2H-naphthalen-1-one

In a quench (0 ° C), a stirred solution of lithium diisopropylamine (prepared from diisopropylamine (0.17 mL) and n-butylipie (0.42 mL, 2.5 μl hexane)) (tetrahydrofuran (9 mL) was added a solution (trans) -8-R, Sa-benzyl-6-ethoxy-3,4,4a, 5,8,8a-hexahydro-2H-naphthalen-1-one (0.25 g) in tetrahydrofuran (4 mL) After 30 minutes, the solution was cooled to -78 ° C and a solution of n-bromosuccinimide (0.2 g) in tetrahydrofuran (9 mL) was added. After 1 hour, the reaction was quenched with saturated aqueous sodium bicarbonate, extracted extracted with ethyl ether, the organic layer was then combined and dried over sodium sulfate and concentrated in vacuo. The resulting oil was purified by flash chromatography on silica gel (0-1% ethyl acetate / hexane) to give the title compound of this production as an oil ( 200 mg).The cis-core of the title product of product 12 can be reacted in an analogous manner.

Preparation 14 (trans) -8a-benzyl-2-bromo-hexahydro-naphthalene-1,6-dione

A solution of the title product of Preparation 13 (0.15 g) in a solution of ethanol (8 mL) containing 2.5% concentrated sulfuric acid and 1% water was stirred for 2 hours. The reaction was diluted with ethyl ether, washed with saturated sodium bicarbonate, brine, dried over sodium sulfate and concentrated in vacuo to give oil. Flash chromatography on silica gel (15% ethyl acetate / hexane) gave the title compound of this product as a colorless solid, 53 mg. The cis-neighborhood can be reversed in the same way.

Preparation 15 (trans) -8-R, Sa-benzyl-6-ethoxy-1-oxo-1,2,3,4,4a, 5,8,8a-octahydro-naphthalene-2-carbaldehyde

To a stirred (0 ° C) stirred solution of the title compound of Preparation 12 (2.1 g) and ethylformate (2.2 g) in tetrahydrofuran (8 mL) was added potassium t-butoxide (15.6 mL, 1 μm in THF). The reaction was then maintained at 0 ° C for 0.5 hours and at room temperature for 6 hours, quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo to give the title compound from this product as a red oil, 2.3 g.

Preparation 16 phenol, 4- [4- (chloroethynyl) -4-hydroxy-1- (phenylmethyl) cyclohexyl] -titil compound in this preparation was prepared by methods similar to those described below in Example 8. MS: 342 (M + 1)⁺.

Preparation 17 1 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -, (4aS-cis)

The title compound in this preparation was prepared by methods analogous to those described below in Example 7. MS: 323 (M + 1)⁺.

Preparation 18 2 (3H) -phenantrenone, 4a - [(4-aminophenyl) methyl] -4,4a, 9,10-tetrahydro-7-hydroxy-, (S) The title compound of this preparation was prepared by methods analogous thereto which is described below in Example 3. MS: 321 (M + 1)⁺.

Preparation 19 2 (1 H) -phenantrenone, 4a - [(3-aminophenyl) methyl] -3,4,4a, 9,10,10ahexahydro-7-hydroxy-, (4aS-cis) 2743

The title compound in this substitution was prepared by means of yields analogous to those described herein. MS: 322 (M + 1)⁺

Preparation of pyridine, 3 - [[[(2R, 4'aS, 10β) -3- (4 ', 9', 10 ', 10'α-hexahydro-4'a- (phenylmethyl) spiro [oxiran- 2,2 '(1'H) -phenanthrene] -7'-yl] oxy] methyl] The title compound of this present invention was prepared by yielding residues which are described in Example 76. MS: 413 (M + 1 )⁺.

Propylene 21 pyridine, 3 - [[[(2R, 4'aS, 10^,S) -3 ', 4^,, 4'a, 9 ', 10'a-hexahydro-4'a (phenylmethyl) spiro [ox [ran-2,2' (TH) -fenantren] -7'-yl] oxy] methyl] -2-methyl title compound in this embodiment was produced by means of power transducers which are protected by those described herein by reference to 76. MS: 427 (M + 1)⁺.

Prepared 22 pyridine, 2 - [[[(2R, 4'aS, 10'R) -3- (4 ', 4'a, 9 (10', 10'a-hexahydro-4'a- (phenylmethyl) spiro [oxirane -2,2 '(1'H) -phenanthrene] -7'-yl] oxy] methyl] The title compound of this invention was prepared by substituting the supernatants as described in Example 76. MS: 413 (M +1)⁺.

EXAMPLE 1 2 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-7-methoxy-4a- (phenylmethyl) -, (S) -Leose of 48 g (143 mmol) of title product from Preparation 2 and 71 mL of 1 M sodium methoxide in 100 mL of methanol was stirred at room temperature for 115 minutes and then heated to 75 ° C for 3 hours. The solution was cooled to 0 ° C, 8.2 mL of acetic acid was added dropwise (and the solution was synergistic. The oil was dissolved in EtOAc, washed with NaHCO₃ and saline, purrkufl over Na₂SO₄, and then evaporated until everything was purred. The crude product was purified by chromatography on SiO₂ Using the 15% EtOAc to 35% EtOAc in hexane as a gradient eluent to give 44 g of 2 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-7-methoxy-4a- (phenylmethyl) -, ( S) - as off-white powder (60% from 1-benzyl-6-methoxy-3,4-dihydro-1H-naphthalen-2-one). Recrystallization in EtOAc / hexane gave 35 g of the title product from this example as a white crystalline solid. Mp. 101-102 ° C; IR (pure) 1667, 1500 cm "¹; ¹HNMR (CDCl3) 1.83-1.90 (m, 1H), 2.02 (dt, 1H, J = 5.5, 14), 2.27 (dt, 1H, J = 4.3, 14) , 2.44-2.51 (m, 2H), 2.64-2.79 (m, 3H), 3.14 (d, 1H, J = 13), 3.21 (d, 1H, J = 13), 3.78 (s, 3H), 5.96 (s, 1H), 6.54 (d, 1H, J = 2.6), 6.71 (d, 2H, J = 7.1) , 6.77 (dd, 1H, J = 2.6, 8.7), 7.06-7.23 (m, 4H); ¹³C NMR (100 MHz, CDCl 3) δ 30.71, 32.10, 34.62, 36.09, 43.62, 46.36, 55.20, 112.78, 112.84, 125.53, 126, 68, 127.96, 128.12, 130.08, 133.01, 137.24, 137.28, 157.75, 169.16, 198.81; MS m / z 319 (M + H)⁺. Article. calculated for C₂₂H₂₂O₂: C, 82.99; H, 6.96; N, 0. Fundifl: C, 83.21; H, 7.08; N, &lt;0.10.

EXAMPLE 2 2 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-7-methoxy-4a- (phenylmethyl) -, (R) -titile compound in this yield was prepared using the analogue of Example 1. Power starting with 3.53 g of the title product from residue 3 gave 2.78 g of the title product from this example as an off-white powder (51% from 1-benzyl-6-methoxy-3,4-dihydro-1H-naphthalen-2-one ). Recrystallization in EtOAc / hexane gave 2.15 g of the title product according to this example as a white crystalline solid. All physical fasteners are the same as is described for the title product in Example 1. Article. calculated for C₂₂H₂₂O₂: C, 82.99; H, 6.96; N, 0. Found: C, 83.17; H, 7.13; N, &lt;0.10.

EXAMPLE 3 2 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-7-hydroxy-4a- (phenylmethyl) -, (S) -Octin a stirred solution of 40 g (0.126 mol) of the title product of Example 1 (formed by the methods described in Example 1) and 46.5 g (0.126 mol) of tetrabutylammonium iodide 1630 mL of dichloromethane at -78 ° C under N₂ air was added 300 mL of 1 M boron trichloride in methylene chloride. The resulting solution was heated at room temperature for 1.5 hours, then poured out of ice and stirred rapidly overnight. The mixture was extracted with dichloromethane, dried over Na₂SO₄, filtered and evaporated until dry. Purification by flash chromatography on SiO₂ using 20% ​​EtOAc to 60% EtOAc in hexane as a gradient eluent gave 33.3 g of the title compound according to this example as an off-white powder (87%). ¹1 H NMR (400 MHz, CD 3 OD) 01.81-2.00 (m, 2H), 2.26 (dt, 1H, J = 4.2, 13), 2.40 (dd, 1H, J = 5, 18), 2.53 (ddd, 1H, J = 1.7, 5.6, 14), 2.58-2.80 (m, 3H), 3.20 (d, 1H, J = 13 ), 3.26 (d, 1H, J = 13), 5.92 (s, 1H), 6.45 (d, 1H, J = 2.5), 6.67 (dd, 1H, J = 2 , 5.8.5), 6.76 (d, 2H, J = 6.6), 7.05-7.14 (m, 4H); ¹³C NMR (100 MHz, CD3 OD) δ30.22, 32.03, 34.08, 36.04, 43.73, 45.97, 113.76, 113.91, 124.50, 126.25, 127, 49, 127.94, 129.84, 131.86, 137.0, 137.71, 155.34, 171.73, 200.33; MS m / z 305 (M + H)⁺.

Example 4 2 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-7-hydroxy-4a- (phenylmethyl) -, (R) -titile product of this example was prepared using a procedure analogous to Example 3. Beginning with 1.8 g of the title product of Example 2 gave 1.3 g of the title product in this example as a white solid (75%). All physical fasteners are the same as described for the title product in Example 3.

Example 5 2,7-phenanthridiol, 2,3,4,4a, 9,10-hexahydro-4a- (phenylmethyl) -2- (1-propynyl), (2R-cis) and 2,7-phenanthridiol, 2,3,4,4a, 9,10-hexahydro-4a- (phenylmethyl) -2- (1-propynyl) -, (2S-trans) To a stirred solution of 5 mL of THF saturated with propylene at 0 ° C was added 4 mL of 0.5 M lithium diisopropylamide in THF and the resulting mixture was stirred under a nitrogen atmosphere for 20 minutes. A solution of 50 mg (0.16 mmol) of the title product of Example 3 12 mL of THF was added dropwise, and the reaction mixture was warmed to room temperature and stirred for 16 hours. Saturated aqueous ammonia chloride was added, and the mixture was extracted with EtOAc, dried over Na₂SO₄, filtered and aggregated pair until everything was dry. Purification by flash chromatography on SiO₂ using 2% acetone in dichloromethane to 4% acetone in dichloromethane with 0.5% triethylamine as a gradient eluent gave 25 mg (45%) of the first listed title product in this example (higher Rf) and 5 mg (9%) of another listed the title product in this example.

The physical properties of the first listed title product in this case are as follows: ¹H NMR (400 MHz, d6 acetone) δ1.67 (s, 3H), 1.67-1.80 (m, 2H), 2.00 2.22 (m, 2H + d6 acetone), 2.26 (ddd, 1H, J = 2.9, 4.2, 7.0), 2.60-2.78 (m, 3H), 3.01 (d, 1H, J = 13), 3.05 (d, 1H , J = 13), 4.30 (s, 1H), 5.52 (s, 1H), 6.49 (d, 1H, J = 2.6), 6.55 (dd, 1H, J = 2 , 6.8.5), 6.67 (d, 1H, J = 8.5), 6.76-6.80 (m, 2H), 7.08-7.13 (m, 3H), 8 , 06, (s, 1H); ¹³C NMR (100 MHz, d6 acetone) δ

2.5, 31.4, 33.3, 35.6, 41.8, 46.8, 54.8, 65.8, 77.8, 83.9, 113.1, 114.4, 126, 0, 127.4, 127.7, 128.4, 130.6, 134.0, 137.2, 138.7, 141.1, 155.1; MS m / z 327 (M-OH)⁺

The physical properties of another listed title product (this example is as follows: ¹1 H NMR (400 MHz, d6-acetone) 51.77 (s, 3H), 1.77-2.30 (m, 5H + d6 acetone), 2.58-2.78 (m, 3H), 2.96 , 1H, J = 13), 3.02 (d, 1H, J = 13), 4.06 (s, 1H), 5.60 (s, 1H), 6.47 (d, 1H, J = 2 , 3), 6.56 (dd, 1H, J = 2.3, 8.3), 6.78-6.82 (m, 3H), 7.10-7.14 (m, 3H), 8 , 03 (s, 1 H); ¹³C NMR (100 MHz, d6 acetone) δ 2.5, 30.9, 31.6, 35.3, 41.9, 46.3, 54.6, 63.1, 76.8, 84.7, 113, 1, 114.3, 126.0, 126.7, 127.4, 128.4, 130.5, 134.0, 137.3, 138.7, 142.3, 155.1; MS m / z 327 (M-OH)⁺.

EXAMPLE 6 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a- (phenylmethyl) -, (4aS-trans) ammonia (1.5L) was concentrated in a boiling vial at -78 ° C which was equipped with a dry reflux condenser at -78 ° C and more mechanical. Into this flask was added 0.7 g (99 mmol) of liium vortex and the solution became dark blue. A solution of 10 g (32.8 mmol) of the title product of Example 3 in 400 mL of 1: 1 dioxane: ether was slowly added to the mixture to keep the reaction dark blue. When the blue color began to lose a small amount of lithium wax was added to the mixture to get the blue color again. The total amount of lithium added to the reaction mixture was not more than 3.5 g (495 mmol). After completion of adding 10 g of the title product of Example 3, the reaction was stirred for another 30 minutes and then 14 g of solid ammonium chloride was added and the blue color immediately disappeared. H₂O was added to the mixture and extracted with EtOAc, dried over Na₂SO₄, filtered and aggregated pair until everything was dry. The crude product was purified by flash chromatography on SiO₂ using 15% EtOAc to 20% EtOAc in hexane as a gradient eluent to give 8.16 g of the title product according to this example as a white solid (81%). ¹1 H NMR (400 MHz, CD 3 OD) δ 1.52 (dt, 1H, J = 4.5, 13), 1.64-1.71 (m, 1H), 1.90-2.15 (m, 2H) , 2.27 (ddd, 1H, J = 2.5, 3.7, 15), 2.39 (dm, 1H, J = 15), 2.48 (ddd, 1H, J = 2.0, 6 , 5.13), 2.72 (t, 1H, J = 14), 2.84 (d, 1H, J = 13), 2.89-3.01 (m, 3H), 3.22 , 1H, J = 13), 6.17 (d, 1H, J = 8.5), 6.24 (dd, 1H, J = 2.5, 8.5), 6.53 (d, 1H, J = 2.5), 6.65-6.68 (m, 1H), 7.04-7.13, (m, 3H); ¹³C NMR (100 MHz, CD 3 OD) δ 27.9, 33.7, 34.8, 36.0, 37.6, 39.4, 43.6, 44.0, 111.3, 114.6, 125, 7, 127.0, 127.9, 130.5, 133.4, 136.8, 138.0, 155.1, 212.7; MS m / z 307 (M + H)⁺.

EXAMPLE 7 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a- (phenylmethyl) -, (4aS-cis) To a solution of 1 g (3.6 mmol) ) of the title product of Example 3 in 75 mL of ethanol and 0.27 mL of 2 M KOH was added 0.15 g of 10% Pd / C. The reaction mixture was shaken under 45 psi (about 3 air weights) of H₂ gas for 4 hours. Acetic acid (0.035 mL) was added and the mixture was filtered through celite, washed with celite with ethanol and then the ethanol was removed under reduced pressure. The resulting residue was partitioned between EtOAc and saturated NaHCO₃, extracted with EtOAc, dried over Na₂SO₄, filtered and copied pair until everything was purred. The crude product was purified by flash chromatography on SiO₂ using 25% EtOAc hexane as the eluent to give 947 mg of the title compound as white solid (86%). ¹1 H NMR (400 MHz, CD 3 OD) δ 1.52-1.60 (m, 1H), 1.87 (ddd, 1H, J = 4.8, 11.14), 2.00-2.35 (m , 6H), 2.39 (dt, 1H, J = 5.2, 14), 2.69-2.92 (m, 2H), 2.96 (d, 1H, J = 13), 3.00 (d, 1H, J = 13), 6.56-6.58 (m, 2H), 6.88-6.92 (m, 3H), 7.13-7.15 (m, 3H); ¹³C NMR (100 MHz, CD 3 OD) 523.7, 25.3, 34.7, 37.2, 39.6, 40.3, 42.8, 47.7, 113.1, 115.1, 127, 3, 128.0, 130.5, 137.2, 137.8, 155.2, 213.9; MS m / z 307 (M + H

Example 8 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -, [2R- (2α, 4aα, 10αβ)] - and 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [25- (23 (43β, 1θ3a)] Out To a stirred solution of 95 mg of cis-dichlorethylene (0.98 mM) in 5 mL of THF at 0 ° C was added 2.5 mL of 0.5 M lipid diisopropylamide in THF and the resulting mixture was heated to room temperature 30 minutes under nitrogen atmosphere A solution of 30 mg (0.098 mmol) of the title product from Example 6 in 0.65 mL of THF was added dropwise and the reaction mixture was stirred for 2 hours. Saturated aqueous ammonium chloride was precipitated in the mixture was extracted with EtOAc, purrkuf over Na₂SO₄, siufi and social life couple to everything was purrt. Initial purification by flash chromatography on SiO₂ using 20% ​​EtOAc in hexane as eluent to give 30 mg of a light brown solid. Further purification by flash chromatography on SiO₂ using a 2% acetone in dichloromethane to 4% acetone. In dichloromethane as a gradient eluent, 20 mg (56%) of the first artistic title product of this case (haerra Rf) and 7.0 mg (19%) of the other artistic title product from time to time daemi (laegra Rf) as a white solid. Physical characteristics of the first artistic product of the title In this case, the following are: bm. 230-232 ° C (nifrile fraction);¹H NMR (300 MHz, CD3OD) 1.40 (mt, 1H, J = 14), 1.64-1.70, (m, 1H), 1.802.13 (m, 7H), 2.59 (d, 1H, J = 13), 2.93-2.97 (m, 3H), 6.13 (d, 1H, J = 8.5), 6.25 (dd, 1H, J = 2.6, 8 , 5), 6.54-6.57 (m, 3H), 7.00-7.07 (m, 3H); ¹³C NMR (75 MHz, CD3OD) δ25.5, 28.7,

31.8, 37.2, 40.52, 41.71, 43.43, 63.1, 70.7, 74.1, 112.4, 116.1, 126.8, 128.3, 138, 9, 132.1, 136.3, 138.3, 139.5, 156.3; MS m / z 366 (M + H)⁺, 349 (M-OH)⁺.

The physical properties of the other art of the title product are as follows: bm. 216-219 ° C (nitrous fraction) 1 H NMR (400 MHz, CD₃OD) 51.47 (mt, 1H, J = 14), 1.56-1.62 (m, 1H), 1.80-2.00 (m, 5H), 2.08 (mt, 1H, J = 13), 2.23 (dt, 1H, J = 3.8, 14), 2.59 (d, 1H, J =

13), 2.82-2.93 (m) and 2.95 (d, 1H, J = 13), 6.08 (d, 1H, J = 8.6), 6.20 (dd, 1H, J = 2.2, 8.6), 6.50 (d, 1H, J = 2.2), 6.54-6.56 (m, 2H), 7.03-7.06 (m, 3H ); ¹³C NMR (75 MHz, CD₃OD) δ 25.4, 28.8, 28.9, 36.0, 36.7, 40.4, 42.5, 65.1, 67.3, 75.9, 112.3, 116.1, 126 , 8, 128.2, 128.8, 132.2, 136.3, 138.3, 139.7, 156.2; MS m / z 366 (M + H)⁺, 349 (M-OH)⁺.

Example 9 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2R- (23,4aα, 10αβ )] and 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2S- (2a, 4ap , 10aa) in a stirred solution of 183 mL of THF saturated with propionase at 0 ° C was added 143 mL of 1 M lithium diisopropylamide in THF and the resulting mixture was stirred under a nitrogen atmosphere for 20 minutes. A solution of 7.3 g (23.8 mmol) of the title product of Example 6 in 250 mL of THF was added dropwise and the reaction mixture was warmed to room temperature and stirred overnight. Saturated aqueous ammonia chloride was added, and the mixture was extracted with EtOAc, dried over Na₂SO₄, filtered and concentrated until dry. Purification by flash chromatography on SiO₂ by using 2% acetone in dichloromethane to 4% acetone in dichloromethane as eluent, gave 4.0 g (49%) of the first product of this example (higher Rf) and 2.4g (29%) of another listed title product in This example as a white solid.

The physical properties of the first listed title product in this example are the following; mp. 227-229 ° C (degradation);¹1 H NMR (400 MHz, CD 3 OD) δ 1.42 (mt, 1H, J = 14), 1.61, (ddd, 1H, J = 3.4, 4.1, 8.8), 1.72 , 3H), 1.73-1.82 (m, 2H), 1.84-2.10 (m, 5H), 2.55 (d, 1H, J = 13), 2.83-2.93 (m) and 2.94 (d, 3H, J = 13), 6.10 (d, 1H, J = 8.3), 6.23 (dd, 1H, J = 2.5, 8.4) , 6.52-6.55 (m, 3H), 7.00-7.05 (m, 3H); ¹³C NMR (62 MHz, CD 3 OD) δ 2.5, 24.1, 27.3, 30.5,

35.8, 36.1, 39.1, 40.2, 42.4, 68.9, 79.5, 82.3, 110.9, 114.7, 125.4, 126.8, 127.5, 130.7, 135.1, 136.9, 138.3, 154.8; MS m / z 346 (M + H)⁺, 329 (M-OH)⁺.

The physical properties of the other listed title product in this example are the following: bm. 222-223 ° C (degradation);¹H NMR (400 MHz, CD3OD) δ1.46 (mt, 1H, J = 14), 1.54-1.60, (m, 1H), 1.83 (s) overlaid 1.75-1.94 (m, 8H), 2.08 (mt, 1H, J = 13), 2.20 (dt, 1H, J = 4.14), 2.57 (d, 1H, J = 13), 2.88 (t, 2H, J = 8.7), 2.94 (d, 1H, J = 13), 6.08 (d, 1H, J = 8.3), 6.20 (dd, 1H, J = 2.4, 8.3), 6.50 (d, 1H, J = 2.4), 6.53-6.56 (m, 2H), 7.01-7.06 (m, 3H); ¹³C NMR (62 MHz, CD 3 OD) δ 1.7, 24.1, 27.4, 27.6, 35.0, 35.2, 36.4, 39.0, 41.6, 65.5, 76, 9, 84.5,

110.8, 114.6, 125.3, 126.8, 127.4, 130.7, 135.0, 136.9, 138.4, 154.7; MS m / z 346 (M + H)⁺, 329 (M-OH)⁺.

Example 10 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl- [2R- (2a, 4aα, 10ab)] A mixture of 975 mg of the first listed title product of Example 9.195 mg of 10% Pd / C and 100 mg of K₂CO₃ in MeOH was shaken under 40 psi (approximately 2.6 gauge) of H₂ gas for hours. The mixture was filtered through celite and concentrated to give 945 mg of the resultant from this example as a white solid. MS: 368 (M + 18)⁺.

Example 11 pentanal, 5 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] - [4bS - (4ba, 7a, 8aP)] To a stirred solution of 157 mg of the title compound of Example 314, region below, 14.8 mL of dioxane and 1.2 mL of H₂O was added 72 mg of 4-methylmorpholine-N-oxide, 0.003 mL of pyridine, and 0.18 mL of 2.5 wt.% Of OsO₄ in t-butanol and the reaction mixture was stirred for 4 hours. Into this mixture was added 776 mg of NalO₄ and the mixture that was released was stirred overnight. The reaction mixture was poured into H₂O and extracted with EtOAc. The organic layer was dried over Na₂SO₄, filter, and simmer until dry. Purification by flash chromatography on SiO₂ using 25% EtOAc in hexane to 10% EtOAc I hexane as a gradient eluent gave 141 mg of the title product in this example as a colorless oil. MS: 417 (M-17)⁺.

Example 12 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [[5- (4-morpholinyl) pentyl] oxy] -4a- (phenylmethyl) -2-propyl, [2R- (23,4aα, 10a b)] To a stirred solution of 34.6 mg of the title product of Example 11 in 1 mL of AcOH was added 0.014 mL of morpholine and 109 mg of Na₂SO₄ and the resulting mixture was stirred for 15 minutes. This mixture was added 24 mg NaHB (OAc) and the resulting mixture was stirred 1.5 hours. The mixture was cooled to 0 ° C and saturated Na₂CO₃ was added until the pH of the mixture was about 8 to 9. The reaction mixture was extracted with EtOAc, purrkud over Na₂SO₄, say and congratulations to everything was purry. Purification by flash chromatography on SiO₂ using 5% MeOH in dichloromethane to MeOH as eluent gave 26.6 mg of the title compound as a white solid. MS: 506 (M + 1)⁺.

Example 13 methanesulfonic acid, trifluoro, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl ester, [4bS- ( 4ba, 7a, 8a8) in a stirred solution of 4.14 g of the first title compound of Example 9 (prepared according to the procedures described in Example 9), 1.95 mL of 2,6-lupidine, and 292 mg of 3-dimethylaminopyridine 1150 mL dichloromethane at -40 ° C under nitrogen was added 2.6 mL of trifluoromethylsulfonic anhydride. The resulting mixture was stirred for 0.5 hours at -40 ° C, 0.5 hours at 0 ° C and for 1.5 hours at room temperature. The reaction mixture was poured into 1N HCl and extracted with dichloromethane. The organic layer was washed with water, saturated NaHCO₃ and saline, purred over Na₂SO₄, siad and gathered couples until everything was purred. Purification by flash chromatography on SiO₂ using 15% EtOAc in hexane to 20% EtOAc in hexane as a gradient eluent gave 4.4 g (77%) of the title product as a white solid. ¹1 H NMR (400 MHz, C₆D_e) d6.07 (d, 1H, J = 8.4), 6.63 (d, 1H, J = 2.5).

EXAMPLE 14 2-phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) methyl ester, [4bS- (4ba , 7a, 8ap)] A mixture of 1.18 g of the title product of Example 13, 0.27 g of 1,3-bis (diphenylphosphino) propanol, 2.54 mL of triethylamine and 0.1 g of palladium acetate in 40 mL of 1: 1 DMF / MeOH was shaken under 60 psi (about 4 psi) of carbon monoxide at 70 ° C for 4 hours. The reaction mixture was concentrated to remove MeOH. The mixture was poured 1: 1 hexane / EtOAc, washed with 50% brine, dried over Na₂SO₄, filtered and aggregated pairs until everything was purred. Purification by flash chromatography on SiO₂ using 23% EtOAc hexane to 28% EtOAc in hexane as a gradient eluent gave 0.79 g (82%) of the title product as white solid. MS: 371 (M-17)⁺.

Example 15 2-Phenanthrenecarbonitrile, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a , 8aP)] A stirred mixture of 1.0 g of the title product of Example 13, 0.4 g of tetrakis (triphenylphosphine) palladium (0) and 0.17 g of zinc (II) cyanide I 9.5 mL of 1- methyl-pyrrolidinone (NMP) under nitrogen was heated to 90 ° C for 4 hours. The reaction mixture was poured into saturated NaHCO₃, filtered through Celite® and extracted with EtOAc. The organic layer was spun over Na₂SO₄, beat and coincide pairs until everything was purred. Purification by flash chromatography on SiO₂ using 20% ​​EtOAc hexane to 30% EtOAc hexane as a gradient eluent gave 0.64 g (86%) of the title compound as a white solid. MS: 338 (M-17)⁺.

Example 16 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (2-pyridinyl) -, [2R- (23.4, 1 Oap)] Nitrogen gas was bubbled through a solution of 300 mg of the title product of Example 13, 70 mg of 1,1'-bis (diphenylphosphino) ferrosen and 28 mg palladium acetate (THF for 5 minutes. Under a nitrogen atmosphere, the solution was quenched in -78 ° C and 3.78 mL of 0.5 M bromo-2-pyridinyl chloride THF was removed. The solution was heated to room temperature and then heated to 70 ° C over ninety. After cooling room temperature was measured NH₄CI was removed and the resulting mixture was extracted with EtOAc, purrkufi Na₂SO₄, siufi and social life couple to everything was purrt. Purification by flash chromatography on SiO₂ using 20% ​​EtOAc in hexane as eluent afforded 173 mg (67%) of the title compound as a white solid. MS: 408 (M + 1f.

Example 17 2-Phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a , 8ββ)] To a stirred solution of 170 mg of the title product from Example 14 mL of THF was added 0.26 mL of 2N KOH and the resulting solution was heated to reflux for 3 days. Ofirum 0.75 mL of 2N KOH was charged and the mixture was heated to reflux over ninety. The reaction mixture was quenched at room temperature, diluted with a small amount of water and purged with diethyl ether. The aqueous layer was acidified with 2N HCl and extracted with EtOAc. The organic layer was a mash over Na₂SO₄, slave and concentrated until all was dry to give 155 mg of the resulting product in this case as an off-white solid. MS: 357 (M-17)⁺.

Example 18 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [3- (1H-imidazol-1-yl) propyl] -4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a, 8aP) in a stirred solution of 1- (3-aminopropyl) imidazole in 1 mL of dichloromethane at 0 ° C under N₂ was added 0.1 mL of 2.0 M trimethyl metal in hexane. The mixture was stirred at 0 ° C for 20 min. and then at room temperature for 1 hour. To this mixture was added 20 mg of the title compound of Example 14 in 1 mL of dichloromethane. The mixture was heated to reflux for 6 hours and then removed from the heat and stirred at room temperature for 3 days. Into the reaction mixture was added dropwise 1N HCl until the aqueous layer had a pH of about 4. The resulting mixture was extracted with EtOAc, dried over Na₂SO₄, filtered and concentrated until dry. Purification by flash chromatography on SiO₂ using 5% MeOH in dichloromethane to 10% MeOH in dichloromethane as a gradient eluent gave 22 mg (88%) of the title product of this example as a white solid. MS: 483 (M + 1)⁺.

Example 19 2-Phenanthenemethanol, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxypidimethyl-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a , 8a) in a stirred solution of 100 mg of the title compound of Example 14 in 2 mL of THF at 0 ° C under N₂ was added 0.77 mL of 1 M methylmagnesium bromide in butyl ether. The mixture was stirred at 0 ° C for 2 hours, warmed to room temperature and stirred for another 1 hour. To the reaction mixture was added 1.2 mL of 1 M methylmagnesium bromide in butyl ether and the resulting mixture was stirred at room temperature for 1 hour. Measured NH₄CI was added and the resulting mixture was extracted with EtOAc, dried over Na₂SO₄, filtered and concentrated until dry. Purification by flash chromatography on SiO₂ using 20% ​​EtOAc I hexane to 30% EtOAc hexane as a gradient eluent gave 80.5 mg of the title product according to this example as a white solid. MS: 371 (M-17)⁺.

Example 20 2-Phenanthenemethanol, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a , 8aP) in a stirred solution of 50 mg of the title compound of Example 14 in 2 mL of dichloromethane at -78 ° C under N₂ was added 0.39 mL of 1 M diisobutylalanhydride in hexane and the resulting mixture was stirred in 35 mL. Methanol (10 drops) was added dropwise to the reaction mixture followed by 2 mL of saturated Rochelle salt. The mixture was extracted with dichloromethane. The organic layer was washed with H₂O and brine, dried over Na₂SO₄, filter and coalesce until dry. The resulting solid was washed with a small amount of EtOAc to give 18 mg of the resulting product according to this example as a white solid. MS: 343 (M-17)⁺.

Example 21 2-Phenanthenemethanol, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl), α-methanesulfonate, [4bS- (4ba, 7a, 8ap) j2743

To a stirred solution of 20 mg of the title product of Example 20 (which was prepared by the methods described in Example 20) gave 0.5 mL of THF at 0 ° C under N₂ was added 0.017 mL of methanesulfonyl chloride and 0.02 mL of diisopropylethylamine. After 3 hours, the reaction mixture was diluted with EtOAc, washed with H₂O and brine, dried over Na₂SO₄, filtered and concentrated to give 18 mg of the resulting product according to this example as a yellow solid. ¹1 H NMR (400 MHz, C₆D₆), 4.79 (s, 2H).

Example 22 2-Phenanthenol, 7- (azidomethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2R- (23 , 4aα, 1αα)] The title product of Example 21 (18 mg) and 20 mg of sodium azide in 0.5 mL of DMF were heated to 100 ° C under N₂ for 3 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc, washed with H₂O and brine, dried over Na₂SO₄, filtered and concentrated until dry. Purification by flash chromatography on SiO₂ using 20% ​​EtOAc in hexane as eluent afforded 18 mg of the title product in this case as a white solid. IR (pure) 2098 cm '¹; ¹1 H NMR (400 MHz, C₆D₆) 54.24 (s, 2H).

Example 23 2-Phenanthenol, 7- (aminomethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2R- (2a , 4aα, 10aβ]] To a stirred solution of 18 mg of the title product of Example 22 in 1 mL of 2: 1: 1 THF: MeOH: H₂O was added 25 mg of triphenylphosphine and the resulting mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated in a white residue. Out of this residue was added diethyl ether and the resulting mixture was extracted with 1N HCl. The aqueous layer was added to a pH greater than 10 with addition of 15% NaOH, extracted with EtOAc, dried over Na₂SO₄, filter and coalesce until dry. Purification by flash chromatography on SiO₂ using 5% MeOH in dichloromethane to 50% MeOH in dichloromethane with 1% triethylamine as a gradient eluent gave 10 mg of the additional product in this example as a white solid. MS: 360 (M + 1)⁺.

EXAMPLE 24 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (1H-tetrazol-5-yl) - [2R- (2) 4aα, 10aβ]] To a stirred solution of 42 mg of the title product of Example 15 in 1 mL of toluene under N₂ was added 4.7 g of dibutylin oxide and 0.032 mL of trimethylsilyl azide. The resulting mixture was stirred at 90 ° C for 7 days and then at room temperature for another 7 days. The reaction mixture was concentrated in vacuo, dissolved in MeOH and concentrated in aerosol. The residue was dissolved in EtOAc, washed with saturated NaHCO₃, dried over Na₂SO₄, filtered and concentrated until dry. Purification by flash chromatography on SiO₂ using 10% MeOH [dichloromethane as eluent afforded 4 mg of the resulting product according to this example as a white solid. MS: 399 (M + 1)⁺.

Example 25 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N-methoxy-N-methyl-4b- (phenylmethyl) -7- (1-propynyl) , [4bS- (4ba, 7a, 8a3) j2743

To a stirred solution of 168 mg of the title compound of Example 17 (prepared by the methods described in Example 17) In dichloromethane was added a conventional 53 mg of N, O-dimethylhydroxylamine hydrochloride, 172 mg of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 121 mg of hydroxybenzotriazole hydrate, and 110 mg of 4-dimethylaminopyridine trifluoroacetic acid under N₂. The resulting mixture was stirred at room temperature over night, poured into 2N HCl and extracted with EtOAc. The organic layer was washed with 2 N HCl, H₂O and mettuflu NaHCO₃, purrkafl over Na₂SO₄, siafl and samsafnafl couple to everything were purr. Purification by flash chromatography on SiO₂ Using the 3% MeOH in dichloromethane as eluant gave 134 mg (71%) of the title product as a colorless oil. MS: 418 (M + 1)⁺.

Example 26 1-Propylene, 1- [4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] , [4bS- (4ba, 7a, 8ap)] To a stirred solution of 119 mg of the title product of Example 25, 11.5 mL of THF -78 ° C under N₂was added 0.86 mL of 1 M ethylmagnesium bromide THF. The reaction mixture was at -78 ° C for 1 hour, 0 ° C for 2 hours, and then at room temperature for 2 hours. The reaction mixture was poured into 5% HCl in EtOH and stirred for 5 minutes. The resulting mixture was poured into brine, and extracted with EtOAc. The organic layer was doped over Na₂SO₄, siafl and samsafnafl couple to everything were purr. Purification by flash chromatography on SiO₂ Mean use of 15% EtOAc in hexane to 20% EtOAc in hexane as a gradient eluent gave 49.5 mg (48%) of the title compound as a white solid. MS: 387 (M + 1)⁺.

Example 27 2-Phenanthenemethanol, acetyl-4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba , 7a, 8aP)] To a stirred solution of 32.3 mg of the title product of Example 26 In 0.8 mL of MeOH was added 3.2 mg of NaBH₄ and the mixture that was released was a room temperature for 2 days. Oflrum 2 mg of NaBH₄ was removed and the reaction mixture was heated to reflux for 2 hours. After kaelingu at room temperature, H was₂O extracted and the mixture concentrated in an air-conditioner to remove distillate MeOH. The resulting mixture was extracted with EtOAc, purrkufl over Na₂SO₄, siufl and samsaturated couples until everything was purred. Purification by flash chromatography on SiO₂ Mean use of 15% EtOAc hexane as eluent gave 24 mg of additional fluorine as a colorless oil. MS: 371 (M-17)⁺.

Example 28 Carbamic acid, [4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] -1,1,1 dimethylsilter, [4bS- (4ba, 7a, 8aP)] A solution of 124 mg of the title compound of Example 17, 91 mg of diphenylphosphorylate and 0.046 mL of triethylamine in 1 mL of t-butanol was heated to a refluxed 116 h. The solution was pooled in a vacuum and the residue released was dissolved in EtOAc. The EtOAc solution was combined with 5% citric acid, H₂O, mettuflu NaHCO₃ and saline, purrkufl over Na₂SO₄, siufl and samsflfnufl couple to everything was purred. Purification by flash chromatography on SiO₂ with 30% use

EtOAc hexane to 50% EtOAc hexane as a gradient eluent gave 34.1 mg of the title product according to this example as a white solid. MS: 328 (M-17)⁺.

Example 29 2-Phenanthenol, 7-amino-1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) - [2R- (2,3,4a, 10a | 3)] To a stirred solution of 20 mg of title product of Example 28 in 0.5 mL of dichloromethane was added 0.7 mL of trifluoroacetic acid. The solution was stirred at room temperature for about 1.5 hours. Saturated NaHCO₃ was added to the solution. The resulting mixture was extracted with EtOAc, washed with brine, dried over Na2₂SO₄, filtered and concentrated until dry. Purification by flash chromatography on SiO₂ using 20% ​​EtOAc in hexane as eluent gave 7.5 mg of the title product according to this example as a white solid. MS: 328 (M + 1)⁺.

Example 30 2-Phenanthrenecarboxamide, 4b- (2,3-dihydroxypropyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1-propynyl) -, [4bS - (4ba, 7a, 8aP) in a stirred suspension of 303 mg of 2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (2-propenyl) 7- (1-propynyl) -, [4bS- (4ba, 7a, 8aP) j- in 13.5 mL of dioxane and 3.3 mL of H₂O was added 186 mg of 4-methylmorpholine-N-oxide, 0.008 mL of pyridine, and 0.47 mL of 2.5 wt% of OsO₄ in t-butanol and the mixture was stirred at room temperature over night. To this mixture was added 1: 1 saturated NaHCO₃ and saturated NaHSO₃. The resulting mixture was extracted with EtOAc, dried over Na₂SO₄, filtered and concentrated to give 292 mg of the resulting product according to this example as a white solid. MS: 358 (M + 1)⁺.

Example 31 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b - [(2-oxo-1,3-dioxolan-4-yl) methyl] -7 - (1-Propynyl) -, [4bS- (4ba, 7a, 8a, 3)] To a stirred solution of 90 mg of the title product of Example 30 in dichloromethane at 0 ° C under N₂ was added 45 mg of carbonyl dimidazole. The reaction mixture was warmed to room temperature and stirred for 3 hours. The mixture was concentrated until everything was dry and purified by flash chromatography on SiO₂ using 3% MeOH in dichloromethane to 5% MeOH in dichloromethane as a gradient eluent to give 46 mg of the title product according to this example as a white solid. MS: 384 (M + 1)⁺.

EXAMPLE 32 4a (2H) -phenanthrenasaldehyde, 2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy- [2R- (2,4a, 10aβ)] In A stirred solution of 1.77 g of the title compound of Example 172 below, in 100 mL of dioxane and 25 mL of H₂O was added 1.11 g of 4-methylmorpholine-N-oxide, 0.045 mL of pyridine and 2.8 mL of 2.5 wt% of OsO₄ in t-butanol and the reaction mixture was stirred for 6 hours. To this mixture was added 12 g of NalO₄ and the mixture that was released was stirred overnight. The reaction mixture was poured₂O and extracted with EtOAc. The organic layer was dried over Na₂SO₄, filter and coalesce until dry. Purification by flash chromatography on SiO₂ using 30% EtOAc hexane as eluent gave 1.04 g of the title product according to this example as a white solid. ¹1 H NMR (400 MHz, D₆acetone) d4.8 (s, 2H).

Example 33 2,7-phenanthridol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [2- (1-piperidinyl) ethyl] -, [2R- (23, 4a a, 10a [3]] To a stirred solution of 100 mg of the title product of Example 32 in 1.5 mL of AcOH was added 0.062 mL of piperidine and 446 mg of Na₂SO₄ and the resulting mixture was stirred for 115 minutes. To this mixture was added 100 mg of NaHB (OAc)₃ in two portions and the resulting mixture was stirred 1.5 hours. The mixture was quenched to 0 ° C and saturated Na₂CO₃ was carried out in pairs until the pH of the blonde was about 8 to 9. The reaction mixture was extracted with EtOAc, purrkud over Na₂SO₄, say and congratulations to everything was purry. Purification by flash chromatography on SiO₂using 5% MeOH in dichloromethane to MeOH as a gradient eluent gave 95 mg of the title compound as a white solid. MS: 388 (M + 1)⁺.

Example 34 4a (2H) -phenanthrenasaldehyde, 2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy, oxime, [2R- [2a, 4aα, 10β] Stirred solution of 150 mg of title product of Example 32 16 mL of MeOH was added 147 mg of KHCO₃ and 141 mg of hydroxylamine hydrogen chloride. The reaction mixture was refluxed for 3 hours and allowed to warm to room temperature and the same mixture until everything was purred. Purification by flash chromatography on SiO₂ using 5% MeOH in dichloromethane to 8% MeOH in dichloromethane as a gradient eluent gave 64 mg of the title compound as a white solid. MS: 316 (M-17)⁺.

Example 35 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (3-phenyl-2-propenyl) -, [2R- [23 , 4aa (E), 10ββ]] To a stirred solution of 410 mg diethylbenzylphosphonate In 5 mL of THF at -78 ° C under N₂ 0.65 mL of 2.5 M butyl lithium in hexane was added. The reaction mixture was heated at 100 DEG C. and stirred for 1 hour. Out of the reaction volume, 104 mg of title product from Example 32 was added in 2 mL of THF and the mixture was stirred for 3.5 hours. The reaction mixture was poured into saturated NH₄CI, extracted with EtOAc, purr quench over Na₂SO₄, say and congratulations to everything was purry. Purification by flash chromatography on SiO₂ using 10% EtOAc in hexane to 20% EtOAc in hexane as a gradient eluent gave 60 mg of the title product as a white solid. MS: 375 (M-17)⁺.

Example 36 2-Butanoic Acid, 4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -, [2R- [2 4a (E), 10aβ] In a stirred solution of 2.2 g of the title compound of Example 183, hereinafter below, in 40 mL of THF was added 11 mL of 2N KOH and the resulting solution was refluxed in 4 hours. The reaction mixture was quenched at room temperature, diluted with a small amount of water, and quenched with diethyl ether. Water slurry was acidified with 2N HCl and extracted with EtOAc,

100 dry over Na₂SO₄, filtered and concentrated to dryness gave 1.55 g of additional surfactant in this example as an off-white solid. ¹1 H NMR (400 MHz, CD₃OD) δ6.66 (d, 1H, J = 15), 6.67-6.80 (m, 1H).

Example 37 pyrrolidine, 1- [4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy4a (2H) -phenanthrenyl] -1-oxo-2-butenyl] -, [2R- [23,4aa (E), 10apJ- (formula F-12: R₂ is OH, R₃ is chloroethynyl, R₅ is H, R₈ is H, R₉ is H, R₁₀ is OH, R₇₎ R₁₄, R₁₅, R₁₆ are each H, m is 2, R₁₂ and r₁₃ taken together with N are pyrrolidinyl) refers to schema F.

To a stirred solution of 168 mg of the title compound of Example 36 in dichloromethane was added 0.67 mL of pyrrolidine, 140 mg of dicyclohexylcarbodiimide, 91 mg of hydroxy-benzotriazole hydrate, and 10 mg of 4-dimethylaminopyridine trifluoroacetic acid under N₂. The resulting mixture was stirred overnight at room temperature. The mixture was diluted with MeOH, filtered through Celite® and concentrated to powders. Purification by flash chromatography on SiO₂ with 90% acetonitrile and 10% dichloromethane with 0.5% to 1% H₂The resulting elution inhibitor gave 90 mg of supplemental trifle in this case as a white solid. MS: 414 (M + 1)⁺.

Example 38 4H-benzo [a] quinolizin-4-one, 1,2,3,6,7,11b-hexahydro-9-hydroxy-11b- (phenylmethyl)

A solution of 973 mg of 2- (3-hydroxyphenyl) ethylamine hydrobromide and 920 mg of 5-oxo-6-phenylhexanoic acid 3 mL of isopropanol was heated to 210 ° C under open air for 5 hours. The resulting residue was purified by flash chromatography on SiO₂ Mean use of 5% MeOH in dichloromethane to 20% MeOH. In dichloromethane, as eluent eluant, to yield 774 mg (56%) of the title compound as a off-white solid. MS: 307 (M + 1)⁺.

Example 39 4H-benzo [a] quinolizin-4-one, 1,2,3,6,7,11b-hexahydro-9- (phenylmethoxy) -11b- (phenylmethyl) To a stirred solution of 770 mg of the title product from Example 38 in DMF, electrical flux was added 3 mL of 1 M potassium t-butoxide in t-butanol followed by 0.35 mL of benzyl bromide. The reaction mixture was heated to 60 ° C for 2 hours. The mixture was quenched at room temperature and 1N HCl was added. The resulting mixture was extracted with EtOAc, purrkufl over Na₂SO₄, siufl and samsaturated couples until everything was purred. Purification by flash chromatography on SiO₂ Mean use of 60% EtOAc in hexane to 100% EtOAc as a gradient eluent gave 797 mg (80%) of the title compound as an off-white solid. MS: 398 (M + 1)⁺.

Example 40 2H-benzo [a] quinolisine-3-carboxylic acid, 1,3,4,6,7,11b-hexahydro-4-oxo-9- (phenylmethoxy) -1b- (phenylmethyl) -3-propyl - methyl ester, (3-cis) To a stirred solution of 0.61 mL of diisopropylamine in 9 mL of THF at 0 ° C under N₂ was added 1.75 mL of 2.5 M n-butyl lithium in hexane. The solution that came out was fasting for a 10-minute fan

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0 DEG C. and then cooled to -78 DEG C. In this solution, 790 mg of the title product of Example 39 was added to 10 mL of THF dropwise over 30 minutes. The resulting solution was stirred at -78 DEG C. for 30 minutes. minutes, heated to 0 ° C for 2 hours, then cooled to -78 ° C. To this was added 0.17 mL of methyl chloroformate. The resulting mixture was stirred for 30 minutes at -78 ° C and then heated to room temperature and stirred for 1 hour. To the reaction mixture was added 0.42 mL of propyl iodide and the resulting mixture was stirred at 0 ° C for 1 hour and then heated to room temperature for 14 hours. In the reaction mixture was added another 0.5 mL of propyl iodide and the resulting mixture was heated at 55 ° C (4 hours). The mixture was poured into EtOAc and washed with 1 N HCl, H₂O, saturated NaHCO₃ and saline. The organic solution was dried over Na₂SO₄, filtered and concentrated until dry. Purification by flash chromatography on SiO₂ using 40% EtOAc in hexane as eluent afforded 768 mg (78%) of the title product of this example as an off-white solid. MS: 498 (M + 1)⁺.

Example 41 2H-benzo [a] quinolisine-3-methanol, 1,3,4,6,7,11b-hexahydro-9- (phenylmethoxy) -11b- (phenylmethyl) -3-propyl-, 3- cis) To a stirred solution of 50 g of the title product of Example 40 in 1 mL of THF was added 3 mL of 1.0 M lithium aluminum hydride in THF. The reaction mixture was heated to reflux under N₂ overnight. The mixture was cooled to 0 ° C and 0.12 mL of H₂0.12 mL of 15% NaOH and 0.36 mL of H₂The reaction mixture was slowly added slowly with stirring on the reaction mixture. After 5 min. With rapid stirring, the mixture was filtered through Celite® and concentrated until dry. Purification by flash chromatography on SiO₂using 3% MeOH in dichloromethane to 10% MeOH in dichloromethane as a gradient eluent gave 36 mg (79%) of the title product in this example as a white solid. MS: 456 (M + 1)⁺.

Example 42 2H-benzo [a] quinolizine-3-methanol, 1,3,4,6,7,11b-hexahydro-9-hydroxy-11b- (phenylmethyl) -3-propyl-, (3-cis) To a stirred solution of 31 mg of the title product of Example 41 in dichloromethane at -78 ° C under N₂ was added 0.05 mL of BBr₃ and the reaction mixture was warmed to room temperature. The reaction mixture was cooled to -78 ° C and MeOH was added dropwise to stop the reaction. The mixture was concentrated until dry, dissolved in MeOH and concentrated until dry. Purification by flash chromatography on SiO₂ using 5% MeOH in dichloromethane with 0.1% triethylamine to 10% MeOH in dichloromethane with 0.1% triethylamine as a gradient eluent gave white solid. This solid was partitioned between EtOAc and saturated NaHCO₃. The EtOAc layer was dried over Na₂SO₄, filtered and concentrated to give 10 mg of the additional product according to this example as a white solid. ¹1 H NMR (400 MHz, CD₃OD) δ 2.45 (d, 1H, J = 12), 2.66 (d, 1H, J = 12).

Example 43 2H-benzo [a] quinolysine-3-carboxylic acid, 1,3,4,6,7,11 b-hexahydro-9-hydroxy-4-oxo-11b- (phenylmethyl) -3-propyl methyl ester, ( 3-cis) A mixture of 50 mg of the title product of Example 40, 63 mg of ammonium formate and 20 mg of 20% palladium hydroxide on carbon in 5 mL of MeOH was heated to reflux for 3 hours.

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The mixture was cooled to room temperature, filtered through Celite® and concentrated to purr. Purification by flash chromatography on SiO₂ using 50% EtOAc hexane as eluent gave 41 mg of the title product as a white solid. MS: 408 (M + 1) -.

Example 44 4H-benzo [a] quinolinyl 4- [1,2,3,6,7,11p-hexahydro-3- (hydroxymethyl) -9 (phenylmethoxy) -1,1- (phenylmethyl) 3-propyl-, (3-cis) To a stirred solution of 50 mg of the title product of Example 40 in 5 mL of THF under N₂ was added 10 mg of lithium borohydride. The resulting mixture was stirred for 2 hours at room temperature and then heated to 40 ° C and stirred for another 2 hours. After cooling at room temperature, saturated ammonium chloride was added and the mixture was extracted with EtOAc. The EtOAc solution was dried over Na₂SO₄, the filter and the combination of pairs until everything was purred. Purification by flash chromatography on SiO₂ Using 40% EtOAc hexane to 80% EtOAc in hexane as a gradient eluent gave 17 mg of the title product as a white solid. MS: 470 (M + 1)⁺.

Example 45 2 (1H) -phenantrenone, 7- (Acetyloxy) -3,4,4a, 9,10,10a-hexahydro-4a- (phenylmethyl) -, (4aS-trans) To a stirred solution of 54 mg of the title compound from Example 6 2 mL of dichloromethane was added 0.037 mL of triethylamine and 0.015 mL of acetyl chloride and the resulting mixture was stirred overnight. The mixture was poured into 1N HCl and extracted with dichloromethane. The dichloromethane solution was purrkufl over Na₂SO₄, siufl and samsflfnufl couple to everything was purred. Purification by flash chromatography on SiO₂ Using 20% ​​EtOAc hexane as eluant gave 55 mg of the resulting product according to this invention. ¹1 H NMR (400 MHz, CDCl3)₃) δ 2.27 (s, 3H).

Example 46 1H-benz [e] indene-2-carboxylic acid, 7- (acetoxyoxy) -2,3,3a, 4,5,9b-hexahydro-9b- (phenylmethyl) - [2R (2β, 3aα, 9bβ) ] To a stirred solution of 50 mg of the title product from Example 45 ml of dichloromethane was added 75 mg of tallium nitrate-3H₂O under N₂ and the mixture was rapid. Out of this reaction was added 75 mg of tallium trinitrate-3H₂Oh, and the mixture was over again. The mixture was filtered through Celite® and the intervening power to yield the resulting catalysts as a direct white solid. MS: 363 (M-1)⁺.

Example 47 1H-benz [e] indene-2-carboxylic acid, 2,3,3a, 4,5,9b-hexahydro-7-hydroxy-9b- (phenylmethyl) methyl ester, [2R (2α, 3aα, 9bβ) ] Continuation of the effervescent activity initiated in Example 46, as a solution of the title product of Example 46 and hydrogenated succinic acid, was heated to the backing of a soxlet extractor filled with an atmosphere of molecular sieves for 4 hours. After cooling at room temperature, a small amount of NaHCO was obtained₃ bumped out [the solution, and it was intertwined until everything was purred.

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Purification by flash chromatography on SiO₂ using 20% ​​EtOAc hexane as eluent gave 28 mg of the additive according to this example. MS: 335 (M-1)⁺.

Example 48 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1H-1,2,4-triazol-1-ylmethyl) [2R- (23,4aα, 10aβ) solution of 50 mg of the title compound of Example 79 below (prepared by the methods described in Example 79), 54 mg of 1,2,4-triazole and 108 mg of potassium carbonate 4 mL of DMF was heated to 90 ° C for 2 hours. After quenching at room temperature, saturated ammonium chloride was added and the resulting mixture was extracted with Et₂OAc. The EtOAc solution was dried over Na₂SO₄, filtered and aggregated pairs until everything was purred. Purification by flash chromatography on SiO₂ using 5% MeOH in dichloromethane as eluent gave 50 mg of the title product according to this example as a white solid. MS: 391 (M + 1)⁺.

Example 49 2 (1H) -phenantrenone, 4a- (2-Butenyl) -3,4,4a, 5,8,9,10,10a-octahydro-7-methoxy- [4aS- [4aα (E), 10ββ ] Ammonia (200 mL) was placed in a welding flask at -78 ° C which was equipped with a reflux condenser at -78 ° C and a machine cooler. Into this bottle was added 80 mL of t-butanol followed by lithium pair until the solution became dark blue. A solution of 5 g of 2 (3H) -phenantrenone, 4a- (2-butenyl) -4,4a, 9,10-tetrahydro-7-methoxy- [S- (E)] 80 mL of THF was added into the mixture, slowly to keep the reaction dark blue. When the blue color began to lose a small amount of lipid wax was added to the mixture until the blue color returned. The total amount of lithium added to the reaction mixture was not more than 4 g. After completion of the addition of the starting compound, the reaction was stirred for another 40 minutes, and then 100 mL of saturated ammonium chloride was added and immediately the blue color began to disappear. H₂O was added to the mixture and extracted with Et₂OAc, dried over Na₂SO₄, the filter and the combined pair until everything was purred. The crude product was purified by flash chromatography on SiO₂ using the 10% EtOAc to 25% EtOAc in hexane as a gradient eluent to give 2.0 g of the title product according to this example as a white solid. MS: 287 (M + 1)⁺.

Example 50 2-Phenanthenol, 4a- (2-Butenyl) -1,2,3,4,4a, 5,8,9,10,10a-decahydro-7-methoxy-2- (1-propynyl) 2R- [2α, 4α (E), 10ββ]] To a stirred solution of 200 mL of THF, which was concentrated with propylene oxide at 0 ° C, was added 16.4 mL of 2.5 M n-butyl lithium i hexane and the mixture as The reaction mixture was stirred under a nitrogen atmosphere for 20 minutes. A solution of 1.96 g of the title product from Example 49 In 50 mL of THF was added dropwise, and the reaction mixture was warmed to room temperature and stirred for 140 minutes. Saturated ammonium chloride was extracted, and the mixture was extracted with EtOAc, pancake over Na₂SO₄, filtered and aggregated pairs until everything was purred. Purification by flash chromatography on SiO₂using the 10% EtOAc I hexane to 15% EtOAc in hexane as eluent gave 879 mg of the title product according to this example as a white solid. MS: 327 (M + 1)⁺.

104

Example 51 2 (3H) -phenantrenone, 4b- (2-Butenyl) -4,4a, 4b, 5,6,7,8,8a, 9,10-decahydro-7-hydroxy-7- (1-propynyl) - [4aR- [4aα, 4bβ (E), 73,8αα]] and 2 (1H) -phenantrenone, 4b- (2-Butenyl) -3,4,4b, 5,6,7,8,8a , 9,10-decahydro-7-hydroxy-7- (1-propynyl) -, [4bS- [4ta (E), 7a, 8s (3)] Following the procedure initiated in Example 50, pouring into a stirred solution of the title product of Example 50 in 20 mL of THF was added 1 mL of 2N HCl. After 3 hours at room temperature, saturated NaHCO₃ added and the mixture was extracted with EtOAc. The organic layer was dried over Na₂SO₄, siad and gathered couples until everything was purred. Purification by flash chromatography on SiO₂ using 20% ​​EtOAc I hexane to 35% EtOAc. In hexane as a gradient eluent, 154 mg of the title title product was obtained in this example as a white solid. MS: 313 (M + 1)⁺. Further purification of low Rf material by flash chromatography on SiO₂ using 3% acetone dichloromethane to 4% acetone in dichloromethane as a gradient eluent gave 215 mg of the previously listed title product according to this example as a white solid. MS: 313 (M + 1)⁺.

Example 52 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4 - [(methylsulfonyl) oxy] -phenyl] methyl] -2-propyl, 7 methanesulfonate, (4aS, 10aS) To a stirred solution of 50 mg of 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -2-propyl-, (4aS, 10aS) - in 0.039 mL of triethylamine and 3 mL of anhydrous THF was slowly added 0.011 mL of MeSO₂CI at 0 ° C under N₂ air. The reaction was allowed to warm to room temperature for 2 hours and then supported with water. The mixture was extracted with EtOAc (X3), washed with brine, purrkud over Na₂SO₄, silent and cohabiting couple to everything was purred. Purification by flash chromatography on SiO₂ using 25% EtOAc in hexane to 45% EtOAc in hexane as a gradient eluent gave 18 mg of the title title product according to this example and 35 mg of the previously listed title product according to this example as a white powder.

MS m / z 540 (M + NH₄)⁺.

Example 53 1-piperazinecarboxamide, N- [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methyl] phenyl] -4-methyl-, (4aS, 10aR) To a stirred solution of 97 mg of carbamic acid [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- ( 1-propynyl) -4a (2H) -phenanthrenyl] methyl] phenyl] -1,1-dimethylethyl ester, [2R- (2J, 4aq 10]] in 0.078 mL of 1-methylpiperazine and 5 mL of anhydrous THF under N₂ air was added 0.56 mL of 2.5 M n-BuLi and the mixture was warmed to 65 ° C. After 2 hours, the reaction was supported by NH₄CI (mettudu), extracted with EtOAc (X3), quenched with brine, purged over Na₂SO₄, siad and gathered couples until everything was purred. Purification by flash chromatography on SiO₂ with the use of 5% MeOH ί CH₂Cl₂ as eluent, gave 40 mg (40%) of the title product according to this example as a white light powder. MS m / z 472 (M-Me)⁺.

105

Example 54 Acetic acid, [4 - [[1,3,4,9,10,10a-hexahydro-2-hydroxy-7- (2-methoxy-2-oxoethoxy) -2- (1-propynyl) -4a- ( 2H) -phenanthrenyl] methyl] phenoxy] methyl ester, [2R- (2a, 4aα, 10aβ)] A solution of 50 mg of 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a octahydro-4a - [(4-hydroxyphenyl) methyl] -2- (1-propynyl) -, [2R- (2a, 4aα, 10ab)] - in mL of anhydrous CH₃CN, 109.5 mg of Cs₂CO₃and 0.067 mL of methyl bromate was stirred at room temperature under N₂ air overnight. The reaction was stopped by NH₄CI (saturated), extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, filter and coalesce until dry. Purification of SiO₂Preparation of TLC using 45% EtOAc I hexane as eluent gave 20 mg (28%) of the title product according to this example as a white light powder. MS m / z489 (M-17)⁺.

Example 55 Acetamide, 2- [4 - [[7- (2-amino-2-oxoethoxy) -1,3,4,9,10,10a-hexahydro-2-hydroxy-2- (1-propynyl) -4a - (2H) -phenanthrenyl] methyl] phenoxy] -, [2R- (2a, 4aα, 10aβ)] A solution of 17 mg of the title product of Example 54 in 2 mL of NH₄OH (water), 0.5 mL of toluene and 10 drops of MeOH was heated at 60 ° C overnight. The reaction was stopped by NH₄CI (saturated), extracted with EtOAc (X3), brine, dried over Na₂SO₄, filter and coalesce until dry. Purification by flash chromatography on SiO₂ with the use of 2% MeOH in CH₂Cl₂to 4% MeOH in CH₂Cl₂ as eluent, gave 5 mg (30%) of the title product according to this example as a white light powder. MS m / z 478 (M + H)⁺.

Example 56 2 (1H) -phenantrenone, 4a - [[3- (dimethylamino) phenyl] methyl] -3,4,4a, 9,10,10a-hexahydro-7-hydroxy-, (4aS-cis) - . See also Subsection 5 province above.

Example 57 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -4a - [[4- (4H, 1,2,4-triazol-4 -yl) phenyl] methyl] - [2R- (2b, 4aα, 10aβ)] A solution of 50 mg of title compound of Example 776, below, 20 mg of dimethylformamidazine and 3 mg of p-toluenesulfonic acid in 5 mL of toluene was caught under the backflap overnight. The reaction was quenched with NaHCO₃ (mettuflu), extracted with EtOAc (X3), washed with brine, supernatant over Na₂SO₄, siafl and samsafnafl couple to everything were purr. Purification by flash chromatography on SiO₂with the use of 1% MeOH in CH₂Cl₂ to 5% MeOH in CH₂Cl₂ as eluent afforded 18 mg (31%) of title compound in this case as a white light powder. MS m / z 398 (M-Me)⁺.

Example 58 4-Morpholinecarboxylic acid, 7- (chloroethynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -2-phenanthrenyl ester, (4bS, 8aR) Out in a solution of 50 mg of 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2S- (2'4ag10) ] 3 mL of anhydrous THF was added 0.019 mL of triethylamine, 1.7 mg of DMAP and followed by the right addition of 0.020 mL of 4-morpholinecarbonyl chloride at 0 ° C under N₂ air. The reaction temperature was at room temperature for 4 hours and then stopped NH with NH₄CI (mettuflu), extracted with EtOAc (X3), washed with brine, purrkafl

106 above Na₂SO₄, filter and simmer until everything was purred. Purification by flash chromatography on SiO₂using 2% EtOAc hexane to 30% EtOAc in hexane as a gradient eluent gave 57 mg (85%) of the title product according to this example as a white light powder. MS m / z 480 (M)⁺.

Example 59 carbamic acid, [2- (dimethylamino) ethyl], 4b - [[3- (dimethylamino) phenyl] methyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy- 7- (1-Propynyl) -2-phenanthrenyl ester [4bS- (4ba, 7a, 8aP) solution of 68 mg of 2,7-phenanthridiol, 4a - [[3- (dimethylamino) phenyl] methyl] -1,2,2- 3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -, (4aS, 10aR) - in 64 mg of triphosgene, 0.03 mL of triethylamine and 2 mL of anhydrous dichloromethane was stirred vifi room temperature for 1.5 hours below N₂ air. Into the mixture was added dropwise 0.099 mL of N, N-dimethylenediamine and stirred overnight under N₂ air. The reaction was stopped by NH₄CI (saturated), extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, filter and simmer until everything was purred. Purification by flash chromatography on SiO₂ with the use of 100% CHCl₃ and 0.1% triethylamine to 2% EtOH in CHCl₃ and 0.1% triethylamine as a gradient eluent gave 20 mg (23%) of the title compound according to this example as a white light powder. MS m / z (M + H)⁺.

Example 60 2-Phenanthenol, 4a - [[3- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a octahydro-7- (2-hydroxyethoxy) -2- (1-propynyl) ) - [2R- (2,3,4a, 10aP)] to a solution of 76 mg of 2,7-phenanthridiol, 4a - [[3- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -, (4aS, 10aR) - in 3 mL of anhydrous DMF was added 1.4 mg of TBAI and 17 mg of ethylene carbonate and the mixture was heated to 100 ° C for 2 hours. The reaction mixture was quenched with water, extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, siafi and samsafnafi couple to everything were purr. Purification by flash chromatography on SiO₂ with the use of 5% EtOAc hexane and 0.1% triethylamine to 40% EtOAc I hexane and 0.1% triethylamine as a gradient eluent gave 30 mg (36%) of the title compound, as a white light powder. MS m / z 435 (M + H)⁺.

Example 61 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7 - [(3-pyrazinyl- 4-oxadiazol-5-yl) methoxy] - [2R- (23,4aα, 10aβ) solution of 29 mg of acetic acid [[4b, 5,6,7,8,8a, 9,10-octahydro -7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy, methyl ester, [4bS- (4ba, 7a, 8aP)] - and 19.5 mg of pyrazine 2- carboxamide oxime in 3 mL of anhydrous THF was added 24 mg NaH (60%) and hot air under reflux overnight. The reaction was cooled to room temperature, siafi and sync until everything was purred. Purification of the presence of TLC SiO₂ using the 5% MeOH in dichloromethane as eluent gave 7 mg (20%) of the title product according to this case. MS m / z 507 (M + H)⁺.

Example 62 2-Phenanthenol, 7 - [(5-amino-1H-1,2,4-triazol-3-yl) methoxy] 1,2,3,4,4a, 9,10,10a-octahydro -4- (phenylmethyl) -2- (1-propynyl) -, (4aS, 10aR) 2743

107

To a cooled (0 ° C) solution of NaOMe produced from 7 mg of sodium and 1 mL of anhydrous MeOH was added 40 mg of aminoguanid nitrate. Next, 30 mg of acetic acid, [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2 -phenoxyethyl] -methyl ester, [4bS- (4ba, 7a, 8aP) j-1 1 mL of anhydrous MeOH into the resulting mixture and heated under reflux under N₂ air overnight. The mixture was concentrated until everything was dry and purified by preparative TLC using 10% MeOH in dichloromethane as eluent to give 11 mg of the title product according to this example (33%) as a white light powder. MS m / z 443 (M + H)⁺.

Example 63 Acetic acid, [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] [4bS- (4ba, 7a, 8aP) solution of 20 mg of acetic acid, [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- 1-propynyl) -2-phenanthrenyl] oxy] methyl ester, [4bS- (4ba, 7a8aP) j and 5.36 mg of KOH in 3 mL of MeOH and 0.5 mL of H₂The reaction mixture was cooled to 80 ° C for 4 hours. The reaction was cooled to room temperature, extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, filter and coalesce until dry. Purification of a tap of SiO₂ using 5% MeOH in CH₂Cl₂as eluant gave 18 mg (93%) of the title product according to this example as white light . MS m / z 387 (M-17)⁺.

Example 64 Acetonitrile, [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] [4bS- (4ba, 7a, 8aP) in a solution of 54 mg of the first listed title product of Example 8 (which was prepared by analogy to those described in Example 8) and 8 mg of 60% NaH in 5 mL of anhydrous CH₃CN was added 0.056 mL of bromethonitrile under N₂ air. The reaction was heated to 85 ° C overnight. The reaction was stopped by NH₄CI (saturated), extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, filter and coalesce until dry. Purification by flash chromatography on SiO₂ with the use of 0.5% acetone in CH₂Cl₂ to 1% acetone in CH₂Cl₂ as a gradient eluent afforded 46 mg (76%) of the title product according to this example as a white light powder. MS m / z (M-17)⁺.

Example 65 2-Phenanthenol, 7- (2-bromoethoxy) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -2- (1-propynyl) -, [2R- ( 2a, 4aa, 10a | 3)] To a solution of 5 mg of the first listed title product of Example 8 and 7 mg of 60% NaH in 5 mL of anhydrous CH₃CN was added 0.125 mL of 1,2-dibromethane under N₂ air. The reaction was heated to 85 ° C overnight. The reaction was stopped by NH₃CI (saturated), extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, filtered and copied pair until everything was dry. Purification by flash chromatography on SiO₂ using 2% EtOAc I hexane to 20% EtOAc in hexane as a gradient eluent gave 29 mg (44%) of the title product as a white light powder. MS m / z 453 (M + H)⁺

108

Example 66 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (1H-tetrazol-5-ylmethoxy) -, [2R- (2α, 4αα, 1αα 3)] - (Refer to Scheme B: B-7 B-10)

Solution of 0.019 mL of TMSN₃ and 0.067 mL of Me₃AI in 5 mL of anhydrous toluene was stirred at 0 ° C under N₂ air. In the solution that was released, 43 mg of the title product was added in Example 64 in 1 mL of toluene, slowly, to maintain the temperature below 5 ° C. The reaction was then allowed to warm to room temperature and heat at 80 ° C overnight. The reaction was cooled to 0 ° C and quenched with 5 mL of 10% HCl and 5 mL of EtOAc. The aqueous phase was acidified with 1N HCl at pH I around 3 and extracted with EtOAc (X3), dried over Na₂SO₄, filtered and sampled pair to everything was purred. Purification by flash chromatography on SiO₂ using 1% MeOH I CH₂Cl₂ and a few drops of AcOH to 10% MeOH I CH₂Cl₂ and a few drops of AcOH as a gradient eluent gave 17 mg (36%) of the title compound in this example as a white light powder. MS m / z 427 (MH)⁺.

Example 67 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7- [2- (4-methyl-1-piperazinyl) ethoxy] -4a- (phenylmethyl) -2- ( 1-propynyl) -, [2R- (2α, 4aα, 10αβ)] To a solution of 30 mg of title compound of Example 65 (which was prepared by the methods described in Example 65), 8 mg of NaF Na₂CO₃ and 12 mg of Nal in 2 mL of anhydrous DMF was added 0.015 mL of 1-methylpiperazine under N₂ air. The reaction was hot at 60 ° C overnight. The reaction was quenched with NaHCO₃ (saturated), extracted with EtOAc (X3), purged with brine, dried over Na₂SO₄, filtered and copied pair until everything was purred. Purification by TLC of SiO₂ using MeOH in methylene chloride as the eluent gave 19 mg (60%) of title compound in this case as a white left powder. MS m / z 473 (M + H)⁺.

Example 68 Ethanimidamide, N-hydroxy-2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2- phenantrenyl] oxy] - [4bS- (4ba, 7a, 8a, 3)] In a solution of 30 mg of title compound In Example 64 and 22 mg of K₂CO₃1 2 mL of anhydrous EtOH was added 8 mg of NH₂OH HCl and heated to reflux for 6 hours. The reaction mixture was quenched with a combined mixture until all was purged and purified by TLC using 5% MeOH₂Cl₂ as eluent to give 11 mg of the title product as a white powder (34%). MS m / z 419 (M + H)⁺.

Example 69 2-Phenanthenol, 7 - [[5 - [(dimethylamino) methyl] -1,2,4-oxadiazol-3-yl] methoxy] -1,2,3,4,4a, 9,10,10a- octahydro-4-phenylphenylmethyl) -2- (1-propynyl) -, [2R- (23,4α, 10aβ) solution of 30 mg of title compound I Example 68 (which was produced by the necropsy described in Example 68) and 3 mg 60% NaH In 3 mL of anhydrous THF was heated at 60 ° C for 20 minutes. The solution was cooled to room temperature and 0.02 mL of ethyl N, N-dimethylglycine was added to the solution. The resulting mixture was heated to reflux for 1 hour and the pvl was then cooled to room temperature, filtered and concentrated until everything was purred. Purification of the presence of TLC mefl

109 use of 10% acetone in CH₂Cl₂ and 0.05% NH₄OH as eluent gave 4 mg of the title product according to this example (11%). MS m / z 486 (M + H)⁺.

Example 70 1,2,4-Oxadiazol-5 (2H) -one, 3 - [[[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7 - (1-propynyl) -2-phenanthrenyl] oxy] methyl] -, [4bS- (4ba, 7a, 8aP)] A solution of 30 mg of title product 68 (which was prepared by the procedures described in Example 68), 0.006 mL of pyridine and 1 mL of DMF 2 mL of xylene were added 0.014 mL of 2-ethyl hexyl chloroformate at 0 ° C under N₂ air. After a reaction time for 30 minutes, pad was diluted with water, extracted with EtOAc (X3), pervidated with brine, purged over Na₂SO₄, siad and gathered couples until everything was purred. The residue was dissolved in xylene and refluxed for 2 days. The mixture was almost the same after all was purred and purified with instantaneous TLC on SiO₂ using 5% MeOH in methylene chloride as the eluent to give 6 mg (19%) of the title product according to this example. MS m / z 443 (MH)⁺.

Example 71 1,2,4-Oxadiazol-4 (2H) -thione, 3 - [[[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) 7- (1-Propynyl) -2-phenylnitryloxy] methyl] - [4bS- (4ba, 7a, 8θβ)] To a solution of 20 mg of title product In Example 68 (which was prepared by the procedures described in Example 68) and 0.029 mL of DBU In 2 mL of CHF₃CN was added 14 mg of 1,1-piocarbonyl dimidazole at room temperature and stirred 1.5 hours. The solution was diluted with water, adjusted to pH 4 around 10% HCl, extracted with EtOAc (X3), purged with brine, pancake over Na₂SO₄, say and congratulations to everything was purry. Purification with TLC on SiO₂ using 5% MeOH in methylene chloride as eluent gave 12 mg (54%) of the title compound in this case as a white light powder. MS m / z 459 (MH)⁺.

Example 72 2-Phenantrendl, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [[5- [2- (4-morpholinyl) ethyl] 1,2,4-oxadiazol-3- yl] methoxy] -4a- (phenylmethyl) -2- (1-propynyl) -, [2R- (2a, 4aα, 10aβ) solution in 30 mg of title product I Example 68 (which was prepared by the procedures described Example 68) and 3 mg of 60% NaH in 3 mL of anhydrous THF was added 0.023 mL of methyl 4-morpholine propionate and refluxed for 2 hours. The solution was quenched, filtered, washed together and purged and purified by auxiliary TLC using 20% ​​acetone CH₂Cl₂ and a few drops of NH₄OH as the eluant to give 14 mg of the title product according to this case (36%) as a white light powder. MS m / z 542 (M + H)⁺.

Example 73 Carbamopionic acid, dimethyl-, S- [4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] ester, [4bS- (4ba, 7a, 8aP)] A solution of 55mg carbamothionic acid, dimethyl O- [4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] ester, [4bS- (4ba, 7a, 8ab)] - in 2 mL of phenol ether was heated under reflux overnight overnight under N₂ air. The solution was synonymous with everything, everything was purred and

110 purified by preparative TLC using 2% MeOH in CH₂Cl₂ as eluent to give 5 mg of the title product according to this example. MS m / z 434 (M + H)⁺.

Example 74 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (pyrazinylloxy) -, [2R- (2a , 4aa, 10a3)] To a solution of 30 mg of the first listed title product In Example 8 (which was prepared by the procedures described in Example 8) and 4 mg of 60% NaH I 2 mL of anhydrous DMF was added 0.01 mL of chlorpyrazine at 0 ° C under N₂ air. The reaction time was then heated to 60 ° C for 2 hours. Hvarfid was stddwad with NH₄CI (mettudu), extracted with EtOAc (X3), quenched with brine, purged over Na₂SO₄, siad and gathered couples until everything was purred. Purification by flash chromatography on SiO₂ using 2% EtOAc in hexane to 25% EtOAc in hexane as a gradient eluent gave 20 mg (54%) of the title product as a white light powder. MS m / z 426 (M + 2)⁺.

Example 75 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [[2- (4-morpholinyl) -4-pyrimidinyl] oxy] -4a- (phenylmethyl) -2 - (1-propynyl) -, [2R- (2q4aa, 10aP)] A solution of 12 mg of 2-phenanthrene, 7 - [(4-chloro-2-pyrimidinyl) oxy] -1,2,3,4,4a , 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2R- (2a, 4aq10)] and 0.011 mL of morpholine in 2 mL of anhydrous THF was warmed at 65 ° C above night below N₂ air. Hvarfid was stddwad with NH₄CI (mettudu), extracted with EtOAc (X3), quenched with brine, purged over Na₂SO₄, siad and gathered couples until everything was purred. Purification with TLC SiO₂ using 50% EtOAc (hexane as eluent gave 10 mg (75%) of the title product as a white light powder. MS m / z 510 (M + H)⁺.

Example 76 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (3-pyridylmethoxy) -, [2R - (2a, 4aα, 1θββ)] To a solution of 30 mg of the first listed title product of Example 8 (which was prepared with the procedures described in Example 8) and 8 mg of 60% NaOH in 2 mL of anhydrous DMF was placed 18 mg of 3-picolyl chloride hydride broth at room temperature below N₂ air over night. HvarfiO was backed by NH₄CI (mettudu), extracted with EtOAc (X3), quenched with brine, purged over Na₂SO₄, siad and gathered couples until everything was purred. Purification with TLC SiO₂ with use of 4% MeOH in CH₂Cl₂ as eluent, gave 32 mg (80%) of the title product as a white light powder. MS m / z 438 (M + H)⁺

Deemi 77 2 (1H) -phenanthrene, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a- (phenylmethyl)

O-etýloxím

Into a solution of 150 mg of the first listed title product of Example 8 (produced according to the procedures described in Example 8) and 80 mg of sodium acetate in 5 mL of EtOH was added 96 mg of O-ethyl hydroxylamine hydrogen chloride and heated to 70 ° C For 30 minutes. The solution was co-ordinated until all was purged and purified by flash chromatography on SiO₂ with the use of 5%

111

EtOAc hexane with 0.1% Et₃N to 7% EtOAc in hexane with 0.1% Et₃N, as a gradient eluent, gave 148 mg (86%) of the title product according to this example as a white light powder. MS m / z 350 (M + H)⁺.

Example 78 2-Phenanthenol, 4b, 5,6,7,8,8a, 9,10-octahydro-4b - [(4-hydroxyphenyl) methyl] -7-propylidene-, [4bS- (4ba, 7Z, 8aα) 170 mg of propyltriphenylphosphinium bromide In 3 mL of DMSO water was added dropwise 0.44 mL of 1M sodium bis (trimethylsilane) amide in an ethereal room temperature below N₂ air in 10 minutes. Into the resulting mixture was added 35 mg of title flask. In eluent 17 11.5 mL of DMSO in a drop and the mixture was heated at 70 DEG C. over elution. The reaction was a substance with NH₄CI (mettuflu), extracted with EtOAc (X3), washed with brine, supernatant over Na₂SO₄, siafl and samsafnafl couple to everything were purr. Purification by flash chromatography on SiO₂ Mean use of 10% EtOAc in hexane to 25% EtOAc in hexane as a gradient eluent gave 34 mg (89%) of title product. In this case, white solid powder. MS m / z 349 (M + H)⁺.

Example 79 Spiro [oxirane-2,2 '(1'H) -phenanthrene] -7'-ol, 3', 4 ', 4'a, 9', 10 ', 10'a-hexahydro-4'a- (phenylmethyl) -, [2'R- (2t, 3,4a, 10'aP)] in a solution of 91 mg of trimethylsulfonyliodide In 1 mL of anhydrous DMF was added 55 mg of t-BuOK vial 0 ° C under N₂ and the mixture was stirred for 5 minutes. Into the solution which was released, 20 mg of the title product of Example 6 was added 11 mL of DMF and stirred for 1 hour at 0 ° C. The reaction was a substance with NH₄CI (methane), extracted with EtOAc (X3), washed with brine, an excess of Na₂SO₄, siafl and samsafnafl couple to everything were purr. Purification by flash chromatography on SiO₂ with the use of 100% CH₂Cl₂ to 2% acetone in CH₂Cl₂ as a gradient eluent gave 13 mg (70%) of title compound in this case as a white light powder. MS m / z 303 (M-17)⁺.

Example 80 2-Phenantrenesetonitrile, 1,2,3,4,4a, 9,10,10a-octahydro-2,7-dihydroxy-4a (phenylmethyl) -, (4aS, 10aR) -, -2R-,

A solution of 9 mg of title flask in case 79 and 22 mg of potassium cyanide 11 mL of ethylene glycol was heated to 100 ° C for 2 hours. The reaction was quenched and diluted with water, extracted with EtOAc (X3), washed with brine, an excess of Na₂SO₄, siafl and samsafnafl couple to everything were purr. Purification with the addition of TLC SiO₂ Mean use of 35% EtOAc hexane as eluent m.p. gave 5 mg (51%) of title compound in this case as a white left powder. MS m / z 330 (M-17)⁺.

Example 81 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (methoxymethyl) -4a- (phenylmethyl) -, [2R- (2R, 4α, 10αβ) of 20 mg of title flask In Example 79 (prepared by the methods described in Example 79) and 0.071 mL of 25% (v / v) sodium methoxide in 5 mL of anhydrous MeOH was heated to reflux for 3 hours. The reaction was cooled and evaporated with NH₄CI (mettuflu), dregifl out

27Λ3

112 with EtOAc (X3), washed with brine, brine over Na₂SO₄, filtered and copied pair until everything was purred. Purification by addition of TLC SiO₂ using 30% EtOAc in hexane as eluent gave 15 mg (69%) of the title compound according to this example as a white light powder. MS m / z 335 (M-17)⁺.

Example 82 2,7-phenanthridiol, 2- (azidomethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2R- (23,4aα, 10aβ)] A solution of 20 mg of the title compound of Example 79 (prepared by the fractions described in Example 79), 20 mg of sodium azide and 17 mg of NH₄Cl in 0.8 mL of MeOH and 0.1 mL of water was refluxed for 3 hours. The reaction was cooled and diluted with NH₄CI (extract), extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, siafi and samsafnafi couple to everything were purr. Purification of the presence of TLC SiO₂ using 27% EtOAc In hexane as eluent, gave 15 mg (66%) of the title product as a white light powder. MS m / z 348 (M-17)⁺.

EXAMPLE 83 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (4-morpholinylmethyl) -4a- (phenylmethyl) -, [2R- (2b, 4aα, 10aβ )] A solution of 20 mg of the title product of Example 79 (produced by the fractions described in Example 79) and 0.055 mL of morpholine 1 mL of anhydrous MeOH was heated to reflux for 2 hours. The weather was chilly and spoiled by NH₄CI (extract), extracted with EtOAc (X3), brine, brine, Na₂SO₄, siafi and samsafnafi couple to everything were purr. Purification of the presence of TLC SiO₂ using the 5% MeOH in methylene chloride as eluent to give 14 mg (55%) of the title compound according to this example as a white light powder. MS m / z 408 (M + H)⁺.

The following compounds were prepared using the fraiferfium which are the equivalent peams described in Example 8 above.

Example 84 piperidine, 4 - [[2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] methyl] -1- (methylsulfonyl) ) -, [2R- (23,4aa, 10aP)] -, bm. = 124-127 ° C.

Example 85 piperidine, 4 - [[2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) phenanthrenyl] methyl] -1- (methylsulfonyl) [2R- (2α, 4αα, 10αβ) -, bm. = 174-176 ° C.

Example 86 pfperidine, 4 - [[2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) phenanthrenyl] methyl] -1- (2-thienylsulfonyl) -, [2R- (23.4aa, 10ap)] -, bm. = 145148 ° C.

Case 87-90

The following compounds were prepared using a peripheral fumigon which is described in Example 35 above.

113

Example 87 benzoic acid, 4- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1-propenyl] methyl ester , [2R- [2e, 4aα (E), 10αβ] bm. = 199-208 ° C (dec.).

Example 88 benzoic acid, 3- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy4a (2H) -phenanthrenyl] -1-propenyl] methyl ester, [ 2R- [2a, 4a a (E), 10apD-, bm. = 9395 ° C.

Example 89 4-Thiazole carboxylic acid 2- [3- [2- (carbonyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1-propenyl] ethyl ester, [2R- [2α, 4αα (E), 10βU-, MS: 472.

Example 90 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [3- [4- (hydroxymethyl) phenyl] -2-propenyl] -, [2R- [2α, 4αα (E), 10ββ]], MS: 405 (M-18)⁺.

Example 91 benzoic acid, 4- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1-propenyl] - [ 2R- [2b, 4aα (E), 10ββ] To a stirred solution of the title compound (Example 87 in methanol (9 mL) was added a solution of potassium hydroxide (250 mg) in water (0.6 mL) and the solution released was heated to reflux for 3 hours. The reaction was cooled. At room temperature, saturated aqueous ammonium chloride was added and the mixture was extracted with ethyl acetate (3x). The combined organic inorganic was collected over magnesium sulfate and concentrated in vacuo to give the title compound This example is an off-white phase material, 381 mg., mp 145-146 ° C (nidurbr.).

Example 92 Morpholine, 4- [4- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy4a (2H) -phenanthrenyl] -1-propenyl] benzoyl ] - [2R- [2ti, 4aα (E), 10α]]] To a stirred solution of the title compound of Example 91 (100 mg) and N-hydroxysuccinimide (26 mg) in dioxane (2.3 mL) at 0 ° C was added 1,3-dicyclohexylcarbodiimide (47 mg) and the resulting solution was allowed to warm to room temperature and stirred for 3 hours. Acetitrile (10 mL) was added and the slurry released was filtered through Celite®. The sampling of the float gave oil (170 mg) as a crystalline resin. The solid residue and morphidine (0.08 mL) were suspended in acetonitrile (3.5 mL) and heated at 50 ° C for 3 hours. Saturated aqueous solution of ammonium chloride was added, extracted with ethyl acetate (3x), organic login was combined, purr cushion over sodium sulfate and concentrated in aerosol to yield. Flash chromatography on silica gel (1: 1 to 3: 1 ethyl acetate hexane) gave the title compound as an off-white 60 mg. Mp. - 129-136 ° C, MS: 506.

Case 93-100

The following styrenylamide compounds were prepared using the methods of hardened peam described above in Examples 91 and 92.

114

Example 93 piperazine, 1- [4- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy4a (2H) -phenanthrenyl] -1-propenyl] benzoyl] -4-methyl-, [2R- [2α, 4αα (E), 10β-MS: 519

Example 94 4-piperidinol, 1- [4- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1 -propenyl] benzoyl] -, [2R- [2α, 4αα (E), 10αβ] ₂-MS: 520

Example 95 benzamide, 4- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1-propenyl] 2R- [23.4aa (E), 10ap]] - MS: 436

Example 96 benzoic acid, 3- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1-propenyl] [2R- [2α, 4αα (E), 10αβ]] - Bm. 101-105 ° C

Example 97 morpholine, 4- [3- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1-propenyl ] benzoyl] -, [2R- [2α, 4αα (E), Ιθθβ]] - Bm. 135 141 ° C

Example 98 piperazine, 1- [3- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy4a (2H) -phenanthrenyl] -1-propenyl] benzoyl ] -4-methyl-, [2R- [2α, 4αα (E), 10β-MS: 519

Example 99 4-Piperidinol, 1- [3- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1 -propenyl] benzoyl] -, [2R- [23,4aa (E), 10ap]] - MS: 520

Example 100 morpholine, 4 - [[2- [3- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy4a (2H) -phenanthrenyl] -1-propenyl] -4-thiazolyl] carbonyl] -, [2R- [2,4,4a (E), 10aPfl-MS: 513

Example 101 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [3- [4- (hydroxymethyl) phenyl] -2-propenyl] , 7-acetate, [2R- [2a, 4aα (E), 10αβ] in a stirred solution of 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a octahydro-4a- [3- [4- (t-butyldimethylsilyloxymethyl) phenyl] -2-propenyl] - [2R- [2], 4ac (E), 10β- (322 mg), tetrabutylammonium hydroxide , 7 mg) and sodium hydroxide (60 mg) in dioxane (1 mL) at 5 ° C was added dropwise a solution of acetyl chloride (57 mg) in dioxane (1 mL). The reaction was warmed to room temperature and stirred for 2 hours. A second portion of acetyl chloride (57 mg) was added and the stirring was continued for another 2 hours. The reaction was quenched with an aqueous solution of ammonium chloride, extracted with ethyl acetate, the liver solid was dried over sodium sulfate and flotifl concentrated in vacuo. Flash chromatography on silica gel (10 to 20% ethyl acetate / hexane) gave oil, 91 mg. To a stirred (0 ° C) stirred solution of this oil in tetrahydrofuran (1.6 mL) was added 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (0.23 mL). After 2 hours, the reaction mixture was washed with aq. Aqueous solution of ammonium chloride, extracted with ethyl acetate, the liver solid was dried over sodium sulfate, concentrated and flash chromatographed on silica gel (10-50% ethyl acetate / hexane) to give the title compound according to this example, 22 mg. Mp. 73-77 ° C. extracted with ethyl acetate, the liver solid was dried over sodium sulfate, concentrated and flash chromatographed on silica gel (10-50% ethyl acetate / hexane) to give the title compound according to this example, 22 mg. Mp. 73-77 ° C. extracted with ethyl acetate, the liver solid was dried over sodium sulfate, concentrated and flash chromatographed on silica gel (10-50% ethyl acetate / hexane) to give the title compound according to this example, 22 mg. Mp. 73-77 ° C.

Example 102 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,9,10,10a-octahydro-4a- [3- [4- [4-morpholinylmethyl] phenyl] -2-propenyl] 7-acetate, [2R- [2α, 4αα (E), 10ββ] 2743

115

To a stirred (0 ° C) stirred solution of the title product of Example 101 (40 mg) (prepared by the methods described in Example 101) in tetrahydrofuran (0.9 mL) was added sequentially to methanesulfonyl chloride (39 mg ) and diisopropylethylamine (33 mg). After 2 hours, the reaction was cooled to -78 ° C, morpholine (0.12 mL) was added and the reaction mixture was heated to 0 ° C. After 4 hours, the reaction was quenched with aqueous solution of ammonium chloride, extracted with ethyl ether, dried over sodium sulfate and concentrated in vacuo to give gum. Flash chromatography on silica gel (40-75% ethyl acetate / hexane) gave the title compound as a colorless gum, 35 mg. MS: 534.

Example 103 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [3- [4- (4-morpholinylmethyl) phenyl] -2- propanyl] - [2R- [2a, 4aα (E), 10β]] A suspension of the title product of Example 102 (25 mg) in methanol (0.5 mL) and water (0.25 mL) was added to a saturated aqueous solution of sodium bicarbonate (0.25 mL) and the reaction mixture was stirred at room temperature for 2 hours. The reaction was quenched with aq. Aqueous solution of ammonium chloride, extracted with ethyl acetate, the organic phase was purged with sodium sulfate and concentrated in vacuo to give a colorless solid. Flash chromatography on silica gel (50-100% ethyl acetate / hexane) gave the title compound as a colorless solid, 15 mg. MS: 492.

Examples 104-106

The following aminomethylsilyl styrene compounds were produced using the use of crown flaps that are peeled peams described herein above in Examples 101-103.

Example 104 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [3- [4 - [(4-hydroxy-1-piperidinyl) methyl] phenyl] -2-propenyl], 7-acetate, [2R- [2,4,4a (E), 10aPI-MS: 548

Example 105 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [3- [4 - [(4-hydroxy-1-piperidinyl) methyl] phenyl] -2-propenyl] -, [2R- [2α, 4αα (E), 10α]] - MS: 506

Example 106 2,7-Phenantrendiol, 2- (chloroethynyl) -4a- [3- [4 - [(dimethylamino) methyl] phenyl] -2-propenyl] -1,2,3,4,4a, 9,10, 10α-octahydro- [2R- [2α, 4αα (E), 10α]] - MS: 450.

Example 107 carbamic acid, dimethyl, 4b- [2- (4-formylphenoxy) ethyl] -4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-7- (1-propynyl) -2- phenanthrenyl ester, [4bS- (4ba, 7a, 8aP) in a stirred solution of the title product of Preparation 10 (1.9 g) in pyridine (50 mL) was added p-toluenesulfonyl chloride (2.0 g). After 18 hours of room temperature, the reaction mixture was partitioned between ethyl ether and 0.5 N aqueous sodium hydrogen sulfate, and the aqueous phase extracted with more ethyl ether (2x), and the combined organic solvent was collected on sodium sulfate, flash chromatography and flash chromatography on silica gel ( 50-60% ethyl acetate / hexane) to give a colorless seed, 1.5 g. Out of solution of this oil In dimethylformamide (9 mL) was applied

116 solution of p-hydroxybenzaldehyde (0.44 g) and potassium t-butoxide (1M in tetrahydrofuran, 3.3 mL) in dimethylformamide (5 mL, stirred at ambient temperature for 0.5 hours) and the solution released heated at 80 ° C for 4 hours. The reaction time was quenched, diluted in ethyl ether, washed with water, brine, dried over sodium sulfate and concentrated in air temperature. The resulting oil was flash-chromatographed to give the title compound in a colorless form, 1.3 g. MS: 476 (M + 1)⁺.

Example 108 carbamic acid, dimethyl, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- [2- [4- (4-morpholinylmethyl) phenoxy] ethyl] -7- ( 1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP) E HCl salt.

A solution of the title product of Example 107 (50 mg), acetic acid (7 mg), morpholine (18 mg) and sodium triacetoxyborohydride (33 mg) in 1,2-dichloroethane (2 mL) was stirred at room temperature for 3 hours. The reaction was supported with a mettadic aqueous solution of sodium bicarbonate, extracted with dichloromethane, the organic phase was purged with sodium sulfate and concentrated to give oil. Flash chromatography on silica gel (ethyl acetate) gave the title compound in this example as a colorless product, 50 mg. MS: 547.

Examples 109-129

The following examples were produced using the analogues of the analogous peams described above in Examples 107 and 108.

Example 109 carbamic acid, dimethyl, 4b- [2- [4 - [(dimethylamino) methyl] phenoxy] ethyl] 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- 1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] -, HCl salt, MS: 505

Example 110 carbamic acid, dimethyl, 4b- [2- [4 - [(ethylamino) methyl] phenoxy] ethyl] 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- 1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)] -, HCl salt, MS: 505

Example 111 carbamic acid, dimethyl, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- [2- [4 - [(methylamino) methyl] phenoxy] ethyl] (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] -, HCl salt, MS: 491

Example 112 carbamic acid, dimethyl, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- [2- [4 - [[methyl (methylsulfonyl) amino] methyl] phenoxy] ethyl ] -7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP) j, Bm. 82-85 ° C

Example 113 carbamic acid, dimethyl, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1-propynyl) -4b- [2- [4- (1-pyrrolidinylmethyl) phenoxy ] ethyl] -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)] -, HCl salt, MS: 531

Example 114 carbamic acid, dimethyl, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- [2- [4 - [(4-methyl-1-piperazinyl) methyl] phenoxy ] ethyl] -7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)] -, HCl salt, MS: 560

Example 115

Example 116

Example 117

Example 118

Example 119

Example 120

Example 121

Example 122

Example 123

Example 124

Example 125

Example 126

Example 127

Example 128

Example 129

117 carbamic acid, dimethyl, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- [2- [4 - [[methyl-1-methyl-4-piperidinyl) amino] methyl] phenoxy] ethyl] -7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)], HCl salt, MS: 588 carbamic acid, dimethyl, 4b, 5,6,7 , 8,8a, 9,10-octahydro-7-hydroxy-4b- [2- [4 - [[(2-methoxyethyl) amino] methyl] phenoxy] ethyl] -7- (1-propynyl) -2-fenantrenýlester , [4bS- (4ba, 7a, 8aP)], HCl salt, MS: 535 carbamic acid, dimethyl, 4b- [2- [4 - [[[2- (dimethylamino) ethyl] amino] methyl] phenoxy] ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)] - HCl salt, MS: 548 carbamic acid, dimethyl- 4b- [2- [4 - [[[2- (dimethylamino) ethyl] methylamino] methyl] phenoxy] ethyl] -4b, 5,6,7,8,8a , 9,10-octahydro-7-hydroxy-7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8a3)], HCl salt, MS: 562 carbamic acid, dimethyl,4b- [2- [4 - [(diethylamino) methyl] phenoxy] ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1-propynyl) -2 -phenantrenyl ester, [4bS- (4ba, 7a, 8b)], HCl salt, MS: 533 carbamic acid, dimethyl, 4b- [2- [4 - [(cyclopropylamino) methyl] phenoxy] ethyl] -4b, 5 , 6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)], HCl salt, MS: 517 carbamic acid, dimethyl, 4b- [2- [4 - [[bis (2-methoxyethyl) amino] methyl] phenoxy] ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7- hydroxy-7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] -, HCl salt, MS: 5934b- [2- [4 - [[bis (2-methoxyethyl) amino] methyl] phenoxy] ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- ( 1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] -, HCl salt, MS: 5934b- [2- [4 - [[bis (2-methoxyethyl) amino] methyl] phenoxy] ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- ( 1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] -, HCl salt, MS: 593

2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [2- [4- (4-morpholinylmethyl) phenoxy] ethyl] 2R- [2, 4aα, 10αβ]], MS: 496 carbamic acid, dimethyl 7- (chloroethynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- [ 2- [4- (4-Morpholinylmethyl) phenoxy] ethyl] -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)], HCl salt, MS: 567

2,7-phenanthridol, 2- (chlorotynyl) -4a- [2- [4 - [(dimethylamino) methyl] phenoxy] ethyl] -1,2,3,4,4a, 9,10,10a-octahydro- [2R- (2α, 4αα, 10αβ)], MS: 454 carbamic acid, dimethyl, 7- (chlorotynyl) -4b- [2- [4 - [(dimethylamino) methyl] phenoxy] ethyl] -4b, 5 , 6,7,8,8a, 9,10-octahydro-7-hydroxy-2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)], HCl salt, MS: 525 sulfamic acid, dimethyl 7- chlorophenyl) -4b- [2- [4 - [(dimethylamino) methyl] phenoxy] ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-2-phenanthrenyl ester, [ 4bS- (4ba, 7a, 8aP) E HCl salt, MS: 561

2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [2- [4- (hydroxyoxy) phenoxy] ethyl] - [2R- [2a , 4aa, 10ap]] -, Bm. 179-186 ° C benzaldehyde, 4- [2- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] ethoxy] [2R- (23.4aa, 10aP)] - MS: 407 (M-18)⁺

2,7-phenanthridol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (2-phenoxyethyl) -, [2R- (23,43a, 1β3β)] - MS: 379 (M-18)⁺

118

Example 130 Naphtho [1,2-d] thiazol-7-ol, 2-amino-7- (chloroethynyl) -4,5,5a, 6,7,8,9,9a-octahydro-9a- (phenylmethyl) , [5aR, S- (5actB9 $!) A solution of the title product of Preparation 14 (46 mg) and thiourea (22 mg) in acetonitrile (2 mL) was heated at reflux for 8 hours. The reaction was concentrated in vacuo, partitioned between saturated aqueous sodium bicarbonate and chloroform, the organic layer was dried over sodium sulfate, concentrated in vacuo and silica gel chromatography (40% ethyl acetate / hexane) to give a colorless solid, 25 mg. Addition of lithium 2-chlorotype was performed using the general procedure described above in Example 8 to give the title compound in this example as a brown solid, 7 mg. MS: 373

Example 131 formamide, N- [7- (chloroethynyl) -4,5,5a, 6,7,8,9,9a-octahydro-7-hydroxy-9a- (phenylmethyl) naphtho [1,2- d] thiazol- 2-yl] -, [5aR, S- (5a, 9R9)] Using methods analogous to those described in Preparations 11-14 and Example 130 above, except that dimethylformamide was substituted in thiourea cyclization reaction to give the corresponding N-formyl derivative, which is the title product of this example. MS: 401

Example 132 2H-benzo [g] indazol-7-ol, 7- (chloroethynyl) -4,5,5a, 6,7,8,9,9a-octahydro-9a- (phenylmethyl) -, [5aR, (5AD $ 9 $) · l

A solution of the title product of Preparation 15 (244 mg) and hydrazine (75 mg) in ethanol (7 mL) / water (1 mL) was stirred at room temperature for 16 hours. The reaction was diluted with ethyl acetate, washed with water, brine, dried over sodium sulfate and flash chromatography to give a colorless foam, 190 mg. To this foam was added a solution of ethanol (10 mL), 20% sulfuric acid / water (v / v) and the resulting solution was heated under reflux for 5 hours. The reaction mixture was diluted with ethyl ether, with saturated aqueous sodium bicarbonate solution, brine, dried over sodium sulfate and co-collected to give a golden oil. Exposure of lithium-2-chloroprotein was performed using the general procedure described above in Example 8 to give the title compound according to this example as brown, 129 mg. MS: 341.

Example 133 2H-benz [g] indazol-7-ol, 7- (chloroethynyl) -4,5,5a, 6,7,7,9,9a-octahydro-9a- (phenylmethyl) -, [5aR, (5a, 3,7, 9a)] The title compound in this example was prepared by the procedures described above above in Example 132. MS: 341.

Example 134 benzo [h] quinazolin-8-ol, 2-amino-8- (chlorotynyl) -5,6,6a, 7,8,9,10,10a-octahydro-10a- (phenylmethyl) -, [6aR, A solution of sodium metal (25 mg) in isopropyl alcohol (1.5 mL) and quinidine sulfate (107 mg) was refluxed for 1 hour, then the title product from Preparation 15 (154 mg) ) was poured out and heating under reflux was continued for 24 hours. Processing and

119 subsequent processing according to the procedures analogous to that described in Example 132 gave the title compound in this example as a colorless seed, 43 mg. MS: 368.

Example 135 2-Phenanthrenol, 2- (chloroethynyl) -2,3,4,4a, 9,10-hexahydro-7-methoxy-4a- (phenylmethyl) - (2R-cis) The title compound in this example was prepared by means of transfusions which are analogous to those described above in case 8. MS: 361 (M-17)⁺.

Example 136 2-Phenanthenol, 2,3,4,4a, 9,10-hexahydro-7-methoxy-2-phenyl-4a- (phenylmethyl) -, (2R-cis) To a flask-dried flask was added 5 mL of THF and 1.3 mL of phenylmagnesium chloride. The title product according to Example 3 (200 mg) of 5 mL of THF was added dropwise to the solution (mettufl) at 0 ° C. The reaction was rapid at 0 ° C for 1 hour and stopped at NH₄CI, extracted with EtOAc, dried over Na₂SO₄ and siafl. The mixture was purified by flash chromatography (25% EtOAc hexane) on silica gel to give the title product as a light yellow solid, 245 mg, yield 98%, MS: 379 (M-17)⁺.

Example 137 2,7-Phenantrendiol, 2,3,4,4a, 9,10-hexahydro-2,4a-bis (phenylmethyl) -, (2S-cis) -Titile compound of this example was prepared by analogues analogous thereto which is described as described in Example 136. MS: 379 (M-17)⁺.

Example 138 2,7-Phenantrendiol, 2,3,4,4a, 9,10-hexahydro-4a- (phenylmethyl) -2- (2-pyridinyl) -, (2R-cis) The title compound of this example was prepared by means of centrifuges which are analogous to those described above in Example 9. MS: 383 (M + 1)⁺.

EXAMPLE 139 2 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-7- (4-nitrophenoxy) -4a- (phenylmethyl) -, (R) The title compound of this example was prepared by means of coefficients analogous to those is described above in Example 74. MS: 426 (M + 1)⁺.

Examples 140-143

The title compounds of Examples 140-143 were prepared by means of yields similar to those described above in Example 136.

Example 140 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1,2-propenyl) -, (4aS, 10aR) -, MS: 329 (M-17)⁺.

EXAMPLE 141 2,7-Phenantrendiol, 2,3,4,4a, 9,10-hexahydro-2- (2-naphthalenylmethyl) -4a- (phenylmethyl) -, (4aS) -, MS: 429 (M-17)⁺.

120

EXAMPLE 142 2,7-Phenantrendiof, 2,3,4,4a, 9,10-hexahydro-2- (2-naphthalenylmethyl) -4a- (phenylmethyl) -, (4aS) -, MS: 429 (M-17)⁺.

Example 143 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2,4a-bis (phenylmethyl) -, (4aS) -, MS: 416 (M + 18)⁺.

EXAMPLE 144 2,7-Phenantrendiol, 2- (chloroethynyl) -2,3,4,4a, 9,10-hexahydro-4a- (phenylmethyl) -, (2R-cis) The title compound of this example was prepared by methods analogous peams described above in Example 8. MS: 347 (M-17)⁺.

EXAMPLE 145 2,7-Phenantrendiol, 2-Ethynyl-2,3,4,4a, 9,10-hexahydro-4a- (phenylmethyl) -, (2R-cis) The title compound of this example was prepared by methods analogous to peam as described above in Example 5. MS: 313 (M-17)⁺.

Examples 146-147

The title compounds of Examples 146-147 were prepared by methods analogous to those described above in Example 136.

EXAMPLE 146 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2-phenyl-4a- (phenylmethyl) -, (4aS, 10aR) - MS: 367 (M- 17)⁺.

Example 147 2,7-phenanthenediol, 1,2,3,4,4a, 9,10,10a-octahydro-2-phenyl-4a- (phenylmethyl) -, (4aS, 10aR) - MS: 367 (M- 17)⁺.

Example 148 2,7-phenanthridiol, 2-ethynyl-1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) - [2R- (2a, 4aα, 10aβ)] The title compound according to This example was prepared by methods analogous to peaks described above in Example 9. MS: 350 (M + 18)⁺.

EXAMPLE 149 2,7-phenanthridiol, 2-cyclopropyl-1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) - [2R- (2a, 4aα, 10ab)] The title compound according to This example was prepared by methods analogous to peaks described above in Example 136. MS: 331 (M-17)⁺.

Example 150 2,7-phenanthridiol, 2- (cyclopropylethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2R- (2a, 4aα, 10aβ)] The title compound of this example was prepared by methods analogous to those described above in Example 9. MS: 355 (M-17)⁺.

121

EXAMPLE 151 2,7-Phenantrendiol, 2-butyl-1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) - (4aS, 10aR) The title compound of this example was prepared by methods which are analogous to those described above in Example 136. MS: 382 (M + 18)⁺.

Examples 152-153

The title compounds of Examples 152-153 were prepared by methods similar to those described above in Example 9.

Example 152 2,7-phenanthridio, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (2-thienyl) -, (4aS, 10aR) -, MS: 373 (M-17)⁺.

EXAMPLE 153 2,7-phenanthene dibut, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (2-pyridinyl) -, [2R- (2α, 4αα, 10α )], MS: 386 (M + 1)⁺.

Example 154 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2R- (2a, 4aα, 10aβ)] The title compound of this example was prepared by methods analogous to peaks described above in Example 8. MS: 349 (M-17)⁺.

EXAMPLE 156 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (3,3,3-trifluoro-1-propynyl) 2R- (2q4aa, 10ap)] 5-L ribbon-necked vial was prepared with purrisite and dropped. (the bottle was poured into 100 mL of anhydrous THF and 3,3,3-trifluoropropyl gas was bubbled through for 10 minutes. Approximately 100 g (about 15 equivalents) of the gas solidifies during this time. The solution is then cooled to -78 ° C and 200 mL of n-BuLi (2.5 M solution in hexane, about 9 equivalents) was slowly added dropwise. The resulting mixture was stirred at -78 ° C for one hour and then 300 mL of anhydrous THF was added to the reaction vessel. A solution of 20 g of the starting compound, 2 (1H) -phenantrenone, 4a- (benzyl) -3,4,4a, 5,8,9,10,10a-octahydro-7-hydroxy - [4aS- [4ac (E), 10μl in 200 mL of THF was added dropwise, followed by addition of another 500 mL of anhydrous THF, and the reaction mixture was stirred at -78 ° C for another hour. A saturated aqueous solution of ammonium chloride was added and the mixture was extracted with EtOAc primer times, dried and concentrated. Purification by flash chromatography on SiO₂ using 2% ethyl acetate in methylene chloride to 5% ethyl acetate in methylene chloride as eluent gave 20.8 g of the title product according to this example as a yellowish white solid. MS: 399 (M-1)⁺.

Example 157 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a- (phenylmethyl) -, (4aR-cis) The title compound of this Example was prepared by analogous procedures peim described above in Section 7. MS: 307 (M + 1) '.

122

Examples 158-159

The title compounds of Examples 158-159 were prepared by methods analogous to those described above in Example 8.

Example 158 2,7-phenanthridol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -, [2S- (2a, 4aα, 10aα)] - , MS: 349 (M-17)⁺.

Example 159 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -, [2R- (23,4aα, 10aα)] - , MS: 349 (M-17)⁺.

EXAMPLE 160 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (2-thiazolyl) -, (4aS, 10aR) The title compound according to this example was prepared by methods analogous to those described above in Example 9. MS: 392 (M + 1).

Example 161 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) - [2R- (2a, 4aP, 10aa)] The title compound according to this example, was prepared by methods analogous to those described above in Example 8. MS: 349 (M-17)⁺.

Example 162 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2S- (23,4a, 10a )] The title compound of this example was prepared by methods analogous to those described above in Example 9. MS: 349 (M-17)⁺.

Examples 163-164

The title compounds of Examples 163-164 were prepared by methods analogous to those described above in Example 8.

Example 163 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -, [2R- (2a, 4aα, 10aα)] - , MS: 349 (M-17)⁺.

Example 164 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -, [2S- (2,3,4a, 10aβ)] - , MS: 349 (M-17)⁺.

Example 165 2-Phenanthrenecarbonitrile, 1,2,3,4,4a, 9,10,10a-octahydro-2,7-dihydroxy-4a (phenylmethyl) -, [2R- (23,4aα, 10aP)] at room temperature and below nitrogen atmosphere, 159 mg of KCN was added to 75 mg of the title product of Example 6 in methanol (4 mL) followed by 0.070 mL of HOAc. The mixture was stirred overnight at room temperature, quenched with NaHCO₃ (saturated), extracted with EtOAc, dried over Na₂SO₄, filtered and aggregated pair until everything was dry. The crude product was purified by column chromatography with 0.5% acetone in CH₂Cl₂ as eluent to give 20.4

123 mg of the title product according to this example as a white solid. MS: 322 (M + 1)¹³C NMR (100 MHz, CD₃OD) δ 24.8, 27.8, 33.6, 36.0, 37.6, 39.3, 43.6, 44.0, 74.6, 111.3, 114.6, 125.6 , 126.8, 127.0, 127.9, 130.7, 133.8, 136.8, 138.0, 155.1.

Example 166 2-Phenanthrenecarbonitrile, 1,2,3,4,4a, 9,10,10a-octahydro-2,7-dihydroxy-4a- (phenylmethyl) -, (4aS, 10aR) Titile compound according to this example was prepared with conduct which are analogous to those described above in example 165.¹³C NMR (100 MHz, CD₃OD) δ 26.2, 29.3, 35.1, 37.4, 39.1, 41.6, 45.1, 45.5, 71.5, 112.7, 116.0, 127.1 , 128.3, 128.4, 129.4, 132.1, 134.9, 138.6, 139.5, 156.5.

Example 167 2-Phenanthrenecarbonitrile, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [[(4-methylphenyl) sulfonyl] oxy] -4a- (phenylmethyl) -, (4aS, 10aR ) Tosyl chloride (0.13 mL) was slowly added to a stirred solution of 106 mg of tertiary phenol in 0.1 mL of triethylamine and 1 mL of anhydrous CH₂Cl₂ at 0 ° C under a nitrogen atmosphere. The reaction temperature was heated at room temperature for 4 hours and then reached at 40 ° C overnight. It was supported with water. The mixture was extracted with CH₂Cl₂ (X3), pewin with saline, purr quench over Na₂SO₄, silent and cohabiting couple to everything was purred. Purification by flash chromatography on SiO₂ using 20% ​​EtOAc In hexane as eluent, gave 63 mg of pure title product according to this example as a white crystalline solid. MS: 489 (M + 18)⁺.

Example 168 2,7-phenanthridiol, 4a- (2,3-dihydroxypropyl) -1,2,3,4,4a, 9,10,10a-octahydro-, [2R- (2a, 4aα, 10aβ) j

The title compound of this example was prepared by the procedures described in Example 6 above. IR (pure) 3380, 2929, 1612 cm '¹.

Example 169 acetamide, N- [5- [3- (3,4,9,10-tetrahydro-7-methoxy-2-oxo-4a (2H) -phenanthrenyl) -1-propenyl] -2-pyridinyl] [S- (E)] -titile compound according to this case was prepared by analogues which are similar to those described above in Example 35. MS: 403 (M + 1)⁺.

Example 170 2-Phenanthrenecarbonitrile, 1,2,3,4,4a, 9,10,10a-octahydro-7-hydroxy-4a- (phenylmethyl) -, (4aS, 10aR) Titile compound of Example 167 (20 mg) and KOH (38 mg) in EtOH (0.7 mL) and water (0.7 mL) were combined. The mixture was heated under reflux overnight and then neutralized with HOAc, extracted with EtOAc, purrkud and co-evaporated until all was purred. The crude mixture was purified by column chromatography with 5% isopropanol in hexane as eluent to give 1.2 mg of pure title product as a white solid. MS: 318 (M + 1)⁺.

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The title compounds of Examples 171-174 were prepared by methods analogous to those described above in Example 8.

Example 171 acetamide, N- [5- [3- [2- (chloroethynyl) -3,4,9,10-tetrahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1-propenyl] -2- pyridinyl] -, [2R, 4α (E)] - MS: 449 (M + 1)⁺.

Example 172 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (2-propylphenyl) - [2R- (23,4aα, 10aβ)] , ¹1 H NMR (400 MHz, CD₃OD) δ 4.90-4.97 (m, 2H), 5.45-5.61 (m, 1H), 6.51-6.53 (m, 2H), 6.95 (d, 1H, J = 9).

Example 173 2,7-phenanthridol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (2-propenyl) -, [2S- (23,4a, 10aq)] , ¹1 H NMR (400 MHz, CD₃OD) 54.90-4.96 (m, 2H), 5.53-5.60 (m, 1H), 6.48-6.51 (m, 2H), 6.93 (d, 1H, J = 9).

Example 174 2,7-phenanthridol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (2-propenyl) -, [2S- (23,4,10,10a )], ¹1 H NMR (400 MHz, CD₃OD) δ 4.87-5.46 (m,

2H), 5.70-5.80 (m, 1H), 6.50 (d, 1H, J = 2.7), 6.57 (dd, 1H, J = 2.7, 8.5), 7.04 (d, 1H, J = 8.5).

Example 175 2 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-7-hydroxy-4a- (2-propenyl) -, (S) -, ¹1 H NMR (400 MHz, CD₃OD) δ4.95-5.01 (m, 2H), 5.60-5.75 (m, 2H), 5.95 (s,

1H), 6.58 (d, 1H, J = 2.6), 6.73 (dd, 1H, J = 2.6, 8.5), 7.12 (d, 1H, J = 8.5 ).

The title compound of this example was prepared with the procedures similar to those described above in Example 3.

EXAMPLE 176 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a- (2-propenyl) -, (4aS-trans) title compound of this example was prepared by are similar to those described above in example 6. MS: 357 (M + 1f.

Example 177 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [2- (4-morpholinyl) ethyl] -, (4aS, 10aR ) The title compound of this example was prepared with analogues similar to those described above in Example 33. MS: 390 (M + 1)⁺.

Example 178 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (2-propenyl) -, [2R- (23,4aα, 10aα )] The title compound of this example was prepared by the procedures similar to those described above for preparation of the title compound of Example 8.¹1 H NMR (400 MHz, CD₃OD) 54.95-4.99 (m, 2H), 5.60-5.80 (m, 2H), 6.50 (d, 1H, J = 2.4), 6.57 (dd, 1H , J = 2.4, 8.5), 7.03 (d, 1H, J = 8.5).

Examples 179-181

125

The title compounds of Examples 179-181 were prepared by methods analogous to those described above (Example 33.

Example 179 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [2- (4-hydroxy-1-piperidinyl) ethyl] [2R- (2α, 4αα, 10αβ)], MS: 404 (M + 1)⁺.

Example 180 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [2- (4-methyl-1-piperazinyl) ethyl] [2R- (2α, 4αα, 10α₃)] - MS: 403 (M + 1)⁺.

Example 181 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [2- [4- [2- (2-hydroxyethoxy) ethyl] -1-piperazinylethyl] -, [2R- (2α, 4αα, 10α₃)] - MS: 477 (M).

Example 182 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (2-hydroxy-2-phenylethyl) -, [2R- (2'- , 4a 10aP)] -

The title compound of this example was prepared by methods similar to those described above (Example 136. MS: 396 (M).

EXAMPLE 183 2-Butenoic Acid, 4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] ethyl ester, [2R- [ 2j, 4aa (E), 10θβ]] The title compound of this example was prepared by methods similar to those described above in Example 35. MS: 406 (M + 18)⁺.

Example 184 4a (2H) -phenanthrenasaldehyde, 2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy, O-methyloxime, [2R- [23,4aα, 10aβ] The title compound of this example was prepared by methods analogous to those described above in Example 34.¹1 H NMR (400 MHz, CD₃OD) δ 3.70 (s) and 3.74 (s, 3H).

EXAMPLE 185 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a-propyl, (4aR-cis) The title compound of this example was prepared by methods analogous to those is described above in case 7. ¹1 H NMR (400 MHz, CD₃OD) 50.826 (t, 3H, J = 7). MS: 276 (M + 18)⁺.

Example 186 2-Phenanthenol, 4b, 5,6,7,8,8a, 9,10-octahydro-4b-propyl-7-propylidene, [4bR- (4ba, 7Z, 8aα)] The title compound of this example was prepared by methods that are described above in Example 78. MS: 285 (M + 1)⁺.

Example 187 2,7-Phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (2-propenyl) -2- (1-propylphenyl) - [2R- (23,4aα, 10aβ )] The title compound of this example was prepared by methods analogous to those described in Example 9. MS: 279 (M-17)⁺.

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Examples 188-189

The title compounds of Examples 188-189 were prepared by methods analogous to those described in Example 7 above.

Example 188 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a-propyl-, (4aR-trans) - MS: 259 (M + 1)⁺.

Example 189 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2,4a-dipropyl-, [2R- (2a, 4aα, 10aβ)] - MS: 285 ( M-17)⁺.

Example 190 piperazine, 1- [4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2 H) -phenanthrenyl] -1-oxo-2 -butenyl] -4- [2- (2-hydroxyethoxy) ethyl] - [2R- [2a, 4aα (E), 10β] title compound of this example was prepared by methods analogous to those described above 37. MS: 517 (M).

Example 191 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-propyl- [2S- (23,43β, 103β)] The title compound of this example was prepared by methods which are analogous to those described above in Example 7. MS: 243 (M-18)⁺.

Examples 192-193

The title compounds of Examples 192-193 were prepared by methods similar to those described above in Example 136.

Example 192 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2,4a-dipropyl-, [2R- (23,4aa, 10aa)] - MS: 285 ( M-17)⁺.

Example 193 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2,4a-dipropyl-, [2S- (23,4a, 10aβ)], MS: 285 ( M-17)⁺

Example 194 piperazine, 1- [4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1-oxo-2- butenyl] -4-methyl- [2R- [23,4aα (E), 1αββ]] The title compound of this example was prepared by analogy to those described above [Example 37. MS: 443 (M + 1)⁺.

Example 195 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [3- (2-thienyl) -2-propenyl] 4aS (E)] The title compound of this example was prepared by methods analogous to those described above in Example 35. MS: 382 (M-18)⁺.

127

Example 196 2-Phenanthenol, 4b, 5,6,7,8,8a, 9,10-octahydro-4b, 7-dipropyl-, (4bR, 8aS) -Titile compound of this example was prepared by methods analogous to those is described in the example of Example 10. MS: 287 (M + 1)⁺.

Examples 197-202

The title compounds of Examples 197-202 were prepared by methods similar to those described above in Example 37.

Example 197 4-Piperidinol, 1- [4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -1-oxo- 2-butenyl] -, [2R- [2α, 4αα (E), 10αβ]], MS: 426 (M-17f.

Example 198 2-Butanamide, 4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy4a (2H) -phenanthrenyl] -N- [3- (dimethylamino) propyl ] -, [2R- [23,4aa (E), 10aP]], MS: 446 (M + 1)⁺.

EXAMPLE 199 2-Butanamide, 4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -N, N-diethyl-, [2R- [2α, 4αα (E), 10αβ]], MS: 416 (M + 1)⁺.

EXAMPLE 200 2-Butanamide, 4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-d (hydroxy-4a (2H) -phenanthrenyl] -N- [3- (4-morpholinyl) propyl] - [2R- [23,4aa (E), 10aP]], MS: 487 (M).

Example 201 2-Butanamide, 4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -N- (2-pyridinylmethyl) -, [2R- [2α, 4αα (E), 10ββ]], MS: 452 (M + 1)⁺.

Example 202 2-Butanamide, 4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -N- (4-pyridinylmethyl) -, [2R- [2α, 4αα (E), 10ββ]], MS: 451 (M + 1)⁺.

Example 203 2,7-phenanthridol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [3- (2-pyridinyl) -2-propenyl] 2R- [2α, 4αα (E), 1αθθβ]] The title compound of this example was prepared by analogy to those described above in Example 35. MS: 394 (M + 1)⁺.

Example 204 2-Butanamide, 4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -N- [2- (4 -pyridinyl) ethyl] - [2R- [2,4,4a (E), 10aβ]] The title compound of this example was prepared by methods analogous to those described above in Example 37. MS: 465 (M + 1 )⁺.

EXAMPLE 205 2,7-Phenanthenephol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- [3- (5-isoxazolyl) -2-propenyl] -, [4aS E), 10aR] The title compound of this example was prepared by methods analogous to those described above in Example 35. MS: 366 (M-17)⁺,

128

Example 206 2-Butanamide, 4- [2- (chloroethynyl) -1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-4a (2H) -phenanthrenyl] -N-ethyl, [2R- [23.4aa (E), 10θβ]] The title compound of this example was prepared by methods analogous to those described above in Example 37. MS: 370 (M-17)⁺.

Example 207 2-Phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (2-propyl) -7- (1-propynyl) -, [4bS- (4ba, 7a , 8ap)] -, ¹³C NMR (100 MHz, CDCl3)₃) δ 116.6, 168.5.

The title compound of this example was prepared with afiferphium analogous to that described in Example 9.

Examples 208-209

The title compounds of Examples 208-209 were prepared with afiferfium analogous to those described above in Example 8.

Example 208 2,7-phenanthridiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (3-phenylpropyl) -, (4aR) -, MS: 377 ( M-17)⁺.

Example 209 2,7-Phenantrendiol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (3-phenylpropyl) -, [2S- (23,4a, 10aα )], MS: 377 (M-17)⁺.

Examples 210-212

The title compounds of Examples 210-212 were prepared with afiferfium analogous to that described in Example 18.

Example 210 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (2-propenyl) -7- (1-propynyl) -, [4bS- (4ba , 7ct, 8aP)] -, MS: 324 (M + 1)⁺.

Example 211 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N, N-dimethyl-4b- (2-propenyl) -7- (1-propynyl) , [4bS- (4ba, 7a, 8a3)], MS: 353 (M + 1)⁺.

Example 212 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a , 8ap)] -, MS: 374 (M + 1)⁺.

Examples 213-214

The title compounds of Examples 213-214 were prepared with afiferfium analogous to those described in Example 9.

Example 213 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2R- (2a, 4aα, 10β) ], MS: 313 (M-17)⁺.

Example 214 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2S- {2a, 4aα, 10aα)] - , MS: 313 (M-17)⁺.

129

Examples 215-216

The title compounds of Examples 215-216 were prepared by methods similar to those described in Example 10.

Example 215 2-Phenanthenol, 7-Fluoro-1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-, (4aS, 10aS) -, MS: 352 ( M).

Example 216 2-Phenanthenol, 7-Fluoro-1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-, (4aS, 10aS) -, MS: 352 ( M).

Example 217 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N-methyl4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba , 7a, 8ap)] The title compound in this example was prepared by analogous peer methods described in Example 18. MS: 388 (M + 1)⁺.

Examples 218-219

The title compounds of Examples 218-219 were prepared by methods analogous to peaks described in Example 9.

Example 218 2-Phenanthenol, 7-Fluoro-1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propyl) -, [2S- (2 R, 4aα, 10aα )], MS: 331 (M-17)⁺.

Example 219 2-Phenanthenol, 7-Fluoro-1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propylphenyl) -, [2R- (2,4,4a, 10a3 )], MS: 331 (M-17)⁺.

Example 220 2-Phenanthrenecarboxamide, 4b - [(2,2-Dimethyl-1,3-dioxolan-4-yl) methyl] 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy- 7- (1-propynyl) -, [4bS- (4ba, 7a, 8a8)] The title compound in this example was prepared by analogous peam methods described in Example 18. MS: 398 (M + 1)⁺.

Example 221 2-Phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) methyl ester, [4bS- (4ba , 7β, 8aβ)] The title compound in this example was prepared by methods analogous to peaks described in Example 14. MS: 371 (M-17)⁺.

Example 222 2-Phenanthenemethanol, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-α, α-dimethyl-4b- (phenylmethyl) -7- (1-propynyl) 4bS- (4ba, 7a, 8aP) The title compound in this example was prepared by methods similar to those described in Example 19. MS: 371 (M-17)⁺.

Example 223 Carbamic acid, [4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] -2- dimethylamino) ethyl ester, [4bS- (4ba, 7a, 8ap)] 2743

130

The title compound in this example was prepared by methods similar to those described in Example 28. MS: 461 (M + 1)⁺.

Example 224 2-Phenanthenol, 7- (chloromethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2R- (2o , 4aa, 10a3)] The title compound of this example was prepared by analogous procedures described in Example 9. MS: 361 (M-17)⁺.

Examples 225-231

The title compoundes in Examples 225-231 were prepared by methods similar to those described in Example 18.

Example 225 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (3-phenyl-2-propenyl) -7- (1-propynyl) 4bS- (4ba, 7a, 8ap)] - MS: 400 (M + 1)⁺

Example 226 3-Phenanthrenecarboxamide, N- [2- (dimethylamino) ethyl] -4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a, 8ap)] -,

MS: 445 (M + 1)⁺

Example 227 2-Phenanthrenecarboxamide, N- [6- (dimethylamino) hexyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1- propynyl) -, 5- (4-chloro-, 7α, 83β)] -,

MS: 501 (M + 1)⁺.

Example 228 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -N- [2- (1-pyrrolidinyl) ) ethyl] - [4bS- (4ba, 7a, 8aP)] -,

MS: 471 (M + 1)⁺.

Example 229 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [3- (4-methyl-1-piperazinyl) propyl] -4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a, 8e #)] - MS: 514 (M + 1)⁺.

Example 230 2-Phenanthrenecarboxamide, N- [3- (dimethylamino) propyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- ( 1-propynyl) -, [4bS- (4ba, 7a, 8aβ)] -,

MS: 459 (M + 1)⁺.

Example 231 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [2- (4-morpholinyl) ethyl] -4b- (phenylmethyl) -7- (1- propynyl) -, [4bS- (4ba, 7a, 8aP)] - MS: 487 (M + 1)⁺.

Example 232 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [2- (4-morpholinyl) ethyl] -4b- (phenylmethyl) -7- ( 1-propynyl) -, [4bS- (4ba, 7a, 8aP)] - HCl salt

The title compound of this example is the HCl salt of the title compound according to Example 231. MS: 487 (M + 1)⁺.

Examples 233-237

131

The title compounds of Examples 233-237 were prepared by methods analogous to those described above in Example 18.

Example 233 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4α, 7β , 8)], MS: 374 (M + 1)⁺.

Example 234 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [3- (1-imidazol-1-yl) propyl] -4b- (phenylmethyl) 7- (1-propynyl) -, [4bS- (4ba, 7a, 8aP)] - HCl salt, MS: 483 (M + 1)⁺

Example 235 2-Phenanthrenecarboxamide, N- [4- (dimethylamino) butyl] -4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a, 8aP)] -,

MS: 473 (M + 1)⁺

Example 236 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [3- (4-morpholinyl) propyl] -4b- (phenylmethyl) -7- (1- propynyl) -, [4bS- (4ba, 7a, 8ap)] -, MS:

501 (M + 1)⁺

Example 237 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [3- (4-morpholinyl) propyl] -4b- (phenylmethyl) -7- (1- propynyl) -, [4bS- (4ba, 7a, 8aP)] - HCl salt, MS: 501 (M + 1)⁺.

Example 238 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-propyl-2- (1-propynyl) -, [2R- (23,4aα, 10aβ)] The title compound of this example was prepared by analogous to those described in Example 9. MS: 281 (M-17)⁺.

Examples 239-240

The title compounds of Examples 239-240 were prepared by methods similar to those described above in Example 18.

Example 239 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- (3-methoxypropyl) -4b- (phenylmethyl) -7- (1-propynyl) 4bS- (4ba, 7a, 8ap)] -, MS: 446 (M + 1)⁺.

Example 240 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [3- (2-methoxyethoxy) propyl] -4b- (phenylmethyl) -7- (1- propynyl) -, [4bS- (4ba, 7a, 8aP)] -,

MS: 490 (M + 1)⁺

Example 241 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -N- (4-pyridinylmethyl) [4bS- (4ba, 7a, 8aP)] To a stirred solution of 779 mg of 4-aminomethylpyridine in 10 mL of dichloromethane at 0 ° C under N₂ was added 3.6 mL of 2.0 M trimethylalumin in toluene. The mixture was stirred at 0 ° C for 20 minutes and then at room temperature for 1 hour. To this mixture was added 350 mg of the title compound of Example 14 in 5 mL of dichloromethane. The mixture was heated to reflux

132 night. Into the reaction mixture was added 1N HCl dropwise until the aqueous layer had a pH of about 4. The resulting mixture was extracted with EtOAc, dried over Na₂SO₄, filtered and concentrated until dry. Purification by flash chromatography on SiO₂ using 5% MeOH in dichloromethane to 10% MeOH in dichloromethane as a gradient eluent gave 362 mg (87%) of the title product according to this example as a white solid. MS: 465 (M + 1)⁺.

Example 242 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -N- (4-pyridylmethyl) [4bS- (4ba, 7a, 8aP)] -, HCl salt

Title compound according to this example is HCl salt of the title compound according to Example 241. MS: 465 (M + 1) *.

Example 243 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N- [2- (4- pyridinyl) ethyl] - [4bS- (4ba, 7a, 8aP)] The title compound of this example was prepared by coagulants analogous to those described in Example 241. MS: 479 (M + 1)⁺.

Example 244 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N- (2-pyridinylmethyl) , [4bS- (4ba, 7a, 8a) in a stirred solution of 6.2 g of 2-aminomethylpyridine in 80 mL of dichloromethane at 0 ° C under N₂was added 26 mL of 2.0 M trimethyl metal in toluene. The mixture was stirred at 0 ° C for 20 minutes and then stirred at room temperature for 1 hour. To this mixture was added 2.2 g of the title compound of Example 14 (which was formed according to the chromatography described in Example 14) in 50 mL of dichloromethane. The mixture was heated by a large backing flask. Into the reaction mixture was added dropwise 1N HCl until the water drop pH of about 4. The resulting mixture was extracted with EtOAc, purrkufl over Na₂SO₄, siufl and samsflfnufl couple to everything was purred. Purification by flash chromatography on SiO₂ Mean use of 5% MeOH [dichloromethane to 10% MeOH in dichloromethane as a gradient eluent afforded 1.4 g (53%) of the title compound as a white solid. MS: 465 (M + 1)⁺.

Daemi 245-247

The compounds according to Examples 245-247 were produced by supernatants which are peeled peams described herein above above 244.

Example 245 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N- (2-pyridinylmethyl ) -, [4bS- (4ba, 7a, 8aP)] - HCl salt

The title basket of this case is HCl salt of the title product 244. MS: 465 (M + 1) *.

133

Example 246 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N- [2- ( 2-pyridinyl) ethyl] - [4bS- (4ba, 7a, 8.3) j-, MS: 479 (M + 1)⁺.

Example 247 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N - [(tetrahydro- 2-furanyl) methyl] -, [4bS- (4ba, 7a, 8aβ) j-,

MS: 458 (M + 1).

Example 248 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N- (3-pyridinylmethyl ) - [4bS- (4ba, 7a, 8ap)] To a stirred solution of 0.21 mL of 3-aminomethylpyridine in 1 mL of dichloromethane at 0 ° C under N₂ was added 0.1 mL of 2.0 M trimethyl metal in hexane. The mixture was stirred at 0 ° C for 20 minutes, then at room temperature for 1 hour. To this mixture was added 20 mg of the title compound of Example 14 in 1 mL of dichloromethane. The mixture was heated to reflux overnight. Into the reaction mixture was added 1N HCl dropwise until the aqueous layer showed approximately pH 4. The resulting mixture was extracted with EtOAc, dried over Na₂SO₄, filtered and aggregated pair until everything was dry. Purification by flash chromatography on SiO₂ using 5% MeOH in dichloromethane to 10% MeOH in dichloromethane as a gradient eluent gave 18 mg (75%) of the title product according to this example as a white solid. MS: 465 (M + 1)⁺.

Example 249 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N- (3-pyridinylmethyl ) -, [4bS- (4ba, 7a, 8ap)] - HCl salt

The title product in this case is HCl salt of the title product according to example 248. MS: 465 (M + 1)⁺.

Example 250 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [2- (1-methyl-2-pyrrolidinyl) ethyl] -4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ha, 7β, 8β)

The title compound of this Example was prepared by conducting peaks described above in Example 248. MS: 485 (M + 1)⁺.

Example 251 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [2- (1-methyl-2-pyrrolidinyl) ethyl] -4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a, 8aP) j-HCl salt

The title product in this case is HCl salt of the title product in case 250. MS: 485 (M + 1)⁺.

Examples 252-253

The title compounds of Examples 252-253 were prepared by adducts which are oblique peams described above in Example 9.

134

EXAMPLE 252 2,7-Phenanthrenephol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2- (1-propynyl) -, [2R- (2a, 4aα, 10aβ)] -, MS: 309 (M-17)⁺.

Example 253 2,7-phenanthridiol, 4α-butyl-1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) - [2R- (2α, 4αα, 10αβ)] - , MS: 295 (M-17)⁺.

Example 254 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N- [3- ( 1-pyrrolidinyl) propyl] - [4bS- (4ba, 7a, 8ab)] The title compound of this example was prepared by analogous peams described above in Example 248. MS: 485 (M + 1)⁺.

EXAMPLE 255 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N- [3- 1-pyrrolidinyl) propyl] -, [4bS- (4ba, 7a, 8ab)] -HCl salt

The title product of this example is the HCI salt of the title product of Example 254. MS: 485 (M + 1)⁺.

Example 256 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N- [3- ( 1 H -1,2,4-triazol-1-yl) propyl] - [4bS- (4ba, 7a, 8aP)] The title compound of this example was prepared by methods analogous to the above described example 248. MS: 483 (M + 1)⁺.

Example 257 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N- [3- 1 H -1,2,4-triazol-1-yl) propyl] -, [4bS- (4ba, 7a, 8aβ)] -HCl salt

The title product of this example is HCl salted from the title product of Example 256. MS: 483 (M + 1)⁺.

Example 258 2,7-phenanthridol, 4a- (3-butenyl) -1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -, [2R- (2α, 4αα , 10a (3)] The title compound of this example was prepared by methods analogous to those described above in Example 9. MS: 293 (M-17f.

Example 259 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [5- (4-morpholinyl) pentyl] -4b- (phenylmethyl) -7- ( 1-propynyl) -, [4bS- (4ba, 7a, 8aβ)] The title compound of this example was prepared by methods analogous to those described above in Example 248. MS: 529 (M + 1)⁺.

Example 260 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- [5- (4-morpholinyl) pentyl] -4b- (phenylmethyl) -7- (1- propynyl) -, [4bS- (4ba, 7a, 8aP)] - HCl salt

The title compound of this example is HCl salted from the title compound of Example 259. MS: 529 (M + 1)⁺.

135

Example 261 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-pentyl-7- (1-propynyl) -N- [3- (1H-1 , 2,4-triazol-1-yl) propyl] - [4bR- (4ba, 7a, 8aβ)] The title compound of this example was prepared by methods similar to those described above in Example 248. MS: 463 (M + 1)⁺.

Example 262 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-pentyl-7- (1-propynyl) -N- [3- (1H-1, 2,4-triazol-1-yl) propyl] -, [4bR- (4ba, 7a, 8β)] -HCl salt

The title product of this example is the HCI salt of the title product of Example 261. MS: 463 (M + 1)⁺.

Examples 263-265

The title compounds of Examples 263-265 were prepared with the procedures similar to those described above for preparation of the title compound of Example 59.

Example 263 Carbamic acid, dimethyl-, 7- (chlorotynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-methoxy-4b- (2-methoxyethyl) -2-phenanthrenyl ester, [4bS- (4ba , 7a, 8a3)] -, MS: 420 (M + 1)⁺.

Example 264 Carbamic acid, dimethyl-, 7- (chlorotynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (2-methoxyethyl) -2-phenanthrenyl ester, [4bS- (4ba , 7a, 8ap)] -, MS: 406 (M + 1)⁺.

Example 265 Carbamic acid, dimethyl-, 7- (chlorotynyl) -4b- [2- [2- (dimethylamino) -2-oxoethoxy] ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro -7-hydroxy-2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] -, ¹1 H NMR (400 MHz, CDCl3)₃) Δ 2.94 (s, 3H), 2.96 (s, 3H), 3.06 (s, 3H), 3.09 (s, 3H), 4.34 (s, 2H).

Examples 266-267

The title compounds of Examples 266-267 were prepared with the procedures similar to those described above in Example 248.

Example 266 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N-2-pyridinyl- , [4bS- (4ba, 7a, 8aP)] - MS: 451 (M + 1)⁺.

Example 267 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N-2-pyridinyl- , [4bS- (4ba, 7a, 8ap)] - HCl salt, MS: 451 (M + 1)⁺.

Example 268 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N-pyrazinyl-, 4bS- (4ba, 7a, 8aP)] -

136

The title compound of this example was prepared with afiferfium analogous to those described above in Example 244. MS: 452 (M + 1)⁺.

Examples 269-270

The title products of Examples 269-270 are the HCl salt and the p-methanesulfonic acid salt of the title compound of Example 268.

<td>Example 269</td><td>2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-pyrazinyl-, [4bS- (4ba , 7a, 8aP)] - HCl salt, MS: 452 (M + 1)⁺.</td>

<td>Example 270</td><td>2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-pyrazinyl-, [4bS- (4ba , 7a, 8aP)] - p-methanesulfonic acid salt, MS: 452 (M + 1)⁺.</td>

<td>Example 271</td><td>2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-3-pyridinyl-, [4bS- (4ba, 7a, 8aP)] -</td>

The title compound of this example was prepared with fragments similar to those described above from Example 248. MS: 450 (M).

Example 272 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-3-pyridinyl- , [4bS- (4ba, 7a, 8aP)] - HCl salt

The title product of this example is HCl salted from the title compound of Example 271. MS: 451 (M + 1)⁺.

Examples 273-274

The title compounds of Examples 273-274 were prepared with afiferphium analogous to those described above from Example 248.

<td>Example 273</td><td>2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N-4-pyrimidinyl-, 4bS- (4ba, 7a, 8aP)] -, MS: 452 (M + 1f.</td>

<td>Example 274</td><td>2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-propyl-7- (1-propynyl) -N- (4-pyridinylmethyl) -, [4bR- (4ba, 7a, 8aβ)], MS: 417 (M + 1)⁺.</td>

<td>Example 275</td><td>2-phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-propyl7- (1-propynyl) -N- (4-pyridylmethyl) - [4bR- (4ba, 7a, 8aP)] - HCl salt</td>

The title compound of this example is HCl salt of the title compound of Example 274. MS: 417 (M + 1)⁺.

Example 276 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N-1,3, 4-thiadiazol-2-yl-, [4bS- (4bα, 7α, 8θβ)] 2743

137

The title compound of this example was prepared by adducts which are described as described above in Example 248. MS: 458 (M + 1)⁺.

Example 277 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenyl-methyl) -7- (1-propynyl) -N-1,3, 4-thiadiazol-2-yl-, [4bS- (4b a, 7a, 8aP)] - HCl salt

The title product according to this example is HCl salt of the title product of Example 276. MS: 458 (M + 1f.

Example 278 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-2-pyrimidinyl-, 4bS- (4ba, 7a, 8aP)] The title compound of this example was prepared by the procedures described in Example 248 above. MS: 452 (M + 1)⁺.

Example 279 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-2-pyrimidinyl-, 4bS- (4ba, 7a, 8aP)] - HCl salt

The title product according to this example is HCl salt of the title product. In Example 278. MS: 452 (M + 1)⁺.

Case 280-283

The title compounds of Examples 280-283 were prepared with analogues which are similar to those described above in Example 248.

Example 280 2-Phenanthrenecarboxamide, N- (Cyclomethyl) -4b, 5,6,7,8,8a, 9,10-octahydro-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba , 7a, 8ap)] -, MS: 413 (M + 1)⁺.

Example 281 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N- (1H-tetrazol- 5-ylmethyl) -, [4bS- (4ba, 7a, 8aP)] -, MS:

454 (M + 1)⁺.

Example 282 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -N-1,2,4- triazin-3-yl, [4bS- (4ba, 7a, 8ap)], MS: 453 (M + 1)⁺.

Example 283 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-methoxy-4b- (phenylmethyl) -7- (1-propynyl) -N-pyrazinyl, [4bS - (4ba, 7a, 8aP)] - MS: 466 (M + 1)⁺.

Example 284 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-methoxy-4b- (phenyl-methyl) -7- (1-propynyl) -N-pyrazinyl, [4bS - (4ba, 7a, 8aP)] - HCl salt

The title product of this example is the HCl salt of the title product of Example 283. MS: 466 (M + 1)⁺.

Example 285 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-propyl-2- (1-propynyl) -7- (2-pyrazolyl) -, [2R- (2a , 4a, 10ap)] 2743

138

The title compound according to this example was prepared by a randomized fraction which is described herein as above in Example 16. MS: 366 (M + 1)⁺.

Examples 286-287

The title compoundes in Examples 286-287 were prepared by substituting supernatants described herein above in Example 248.

Example 286 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- (5-methyl-1H-pyrazol-3-yl) -4b- (phenylmethyl) -7 - (1-propynyl) -, [4bS- (4ba, 7a, 8aP)] - MS: 454 (M + 1)⁺.

Example 287 1 H -pyrazole-3-amine, 5-methyl-1 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1 -propynyl) -2-phenanthrenyl] carbonyl] - [4bS- (4ba, 7a, 8aP)] - MS: 454 (M + 1)⁺.

Example 288 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-propyl-2- (1-propynyl) -7- (3-pyridinyl) -, [2R- (23 , 4aa, 10a (3)] The title compound of this example was prepared by coagulant analogs described herein above in Example 16. MS: 360 (M + 1)⁺.

Example 289 2-Phenanthrenyl, 1,2,3,4,4a, 9,10,10a-octahydro-4a-propyl-2- (1-propynyl) -7- (3-pyridinyl) -, [2R- (2tx , 4aa, 10a (3)] - HCl salt

The title curve according to this example is the HCl salt of the product of Example 288. MS: 360 (M + 1)⁺.

Example 290 Carbamic acid, [2- (4-morpholinyl) ethyl], 4b-butyl-4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-1- (1-propynyl) 2-phenanthrenyl ester, [4bR- (4ba, 7a, 8aP)] The title compound of this example was prepared by coagulants which are analogous peams described in Example 59. MS: 469 (M + 1)⁺

Example 291 Carbamic acid, [2- (4-morpholinyl) ethyl], 4b-butyl-4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1-propynyl) 2-phenanthrenyl ester, [4bR- (4ba, 7a, 8aP)] -HCl salt

The title flask of this example is the HCI salt of the title product of Example 290. MS: 469 (M + 1)⁺.

Example 292 Carbamic acid, [2- (1-pyrrolidinyl) ethyl], 4b-butyl-4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-7- (1-propynyl) -2- phenanthrenyl ester, [4bR- (4ba, 7a, 8aP)] The title compound of this invention was prepared by coagulant analogs described above in Example 59. MS: 453 (M + 1f.

Example 293 2 (3H) -phenantrenone, 7-fluoro-4,4a, 9,10-tetrahydro-4a- (phenylmethyl) -, (S) -, ¹1 H NMR (400 MHz, CDCl3)₃) 5.99 (s, 1H), 6.88-6.93 (m, 1H).

139

The title compound of this example was prepared by methods similar to those described above in Example 1.

Example 294 Carbamic acid, [2- (dimethylamino) ethyl], 4b-butyl-4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-7- (1-propynyl) -2-phenanthrenyl ester, [4bR- (4ba, 7a, 8a, 3)] The title compound of this example was prepared with the procedures similar to those described above in Example 59. MS: 427 (M + 1)⁺.

Dasmi 295-296

The title compounds of Examples 295-296 were prepared with the procedures similar to those described above in Example 16.

Example 295 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7- (5-methyl-1H-1,2,4-triazol-3-yl) -4a- ( phenylmethyl) -2- (1-propynyl) -, [2R- (2a, 4aα, 10aβ)] - and 2-phenanthrenol,

1,2,3,4,4a, 9,10,10a-octahydro-7- (5-methyl-1H-1,2,4-triazol-3-yl) -4a- (phenylmethyl) -2-propyl -, [2R- (2i, 4aα, 10aβ)], MS: 413 (M + 2)⁺.

Example 296 2-Phenanthrenecarbonitrile, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-propyl-7- (1-propynyl) -, [4bR- (4ba, 7aOa)] -, MS: 290 (M-17)⁺.

Example 297 2-Phenanthrenol, 4α-butyl-1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -7- (pyrazinyloxy) -, [2R- (2,4,4a , 1-ol)] The title compound of this example was prepared with the procedures similar to those described above in Example 74. MS: 391 (M + 1)⁺

Examples 298-299

The title compounds of Examples 298-299 were prepared with similarities to those described in Example 16.

Example 298 2-Phenanthenol, 4α-butyl-1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -7- (2-thiazolyl) -, [2R- (2α , 4aa, 10aP3, MS: 380 (M + 1)⁺

Example 299 2-Phenanthenol, 4α-butyl-1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -7- (2-thiazolyl) -, [2R- (23 , 4aa, 10ap1, MS: 3374 [sic] (M + 1)⁺.

Example 300 2-Phenanthenol, 4α-butyl-1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -7- (2-pyridinyl) -, [2R- (23 , 4aα, 10αβ)] -HCl salt

The title product of this example is HCl salt of the title product of Example 299. MS: 3374 [sic] (M + 1)⁺.

Example 301 2-Phenanthenol, 4a-butyl-1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -7- (2-pyrimidinylloxy) -, [2R- (2i , 4a, 10ap)] 2743

140

The title compound of this example was prepared by methods analogous to those described above in Example 74. MS: 391 (M + 1)⁺

Example 302 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (2-thiazolyl) -, [2R - (2a, 4aα, 1αp)] The title compound of this example was prepared by methods analogous to those described above in Example 16. MS: 414 (M + 1)⁺.

Example 303 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (2-pyridinyl) -, [2R- (&amp; 4aa, 10ap)] -HCl salt

The title product of this example is the HCI salt of the title product of Example 16. MS: 408 (M + 1)⁺.

Example 304 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (3-pyridinyl) -, [2R- (23.4aa, 10ap)] The title compound of this example was prepared by analogous procedures described in Example 16. MS: 408 (M + 1)⁺.

Example 305 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (3-pyridinyl) -, [2R- (2i, 4aα, 10aβ)] -HCl salt

The title product of this example is the HCl salt of the title product of Example 304. MS: 408 (M + 1)⁺.

Example 306 2-Phenanthenol, 4α-butyl-1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -7- (pyrazinylmethoxy) -, [2R- (2α, 4αα , 10aP)] The title compound of this example was prepared by methods analogous to those described above in Example 76. MS: 405 (M + 1)⁺.

Example 307 2-Phenanthenol, 4a-butyl-1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -7- (pyrazinylmethoxy) -, [2R- (2n, 4aα , 10aP)] - HCl salt

The title product of this example is the HCl salt of the title product of Example 306. MS: 405 (M + 1)⁺.

Example 308 4H-benzo [a] quinolizin-4-one, 1,2,3,6,7,11b-hexahydro-9-hydroxy-11b- (phenylmethyl) -3-propyl] title compound of this example was prepared by methods which are analogous to those described above in Example 40. MS: 350 (M + 1)⁺.

Examples 309-311

141

The title compounds of Examples 309-311 were prepared by methods similar to those described above in Example 15.

Example 309 2-Phenanthrenecarbonitrile, 4b-butyl-4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1-propynyl) -, [4bR- (4ba, 7a8ap)] - , MS: 322 (M + 1)⁺.

Example 310 2-Phenanthrenecarbonitrile, 4b, 5,6,7,8,8a, 9,10-octahydro-7- (2-propentyloxy) -4b-propyl-7- (1-propynyl) -, [4bR- (4ba , 7a, 8aP)] - ¹1 H NMR (400 MHz, CD₃OD) δ 5.88-5.97 (m, 1H).

Example 311 Acetic acid, [[7-cyano-1,2,3,4,4a, 9,10,10a-octahydro-4a-propyl-2- (1-propynyl) -2-phenanthrenyl] oxy] ethyl ester, [2R- (2u, 4ao, 10ap)] -, ¹1 H NMR (400 MHz, CD₃OD) δ4.25 (s, 1H).

Example 312 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (4-pyridinylmethoxy) -, [2R- (2α, 4αα , 10aP)] The title compound was obtained as described in Example 627 below, with the exception that 4-picol chloride hydrochloride was used in place of 2-picolyl chloride hydrochloride.

Mass: 442 (M + 1)⁺.

Example 313 2-Phenanthrenecarbonitrile, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-, [4bS- (4ba, 7a, 8b)] -, ¹1 H NMR (400 MHz, CD₃OD) δO, 88 (t, 3H, J = 7.3), 6.43 (d, 1H, J = 8.3)

The title compound of this example was prepared by adducts which are oblique peams described above in Example 15.

Example 314 2-Phenanthenol, 7- (5-Hexyloxy) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-, [2R- (23,4aa , 10aP)] The title compound of this example was prepared by methods similar to those described above in Example 63. MS: 415 (M-17) *.

Example 315 2-Phenanthenol, 7 - [(4-ethylphenyl) methoxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-, (4aS, 10aR ) The title compound of this example was prepared with the procedures similar to those described above in Example 39. MS: 449 (M-17)⁺.

Example 316 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- (6-methyl-2-pyridinyl) -4b- (phenylmethyl) -7-propyl- [4bS - (4ba, 7a, 8a) pyridazine A compound of this Example was prepared by means of a solid solid described above in Example 244. MS: 469 (M + 1)⁺.

142

Example 317 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- (6-methyl-2-pyridinyl) -4b- (phenylmethyl) -7-propyl- , [4bS- (4ba, 7a, 8apl-HCl salt

The title product of this example is the HCI salt of the title product of Example 316. MS: 534 (M + 1)⁺.

Example 318 2-Phenanthenol, 7 - [[5- (2,6-Dimethyl-4-morpholinyl) pentyl] oxy] 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl, [2R- (2a, 4aα, 10aβ)] The title compound of this example was prepared by methods similar to those described above in Example 12. MS: 469 (M + 1)⁺.

Examples 319-320

The title compounds according to Examples 319-320 were prepared by methods similar to those described above in Example 136.

Example 319 2,7-phenanthridiol, 2- (4-fluorophenyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -, (4aS, 10aR) -, MS: 385 (M-17)⁺.

Example 320 2,7-phenanthridol, 2- (4-fluorophenyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, (4aS, 10aR) -, MS: 385 (M-17)⁺.

Example 321 2-Phenanthenol, 4b, 5,6,7,8,8a, 9,10-octahydro-7-phenyl-4b- (phenylmethyl) -, (4bS, 8aR) -, ¹1 H NMR (400 MHz, CDCl3)₃) δ6.58-6.63 (m, 2H)

The title compound of this Example was prepared by methods analogous to those described above in Example 10.

Examples 322-323

The title compounds of Examples 322-323 were prepared by methods analogous to those described above in Example 12.

Example 322 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7 - [[5- (1-piperidinyl) pentyl] oxy] -2-propyl, [2R- (2α, 4αα, 10αβ)], MS: 504 (M + 1)⁺.

Example 323 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7 - [[5- (1-pyrrolidinyl) pentyl] oxy] , [2R- (2α, 4αα, 10αβ)], MS: 490 (M + 1)⁺.

Example 324 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(6-methyl-2-pyridylmethyl) -4b- (phenylmethyl) -7-propyl- [4bS- (4ba, 7a, 8aβ)] The title compound according to this example was prepared by methods analogous to those described above in Example 332. MS: 483 (M-17)⁺.

Example 325 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(6-methyl-2-pyridinyl) methyl] -4b- (phenylmethyl) -7-propyl -, [4bS- (4ba, 7a, 8ap)] - HCl salt

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The title curve of this example is the HCl salt according to the title product of Example 324. MS: 483 (M-17)⁺.

Example 326 2-Phenanthrenecarboxamide, 7- (4,6-Dimethyl-2-pyridinyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- propyl, [4bS- (4ba, 7a, 8aP)] The title compound of this example was prepared by substituting coagulants which were analogous to Example 332. MS: 483 (M-17)⁺.

Example 327 2-Phenanthrenecarboxamide, N- (4,6-Dimethyl-2-pyridinyl) -4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl- , [4bS- (4ba, 7a, 8aP)] - HCl salt

The title compound according to this example is HCl salt of the title compound of Example 326. MS: 483 (M-17)⁺.

Examples 328-331

The title compounds of Examples 328-331 were prepared by coagulant analogs described herein below in Example 332.

Example 328 2-Phenanthrenecarboxamide, 7- (4,6-Dimethyl-2-pyridyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) 7- (1-propynyl) -, [4bS- (4ba, 7a, 8aP)] -,

MS: 479 (M + 1)⁺.

Example 329 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- (6-methyl-2-pyridinyl) -4b- (phenylmethyl) -7- (1 -propynyl) -, [4bS- (4ba, 7a, 8aP)] - MS: 465 (M + 1)⁺.

Example 330 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(6-methyl-2-pyridinyl) methyl] -4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a, 8ap)] - MS: 479 (M + 1)⁺.

Example 331 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(6-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- ( 1-propynyl) -, [4bS- (4ba, 7a, 8aP)] - MS: 479 (M + 1)⁺.

Example 332 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- ( 1-propynyl) -, [4bS- (4ba, 7a, 8aP)] To a stirred solution of 250 mg of 2-methyl-3-aminomethylpyridine in 5 mL of dichloromethane at 0 ° C under N₂ was added 1.02 mL of 2.0 M trimethyl metal in toluene. The mixture was stirred at 0 ° C for 20 min, and then heated to room temperature for 1 hour. In this example, 100 mg of the title compound of Example 14 ml of dichloromethane was added. The mixture was heated by a large backing flask. Out of the reaction mixture was added dropwise 1 N HCI pair to water drop pH over volume 4. The resulting mixture was extracted with EtOAc, purrkufl over Na₂SO₄, siufl and samsflfnufl couple to everything was purred. Purification by flash chromatography on SiO₂ with 90% use

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EtOAc hexane as eluant gave 99 mg (80%) of the supplemental product according to this example as a white solid. MS: 479 (M + 1)⁺.

Examples 333-336

The title compounds of Examples 333-336 were prepared by methods analogous to those described above in Example 244.

Example 333 2-Phenanthrenecarboxamide, N- (4,6-Dimethyl-2-pyrimidinyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a, 8aP)] -,

MS: 480 (M + 1)⁺.

Example 334 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N- (4-methyl-2-pyrimidinyl) -4b- (phenylmethyl) -7- (1 -propynyl) -, [4bS- (4ba, 7a, 8ap)] - MS: 466 (M + 1)⁺.

Example 335 2-Phenanthrenecarboxamide, N- (2,6-Dimethyl-4-pyrimidinyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -, [4bS- (4ba, 7a, 8aβ)] -,

MS: 480 (M + 1)⁺.

Example 336 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propenyl) -, [2R- [2} 2 (E ), 4αq10]], MS: 347 (M-1)⁺.

Example 337 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- ( 1-propynyl) -, [4bS- (4ba, 7a, 8aP)] The title compound of this example was prepared by methods analogous to those described above in Example 332. MS: 479 (M + 1 f.

Example 338 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7 -propyl- [4bS- (4ba, 7a, 8aP)] To a stirred solution of 232 mg of 2-methyl-3-aminomethylpyridine in 10 mL of dichloromethane at 0 ° C under N₂ was added 0.95 mL of 2.0 M trimethyl metal in toluene. The mixture was stirred at 0 ° C for 20 min. and then room temperature for 1 hour. To this end, 300 mg of 2-phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propyl) methyl ester, [4bS- (4bn, 7β, 8β)] - in 10 mL of dichloromethane. The mixture was heated to reflux overnight. Into the reaction mixture was added dropwise 1N HCl until water-resistant at about pH 4. The resulting mixture was extracted with EtOAc, NaCl over Na₂SO₄, siufi and social life couple to everything was purrt. Purification by flash chromatography on SiO₂ including the use of 10% isopropanol and 1% acetone in hexane to 30% isopropanol and 5% acetone hexane as a gradient eluent gave 303 mg (80%) of the title compound as a white solid. ¹1 H NMR (400 MHz, CDCl3)₃) Δ 2.56 (s, 2H), MS: 483 (M + 1)⁺.

Example 339 2-Phenanthrenecarboxamid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7-propyl -, [4bS- (4ba, 7a, 8a3)] - HCl salt

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The title product of this example is the HCl salt of the title product of Example 338.¹1 H NMR (400 MHz, CD₃OD) δ 2.56 (s, 2H), MS: 483 (M + 1)⁺.

Examples 340-342

The title compounds of Examples 340-342 were prepared by methods similar to those described in Example 338.

Example 340 2-Phenanthrenecarboxamide, N - [[2-Chloro-6-methyl-4-pyridinyl) methyl] 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl ) -7-propyl-, [4bS- (4ba, 7a, 8aP)] - MS: 517 (M).

Example 341 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2methyl-4-pyridinyl) methyl] -4b- (phenylmethyl) -7-propyl -, [4bS- (4ba, 7ct, 8aP)] - MS: 483 (M + 1)⁺.

Example 342 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-N- (2-pyridinylmethyl) -, [4bS- ( 4ba, 7q8ap)], MS: 469 (M + 1f.

Example 343 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-N- (2-pyridinylmethyl) -, [4bS- (4ba, 7a, 8aP)] - HCl salt

The title product of this example is the HCI salt of the title product of Example 342. MS: 469 (M + 1)⁺.

Examples 344-345

The title compounds of Examples 344-345 were prepared by methods similar to those described in Example 338.

Example 344 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-N- (4-pyridinylmethyl) -, [4bS- ( 4ba, 7q8aP)], MS: 469 (M + 1)⁺.

Example 345 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-N- (3-pyridinylmethyl) -, [4bS- ( 4ba, 7q8a3)], MS: 469 (M + 1)⁺.

Examples 346-347

The title compounds of Examples 346-347 were prepared by methods analogous to those described above in Example 9.

Example 346 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (4-methyl-1-pentynyl) -4a- (phenylmethyl) -, [2R- (2a , 4aaW)], MS: 371 (M-17)⁺.

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Example 347 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-methyl-1-butynyl) -4a- (phenylmethyl) -, [2R- (2i , 4aa, 10a8)] -, MS: 357 (M-17)⁺.

Example 348 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (3,3,3-trifluoropropyl) -, [2S- (23 , 4aα, 10aβ)] The title compound of this example was prepared by methods analogous to those described above in Example 10. MS: 487 (M-17)⁺.

Examples 349-350

The title compounds of Examples 349-350 were prepared by methods analogous to those described above in Example 338.

Example 349 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-N-pyrazinyl-, [4bS- (4ba, 7a , 8aP)] -, MS: 456 (M + 1)⁺.

Example 350 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-N-2-pyridinyl- [4bS- (4ba, 7a , 8ap)] -, ¹1 H NMR (400 MHz, CD₃OD) δ 7.22 (d, 1H, J = 1).

Examples 351-353

The title compounds of Examples 351-353 were prepared by methods analogous to those described in Example 10 above.

Example 351 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (2-methylpropyl) -4a- (phenylmethyl) -, [2R- (2α, 4α, 10αα )], MS: 347 (M-17)⁺.

Example 352 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (2-methylpropyl) -4a- (phenylmethyl) -, [2R- (23,4aP, 10aa )], MS: 347 (M-17)⁺.

Example 353 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-methylbutyl) -4a- (phenylmethyl) -, [2R- (2α, 4α, ), MS: 361 (M-17)⁺.

Examples 354-355

The title compounds of Examples 354-355 were prepared by methods similar to those described above in Example 74.

Example 354 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-methyl-1-butynyl) -4a- (phenylmethyl) -7- (3-pyridinylmethoxy) , [2β- (23,43α, 103β)], MS: 448 (M-17)⁺.

Example 355 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridylmethyl) -2- (3,3,3-trifluoropropyl) ) -, [2S- (2α, 4αα, 10α₈)] - MS: 496 (M + 1)⁺.

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Example 356 4H-benzo [a] quinolizin-4-one, 1,2,3,6,7,11b-hexahydro-9-hydroxy-9-hydroxy-3- (hydroxymethyl) -1- (phenylmethyl) 3-propyl-, (3-cis) -, ¹1 H NMR (400 MHz, CD₃OD) δ4.53 (dm, 1H, J = 13).

The title compound of this example was prepared by the procedures described above in Example 42.

Examples 357-358

The title compounds of Examples 357-358 were prepared by methods that are described above in Example 9.

Example 357 2-Phenantrenesetonitrile, 1,2,3,4,4a, 9,10,10a-octahydro-2,7-dihydroxy-4a- (phenylmethyl) -, (4aS, 10aR) -, MS: 346 (M- 1)⁺.

Example 358 2-Phenantrenesetonitrile, 1,2,3,4,4a, 9,10,10a-octahydro-2,7-dihydroxy-4a- (phenylmethyl) -, (4aS, 10aR) -, MS: 346 (M- 1)⁺.

Case 359-360

The title compounds according to Examples 359-360 were prepared with conductive peaks described above in Example 136.

Example 359 2,7-phenanthridiol, 2-cyclopentyl-1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, (4aS, 10aR) -, MS: 359 (M- 17)⁺.

Example 360 ​​2,7-phenanthridiol, 2-cyclohexyl-1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, (4aS, 10aR) -, MS: 389 (M- 1)⁺.

Case 361-363

The title compounds of Examples 361-363 were prepared using behaviors that are superseded as described above in Example 332.

Example 361 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-N-4-pyridinyl-, [4bS- (4ba, 7a, 8aP)] -, MS: 455 (M + 1)⁺.

Example 362 2-Phenanthrenecarboxamide, N- (2,6-dichloro-4-pyridinyl) -4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl- , [4bS- (4ba, 7a, 8aP)] - MS: 523 (M).

Example 363 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-N-3-pyridinyl-, [4bS- (4ba, 7a, 8ap)] -, MS: 455 (M + 1)⁺.

Case 364-365

The title compounds of Examples 364-365 were prepared with conductive peams described above in Example 76.

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Example 364 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (2-methylpropyl) -4a (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2S- ( 2 s, 4aa, 1 Oap)], MS: 456 (M + 1)⁺.

Example 365 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-methylbutyl) -4a (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- ( 23.4aa, 10aP)], MS: 370 (M + 1)⁺.

Examples 366-368

The title compounds of Examples 366-368 were prepared by methods similar to those described in Example 10.

Example 366 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (4-methylpentyl) -4a- (phenylmethyl) - [2R- (2,3,4a, 10a3)] -, MS: 391 (M-1)⁺.

Example 367 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (4-methylphenyl) -4a- (phenylmethyl) -, [2S- (3α, 4α, 10αα ) J-, MS: 391 (M-1)⁺.

Example 368 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-hydroxy-3-methylbutyl) -4a- (phenylmethyl) -, [2S- (2a , 4α, 10αβ)], MS: 393 (M-1)⁺.

Examples 369-370

The title compounds of Examples 369-370 were prepared by methods analogous to those described above in Example 76.

Example 369 2-Phenanthrenepropanol, 1,2,3,4,4a, 9,10,10a-octahydro-2-hydroxy-α, α-dimethyl-4α- (phenylmethyl) -7- (3-pyridinylmethoxy) 2S- (2α, 4αα, 10αβ)] - MS: 486 (M + 1)⁺.

Example 370 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (4-methylpentyl) -4a (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- ( 23.4aa, 10aP)], MS: 484 (M + 1)⁺.

Examples 371-372

The title compounds of Examples 371-372 were prepared by methods similar to those described above in Example 9.

Example 371 2,7-Phenanthrenediol, 2- (Cyclopropylmethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2S- (2a, 4aα, 10aβ)] -, MS: 363 (M + 1)⁺.

Example 372 2,7-phenanthrene diol, 2- (cyclopropylmethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2R- (2α, 4α, 10αα )], MS: 363 (M + 1)⁺.

Example 373 2,7-phenanthrenediol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-hydroxypropyl) -4a- (phenylmethyl) - (4aS, 10aR) The title compound according to this example was prepared by methods analogous to those described above in Example 10. MS: 365 (M-1)

Examples 374-375

149

The title compounds of Examples 374-375 were prepared by methods analogous to those described above in Example 9.

<td>Example 374</td><td>2,7-phenanthridol, 2- (3,3-dimethyl-1-butynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2R- ( 23.4aq10ap)], MS: 387 (M-1)⁺.</td>

<td>Case 375</td><td>2,7-phenanthridol, 2- (3,3-dimethyl-1-butynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, (2S- 2o, 4a, 3.10a)], MS: 387 (M-1)⁺.</td>

<td>Example 376</td><td>2-phenanthrene, 2- (cyclopropylethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- (2,3,4a, 10ap)] -</td>

The title compound of this example was prepared by the procedures similar to those described above in Example 76. MS: 464 (M + 1)⁺.

Example 377 2,7-phenanthridiol, 2- (2-cyclopropylethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2R- (2a, 4aα, 10aP )] The title compound of this example was prepared with the procedures similar to those described above in Example 10. MS: 361 (M-17)⁺.

<td>Example 378</td><td>2-phenanthrene, 2- (3,3-dimethyl-1-butynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) , [2R- (2α, 4αα, 10αβ)] -, ¹1 H NMR (400 MHz, CD₃OD) δ8.61 (s, 1H).</td>

<td>Example 379</td><td>2-phenanthrenepropanol, 1,2,3,4,4a, 9,10,10a-octahydro-2-hydroxy-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2S- (2α, 4aα, 1α Σθβ)] -, MS: 458 (M + 1)⁺.</td>

Examples 380-381

The title compounds according to Examples 380-381 were prepared with conductors which are similar to those described above in Example 9.

<td>Example 380</td><td>2,7-phenanthridol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (phenylethynyl) -4a- (phenylmethyl) -, (2R- (2,3,4a, 10aβ)] - MS: 407 (M-1)⁺.</td>

<td>Example 381</td><td>2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (phenylethynyl) -4a- (phenylmethyl) -, [2S- (M4ap, 10aa)] - MS: 407 (M-1)⁺.</td>

<td>Example 382</td><td>2,7-phenanthridol, 2- (3,3-dimethylbutyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -, (2R- (2x4a, 10aβ)] -</td>

The title compound of this example was prepared by analogy, as described above, in Example 10. MS: 391 (M-1)⁺.

150

Example 383 2-Phenanthenol, 2- (2-Cyclopropylethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- ( 2a, 4aα, 10aβ)] The title compound of this example was prepared by analogous procedures described in Example 76. MS: 450 (M-17)⁺.

Example 384 2 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -, (S) The title compound of this example was prepared using methods are analogous to those described above in Example 3. Mass 321 (M + 1)⁺.

Example 385 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-4a - [(4-hydroxyphenyl) methyl] -7-methoxy-, (S) The title compound of this example was prepared using analogous methods those described above in Example 1. Mass 335 (M + 1 f.

Examples 386-387

The title compounds of Examples 386-387 were prepared using methods analogous to those described above in Example 6.

Example 386 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -, (4aS) - mass 321 (M-1 )⁺.

Example 387 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-4a - [(4-hydroxyphenyl) methyl] -7-methoxy-, (4aS) + mass 335 (M-1 )⁺.

Example 388 2,7-phenanthridol, 2- (chloroethynyl) -2,3,4,4a, 9,10-hexahydro-4a - [(4-hydroxyphenyl) methyl] -, (2R-cis) The title compound of this example was prepared using methods analogous to those described above in Example 8. Mass 363 (M-17)⁺.

Example 389 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] - (4aS) The title compound of this example was prepared by use in analogy to those described in Example 6. Mass 325 (M + 1)⁺.

Examples 390-391

The title compounds of Examples 390-391 were prepared using methods analogous to those described above in Example 8.

Example 390 2-Phenanthenol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -7-methoxy mass: 397 (M + 1)⁺.

151

Example 390 [sic] 2-Phenanthenol, 2- (chloroethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -7-methoxy- : 397 (M + 1)⁺.

Examples 392-393

The title compounds of Examples 392-393 were prepared using methods analogous to those described above in Example 10.

Example 392 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -2-propyl-, (4aS) - mass: 366 (M), 384 (M + 18)⁺.

Example 393 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -2-propyl-, (4aS) - mass: 366 (M), 384 (M + 18)⁺.

Examples 394-406

The title compounds of Examples 394-406 were prepared using methods described in Example 77.

Example 394 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a- (phenylmethyl) oxime, (4aS) - mass 322 (M + 1)⁺.

Example 395 2 (1 H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a- (phenylmethyl)

O- (phenylmethyl) oxime, (4aS), mass 412 (M + 1)⁺.

Example 396 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a- (phenylmethyl) - O - [(4-nitrophenyl) methyl] oxime, (4aS) - , mass 457 (M + 1f.

EXAMPLE 397 2 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -O-ethyloxime, (S) - mass 364 (M + 1)⁺.

Example 398 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-1,7,10a-trihydroxy-4a - [(4-hydroxyphenylmethyl), O-ethyl oxime, mass 398 (M + 1)⁺.

Example 399 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-1,7,10a-trihydroxy-4a - [(4-hydroxyphenyl) methyl] -O-ethyloxime, mass 398 M + 1)⁺.

Example 400 benzoic acid, [3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -2 (1H) -phenanthrenylidene] hydrazide, (4aS-trans) - , mass 441 (M + 1)⁺

Example 401 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxy-phenyl) methyl] -2,2-propenyloxime, (4aS- trans) - mass 378 (M + 1) *.

Example 402 acetic acid, [[[3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -2 (1H) -phenanthrenylidene] amino] oxy] -, ( 4aS trans), mass 396 (M + 1)⁺.

Example 403 hydrazinecarboxylic acid, [3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -2 (1H) -phenanthrenylidene] ethyl ester, (4aS-trans) , mass 409 (M + 1)⁺.

Example 404 acetic acid, [[[3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -2 (1H) -phenanthrenylidene] amino] oxy] , methyl ester, (4aS-trans), mass 410 (M + 1)⁺.

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Example 405 2 (3H) -phenantrenone, 4,4a, 9,10-tetrahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -O-methyloxime, mass 350 (M + 1)⁺.

Example 406 3-Pyridinecarboxylic acid, [3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -2 (1H) -phenanthrenylidene] hydrazide, (4aS-trans) mass 442 (M + 1)⁺.

Example 407 acetic acid, [4,4a, 9,10-tetrahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -2 (3H) -phenanthrenylidene] ethyl ester, [S- (E)] The title compound according to This example was prepared by methods analogous to those described above in Example 78. Mass 391 (M + 1)⁺.

Example 408 acetic acid, cyano, [3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxy-phenyl) methyl] -2 (1H) -phenanthrenylidene hydrazide, (4aS- trans) The title compound of this example was prepared by methods similar to those described above in Example 77. Mass 404 (M + 1)⁺.

Example 409 2,7-Phenanthridol, 4a - [(4-aminophenyl) methyl] -1,2,3,4,4a, 9,10,10a-octahydro- [2R- (2a, 4aα, 10aβ)] The title compound according to this example, was prepared by methods analogous to those described above in Example 6. MS: 322 (M-1)⁺.

Examples 410-411

The title compounds of Examples 410-411 were prepared by methods analogous to those described above in Example 77.

Example 410 hydrazinecarboxylic acid, [4,4a, 9,10-tetrahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -2 (3H) -phenanthrenylidene] ethyl ester, (S) - mass: 407 (M + 1)⁺

Example 411 2 (1H) -phenantrenone, 4a - [(4-aminophenyl) methyl] -3,4,4a, 9,10,10a-hexahydro-7-hydroxy, O-ethyloxime, mass: 365 (M + 1 )⁺.

Examples 412-413

The title compounds of Examples 412-413 were prepared by methods analogous to those described above in Example 10.

Example 412 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4 - [(1-methylethyl) amino] -phenyl] methyl] -2-propyl- , (4aS, 10aR) - mass: 408 (M + 1)⁺.

Example 413 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4 - [(1-methylethyl) amino] -phenyl] methyl] -2-propyl- (4aS, 10aR) - mass: 408 (M + 1) *.

Examples 414-415

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The title compounds of Examples 414-415 were prepared by methods similar to those described above in Example 77.

Example 414 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [[4 - [(1-methylethyl) amino] phenyl] methyl] -O-ethyloxime, ( 4aS-trans) - mass: 407 (M + 1)⁺.

Example 415 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [[4 - [(1-methylethyl) amino] phenyl] methyl] -O-methyloxime, ( 4aS-trans) - mass: 393 (M + 1)⁺.

Examples 416-418

The title compounds of Examples 416-418 were prepared by methods similar to those described above in Example 78.

Example 416 2-Phenanthenol, 4b, 5,6,7,8,8a, 9,10-octahydro-4b - [(4-hydroxyphenyl) methyl] -7-propylidene, (4b, s, 7Z) - mass : 349 (M + 1)⁺.

Example 417 2-Phenanthenol, 7-butylidene-4b, 5,6,7,8,8a, 9,10-octahydro-4b - [(4-hydroxy-phenyl) methyl] -, (4b, S, 7Z) - , mass: 363 (M + 1)⁺.

Example 418 acetonitrile, [3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxyphenyl) methyl] -2 (1H) -phenanthrenylidene] -, [4aS- (2Z, 4ap10 $] - mass: 363 (M + 18)⁺.

Examples 419-421

The title compounds of Examples 419-421 were prepared by methods similar to those described above in Example 136.

Example 419 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4 - [(tetrahydro-2H-pyran-4-yl) amino] phenyl] methyl] -2-propyl-, (4aS, 10aR) - mass: 450 (M + 1)⁺.

Example 420 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4 - [(tetrahydro-2H-pyran-4-yl) amino] phenyl] methyl] -2-propyl-, (4aS, 10aR) - mass: 450 (M + 1)⁺

Example 421 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4 - [(1-methylethyl) amino] -phenyl] methyl] -2-propyl- , (4aS, 10aR) - mass: 409 (M + 1)⁺.

Example 422 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4-hydroxyphenyl] methyl] -2- (1-hydroxypropyl) -, (4aS) The title compound of this example was prepared by methods analogous to those described above in Example 30. Mass: 400 (M + 18)⁺.

Examples 423-426

The title compounds of Examples 423-426 were prepared by methods analogous to those described above in Example 136.

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<td>Example 423</td><td>2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -2-propyl-, (4aS, 10aR) - mass: 349 (M + 17)⁺.</td>

<td>Example 424</td><td>2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -2-propyl, (4aS, 10aR) - mass: 349 (M + 17)⁺.</td>

<td>Example 425</td><td>2,7-phenanthranediol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4 - [[1- (1-methylethyl) -4-piperidinyl] amino] phenyl] methyl] -2-propyl-, (4aS, 10aR) - mass: 491 (M + 1f.</td>

<td>Example 426</td><td>2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[3 - [(1-methylethyl) amino] -phenyl] methyl] -2-propyl, 4aS, 10aR) - mass: 408 (M + 1) *.</td>

<td>Example 427</td><td>2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -2- (1-hydroxypropyl) -, (4aS, 10aS) -</td>

The title compound of this example was prepared by methods analogous to those described above in Example 30. Mass: 382 (M).

Examples 428-429

The title compounds of Examples 428-429 were prepared by methods analogous to those described above in Example 78.

<td>Example 428</td><td>2-phenanthrene, 7-butylidene-4b, 5,6,7,8,8a, 9,10-octahydro-4b - [(4-hydroxy-phenyl) methyl] - [4bS- (4bg7Z, 8an)] - , mass: 363 (M + 1)⁺.</td>

<td>Example 429</td><td>2-phenanthrene, 4b, 5,6,7,8,8a, 9,10-octahydro-4b - [(4-hydroxyphenyl) methyl] -7-pentylidene, [4bS- (4', 7Z, 8a)] - , mass: 377 (M + 1)⁺.</td>

Examples 430-432

The title compounds of Examples 430-432 were prepared by methods similar to those described above in Example 77.

<td>Example 430</td><td>2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxy-phenyl) methyl] - O- (phenylmethyl) oxime, (4aS- cis) - mass: 428 (M + 1)⁺.</td>

<td>Example 431</td><td>2 (1 H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxy-phenyl) methyl] -2,2-propenyloxime, (4aS-cis ) - mass: 378 (M + 1)⁺.</td>

<td>Example 432</td><td>2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a - [(4-hydroxy-phenyl) methyl] -O-ethyloxime, (4aS-cis) - , mass: 366 (M + 1)⁺.</td>

<td>Example 433</td><td>2,7-phenanthridiol, 4a - [(3-aminophenyl) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-2-propyl-, (4aS, 10aS) -</td>

The title compound of this example was prepared by methods analogous to those described above in Example 136. Mass: 366 (M + 1)⁺.

Examples 434-435

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The title compounds of Examples 434-435 were prepared by methods analogous to the above described in Example 9.

Example 434 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -2- [3 - [(tetrahydro-2H-pyran- 2-yl) oxy] -1-propynyl] -, (4aS, 10aS) - mass: 481 (M + 18) *

Example 435 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -2- [3 - [(tetrahydro-2H-pyran- 2-yl) oxy] -1-propynyl] -, (4aS, 1 OaS) - mass: 481 (M + 18) *.

Examples 436-438

The title compounds of Examples 436-438 were prepared by methods analogous to peaks described above in Example 136.

Example 436 2,7-phenanthridiol, 2-butyl-1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -, (4aS, 10aS) - mass: 380 (M).

Example 437 2,7-phenanthridiol, 2-butyl-1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -, (4aS, 10aS) - mass : 381 (M + 1)⁺.

Example 438 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[3 - [(1-methyl-4-piperidinyl) amino] phenyl] methyl] -2-propyl -, (4aS, 10aR) - mass: 463 (M + 1)⁺.

Example 439 2,7-Phenanthridol, 4a - [(3-aminophenyl) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -, (4aS, 10aR) The title compound of this example was prepared by methods analogous to peaks described above in Example 9. Mass: 362 (M + 1)⁺.

Examples 440-442

The title compound according to Examples 440-442 was prepared by methods similar to those described in Example 136.

Example 440 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[3- (methylamino) phenyl] methyl] -2-propyl, (4aS, 1 OaS) - mass: 380 (M + 1)⁺.

Example 441 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[3 - [(1-methylethyl) amino] phenyl] methyl] -2-propyl- ( 4aS, 10aR) - mass: 408 (M + 1f.

Example 442 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[3 - [(1-methylethyl) amino] -phenyl] methyl] -2-propyl- , (4aS, 10aR) - mass: 408 (M + 1)⁺.

Examples 443-444

The title compounds according to Examples 443-444 were prepared by methods analogous to peaks described above in Example 9.

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Example 443 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[3 - [(1-methylethyl) amino] phenyl] methyl] -2- (1- propynyl) -, (4aS, 10aS) - mass: 404 (M + 1)⁺.

Example 444 2,7-phenanthridiol, 2-ethynyl-1,2,3,4,4a, 9,10,10a-octahydro-4a - [[3 - [(methylethyl) amino] phenyl] methyl] -, (4aS , 10aS) - mass: 390 (M + 1)⁺.

Example 445 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4 - [(methylsulfonyl) oxy] phenyl] methyl] -2-propyl-, (4aS , 10aS) The title compound of this example was prepared by methods analogous to those described above in Example 77.

Example 446 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a- (phenylmethyl), O-ethyloxime, (4aS-trans) - mass: 350 (M +1)⁺.

Example 447 2 (1H) -phenantrenone, 3,4,4a, 9,10,10a-hexahydro-7-hydroxy-4a- (phenylmethyl), O-ethyloxime, (4aS-trans) - mass: 350 (M +1)⁺.

Examples 448-449

The title compounds of Examples 448-449 were prepared by methods analogous to those described above in Example 9.

Example 448 2 (1H) -phenantrenone, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (2-pyridinylethynyl) -, (4aS, 10aR) - mass : 410 (M + 1)⁺.

Example 449 2 (1H) -phenantrenone, 4a - [[3- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a octahydro-2- (1-propynyl) -, (4aS , 10aR) - mass: 390 (M + 1)⁺.

Example 450 2-Phenanthenol, 4b - [[3- (dimethylamino) phenyl] methyl] -7,7-diethoxy-4b, 5,6,7,8,8a, 9,10-octahydro, (4bS-trans) Titile compound according to this example was produced by methods analogous to those described above in production 5. Mass: 424 (M + 1)⁺.

Example 451 2-Phenanthenol, 7,7-Diethoxy-4b, 5,6,7,8,8a, 9,10-octahydro-4b- (phenylmethyl) - (4bS-trans) The title compound of this example was prepared by methods which are analogous to those described above in Example 77. Mass: 335 (M-45)⁺.

Example 452 2,7-phenanthridiol, 2- [3- (dimethylamino) -1-propynyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, (4aS , 10aR) The title compound of this example was prepared by methods analogous to those described above in Example 9. Mass: 393 (M + 1)⁺.

Examples 454-456

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The title compounds of Examples 454-456 were prepared with afiferfium analogous peams described above in Example 136.

Example 454 2,7-phenanthridiol, 4a - [(4-aminophenyl) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-2-propyl-, (4aS, 10aS) - mass: 348 (M-17)⁺.

Example 455 acetamide, N- [4 - [(1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2-propyl-4a (2H) -phenanthrenyl) methyl] phenyl] -, (4aS , 10aS) - mass: 407 (M).

Example 456 acetamide, N- [3 - [[2- (acetyloxy) -1,3,4,9,10,10a-hexahydro-7-hydroxy-2-propyl-4a (2H) -phenanthrenyl] methyl] phenyl] -, (4aS, 10aS) - mass: 450 (M + 1)⁺.

Example 457 2,7-phenanthridol, 4a - [[4- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a octahydro-2- (1-propynyl) -, (4aS, 10aR) The title compound of this example was prepared by methods similar to those described above in Example 9. Mass: 390 (M + 1)⁺.

Example 458 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4 - [(1-methylethyl) amino] -phenyl] methyl] -2-propyl- , (4aS, 10aS) The title compound of this example was prepared by dissociation analogous to those described in Example 136. Mass: 408 (M + 1f.

Example 459 Carbamic acid, dimethyl, 7- (chloroethynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -2-phenanthrenyl ester, (4bS, 8aR) The title compound according to This example was prepared by methods analogous to peaks described above in Example 58. Mass: 438 (M + 1)⁺.

Example 460 Acetamide, N- [3 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methyl] phenyl] -, [2R- (23,4aa, 10aβ)] -,

The title compound according to this example was prepared with fragments similar to those described above from Example 9. Mass: 386 (M-17)⁺.

Example 461 1-Pyrrolidinecarboxylic acid, 7- (chloroethynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -2-phenanthrenyl ester, (4bS, 8aR) The title compound according to this an example was prepared with fragments similar to those described above in Example 85. Mass: 464 (M).

Examples 462-465

The title compounds according to the examples were prepared with the fragments similar to the peams described above in Example 136.

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Example 462 cyanamide, [3 - [(1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2-propyl-4a (2H) -phenanthrenyl) methyl] phenyl] -, (4aS, 10aS ) - mass: 389 (M-1)⁺.

Example 463 cyanamide, [3 - [(1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2-propyl-4a (2H) -phenanthrenyl) methyl] phenyl] -, (4aS, 10aS ) - mass: 389 (M-1)⁺.

Example 464 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2-propyl-4a - [[3 - (tetrahydro-2H-pyran-4-yl) amino] phenyl ] methyl] -, (4aS, 10aS) - mass: 450 (M + 1)⁺.

Example 465 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2-propyl-4a - [[3 - (tetrahydro-2H-pyran-4-yl) amino] phenyl ] methyl] -, (4aS, 10aS) - mass: 450 (M + 1)⁺.

Example 466 carbamic acid, dimethyl, 4 - [[7 - [[(dimethylamino) carbonyl] oxy] -1,3,4,9,10,10a-hexahydro-2-hydroxy-2-propyl-4a (2H) -phenadrenyl] methyl] phenyl ester, (4aS, 10aS) The title compound of this example was prepared by methods analogous to those described above in Example 58. Mass: 526 (M + 18)⁺.

Example 467 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [[4 - [(1-methylethyl) amino] -phenyl] methyl] -2-propyl- , (4aS, 10aS) The title compound of this example was prepared by analogous procedures described in Example 136. Mass: 408 (M + 1)⁺.

Example 468 2 (1H) -phenantrenone, 4a - [(3-aminophenyl) methyl] -3,4,4a, 9,10,10a-hexahydro-7-hydroxy, O-ethyloxime, (4aS-trans) The title compound according to This example was prepared by analogous procedures described in Example 77. Mass: 365 (M + 1)⁺.

Example 469 carbamic acid, dimethyl, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b - [[4 - [(1-methylethyl) amino] phenyl] methyl] -7- propyl-2-phenanthrenyl ester, (4bS, 8aS) The title compound of this example was prepared by analogy to those described in Example 58. Mass: 479 (M + 1)⁺.

Example 470 2-Phenanthenol, 4b - [(3-aminophenyl) methyl] -7- (ethoxyamino) -4b, 5,6,7,8,8a, 9,10 octahydro-, (4bS, 8aR) The title compound of this example was prepared by methods analogous to those described in Example 10. Mass: 367 (M + 1)⁺.

Examples 471-472

The title compounds of Examples 471-472 were prepared by methods similar to those described in Example 58.

159

Example 471 carbamic acid, dimethyl, 4b - [(3-aminophenyl) methyl] -7- (ethoxyimino) 4b, 5,6,7,8,8a, 9,10-octahydro-2-phenanthrenyl ester, (4aS-trans) - mass: 436 (M + 1)⁺.

Example 472 carbamic acid, dimethyl, 4b - [[3 - [[(dimethylamino) carbonyl] amino] phenyl] methyl] -7- (ethoxyimino) -4b, 5,6,7,8,8a, 9,10-octahydro -2-phenanthrenyl ester, (4aS-trans) - mass: 407 (M + 1)⁺.

Example 473 2,7-phenanthridol, 4a - [[4- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a octahydro-2- (1-propynyl) -, (4aS, 10aS) The title compound of this example was prepared by methods analogous to those described above in Example 9. Mass: 390 (M + 1)⁺.

Example 474 carbamic acid, dimethyl, 4b - [[4- (dimethylamino) phenyl] methyl] 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1-propynyl) 2-phenanthrenyl ester, (4bS-8aR) The title compound of this example was prepared with similarities to those described in Example 58. Mass: 461 (M + 1)⁺.

Example 475 2-Phenanthenol, 4b - [[3- (dimethylamino) phenyl] methyl] -7- (ethylamino) -4b, 5,6,7,8,8a, 9,10-octahydro-, (4bS, 8aS) The title compound of this example was prepared by methods similar to those described above in Producer 4. Mass: 379 (M + 1)⁺.

Example 476 acetamid, N- [4a - [[3- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a-octahydro-7-hydroxy-3-phenanthrenyl] -N- ethyl), (4aR, 10aS) The title compound of this example was prepared with the procedures similar to those described above in Example 47. Mass: 421 (M + 1)⁺.

Example 477 acetamide, N- [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methyl] phenyl] - (4aS, 1aRa) The title compound of this Example was prepared by conducting the above-described peams described above. Example 9. Mass: 404 (M + 1)⁺.

Case 478-479

The title compounds of Examples 478-479 were prepared with conductors which are oblique peams as described above in Example 58.

Example 478 1-piperazinecarboxylic acid, 4-methyl-, 4b - [[3- (dimethylamino) phenyl] methyl] 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1 -propynyl) -2-phenanthrenester, (4bS, 8aR) - mass: 516 (M + 1)⁺.

43

160

Example 479 2,7-Phenantrendiol, 4a - [[3- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) carbamate, (4aS, 10aR) - mass: 433 (M + 1)⁺.

EXAMPLE 480 4-Morpholinecarboxamide [N-, 4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methyl] phenyl] - [2R- (23,4aa, 10aP)] - The title compound of this example was prepared by analogous procedures described in Example 9. Mass: 476 (M + 2)⁺.

Example 481 carbamic acid, [3- (dimethylamino) propyl], 4b - [[3- (dimethylamino) phenyl] methyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy- 7- (1-propynyl) -2-phenanthrenyl ester, (4bS, 8aR) The title compound of this example was prepared by analogy to those described in Example 59. Mass: 518 (M + 1)⁺

Example 482 acetamide, N- [4 - [[7 - [(aminocarbonyl) oxy] -1,3,4,9,10,10a-hexahydro-2-hydroxy-2- (1-propynyl) -4a (2H) -phenadrenyl] methyl] phenyl] - (4aS, 10aR) The title compound of this example was prepared by methods similar to those described above in Example 55. Mass: 447 (M + 1)⁺.

Example 483 Benzonitrile, 4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2-propyl-4a (2H) -phenanthrenyl] methyl] - (4aS, 10aS) The title compound corresponds This example was prepared by methods analogous to those described in Example 136. Mass: 375 (M).

Examples 484-487

The title compounds of these examples were prepared by methods analogous to those described above in Example 136. Mass: 375 (M).

Example 484 carbamic acid, [2- (1-pyrrolidinyl) ethyl] - 4b - [[3- (dimethylamino) phenyl] methyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy -7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] - mass. 530 (M + 1)⁺.

Example 485 1-piperidinecarboxylic acid, 4- (dimethylamino), 4b - [[3- (dimethylamino) phenyl] methyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7 - (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)] - mass: 544 (M + 1f.

Example 486 1-piperazinecarboxylic acid, 4-acetyl-, 4b - [[3- (dimethylamino) phenyl] methyl] 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (1 -propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)], mass: 544 (M + 1)⁺.

Example 487 2,7-Phenantrendiol, 4a - [[3- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a-octahydro-2- (1-propynyl) -7 - (methylcarbamate), [2R- (23,4aa, 10aP)] - mass:

447 (M + 1)⁺.

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Examples 488-489

The title compounds of Examples 488-489 were prepared by methods analogous to those described above in Example 6.

<td>Example 488</td><td>2 (1H) -phenantrenone, 4a - [[3- (dimethylamino) phenyl] methyl] -3,4,4a, 9,10,10a-hexahydro-7-hydroxy-, (4aS-trans) - mass: 350 (M + 1)⁺.</td>

<td>Case 489</td><td>carbamic acid, [4 - ((1,3,4,9,10,10a-hexahydro-7-hydroxy-2-oxo-4a (2H) phenanthrenyl) methyl] phenyl] -1,1-dimethylethyl ester, (4aS- trans) - mass: 423 (M + 2f.</td>

<td>Case 490</td><td>4-thiazol-3-yl, 4b - [[3- hydroxy-7- (1-propynyl) -2-fenantrenýlester, (4BS, 8aR) -</td>

The title compound of this example was prepared by means of coagulants analogous to peaks described above in Example 59. Mass: 500 (M + 1)⁺.

Example 491 2,7-Phenantrendiol, 4a - [[3- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a octahydro-2-propyl- [2R- (2α, 4aα, 10αα )] The title compound of this example was prepared by means of buffering agents which are as described above in Example 136. Mass: 395 (M + 2)⁺.

Daemi 492-495

The title compounds of Examples 492-495 were prepared by means of supernatants which are as described above in Example 9.

<td>Example 492</td><td>2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a - [(4-hydroxyphenyl) methyl] -</td>

<td>Example 493</td><td>2- (1-propynyl) -, [2R- (23,4aa, 10aα)] - mass: 362 (M). glycine, N- [3 - [[1,3,4,9,10,10a-hexahydro-2-hydroxy-7- (2-methoxy-2-oxoethoxy) -2- (1-propynyl) -4a (2H ) -phenantrenyl] methyl] phenyl] -N-methyl, methyl ester, [2R- (2,4,4a, 10aP)] - mass: 521 (M + 2)⁺.</td>

<td>Example 494</td><td>glycine, N- [3 - [[1,3,4,9,10,10a-hexahydro-2-hydroxy-7- (2-methoxy-2-oxoethoxy) 2- (1-propynyl) -4a (2H) -phenadrenyl] methyl] phenyl] -N- (2-methoxy-2-oxoethyl), methyl ester, [2R- (2,4,4a, 10aβ)], mass: 579 (M + 2)⁺</td>

<td>Case 495</td><td>urea, N- [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H)</td>

<td>Case 496</td><td>phenanthrenyl] methyl] phenyl] -N, N-dimethyl- [2R- (23,4aα, 10aβ) E mass: 435 (M + 2)⁺. acetamide, 2 - [[3 - [[7- (2-amino-2-oxoethoxy) -1,3,4,9,10,10a-hexahydro-2-hydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methyl] phenyl] methylamino] - [2R (2R, 4aα, 10aβ)] -</td>

162

The title compound of this example was prepared by methods analogous to those described above in Example 55. Mass: 491 (M + 2)⁺.

Examples 497-499

The title compounds of Examples 497-499 were prepared by methods similar to those described above in Example 9.

Example 497 Methanesulphonamide, N- [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methyl] phenyl] -, [2R- (2a, 4aa, 1 Oap)] - mass: 442 (M + 3f.

Example 498 acetamide, N- [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methyl] phenyl] -, [2R- (2α, 4αα, WaP)] - mass: 404 (M + 1)⁺.

Example 499 acetamide, N- [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methyl] phenyl] -, [2R- (2α, 4αα, 10αβ)] - mass: 404 (M + 1 f.

Example 500 carbamic acid, [2- (1-pyrrolidinyl) ethyl] -, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propylphenyl) ) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] -,

The title compound of this example was prepared by methods analogous to those described above in Example 59. Mass: 470 (M-16)⁺.

Example 501 2-Pyridinecarboxamide, N- [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenadrenylmethylphenyl] [2R- (2R, 4aα, 1αβ)] The title compound of this example was prepared by methods analogous to those described above in Example 9. Mass: 434 (M-32)⁺.

Example 502 carbamic acid, [2- (1-pyrrolidinyl) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) 2-phenanthrenyl ester, monohydrochloride, [4bS- (4ba, 7a, 8ap)] The title compound of this example was prepared by methods similar to those described above in Example 59. Mass: 506 (M-17)⁺.

Example 503 5-Isoxazolecarboxamide, N- [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methylphenyl] - [2R- (2α, 4αα, 1βββ)] - The title compound of this example was prepared by methods analogous to those described above in Example 9. Mass: 459 (M + 3)⁺.

Example 504 acetamide, 2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] -, [4bS- (4ba, 7a, 8aP)] 2743

163

The title compound of this example was prepared by the procedures described above in Example 55. Mass: 404 (M + 1)⁺.

Example 505 1 (2H) -pyridinecetamide, N- [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl ] methyl] phenyl] -3,4-dihydro-5-methyl-2,4-dioxo-, [2R- (2a, 4aα, 10a3)] The title compound of this example was prepared by means of hardened peams described herein above in Example 9. Mass: 546 (M + 18)⁺.

Example 506 carbamic acid, dimethyl, 2 - [[7 - [[(dimethylamino) carbonyl] oxy] -4b - [[3- (dimethylamino) phenyl] methyl] -4b, 5,6,7,8,8a, 9, 10-octahydro-7- (1-propynyl) -2-phenylnitrile] oxyethyl ester, [4bS- (4b, 7a, 8a0)] The title compound of this example was prepared by means of hardened peams described above in Example 59. Mass: 576 (M + 1)⁺.

Example 507 acetamide, N- [2- (dimethylamino) ethyl] -2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- ( 1-propynyl) -2-phenanthrenyl] oxy] - [4bS- (4ba, 7a, 8aβ)] The title compound of this Example was prepared by the procedures described in Table 244 above. Mass: 476 M + 2)⁺.

Case 508-511

The title compounds according to Examples 508-511 were prepared by methods described in the above paragraph 59.

Example 508 carbamic acid, [3- (dimethylamino) propyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) 2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)], mass: 457 (M-17)⁺.

Example 509 carbamic acid, dimethyl, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -2,7-phenanthrenedioyl ester, [2R- (23 , 4aa, 10aP)] - mass: 489 (M + 1f.

Example 510 carbamic acid, [2- (4-morpholinyl) ethyl] -, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl ) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)], mass: 485 (M-17)⁺.

Example 511 carbamic acid, [3- (1H-imidazol-1-yl) propyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7 - (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)], mass: 498 (M + 1)⁺.

Example 512 acetic acid, [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] methyl ester, [4bS- (4ba, 7a? aP)] 2743

164

The title compound of this example was prepared by means of buffers which are peeled peams which are described herein as above in Example 54. Mass: 418 (M).

Example 513 1H-imidazole-4-sulfonamide, N- [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) - phenanthrenyl] methyl] phenyl] -1-methyl- [2R- (2a, 4aα, 10aβ)] The title compound of this example was prepared by means of supernatants which are as described above above. Mass: 523 (M +18)⁺.

Example 514 acetamide, N- [2- (4-morpholinyl) ethyl] -2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7 - (1-propynyl) -2-phenanthrenyl] oxy] - [4bS- (4ba, 7a, 8aβ)] The title compound of this example was prepared by means of supernatants which are described as above in section 244. Mass: 517 (M + 1)⁺.

Example 515 acetamide, 2,2 '- [[1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -2,7-phenanthridyl] bis (oxy)] bis- [2R- (2,4,4a, 10aβ)] The title compound of this Example was prepared by means of buffers which are sublimated peams described in Example 55. Mass: 459 (M-1)⁺.

Example 516 acetamide, N- [3- (1H-imidazol-1-yl) propyl] -2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] - [4bS- (4ba, 7a, 8aβ)] The title compound of this Example was prepared by subdivisions which are peeled peel described above. Example 244, Mass: 512 (M + 1)⁺.

Example 517 carbamic acid, [2- (dimethylamino) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) 2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aβ)] The title compound of this example was prepared by means of supernatants which are peeled peel described herein above in Example 59. Mass: 461 (M + 1)⁺.

Example 518 carbamic acid, [2- (dimethylamino) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) 2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] - HCl

The title compound according to this invention is HCl salt of the title product 517. Mass: 498 (M + 1)⁺.

Case 519-523

The title compoundes of Examples 519-523 were prepared by means of breakers which are peeled peels described hereinabove above in Example 244.

165

Example 519 acetamide, 2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] -N- [2- (3-pyridinyl) ethyl] -, [4bS- (4-methoxy) mass: 509 (M + 1)⁺.

Example 520 piperazine, 1-methyl-4 - [[[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2- phenanthrenyl] oxy] acetyl] -, [4bS- (4ba, 7a, 8aP)] - mass: 487 (M + 1)⁺.

Example 521 acetate, N- [3- (4-methyl-1-piperazinyl) propyl] -2 - [[4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] -, [4bS- (4ba, 7a, 8ap)] - mass: 544 (M + 1)⁺

Example 522 piperidine, 1 - [[[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy ] acetyl] -4- (1-pyrrolidinyl) -, [4bS- (4ba, 7a, 8a3)] - mass: 541 (M + 1)⁺.

Example 523 acetamide, N-methoxy-2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl ] oxy] -, [4bS- (4tD, 7.alpha.)], mass: 432 (M-1)⁺.

Example 524 2-Phenanthenol, 7 - [(4,5-Dihydro-1H-imidazol-2-yl) methoxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl ) -2- (1-propynyl) -, [2R- (2a, 4aα, 10aα)] - The title compound of this example was prepared by methods analogous to those described above in Example 74. Mass: 429 (M +1)⁺

Examples 525-526

The title compounds of Examples 525-526 were prepared by methods similar to those described above in Example 59.

Example 525 carbamic acid, [3- (1-pyrrolidinyl) propyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl ) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8a6)], mass: 501 (M + 1)⁺.

Example 526 acetamide, N-hydroxy-2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl ] oxy] - [4bS- (4ba, 7a, 8aP)] - mass: 418 (M-1)⁺.

Examples 527-528

The title compounds of Examples 527-528 were prepared by methods analogous to those described above in Example 67.

Example 527 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- [2- (1-pyrrolidinyl) ethoxy] - mass: 444 (M + 1)⁺; disappear according to the title compound of Example 528.

166

Example 528 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- [2- (1-pyrrolidinyl) ethoxy] - mass: 444 (M + 1)⁺; disappear according to the title compound of Example 527.

Examples 529-535

The title compounds of Examples 529-535 were prepared by methods similar to those described above in Example 244.

<td>Example 529</td><td>acetamido, N- (methylsulfonyl) -2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-</td>

<td>Example 530</td><td>(phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] -, [4bS- (4ba, 7a, 8aP)] - mass: 480 (M-1)⁺. acetamide, 2 - [[4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] -N- 2-pyridinylmethyl) -, [4bS- (4ba, 7a, 8aP)] - mass: 495 (M + 1)⁺.</td>

<td>Example 531</td><td>acetamido, 2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propyl) -2-phenanthrenyl] oxy] -N- 3-pyridinylmethyl) - [4bS- (4ba, 7a, 8aP) j, mass: 495 (M + 1)⁺.</td>

<td>Example 532</td><td>acetamide, 2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-</td>

<td>Example 533</td><td>propynyl) -2-phenanthrenyl] oxy] -N-3-pyridinyl-, [4bS- (4ba, 7a, 8ap)] - mass: 481 (M + 1)⁺. acetamide, 2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-</td>

<td>Example 534</td><td>propanyl) -2-phenanthrenyl] oxy] -N-pyrazinyl-, [4bS- (4ba, 7a, 8aP)] - mass: 482 (M + 1)⁺. ethanimidamide, 2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-</td>

<td>Example 535</td><td>(1-propynyl) -2-phenanthrenyl] oxy] -, [4bS- (4ba, 7a, 8ap)] - mass: 403 (M + 1)⁺. carbamic acid, [2- (1-pyrrolidinyl) ethyl] - 4b - [[4- (acetylamino) phenyl] methyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy- 7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)], mass: 544 (M + 1)⁺.</td>

<td>Example 536</td><td>carbamothioic acid, dimethyl-, O- [4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] ester, [ 4bS- (4ba, 7a, 8aP) j</td>

The title compound according to this example was prepared with fragments similar to those described above in Example 59. Mass: 434 (M + 1)⁺.

Examples 537-538

The title compounds of Examples 537-538 were prepared with fraipherals which are protective agents described above in Example 74.

Example 537 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (2-pyrimidinyloxy) -, [2R- (23.4aa, 1 Oap)] - mass: 425 (M + 1) *.

167

Example 538 2-Phenanthenol, 7 - [[2-amino-6-methyl-4-pyrimidinyl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) 2- (1-propynyl) -, [2R- (23,4aa, 10ap)] - mass: 454 (M + 1)⁺.

Example 539 acetamide, N- [2- (1-methyl-2-pyrrolidinyl) ethyl] -2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- ( phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] -, [4bS- (4ba, 7a, 8aP)] The title compound of this example was prepared by methods analogous to those described above for an example 244. Mass: 515 (M + 1)⁺.

Example 540 carbamic acid, [2- (1-methyl-2-pyrrolidinyl) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- ( 1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] The title compound of this example was prepared by methods analogous to those described above in Example 59. Mass: 501 (M + 1)⁺.

Example 541 3-Pyridinecarboxamide, 6 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] - [4bS- (4ba, 7a, 8aP)] The title compound of this example was prepared by methods similar to those described above in Example 74. Mass: 467 (M + 1)⁺.

Example 542 carbamic acid, [2- (1-pyrrolidinyl) ethyl] -, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (2-propenyl) -7- (1 -propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] The title compound of this example was prepared by methods analogous to those described above in Example 59. Mass: 437 (M + 1)⁺.

Examples 543-544

The title compounds of Examples 543-544 were prepared by methods similar to those described above in Example 69.

Example 543 2-Phenanthenol, 7 - [[5- [2- (dimethylamino) ethyl] -1,2,4-oxadiazol-3-yl] methoxy] -1,2,3,4,4a, 9,10, 10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2R- (2a, 4aα, 10aβ)], mass: 500 (M + 1)⁺.

Example 544 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7 - [[5- (1-piperidinylmethyl) -1,2,4-oxadiazol- 3-yl] methoxy] -2- (1-propynyl) -, [2R- (2α, 4αα, 10αβ)] - mass: 526 (M + 1)⁺.

Example 545 2-Phenanthenol, 7 - [(4,6-dimethoxy-1,3,5-triazin-2-yl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a - (phenylmethyl) -2- (1-propynyl) -, [2R- (2α, 4αα, 10αβ)] 2743

168

The title compound according to this example was prepared by substituting coagulants which are the analogous peams described herein above in Example 74. Mass: 486 (M + 1)⁺.

Examples 546-547

The title compounds of the Examples were prepared by means of solid-state micronucleus described in Example 72.

Example 546 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7 - [[3- (1-piperidinylmethyl) -1,2,4-oxadiazol- 5-yl] methoxy] -2- (1-propynyl) -, [2R- (2α, 4αα, 10αβ)] - mass: 526 (M + 1)⁺.

Example 547 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7 - [[3- (2-pyridinyl) 1,2,4-oxadiazol-5-yl] methoxy] - [2R- (2q4aa, 10aP)] - mass: 506 (M + 1)⁺.

Examples 548-550

The title compounds of Examples 548-550 were prepared by means of coagulants which are the analogous peams described herein above in Example 59.

Example 548 carbamic acid, [2- (3-pyridinyl) ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl ) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)], mass: 495 (M + 1)⁺.

Example 549 carbamic acid, (2-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl ester , [4bS- (4ba, 7a, 8aP)], mass: 481 (M + 1)⁺.

Example 550 carbamic acid, [2- (2-pyridinyl) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl ) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)], mass: 495 (M + 1)⁺.

Example 551 2-Phenanthenol, 4b, 5,6,7,8,8a, 9,10-octahydro-4b-pentyl-7-propyl-, (4bR, 8aR) -Titile compound according to this example was prepared by analogue vectors peim which is described as described in Example 10. Mass: 313 (M-1)⁺.

Examples 552-553

The title compounds of Examples 552-553 were prepared by substituting supernatants described above in Example 59.

Example 552 carbamic acid, [2- (1-pyrrolidinyl) ethyl] -, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-propyl-7- (1-propynyl) 2-phenanthrenyl ester, [4bR- (4ba, 7a, 8aP)], mass: 439 (M + 1)⁺.

169

Example 553 carbamic acid, [2- (dimethylamino) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-propyl-7- (1-propynyl) -2- phenanthrenyl ester, [4bR- (4ba, 7a, 8aP)], mass: 413 (M + 1)⁺.

Example 554 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-propyl-2- (1-propynyl) -7 (pyrazinyloxy) -, [2R- (2b, 4α, 1-ol)] The title compound of this example was prepared by means of yields similar to those described in Example 74. Mass: 377 (M + 1)⁺.

Example 555 carbamic acid, (1 H -tetrasol-5-ylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl ) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8ap)] The title compound according to this example was prepared by means of extractors analogous to those described above in Example 59. Mass: 470 (M-1)⁺.

Example 556 2-Phenanthenol, 7 - [(4-chloro-2-pyrimidinyl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1- propynyl) -, [2R- (2 R, 4aα, 10aβ)] The title compound of this example was prepared by means of extractors analogous to those described above in Example 74. Mass: 460 (M + 1)⁺.

Examples 557-558

The title compounds of Examples 557-558 were prepared by means of yields similar to those described above in Example 72.

Example 557 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [[3- (1-piperidinylmethyl) 1,2,4-oxadiazol-5-yl] methoxy] 4a-propyl-2- (1-propynyl) -, [2R- (23,4aα, 10aβ)], mass: 478 (M + 1)⁺.

Example 558 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-propyl-2- (1-propynyl) -7 - [[3- (2-pyridinyl) -1, 2,4-oxadiazol-5-yl] methoxy] - [2R- (23,4aa, 1θβ)] - mass: 458 (M + 1)⁺.

Examples 559-561

The title compounds of Examples 559-561 were prepared by yielding the analogues described above in Example 59.

Example 559 carbamic acid, (4-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl ester , [4bS- (4ba, 7a, 8aP)], mass: 481 (M + 1)⁺.

170

<td>Example 560</td><td>carbamic acid, (3-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] - mass: 481 (M + 1)⁺.</td>

<td>Example 561</td><td>carbamic acid, (3-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy4b-propyl-7- (1-propynyl) -2-phenanthrenyl ester, [4bR- (4ba , 7a, 8aP)] - mass: 433 (M + 1)⁺.</td>

<td>Example 562</td><td>2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(5-methoxy-2-pyrimidinyl) oxy] -4a- (phenylmethyl) -2- (1-propynyl ) -, [2R- (2α, 4αα, 10αβ)] -</td>

The title compound of this example was prepared by methods analogous to those described above in Example 74. Mass: 455 (M + 1)⁺.

Example 563 Morpholine, 4 - [[6 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2- phenanthrenyl] oxy] -3-pyridinyl] carbonyl] - [4bS- (4ba, 7a, 8aβ)] The title compound of this example was prepared by methods analogous to those described above in Example 244. Mass: 537 M + 1)⁺.

Examples 564-565

The title compounds of Examples 564-565 were prepared by methods analogous to those described above in Example 59.

<td>Example 564</td><td>carbamic acid, (2-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy4b-propyl-7- (1-propynyl) -2-phenanthrenyl ester, [4bR- (4ba , 7a, 8aP)] - mass: 433 (M + 1)⁺.</td>

<td>Example 565</td><td>carbamic acid, (4-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy4b-propyl-7- (1-propynyl) -2-phenanthrenyl ester, [4bR- (4ba , 7a, 8ap)] - mass: 433 (M + 1)⁺.</td>

<td>Example 566</td><td>2-phenanthrene, 7 - [(5-amino-1H-1,2,4-triazol-3-yl) methoxy] 1,2,3,4,4a, 9,10,10a-octahydro-4a-propyl -2- (1-propynyl) -, [2R- (2α, 4α, 10αβ)] -</td>

The title compound of this example was prepared by methods analogous to those described above in Example 62.

Examples 567-568

The title compounds of Examples 567-568 were prepared by analogy analogous to those described above in Example 76. Mass: 395 (M + 1)⁺.

Example 567 pyridine, 3,3 '- [[1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) 2,7-phenanthridyl] bis oxymethylene)] bis-, [2R- (2zi, 4aα, 10aβ)], mass: 529 (M + 1f.

171

Example 568 pyridine, 4,4 '- [[1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) 2,7-phenanthenediyl] bis oxymethylene)] bis, [2R- (23,4aα, 10aβ)], mass: 529 (M + 1)⁺.

Example 569 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (4-pyridinylmethoxy) -, [2R- (2j4ac (10 $)]

The title compound was obtained as described in Example 76, with the exception of 4-picolyl chloride hydrogen chloride was used in the city for 3-picolyl chloride hydrochloride. MS m / z 438 (M + H

Example 570 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2-propyl- [2R- (2,4,4a, 10aα)] The title compound of this example was produced with behaviors that are oblique peams described above in Example 10. Mass: 313 (M-17)⁺.

Example 571 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2- (1-propynyl) -7- (pyrazinyloxy) -, [2R- (2J, 4ax10) $)]

The title compound of this example was prepared by conductive techniques described hereinabove 74. Mass: 405 (M + 1)⁺.

Example 572 carbamic acid, [2- (1-pyrrolidinyl) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-pentyl-7- (1-propynyl) 2-phenanthrenyl ester, [4bR- (4ba, 7a, 8aP)] The title compound of this Example was prepared by the procedures described in Example 59 above. Mass: 467 (M + 1)⁺.

Example 573 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-propyl-2- (1-propynyl) -7- (4-pyridinylmethoxy) -, [2R- (2ylan 10 $)]

The title compound of this Example was prepared by conducting the above-described peaks described in Example 76. Mass: 390 (M + 1)⁺.

Example 574 carbamic acid, [2- (4-pyridinyl) ethyl], 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl ) -2-phenanthrenyl ester, [4bS- (4ba, 7a, 8aP)] The title compound of this Example was prepared by the procedures described in Example 59 above. Mass: 495 (M + 1)⁺.

Example 575 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2- (1-propynyl) -7- (2-pyridylmethylmethoxy) -, [2R To a solution of 50 mg of the title compound of Example 252 and 9.2 mg of 60% NaH in 2 mL of anhydrous DMF was added 30 mg of 2-picolyl chloride hydrochloride at room temperature under N₂air overnight. Hvarfid was backed by NH₄CI (mettudu), extracted with EtOAc (X3), pvegid

172 with brine, dried over Na₂SO₄, beat and coalesce until dry. Purification by preparation of TLC SiO₂ using 4% MeOH in CH₂Cl₂ as eluant gave 40 mg (65%) of the title product according to this example as a white gaseous powder. Mass: 419 (M + 2)⁺.

Examples 576-577

The title compounds of Examples 576-577 were prepared with conductivity peaks described above in Example 244.

<td>Case 576</td><td>acetamid, 2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] -N - [2- (4-pyridinyl) ethyl] - (4bS- (4ba, 7a, 8aP)] - mass: 509 (M + 1)⁺.</td>

<td>Case 577</td><td>acetamide, 2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] -N- [2- (2-pyridinyl) ethyl] - (4bS- (4ba, 7a, 8aP)] - mass: 509 (M + 1)⁺.</td>

<td>Example 578</td><td>2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) 7- (2-pyridylmethylmethoxy) -, [2R- (2i , 4aG 0 $]</td>

The title compound was obtained as described in Example 76 with the exception of 2-picolyl chloride hydrochloride was used in the city for 3-picolyl chloride hydrochloride. MS m / z 438 (M + H)⁺.

Examples 579-580

The title compound according to Examples 579-580 was prepared by methods of oblique peel described above in Example 59.

<td>Case 579</td><td>carbamic acid, [2- (2-pyridinyl) ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-pentyl-7- (1-propynyl) -2- phenanthrenyl ester, (4bR- (4ba, 7a, 8aP)] - mass: 476 (M + 2)⁺.</td>

<td>Example 580</td><td>carbamic acid, [2- (4-morpholinyl) ethyl] -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-pentyl-7- (1-propynyl) -2- phenanthrenyl ester, (4bR- (4ba, 7a, 8a (3)] - mass: 483 (M + 1)⁺.</td>

<td>Example 581</td><td>2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-7- [2- (4-morpholinyl) ethoxy] -4a (phenylmethyl) -2- (1-propynyl) 2 R- (2b, 4aa, 1 Oap)] -</td>

The title compound of this Example was prepared by the methods described in Table 6 above. Mass: 460 (M + 1)⁺.

Example 582 2-Phenanthenol, 7 - ((2,6-dimethoxy-4-pyrimidinyl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- ( 1-propynyl) -, [2R- (2α, 4αα, 1αββ)] 2743

173

Title compound according to this example was prepared by means of extractors analogous to those described herein above in Example 74. Mass: 485 (M + 1f.

Examples 583-584

The title compound according to Examples 583-584 was prepared by eluent analogs similar to those described above in Example 59.

Example 583 carbamic acid, (4-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-pentyl-7- (1-propynyl) -2-phenanthrenyl ester, [ 4bR- (4ba, 7a, δθβ)], mass: 461 (M + 1)⁺.

Example 584 carbamic acid, (3-pyridinylmethyl), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-pentyl-7- (1-propynyl) -2-phenanthrenyl ester, [ 4bR- (4ba, 7a, 8aP)] - mass: 461 (M + 1)⁺.

Examples 585-588

The title compound according to Examples 585-588 was prepared by means of yields similar to those described hereinabove above in Example 75.

Example 585 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7 - [[3- (1-pyrrolidinyl) pyrazolyl ] oxy] -, [2R- (2α, 4αα, 1αα)], mass: 494 (M + 1)⁺.

Example 586 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7 - [[6- (1-pyrrolidinyl) - 4-pyrimidinyl] oxy] - [2R- (2,4,4a, 10aP)] - mass: 494 (M + 1)⁺.

Example 587 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7 - [[6- (1-pyrrolidinyl) - 2-pyridinyl] oxy] - [2R- (2a, 4aα, 10a, 3β), mass: 493 (M + 1)⁺.

Example 588 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7 - [[6- (1-pyrrolidinyl) pyrazinyl ] oxy] - [2R- (2α, 4αα, 10αβ)] - mass: 494 (M + 1)⁺

Example 589 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (pyrazinylmethoxy) -, [2R- (2a , 4aα, 10β)] The title compound of this example was prepared by means of yields analogous to those described herein above in Example 74. Mass: 439 (M + 1)⁺.

Examples 590-591

The title compound according to Examples 590-591 was prepared by means of yields similar to those described herein above in Example 67.

Example 590 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- [2- (1-piperazinyl) ethoxy] -2- (1-propynyl) [2R- (2α, 4αα, 10αβ)] - mass: 459 (M + 1)⁺.

174

Example 591 piperazine, 1-acetyl-4- [2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] ethyl] -, [4bS- (4ba, 7a, 8aP)] - mass: 501 (M + 1f.

Example 592 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2- (1-propynyl) -7- (2-pyrimidinylloxy) -, [2R- (2x4a α, ΙΟθβ)] The title compound of this example was prepared by analogous peams described above in Example 74. Mass: 405 (M + 1)⁺.

Example 593 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2- (1-propynyl) -7 (pyrazinylmethoxy) -, [2R- (2S, 4aα, 10ap)] The title compound of this example was prepared by methods analogous to the above described in Example 76. Mass: 419 (M + 1)⁺.

Example 594 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2- (1-propynyl) -7- (3-pyridylmethoxy) -, [2R- (2a, 4aα, 10aβ)] The title compound was obtained as described in Example 575 with the exception that 3-picolyl chloride hydrogen chloride was used in place of 2-picolyl chloride hydrochloride. Mass: 418 (M + 1)⁺.

Example 595 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2- (1-propynyl) -7- (4-pyridinylmethoxy) -, [2R- (2i , 4an, $ 10)]

The title compound was obtained as described in Example 575, with the exception that 4-picolyl chloride hydrogen chloride was used in the presence of 2-picolyl chloride hydrochloride. Mass: 418 (M + 1)⁺.

Examples 596-597

The title compounds of Examples 596-597 were prepared with afiferfium analogous peams described above in Example 67.

Example 596 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- [2- [4- (2-pyrimidinyl) ) -1-piperazinyl] ethoxy] -, [2R- (2a, 4aα, 10β)] - mass; 537 (M + 1)⁺.

Example 597 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- [2- (4-pyridinylamino) ethoxy] - mass: 467 (M + 1)⁺, disappear according to the title compound of Example 598.

Example 598 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- [2- (4-pyridinylamino) ethoxy] - mass: 467 (M + 1)⁺, disappearing according to the title compound of Example 597.

175

Example 599 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7- [2- (4-morpholinyl) ethoxy] -4a-pentyl-2- (1-propynyl) [2R- (2a, 4aα, 10aO)] - mass: 441 (M + 2)⁺.

Examples 600-601

The title compounds of Examples 600-601 were prepared by methods similar to those described in Example 76.

Example 600 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2- (1-propynyl) -7- (5-pyrimidinylmethoxy) -, [2R- (2q4aa) , 1050)] - mass: 419 (M + 1)⁺.

Example 601 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (4-pyrimidinylmethoxy) -, [2R- (2u, 4aa, 10ap)] - mass: 439 (M + 1)⁺.

Examples 602-603

The title compounds of Examples 602-603 were prepared by methods similar to those described in Example 75.

Example 602 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7 - [[2- (1-pyrrolidinyl) - 4-pyridinyl] methoxy] - [2R- (23,4aa, 10aP)] - mass: 507 (M + 1)⁺.

Example 603 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2- (1-propynyl) -7 - [[6- (1-pyrrolidinyl) -3- pyridinyl] methoxy] - [2R- (2a, 4aα, 10a3) E mass: 487 (M + 1)⁺.

Example 604 2-Phenanthrenecarbonitrile, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b-pentyl-7 (1-propynyl) -, [4bR- (4ba, 7aαp)] The title compound according to this example, was prepared by methods analogous to those described above in Example 15. Mass: 335 (M).

Example 605 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7- [2- (4-morpholinyl) ethoxy] -4a- (phenylmethyl) -2-propyl-, [2R - (2x4aa, 10ap)] The title compound of this example was prepared by analogy to those described above in Example 67. Mass: 464 (M + 1)⁺.

Example 606 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7- [2- (4-morpholinyl) ethoxy] -4a- (phenylmethyl) -2-propyl-, [2R - (2a, 4α, 10aβ)] - HCl

The title product of this example is the HCl salt of the title product of Example 605. Mass: 464 (M + 1-HCl) *.

Example 607 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-7- [2- (4-morpholinyl) ethoxy] -2,4-dipropyl-, [2R- (2,3,4a, 1Oa0)] 2743

176

The title compound of this example was prepared by methods analogous to those described above in Example 67. Mass: 416 (M + 1)⁺.

Examples 608-609

The title compounds of Examples 608-609 were prepared by methods similar to those described above in Example 76.

Example 608 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-7- (2-piperidinylmethoxy) -2-propyl, [2R- (2a, 4aα, 10a3) ] - mass: 428 (M + 1)⁺.

Example 609 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -2-propyl-7- [1- (4-pyridinyl) ethoxy] - [2R- (2a, 4aa, 10a3)] - mass: 456 (M + 1)⁺.

Example 610 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7- [2- (4-morpholinyl) ethoxy] -4-propyl-2-propyl, [2R- (2,3,4a , 10s)] The title compound of this example was prepared by analogy to those described above in Example 67. Mass: 444 (M + 1)⁺.

Example 611 acetamide, N- [2- (4-morpholinyl) ethyl] -2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl -2-phenantrenyl] oxy] -, [4bS- (4ba, 7a, 8aβ)] The title compound of this example was prepared by analogy to those described above in Example 244. Mass: 521 (M + 1)⁺.

Example 612 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a-pentyl-2-propyl-7- (4-pyridinylmethoxy) -, [2R- (2a, 4aα, 10aP )] The title compound of this example was prepared by analogous procedures described in Example 76. Mass: 422 (M + 1)⁺.

Examples 613-614

The title compounds of Examples 613-614 were prepared by methods similar to those described in Example 15.

Example 613 2-Phenanthrenecarbonitrile, 4b, 5,6,7,8,8a, 9,10-octahydro-7-methoxy-4b-pentyl-7- (1-propynyl) -, [4bR- (4ba, 7a, 8aP)] - mass: 367 (M + 18)⁺.

Example 614 2-Phenanthrenecarbonitrile, 4b, 5,6,7,8,8a, 9,10-octahydro-7-methoxy-4b-pentyl-7-propyl- [4bR- (4ba, 7a, 8aP)] - mass: 371 (M + 18)⁺.

Examples 615-619

The title compounds of Examples 615-619 were prepared by methods analogous to those described in Example 74 above.

177

Example 615 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (pyrazinyloxy) -, [2R- (2α, 4αα, 10α )] - mass: 429 (M + 1)⁺.

Example 616 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (pyrimidinylloxy) -, [2R- (2a, 4aα, 10a3 )] - mass: 429 (M + 1)⁺.

Example 617 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(3-methylpyrazinyl) oxy] -4a- (phenylmethyl) -2- (1-propynyl) [2R- (2α, 4αα, 10α₃)], mass: 439 (M + 1)⁺

Example 618 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(3-methyl-2-quinoxalinyl) oxy] -4a- (phenylmethyl) -2- (1- propynyl) -, [2R- (2α, 4αα, 10αβ)], mass: 489 (M + 1)⁺.

Example 619 2-Phenanthenol, 7 - [(3,6-dimethylpyrazinyl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -, [2R- (2a, 4aa, 10ap)] - mass: 453 (M + 1)⁺.

Example 620 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2- (1 -propynyl) -, [2R- (2a, 4aα, 10aβ)] The title compound of this example was prepared by the procedures analogous to those described above in Example 76. Mass: 452 (M + 1)⁺.

Example 621 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2-propyl- , [2R- (2), 4a; 10 $]]

The title compound was obtained as described in Example 627 below, with the exception that 2-methyl-3-picolyl chloride hydrogen chloride was used in place of 2-picolyl chloride hydrogen chloride. Mass: 456 (M + 1)⁺.

Example 622 3-Phenanthenol, 7 - [(2-amino-6-methyl-4-pyrimidinyl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) 2-propyl-, [2R- (2a, 4aα, 10aβ)] The title compound of this example was prepared by methods analogous to those described above in Example 74. Mass: 458 (M + 1 f.

Example 623 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(6-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2-propyl- , [2R- (2a, 4aα, 10aβ)] The title compound of this example was prepared by methods analogous to those described above in Example 76. Mass: 456 (M + 1)⁺.

Example 624 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(6-methyl-2-pyridinyl) methoxy] -4a- (phenylmethyl) -2-propynyl- , [2R- (2x4au10 ^ S)]

The title compound was obtained as described in Example 76, with the exception that 3-methyl-2-picolyl chloride hydrochloride was used in place of 3-picolyl chloride hydrochloride, yielding 90%. MS m / z 452 (M + H)⁺.

Examples 625-626

The title compounds of Examples 625-626 were prepared by methods similar to those described above in Example 74.

178

Example 625 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7 - [[4- (trifluoromethyl) -2-pyrimidinyl] oxy] -, [2R- (2α, 4αα, 10αβ)], mass: 479 (M-17)⁺.

Example 626 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7 - [[4- (trifluoromethyl) -2- pyrimidinyl] oxy] -, [2R- (2a, 4aα, 10aP)], mass: 493 (M + 1)⁺.

Example 627 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (2-pyridinylmethoxy) -, [2R- (23,4α 10 $)]

To a solution of 30 mg of the title compound of Example 10 and 8 mg of 60% NaH in 2 mL of anhydrous DMF was added 17 mg of 2-picolyl chloride hydrochloride at room temperature under N₂air overnight. The reaction was stopped by NH₄CI (saturated), extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, filtered and collected until everything was dry. Purification with TLC SiO₂ using 30% EtOAc in hexane as eluent, gave 32 mg (84%) of the title product in this example as a white gaseous powder. Mass: 442 (M + 1)⁺.

Example 628 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (3-pyridinylmethoxy) -, [2R- (20a) 10 $)]

The title compound was obtained as described in Example 627 with the exception of 3-picolyl chloride hydrogen chloride was used for 2-picolyl chloride hydride. Mass: 442 (M + 1)⁺.

Examples 629-633

The title compounds of Examples 629-633 were prepared with the procedures similar to those described above in Example 76.

Example 629 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(6-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2-propyl, (2R- (23.4aa, 10ap)] - mass: 456 (M + 1)⁺.

Example 630 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(6-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2- (1 -propynyl) -, [2R- (2R, 4aα, 10aβ)], mass: 452 (M + 1)⁺.

Example 631 pyridine, 3,3 '- [[1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -2,7-phenanthridyl] bis (oxymethylene)] bis [6-methyl] -, [2R- (2,4a, 10aP)] - mass: 557 (M + 1)⁺.

Example 632 2-Pyridinecarbonitrile, 6 - [[[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] methyl] -, [4bS- (4ba, 7a, 8ap)] - mass: 467 (M + 1)⁺.

Example 633 2-Pyridinecarbonitrile, 6 - [[[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] methyl] - [4bS- (4ba, 7a, 8aP)] - mass: 481 (M + 18)⁺.

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Examples 634-646

The title compounds of Examples 634-646 were prepared by methods similar to those described above (Example 74.

<td>Example 634</td><td>2-phenanthrene, 7 - [(3-amino-4-methyl-2-pyridinyl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl -, [2R- (2j, 4aa, 10aP)] - mass: 457 (M + 1) *.</td>

<td>Example 635</td><td>2-phenanthrene, 7 - [(3-amino-2-pyridinyl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl- [2R- (23.4aa, 10aP)] - mass: 443 (M + 1)⁺</td>

<td>Example 636</td><td>3-pyridinecarbonitrile, 6-methyl-2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl ] oxy] - [4bS- (4ba, 7a, 8aP)] - mass: 463 (M + 1)⁺.</td>

<td>Example 637</td><td>3-pyridinecarbonitrile, 6-methyl-2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] , [4bS- (4ba, 7a, 8ap)] - mass: 467 (M + 1)⁺.</td>

<td>Example 638</td><td>3-pyridinecarbonitrile, 2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] -, [4bS- (4ba, 7a, 8ap)] - mass: 453 (M + 1)⁺.</td>

<td>Example 639</td><td>2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- [2- (trifluoromethyl) phenoxy] -, [2R- (2a, 4aa, 1 Oap)] - mass: 496 (M + 1)⁺.</td>

<td>Example 640</td><td>2-pyridinecarbonitrile, 6 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] - mass: 449 (M + 1)⁺.</td>

<td>Example 641</td><td>2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7 - [[6- (trifluoromethyl) -2-pyridinyl] oxy] mass: 492 (M + 1)⁺.</td>

<td>Example 642</td><td>2-pyridinecarbonitrile, 6 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] - [4bS - (4ba, 7a, 8aP)] - mass: 471 (M + 18)⁺.</td>

<td>Example 643</td><td>3-pyridinecarbonitrile, 4,6-dimethyl-2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy4b- (phenylmethyl) -7- (1-propynyl) -2- phenanthrenyl] oxy] - [4bS- (4ba, 7a, 8aP)] - mass: 477 (M + 1)⁺.</td>

<td>Example 644</td><td>2-pyridinecarbonitrile, 6 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl] oxy] , [4bS- (4ba, 7a, 8ap)], mass: 449 (M + 1)⁺.</td>

<td>Example 645</td><td>2-pyridinecarbonitrile, 6 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] -, [4bS- (4ba, 7q8aP)] - mass: 453 (M + 1)⁺.</td>

<td>Example 646</td><td>3-pyridinecarbonitrile, 4,6-dimethyl-2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy4b- (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] -, [4bS- (4ba, 7a, 8ap)] -_t mass: 481 (M + 1)⁺.</td>

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Examples 647-649

The title compounds of Examples 647-649 were prepared by methods analogous to those described above in Example 76.

Example 647 2-Phenanthenol, 7 - [(2,6-dichloro-4-pyrimidinyl) methoxy] -1,2,3,4,4a, 9,10,10a octahydro-4a- (phenylmethyl) -2-propyl, [2R- (2a, 4aα, 10aβ)], mass: 511 (M).

Example 648 2-Phenanthenol, 7 - [(2,6-dimethoxy-4-pyrimidinyl) methoxy] -1,2,3,4,4a, 9,10,10a octahydro-4a- (phenylmethyl) -2-propyl, [2R- (2α, 4αα, 10αβ)], mass: 503 (M + 1)⁺.

Example 649 2-Phenanthenol, 7 - [(2-chloro-6-methyl-4-pyridinyl) methoxy] -1,2,3,4,4a, 9,10,10a octahydro-4a- (phenylmethyl) -2-propyl -, [2R- (23,4aa, 10aP)] - mass: 490 (M).

Example 650 2-Phenanthenol, 7 - [(6-chloro-2-pyridinyl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -2-propyl- [ 2R- (2 R, 4aα, 10aβ)] The title compound of this example was prepared by methods analogous to those described above in Example 74. Mass: 444 (M-18)⁺.

Example 651 2-Pyridinecarbonitrile, 3 - [[[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (1-propynyl) -2-phenanthrenyl ] oxy] methyl] -, [4bS- (4'B, 748)]]

The title compound was obtained as described (Example 627 with the exception that 2-cyano-3-picolyl chloride hydrogen chloride was used in the column for 3-picolyl chloride hydrochloride, yield 90%. MS m / z 463 (M + H)⁺.

Example 652 2-Pyridinecarbonitrile, 3 - [[[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] methyl ] -, [4bS- (4tn748 $]

The title compound was obtained as described in Example 627, with the exception that 2-cyano-3-picolyl chloride hydrogen chloride was used in the column for 3-picolyl chloride hydrochloride. Mass: 449 (M-17)⁺.

Examples 653-660

The title compounds of Examples 653-660 were prepared by means of yields analogous to those described above in Example 76.

Example 653 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methoxy-6-methyl-4-pyridinyl) methoxy] -4a- (phenylmethyl) -2-propyl -, [2R- (2α, 4αα, 10αβ)] - mass: 486 (M + 1)⁺,

Example 654 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-4-pyridinyl) methoxy] -4a- (phenylmethyl) -2-propyl, [2R- (23,4aa, 10ap)] -_t mass: 456 (M + 1)⁺.

Example 655 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1-propynyl) -7- (2-quinolinylmethoxy) -, [2R- (23.4aa, 10aP)] - mass: 488 (M + 1)⁺.

181

Example 656 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (2-quinolinylmethoxy) -, [2R- (2a, 4aα , 10ap)] - mass: 492 (M + 1)⁺.

Example 657 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methoxy-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2-propyl- , [2R- (2α, 4αα, 10αβ)], mass: 472 (M + 1)⁺.

Example 658 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (pyrazinylmethoxy) -, [2R- (2b, 4aα, 10aP )] - mass: 443 (M + 1)⁺.

Example 659 2 (1H) -pyridinone, 3 - [[[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] methyl] - [4bS- (4ba, 7a, 8ap)] - mass: 458 (M + 1)⁺.

Example 660 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (4-pyrimidinylmethoxy) -, [2R- (2q4aa, 10aP )] - mass: 443 (M + 1)⁺.

Example 661 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-methoxy-1-propynyl) -4a- (phenylmethyl) -, [2R- (23 , 4aα, 1αββ)] The title compound according to this example was prepared by eluent yielding those described above in Example 9. Mass: 359 (M-17)⁺.

Example 662 3-Pyridinecarboxamide, 6-methyl-2 - [[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] - [4bS- (4ba, 7a, 8a8)] The title compound of this example was prepared by means of yields similar to those described above in Example 74. Mass: 485 (M + 1)⁺.

Examples 663-665

The title compounds of Examples 663-665 were prepared by means of yields similar to those described above in Example 76.

Example 663 2-Phenanthenol, 7 - [(4,6-dimethyl-2-pyrimidinyl) methoxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl -, [2R- (2α, 4αα, 10αβ)] - mass: 471 (M + 1)⁺.

Example 664 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (3-quinolinylmethoxy) -, [2R- (23,4aa , 10a3)] - mass: 492 (M + 1)⁺.

Example 665 2-Phenanthrino, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl-7- (4-quinolinylmethoxy) -, [2R- (2a, 4aα , 10aP)] - mass: 492 (M + 1)⁺.

Example 666 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(3-methyl-2-quinoxalinyl) oxy] -4a- (phenylmethyl) -2-propyl, [2R- (2 R, 4aα, 10aβ)] The title compound of this example was prepared by means of extractors analogous to those described above in Example 74. Mass: 493 (M + 1)⁺.

Example 667 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(5-methyl-3-isoxazolyl) methoxy] -4a- (phenylmethyl) -2-propyl- , [2R- (23,4aa, 10aP)] 2743

182

The title compound of this example was prepared by methods analogous to those described above in Example 76. Mass: 428 (M-17)⁺.

Example 668 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-methoxypropyl) -4a- (phenylmethyl) -, [2S- (2,4,4a, 10aP )] The title compound of this example was prepared by methods analogous to those described above in Example 10. Mass: 363 (M-17)⁺.

Example 669 2,7-phenanthridol, 2- (ethoxyethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) - [2R- (z, 4aα, 10aβ)] The title compound according to this example was prepared by methods analogous to those described in Example 9. Mass: 359 (M-17)⁺.

Examples 670-671

The title compounds of Examples 670-671 were prepared by methods similar to those described in Example 10.

Example 670 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (3-phenyl-2-propynyl) -, [2R- (2'- , 4aa, 10aP)] - mass: 405 (M-17)⁺.

Example 671 2,7-phenanthridiol, 2- (2-ethoxyethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2R- (2a, 4aα, 10aβ )] - mass: 363 (M-17)⁺.

Example 672 3-Pyridinecarbonitrile, 6 - [[[4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7-propyl-2-phenanthrenyl] oxy] methyl] - [4bS- (4ba, 7a, 8aP)] The title compound of this example was prepared by methods analogous to that described in Example 76. Mass: 467 (M + 1 f.

Example 673 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-methoxypropyl) -4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2S- (2-4ac 10 ^ $!)]

To a solution of 28 mg of the title compound of Example 668 and 7 mg of 60% NaH in 2 mL of anhydrous DMF was added 15 mg of 3-picolyl chloride hydrochloride at room temperature under N₂air overnight. The reaction was stopped by NH₄CI (saturated), extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, filtered and copied pair until everything was dry. Purification using TLC SiO₂ using 35% EtOAc in hexane as eluent gave 30 mg (87%) of the title product in this example as a white light powder. Mass: 472 (M + 1)⁺

Example 674 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(6-methoxy-2-pyridinyl) methoxy] -4a- (phenylmethyl) -2-propyl- , [2R- (2b, 4aα, 10aβ)] The title compound of this example was prepared by methods analogous to those described above in Example 76. Mass: 472 (M + 1)⁺.

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Examples 675-677

The title compounds of Examples 675-677 were prepared by methods analogous to those described above in Example 81.

<td>Example 675</td><td>2,7-phenanthridol, 2 - [(cyclopropylmethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2R- (2a, 4aα, 10aβ) ] - mass: 375 (M-17)⁺.</td>

<td>Example 676</td><td>2,7-phenanthridiol, 2- (ethoxymethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -, [2R- (2a, 4aα, 10aβ)] - mass: 349 (M-17)⁺.</td>

<td>Example 677</td><td>2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2 - [(2,2,2-trifluoromethoxy) methyl] -, [2R- ( 2a, 4aa, 10aP)] - mass: 403 (M-17)⁺.</td>

<td>Example 678</td><td>2,7-phenanthenediol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (1-piperidinylmethyl) -4a (phenylmethyl) -, [2R- (2a, 4aα, 10aβ)] -</td>

The title compound of this example was prepared by means of those analogous to those described above in Example 83. Mass: 406 (M + 1)⁺.

The title compounds of Examples 679-682 were prepared with the procedures similar to those described above in Example 81.

<td>Example 679</td><td>2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2 - [[2- (1-methylethoxy) ethoxy] methyl] -4a- (phenylmethyl) -, [2R - (2a, 4aa, 10aP)] - mass: 423 (M + 1)⁺.</td>

<td>Example 680</td><td>2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-2- (methoxymethyl) -4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- (2α, 4αα , 10aP)] - mass: 444 (M + 1)⁺.</td>

<td>Example 681</td><td>2-phenanthrene, 2- (ethoxymethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- (23,4aa , 10aP)] - mass: 458 (M + 1)⁺.</td>

<td>Example 682</td><td>2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2 - [(2-methoxyethoxy) methyl] -4a- (phenylmethyl) -, (4aS, 10aR) - mass : 397 (M + 1f.</td>

<td>Example 683</td><td>2-phenanthrene, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-5-thiazol) methoxy] -4a- (phenylmethyl) -2-propyl-, [2R- (2a, 4a 10aP)] -</td>

The title compound of this example was prepared with analogues similar to those described above in Example 76. Mass: 462 (M + 1)⁺.

Case 684-685

The title compoundes in Examples 684-685 were prepared with the procedures similar to those described above in Example 72.

Example 684 2-Phenanthenol, 7 - [[5- (1,1-Dimethylethyl) -1,2,4-oxadiazol-3-yl] methoxy] 1,2,3,4,4a, 9,10,10a- octahydro-4a- (phenylmethyl) -2-propyl, [2R- (2n, 4aα, 10aβ)], mass: 489 (M + 1)⁺.

184

Example 685 2-Phenanthenol, 7 - [[5- (3,5-Dimethyl-4-isoxazolyl) -1,2,4-oxadiazol-3-yl] methoxy] -1,2,3,4,4a, 9 , 10,10a-octahydro-4a- (phenylmethyl) -2-propyl, [2R- (2n, 4aα, 1θββ)] mass: 510 (M + 17)⁺.

Example 686 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-methoxy-1-propynyl) -4a- (phenylmethyl) -7- (2-pyridinylmethoxy) , [2R- (2 R, 4aα, 10aβ)] The title compound of this example was prepared by the procedures analogous to those described above in Example 76. Mass: 468 (M + 1)⁺.

Example 687 2-Phenanthenol, 4b, 5,6,10-tetrahydro-7-phenyl-4b- (phenylmethyl) -, (S) The title compound of this example was prepared by methods analogous to those described above 136. Mass: 364 (M + 1)⁺.

Examples 688-691

The title compounds of Examples 688-691 were prepared by methods analogous to those described above in Example 51.

Example 688 2 (1H) -phenantrenone, 4b- (2-Butenyl) -3,4,4b, 5,6,7,8,8a, 9,10-decahydro-7-hydroxy-7- (1-propynyl) -, [4bS- (4ba (E), 7a, 8aP)] -;

See also example 51.

Example 689 2 (3H) -phenantrenone, 4b- (2-Butenyl) -4,4a, 4b, 5,6,7,8,8a, 9,10-decahydro-7-hydroxy-7- (1-propynyl) -, [4bS (E), 7S, 8aR] -, MS: 312 (M + 1)⁺.

Example 690 2 (3H) -phenantrenone, 4b- (2-Butenyl) -4,4a, 4b, 5,6,7,8,8a, 9,10-decahydro-7-hydroxy-7- (1-propynyl) -, [4aR- [4ax4bP (E), 7β, 8aα]] -; see also example 51.

Example 691 2 (1H) -phenantrenone, 4b- (2-Butenyl) -3,4,4b, 5,6,7,8,8a, 9,10-decahydro-7-hydroxy-7- (1-propynyl) - [4bS- [4ba (E), 7β, 8β]] - MS: 313 (M + 1)⁺.

Example 692 2 (3H) -phenantrenone, 4b- (2-Butenyl) -4,4a, 4b, 5,6,7,8,8a, 9,10-decahydro-7-hydroxy-7- (1-propynyl) oxime, [4bS (E), 7R, 8aR] The title compound of this example was prepared by methods analogous to those described above in Example 77. Mass: 328 (M + 1)⁺.

Examples 693-695

The title compounds of Examples 693-695 were prepared by methods analogous to those described above in Example 136.

Example 693 2-Phenanthenol, 4b, 5,6,8a, 9,10-hexahydro-4b - [(4-hydroxyphenyl) methyl] -7-propyl-, (4bS-cis), MS: 349 (M + 1)⁺.

185

Example 694 2,7-Phenantrendiol, 4a - [[4- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a octahydro-2-propyl, (4aS, 10aS) -, MS ; 370 (M + 1)⁺, disappear from the title product according to example 695.

Example 695 2,7-Phenantrendiol, 4a - [[4- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a-octahydro-2-propyl, (4aS, 10aS) -, MS: 370 (M + 1)⁺, disappear from the title product according to Example 694.

Example 696 2-Phenanthenol, 4a - [[3- (dimethylamino) phenyl] methyl] -1,2,3,4,4a, 9,10,10a octahydro-7- (2-hydroxyethoxy) -2- (1-propynyl) ) -, [2R- (2e, 4aα, 10aβ)] -; see also example 60.

Examples 697-699

The title compounds of Examples 697-699 were prepared according to the procedures described above in Example 9.

Example 697 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-1,1,4a-trimethyl-2- (1-propynyl) - MS: 299 (M + 1 )⁺.

Example 698 2,7-Phenanthridol, 2- (3-Fluoro-3-methyl-1-butynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) 2R- (2α, 4αα, 10αβ)] - MS: 394 (M + 1)⁺.

EXAMPLE 699 2,7-Phenantrendiol, 2- (3-Fluoro-3-methyl-1-butynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) [2S- (2e, 4a, 10aa)], MS: 394 (M + 1)⁺.

Example 700 2-Phenanthenol, 2- (3,3-Dimethylbutyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R - (23.4aa, 10ap)] The title compound of this example was prepared by methods that are described above in Example 76. MS: 485 (M + 1)⁺.

Example 701 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (2-phenylethyl) -4a- (phenylmethyl) - [2R- (2 R, 4aα, 1 The title compound of this example was prepared by the procedures described above in Example 10. MS: 414 (M + 1)⁺.

Example 702 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2 - [(methylthio) methyl] -4a- (phenylmethyl) - [2R- (2R, 4aα, 10aP)] The title compound of this example was prepared by conducting peaks described above in Example 81. MS: 370 (M + 1)⁺.

Case 703-705

The title compounds of Examples 703-705 were prepared with conductive peams described above in Example 76.

186

Example 703 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (2-phenylethyl) -4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- (23.4aa, 10ap)], MS: 505 (M + 1)⁺.

Example 704 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-5-thiazolyl) methoxy] -4a- (phenylmethyl) -2-propyl, [ 2R- (2α, 4αα, 1αα)], MS: 463 (M + 1)⁺.

Example 705 2-Phenanthenol, 7 - [[5- (1,1-Dimethylethyl) -1,2,4-oxadiazol-3-yl] methoxy] 1,2,3,4,4a, 9,10,10a- octahydro-4a- (phenylmethyl) -2-propyl-, [2R- (2α, 4αα, 10αβ)] - MS: 490 (M + 1)⁺.

Example 706 2-Phenanthenol, 7 - [[5- (3,5-Dimethylethyl-4-isoxazolyl) -1,2,4-oxadiazol-3-yl] -methoxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2-propyl- [2R- (23,4aα, 10aβ)] The title compound of this example was prepared by methods analogous to those described above 69. MS: 529 (M + 1)⁺.

Example 707 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (3-methoxy-1-propynyl) -4a- (phenylmethyl) -7- (2-pyridinylmethoxy) , [2R- (2b, 4aα, 10aβ)] The title compound of this example was prepared by methods analogous to those described above in Example 76. MS: 469 (M + 1)⁺.

Examples 708-710

The title compounds of Examples 708-710 were prepared by methods similar to those described above in Example 81.

Example 708 2-Phenanthenol, 2 - [(Cyclopropylmethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydroda- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- ( 2a, 4aa, 10a β)], MS: 485 (M + 1)⁺.

Example 709 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -2 - [(2,2,2-trifluoroethoxy) methyl] -, [2R- (2α, 4αα, 10αβ)] - MS: 513 (M + 1)⁺.

Example 710 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2 - [(1-methylethoxy) methyl] -4a (phenylmethyl) -7- (2-pyridinylmethoxy) 2R- (2α, 4αα, 10αβ)], MS: 458 (M + 1)⁺.

Example 711 2-Phenanthrenol, 2- (azidomethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) 7- (2-pyridinylmethoxy) -, [2R- (23, 4aα, 10β)] The title compound of this example was prepared by methods similar to those described above in Example 82. MS: 473 (M + 1)⁺.

Examples 712-717

The title compounds of Examples 712-717 were prepared by methods analogous to those described above in Example 81.

187

Example 712 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -2 - [(2-pyridinylmethoxy) methyl] - [2R - (23.4aa, 10aP)] - MS: 522 (M + 1)⁺.

Example 713 Propanitrile, 3 - [[1,2,3,4,4a, 9,10,10a-octahydro-2-hydroxy-4a- (phenylmethyl) -7 (2-pyridinylmethoxy) -2-phenanthrenyl] methoxy] , [2R- (2α, 4αα, 1θθβ)], MS: 484 (M + 1)⁺.

Example 714 2-Phenanthenol, 2 - [(cyclopentyloxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) 2R- (2i, 4aα, 10aβ)], MS: 499 (M + 1)⁺.

Example 715 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2 - [[(3-methyl-3-oxetanyl) methoxy] methyl] -4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- (23,4aα, 10aβ)] -,

MS: 515 (M + 1)⁺

Example 716 2-Phenanthenol, 2 - [(1,1-Dimethylethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2β- (2α, 4θα, 103β)], MS: 487 (M + 1)⁺.

Example 717 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (phenoxymethyl) -4a (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- (2R, 4aa, 10aP)] -, MS: 507 (M + 1)⁺.

Example 718 1 H-benz [e] indene-2-carboxylic acid, 2,3,3a, 4,5,9b-hexahydro-9b- (phenylmethyl) -7 (3-pyridinylmethoxy) methyl ester, [2R- (2 The title compound of this example was prepared by methods analogous to those described above in Example 76. MS: 429 (M + 1)⁺.

Example 719 Spiro [1,3-dioxolane-2,2 '(1'H) -phenanthrene] -7'-ol, 3', 4 ', 4'a, 9', 10 ', 10'a-hexahydro- 4'a- (phenylmethyl) -, (4'-S-trans)

The title compound according to this example was prepared by means of successors similar to those described above in Example 7. MS: 351 (M + 1)⁺.

Example 720 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (1H-imidazol-1-ylmethyl) -4a- (phenylmethyl) -, [2R- ( 23.4aa, 10ap)] The title compound according to this example was prepared by means of extractors analogous to those described above in Example 48. MS: 390 (M + 1)⁺.

Example 721 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -1- (1H-1,2,4-triazol-1-ylmethyl) -, [2R- (23,4aa, 10a3)] -; see also example 48.

Example 722 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- [2- (2-pyridinylethyl) -, [25- (23, 43α, 1β3β)] The title compound of this example was prepared by means of eluants analogous to those described above in Example 10. MS: 415 (M + 1)⁺.

Examples 723-724

188

The title compounds of Examples 723-724 were prepared by methods analogous to those described above in Example 76. MS: 506 (M + 1)⁺.

Example 723 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- [2- (2-pyridinyl) ethyl] -7- (3-pyridinylmethoxy) -, [2S- (2α, 4αα, 10αβ)] -.

EXAMPLE 724 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2 - [(methylpio) methyl] -4a- (phenylmethyl) -7- (3-pyridinylmethoxy) [2R- (2α, 4αα, 1αββ)], MS: 461 (M + 1)⁺.

Example 725 2,7-Phenanthrenol, 2 - [(Cyclobutyloxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) [2R- (2a, 4aα, 10aβ)] To a solution of 20 mg of the title compound of Preparation 20 and 6 mg of Na in 1 mL of anhydrous DMF was added 0.019 mL of cyclobutanol vifl 85 ° C under N₂ air overnight. The reaction was stopped by NH₄CI (saturated), extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, siafl and samsafnafl couple to everything were purr. Purification with the addition of TLC SiO₂ Mean use of 8% acetone methylene chloride as eluent gave 18 mg (76%) of title compound in this case as a white light powder. Mass: 484 (M + 1)⁺.

Daemi 726-734

The title compoundes according to Examples 726-734 were prepared by means of coagulators which are the equivalent peams described herein above in Example 725.

Example 726 2-Phenanthenol, 2 - [(fluoroethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R - (2i, 4aα, 10aβ)] - MS: 477 (M + 1f.

Example 727 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2 - [[2- (methylpio) ethoxy] methyl] -4a- (phenylmethyl) -7- (3-pyridinylmethoxy) ), [2R- (2α, 4αα, 10αβ)], MS: 505 (M + 1)⁺.

Example 728 2-Phenanthenol, 2 - [(2,2-dimethylpropoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R- (23.4ao, 10ap) J-, MS: 501 (M + 1)⁺.

Example 729 2-Phenanthenol, 2 - [(ethylbutoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R - (2α, 4αα, 10αβ)] -, MS: 515 (M + 1)⁺.

Example 730 2-Phenanthenol, 2 - [(2-butynyloxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) [2R- (2α, 4αα, 10αβ)], MS: 483 (M + 1)⁺.

Example 731 2-Phenanthenol, 2 - [(cyclohexylmethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R - (2α, 4αα, 10αβ)] -, MS: 527 (M + 1)⁺.

Example 732 2-Phenanthenol, 2 - [(cyclopentylmethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R - (23.4ao, 10ap) ν MS: 513 (M + 1)⁺.

Example 733 2-Phenanthenol, 2 - [(Cyclobutylmethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -, [2R - (23.4α, 10αβ)), MS: 499 (M + 1)⁺.

Example 734 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2 - [[(3-phenyl-1-propynyl) oxy] methyl] -7- (3-pyridinylmethoxy) -, [2R- (23,4aa, 10ap)] - MS: 545 (M + 1)

189

Example 735 2-Phenanthenol, 2- (3-Fluoro-3-methyl-1-butynyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- ( 3-pyridinylmethoxy) -, [2R- (2R, 4aα, 10aβ)] The title compound of this example was prepared by analogy to those described above in Example 9. MS: 485 (M + 1 f.

Examples 736-738

The title compounds of Examples 736-738 were prepared by methods analogous to those described above in Example 76.

Example 736 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (1H-imidazol-1-ylmethyl) -4a- (phenylmethyl) -7- (3-pyridinylmethoxy) , [2R- (ax, 4aa, 10ap)], MS: 481 (M + 1)⁺.

Example 737 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (3-pyridinylmethoxy) -2- (1H-1,2,4-triazol- 1-ylmethyl) -, (2R- (2α, 4α, 10αP)] - MS: 482 (M + 1)⁺.

Example 738 pyridine, 3 - [[[3 ', 4', 4'a, 9 ', 10', 10'α-hexahydro-4'a- (phenylmethyl) spiro [1,3-dioxolane-2,2'- (1'H) -phenanthrene] -7'-yl] oxy] methyl] -, (4'S-trans) - MS: 443 (M + 1)⁺.

Example 739 2-Phenanthenol, 2- (ethoxymethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (2-pyridinylmethoxy) -, [2R- (23 , 4aα, 10aβ)] To a solution of 20 mg of the title compound of Example 676 and 5 mg of 60% NaH in 2 mL of anhydrous DMF was added 11 mg of 2-picolyl chloride hydrochloride at room temperature under N₂night's sleep The reaction was stopped by NH₄CI (saturated), extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, filtered and collected until everything was dry. Purification by preparative TLC (SiO₂) using 45% EtOAc in hexane as eluent afforded 24 mg (96%) of the title product according to this example as a white light powder. Mass: 458 (M + 1)⁺.

Example 740 2-Phenanthenol, 2- (Ethoxymethyl) -1,2,3,4,4a, 9,10,10a-octahydro-7 - [(5-methyl-3-isoxazolyl) methoxy] -4a- (phenylmethyl) - [2R- (2 R, 4aα, 10aβ)] The title compound of this example was prepared with the procedures described above described in Example 81. MS: 463 (M + 1)⁺

Example 741 2-Phenanthenol, 2- (Ethoxymethyl) -1,2,3,4,4a, 9,10,10a-octahydro-7- [2- (4-morpholinyl) ethoxy] -4a- (phenylmethyl) [2R- (2,3,4a, 10aP)] The title compound of this Example was prepared by the procedures described in Table 67 above. MS: 481 (M + 1)⁺.

Daemi 742-744

190

The title compounds of Examples 742-744 were prepared by methods analogous to those described above in Example 74.

Example 742 2-Phenanthrenol, 2- (Ethoxymethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) 7- (pyrazinyloxy) -, [2R- (2 R, 4aα, 10aP) j-, MS: 446 (M + 1)⁺.

Example 743 2-Phenanthenol, 7 - [(2-amino-6-methyl-4-pyrimidinyl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) [2R- (2α, 4αα, 10αβ)] - MS: 475 (M + 1)⁺

Example 744 3-Pyridinecarboxamide, 6 - [[7- (Ethoxymethyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -2-phenanthrenyl] oxy] -, [4bS- (4ba, 7a, 8ap)] - MS: 488 (M + 1)⁺.

Example 745 2,7-phenanthridio, 1,2,3,4,4a, 9,10,10a-octahydro-2 - [(methylsulfonyl) methyl] -4a- (phenylmethyl) -, [2R- (2,3,4a, 10aP)] At room temperature under nitrogen, metha-chloroperoxybenzoic acid (58 mg) was added to the title product of Example 702 (20 mg) in CH2Cl2 and monitored by TLC. When no starting material was left, the reaction was quenched with 10% sodium bisulfite solution and extracted with CH₂Cl₂ (3X). The organics were combined and dried with Na₂SO₄, filtered and coincided. Purification by flash chromatography with 10% MeOH in CH₂Cl₂ gave 15 mg of white solid. Mass 402 (M + 1)⁺.

Example 746 2-Phenanthenol, 2- (Cyclopropylethynyl) -1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) - [2R- (2a, 4aα, 1αββ)] The title compound was obtained as described in Example 764, with the exception that the title compound of Example 150 was used as the starting material. Mass: 478 (M + 1)⁺.

Examples 747-748

The title compounds of Examples 747-748 were prepared by eluants corresponding to those described above in Example 76.

Example 747 2-Phenanthenol, 2- (Cyclopropylethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (2-pyridinylmethoxy) -, [2R- (2u , 4aa, 10aP)] -, MS: 465 (M + 1)⁺.

Example 748 2-Phenanthenol, 2- (2-Cyclopropylethyl) -1,2,3,4,4a, 9,10,10a-octahydro-4a (phenylmethyl) -7- (2-pyridinylmethoxy) -, [2R- ( 2j, 4aα, 1θββ)], MS: 469 (M + 1)⁺.

Example 749 2-Phenanthenol, 2- (2-Cyclopropylethyl) -1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) - [2R- (2,3,4a, 10aP)] The title compound was obtained as described in Example 764, with the exception that the title compound of Example 377 was used as the starting material. MS: 482 (M + 1)⁺.

Example 749a 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2- (trifluoromethyl) ) -, (2R, 4aS, 10aR) 2743

191

The title compound was obtained as described in Example 764 by way of exception, the title compound of Example 799 was used as the starting material. MS: 482 (M + 1)⁺.

Example 749b 2-Pyridinecarbonitrile, 3 - [[[(4bS, 7R, 8aR) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7-methyl-4b- (phenylmethyl) -2-phenantrenyl] oxy] methyl] To a solution of 222 mg of the title compound of Example 750 and 55 mg of 60% NaH in 5 mL of anhydrous DMF was added 400 mg of 2-cyano-3-picolyl chloride hydrochloride at room temperature below N₂ air over the air. The reaction was the reaction of NH₄CI (methane), extracted with EtOAc (X3), washed with brine, an excess of Na₂SO₄, siafl and samsafnafl couple to everything were purr. Purification of column chromatography using 35% EtOAc in hexane as eluant gave 220 mg (74%) of the title product in this case as a white light powder. MS: 439 (M + 1)⁺.

Example 750 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2-methyl-4a- (phenylmethyl) - [2R- (23,4a, 10e)] Title compound According to this case, there was produced a coefficient of interaction which is described herein above in Example 9. MS: 232 (M + 1)⁺.

Example 751 2-Phenanthenol, 2 - [(Cyclobutyloxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-7 - [(1-oxido-3-pyridinyl) methoxy] -4a- (phenylmethyl ), [2R- (2a, 4aα, 1αβ)] The title compound of this Example was prepared by substituting the supernatants described herein above in Example 76. MS: 503 (M + 1)⁺

Example 752 carbamic acid, dimethyl-, 7- (ethoxymethyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -2-phenanthrenyl ester, [4bS- (4'-naphthyl) The title compound according to this example was prepared by means of supernatants which are peeled peams which are described herein as above in Example 58. MS: 439 (M + 1) *.

Example 753 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7- (1-methylethoxy) -4a- (phenylmethyl) -2 - [(2-pyridinylmethoxy) methyl] [2R- (2a, 4aα, 1α)] The title compound of this Example was prepared by substituting supernatants described herein above in Example 81. MS: 473 (M + 1)⁺.

Example 754 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2 - [[2- (1H-pyrazol-1-yl) ethoxy] methyl] -7- (3-pyridinylmethoxy) -, [2R- (2α, 4aα, 10αβ)] The title compound of this Example was prepared by substituting the supernatants described above in Example 725. MS: 525 (M + 1)⁺.

Dissemin 755 2-phenanthrenecarboxylic acid, 7- (cyclopropylethynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) methyl ester, [4bS- (4ba, 7i 8 ^ B)] 2743

192

The title compounds of this example were prepared by coagulants analogous to those described in Example 14. MS: 416 (M + 1)⁺.

Example 756 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2- 3,3-trifluoropropyl) - [2S- (2,4,4a, 10aP)] The title compound was obtained as described in Example 764, with the exception that the title product of Example 348 was used as the starting material. MS: 510 (M + 1)⁺.

Example 757 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -7- (2-pyridinylmethoxy) -2- (3,3,3-trifluoropropyl) , [2S- (2 R, 4aα, 10aβ)] The title compound of this example was prepared by means of yields analogous to those described above in Example 76. MS: 497 (M + 1)⁺.

Example 758 2-Phenanthenemethanol, 7- (Cyclopropylethynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxypyridin-4b- (phenylmethyl) -, [4bS- (4ba, 7a, 8aβ)] The title compound according to this example was prepared by means of yields analogous to the semisubstituted region in Example 19. MS: 415 (M + 1)⁺.

Examples 759-760

The title compounds of Examples 759-760 were prepared by means of yields similar to those described above in Example 725.

Example 759 2-Phenanthenol, 2 - [(Cyclopropylmethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-4-thiazolyl) methoxy] -4a- (phenylmethyl) -, [2R- (2} 4aα, 10αβ)], MS: 505 (M + 1)⁺.

Example 760 2-Phenanthenol, 2 - [(Cyclopropylmethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-7 - [(5-methyl-3-isoxazolyl) methoxy] -4a- (phenylmethyl) -, [2R- (2,4a, 10aP)] - MS: 489 (M + 1)⁺.

Example 761 2-Phenanthenol, 2- (Ethoxymethyl) -1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-4-thiazolyl) methoxy] -4a- (phenylmethyl) - [2R- (2a, 4aα, 10aβ)] The title compound of this example was prepared by coagulants analogous to those described above in Example 81. MS: 479 (M + 1)⁺.

Example 762 2-Phenanthrenol, 2 - [(cyclopropylmethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydroda- (phenylmethyl) -7- (2-pyridinylmethoxy) -, [2R- ( 2a, 4a, 10aβ)} ·

The title compound of the example was prepared by means of yields analogous to those described in Example 725. MS: 485 (M + 1)⁺.

Example 763 2-Phenanthenol, 2 - [(Cyclopropylmethoxy) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -, [2R- (2a4aa, 10aP)] 2743

193

The title compound was obtained as described in Example 764, with the exception that the title product of Example 675 was used as the starting material. MS: 498 (M + 1)⁺.

Example 764 2-Phenanthenol, 2- (Ethoxymethyl) -1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) - [2R- (2a, 4aα, 10aP)] A solution of 20 mg of the title compound of Example 676 and 3 mg of 60% NaH in 2 mL of anhydrous DMF was added 9 mg of 2-methyl-3-picolyl chloride hydrochloride at room temperature below N₂ air with stirring overnight. The reaction was stopped by NH₄CI (saturated), extracted with EtOAc (X3), washed with brine, dried over Na₂SO₄, filter and coalesce until dry. Purification by preparation of TLC (SiO₂) using 55% EtOAc in hexane as eluent gave 21 mg (81%) of the title product according to this example as a lightweight powder. Mass: 472 (M + 1)⁺.

Example 765 2-Phenanthrenecarboxamide, 7- (Ethoxymethyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -N-3-pyridinyl-, [4bS- $ a) l ·

The title compound of this example was prepared by methods analogous to those described above in Example 244. MS: 472 (M + 1)⁺.

Example 766 2-Phenanthenol, 2- (2-Cyclopropylethyl) -1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methylphenyl) methoxy] -4a- (phenylmethyl) [2R- (2x4a, 10aP)] The title compound of this example was prepared by methods similar to those described above in Example 76. MS: 482 (M + 1)⁺.

Example 767 2-Phenanthenol, 2- (2-Cyclopropylethyl) -1,2,3,4,4a, 9,10,10a-octahydro-7- (phenylmethoxy) -4a- (phenylmethyl) -, [2R- (23 , 4aα, 10aβ)] The title compound of this example was prepared by methods analogous to those described above in Example 10. MS: 468 (M + 1)⁺.

Example 768 2-Phenanthrenecarbonitrile, 7- (Ethoxymethyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) - [4bS- (4H, 7x8)] The title compound of this Examples were prepared by methods analogous to those described above in Example 81. MS: 377 (M + 1)⁺.

Examples 769-770

The title compounds of Examples 769-770 were prepared by methods similar to those described above in Example 725.

Example 769 2-Phenanthrenecarbonitrile, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7 - [(2,2,2-trifluoroethoxy) methyl] 4bS- (4ba, 7a, 8ap)] -, MS: 430 (M + 1)⁺.

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Example 770 2-Phenanthrenecarbonitrile, 7 - [(Cyclopropylmethoxy) methyl] -4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-4b- (phenylmethyl) -, [4bS- (4ba, 7a, 8a0)], MS: 403 (M + 1)⁺.

Example 771 2-Phenanthrenecarboxamide, 7- (2-pentyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b - (phenylmethyl) -, [4bS- (4ba, 7a, 8aP)] To a stirred solution of 150 mg of 2-phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy -4b- (phenylmethyl) -7- (pentyl) - methyl ester, [4bS- (4ba, 7a, 8a0)] - in 7 mL of dichloromethane was added 2 mL of 0.5 M 2-methyl-3-aminomethylpyridinamide solution was prepared as in Example 772. The mixture was refluxed for 3 hours. Odrum 1 mL of 0.5 M 2-methyl-3-aminomethylpyridinaldehyde solution was added and the mixture was refluxed for 2 hours. The mixture was quenched to 0 ° C. Into the reaction mixture was added 1N HCl dropwise to a water layer at about pH 4. The resulting mixture was extracted with EtOAc, purrkud over Na₂SO₄, siud and coincided couple to everything was purrt. Purification by flash chromatography on SiO₂ using 10% MeOH in dichloromethane as eluentamide gave 172 mg (94%) of the title compound as a white solid. MS: 511 (M + 1) +.

Example 771A-1 2- (2-phenanthrenecarboxylic acid), 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy4b- (phenylmethyl) -7- (butyl) methyl ester, [4bS- ( 4ba, 7a, 8aP) E

The title compound of this example was prepared with conductive peaks described in Example 14. MS: 421 (M + 1)⁺.

Example 771A-2 2-phenanthrenecarboxamide, 7-butyl-4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- phenylmethyl) -, (4bS, 7R, 8aR) To a stirred solution of 210 mg of the title compound of Example 771A-1 10 mL of dichloromethane was added 3 mL of 0.5 M 2-methyl-3-aminomethylpyridinamide amide which was produced as and in case 772. The mixture was heated by the backing. The mixture was cooled to 0 ° C. To the reaction mixture was added 1N HCl dropwise to a water layer at about pH 4. The resulting mixture was extracted with EtOAc, purrkud over Na₂SO₄, siud and coincided couple to everything was purrt. Purification by flash chromatography on SiO₂ using 40% acetone in hexane to 50% acetone In hexane as a gradient eluent afforded 163 mg (63%) of the title compound as a white solid. MS: 497 (M + 1)⁺.

Example 771B 2-Phenanthrenecarboxamide, 7- (Cyclopropylethynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b - (phenimethyl) -, (4bS, 7R, 8aR) -, (shown in Scheme C: C-5-&gt; C-8)

A precipitated solution of 200 mg of 2-phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (cyclopropylethynyl) methyl ester, [4bS - (4ba, 7a, 8aP)] 10 mL of dichloromethane was added 3 mL of 0.5 M 2-methyl-3-aminomethylpyridinamide amide which was prepared as in Example 772. The mixture was refluxed overnight. The mixture was quenched in

195

0 ° C. To the reaction mixture was added dropwise 1N HCl until the aqueous layer was approximately pH 4. The resulting mixture was extracted with EtOAc, dried over Na₂SO₄, filtered and aggregated pairs until everything was purred. Purification by flash chromatography on SiO₂ using 40% acetone hexane to 50% acetone hexane as a gradient eluent gave 196 mg (81%) of the supplemental product according to this example as a white solid. MS: 505 (M + 1 f.

Example 771C-1 Methanesulfonic acid, trifluoro, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (3,3,3-trifluoropropyl) -2- phenanthrenyl ester, [4bS, 7S, 8aR] The title compound of this example was prepared with the fractions similar to those described above for the production of the title compound according to Example 13. MS: 537 (M + 1)⁺; ¹1 H NMR (400 MHz, d₆-azetone) δ 7.18 (d, 1H, J = 2.9), 6.83 (dd, 1H, J = 2.9, 8.7), 6.43 (d, 1H, J = 8.7 ).

Example 771C-2 2-phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (3,3,3-trifluoropropyl) , methyl ester, [4bS, 7S, 8aR] title compound according to this example was prepared by subdivides which are the analogous peams described above for the production of the title compound according to Example 14. MS: 447 (M + 1)⁺; ¹1 H NMR (400 MHz, CDOD₃) 7.75 (d, 1H, J = 1.7), 7.40 (dd, 1H, J = 1.7, 8.2), 6.39 (d, 1H, J = 8.2).

Example 771C-3 2-phenanthrenecarboxamid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7- (3,3,3-trifluoropropyl) -, (4bS, 7S, 8aR) To a stirred solution of 286 mg of the title compound according to Example 771C-2 In 12 mL of dichloromethane was added 4 mL of 0.5 M 2 -methyl-3-aminomethylpyridinamide amide which was prepared as in Example 772. The mixture was refluxed over nit. The mixture was quenched at 0 ° C. Into the reaction mixture was added a drop of 1N HCI pair to a water-coolant solution at about pH 4. The resulting mixture was extracted with EtOAc, pancake over Na₂SO₄, siufi and social life couple to everything was purrt. Purification by flash chromatography on SiO₂ using 40% acetone in hexane to 50% acetone In hexane as a gradient eluent, gave 272 mg (79%) of the supplemental product according to this example as a white solid. MS: 537 (M + 1)⁺.

Example 771D 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (propoxymethyl) -N-3-pyridinyl-, (4bS, 7S, 8aR) To a stirred solution of 50 mg of 2-phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (propoxymethyl) , methyl ester, [4bS- (4t, 7β)] - in 5 mL of dichloromethane was added 4 mL of 0.5 M 3-aminopyridinamide amide which was prepared as in Example 772. The mixture was heated to reflux over ninety. The mixture was quenched at 0 ° C. Into the reaction mixture was added dropwise 1N HCl par to aqueous solution at pH 4. pH. The resulting extract was extracted with EtOAc, pancake over Na₂SO₄, siufi and social networking

196 until everything was dry. Purification by preparative TLC (SiO₂) with 3% MeOH dichloromethane gave 8 mg (16%) of the title product according to this example as a white solid. MS: 485 (M + 1)⁺.

Example 771E-3 (2-phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b (phenylmethyl) -7- (methyl) methyl ester, [4bS- (4ba , 7a, 8aP)] -)

The title compound of this example was prepared by the procedures described in Example 14 above.¹1 H NMR (400 MHz, CD₃OD) δ 7.81 (s, 1H), 3.90 (s, 1H), 1.29 (s, 1H); MS: 365 (M + 1)⁺.

Example 771E-3 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7-methyl-N - [(2-methyl-3-pyridinyl) methyl] -4b - (phenylmethyl) -, (4bS, 7S, 8aR) To a stirred solution of 300 mg of the title compound of Example 771E-1 In 16 mL of dichloromethane was added 8.2 mL of 0.5 M 2-methyl-3-aminomethylpyridinaldehyde solution which was prepared as in Example 772. The mixture was heated backwards overnight. The mixture was chilled at 0 ° C. Into the reaction mixture was added dropwise 1N HCl until water layer was maintained at pH 4. The resulting mixture was extracted with EtOAc, dried over Na₂SO₄, sir and samsdfnud until everything was dry. Purification by flash chromatography on SiO₂ using 40% acetone hexane to 50% acetone hexane as a gradient eluent gave 344 mg (92%) of the title product according to this example as a white solid. MS: 455 (M + 1)⁺.

Example 772 2-Phenanthrenecarboxamide, 7- (Ethoxymethyl) -4b, 5,6,7,8,8a, 9,10-octahyd-7-hydroxy-8a-methyl-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) - [4bS- (4ba, 7a, 8ap)] In a stirred solution of 31 mL of 2.0 M trimethylalumin in toluene and 24 mL of dichloromethane was added 8.25 g of 2-methyl- 3-aminomethylpyridine In 80 mL of dichloromethane at 0 ° C under N₂. The mixture was stirred at 0 ° C for 20 min, and then at room temperature for 1 hour to give 2-methyl-3-aminomethylpyridinamide amide. In the reaction mixture, 1.68 g of 2-phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (ethoxymethyl) , methyl ester, [4bS- (4ba, 7a, 8aP) j-80 mL of dichloromethane. Into this solution was added 32 mL of 2-methyl-3-aminomethylpyridinaldehyde, which was prepared as described above. The mixture was refluxed overnight. The mixture was cooled to 0 ° C. Out of the reaction mixture, dropwise 1N HCl was added dropwise until water pH was approximately pH 4. The resulting mixture was extracted with dichloromethane, dried over Na₂SO₄, sir and samsdfnud until everything was dry. Purification by flash chromatography on SiO₂ using a 40% acetone in hexane to 50% acetone in hexane as a gradient eluent gave 1.9 g (96%) of the title product according to this example as a white solid. MS: 499 (M + 1)⁺.

Example 773 2-Phenantrendl, 1,2,3,4,4a, 9,10,10a-octahydro-2 - [(1-methylethoxy) methyl] -7 - [(2-methyl-3-pyridinyl) methoxy] 4a- (phenylmethyl) -, [2R- (2α, 4αα, 1αα)] 2743

197

To a solution of 500 mg of the title compound of Preparation 21 and 135 mg of NaOH 5 mL of anhydrous DMF was added 10 mL of isopropanol vifi 85 ° C under N₂ air above nineteen. The reaction was stopped by NH₄CI (methane), extracted with EtOAc (X3), treated with brine, dried over Na₂SO₄, siafi and samsafnafi couple to everything were purr. Purification by column chromatography with use of 1.5% methanol in methylene chloride as eluent afforded 528 mg (93%) of the title product as a white light powder. MS: 486 (M + 1)⁺.

Example 774 2-Phenanthenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) -2 - [(2 , 2,2-trifluoroethoxy) methyl] - [2R- (2a, 4aα, 10a6)] The title compound of this Example was prepared by subversion analogues described above from Example 773. MS: 525.6 ( M + 1)⁺.

Example 775 2 (3H) -phenantrenone, 4a - [(4-isopropylaminophenyl) methyl] -4,4a, 9,10-tetrahydro-7-hydroxy-, (S). MS: 362 (M + H)⁺; see also subsection 4.

Example 776 2,7-Phenantrendiol, 4a - [(4-aminophenyl) methyl] -1,2,3,4,4a, 9,10,10a-octahydro-2 (1-propynyl) -, [2R- (2a , 4aα, 10aβ)] The title compound of this example was prepared by subversion analogues described above. MS: 462 (M + 1)⁺.

Example 777 2-Phenanthenol, 7 - [(2-chloro-4-pyrimidinyl) oxy] -1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (1 -propynyl) -, [2R- (2a, 4aα, 10aβ)] The title compound of this Example was prepared by subdivides which are analogous to the above described above. MS: 460 (M + 1)⁺.

Example 778 3 H -naphtho [2,1-b] pyran-3-one, 1,2,4a, 5,6,10b-hexahydro-8-hydroxy-10b (phenylmethyl) The title compound of this example was prepared with afiferfium which are a slight peel described above from Example 3. MS: 309 (M + 1)⁺.

Example 779 1 H -naphtho [2,1-b] pyran-3,8-diol, 2,3,4a, 5,6,10b-hexahydro-10b- (phenylmethyl) -3 (1-propynyl) title compound according to this an example was prepared with fragments that are analogous to the fragments described above in Example 9. MS: 349 (M + 1)⁺.

Example 780 1H-Naphtho [2,1-b] pyran-8-diol, 2,3,4a, 5,6,10b-hexahydro-10b- (phenylmethyl) -3 - [(phenylmethyl) imino] -, (4aS , 10bR) The title compound of this Example was prepared by subversion analogues described above from Example 77. MS: 397 (M + 1)⁺.

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Example 781 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-2- (methoxymethyl) -4a- (phenylmethyl) -, (2S, 4aS, 10aR) The title compound according to this example was prepared by methods similar to those described in Example 81. MS: 353 (M + 1)⁺.

Example 782 Benzonitrile, 4 - [[(2R, 4aS) -3,4,9,10-tetrahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methyl] The title compound of this Examples were prepared by methods analogous to those described above in Example 5. MS: 370 (M + 1)⁺.

Example 783 2-Phenanthrenecarbonitrile, 4b - [(4-cyanophenyl) methyl] -4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-7- (1-propynyl) -, (4bS, 7R , 8aR) The title compound of this example was prepared by methods analogous to those described above in Example 9. Mass: 381 (M + 1)⁺.

Example 784 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7 - (Propoxymethyl) -, (4bS, 7R, 8aR) The title compound of this example was prepared by analogy to those described above in Example 244. Mass: 514 (M + 1)⁺.

Example 785 2-Phenanthrenol, 1,2,3,4,4a, 9,10,10a-octahydro-7 - [(2-methyl-3-pyridinyl) methoxy] -2- (1-pentynyl) -4a- (phenylmethyl) -, (2R, 4aS, 10aR) The title compound of this example was prepared by methods analogous to those described above in Example 76. MS: 481 (M + 1)⁺.

Examples 786-793

The title compounds of Examples 786-793 were prepared by methods similar to those described above in Example 244.

Example 786 2-Phenanthrenecarboxamide, 7- (1-Butynyl) -4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -, (4bS, 7R, 8aR) -; MS: 494 (M + 1)⁺.

Example 787 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7 - [(2,2,2-trifluoroethoxy) methyl] -, (4bS, 7R, 8aR) -; MS: 554 (M + 1)⁺.

Example 788 2-Phenanthrenecarboxamide, 7 - [(Cyclopropylmethoxy) methyl] -4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] 4b- (phenylmethyl) -, (4bS, 7R, 8aR) -; MS: 526 (M + 1)⁺.

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Example 789 2-Phenanthrenecarboxamide, 7 - [(Cyclopropylmethoxy) methyl] -4b, 5,6,7,8,8a, 9,10 octahydro-7-hydroxy-4b- (phenylmethyl) -N-3-pyridinyl-, (4bS , 7R, 8aR) -; MS: 498 (M + 1)⁺.

Example 790 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7 - [(1-methylethoxy) methyl] -, (4bS, 7R, 8aR) -; MS: 514 (M + 1)⁺

Example 791 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7-methyl-4b- (phenylmethyl) -N-3-pyridinyl-, (4bS, 7R, 8aR) -; MS: 428 (M + 1)⁺.

Example 792 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (3-methylbutyl) -N - [(2-methyl-3-pyridyl) -4b- (phenylmethyl) -, (4bS, 7R, 8aR) -; MS: 512 (M + 1)⁺.

Example 793 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7- (3-methyl-1-butynyl) -N - [(2-methyl-3- pyridinyl) methyl] -4b- (phenylmethyl) -, (4bS, 7R, 8aR) -;

MS: 508 (M + 1)⁺.

Example 794 2-Phenanthenol, 2- (1-Butynyl) -1,2,3,4,4a, 9,10,10a-octahydro - [(2-methyl-3-pyridyl) methoxy] -4a- ( phenylmethyl) -, (2R, 4aS, 10aR) The title compound of this example was prepared by methods analogous to those described above in Example 76. MS: 467 (M + 1)⁺.

Example 795 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7 - [(2-methylpropoxy) methyl] -N - [(2-methyl-3-pyridinyl) ) methyl] -4b- (phenylmethyl) -, (4bS, 7R, 8aS) The title compound of this example was prepared by methods analogous to those described above in Example 81. Mass: 528 (M + 1)⁺.

The title compounds of Examples 796-798 were prepared by methods similar to those described above in Example 9.

Example 796 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2-methyl-4a- (phenylmethyl) -, (2R, 4aS, 10aS) -; MS: 323 (M + 1)⁺.

Example 797 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2-methyl-4a- (phenylmethyl) -, (2S, 4aS, 10aS) -; MS: 323 (M + 1)⁺

Example 798 2,7-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2-methyl-4a-propyl, (2R, 4aR, 10aS) -; MS: 275 (M + 1)⁺.

Example 799 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -1- (trifluoromethyl) -, (2R, 4aS, 10aS) -;

To a solution of 455 mg of the title product of Example 6 in 20 mL of anhydrous THF and 15 mL of 1M trifluoromethyl trimethylsilane was added 194 mg of TBAF at 0 ° C under a nitrogen atmosphere for 10 min. The mixture was then stirred at room temperature for 3 hours. Two equivalents of TBAF were added and stirred for 1 hour at room temperature. The mixture was

200 co-collected and purified by flash chromatography on SiO₂ using 100% hexane to 20% ethyl acetate in hexane as a gradient eluent to give 518 mg (93%) of the product as a white left powder. MS m / z 375 (M-1)⁺.

Example 800 2,7-phenanthridiol, 1,2,3,4,4a, 9,10,10a-octahydro-4a- (phenylmethyl) -2- (trifluoromethyl) -, (4aS, 10aS) The title compound of this example was produced by methods that are superseded to those described above in Example 799. Mass: 377 (M + 1)⁺.

Example 801 2-Phenantrendiol, 1,2,3,4,4a, 9,10,10a-octahydro-2-methyl-7 - [(2-methyl-3-pyridinyl) methoxy] -4a- (phenylmethyl) (2R, 4aS, 10aS) The title compound of this example was prepared by methods similar to those described above in Example 76. MS: 429 (M + 1)⁺.

Example 802 2-Phenanthrenecarboxamide, 7- (Ethoxyimino) -4b, 5,6,7,8,8a, 9,10-octahydro-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) - (4bS, 7Z, 8aR) The title compound of this example was prepared by methods similar to those described above in Example 244. MS: 483 (M + 1)⁺.

Example 803 Methanesulfonic acid, trifluoro, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (trifluoromethyl) -2-phenanthrenyl ester, [(4H, 748) ) j

A solution of 40 mg of the title compound of Example 799, 55 mg of K₂CO₃, 43 mg of 4-nitrophenyl triflate in 5 mL of anhydrous DMF was stirred under N₂ at room temperature overnight. The reaction mixture was quenched with NaHCO₃ (saturated), extracted with EtOAc, dried over MgSO₄, filtered and concentrated until dry. Purification by preparative TLC using 25% EtOAc in hexane as eluent gave 45 mg (66%) of the title product of this Example as a white solid. MS: 509 (M + 1)⁺.

Example 803B 2-Phenanthrenecarboxylic acid, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-4b- (phenylmethyl) -7- (trifluoromethyl) methyl ester, [4bS- (4ta, 748 $]

Starting with the title product of Example 803A and using methods analogous to those described in Example 14, the title product was obtained according to this example. MS: 419 (M + 1)⁺.

Example 803C 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-N - [(2-methyl-3-pyridinyl) methyl] -4b- (phenylmethyl) -7 - (trifluoromethyl) -, (4bS, 7R, 8aR) To a stirred solution of 300 mg of the title compound of Example 803B in 12 mL of dichloromethane was added 4 mL of 0.5 M 2-methyl-3-aminomethylpyridinamide solution which was produced as and in Example 772. The mixture was heated to reflux overnight. The mixture was cooled to 0 ° C. The reaction mixture was added dropwise with 1N HCl par to the water layer, the pH was about pH 4. The resulting mixture was extracted with EtOAc, Purrkufl over Na₂SO₄, siufl and samsflfnufl

201 pairs for everything were purr. Purification by flash chromatography on SiO₂ using 40% acetone in hexane to 50% acetone. In hexane as a gradient eluent, 290 mg (80%) of the title compound was obtained as a white solid. MS: 509 (M + 1)⁺.

Example 804 2-Phenanthrenecarboxamide, 4b, 5,6,7,8,8a, 9,10-octahydro-7-hydroxy-7-methyl-N - [(2-methyl-3-pyridinyl) methyl] -4b-propyl, (4bR, 7R, 8aS) The title compound of this Example was prepared by conductive peaks described above in Example 244. MS: 408 (M + 1)⁺.

EXAMPLE 805 2 (3H) -phenantrenone, 4a- (2-Butenyl) -4,4a, 9,10-tetrahydro-7-methoxy- [S- (E)] Tithium compound according to this example was prepared by means of hardened peams which is described above above in case 1. MS: 283 (M + 1)⁺.

Example 806 carbamic acid, [4 - [[1,3,4,9,10,10a-hexahydro-2,7-dihydroxy-2- (1-propynyl) -4a (2H) -phenanthrenyl] methyl] phenyl] -1 , 1-dimethylethyl ester, [2R- (2E, 4aα, 10αβ)] The title compound of this example was prepared by the procedures described in Example 9 above. MS: 463 (M + 1)⁺.

The compounds of this invention, whether alone or in combination with each of the compounds of the invention, will generally be given in a suitable composition. The following combination of examples will illustrate the invention.

In the accompanying compositions, "active ingredient" comprises a compound of the invention.

Composition 1: gelatin capsule

Hdrd gelatin capsules are manufactured using the following:

<td>ingredients</td><td>amount (mg / capsule)</td>

<td>Active substance</td><td>0.25-100</td>

<td>Sterkja, NF</td><td>0-650</td>

<td>Starch flowable powder</td><td>0-50</td>

<td>Silicon fluid 350 centipedes</td><td>0-15</td>

<td colspan="2">Tdflus composition is produced using the ingredients listed herein below: Composition 2: for example</td>

<td>ingredients</td><td>amount (mg / tdflu)</td>

<td>Active substance</td><td>0.25-100</td>

<td>Cellulose, drkristalladur</td><td>200-650</td>

<td>Silicon dioxide, smoked</td><td>10-650</td>

202

Steric acid 5-15

The ingredients are mixed and peer pressed to form a mixture.

Tablets, each containing 0.25-100 mg of active ingredient, are formed as follows: Composition 3: Tablets

Ingredient amount (mg / tablet)

<td>Active substance</td><td>0.25-100</td>

<td>starch</td><td>45</td>

<td>Cellulose, square crystals</td><td>35</td>

<td>Polyvinylpyrrolidone (as a 10% solution in water)</td><td>4</td>

<td>sodium</td><td>4.5</td>

<td>Magnesium</td><td>0.5</td>

<td>Talk</td><td>1</td>

<td colspan="2">The active ingredient, starch and cellulose are sent through no. 45 mesh US sieve and mixer well together. A solution of polyvinylpyrrolidone is a blend of a powder that comes out which is pvi</td>

<td>next late through no. 14 mesh US sieve.</td><td>Kirni that are shaped by the pen can be found</td>

<td>Purrkufi vifi 50 ° -60 ° C and sent through no.</td><td>18 mfiskva US sieve. Natríumkarboxýmetýl-</td>

<td colspan="2">starch, magnesium stearate and talc, which have been verified through no. 60 US siege is pvi next added to the core which, after reconstitution, are pressed into a tablet machine for disposal, give a finger.</td>

<td colspan="2">Suspensions each containing 0.25-100 mg of active substance every 5 mL dose are</td>

<td>formed as follows: Composition 4: suspensions</td><td></td>

<td>ingredients</td><td>amount (mg / 5 mL)</td>

<td>Active substance</td><td>0.25-100</td>

<td>sodium</td><td>50 mg</td>

<td>syrup</td><td>1.25 mg</td>

<td>Benzoic acid solution</td><td>0.10 mL</td>

<td>flavoring</td><td>qv</td>

<td>Coloring</td><td>qv</td>

<td>Purified water to</td><td>5 mL</td>

<td colspan="2">The active content is sent through no. 45 mfiskva US sieve and mixer together with sodium carboxymethylcellulose and the syrup to form a smooth paste. The benzoic acid solution, flavorings and pigments are diluted with a little of water and added with stirring. Adequate amount of water is</td>

to be added to form the required volume.

Aerosol solution is formed containing the following ingredients: Composition 5: aerosol

203

<td>ingredients</td><td>amount (weight%)</td>

<td>Active substance</td><td>0.25-100</td>

<td>Etanfll</td><td>25.75</td>

<td>Propellant 22 (chlorodifluoromethane)</td><td>70.00</td>

The active ingredient is mixed with hydrogen and the mixture is added to the propellant 22, cooled to 30 ° C and transferred to the filling equipment. The required quantity is then placed in a rigid steel container and diluted with the remainder of the propellant. The lid is the figure shown on the container.

Endometrial styles are formed as follows:

Composition 6: anal styles

<td>ingredients</td><td>amount (mg / endarm style)</td>

<td>Active substance</td><td>250</td>

<td>Mettufl fatty acid glyceride</td><td>2000</td>

<td colspan="2">Active substance is sent through no. 60 micron US sieve and suspended in saturated fatty acid glycerides that have previously been confirmed by the use of minimum sensitivity. The mixture is then poured into rectangular form with 2 g of volume and allowed to cool.</td>

<td colspan="2">Composition for intravenous administration is formed as follows: Composition 7: intravenous solution</td>

<td>ingredients</td><td>amount (mg / rectum [sic])</td>

<td>Active substance</td><td>250</td>

<td>Equilibrated saline</td><td>1000 mL</td>

A solution of the ingredients listed above is administered to the patient at a rate of approximately 1 mL per minute.

The active substance of any of the combinations listed above can also verify a combination of molecules.