US2004082556A1PendingUtilityA1
Inhibitors of type 5 and type 3 17beta-hydroxysteroid dehydrogenase and methods for their use
Est. expiryMar 11, 2018(expired)· nominal 20-yr term from priority
Inventors:Fernand LabrieAlain BelangerSylvain GauthierVan Luu-TheYves MerandDonald PoirierLouis ProvencherShankar Mohan Singh
A61P 43/00A61P 5/24A61P 5/28A61P 35/00A61P 17/00A61P 17/10A61K 31/5685A61K 45/06A61K 31/585C07J 21/00A61P 13/08A61P 17/14A61P 17/08A61P 15/00A61K 31/566
45
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Claims
Abstract
Novel methods of medical treatment and/or inhibition of development of diseases are disclosed for diseases that are sensitive to androgenic or estrogenic activity. The treatments utilize inhibitors of type 5 and/or type 3 17β-hydroxysteroid dehydrogenase. Novel inhibitors of type 5 17β-hydroxysteroid dehydrogenase are also disclosed, as are novel inhibitors of type 3 17β-hydroxysteroid dehydrogenase.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is optional pi bond;
wherein A is selected from the group consisting of straight or branched C 1 -C 4 alkyl, —OR c (R c being a C 1 -C 8 alkyl radical), and —N(R d )R e (R d and R e being independently hydrogen or C 1 -C 8 alkyl or aryl), and unsaturated analogs of any of the foregoing definitions for substituent A;
wherein R 1 is selected from the group consisting of hydrogen and methyl and ethyl;
wherein R 6 is selected from the group consisting of hydrogen, and halogen, and C 1 -C 8 alkyl;
wherein R a is selected from the group consisting of straight or branched C 1 -C 8 alkylene, C 3 -C 7 cycloalkylene; and
R b is selected from the group consisting of hydrogen, substituted or unsubstituted phenyl, C 2 -C 10 acyl, C 2 -C 10 acyloxy, C 2 -C 10 alkoxycarbonyl, and halogen.
2 . The method of claim 1 wherein the optional pi bond at 6 is present.
3 . The method of claim 1 wherein R 6 is methyl.
4 . The method of Cairn 1 wherein R a is C 1 -C 6 alkylene.
5 . The method of claim 1 where A is either methyl or —N(R d )R e .
6 . The method of claim 1 where A is —N(R d )R e .
7 . The method of claim 6 wherein R d is methyl.
8 . The method of claim 6 wherein R e is C 1 -C 6 alkyl or C 7 -C 12 phenyl alkyl.
9 . A method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is an optional pi bond;
wherein R 16β is selected from the group consisting of hydrogen, C 1 -C 8 alkyl, fluoro, chloro, C 1 -C 8 haloalkyl, a moiety which together with R 16α is C 4 -C 7 spirocycloalkyl, C 4 -C 7 halospirocycloalkyl, or ═—R′ 16 (R′ 16 being C 1 -C 3 alkyl) and unsaturated analogs of any of the foregoing definitions of R 16β ;
wherein R 16α is selected from the group consisting of hydrogen, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, a moiety which together with R 16β forms C 4 -C 7 spirocycloalkyl, C 4 -C 7 halospirocycloalkyl, or ═—R′ 16 (R′ 16 being C 1 -C 3 alkyl) and unsaturated analogs of any of the foregoings;
wherein R 15α is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkenyl and C 1 -C 4 alkynyl;
wherein R 19 is either —H or —CH 3 ; and
wherein R 6 is selected from the group consisting of —H, —CH 3 , and halo;
provided that R 16β , R 16α , and R 15α are not simultaneously hydrogen.
10 . The method of claim 9 wherein R 16α is a larger substituent than R 16β .
11 . The method of claim 9 wherein R 6 is hydrogen.
12 . The method of claim 9 wherein the optional pi bond at position 1 is not present.
13 . The method of claim 9 wherein R 16α is a C 3 -C 5 alkyl chain.
14 . A method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is optional pi bond
wherein X is C 1 -C 3 alkyl;
wherein Y is hydrogen or an acyloxy moiety;
wherein R 6 is —H or —CH 3 ;
wherein R 16 is —H or halo;
wherein R 1 is —H or —CH 3 .
15 . The method of claim 14 wherein R 6 is methyl.
16 . The method of claim 14 wherein the optional pi bond at position 1 is present.
17 . The method of claim 14 wherein Y is a C 3 -C 6 fluoroacyloxy.
18 . The method of claim 14 wherein X is methyl.
19 . A method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein n is an integer from 1-2;
wherein the dotted lines are optional double bonds;
wherein X and Y are independently selected from the group consisting of —H, (C 1 -C 3 )alkyl, (C 2 -C 3 ) alkenyl, and methoxycarbonyl;
wherein Z is selected from the group consisting of —H and (C 1 -C 3 )alkyl;
wherein R 3 is selected from the group consisting of hydrogen, acyl, carboxyl, alkoxycarbonyl, substituted or unsubstituted carboxamide, cyano, alkoxy, alkoxyalkoxy, alkythioalkoxy, acyloxy; hydroxy, halo, —O—SO 2 R a (R a being selected from the group consisting of C 1 -C 6 alkyl and C 6 -C 10 aryl), and a moiety which, together with R 2 , is a 5-6 member ring containing at least one oxygen and one nitrogen atom;
wherein R 2 is selected from the group consisting of hydrogen, amido, acyloxy, carboxyl, carboxamide, alkoxycarbonyl, cyano, halo, nitro, C 1 -C 8 alkyl, and CF 3 and a moiety which, together with R 3 , is a 5-6 member ring containing at least one oxygen and one nitrogen atom;
wherein R 4 is hydrogen or halo;
wherein R 6 is selected from the group consisting of hydrogen and oxo;
wherein R 9 is —H or —OH
provided that X, Y, and Z are not all hydrogen when R 3 is methoxy.
20 . The method of claim 19 wherein R 3 is alkoxyalkoxy.
21 . The method of claim 19 wherein R 3 is carboxyl or alkoxyl;
22 . The method of claim 19 wherein at least one of X, Y or Z is methyl.
23 . The method of claim 19 wherein R 3 is carboxamide.
24 . The method of claim 19 wherein both X and Y are methyl.
25 . The method of claim 19 wherein n=1 or 2.
26 . The method of claim 19 wherein R 6 is oxo.
27 . A method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted lines are optional pi bonds;
wherein n=1 or 2; and
wherein a is either —H or —CH 3 ,
wherein b and c are independently hydrogen or methyl;
wherein Z is oxygen or sulfur.
28 . The pharmaceutical composition of claim 27 wherein n=1.
29 . The method of claim 27 wherein at least one of b or c is methyl.
30 . The method of claim 27 wherein both b and c are methyl.
31 . The method of claim 27 wherein Z is oxygen.
32 . A method of inhibiting the activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase selected from the group consisting of:
33 . The method of claim 32 wherein an inhibitor of 17β-hydroxysteroid dehydrogenase selected from the group consisting of:
is administered.
34 . The method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase selected from the group consisting of:
and compounds having the molecular structure:
wherein the dotted lines are optional pi bonds;
wherein A is selected from the group consisting of straight or branched C 1 -C 4 alkyl, —OR c (R c being a C 1 -C 4 alkyl radical), and —N(R d )R e (R d and R e being independently hydrogen or C 1 -C 8 alkyl or aryl), and unsaturated analogs of any of the foregoing definitions for substituent A;
wherein R 1 is selected from the group consisting of hydrogens, and methyl;
wherein R 6 is selected from the group consisting of hydrogen, halogen, and C 1 -C 8 alkyl;
wherein R 16 is selected from the group consisting of H,H and CH 2 ;
wherein R a is selected from the group consisting of straight or branched C 1 -C 8 alkylene, C 3 -C 7 cycloalkylene; and R b is selected from the group consisting of hydrogen, substituted or unsubstituted phenyl, C 2 -C 10 acyl, C 2 -C 10 acyloxy, C 2 -C 10 alkoxycarbonyl, and halogen.
35 . A method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is an optional pi bond;
wherein R 16β is selected from the group consisting of hydrogen, C 1 -C 8 alkyl fluoro, chloro, C 1 -C 8 haloalkyl, a moiety which together with R 16α forms C 4 -C 7 spirocycloalkyl, C 4 -C 7 halospirocycloalkyl, or ═—R′ 16 (R′ 16 being C 1 -C 3 alkyl) and unsaturated analogs of any of the foregoing definitions of R 16β ;
wherein R 16α is selected from the group consisting of hydrogen, C 1 -C 8 alkyl C 1 -C 8 haloalkyl, a moiety which together with R 16β forms C 4 -C 7 spirocycloalkyl C 4 -C 7 halospirocycloalkyl, or ═—R′ 16 (R′ 16 being C 1 -C 3 alkyl) and unsaturated analogs of any of the foregoing;
wherein R 15α is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkenyl and C 1 -C 4 alkynyl;
wherein R 19 is either —H or —CH 3 ; and
wherein R 6 is selected from the group consisting of —H, —CH 3 , and halo;
provided that R 16β, R 16α , and R 15α are not simultaneously hydrogen.
36 . A method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein n=1 or 2;
wherein the dotted lines are optional pi bonds;
wherein X and Y are independently selected from the group consisting of —H, (C 1 -C 3 )alkyl, (C 2 -C 3 ) alkenyl, and methoxycarbonyl;
wherein Z is selected from the group consisting of —H and (C 1 -C 3 )alkyl;
wherein R 3 is selected from the group consisting of acyl, carboxyl, alkoxycarbonyl, substituted or unsubstituted carboxamide, cyano, alkoxy, alkoxyalkoxy, alkythioalkoxy, acyloxy; hydroxy, halo, —O—SO 2 R a (R a being selected from the group consisting of C 1 -C 6 alkyl and C 6 -C 10 aryl), and a moiety which, together with R 2 , is a 5-6 member ring containing at least one oxygen and one nitrogen atom;
wherein R 2 is selected from the group consisting of hydrogen, amido, acyloxy, carboxyl, carboxmide, alkoxycarbonyl, cyano, halo, nitro, C 1 -C 8 alkyl and CF 3 and a moiety which, together with R 3 , is a 5-6 member ring containing at least one oxygen and one nitrogen atom;
wherein R 4 is hydrogen or halo;
wherein R 6 is selected from the group consisting of hydrogen and oxo;
wherein R 9 is —H or —OH;
provided that X, Y and Z are not all hydrogen.
37 . A method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted lines are optional pi bonds;
wherein n=1 or 2; and
wherein a is either —H or —CH;
wherein b and c are independently hydrogen or methyl;
wherein Z is oxygen or sulfur.
38 . A method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is an optional pi bond;
wherein A is selected from the group consisting of straight or branched C 1 -C 4 alkyl, OR c (R c being a C 1 -C 8 alkyl radical), and —N(R d )R e (R d and R e being independently hydrogen or C 1 -C 8 alkyl or aryl), and unsaturated analogs of any of the foregoing definitions for substituent A;
wherein R 1 is selected from the group consisting of hydrogen and methyl;
wherein R 6 is selected from the group consisting of hydrogen, halogen, and C 1 -C 8 alkyl;
wherein R a is selected from the group consisting of straight or branched C 1 -C 8 alkylene, C 3 -C 7 cycloalkylene; and
R b is selected from the group consisting of hydrogen, substituted or unsubstituted phenyl, C 2 -C 10 acyl, C 2 -C 10 acyloxy, C 2 -C 10 alkoxycarbonyl, and halogen;
provided that wherein A is methyl, R a and R b together have at least two carbon atoms and R 1 is methyl.
39 . A method of inhibiting activity of type 5 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted lines are optional pi bonds
wherein X is C 1 -C 3 alkyl;
wherein Y is hydrogen or an acyloxy moiety;
wherein R 6 is —H or —CH 3 ;
wherein R 16α is —H or halo;
wherein R 1 is —H or —CH 3 .
40 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient, diluent or carrier and a therapeutically acceptable amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted lines are optional pi bonds;
wherein A is selected from the group consisting of straight or branched C 1 -C 4 alkyl, —OR c (R c being a C 1 -C 8 alkyl radical), and —N(R d )R e (R d and R e being independently hydrogen or C 1 -C 8 alkyl or aryl), and unsaturated analogs of any of the foregoing definitions for substituent A;
wherein R 1 is selected from the group consisting of hydrogen and methyl;
wherein R 6 is selected from the group consisting of hydrogen, halogen, and C 1 -C 8 alkyl;
wherein R a is selected from the group consisting of straight or branched C 1 -C 8 alkylene, C 3 -C 7 cycloalkylene; and
R b is selected from the group consisting of hydrogen, substituted or unsubstituted phenyl, C 2 -C 10 acyl, C 2 -C 10 acyloxy, C 2 -C 10 alkoxycarbonyl, and halogen;
provided that when A is methyl, R a and R b together have at least two carbon atoms, and R 1 is methyl.
41 . The pharmaceutical composition of claim 40 wherein the optional pi bond at 6 is present.
42 . The method of claim 40 wherein R 6 is methyl.
43 . The pharmaceutical composition of claim 40 wherein R a is C 1 -C 6 alkylene.
44 . The pharmaceutical composition of claim 40 where A is either methyl or —N(R d )R e .
45 . The pharmaceutical composition of claim 40 where A is —N(R d )R e .
46 . The pharmaceutical composition of claim 45 wherein R d is methyl.
47 The pharmaceutical composition of claim 45 wherein R e is C 1 -C 6 alkyl or phenyl C 1 -C 6 alkyl.
48 . A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically acceptable amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is an optional pi bond;
wherein R 16β is selected from the group consisting of hydrogen, C 1 -C 8 alkyl, fluoro, chloro, C 1 -C 8 haloalkyl, a moiety which together with R 16α is C 4 -C 7 spirocycloalkyl, C 4 -C 7 halospirocycloalkyl, or ═—R′ 16 (R′ 16 being C 1 -C 3 alkyl) and unsaturated analogs of any of the foregoing definitions of R 16β ;
wherein R 16α is selected from the group consisting of hydrogen, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, a moiety which together with R 16β forms C 4 -C 7 spirocycloalkyl, C 4 -C 7 halospirocycloalkyl, or ═—R(R′ 16 being C 1 -C 3 alkyl) and unsaturated analogs of any of the foregoings;
wherein R 15α is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkenyl and C 1 -C 4 alkynyl;
wherein R 19 is either —H or —CH 3 ; and
wherein R 6 is selected from the group consisting of —H, —CH 3 , and halo;
provided that R 16β , R 16α , and R 15α are not simultaneously hydrogen.
49 . The pharmaceutical composition of claim 48 wherein R 16α is a large substituent than R 16β .
50 . The pharmaceutical composition of claim 48 wherein R 6 is hydrogen.
51 . The pharmaceutical composition of claim 48 wherein the optional pi bond at position 1 is not present.
52 . The pharmaceutical composition of claim 48 wherein R 16α is a C 3 -C 5 alkyl chain.
53 . A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically acceptable amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is an optional pi bond
wherein X is C 1 -C 3 alkyl;
wherein Y is hydrogen or an acyloxy moiety;
wherein R 6 is —H or —CH 3 ;
wherein R 16 is —H or halo;
wherein R 1 is —H or CH 3 .
54 . The pharmaceutical composition of claim 53 wherein R 6 is methyl.
55 . The pharmaceutical composition of claim 53 wherein the optional pi bond at position 1 is present.
56 . The pharmaceutical composition of claim 53 wherein Y is a C 3 -C 6 fluoroacyloxy.
57 . The pharmaceutical composition of claim 53 wherein X is methyl.
58 . A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically acceptable amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein n is an integer from 1-2;
wherein the dotted lines are optional pi bonds;
wherein X and Y are independently selected from the group consisting of —H, (C 1 -C 3 )alkyl, (C 2 -C 3 ) alkenyl, and methoxycarbonyl;
wherein Z is selected from the group consisting of —H and (C 1 -C 3 )alkyl;
wherein R 3 is selected from the group consisting of hydrogen acyl, carboxyl, alkoxycarbonyl, substituted or unsubstituted carboxamide, cyano, alkoxy, alkoxyalkoxy, alkythioalkoxy, acyloxy; hydroxy, halo, —O—SO 2 R a (R a being selected from the group consisting of C 1 -C 6 alkyl and C 6 -C 10 aryl), and a moiet which, together with R 2 , is a 5-6 member ring containing at least one oxygen and one nitrogen atom;
wherein R 2 is selected from the group consisting of hydrogen, amido, acyloxy, carboxyl, carboxamide, alkoxycarbonyl, cyano, halo, nitro, C 1 -C 8 alkyl, and CF 3 and a moiety which, together with R 3 , is a 5-6 member ring containing at least one oxygen and one nitrogen atom;
wherein R 4 is hydrogen or halo;
wherein R 6 is selected from the group consisting of hydrogen and oxo;
wherein R 9 is —H or —OH;
provided that X, Y, and Z are not all hydrogen.
59 . The pharmaceutical composition of claim 58 wherein R 3 is alkoxyalkoxy.
60 . The pharmaceutical composition of claim 58 wherein R 3 is carboxyl or alkoxyl;
61 . The pharmaceutical composition of claim 58 wherein at least one of X, Y or Z is methyl.
62 . The pharmaceutical composition of claim 58 wherein both X and Y are methyl.
63 . The pharmaceutical composition of claim 58 wherein n=1 or 2.
64 . The pharmaceutical composition of claim 58 wherein R 6 is oxo.
65 . The pharmaceutical composition of claim 58 wherein R 3 is carboxamide.
66 . A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically acceptable amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted lines are optional pi bonds;
wherein n=1 or 2; and
wherein a is either —H or —CH 3 ;
wherein b and c are independently hydrogen or methyl;
wherein Z is oxygen or sulfur.
67 . The pharmaceutical composition of claim 66 wherein n=1.
68 . The pharmaceutical composition of claim 66 wherein at least one of b or c is methyl.
69 . The pharmaceutical composition of claim 66 wherein both b and c are methyl.
70 . The pharmaceutical composition of claim 66 wherein Z is oxygen.
71 . A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically acceptable amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having a molecular structure selected from the group consisting of:
72 . The pharmaceutical composition of claim 71 wherein said inhibitor of 17β-hydroxysteroid dehydrogenase is selected from the group consisting of:
73 . A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is optional pi bond;
wherein A is selected from the group consisting of straight or branched C 1 -C 4 alkyl, —OR c (R c being a C 1 -C 8 alkyl radical), and —N(R d )R e (R d and R e being independently hydrogen or C 1 -C 8 alkyl or aryl), and unsaturated analogs of any of the foregoing definitions for substituent A;
wherein R 1 is selected from the group consisting of hydrogen and methyl;
wherein R 6 is selected from the group consisting halogen and C 1 -C 8 alkyl;
wherein R a is selected from the group consisting of straight or branched C 1 -C 8 alkylene, C 3 -C 7 cycloalkylene; and
R b is selected from the group consisting of hydrogen, substituted or unsubstituted phenyl, C 2 -C 10 acyl, C 2 -C 10 acyloxy, C 2 -C 10 alkoxycarbonyl, and halogen;
provided that when A is methyl, R 1 is methyl.
74 . A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically acceptable amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted lines are optional pi bonds
wherein X is C 1 -C 3 alkyl;
wherein Y is hydrogen or an acyloxy moiety;
wherein R 6 is —H or
wherein R 16 is —H or halo;
wherein R 1 is —H or —CH 3 .
75 . An inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is optional pi bond;
wherein A is selected from the group consisting of straight or branched C 1 -C 4 alkyl, —OR c (R c being a C 1 -C 8 alkyl radical), and —N(R d )R e (Rd and R e being independently hydrogen or C 1 -C 8 alkyl or aryl), and unsaturated analogs of any of the foregoing definitions for substituent A;
wherein R 1 is selected from the group consisting of hydrogen and methyl;
wherein R 6 is selected from the group consisting of halogen and C 1 -C 8 alkyl;
wherein R a is selected from the group consisting of straight or branched C 1 -C 8 alkylene, C 3 -C 7 cycloalkylene; and
R b is selected from the group consisting of hydrogen, substituted or unsubstituted phenyl, C 2 -C 10 acyl, C 2 -C 10 acyloxy, C 2 -C 10 alkoxycarbonyl, and halogen;
provided that when A is methyl, R a and R b together have at least two carbon atoms, and R 1 is methyl.
76 . The inhibitor of claim 75 wherein the optional pi bond at 6 is present.
77 . The inhibitor of claim 75 wherein R 6 is methyl.
78 . The inhibitor of claim 75 wherein R a is C 1 -C 6 alkylene.
79 . The inhibitor of claim 75 where A is either methyl or —N(R d )R e .
80 . The inhibitor of claim 75 where A is —N(R d )R e .
81 . The inhibitor of claim 80 wherein R d is methyl.
82 . The inhibitor of claim 80 wherein R e is C 1 -C 6 alkyl or phenyl C 1 -C 6 alkyl.
83 . An inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is an optional pi bond;
wherein R 16β is selected from the group consisting of hydrogen, C 1 -C 8 alkyl, fluoro, chloro, C 1 -C 8 haloalkyl, a moiety which together with R 16α is C 4 -C 7 spirocycloalkyl, C 4 -C 7 halospirocycloalkyl, or ═—R′ 16 (R′ 16 being C 1 -C 3 alkyl) and unsaturated analogs of any of the foregoing definitions for R 16β ;
wherein R 16α is selected from the group consisting of hydrogen, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, a moiety which together with R 16β is C 4 -C 7 spirocycloalkyl, C 4 -C 7 halospirocycloalkyl, or ═—R(R′ 16 being C 1 -C 3 alkyl) and unsaturated analogs of any of the foregoings;
wherein R 15α is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkenyl and C 1 -C 4 alkynyl;
wherein R 19 is either —H or —CH 3 ; and
wherein R 6 is selected from the group consisting of —H, —CH 3 , and halo;
provided that R 16β , R 16α , and R 15α are not simultaneously hydrogen.
84 . The inhibitor of claim 83 wherein R 16α is a larger substituent than R 16β .
85 . The inhibitor of claim 83 wherein R 6 is hydrogen.
86 . The inhibitor of claim 83 wherein the optional pi bond at position 1 is not present.
87 . The inhibitor of claim 83 wherein R 16 l is a C 3 -C 5 alkyl.
88 . An inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted line is optional pi bond
wherein X is C 1 -C 3 alkyl;
wherein Y is hydrogen or an acyloxy moiety;
wherein R 6 is —H or —CH 3 ;
wherein R 16 is —H or halo;
wherein R 1 is —H or CH 3 .
89 . The inhibitor of claim 88 wherein R 6 is methyl.
90 . The inhibitor of claim 88 wherein the optional pi bond at position 1 is present.
91 . The inhibitor of claim 88 wherein Y is a C 3 -C 6 fluoroacyloxy.
92 . The inhibitor of claim 88 wherein X is methyl.
93 . An inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein n is an integer from 1-2;
wherein the dotted lines are optional pi bonds;
wherein X and Y are independently selected from the group consisting of —H, (C 1 -C 3 )alkyl, (C 2 -C 3 ) alkenyl, and methoxycarbonyl;
wherein Z is selected from the group consisting of —H and (C 1 -C 3 )alkyl;
wherein R 3 is selected from the group consisting of hydrogen, acyl, carboxyl, alkoxycarbonyl, substituted or unsubstituted carboxamide, cyano, alkoxy, alkoxyalkoxy, alkythioalkoxy, acyloxy; hydroxy, halo, —O—SO 2 R a (R a being selected from the group consisting of C 1 -C 6 alkyl and C 6 -C 10 aryl), and a moiety which, together with R 2 , is a 5-6 member ring containing at least one oxygen and one nitrogen atom;
wherein R 2 is selected from the group consisting of hydrogen, amido, acyloxy, carboxyl, carboxamide, alkoxycarbonyl, cyano, halo, nitro, C 1 -C 8 alkyl, and CF 3 and a moiety which, together with R 3 , is a 5-6 member ring containing at least one oxygen and one nitrogen atom;
wherein R 4 is hydrogen or halo;
wherein R 6 is selected from the group consisting of hydrogen and oxo;
wherein R 9 is —H or H;
provided that X, Y, and Z are not all hydrogen.
94 . The inhibitor of claim 93 wherein R 3 is alkoxyalkoxy.
95 . The inhibitor of claim 93 wherein R 3 is carboxyl unsubstituted carboxamide or alkoxyl;
96 . The inhibitor of claim 93 wherein at least one of X, Y or Z is methyl.
97 . The inhibitor of claim 93 wherein both X and Y are methyl.
98 . The inhibitor of claim 93 wherein n=1.
99 . The inhibitor of claim 93 wherein R 6 is oxo.
100 . The inhibitor of claim 93 wherein R 3 is carboxamide.
101 . An inhibitor of type 5 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein the dotted lines are optional pi bonds;
wherein n=1 or 2; and
wherein a is either —H or
wherein b and c are independently hydrogen or methyl;
wherein Z is oxygen or sulfur.
102 . The inhibitor of claim 101 wherein n=1.
103 . The inhibitor of claim 101 wherein at least one of b or c is methyl.
104 . The inhibitor of claim 101 wherein both b and c are methyl.
105 . The inhibitor of claim 101 wherein Z is oxygen.
106 An inhibitor of type 5 17β-hydroxysteroid dehydrogenase having a molecular structure selected from the group consisting of:
107 . The inhibitor of claim 106 wherein said inhibitor of 17β-hydroxysteroid dehydrogenase selected from the group consisting of:
108 . A method of inhibiting type 3 17β-hydroxysteroid dehydrogenase comprising administering to a patient in need of such treatment a therapeutically effective amount of an inhibitor of type 3 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein R is selected from the group consisting of alkoxy, alkylthio, alkoxyalkoxy, alkoxyalkylthio, alkylthioalkoxy, and alkylthioalkylthio, or
wherein n is an integer from 1 to 4.
109 . The method of claim 108 wherein said inhibitor is selected from the group consisting of:
110 . A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically acceptable amount of an inhibitor of type 3 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein R is selected from the group consisting of alkoxy, alkylthio, alkoxyalkoxy, alkoxyalkylthio, alkylthioalkoxy, and alkylthioalkylthio, or
wherein n is an integer from 1 to 4.
111 . The pharmaceutical composition of claim 110 wherein said inhibitor is selected from the group consisting of:
112 An inhibitor of type 3 17β-hydroxysteroid dehydrogenase having the molecular structure:
wherein R is selected from the group consisting of alkoxyethoxy, alkoxyalkylthio, alkylthioalkoxy, and alkylthioalkylthio, or
wherein n is an integer from 1 to 4.
113 The inhibitor of claim 112 wherein said inhibitor is selected from the group consisting of:
114 . A method of treating, or reducing the risk of developing, prostate cancer, comprising administering to a patient in need of such treatment or reduction a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase, and an amount of an LHRH agonist or antagonist effective to reduce testicular secretion of sex steroids.
115 . The method of claim 114 , further comprising administering a therapeutically effective amount of an antiandrogen.
116 . The method of claim 115 , further comprising administering a therapeutically effective amount of a 5α-reductase inhibitor.
117 . The method of claim 114 , further comprising administering a therapeutically effective amount of a 5α-reductase inhibitor.
118 . A method of treating, or reducing the risk of developing prostate cancer, comprising administering to a patient in need of such treatment or reduction a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase and of an inhibitor of type 3 17β-hydroxysteroid dehydrogenase.
119 . The method of claim 118 further comprising a therapeutically effective amount of a 5α-reductase inhibitor.
120 . The method of claim 118 further comprising a therapeutically effective amount of an LHRH agonist or antagonist.
121 . The method of claim 118 further comprising a therapeutically effective amount of an antiandrogen.
122 . The method of claim 118 further comprising a therapeutically effective amount of an LHRH agonist or antagonist and an antiandrogen.
123 . The method of claim 118 further comprising a therapeutically effective amount of an LHRH agonist or antagonist, an antiandrogen, and a 5α-reductase inhibitor.
124 . The method of claim 118 further comprising a therapeutically effective amount of an antiandrogen and a 5α-reductase inhibitor.
125 . The method of claim 118 further comprising a therapeutically effective amount of an LHRH agonist (or antagonist) and a 5α-reductase inhibitor.
126 . A method of treating, or reducing the risk of developing, benign prostatic hyperplasia comprising administering to a patient in need of such treatment or reduction, a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase.
127 . The method of claim 126 , further comprising administering to said patient a therapeutically effective amount of an agent selected from the group consisting of an antiestrogen or an aromatase inhibitor.
128 . The method of claim 126 , further comprising administering to said patient a therapeutically effective amount of an antiandrogen.
129 . The method of claim 126 , further comprising administering to said patient a therapeutically effective amount of an antiandrogen and a 5α-reductase inhibitor.
130 . The method of claim 126 , further comprising administering to said patient a therapeutically effective amount of a 5α-reductase inhibitor.
131 . The method of claim 126 , further comprising administering to said patient a therapeutically effective amount of a 5α-reductase inhibitor and an antiestrogen or an aromatase inhibitor.
132 . The method of claim 126 , further comprising administering to said patient a therapeutically effective amount of a 5α-reductase inhibitor, an antiandrogen, an antiestrogen or an aromatase inhibitor.
133 . A method of treating or reducing the risk of developing, acne, seborrhea, hirsutism or androgenic alopecia, comprising administering to a patient in need of such treatment or reduction, a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase.
134 . The method of claim 133 , further comprising administering to said patient at therapeutically effective amount of an antiandrogen.
135 . The method of claim 133 , further comprising administering to said patient at therapeutically effective amount of a 5α-reductase inhibitor.
136 . The method of claim 133 , further comprising administering to said patient at therapeutically effective amount of a 5α-reductase inhibitor and an antiandrogen.
137 . A method of treating, or reducing the risk of developing, polycystic ovarian syndrome comprising administering to a patient in need of such treatment or reduction a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase.
138 . The method of claim 137 , further comprising administering a therapeutically effective amount of an inhibitor of type 3 17β-hydroxysteroid dehydrogenase.
139 . A method of treating, or reducing the risk of developing, polycystic ovarian syndrome comprising administering to a patient in need of such treatment or reduction, a therapeutically effective amount of an inhibitor of type 3 17β-hydroxysteroid dehydrogenase.
140 . The method of claim 137 further comprising administering a therapeutically effective amount of an antiandrogen.
141 . A method of treating, or reducing the risk of developing, polycystic ovarian syndrome comprising administering to a patient in need of such treatment or reduction a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase, an inhibitor of type 3 17β-hydroxysteroid dehydrogenase, and an antiandrogen.
142 . The method of claim 139 further comprising administering a therapeutically effective amount of an antiandrogen.
143 . A method of treating, or reducing the risk of developing, breast cancer comprising administering to a patient in need of such treatment or reduction, a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase and a therapeutically effective amount of an antiestrogen.
144 . The method of claim 143 further comprising administering a therapeutically effective amount of an LHRH agonist or antagonist.
145 . The method of claim 143 , further comprising administering a therapeutically effective amount of an androgenic compound.
146 . The method of claim 145 , further comprising administering an amount of an LHRH agonist effective to reduce ovarian secretion of sex steroids.
147 . A method of treating, or reducing the risk of developing, endometriosis or leiomyoma comprising administering to a patient in need of such treatment or reduction, a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase.
148 . The method of claim 147 , further comprising administering to said patient a therapeutically effective amount of an antiestrogen or of an inhibitor of aromatase.
149 . The method of claim 147 , further comprising administering to said patient an amount of an LHRH agonist (or antagonist) effective to reduce ovarian secretion of sex steroids.
150 . The method of claim 149 , further comprising administering a therapeutically effective amount of an antiestrogen or of an aromatase inhibitor.
151 . A method of inhibiting testicular hormonal secretions comprising administering to a patient in need of such inhibition an amount of an inhibitor of type 3 17β-hydroxysteroid dehydrogenase effective to reduce testicular production of sex steroids.
152 . The method of claim 151 further comprising administering a therapeutically effective amount of an antiandrogen.
153 . The method of claim 152 further comprising administering a therapeutically effective amount of a 5α-reductase inhibitor.
154 . The method of claim 151 , further comprising administering an LHRH agonist.
155 . The method of claim 154 , further comprising administering an antiandrogen.
156 . The method of claim 154 , further comprising administering an antiandrogen and a 5α-reductase inhibitor.
157 . The method of claim 151 , further comprising administering an LHRH antagonist.
158 . The method of claim 157 , further comprising administering an antiandrogen.
159 . The method of claim 157 , further comprising administering an antiandrogen and a 5×-reductase inhibitor.
160 . A method of treating precocious puberty comprising administering to a male or female patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase.
161 . The method of claim 160 comprising administering to a male patient a therapeutically effective amount of an LHRH agonist or antagonist.
162 . The method of claim 160 comprising administering to a male or female patient a therapeutically effective amount of an antiandrogen.
163 . The method of claim 160 comprising administering to a male patient a therapeutically effective amount of an antiandrogen and an LHRH agonist or antagonist.
164 . The method of claim 160 comprising administering to a male patient a therapeutically effective amount of an inhibitor of type 3 17β-hydroxysteroid dehydrogenase.
165 . A method of treating precocious puberty comprising administering to a male or female patient in need of such treatment a therapeutically effective amount of an inhibitor of type 3 17β-hydroxysteroid dehydrogenase.
166 . The method of claim 165 further comprising administering to a male patient a therapeutically effective amount of an LHRH agonist or antagonist.
167 . The method of claim 165 further comprising administering to a male or female patient a therapeutically effective amount of an antiandrogen.
168 . The method of claim 165 further comprising administering to a male patient a therapeutically effective amount of an antiandrogen and an LHRH agonist or antagonist.
169 . A pharmaceutical composition comprising:
a) a pharmaceutically acceptable excipient, diluent or carrier; b) a therapeutically effective amount of at least one inhibitor of type 5 17β-hydroxysteroid dehydrogenase; and c) a therapeutically effective amount of at least one antiandrogen.
170 . A pharmaceutical composition of claim 169 wherein said composition further comprising a therapeutically effective amount of a 5α-reductase inhibitor.
171 . A pharmaceutical composition of claim 169 wherein said composition further comprising a therapeutically effective amount of at least one antiestrogen or one aromatase inhibitor.
172 . A pharmaceutical composition of claim 170 wherein said composition further comprising a therapeutically effective amount of at least one antiestrogen or one aromatase inhibitor.
173 . A pharmaceutical composition comprising:
a) a pharmaceutically acceptable excipient, diluent or carrier; b) a therapeutically effective amount of at least one inhibitor of type 5 17β-hydroxysteroid dehydrogenase; and c) a therapeutically effective amount of at least one inhibitor of type 3 17β-hydroxysteroid dehydrogenase
174 . A pharmaceutical composition comprising:
a) a pharmaceutically acceptable excipient, diluent or carrier; b) a therapeutically effective amount of at least one inhibitor of type 3 17β-hydroxysteroid dehydrogenase; and c) a therapeutically effective amount of at least one antiandrogen.
175 . A pharmaceutical composition comprising:
a) a pharmaceutically acceptable excipient, diluent or carrier; b) a therapeutically effective amount of at least one inhibitor of type 3 17β-hydroxysteroid dehydrogenase; and c) a therapeutically effective amount of at least one 5α-reductase inhibitor.
176 . A pharmaceutical composition of claim 174 wherein said composition further comprising a therapeutically effective amount of at least one 5α-reductase inhibitor.
177 . A pharmaceutical composition of claim 173 wherein said composition further comprising a therapeutically effective amount of at least one antiandrogen.
178 . A pharmaceutical composition of claim 173 wherein said composition further comprising a therapeutically effective amount of at least one 5α-reductase inhibitor.
179 . A pharmaceutical composition of claim 177 wherein said composition further comprising a therapeutically effective amount of at least one 5α-reductase inhibitor.
180 . A pharmaceutical composition comprising:
a) a pharmaceutically acceptable excipient, diluent or carrier; b) a therapeutically effective amount of at least one inhibitor of type 5 17β-hydroxysteroid dehydrogenase; and c) a therapeutically effective amount of at least one 5α-reductase inhibitor.
181 . A pharmaceutical composition of claim 180 wherein said composition further comprising a therapeutically effective amount of at least one antiestrogen or one aromatase inhibitor.
182 . A pharmaceutical composition comprising:
a) a pharmaceutically acceptable excipient, diluent or carrier; b) a therapeutically effective amount of at least one inhibitor of type 5 17β-hydroxysteroid dehydrogenase; and c) a therapeutically effective amount of at least one antiestrogen or one aromatase inhibitor.
183 . A kit having a plurality of containers wherein contents of each container differ in whole or in part from content of another container, said kit comprising a therapeutically effective amount of at least one inhibitor of type 5 17β-hydroxysteroid dehydrogenase and a therapeutically effective amount of at least one antiandrogen.
184 . A kit having a plurality of containers wherein contents of each container differ in whole or in part from content of another container, said kit comprising a therapeutically effective amount of at least one inhibitor of type 5 17β-hydroxysteroid dehydrogenase and a therapeutically effective amount of at least one inhibitor of type 3 17β-hydroxysteroid dehydrogenase
185 . A kit having a plurality of containers wherein contents of each container differ in whole or in part from content of another container, said kit comprising a therapeutically effective amount of at least one inhibitor of type 3 17β-hydroxysteroid dehydrogenase and a therapeutically effective amount of at least one antiandrogen.
186 . A kit having a plurality of containers wherein contents of each container differ in whole or in part from content of another container, said kit comprising a therapeutically effective amount of at least one inhibitor of type 3 17β-hydroxysteroid dehydrogenase and a therapeutically effective amount of at least one 5α-reductase inhibitor.
187 . A kit having a plurality of containers wherein contents of each container differ in whole or in part from content of another container, said kit comprising a therapeutically effective amount of at least one inhibitor of type 5 17β-hydroxysteroid dehydrogenase and a therapeutically effective amount of at least one 5×-reductase inhibitor.
188 . A kit having a plurality of containers wherein contents of each container differ in whole or in part from content of another container, said kit comprising a therapeutically effective amount of at least one inhibitor of type 5 17β-hydroxysteroid dehydrogenase and a therapeutically effective amount of at least one antiestrogen or one aromatase inhibitor.
189 . A kit having a plurality of containers wherein contents of each container differ in whole or in part from content of another container, said kit comprising a therapeutic effective amount of at least one inhibitor of type 5 17β-hydroxysteroid dehydrogenase and an amount of at least one LHRH agonist or antagonist.
190 . A kit having a plurality of containers wherein contents of each container differ in whole or in part from content of another container, said kit comprising a therapeutic effective amount of at least one inhibitor of type 3 17β-hydroxysteroid dehydrogenase and an amount of at least one LHRH agonist or antagonist.
191 . A method of treating, or reducing the risk of developing, prostate cancer, comprising administering to a patient in need of such treatment or reduction a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase, and an amount of an LHRH agonist or antagonist effective to reduce testicular secretion of sex steroids wherein the inhibitor of type 5 17β-hydroxysteroid dehydrogenase is not medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, 1-dehydromegestrol acetate, melengestrol acetate, nomegestrol acetate, 1-dehydromelengestrol acetate, and cyproterone acetate.
192 . A method of treating, or reducing the risk of developing, benign prostatic hyperplasia comprising administering to a patient in need of such treatment or reduction, a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase wherein the inhibitor of type 5 17β-hydroxysteroid dehydrogenase is not medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, 1-dehydromegestrol acetate, melengestrol acetate, nomegestrol acetate, 1-dehydromelengestrol acetate, and cyproterone acetate.
193 . A method of treating or reducing the risk of developing, acne, seborrhea, hirsutism or androgenic alopecia, comprising administering to a patient in need of such treatment or reduction, a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase wherein the inhibitor of type 5 17β-hydroxysteroid dehydrogenase is not medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, 1-dehydromegestrol acetate, melengestrol acetate, nomegestrol acetate, 1-dehydromelengestrol acetate, and cyproterone acetate.
194 . A method of treating, or reducing the risk of developing, polycystic ovarian syndrome comprising administering to a patient in need of such treatment or reduction a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase wherein the inhibitor of type 5 17β-hydroxysteroid dehydrogenase is not medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, 1-dehydromegestrol acetate, melengestrol acetate, nomegestrol acetate, 1-dehydromelengestrol acetate, and cyproterone acetate.
195 . A method of treating, or reducing the risk of developing, breast cancer comprising administering to a patient in need of such treatment or reduction, a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase and a therapeutically effective amount of an antiestrogen wherein the inhibitor of type 5 17β-hydroxysteroid dehydrogenase is not medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, 1-dehydromegestrol acetate, melengestrol acetate, nomegestrol acetate, 1-dehydromelengestrol acetate, and cyproterone acetate.
196 . A method of treating, or reducing the risk of developing, endometriosis or leiomyoma comprising administering to a patient in need of such treatment or reduction, a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase wherein the inhibitor of type 5 17β-hydroxysteroid dehydrogenase is not medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, 1-dehydromegestrol acetate, melengestrol acetate, nomegestrol acetate, 1-dehydromelengestrol acetate, and cyproterone acetate.
197 . A method of treating precocious puberty comprising administering to a male or female patient in need of such treatment a therapeutically effective amount of an inhibitor of type 5 17β-hydroxysteroid dehydrogenase.
198 . The method of claim 1 wherein the inhibitor of type 5 17β-hydroxysteroid dehydrogenase is not medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, 1-dehydromegestrol acetate, melengestrol acetate, nomegestrol acetate, 1-dehydromelengestrol acetate, and cyproterone acetate.
199 . The method of claim 38 wherein the inhibitor of type 5 17β-hydroxysteroid dehydrogenase is not medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, 1-dehydromegestrol acetate, melengestrol acetate, nomegestrol acetate, 1-dehydromelengestrol acetate, and cyproterone acetate.
200 . The pharmaceutical composition of claim 40 wherein the inhibitor of type 5 17β-hydroxysteroid dehydrogenase is not medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, 1-dehydromegestrol acetate, melengestrol acetate, nomegestrol acetate, 1-dehydromelengestrol acetate, and cyproterone acetate.
201 . The pharmaceutical composition of claim 73 wherein the inhibitor of type 5 17β-hydroxysteroid dehydrogenase is not medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, 1-dehydromegestrol acetate, melengestrol acetate, nomegestrol acetate, 1-dehydromelengestrol acetate, and cyproterone acetate.
202 . The method of claim 139 wherein the inhibitor of type 3 17β-hydroxysteroid dehydrogenase is not androsterone.
203 . The method of claim 151 wherein the inhibitor of type 3 17β-hydroxysteroid dehydrogenase is not androsterone.
204 . The method of claim 165 wherein the inhibitor of type 3 17β-hydroxysteroid dehydrogenase is not androsterone.Cited by (0)
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