IP Library › Granted Patent US 7,446,110

Granted Patent B2

US 7,446,110 · App. 10/569,302 · Granted Nov 4, 2008

17-Heterocyclic-4-azasteroid derivatives as androgen receptor modulators

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Quick Facts

Patent No.: US 7,446,110
App. No.: 10/569,302
Granted: Nov 4, 2008
Kind: B2

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USPTO Patent Center↗ Full Patent PDF↗

Abstract

Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

Claims (692)

1. A compound of structural formula I:

a pharmaceutically acceptable salt or a stereoisomer thereof,

wherein:

a and b are each independently chosen from a double bond and a single bond;

X is hydrogen or halogen;

when a is a single bond, Y and Z are each independently chosen from hydrogen, C 1-4 alkyl, and halogen, or Y and Z, together with the carbon atom to which they are attached, form a cyclopropyl group;

when a is a double bond, Y is chosen from hydrogen, C 1-4 alkyl, and halogen;

n is 0, 1, 2, or 3;

U, V, W, and D are each independently chosen from CH, N, and S, provided that at least one of U, V, W, and D is chosen from N, and S, and further provided that when one of U, V, W, and D is S, then the other ring members are independently chosen from N and CH;

R 1 is chosen from hydrogen, CF 3 , carbonyl(C 1-3 alkyl), hydroxyl, C 1-4 alkoxy, halogen, C 1-3 alkyl, hydroxymethyl, and (C 0-6 alkyl) 2 amino, wherein said alkyl and alkoxy are each optionally substituted with one to seven fluorine atoms;

R 2 is chosen from:

halogen,

(carbonyl) 0-1 C 1-10 alkyl,

(carbonyl) 0-1 C 2-10 alkenyl,

(carbonyl) 0-1 C 2-10 alkynyl,

C 1-10 alkenylamino,

(carbonyl) 0-1 aryl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl,

(C 3-8 )heterocyclyl C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl,

C 1-4 acylamino C 0-10 alkyl,

C 0-10 alkylamino C 0-10 alkyl,

di-(C 1-10 alkyl)amino C 0-10 alkyl,

arylC 0-10 alkylamino C 0-10 alkyl,

(arylC 0-10 l alkyl) 2 amino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkylamino C 0-10 alkyl,

(C 3-8 cycloalkyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

(C 3-8 heterocyclyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

(C 3-8 heterocycloalkyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl aminocarbonylamino,

(C 1-10 alkyl) 2 aminocarbonylamino,

(aryl C 1-10 alkyl) 1-2 aminocarbonylamino,

C 0-10 alkyl aminocarbonylamino,

C 3-8 heterocyclyl C 0-10 alkyl aminocarbonylamino,

C 3-8 heterocycloalkyl C 0-10 alkyl aminocarbonylamino,

(C 1-10 alkyl) 2 aminocarbonyl C 0-10 alkyl,

(aryl C 1-10 alkyl) 1-2 aminocarbonyl C 0-10 alkyl,

C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 3-8 heterocyclyl CO 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

aryl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

aryl C 0-10 alkyl carbonylamino C 0-10 alkyl,

amino C 0-10 alkyl carbimidoylC 0-10 alkylamino,

(C 1-10 alkyl) 2 aminocarbonyl,

(aryl C 1-10 alkyl) 1-2 aminocarbonyl,

C 1-10 alkoxy (carbonyl) 0-1 C 0-10 alkyl,

C 0-10 alkylcarboxy C 0-10 alkylamino,

carboxy C 0-10 alkyl,

carboxy aryl,

carboxy C 3-8 cycloalkyl,

carboxy C 3-8 heterocyclyl,

carboxy C 3-8 heterocycloalkyl,

C 1-10 alkoxy,

C 1-10 alkyloxy C 0-10 alkyl,

aryloxy,

C 3-8 cycloalkyloxy,

C 3-8 heterocyclyloxy,

C 3-8 heterocycloalkyloxy,

C 1-10 alkylcarbonyloxy,

C 3-8 heterocyclyl C 0-10 alkylcarbonyloxy,

C 3-8 heterocycloalkyl C 0-10 alkylcarbonyloxy,

C 3-8 cycloalkyl C 0-10 alkylcarbonyloxy,

aryl C 0-10 alkylcarbonyloxy,

C 1-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 heterocyclyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 heterocycloalkyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 cycloalkyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

aryl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

(C 1-10 alkyl) 2 aminocarbonyloxy,

(aryl C 0-10 alkyl) 1-2 aminocarbonyloxy,

(C 3-8 heterocyclyl C 0-10 alkyl) 1-2 aminocarbonyloxy,

(C 3-8 heterocycloalkyl C 0-10 alkyl) 1-2 aminocarbonyloxy,

(C 3-8 cycloalkyl C 0-10 alkyl) 1-2 aminocarbonyloxy,

hydroxy C 0-10 alkyl,

hydroxycarbonylC 0-10 alkoxy,

hydroxycarbonylC 0-10 alkyloxy,

C 1-10 alkylthio,

C 1-10 alkylsulfinyl,

aryl C 1-10 alkylsulfinyl,

C 3-8 heterocyclyl C 0-10 alkylsulfinyl,

C 3-8 heterocycloalkyl C 0-10 alkylsulfinyl,

C 3-8 cycloalkyl C 0-10 alkylsulfinyl,

C 1-10 alkylsulfonyl,

aryl C 1-10 alkylsulfonyl,

C 3-8 heterocyclyl C 0-10 alkylsulfonyl,

C 3-8 heterocycloalkyl C 0-10 alkylsulfonyl,

C 3-8 cycloalkyl C 0-10 alkylsulfonyl,

C 1-10 alkylsulfonylamino,

aryl C 1-10 alkylsulfonylamino,

C 3-8 heterocyclyl C 1-10 alkylsulfonylamino,

C 3-8 heterocycloalkyl C 1-10 alkylsulfonylamino,

C 3-8 cycloalkyl C 1-10 alkylsulfonylamino,

cyano,

nitro,

perfluoroC 1-6 alkyl, and

perfluoroC 1-6 alkoxy, and

wherein R 2 is optionally substituted with at least one substituent, R 3 , chosen from:

halogen,

(carbonyl) 0-1 C 1-10 alkyl,

(carbonyl) 0-1 C 2-10 alkenyl,

(carbonyl) 0-1 C 2-10 alkynyl,

(carbonyl) 0-1 aryl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl,

(C 3-8 )heterocyclyl C 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl,

C 1-4 acylamino C 0-10 alkyl,

C 0-10 alkylamino C 0-10 alkyl,

di-(C 1-10 alkyl)amino C 0-10 alkyl,

arylC 0-10 alkylamino C 0-10 alkyl,

(arylC 0-10 alkyl) 2 amino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino C 1-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 0-10 alkyl carbimidoylC 0-10 alkyl,

(C 1-10 alkyl) 2 aminocarbonyl,

C 1-10 alkoxy (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 alkyloxy C 0-10 alkyl,

(C 1-10 alkyl) 2 aminocarbonyloxy,

hydroxycarbonylC 0-10 alkoxy,

(C 1-10 alkyl) 2 aminocarbonyloxy,

(aryl C 0-10 alkyl) 1-2 aminocarbonyloxy,

hydroxy C 0-10 alkyl,

C 1-10 alkylsulfonyl,

C 1-10 alkylsulfonylamino,

aryl C 1-10 alkylsulfonylamino,

C 3-8 heterocyclyl C 1-10 alkylsulfonylamino,

C 3-8 heterocycloalkyl C 1-10 alkylsulfonylamino,

C 3-8 cycloalkyl C 1-10 alkylsulfonylamino,

cyano,

nitro,

perfluoroC 1-6 alkyl, and

perfluoroC 1-6 alkoxy,

wherein R 3 is optionally substituted with one or more groups chosen from hydrogen, OH, (C 1-6 )alkoxy, halogen, CO 2 H, CN, O(C═O)C 1 -C 6 alkyl, NO 2 , trifluoromethoxy, trifluoroethoxy, —O (0-1) (C 1-10 )perfluoroalkyl, and NH 2 .

2. A compound according to claim 1 , wherein X is fluorine.

3. A compound according to claim 1 , wherein X is hydrogen.

4. A compound according to claim 1 , wherein a is a single bond and b is a double bond.

5. A compound according to claim 1 and of structural formula II, wherein:

a pharmaceutically acceptable salt or a stereoisomer thereof,

wherein:

a and b are each independently chosen from a double bond and a single bond;

n is 0, 1, 2, or 3;

X is hydrogen or halogen;

when a is a single bond, Y and Z are each independently chosen from hydrogen, C 1-4 alkyl, and halogen, or Y and Z, together with the carbon atom to which they are attached, form a cyclopropyl group;

when a is a double bond, Y is chosen from hydrogen, C 1-4 alkyl, and halogen;

is chosen from:

E is S;

R 1 is chosen from: hydrogen, CF 3 , carbonyl(C 1-3 alkyl), hydroxyl, C 1-4 alkoxy, halogen, C 1-3 alkyl, hydroxymethyl, and (C 0-6 alkyl) 2 amino, wherein said alkyl and alkoxy are each optionally substituted with one to seven fluorine atoms;

R 2 is chosen from:

halogen,

(carbonyl) 0-1 C 1-10 alkyl,

(carbonyl) 0-1 C 2-10 alkenyl,

(carbonyl) 0-1 C 2-10 alkynyl,

C 1-10 alkenylamino,

(carbonyl) 0-1 aryl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl,

(C 3-8 )heterocyclyl C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl,

C 1-4 acylamino C 0-10 alkyl,

C 0-10 alkylamino C 0-10 alkyl,

di-(C 1-10 alkyl)amino C 0-10 alkyl,

arylC 0-10 alkylamino C 0-10 alkyl,

(arylC 0-10 alkyl) 2 amino C 0-10 alkyl,

C 1-10 alkoxy (carbonyl) 0-1 C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkylamino C 0-10 alkyl,

(C 3-8 cycloalkyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

(C 3-8 heterocyclyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

(C 3-8 heterocycloalkyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl aminocarbonylamino,

(C 1-10 alkyl) 2 aminocarbonylamino,

(aryl C 1-10 alkyl) 1-2 aminocarbonylamino,

C 0-10 alkyl aminocarbonylamino,

C 3-8 heterocyclyl C 0-10 alkyl aminocarbonylamino,

C 3-8 heterocycloalkyl C 0-10 alkyl aminocarbonylamino,

(C 1-10 alkyl) 2 aminocarbonyl C 0-10 alkyl,

(aryl C 1-10 alkyl) 1-2 aminocarbonyl C 0-10 alkyl,

C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

aryl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

aryl C 0-10 alkyl carbonylamino C 0-10 alkyl,

amino C 0-10 alkyl carbimidoylC 0-10 alkylamino,

(C 1-10 alkyl) 2 aminocarbonyl,

(aryl C 1-10 alkyl) 1-2 aminocarbonyl,

C 1-10 alkoxy (carbonyl) 0-1 C 0-10 alkyl,

C 0-10 alkylcarboxy C 0-10 alkylamino,

carboxy C 0-10 alkyl,

carboxy aryl,

carboxy C 3-8 cycloalkyl,

carboxy C 3-8 heterocyclyl,

carboxy C 3-8 heterocycloalkyl,

C 1-10 alkoxy,

C 1-10 alkyloxy C 0-10 alkyl,

aryloxy,

C 3-8 cycloalkyloxy,

C 3-8 heterocyclyloxy,

C 3-8 heterocycloalkyloxy,

C 1-10 alkylcarbonyloxy,

C 3-8 heterocyclyl C 0-10 alkylcarbonyloxy,

C 3-8 heterocycloalkyl C 0-10 alkylcarbonyloxy,

C 3-8 cycloalkyl C 0-10 alkylcarbonyloxy,

aryl C 0-10 alkylcarbonyloxy,

C 1-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 heterocyclyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 heterocycloalkyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 cycloalkyl C 0-10 alkyloxy(carbonyl) 0-1 C 1-10 alkylamino,

aryl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

(C 1-10 alkyl) 2 aminocarbonyloxy,

(aryl C 0-10 alkyl) 1-2 aminocarbonyloxy,

(C 3-8 heterocyclyl C 0-10 alkyl) 1-2 aminocarbonyloxy,

(C 3-8 heterocycloalkyl C 0-10 alkyl) 1-2 aminocarbonyloxy,

(C 3-8 cycloalkyl C 0-10 alkyl) 1-2 aminocarbonyloxy,

hydroxy C 0-10 alkyl,

hydroxycarbonylC 0-10 alkoxy,

hydroxycarbonylC 0-10 alkyloxy,

C 1-10 alkylthio,

C 1-10 alkylsulfinyl,

aryl C 0-10 alkylsulfinyl,

C 3-8 heterocyclyl C 0-10 alkylsulfinyl,

C 3-8 heterocycloalkyl C 0-10 alkylsulfinyl,

C 3-8 cycloalkyl C 0-10 alkylsulfinyl,

C 1-10 alkylsulfonyl,

aryl C 0-10 alkylsulfonyl,

C 3-8 heterocyclyl C 0-10 alkylsulfonyl,

C 3-8 heterocycloalkyl C 0-10 alkylsulfonyl,

C 3-8 cycloalkyl C 0-10 alkylsulfonyl,

C 1-10 alkylsulfonylamino,

aryl C 1-10 alkylsulfonylamino,

C 3-8 heterocyclyl C 1-10 alkylsulfonylamino,

C 3-8 heterocycloalkyl C 1-10 alkylsulfonylamino,

C 3-8 cycloalkyl C 1-10 alkylsulfonylamino,

cyano,

nitro,

perfluoroC 1-6 alkyl, and

perfluoroC 1-6 alkoxy, and

wherein R 2 is optionally substituted with at least one substituent R 3 ;

R 3 is chosen from:

halogen,

(carbonyl) 0-1 C 1-10 alkyl,

(carbonyl) 0-1 C 2-10 alkenyl,

(carbonyl) 0-1 C 2-10 alkynyl,

(carbonyl) 0-1 aryl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl,

(C 3-8 )heterocyclyl C 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl,

C 1-4 acylamino C 0-10 alkyl,

C 0-10 alkylamino C 0-10 alkyl,

di-(C 1-10 alkyl)amino C 0-10 alkyl,

arylC 0-10 alkylamino C 0-10 alkyl,

(arylC 0-10 alkyl) 2 amino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 0-10 alkyl carbimidoylC 0-10 alkyl,

(C 1-10 alkyl) 2 aminocarbonyl,

C 1-10 alkoxy (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 alkyloxy C 0-10 alkyl,

(C 1-10 alkyl) 2 aminocarbonyloxy,

hydroxycarbonylC 0-10 alkoxy,

(C 1-10 alkyl) 2 aminocarbonyloxy,

(aryl C 0-10 alkyl) 1-2 aminocarbonyloxy,

hydroxy C 0-10 alkyl,

C 1-10 alkylsulfonyl,

C 1-10 alkylsulfonylamino,

aryl C 1-10 alkylsulfonylamino,

C 3-8 heterocyclyl C 1-10 alkylsulfonylamino,

C 3-8 heterocycloalkyl C 1-10 alkylsulfonylamino,

C 3-8 cycloalkyl C 1-10 alkylsulfonylamino,

cyano,

nitro,

perfluoroC 1-6 alkyl, and

perfluoroC 1-6 alkoxy,

6. A compound according to claim 5 , wherein R 1 is chosen from:

hydrogen, CF 3 , hydroxyl, and C 1-3 alkyl optionally substituted with one to seven fluorine atoms.

7. A compound according to claim 6 , wherein R 1 is chosen from:

hydrogen and C 1-3 alkyl.

8. A compound according to claim 7 , wherein R 1 is methyl.

9. A compound according to claim 8 , wherein R 2 is chosen from:

halogen,

(carbonyl) 0-1 C 1-10 alkyl,

(carbonyl) 0-1 C 2-10 alkenyl,

(carbonyl) 0-1 C 2-10 alkynyl,

C 1-10 alkenylamino,

(carbonyl) 0-1 aryl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl,

(C 3-8 )heterocyclyl C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl,

C 1-4 acylamino C 0-10 alkyl,

C 0-10 alkylamino C 0-10 alkyl,

di-(C 1-10 alkyl)amino C 0-10 alkyl,

arylC 0-10 alkylamino C 0-10 alkyl,

(arylC 1-10 alkyl) 2 amino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkylamino C 0-10 alkyl,

(C 3-8 cycloalkyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

(C 3-8 heterocyclyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

(C 3-8 heterocycloalkyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl aminocarbonylamino,

(C 1-10 alkyl) 2 aminocarbonylamino,

(aryl C 1-10 alkyl) 1-2 aminocarbonylamino,

C 0-10 alkyl aminocarbonylamino,

C 3-8 heterocyclyl C 0-10 alkyl aminocarbonylamino,

C 3-8 heterocycloalkyl C 0-10 alkyl aminocarbonylamino,

C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

aryl C 0-10 alkyl carbonylamino C 0-10 alkyl,

amino C 0-10 alkyl carbimidoylC 0-10 alkylamino,

C 0-10 alkylcarboxy C 0-10 alkylamino,

C 1-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 heterocyclyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 heterocycloalkyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 cycloalkyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

aryl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 1-10 alkylsulfonylamino,

aryl C 1-10 alkylsulfonylamino,

C 3-8 heterocyclyl C 1-10 alkylsulfonylamino,

C 3-8 heterocycloalkyl C 1-10 alkylsulfonylamino,

C 3-8 cycloalkyl C 1-10 alkylsulfonylamino,

cyano,

nitro,

perfluoroC 1-6 alkyl, and

perfluoroC 1-6 alkoxy, and

wherein R 2 is optionally substituted with at least one substituent R 3 .

10. A compound according to claim 9 , wherein E is S.

11. A compound according to claim 10 , wherein

is:

12. A compound according to claim 11 , wherein b is a double bond.

13. A compound according to claim 12 , wherein a is a single bond and b is a double bond.

14. A compound according to claim 1 and of structural formula III,

a pharmaceutically acceptable salt or a stereoisomer thereof, wherein:

X is hydrogen or halogen;

n is 0, 1, 2, or 3;

Y and Z are each independently chosen from hydrogen, C 1-4 alkyl, and halogen, or Y and Z, together with the carbon atom to which they are attached, form a cyclopropyl group;

U, V, W, and D are each independently chosen from N and CH, provided that at least one of U, V, W, and D is CH;

R 2 is chosen from:

halogen,

(carbonyl) 0-1 C 1-10 alkyl,

(carbonyl) 0-1 C 2-10 alkenyl,

(carbonyl) 0-1 C 2-10 alkynyl,

C 1-10 alkenylamino,

(carbonyl) 0-1 aryl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl,

(C 3-8 )heterocyclyl C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl,

C 1-4 acylamino C 0-10 alkyl,

C 0-10 alkylamino C 0-10 alkyl,

di-(C 1-10 alkyl)amino C 0-10 alkyl,

arylC 0-10 alkylamino C 0-10 alkyl,

(arylC 0-10 alkyl) 2 amino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkylamino C 0-10 alkyl,

(C 3-8 cycloalkyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

(C 3-8 heterocyclyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

(C 3-8 heterocycloalkyl C 0-10 alkyl) 2 amino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl aminocarbonylamino,

(C 1-10 alkyl) 2 aminocarbonylamino,

(aryl C 1-10 alkyl) 1-2 aminocarbonylamino,

C 0-10 alkyl aminocarbonylamino,

C 3-8 heterocyclyl C 0-10 alkyl aminocarbonylamino,

C 3-8 heterocycloalkyl C 0-10 alkyl aminocarbonylamino,

(C 1-10 alkyl) 2 aminocarbonyl C 0-10 alkyl,

(aryl C 1-10 alkyl) 1-2 aminocarbonyl C 0-10 alkyl,

C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

aryl C 0-10 alkyl aminocarbonyl C 0-10 alkyl,

C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

aryl C 0-10 alkyl carbonylamino C 0-10 alkyl,

amino C 0-10 alkyl carbimidoylC 0-10 alkylamino,

(C 1-10 alkyl) 2 aminocarbonyl,

(aryl C 1-10 alkyl) 1-2 aminocarbonyl,

C 1-10 alkoxy (carbonyl) 0-10 C 0-10 alkyl,

C 0-10 alkylcarboxy C 0-10 alkylamino,

carboxy C 0-10 alkyl,

carboxy aryl,

carboxy C 3-8 cycloalkyl,

carboxy C 3-8 heterocyclyl,

carboxy C 3-8 heterocycloalkyl,

C 1-10 alkoxy,

C 1-10 alkyloxy C 0-10 alkyl,

aryloxy,

C 3-8 cycloalkyloxy,

C 3-8 heterocyclyloxy,

C 3-8 heterocycloalkyloxy,

C 1-10 alkylcarbonyloxy,

C 3-8 heterocyclyl C 0-10 alkylcarbonyloxy,

C 3-8 heterocycloalkyl C 0-10 alkylcarbonyloxy,

C 3-8 cycloalkyl C 0-10 alkylcarbonyloxy,

aryl C 0-10 alkylcarbonyloxy,

C 1-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 heterocyclyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 heterocycloalkyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 cycloalkyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

aryl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

(C 1-10 alkyl) 2 aminocarbonyloxy,

(aryl C 0-10 alkyl) 1-2 aminocarbonyloxy,

(C 3-8 heterocyclyl C 0-10 alkyl) 1-2 aminocarbonyloxy,

(C 3-8 heterocycloalkyl C 0-10 alkyl) 1-2 aminocarbonyloxy,

(C 3-8 cycloalkyl C 0-10 alkyl) 1-2 aminocarbonyloxy,

hydroxy C 0-10 alkyl,

hydroxycarbonylC 0-10 alkoxy,

hydroxycarbonylC 0-10 alkyloxy,

C 1-10 alkylthio,

C 1-10 alkylsulfinyl,

aryl C 0-10 alkylsulfinyl,

C 3-8 heterocyclyl C 0-10 alkylsulfinyl,

C 3-8 heterocycloalkyl C 0-10 alkylsulfinyl,

C 3-8 cycloalkyl C 0-10 alkylsulfinyl,

C 1-10 alkylsulfonyl,

aryl C 0-10 alkylsulfonyl,

C 3-8 heterocyclyl C 1-10 alkylsulfonyl,

C 3-8 heterocycloalkyl C 0-10 alkylsulfonyl,

C 3-8 cycloalkyl C 0-10 alkylsulfonyl,

C 1-10 alkylsulfonylamino,

aryl C 1-10 alkylsulfonylamino,

C 3-8 heterocyclyl C 1-10 alkylsulfonylamino,

C 3-8 heterocycloalkyl C 1-10 alkylsulfonylamino,

C 3-8 cycloalkyl C 1-10 alkylsulfonylamino,

cyano,

nitro,

perfluoroC 1-6 alkyl, and

perfluoroC 1-6 alkoxy, and

wherein R 2 is optionally substituted with at least one substituent, R 3 , chosen from:

halogen,

(carbonyl) 0-1 C 1-10 alkyl,

(carbonyl) 0-1 C 2-10 alkenyl,

(carbonyl) 0-1 C 2-10 alkynyl,

(carbonyl) 0-1 aryl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl,

(C 3-8 )heterocyclyl C 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl,

C 1-4 acylamino C 0-10 alkyl,

C 0-10 alkylamino C 0-10 alkyl,

di-(C 1-10 alkyl)amino C 0-10 alkyl,

arylC 0-10 alkylamino C 0-10 alkyl,

(arylC 1-10 alkyl) 2 amino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 0-10 alkyl carbimidoylC 0-10 alkyl,

(C 1-10 alkyl) 2 aminocarbonyl,

C 1-10 alkoxy (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 alkyloxy C 0-10 alkyl,

(C 1-10 alkyl) 2 aminocarbonyloxy,

hydroxycarbonylC 0-10 alkoxy,

(C 1-10 alkyl) 2 aminocarbonyloxy,

(aryl C 0-10 alkyl) 1-2 aminocarbonyloxy,

hydroxy C 0-10 alkyl,

C 1-10 alkylsulfonyl,

C 1-10 alkylsulfonylamino,

aryl C 1-10 alkylsulfonylamino,

C 3-8 heterocyclyl C 1-10 alkylsulfonylamino,

C 3-8 heterocycloalkyl C 1-10 alkylsulfonylamino,

C 3-8 cycloalkyl C 1-10 alkylsulfonylamino,

cyano,

nitro,

perfluoroC 1-6 alkyl, and

perfluoroC 1-6 alkoxy, and

15. A compound according to claim 14 , wherein X is hydrogen.

16. A compound according to claim 15 , wherein R 2 is chosen from:

halogen,

(carbonyl) 0-1 C 1-10 alkyl,

(carbonyl) 0-1 C 2-10 alkenyl,

(carbonyl) 0-1 aryl C 0-10 alkyl,

C 3-8 cycloalkyl C 1-10 alkyl,

(C 3-8 )heterocyclyl C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl,

C 0-10 alkylamino C 0-10 alkyl,

arylC 0-10 alkylamino C 1-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl aminocarbonylamino,

(aryl C 1-10 alkyl) 1-2 aminocarbonylamino,

C 0-10 alkyl aminocarbonylamino,

C 3-8 heterocyclyl C 0-10 alkyl aminocarbonylamino,

C 3-8 heterocycloalkyl C 0-10 alkyl aminocarbonylamino,

C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl carbonylamino C 0-10 alkyl,

aryl C 0-10 alkyl carbonylamino C 0-10 alkyl,

C 0-10 alkylcarboxy C 0-10 alkylamino,

C 1-10 alkoxy,

C 1-10 alkyloxy C 0-10 alkyl,

aryloxy,

C 3-8 cycloalkyloxy,

C 3-8 heterocyclyloxy,

C 3-8 heterocycloalkyloxy,

C 1-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 heterocyclyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

C 3-8 heterocycloalkyl C 0-10 alkyloxy(carbonyl) 01 C 1-10 alkylamino,

C 3-8 cycloalkyl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

aryl C 0-10 alkyloxy(carbonyl) 0-1 C 0-10 alkylamino,

hydroxy C 0-10 alkyl,

C 1-10 alkylthio,

C 1-10 alkylsulfonyl,

aryl C 1-10 alkylsulfonyl,

C 3-8 heterocyclyl C 0-10 alkylsulfonyl,

C 3-8 heterocycloalkyl C 0-10 alkylsulfonyl,

C 3-8 cycloalkyl C 0-10 alkylsulfonyl,

C 1-10 alkylsulfonylamino,

aryl C 1-10 alkylsulfonylamino,

C 3-8 heterocyclyl C 1-10 alkylsulfonylamino,

C 3-8 heterocycloalkyl C 1-10 alkylsulfonylamino,

C 3-8 cycloalkyl C 1-10 alkylsulfonylamino,

cyano,

nitro,

perfluoroC 1-6 alkyl, and

perfluoroC 1-6 alkoxy, and

wherein R 2 is optionally substituted with at least one substituent R 3 .

17. A compound according to claim 16 , wherein at least two of U, V, W, and D are each N and provided that at least one of U, V, W, and D is CH.

18. A compound according to claim 1 , selected from:

17β-[2-(butylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(anilino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(pyridin-2-ylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[(2-methylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{[2-methyl(phenyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{[2-(4-fluorophenyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(benzylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(isopropylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(pyridin-3-ylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{[2-(2-fluorophenyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{[2-(methoxyethyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{2-[(2-piperid-1-ylethyl)amino]-1,3-thiazol-4-yl})-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{[2-(t-butyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{[2-(4-cyanophenyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{2-[(cyclohexyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5(-androst-1-en-3-one;

17β-{2-[(pyridin-4-ylmethyl]amino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(pyrimidin-2-ylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(pyridin-4-ylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{2-[(cyclopropylmethyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(propylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(allylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(heptylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(octylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(hexylamino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{2-[(5-methyl-1,2,3-thiadiazol-2-yl)amino]-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{[2-(methoxypropyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{2-[(2-morphilin-1-ylethyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{2-[(2,2,2-trifluoroethyl)amino]-1,3-thiazol-4-yl}-4-methyl-4-aza-5(-androst-1-en-3-one;

17β-{2-[(pyridin-2-ylethyl]amino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(amino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(guanidino)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(1-methyl-1H-imidazole-5-carboxado)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(acetamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(phenyl carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(thiephene-3-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(furan-2-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(pyrizine-2-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(pyridine-2-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(thiephene-2-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(pyridine-3-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(pyridine-4-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(1-t-butyl-3-methyl-1H-pyrazole-5-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(1-methyl-proline-2-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(1-methyl-1H-imidazole-2-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(1H-imidazole-2-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(methanesulfonamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(ethyl carbamate)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(isopropyl carbamate)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(2-fluoroethyl carbamate)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(t-butylcarbamate)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(ureyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(N′-pyridin-2ylureyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(N′-cyclopropylureyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(N′-cyclohexylureyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(N′-cyclohexylmethylureyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(morpholine-4-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(piperizine-1-carboxamido)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[N′-isopropylureyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(pyridyl-3-ureyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-{2-[N′-(methylamino)ethethylureyl]-1,3-thiazol-4-yl}-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(ureyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androstan-3-one;

17β-[2-(pyridin-2-yl)-1,3-thiazol-4-yl] -4-methyl-4-aza-5α-androstan-3-one;

17β-[2-(methyl)-1,3-thiazol-4-yl] -4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(pyrid-3-yl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(ethyl acetyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(acetonitrilyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(2-chlorophenyl)-1,3-thiazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(methyl)-1,3-imidazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(phenyl)-1,3-imidazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(3,5-dimethylpyrazol-1-yl)-1,3-imidazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[2-(aminoacetyl)-1,3-imidazol-4-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[5-(amino)-1,2,4-triazol-3-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[5-(ureyl)-1, 2 ,-4-triazol-3-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[5-(N-methyl-ureyl)-1,2,4-triazol-3-yl]-4-methyl-4-aza-5α-androst-1-en-3-one;

17β-[5-(N,N-dimethyl-ureyl)-1,2,4-triazol-3-yl]-4-methyl-4-aza-5α-androst-1-en-3-one; and

pharmaceutically acceptable salts and stereoisomers thereof.

19. A compound according to claim 18 , selected from: