Androgen Receptor Modulator Compounds and Methods

• US 20070254875A1
• Filed: 03/11/2005
• Published: 11/01/2007
• Est. Priority Date: 03/12/2004
• Status: Active Grant

• Current Assignee: Ligand Pharmaceuticals, Inc.
• Original Assignee: Ligand Pharmaceuticals, Inc.
• Inventors: Zhi, Lin, Higuchi, Robert, Chen, Jyun-Hung, Kallel, E., Pedram, Bijan, Stevens Lau, Thomas, Ruppar, Daniel, Miller, T., Van Oeveren, Cornelis
• Granted Patent: US 8,519,158 B2
• Time in Patent Office: Days
• US Class Current: 514/230.500
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 15/16 Masculine contraceptives
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07C 205/55 having nitro groups or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the carbon skeleton
• CPC Class Codes: C07C 211/52 the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
• CPC Class Codes: C07C 255/58 containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07D 207/08 with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 207/09 Radicals substituted by nitrogen atoms, not forming part of a nitro radical
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 207/16 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 207/26 : 2-Pyrrolidones
• CPC Class Codes: C07D 207/27 : with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 207/46 : with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 209/04 : Indoles; Hydrogenated indoles
• CPC Class Codes: C07D 209/08 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/12 : Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 211/22 : by oxygen atoms
• CPC Class Codes: C07D 211/56 : Nitrogen atoms nitro radicals C07D211/38
• CPC Class Codes: C07D 211/60 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 215/04 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
• CPC Class Codes: C07D 215/18 : Halogen atoms or nitro radicals
• CPC Class Codes: C07D 265/36 : condensed with one six-membered ring
• CPC Class Codes: C07D 295/073 : with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07F 7/1804 : Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: G01N 2333/723 : Steroid/thyroid hormone superfamily, e.g. GR, EcR, androgen receptor, oestrogen receptor

Abstract

Provided herein are compounds having a structure selected from among Formula (I), Formula (II), Formula (III), Formula (IV), Formula (V) and Formula (VI) that are androgen receptor modulators and/or androgen receptor binding agents. Also disclosed are methods of making and using such compounds, including, but not limited to, using such compounds for treating various conditions.

Claims

1. A compound of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI:

wherein;

R¹ and R² each independently is selected from among hydrogen, F, Cl, Br, I, OR^A, SR^A, NO₂, CN, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, COR^A, CO₂R^A, CONR^AR^B, SOR^A, SO₂R^A, and SO₂NR^AR^B, NHCOR^A, and NHCONR^AR^B, provided that at least one of R¹ and R² is not hydrogen;

R³, R^3a, R⁴, and R⁵ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₄ alkyl, and an optionally substituted C₁-C₄ haloalkyl;

provided that if R¹ is NO₂ and R^3a is F, then at least one of R² and R⁴ and R⁵ is not hydrogen; and

provided that if R¹ is NO₂ and R³ is F, then Z is not O;

R⁶, R⁷, R¹⁰, and R¹¹ each independently is selected from among hydrogen, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ haloalkyl, an optionally substituted C₁-C₆ heteroalkyl, an optionally substituted C₂-C₆ alkynyl, and an optionally substituted C₂-C₆ alkenyl;

R^6a and R^7a each independently is selected from among hydrogen, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ haloalkyl, an optionally substituted C₁-C₆ heteroalkyl, an optionally substituted C₂-C₆ alkynyl, and an optionally substituted C₂-C₆ alkenyl;

or R^6a and R^7a together form a carbonyl;

R⁸ and R⁹ each independently is selected from among hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₂-C₈ haloalkenyl, C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(R^D)OR^A, CH(R^D)NR^AR^B, and (CH₂)_mR^C;

R¹² and R¹³ each independently is selected from among hydrogen, F, Cl, OR^A, NR^AR^B, SR^A, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ haloalkyl, an optionally substituted C₁-C₆ heteroalkyl, an optionally substituted C₂-C₆ alkynyl, an optionally substituted C₂-C₆ alkenyl, and (CH₂)_mR^C;

R¹⁴ and R¹⁵ each independently is selected from among hydrogen, F, Cl, Br, I, OR^A, SR^A, NO₂, CN, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, NHCOR^A, NHCONR^AR^B, COR^A, CO₂R^A, CONR^AR^B, SOR^A, SO₂R^A, and SO₂NR^AR^B;

R¹⁶ and R¹⁷ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₄ alkyl, and an optionally substituted C₁-C₄ haloalkyl;

R¹⁸ and R¹⁹ each independently is selected from among hydrogen, F, Cl, Br, I, OR^A, SR^A, NO₂, CN, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, NHCOR^A, NHCONR^AR^B, COR^A, CO₂R^A, CONR^AR^B, SOR^A, SO₂R^A, and SO₂NR^AR^B;

R²⁰ and R²¹ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₄ alkyl, and an optionally substituted C₁-C₄ haloalkyl;

wherein if R¹⁸ is NO₂ and X is O, then at least one of R¹⁹, R²⁰, and R²¹ is not hydrogen, and wherein if R¹⁹ is NO₂ and X is C, then at least one of R¹⁸, R²⁰, and R²¹ is not hydrogen;

R²² is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, COR⁶, CO₂R^A, CONR^AR^B, SO₂R^A, an optionally substituted aryl, an optionally substituted heteroaryl, CH₂CH(R^D)OR^A, CH₂CH(R^D)NR^AR^B, and (CH₂)_mR^C, wherein the optionally substituted aryl or optionally substituted heteroaryl is optionally substituted with a substituent selected from among F, Cl, Br, I, CN, OR^A, NO₂, NR^AR^B, SR^A, SOR^A, SO₂R^A, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R²³ and R²⁴ each independently is selected from among hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₂-C₈ haloalkenyl, an optionally substituted C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(R^D)OR^A, CH(R^D)NR^AR^B, and (CH₂)_mR^C;

or R²³ and R²⁴ together form a carbonyl group, provided that if R¹⁸ is NO₂ and X is NH, then R²³ and R²⁴ do not together form a carbonyl group;

R²² and R²³ are optionally linked to form a ring;

R²³ and R²⁵ are optionally linked to form a ring;

X is selected from among O, S, CR^AR^B, NR^D, and a bond;

wherein if X is CR^AR^B or a bond, then R²⁵ and R²⁶ each independently is selected from among a halogen, OR^A, NR^AR^B, hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₂-C₈ haloalkenyl, an optionally substituted C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, and (CH₂)_mR^C;

or R²⁵ and R²⁶ together form a carbonyl group;

and wherein if X is selected from among O, S, or NR^D, then R²⁵ and R²⁶ each independently is selected from among hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₂-C₈ haloalkenyl, an optionally substituted C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, and (CH₂)_mR^C;

or R²⁵ and R²⁶ together form a carbonyl group;

R^A and R^B each independently is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R^C is selected from among an optionally substituted aryl and an optionally substituted heteroaryl that is optionally substituted with a substituent selected from among F, Cl, Br, I, CN, OR^A, NO₂, NR^AR^B, SR^A, SOR^A, SO₂R^A, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R^D is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

Z is selected from among O, S, CR^AR^B, and NR^D;

n is 0, 1, or 2; and

m is 1 or 2;

or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

2. The compound of claim 1 of Formula II or Formula IV:

wherein;

R¹ and R² each independently is selected from among hydrogen, F, Cl, Br, I, OR^A, SR^A, NO₂, CN, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, COR^A, CO₂R^A, CONR^AR^B, SOR^A, SO₂R^A, and SO₂NR^AR^B, NHCOR^A, and NHCONR^AR^B, provided that at least one of R¹ and R² is not hydrogen;

R³, R⁴, and R⁵ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₄ alkyl, and an optionally substituted C₁-C₄ haloalkyl;

provided that if R¹ is NO₂ and R³ is F, then Z is not O;

R⁶, R⁷, and R¹⁰ each independently is selected from among hydrogen, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ haloalkyl, an optionally substituted C₁-C₆ heteroalkyl, an optionally substituted C₁-C₆ heterohaloalkyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, an optionally substituted C₂-C₆ alkynyl, and an optionally substituted C₂-C₆ alkenyl;

R^6a and R^7a each independently is selected from among hydrogen, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ haloalkyl, an optionally substituted C₁-C₆ heteroalkyl, an optionally substituted C₁-C₆ heterohaloalkyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, an optionally substituted C₂-C₆ alkynyl, and an optionally substituted C₂-C₆ alkenyl;

or R^6a and R^7a together form a carbonyl;

R⁹ is selected from among hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₁-C₆ heterohaloalkyl, an optionally substituted C₂-C₈ haloalkenyl, C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(R^D)OR^A, CH(R^D)NR^AR^B, COR^A, CO₂R^A and (CH₂)_mR^C;

R¹² and R¹³ each independently is selected from among hydrogen, F, Cl, OR^A, NR^AR^B, SR^A, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ haloalkyl, an optionally substituted C₁-C₆ heteroalkyl, an optionally substituted C₁-C₆ heterohaloalkyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, an optionally substituted C₂-C₆ alkynyl, an optionally substituted C₂-C₆ alkenyl, and (CH₂)_mR^C;

R¹⁴ and R¹⁵ each independently is selected from among hydrogen, F, Cl, Br, I, OR^A, SR^A, NO₂, CN, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, NHCOR^A, NHCONR^AR^B, COR^A, CO₂R^A, CONR^AR^B, SOR^A, SO₂R^A, and SO₂NR^AR^B;

R¹⁶ and R¹⁷ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₄ alkyl, and an optionally substituted C₁-C₄ haloalkyl;

R^A and R^B each independently is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R^C is selected from among an optionally substituted aryl and an optionally substituted heteroaryl that is optionally substituted with a substituent selected from among F, Cl, Br, I, CN, OR^A, NO₂, NR^AR^B, SR^A, SOR^A, SO₂R^A, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R^D is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

Z is selected from among O, S, CR^AR^B, and NR^D;

n is 0, 1, or 2; and

m is 1 or 2.

3. The compound of claim 1, wherein R¹ is NO₂ or CN.

4. The compound of claim 1, wherein R¹ is NO₂.

5. The compound of claim 1, wherein R¹ is CN.

6. The compound of claim 1, wherein R² is an optionally substituted C₁-C₄ alkyl or an optionally substituted C₁-C₄ haloalkyl.

7. The compound of claim 1, wherein R² is C₁-C₄ alkyl or trifluoromethyl.

8. The compound of claim 1, wherein R³, R⁴, and R⁵ each independently is selected from among hydrogen, F, Cl, and an optionally substituted C₁-C₄ alkyl.

9. The compound of claim 1, wherein R³ is hydrogen.

10. The compound of claim 1, wherein R⁴ is hydrogen.

11. The compound of claim 1, wherein R⁵ is hydrogen.

12. The compound of claim 1, wherein R^6a and R^7a each independently is selected from among hydrogen, an optionally substituted C₁-C₆ alkyl, and an optionally substituted C₁-C₆ heterohaloalkyl or R^6a and R^7a together form a carbonyl.

13. The compound of claim 1, wherein R^6a is hydrogen.

14. The compound of claim 1, wherein R^7a is hydrogen or an optionally substituted C₁-C₆ alkyl.

15. The compound of claim 1, wherein R^7a is hydrogen or methyl.

16. The compound of claim 1, wherein R^7a is hydrogen.

17. The compound of claim 1, wherein R^7a is methyl.

18. The compound of claim 1, wherein R^6a and R^7a together form a carbonyl.

19. The compound of claim 1, wherein R¹⁰ is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ heterohaloalkyl and (CH₂)_mR^C.

20. The compound of claim 1, wherein R¹⁰ is hydrogen.

21. The compound of claim 1, wherein R⁹ is selected from among hydrogen, F, Cl, Br, I, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₆ heterohaloalkyl, COR^A, CO₂R^A, CH(R^D)OR^A, and CH(R^D)NR^AR^B.

22. The compound of claim 1, wherein R⁹ is hydrogen, formyl, hydroxy C₁-C₆alkyl, hydroxyhalo C₁-C₆alkyl, C₁-C₆alkylsilyloxy C₁-C₆alkyl, C₁-C₆alkoxycarbonyl, amino C₁-C₆alkyl, carboxy, or C₁-C₆alkylcarbonyloxyC₁-C₆alkyl.

23. The compound of claim 1, wherein R⁹ is hydrogen, formyl, hydroxymethyl, 1-hydroxy-2,2,2-trifluoromethyl, tributylsilyloxymethyl, ethoxycarbonyl, aminomethyl, carboxy, or acetyoxymethyl.

24. The compound of claim 1, wherein R¹² and R¹³ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ heterohaloalkyl and (CH₂)_mR^C.

25. The compound of claim 1, wherein R¹³ is hydrogen, F, OH or benzyl.

26. The compound of claim 1 of formula IIA:

27. The compound of claim 1 of formula IIB:

28. The compound of claim 1, wherein R¹ is NO₂ or CN;

R² is hydrogen, optionally substituted C₁-C₄ alkyl or an optionally substituted C₁-C₄ haloalkyl;

R³, R⁴, and R⁵ each independently is selected from among hydrogen, F, Cl, and an optionally substituted C₁-C₄ alkyl;

R^6a and R^7a each independently is selected from among hydrogen and an optionally substituted C₁-C₆ alkyl;

an optionally substituted C₁-C₆ heterohaloalkyl, or R^6a and R^7a together form a carbonyl;

R⁹ is selected from among hydrogen, F, Cl, Br, I, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₆ heterohaloalkyl, COR^A, CO₂R^A, CH(R^D)OR^A, and CH(R^D)NR^AR^B;

R¹⁰ is hydrogen; and

R¹² and R¹³ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ heterohaloalkyl and (CH₂)_mR^C.

29. The compound of claim 1, wherein R¹ is NO₂ or CN;

R² is hydrogen or trifluoromethyl;

R³, R⁴, and R⁵ each is hydrogen;

R^7a is hydrogen or methyl and R^6a is hydrogen;

or R^6a and R^7a together form a carbonyl;

R⁹ is selected from among hydrogen, formyl, hydroxymethyl, 1-hydroxy-2,2,2-trifluoromethyl, tributylsilyloxymethyl, ethoxycarbonyl, aminomethyl, carboxy, and acetyloxymethyl;

R¹⁰ is hydrogen;

R¹² is hydrogen; and

R¹³ is selected from among hydrogen, F, OH and benzyl.

30. The compound of claim 1, wherein the compound is selected from among:

31. The compound of claim 30, wherein R^7a is an optionally substituted C₁-C₆ heterohaloalkyl.

32. The compound of claim 30, wherein R⁹ is an optionally substituted C₁-C₆ heterohaloalkyl.

33. The compound of claim 30, wherein R¹³ is an optionally substituted C₁-C₆ heterohaloalkyl.

34. The compound of claim 30, wherein the compound is:

35. The compound of claim 30, wherein the compound is:

36. The compound of claim 1 of Formula IIC or Formula IID:

37. The compound of claim 36, wherein R¹ is NO₂;

R₂ is hydrogen or haloalkyl;

R³, R⁴, R⁵, R^6a, R^7a, R⁹, R¹², and R¹³ each is hydrogen; and

R⁹ is selected from among CO₂R^A, CH(R^D)OR^A, and CH(R^D)NR^AR^B.

38. The compound of claim 36, wherein R¹ is NO₂;

R₂ is hydrogen or trifluoromethyl;

R³, R⁴, R⁵, R^6a, R^7a, R⁹, R¹², and R¹³ each is hydrogen; and

R⁹ is selected from among hydroxymethyl, ethoxycarbonyl and acetyoxymethyl.

39. The compound of claim 1, wherein the compound is:

40. The compound of claim 1, wherein the compound is:

41. The compound of claim 1, wherein the compound is:

42. The compound of claim 1 of Formula V or Formula VI:

wherein R¹⁸ and R¹⁹ each independently is selected from among hydrogen, F, Cl, Br, I, OR^A, SR^A, NO₂, CN, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, NHCOR^A, NHCONR^AR^B, COR^A, CO₂R^A, CONR^AR^B, SOR^A, SO₂R^A, and SO₂NR^AR^B;

R²⁰ and R²¹ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₄ alkyl, and an optionally substituted C₁-C₄ haloalkyl;

wherein if R¹⁸ is NO₂ and X is O, then at least one of R¹⁹, R²⁰, and R²¹ is not hydrogen, and wherein if R¹⁹ is NO₂ and X is C, then at least one of R¹⁸, R²⁰, and R²¹ is not hydrogen;

R²² is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, an optionally substituted C₁-C₄ heterohaloalkyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, COR⁶, CO₂R^A, CONR^AR^B, SO₂R^A, an optionally substituted aryl, an optionally substituted heteroaryl, CH₂CH(R^D)OR^A, CH₂CH(R^D)NR^AR^B, and (CH₂)_mR^C, wherein the optionally substituted aryl or optionally substituted heteroaryl is optionally substituted with a substituent selected from among F, Cl, Br, I, CN, OR^A, NO₂, NR^AR^B, SR^A, SOR^A, SO₂R^A, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R²³ and R²⁴ each independently is selected from among hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₂-C₈ haloalkenyl, an optionally substituted C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted C₂-C₈ heterohaloalkenyl, an optionally substituted C₂-C₈ heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(R^D)OR^A, CH(R^D)NR^AR^B, and (CH₂)_mR^C;

or R²³ and R²⁴ together form a carbonyl group, provided that if R¹⁸ is NO₂ and X is NH, then R²³ and R²⁴ do not together form a carbonyl group;

or

R²² and R²³ are optionally linked to form a ring;

or

R²³ and R²⁵ are optionally linked to form a ring;

R²⁵ is selected from among a halogen, OR^A, NR^AR^B, hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₂-C₈ haloalkenyl, an optionally substituted C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heterohaloalkenyl, an optionally substituted C₂-C₈ heterohaloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, and (CH₂)_mR^C;

X is selected from among O, S, CR^AR^B, NR^D, and a bond;

wherein if X is CR^AR^B or a bond, then R²⁵ and R²⁶ each independently is selected from among a halogen, OR^A, NR^AR^B, hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₂-C₈ haloalkenyl, an optionally substituted C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted C₁-C₆ heterohaloalkyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, and (CH₂)_mR^C;

or R²⁵ and R²⁶ together form a carbonyl group;

and wherein if X is O, S, or NR^D, then R²⁵ and R²⁶ each independently is selected from among hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₂-C₈ haloalkenyl, an optionally substituted C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted C₁-C₆ heterohaloalkyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, and (CH₂)_mR^C;

or R²⁵ and R²⁶ together form a carbonyl group;

R^A and R^B each independently is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R^C is selected from among an optionally substituted aryl and an optionally substituted heteroaryl that is optionally substituted with a substituent selected from among F, Cl, Br, I, CN, OR^A, NO₂, NR^AR^B, SR^A, SOR^A, SO₂R^A, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R^D is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

Z is selected from among O, S, CR^AR^B, and NR^D;

n is 0, 1, or 2; and

m is 1 or 2.

43. The compound of claim 1 of Formula V, wherein n is 1:

44. The compound of claim 1 of Formula V, wherein X is CR^AR^B, and R^A and R^B each is hydrogen:

45. The compound of claim 1 of Formula V, wherein X is O:

46. The compound of claim 1, wherein R¹⁸ and R¹⁹ each independently is selected from among hydrogen, NO₂, and an optionally substituted C₁-C₄ alkyl;

R²² is hydrogen, an optionally substituted C₁-C₄ alkyl and an optionally substituted C₁-C₄ haloalkyl;

R²³ and R²⁴ each independently is hydrogen or an optionally substituted C₁-C₄ alkyl; and

R²⁵ and R²⁶ each is hydrogen.

47. The compound of claim 1, wherein R¹⁸ is NO₂.

48. The compound of claim 1, wherein R¹⁹ is NO₂.

49. The compound of claim 1, wherein R²² is hydrogen, heterohaloalkyl or haloalkyl.

50. The compound of claim 1, wherein R²² is hydrogen or trifluoroethyl.

51. The compound of claim 1, wherein R²³ and R²⁴ each independently is hydrogen or methyl.

52. The compound of claim 1 of Formula VI:

53. The compound of claim 52, wherein R¹⁸ is NO₂.

54. The compound of claim 53, wherein R¹⁹ is NO₂.

55. The compound of claim 52, wherein R²² is hydrogen, haloalkyl, an optionally substituted C₁-C₄ heteroalkyl or an optionally substituted C₁-C₄ heterohaloalkyl.

56. The compound of claim 52, wherein R²² is hydrogen or trifluoroethyl.

57. The compound of claim 52, wherein R²³ is hydrogen, an optionally substituted aryl, an optionally substituted heteroaryl or an optionally substituted C₁-C₄ alkyl.

58. The compound of claim 1, wherein R²⁵ is hydrogen, methyl or methoxyphenyl.

59. The compound of claim 1 of Formula III:

wherein;

R¹ and R² each independently is selected from among hydrogen, F, Cl, Br, I, OR^A, SR^A, NO₂, CN, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, COR^A, CO₂R^A, CONR^AR^B, SOR^A, SO₂R^A, and SO₂NR^AR^B, NHCOR^A, and NHCONR^AR^B, provided that at least one of R¹ and R² is not hydrogen;

R^3a, R⁴, and R⁵ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₄ alkyl, and an optionally substituted C₁-C₄ haloalkyl;

provided that if R¹ is NO₂ and R^3a is F, then at least one of R² and R⁴ and R⁵ is not hydrogen;

R⁶, R⁷, R¹⁰, and R¹¹ each independently is selected from among hydrogen, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ haloalkyl, an optionally substituted C₁-C₆ heteroalkyl, an optionally substituted C₁-C₆ heterohaloalkyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, an optionally substituted C₂-C₆ alkynyl, and an optionally substituted C₂-C₆ alkenyl;

R⁸ and R⁹ each independently is selected from among hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₂-C₈ haloalkenyl, C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted C₁-C₆ heterohaloalkyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(R^D)OR^A, CH(R^D)NR^AR^B, and (CH₂)_mR^C;

R¹⁴ and R¹⁵ each independently is selected from among hydrogen, F, Cl, Br, I, OR^A, SR^A, NO₂, CN, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, NHCOR^A, NHCONR^AR^B, COR^A, CO₂R^A, CONR^AR^B, SOR^A, SO₂R^A, and SO₂NR^AR^B;

R¹⁶ and R¹⁷ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₄ alkyl, and an optionally substituted C₁-C₄ haloalkyl;

R^A and R^B each independently is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R^C is selected from among an optionally substituted aryl and a heteroaryl that is optionally substituted with a substituent selected from among F, Cl, Br, I, CN, OR^A, NO₂, NR^AR^B, SR^A, SOR^A, SO₂R^A, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R^D is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl; and

m is 1 or 2;

provided that at least one of R⁶, R⁷, R¹⁰, and R¹¹ is other than hydrogen and at least one of R⁸ and R⁹ is other than hydrogen, alkyl, haloalkyl, alkenyl, and alkynyl.

60. The compound of claim 59, wherein at least one of R⁶, R⁷, R¹⁰, and R¹¹ is other than hydrogen and at least one of R⁸ and R⁹ is heterohaloalkyl.

61. The compound of claim 1 of Formula I:

wherein;

R¹ and R² each independently is selected from among hydrogen, F, Cl, Br, I, OR^A, SR^A, NO₂, CN, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, an optionally substituted C₁-C₄ heteroalkyl, COR^A, CO₂R^A, CONR^AR^B, SOR^A, SO₂R^A, and SO₂NR^AR^B, NHCOR^A, and NHCONR^AR^B, provided that at least one of R¹ and R² is not hydrogen;

R^3a, R⁴, and R⁵ each independently is selected from among hydrogen, F, Cl, OR^A, an optionally substituted C₁-C₄ alkyl, and an optionally substituted C₁-C₄ haloalkyl;

provided that if R¹ is NO₂ and R^3a is F, then at least one of R² and R⁴ and R⁵ is not hydrogen;

R⁶, R⁷, R¹⁰, and R¹¹ each independently is selected from among hydrogen, an optionally substituted C₁-C₆ alkyl, an optionally substituted C₁-C₆ haloalkyl, an optionally substituted C₁-C₆ heteroalkyl, an optionally substituted C₁-C₆ heterohaloalkyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, an optionally substituted C₂-C₆ alkynyl, and an optionally substituted C₂-C₆ alkenyl;

R⁸ and R⁹ each independently is selected from among hydrogen, an optionally substituted C₁-C₈ alkyl, an optionally substituted C₂-C₈ alkenyl, an optionally substituted C₁-C₈ haloalkyl, an optionally substituted C₂-C₈ haloalkenyl, C₁-C₈ heteroalkyl, an optionally substituted C₂-C₈ heteroalkenyl, an optionally substituted C₂-C₈ alkynyl, an optionally substituted C₂-C₈ haloalkynyl, an optionally substituted C₂-C₈ heteroalkynyl, an optionally substituted C₁-C₆ heterohaloalkyl, an optionally substituted C₂-C₆ heterohaloalkenyl, an optionally substituted C₂-C₆ heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(R^D)OR^A, CH(R^D)NR^AR^B, and (CH₂)_mR^C;

R^A and R^B each independently is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R^C is selected from among an optionally substituted aryl and a heteroaryl that is optionally substituted with a substituent selected from among F, Cl, Br, I, CN, OR^A, NO₂, NR^AR^B, SR^A, SOR^A, SO₂R^A, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl;

R^D is selected from among hydrogen, an optionally substituted C₁-C₄ alkyl, an optionally substituted C₁-C₄ haloalkyl, and an optionally substituted C₁-C₄ heteroalkyl; and

m is 1 or 2;

provided that at least one of R⁶, R⁷, R¹⁰, and R¹¹ is other than hydrogen and at least one of R⁸ and R⁹ is heterohaloalkyl.

62. A compound of claim 1, wherein the compound is selected from among:

N,N-bis(2,2,2-trifluoroethyl)-3-methyl-4-nitroaniline (compound

     101);

N,N-bis(2,2,2-trifluoroethyl)-4-nitroaniline (compound

     102);

4-(Bis(2,2,2-trifluoroethyl)amino)-2-(trifluoromethyl)benzonitrile (compound

     103);

(5R)—

N-(4-nitrophenyl)-5-(dimethyl-tert-butylsilyloxymethyl)-2-pyrrolidone (compound

     104);

(5R)—

N-(4-nitrophenyl)-5-(hydroxymethyl)-2-pyrrolidone (compound

     105);

(2R)—

N-(4-nitro-3-trifluoromethylphenyl)-2-(dimethyl-tert-butylsilyloxymethyl)pyrrolidine (compound

     106);

(2R)—

N-(4-nitro-3-trifluoromethylphenyl)-2-(hydroxymethyl)pyrrolidine (compound

     108);

(2R)—

N-(4-nitrophenyl)-2-(hydroxymethyl)pyrrolidine (compound

     109);

(2R)—

N-(3-Trifluoromethyl-4-nitrophenyl)-2-formylpyrrolidine (compound

     110);

(2R)—

N-(3-Trifluoromethyl-4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound

     111);

(2R)—

N-(3-Trifluoromethyl-4-nitrophenyl)-2-(1-(R)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound

     112);

(2S)—

N-(4-nitrophenyl)-2-(hydroxymethyl)pyrrolidine (compound

     113);

(2R)—

N-(4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound

     114);

(2R)—

N-(4-nitrophenyl)-2-(R)-(1-(R)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound

     115);

(2S)—

N-(4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound

     116);

(2S)—

N-(4-nitrophenyl)-2-(1-(R)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound

     117);

3-(3-Methoxyphenyl)-6-nitro-2,7-dimethyl-1H-indole (compound

     118);

4-[Bis-(2,2,2-trifluoroethyl)amino]-2-chloro-3-methyl-benzonitrile (compound

     119);

cis-2,5-Dimethyl-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidine (compound

     120);

trans-2,5-dimethyl-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidine (compound

     121);

1-(4-Nitro-3-trifluoromethylphenyl)-piperidine-2-carboxylic acid ethyl ester (compound

     122);

1-(4-Nitro-3-trifluoromethylphenyl)-4-(hydroxymethyl)-piperidine (compound

     123);

(1-(3-trifluoromethyl-4-nitrophenyl)piperidin-2-yl)methyl acetate (compound

     124);

4-(2-Hydroxymethyl-pyrrolidin-1-yl)-benzonitrile (compound

     125);

4-Benzyl-2-hydroxymethyl-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidine (compound

     126);

2-Fluoro-4-(2-hydroxymethyl-pyrrolidin-1-yl)-benzonitrile (compound

     127);

4-Hydroxy-1-(4-nitrophenyl)-pyrrolidine-2-carboxylic acid ethyl ester (compound

     128);

4-Hydroxy-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidine-2-carboxylic acid ethyl ester (compound

     129);

5-Hydroxymethyl-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidin-3-ol (compound

     130);

2-(Aminomethyl)-1-(4-Nitro-3-trifluoromethylphenyl)-pyrrolidine (compound

     131);

4-Hydroxy-1-(4-nitrophenyl)-pyrrolidine-2-carboxylic acid (compound

     132); and

4-Hydroxy-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidine-2-carboxylic acid (compound

     133);

and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.

63. The compound of claim 1, wherein the compound is a selective androgen receptor modulator.

64. The selective androgen receptor modulator of claim 63, wherein the compound is an androgen receptor agonist.

65. The selective androgen receptor modulator of claim 63, wherein the compound is an androgen receptor antagonist.

66. The selective androgen receptor modulator of claim 63, wherein the compound is an androgen receptor partial agonist.

67. The selective androgen receptor modulator of claim 63, wherein the compound is a tissue-specific modulator.

68. The compound of claim 1, wherein the compound is a selective androgen binding compound.

69. A method for modulating an activity of an androgen receptor, comprising contacting an androgen receptor with a compound of claim 1.

70. The method of claim 68, wherein the androgen receptor is in a cell.

71. A method for identifying a compound that modulates an activity of an androgen receptor comprising:

contacting a cell expressing an androgen receptor with a compound of claim 1;

and

monitoring an effect of the compound upon the cell.

72. A method for treating a patient having a condition susceptible to treatment with an androgen receptor modulator, comprising administering to the patient a pharmaceutical agent comprising a compound of claim 1.

73. The method of claim 72, wherein the condition is selected from among maintenance of muscle strength and function;

reversal or prevention of frailty or age-related functional decline in the elderly;

treatment of catabolic side effects of glucocorticoids;

treatment of reduced bone mass, density or growth;

treatment of chronic fatigue syndrome;

chronic myalgia;

treatment of acute fatigue syndrome and muscle loss;

accelerating of wound healing;

accelerating bone fracture repair;

accelerating healing of complicated fractures;

in joint replacement;

prevention of post-surgical adhesion formation;

acceleration of tooth repair or growth;

maintenance of sensory function;

treatment of periodontal disease;

treatment of wasting secondary to fractures and treatment of wasting in connection with chronic obstructive pulmonary disease, treatment of wasting in connection with chronic liver disease, treatment of wasting in connection with AIDS, cancer cachexia, burn and trauma recovery, chronic catabolic state, eating disorders and chemotherapy;

treatment of cardiomyopathy;

treatment of thrombocytopenia;

treatment of growth retardation in connection with Crohn'"'"'s disease;

treatment of short bowel syndrome;

treatment of irritable bowel syndrome;

treatment of inflammatory bowel disease;

treatment of Crohn'"'"'s disease and ulcerative colitis;

treatment of complications associated with transplantation;

treatment of physiological short stature including growth hormone deficient children and short stature associated with chronic illness;

treatment of obesity and growth retardation associated with obesity;

treatment of anorexia;

treatment of hypercortisolism and Cushing'"'"'s syndrome;

Paget'"'"'s disease;

treatment of osteoarthritis;

induction of pulsatile growth hormone release;

treatment of osteochondro-dysplasias;

treatment of depression, nervousness, irritability and stress;

treatment of reduced mental energy and low self-esteem;

improvement of cognitive function;

treatment of catabolism in connection with pulmonary dysfunction and ventilator dependency;

treatment of cardiac dysfunction;

lowering blood pressure;

protection against ventricular dysfunction or prevention of reperfusion events;

treatment of adults in chronic dialysis;

reversal or slowing of the catabolic state of aging;

attenuation or reversal of protein catabolic responses following trauma;

reducing cachexia and protein loss due to chronic illness;

treatment of hyper-insulinemia;

treatment of immunosuppressed patients;

treatment of wasting in connection with multiple sclerosis or other neurodegenerative disorders;

promotion of myelin repair;

maintenance of skin thickness;

treatment of metabolic homeostasis and renal homeostasis;

stimulation of osteoblasts, bone remodeling and cartilage growth;

regulation of food intake;

treatment of insulin resistance;

treatment of insulin resistance in the heart;

treatment of hypothermia;

treatment of congestive heart failure;

treatment of lipodystrophy;

treatment of muscular atrophy;

treatment of musculoskeletal impairment;

improvement of the overall pulmonary function;

treatment of sleep disorders; and

the treatment of the catabolic state of prolonged critical illness;

treatment of hirsutism, acne, seborrhea, androgenic alopecia, anemia, hyperpilosity, benign prostate hypertrophy, adenomas and neoplasies of the prostate and malignant tumor cells containing the androgen receptor;

osteosarcoma;

hypercalcemia of malignancy;

metastatic bone disease;

treatment of spermatogenesis, endometriosis and polycystic ovary syndrome;

counteracting preeclampsia, eclampsia of pregnancy and preterm labor;

treatment of premenstrual syndrome;

treatment of vaginal dryness;

age related decreased testosterone levels in men, male menopause, hypogonadism, male hormone replacement, male and female sexual dysfunction, male and female contraception, hair loss, Reaven'"'"'s Syndrome and the enhancement of bone and muscle strength.

74. A method according to claim 72, wherein the patient has a condition selected from among acne, male-pattern baldness, wasting diseases, hirsutism, hypogonadism, osteoporoses, infertility, impotence and cancer.

75. A method for stimulating hematopoiesis in a patient, comprising administering to the patient a pharmaceutical agent comprising a compound of claim 1.

76. A method of contraception, comprising administering to a patient a pharmaceutical agent comprising a compound of claim 1.

77. A method of improving athletic performance in an athlete, comprising administering to the athlete a pharmaceutical agent comprising a compound of claim 1.

78. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

82. An article of manufacture, comprising:

packaging material;

a compound of claim 1 that is effective for modulating the activity of androgen receptor, or for treatment, prevention or amelioration of one or more symptoms of androgen receptor mediated diseases or disorders, or diseases or disorders in which androgen receptor activity is implicated, within the packaging material; and

a label that indicates that the compound or composition, or pharmaceutically acceptable derivative thereof, is used for modulating the activity of androgen receptor or for treatment, prevention or amelioration of one or more symptoms of androgen receptor mediated diseases or disorders, or diseases or disorders in which androgen receptor activity is implicated.

79-81. -81. (canceled)