Selective androgen receptor modulators (SARMs) and uses thereof

1. A method of treating a disease, disorder or condition selected from the group consisting of osteopenia, bone damage and bone fracture in a subject having said disease, disorder or condition comprising:

administering to the subject a therapeutically effective amount of a compound of formula I;

wherein:

R 1 is CF 3 , F or Cl;

R 2 is H or methyl; and

R 3 is H or methyl,

or a pharmaceutically acceptable salt or ester thereof,

thereby treating the disease, disorder or condition.

2. The method of claim 1 , wherein R 1 is CF 3 , R 2 is H and R 3 is H.

3. The method of claim 1 , wherein R 1 is CF 3 , R 2 is H and R 3 is methyl.

4. The method of claim 1 , wherein R 1 is CF 3 , R 2 is methyl and R 3 is hydrogen.

5. The method of claim 1 , wherein R 1 is F or Cl, R 2 is H and R 3 is H.

6. The method of claim 1 , wherein R 1 is F or Cl, R 2 is H and R 3 is methyl.

7. The method of claim 1 , wherein R 1 is F or Cl, R 2 is methyl and R 3 is hydrogen.

8. The method of claim 1 , wherein the compound of formula I is selected from among:

R,R-4-(2-(1-Hydroxyl-2,2,2-trifluoroethyl)pyrrolidinyl)-2-trifluoromethyl-benzonitrile;

4-(2(R)-(1(S)-hydroxyl-2,2,2-trifluoroethyl)pyrrolidinyl)-2-trifluoromethyl-benzonitrile;

R,R,R-4-(2-(1-Hydroxyl-2,2,2-trifluoroethyl)-5-methylpyrrolidinyl)-2-trifluoromethyl-benzonitrile;

4-(2(R)-(1(S)-hydroxyl-2,2,2-trifluoroethyl)-5(R)-methylpyrrolidinyl)-2-trifluoromethyl-benzonitrile;

R,R-4-(2-(1-Hydroxyl-2,2,2-trifluoroethyl)pyrrolidinyl)-2-chlorobenzonitrile;

4-(2(R)-(1(S)-hydroxyl-2,2,2-trifluoroethyl)pyrrolidinyl)-2-chlorobenzonitrile;

R,R,R-4-(2-(1-hydroxyl-2,2,2-trifluoroethyl)-5-methylpyrrolidinyl)-2-chlorobenzonitrile;

4-(2(R)-(1(S)-hydroxyl-2,2,2-trifluoroethyl)-5(R)-methylpyrrolidinyl)-2-chlorobenzonitrile;

R,R-4-(2-(1-hydroxyl-2,2,2-trifluoroethyl)pyrrolidinyl)-2-chloro-3-methylbenzonitrile;

4-(2(R)-(1(S)-hydroxyl-2,2,2-trifluoroethyl)-pyrrolidinyl)-2-chloro-3-methylbenzonitrile;

3-methyl-4-((R)-2-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-2-(trifluoromethyl)-benzonitrile;

3-methyl-4-((R)-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-2-(trifluoromethyl)-benzonitrile;

3-methyl-4-((2R,5R)-2-methyl-5-((S)-2,2,2-trifluoro-1-hydroxyethyl)-pyrrolidin-1-yl)-2-(trifluoromethyl)benzonitrile;

2-fluoro-4-((2R,5R)-2-methyl-5-((S)-2,2,2-trifluoro-1-hydroxyethyl)-pyrrolidin-1-yl)-benzonitrile;

2-fluoro-3-methyl-4-((2R,5R)-2-methyl-5-((S)-2,2,2-trifluoro-1-hydroxyethyl)-pyrrolidin-1-yl)benzonitrile;

2-fluoro-3-methyl-4-((R)-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-benzonitrile;

2-fluoro-4-((R)-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)benzonitrile;

2-chloro-4-((2R,5R)-2-methyl-5-((S)-2,2,2-trifluoro-1-hydroxyethyl)-pyrrolidin-1-yl)-benzonitrile;

2-chloro-3-methyl-4-((2R,5R)-2-methyl-5-((S)-2,2,2-trifluoro-1-hydroxyethyl)-pyrrolidin-1-yl)benzonitrile;

2-chloro-3-methyl-4-((R)-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-benzonitrile; and

2-chloro-4-((R)-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-benzonitrile;

or a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein the compound of formula I is 4-(2(R)-(1(S)-hydroxyl-2,2,2-trifluoroethyl)pyrrolidinyl)-2-trifluoromethyl-benzonitrile, or a pharmaceutically acceptable salt thereof.

10. The method of claim 1 , wherein the disease, disorder or condition is a bone fracture.

11. The method of claim 10 , wherein the bone fracture is a hip fracture.

12. The method of claim 1 , wherein the bone fracture is treated by accelerating bone fracture repair.

13. The method of claim 12 , wherein the bone fracture is a hip fracture.

14. The method of claim 12 , wherein the compound of formula I is 4-(2(R)-(1(S)-hydroxyl-2,2,2-trifluoroethyl)pyrrolidinyl)-2-trifluoromethyl-benzonitrile, or a pharmaceutically acceptable salt thereof.

15. The method of claim 14 , wherein the bone fracture is a hip fracture.