Selective androgen receptor modulators
View Patent ↗This invention provides compounds as described herein or pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound as described herein or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, methods of modulating the androgen receptor using the compounds or compositions described herein, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type 2 diabetes related disorders or diseases, anemia, depression, and renal disease) using the compounds and compositions described herein and processes for making compounds described herein and intermediates useful in the preparation of same.
1. A compound selected from:
(R)-4-(1-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-2-(trifluoromethyl)benzonitrile;
(R)-4-(1-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methyl-2-(trifluoromethyl)benzonitrile;
(R)-4-(1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methyl-2-(trifluoromethyl)benzonitrile;
(R)-2-chloro-4-(1-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methylbenzonitrile; and
(R)-2-chloro-4-(1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methylbenzonitrile;
or pharmaceutically acceptable salt of any of the foregoing.
2. A compound according to claim 1 , selected from:
(R)-2-chloro-4-(1-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methylbenzonitrile; and
(R)-2-chloro-4-(1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methylbenzonitrile,
or a pharmaceutically acceptable salt of any of the foregoing.
3. A pharmaceutical composition comprising a compound according claim 1 and at least one pharmaceutically acceptable excipient.
4. A method of modulating an androgen receptor in a cell, comprising contacting a cell expressing the androgen receptor with a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
5. A method of identifying a compound capable of modulating an androgen receptor comprising contacting a cell expressing an androgen receptor with a compound according to claim 1 , and monitoring the effect of the compound on the cell.
6. A method of treating ameliorating the symptoms of sarcopenia, frailty, cachexia, muscular dystrophy, low body weight, and AIDS wasting in a mammal in need thereof, comprising the administration to said mammal of an effective amount of a compound, or a pharmaceutically acceptable salt thereof, according to claim 1 .
7. The method of claim 6 , wherein the mammal is a human.
8. A method of modulating an androgen receptor in a cell, comprising contacting a cell expressing the androgen receptor with the pharmaceutical composition of claim 3 .
9. A method of treating ameliorating the symptoms of sarcopenia, frailty, cachexia, muscular dystrophy, low body weight, and AIDS wasting in a mammal in need thereof, comprising the administration to said mammal of an effective amount of the pharmaceutical composition of claim 3 .
10. 2-Chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-3-propylbenzonitrile,
or pharmaceutically acceptable salt thereof.
11. 2-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-3,3,3-trifluoro-2-hydroxypropylamino)-3-methylbenzonitrile,
or pharmaceutically acceptable salt thereof.
12. A pharmaceutical composition comprising a compound according claim 10 and at least one pharmaceutically acceptable excipient.
13. A pharmaceutical composition comprising a compound according claim 11 and at least one pharmaceutically acceptable excipient.
14. A method of modulating an androgen receptor in a cell, comprising contacting a cell expressing the androgen receptor with the compound according to claim 10 or a pharmaceutically acceptable salt thereof.
15. A method of modulating an androgen receptor in a cell, comprising contacting a cell expressing the androgen receptor with the compound according to claim 11 or a pharmaceutically acceptable salt thereof.
16. A method of ameliorating the symptoms of sarcopenia, frailty, cachexia, muscular dystrophy, low body weight, AIDS wasting in a mammal in need thereof, comprising the administration to said mammal of an effective amount of a compound, or a pharmaceutically acceptable salt thereof, according to claim 10 .
17. A method of ameliorating the symptoms of sarcopenia, frailty, cachexia, muscular dystrophy, low body weight, and AIDS wasting in a mammal in need thereof, comprising the administration to said mammal of an effective amount of a compound, or a pharmaceutically acceptable salt thereof, according to claim 11 .
18. The method of claim 16 wherein the mammal is a human.
19. The method of claim 17 , wherein the mammal is a human.
20. A method of modulating an androgen receptor in a cell, comprising contacting a cell expressing the androgen receptor with the pharmaceutical composition of claim 12 .
21. A method of modulating an androgen receptor in a cell, comprising contacting a cell expressing the androgen receptor with the pharmaceutical composition of claim 13 .
22. A method of ameliorating the symptoms of sarcopenia, frailty, cachexia, muscular dystrophy, low body weight, and AIDS wasting in a mammal in need thereof, comprising the administration to said mammal of an effective amount of the pharmaceutical composition of claim 12 .
23. A method of ameliorating the symptoms of sarcopenia, frailty, cachexia, muscular dystrophy, low body weight, and AIDS wasting in a mammal in need thereof, comprising the administration to said mammal of an effective amount of the pharmaceutical composition of claim 13 .
24. A method of identifying a compound capable of modulating an androgen receptor comprising contacting a cell expressing an androgen receptor with a compound according to claim 10 , and monitoring the effect of the compound on the cell.
25. A method of identifying a compound capable of modulating an androgen receptor comprising contacting a cell expressing an androgen receptor with a compound according to claim 11 , and monitoring the effect of the compound on the cell.
26. The method of any one of claims 6 , 9 , 16 , 17 , 22 or 23 , wherein the cachexia is cancer cachexia.