Selective androgen receptor modulators (SARMs) and uses thereof
Provided herein are compounds of formulae I to II that bind to androgen receptors and/or modulate activity of androgen receptors; and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.
1. 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.
2. The compound of claim 1 selected from among:
the compound wherein R 1 is CF 3 , R 2 is H and R 3 is H;
the compound wherein R 1 is CF 3 , R 2 is H and R 3 is methyl;
the compound wherein R 1 is CF 3 , R 2 is methyl and R 3 is hydrogen;
the compound wherein R 1 is F, R 2 is H and R 3 is H;
the compound wherein R 1 is F, R 2 is H and R 3 is methyl;
the compound wherein R 1 is F, R 2 is methyl and R 3 is hydrogen;
the compound wherein R 1 is Cl, R 2 is H and R 3 is H;
the compound wherein R 1 is Cl, R 2 is H and R 3 is methyl; and
the compound wherein R 1 is Cl, R 2 is methyl and R 3 is hydrogen.
3. The A compound of claim 1 selected from among:
4-(2(R)-(1(R)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-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(5)-hydroxyl-2,2,2-trifluoroethyl)-5(R)-methylpyrrolidinyl)-2-trifluoro-methylbenzonitrile;
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-chloro-benzonitrile;
4-(2(R)-(1(S)-hydroxyl-2,2,2-trifluoroethyl)-5(R)-methylpyrrolidinyl)-2-chloro-benzonitrile;
R,R-4-(2-(1-hydroxyl-2,2,2-trifluoroethyl)pyrrolidinyl)-2-chloro-3-methyl-benzonitrile;
4-(2(R)-(1 (5)-hydroxyl-2,2,2-trifluoroethyl)-pyrrolidinyl)-2-chloro-3-methyl-benzonitrile;
3-methyl-4-((R)-2-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-2-(trifluoro-methyl)benzonitrile;
3-methyl-4-((R)-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-2-(trifluoro-methyl)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 or ester thereof.
4. A pharmaceutical composition, comprising:
a compound of claim 1 ; and
a pharmaceutical acceptable carrier.
5. The composition of claim 4 , wherein the composition is formulated for oral, rectal, transmucosal, intestinal, enteral, topical, transdermal, intrathecal, intraventricular, intraperitoneal, intranasal, intraocular, parenteral, intravenous, intramuscular, intramedullary or subcutaneous administration.