Selective androgen receptor modulators

Abstract

This invention provides compounds of Formula (II), or (IIa) and or salts thereof, pharmaceutical compositions comprising a compound of Formula (II), or (IIa) and a pharmaceutically acceptable excipient, processes for making compounds for Formula (II), or (IIa) and intermediates useful in the preparation of same; and methods of modulating the androgen receptor, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type II diabetes related disorders or diseases, anemia, depression, and renal disease) using compounds of Formula (I), (II), or (IIa).

What is claimed is: 
     
         1 . A compound according to Formula (II), or a pharmaceutically acceptable salt thereof;
 wherein the compound of Formula (II) is:   
       
         
           
           
               
               
           
         
         wherein:
 c is 0, 1, 2, or 3; and 
 X, Y and Z are independently selected from the group consisting of hydrogen, halogen, CN, C 1-4  alkyl, C 1-3  hydroxyalkyl, C 1-3  haloalkyl, NO 2 , NH 2 , C 1-3 alkyl and OH; 
 each R a  is independently selected from halogen, OH, NH(CO)C 1-6  alkyl, C 1-4  alkyl (wherein said C 1-4  alkyl is optionally substituted with from 1-2 substituents each independently selected from CN, OH and C 1-3  alkyl), C 1-5  haloalkyl, monocyclic aryl (wherein said monocyclic aryl is optionally substituted with from 1-3 substituents each independently selected from C 1-3  alkyl, C 1-5  haloalkyl, CN, halogen, OH and C 1-3  alkyl), benzyl (wherein the phenyl group of said benzyl is optionally substituted with from 1-3 substituents each independently selected from halogen, C 1-3  alkyl, S(O) 0-2 C 1-3  alkyl, S(O) 0-2 phenyl, O—C 1-6  alkyl, and OCF 3 ), C(O)—C 1-10  alkyl, SO 3 —, PO 3 —, SO 2 NR b R b′  and C(O)phenyl; 
 with the proviso that at least two of X, Y and Z are each independently halogen, C 1-3  haloalkyl, NO 2  or CN; and provided that two of X, Y and Z are not both Br. 
 
       
     
     
         2 . A compound according to  claim 1 , wherein:
 X, Y and Z are independently selected from hydrogen, chlorine, bromine, CF 3  and CN; with the proviso that at least two of X, Y and Z are each independently halogen, C 1-3  haloalkyl, or CN; and provided that two of X, Y and Z are not both Br.   
     
     
         3 . A compound according to  claim 1 , wherein:
 each R a  is independently selected from chlorine, fluorine, bromine, CH 3  and benzyl.   
     
     
         4 . A compound according to  claim 1 , wherein:
 c is 0, or 1.   
     
     
         5 . A compound according to  claim 1 , wherein:
 X and Y are hydrogen;   Z is CN;   each R a  is independently selected from bromine and benzyl; and   c is 0 or 1.   
     
     
         6 . A compound according to  claim 1 , wherein:
 X and Y are hydrogen; Z is bromine;   Each R a  is independently selected from bromine and benzyl; and   c is 0 or 1.   
     
     
         7 . A compound according to  claim 1 , wherein:
 X and Y are chlorine;   Z is hydrogen;   each R a  is independently selected from bromine and benzyl; and   c is 0 or 1.   
     
     
         8 . A compound according to  claim 1 , wherein the compound of Formula (II) is a compound of Formula (IIa); or a pharmaceutically acceptable salt thereof;
 wherein the compound of Formula (IIa) is:   
       
         
           
           
               
               
           
         
         wherein: 
         c is 0, 1, 2, or 3; and 
         R a , X, Y and Z are as defined in  claim 1 ; 
         with the proviso that at least two of X, Y and Z are each independently halogen, C 1-3  haloalkyl, NO 2  or CN; and provided that two of X, Y and Z are not both Br. 
       
     
     
         9 . A compound selected from the following:
 6-Bromo-9H-carbzol-1-ol, 8-Hydroxy-9H-carbazole-3-carbonitrile, 5,6-Dichloro-9H-carbazol-1-ol, 2-Bromo-6,7-dichloro-9H-carbazol-1-ol, 2-Benzyl-5,6-dichloro-9H-carbazol-1-ol, and 2-Benzyl-6,7-dichloro-9H-carbazol-1-ol, or a pharmaceutically acceptable salt of any of the foregoing.   
     
     
         10 . A pharmaceutical composition comprising a compound according to  claim 1  or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. 
     
     
         11 . A compound having the Formula (IIa), or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein:
 c is 0, 1, 2, or 3; and 
 R a , X, Y, Z and c are as defined in  claim 1 ; and 
 the compound is useful for the production of an androgen receptor modulator; 
 with the proviso that at least two of X, Y and Z are each independently halogen, C 1-3  haloalkyl, NO 2  or CN; and provided that two of X, Y and Z are not both Br.