Aminophenyl derivatives as selective androgen receptor modulators

Abstract

Disclosed herein is a novel class of aminophenyl compounds having the structure: wherein R 1 is cyano or nitro and ring A is a bi- or tricyclic bridged heterocycle and to their use as modulators of androgen receptor for the treatment or prevention of conditions relating thereto.

1 . A compound selected from the group consisting of:
 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile;   a prodrug ester thereof,   a stereoisomer thereof,   a pharmaceutically acceptable salt thereof,   
     and/or a combination thereof. 
   
   
       2 . The compound of  claim 1  wherein the pharmaceutically acceptable salt is 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile hydrochloride and/or an enantiomer thereof. 
   
   
       3 . The compound of  claim 1  wherein the pharmaceutically acceptable salt is 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile mesylate and/or an enantiomer thereof. 
   
   
       4 . The compound of  claim 1  wherein the stereoisomer is an enantiomer. 
   
   
       5 . A pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of:
 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile;   a prodrug ester thereof,   a stereoisomer thereof,   a pharmaceutically acceptable salt thereof,   
     and/or a combination thereof. 
   
   
       6 . The pharmaceutical composition of  claim 5  further comprising a pharmaceutically acceptable carrier, a diluent, an excipient, or a combination thereof. 
   
   
       7 . The pharmaceutical composition of  claim 5  wherein the pharmaceutically acceptable salt is 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile hydrochloride and/or an enantiomer thereof. 
   
   
       8 . The pharmaceutical composition of  claim 5  wherein the pharmaceutically acceptable salt is 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile mesylate and/or an enantiomer thereof. 
   
   
       9 . The pharmaceutical composition of  claim 5  wherein the stereoisomer is an enantiomer. 
   
   
       10 . A compound selected from the group consisting of: 
     2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile; 
     2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile hydrochloride; and 
     2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile mesylate. 
   
   
       11 . A pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of: 
     2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile; 
     2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile hydrochloride; and 
     2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile mesylate. 
   
   
       12 . The pharmaceutical composition of  claim 5  wherein the pharmaceutically acceptable salt is an enantiomer of 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile hydrochloride. 
   
   
       13 . The pharmaceutical composition of  claim 5  wherein the pharmaceutically acceptable salt is an enantiomer of 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile mesylate. 
   
   
       14 . The compound of  claim 10  wherein the compound is 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile. 
   
   
       15 . The compound of  claim 10  wherein the compound is 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile hydrochloride. 
   
   
       16 . The compound of  claim 10  wherein the compound is 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile mesylate. 
   
   
       17 . The pharmaceutical composition of  claim 11  wherein the compound is 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile. 
   
   
       18 . The pharmaceutical composition of  claim 11  wherein the compound is 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile hydrochloride. 
   
   
       19 . The pharmaceutical composition of  claim 11  wherein the compound is 2-Chloro-4-(3-endo-hydroxy-3-exo-methyl-8-azabicyclo[3.2.1]oct-8-yl)-3-methylbenzonitrile mesylate.