Small molecule inhibitors of the nuclear translocation of androgen receptor for the treatment of castration-resistant prostate cancer

Abstract

A compound, or a pharmaceutically acceptable salt or ester thereof, according to formula I: R 20 —(Z) b —(Y) c —(R 21 ) a —(X) d —R 22 —R 23 wherein R 20 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; Z is alkanediyl, substituted alkanediyl, cycloalkanediyl, or substituted cycloalkanediyl; Y is S, O, S(═O), —S(═O)(═O)—, or NR 10 , wherein R 10 is H or alkyl; R 21 is alkanediyl, substituted alkanediyl, cycloalkanediyl, substituted cycloalkanediyl alkadienyl, substituted alkadienyl, alkatrienyl, substituted alkatrienyl; X is —C(═O)—, —S(═O)(═O)—, or —N(H)C(═O)—; R 22 includes at least one divalent amino radical; R 23 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; a, b, c, and d independently are 0 or 1.

What is claimed is: 
     
         1 . A compound, or a pharmaceutically acceptable salt or ester thereof, selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         2 . The compound of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         5 . A pharmaceutical composition comprising at least one pharmaceutically acceptable additive, and a compound of  claim 1 . 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The pharmaceutical composition of  claim 5 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The pharmaceutical composition of  claim 5 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         9 . A method for treating prostate cancer in a subject, comprising administering to the subject a therapeutically effective amount of a compound of  claim 1 . 
     
     
         10 . The method of  claim 9 , wherein the prostate cancer is castration-resistant prostate cancer. 
     
     
         11 . The method of  claim 9 , wherein the compound is orally administered. 
     
     
         12 . The method of  claim 9 , wherein the method is used in combination with androgen deprivation therapy. 
     
     
         13 . The method of  claim 9 , wherein the agent is co-administered with abiratrone. 
     
     
         14 . The method of  claim 9 , wherein the agent is co-administered with enzalutamide. 
     
     
         15 . The method of  claim 9 , wherein the method further comprises identifying a subject that is in need of treatment with the agent. 
     
     
         16 . The method of  claim 9 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The method of  claim 9 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         18 . The method of  claim 9 , wherein the compound is: