Anticancer drugs including the chemical structures of an androgen receptor ligand and a histone deacetylase inhibitor

Abstract

A novel class of drugs for treating androgen receptor (AR) positive cancer including prostate cancer and breast cancer are described. The drugs include the chemical scaffolds of a high affinity androgen receptor ligand and a histone deacetylase inhibitor. Also described are compositions including the novel drugs and methods of treating AR positive cancer using the compositions.

What is claimed is: 
     
         1 . A drug of Formula (I) or Formula (II), 
       
         
           
           
               
               
           
         
       
       wherein:
 n is 1 to 10; and 
 R is a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, an amino group, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an aryl group, an aralkyl group, or a heterocyclic group. 
 
     
     
         2 . The drug of  claim 1 , wherein R is —NHOH. 
     
     
         3 . The drug of  claim 1 , wherein the drug has Formula (II) and wherein n is 6 and R is —NHOH. 
     
     
         4 . A drug of Formula (III), 
       
         
           
           
               
               
           
         
       
       wherein:
 n is 0 to 10; 
 A and B are independently, an aryl group or a heteroaryl group; 
 X is a CH 2  group, a CH group, a nitrogen atom, an oxygen atom, a sulfur atom, or a carbonyl group; 
 Y is a CH 2  group, CH group, a nitrogen atom, an oxygen atom, a sulfur atom, or a carbonyl group; 
    is either present so as to form a double bond, or is absent; 
 W is —CF 3 , —CHF 2 , —CH 2 F, —CH 3 , —C 2 H 6 , 
 
       
         
           
           
               
               
           
         
       
       and
 R is a zinc binding group (ZBG). 
 
     
     
         5 . The drug of  claim 4 , wherein the ZBG is 
       
         
           
           
               
               
           
         
       
       wherein:
 Z is a alkyl group; and 
 Q is an alkyl group, a halogen atom, or an amino group. 
 
     
     
         6 . A pharmaceutical composition comprising the drug of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         7 . A pharmaceutical composition comprising the drug of  claim 4  and a pharmaceutically acceptable carrier. 
     
     
         8 . A method of providing an anti-cancer effect in a subject having androgen receptor (AR) positive cancer, wherein the method comprises administering a therapeutically effective amount of the pharmaceutical composition of  claim 6  to the subject, thereby providing an anti-cancer effect in the subject. 
     
     
         9 . The method of  claim 8 , wherein the AR positive cancer is prostate cancer or breast cancer. 
     
     
         10 . The method of  claim 9 , wherein the prostate cancer is castration-resistant prostate cancer (CRPC). 
     
     
         11 . The method of  claim 8 , wherein the pharmaceutical composition further comprises an additional active ingredient. 
     
     
         12 . The method of  claim 8 , wherein the pharmaceutical composition is administered in conjunction with a second pharmaceutical composition comprising an active ingredient. 
     
     
         13 . The method of  claim 12 , wherein the pharmaceutical composition and the second pharmaceutical composition are administered simultaneously or sequentially. 
     
     
         14 . A method of inhibiting growth of AR positive cancer cells, wherein the method comprises contacting AR positive cancer cells with an effective amount of the drug of  claim 1 . 
     
     
         15 . A method of degrading a full length androgen receptor (AR), wherein the method comprises contacting AR positive cancer cells expressing the full length AR with an effective amount of the drug of  claim 1 . 
     
     
         16 . A method of degrading a full length androgen receptor (AR), wherein the method comprises contacting AR positive cancer cells expressing the full length AR with an effective amount of the drug of  claim 4 . 
     
     
         17 . A method of providing an anti-cancer effect in a subject having androgen receptor (AR) positive cancer, wherein the method comprises administering a therapeutically effective amount of the pharmaceutical composition of  claim 7  to the subject, thereby providing an anti-cancer effect in the subject. 
     
     
         18 . The method of  claim 17 , wherein the AR positive cancer is prostate cancer or breast cancer. 
     
     
         19 . The method of  claim 18 , wherein the prostate cancer is castration-resistant prostate cancer (CRPC). 
     
     
         20 . The method of  claim 17 , wherein the pharmaceutical composition further comprises an additional active ingredient. 
     
     
         21 . The method of  claim 17 , wherein the pharmaceutical composition is administered in conjunction with a second pharmaceutical composition comprising an active ingredient. 
     
     
         22 . The method of  claim 21 , wherein the pharmaceutical composition and the second pharmaceutical composition are administered simultaneously or sequentially. 
     
     
         23 . A method of inhibiting growth of AR positive cancer cells, wherein the method comprises contacting AR positive cancer cells with an effective amount of the drug of  claim 4 .