Treatment of Breast Cancer

Abstract

The disclosure describes compounds useful for treating breast cancers.

1 . A method of treating triple negative breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 X is selected from the group consisting of trifluoromethyl and iodo; 
 W is selected from the group consisting of O and NR5, wherein R5 is selected from the group consisting of H, methyl, and 
 
       
         
           
           
               
               
           
         
       
       wherein D is S or O and E is N or O and G is alkyl, aryl, substituted alkyl or substituted aryl; or D is S or O and E-G together are C1-C4 lower alkyl;
 R 1  and R 2  together comprise eight or fewer carbon atoms and are selected from the group consisting of alkyl, substituted alkyl including haloalkyl, and, together with the carbon to which they are linked, a cycloalkyl or substituted cycloalkyl group; 
 R3 is selected from the group consisting of hydrogen, halogen, methyl, C1-C4 alkoxy, formyl, haloacetoxy, trifluoromethyl, cyano, nitro, hydroxyl, phenyl, amino, methylcarbamoyl, methoxycarbonyl, acetamido, methanesulfonamino, methanesulfonyl, 4-methanesulfonyl-1-piperazinyl, piperazinyl, and C1-C6 alkyl or alkenyl optionally substituted with hydroxyl, methoxycarbonyl, cyano, amino, amido, nitro, carbamoyl, or substituted carbamoyl including methylcarbamoyl, dimethylcarbamoyl, and hydroxyethylcarbamoyl, with the proviso that R3 is not methylaminomethyl or dimethylaminomethyl; and 
 R4 is selected from the group consisting of hydrogen, halogen, alkyl, and haloalkyl. 
 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . A method of treating triple negative breast cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (II): 
       
         
           
           
               
               
           
         
       
       wherein:
 Het represents a heterocyclic unit of 5 or 6 atoms; 
 A and B are independently selected from oxygen, sulfur, and N—R 9 ; 
 R1 is selected from hydrogen, aryl, substituted aryl, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, halogenated alkyl, halogenated alkenyl, halogenated alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic, cycloalkyl, substituted cycloalkyl, SO 2 R 11 , NR 11 R 12 , NR 12 (CO)OR 11 , NH(CO)NR 11 R 12 , NR 12 (CO)R 11 , O(CO)R 11 , O(CO)OR 11 , O(CS)R 11 , NR 12 (CS)R 11 , NH(CS)NR 11 R 12 , or NR 12 (CS)OR 11 ; 
 R 2  and R 3  are independently selected from hydrogen, aryl, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, halogenated alkyl, halogenated alkenyl, halogenated alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic, cycloalkyl, or substituted cycloalkyl, or, together with the carbon to which they are linked, form a cycle which can be cycloalkyl, substituted cycloalkyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic; or R 2  and R 3  can be connected to form a cycle which can be heterocyclic aromatic or non aromatic, substituted heterocyclic aromatic or non aromatic; 
 R 9  is selected from hydrogen, aryl, substituted aryl, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, halogenated alkyl, halogenated alkenyl, halogenated alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic or non-aromatic, cycloalkyl, substituted cycloalkyl, SO 2 R 11 , NR 11 R 12 , NR 12 (CO)OR 11 , NH(CO)NR 11 R 12 , NR 12 (CO)R 11 , O(CO)R 11 , O(CO)OR 11 , O(CS)R 11 , NR 12 (CS)R 11 , NH(CS)NR 11 R 12 , or NR 12 (CS)OR 11 ; and 
 R 11  and R 12  are independently selected from hydrogen, alkyl, substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, aryl, substituted aryl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic aromatic or non-aromatic, or substituted heterocyclic aromatic or non-aromatic; or R 11  and R 12  can be connected to form a cycle which can be heterocyclic aromatic or non-aromatic, substituted heterocyclic aromatic, cycloalkyl, or substituted cycloalkyl. 
 
     
     
         5 - 9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the triple negative breast cancer is a subtype selected from the group consisting of basal-like type 1 (BL1), basal-like type 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem0like (MSL), and luminal androgen receptor (LAR) subtypes. 
     
     
         11 . The method of  claim 1 , wherein cells of the triple negative breast cancer comprise a BRAC1 mutation. 
     
     
         12 - 23 . (canceled) 
     
     
         24 . The method of  claim 1 , wherein the breast cancer comprises cells that do not express detectable androgen receptor. 
     
     
         25 . The method of  claim 1 , wherein the breast cancer comprises cells that express an androgen receptor. 
     
     
         26 . The method of  claim 1 , further comprising administering to the patient a second therapeutic treatment. 
     
     
         27 . The method of  claim 4 , wherein the triple negative breast cancer is a subtype selected from the group consisting of basal-like type 1 (BL1), basal-like type 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem0like (MSL), and luminal androgen receptor (LAR) subtypes. 
     
     
         28 . The method of  claim 4 , wherein cells of the triple negative breast cancer comprise a BRAC1 mutation. 
     
     
         29 . The method of  claim 4 , wherein the breast cancer comprises cells that do not express detectable androgen receptor. 
     
     
         30 . The method of  claim 4 , wherein the breast cancer comprises cells that express an androgen receptor. 
     
     
         31 . The method of  claim 4 , further comprising administering to the patient a second therapeutic treatment.