Compounds and methods for the treatment of cancer

Abstract

The present invention provides organic arsenicals. Many of these compounds have potent in vitro cytotoxic activity against numerous human tumor cell lines, both of solid and hematological origin, as well as against malignant blood cells from patients with leukemia.

1 . A compound having a structure of formula (I) or a pharmaceutically acceptable salt thereof  
       
         
           
           
               
               
           
         
       
       wherein 
 X is S or Se;  
 W is O, S, or (R)(R), where each occurrence of R is independently H or C 1-2 alkyl;  
 n is 0 or 1;  
 R 1  and R 2  are each independently C 1-10 alkyl;  
 R 3  is —H, C 1-10 alkyl, or C 0-6 alkyl-COOR 6 ;  
 R 3′  is H, amino, cyano, halogen, aryl, aralkyl, heteroaryl, heteroaralkyl, carboxyl, C 1-10 alkyl, C 1-10 alkenyl, or C 1-10 alkynyl;  
 R 4  is —OH, —H, —CH 3 , amino, —OC(O)C 1-10 aralkyl, —OC(O) C 1-10 alkyl, or —OC(O)aryl; and  
 R 5  is —OH, cyano, C 1-6 alkoxy, amino, O—C 1-10 alkyl, O-aralkyl, —OC(O) C 1-10 aralkyl, —OC(O) C 1-10 alkyl, —OC(O)aryl, or a glycine substituent; and  
 R 6  is H or C 1-10 alkyl.  
 
     
     
         2 - 19 . (canceled)  
     
     
         20 . A compound of  claim 1  selected from  
       
         
           
           
               
               
           
         
       
     
     
         21 . A compound having a structure of formula (II) or a pharmaceutically acceptable salt thereof  
       
         
           
           
               
               
           
         
       
       wherein the melting point of the compound in its crystalline form is greater than 125° C.  
     
     
         22 - 28 . (canceled)  
     
     
         29 . A compound of  claim 21 , wherein a compound of formula (II) is substantially free of pyridine hydrochloride.  
     
     
         30 . A compound having a structure of formula (IV) or a pharmaceutically acceptable salt thereof  
       
         
           
           
               
               
           
         
       
       wherein 
 X is S or Se;  
 W is O, S, or (R)(R), where each occurrence of R is independently H or a C 1-2 alkyl;  
 Z is CH or N;  
 R 1  and R 2  are independently C 1-10 alkyl, preferably R 1  and R 2  are independently selected from methyl, ethyl, propyl, and isopropyl; and  
 R 5  is —OH, cyano, C 1-10 alkoxy, amino, O-aralkyl, O-aralkyl, —OC(O) C 1-10 aralkyl, —OC(O) C 1-10 alkyl, —OC(O)aryl, or a glycine substituent;  
 R 6  is H or C 1-10 alkyl;  
 R 7  is selected from halogen, —OH, C 0-6 alkyl-COOR 6 , C 1-6 alkyl, C 1-6 alkoxy, amino, amido, cyano, and nitro;  
 m is an integer from 0 to 4.  
 
     
     
         31 - 37 . (canceled)  
     
     
         38 . A compound of  claim 30 , selected from  
       
         
           
           
               
               
           
         
       
     
     
         39 . A method for treating cancer, comprising administering a therapeutically effective amount of a compound of any one of claims  1 ,  21 , or  30 .  
     
     
         40 . The method of  claim 39 , wherein said cancer comprises a solid tumor.  
     
     
         41 . (canceled)  
     
     
         42 . The method of  claim 39 , wherein said cancer is a hematological cancer.  
     
     
         43 - 55 . (canceled)