Compounds and methods for use thereof in the treatment of cancer

Abstract

Benzimidazole derivatives and salts and prodrugs thereof are disclosed, together with methods for the treatment of cancers or viral infections in warm blooded animals by administration of these compounds. Such compounds may be used in combination with a chemotherapeutic agent and/or a potentiator.

1 . A method for treating cancer susceptible to treatment in a warm-blooded animal comprising administering to the warm-blooded animal a therapeutically effective amount of a compound of the following formula:  
       
         
           
           
               
               
           
         
         wherein,  
         R is —COOR 2  or —CONHR 2 ;  
         R 2  is alkyl, haloalkyl, alkenyl, haloalkenyl, cycloalkyl, cycloalkalkyl, heterocycloalkyl, heterocycloalkalkyl, substituted or unsubstituted benzyl, hydroxyalkyl, alkoxyalkyl, poly(alkoxy)alkyl, hydroxyalkoxyalkyl, hydroxypoly(alkoxy)alkyl, haloalkoxyalkyl, halopoly(alkoxy)alkyl, or aminoalkyl; and  
         each of X and Y is independently hydrogen, alkyl, alkenyl, cycloalkyl, haloalkyl, haloalkenyl, halogen, nitro, or amino;  
         wherein the compound is in the form of a liposome delivery system.  
       
     
     
         2 . The method of  claim 1  wherein the liposome delivery system is in the form of multilamellar vesicles.  
     
     
         3 . The method of  claim 1  wherein the liposome delivery system is in the form of unilamellar vesicles.  
     
     
         4 . A method according to  claim 1  wherein said compound is of the following formula A-1:  
       
         
           
           
               
               
           
         
       
     
     
         5 . A method according to  claim 4  wherein R 2  is selected from the group consisting of alkyl, haloalkyl, alkenyl, and substituted or unsubstituted benzyl.  
     
     
         6 . A method according to  claim 1  wherein said compound is of the following formula A-2:  
       
         
           
           
               
               
           
         
       
     
     
         7 . A method according to  claim 6  wherein R 2  is selected from the group consisting of alkyl, haloalkyl, and substituted or unsubstituted benzyl.  
     
     
         8 . A method for treating cancer susceptible to treatment in a warm-blooded animal comprising administering to the warm-blooded animal a therapeutically effective amount of a compound of the following formula:  
       
         
           
           
               
               
           
         
         wherein,  
         R is —COOR 2  or —CONHR 2 ;  
         R 2  is heterocycloalkyl or heterocycloalkalkyl; and  
         each of X and Y is independently hydrogen, alkyl, alkenyl, cycloalkyl, haloalkyl, haloalkenyl, halogen, nitro, or amino.  
       
     
     
         9 . A method according to  claim 8  wherein said compound is of the following formula A-1:  
       
         
           
           
               
               
           
         
       
     
     
         10 . A method according to  claim 8  wherein said compound is of the following formula A-2:  
       
         
           
           
               
               
           
         
       
     
     
         11 . A method according to  claim 8  wherein said compound is in the form of a pharmaceutically acceptable salt thereof.  
     
     
         12 . A method according to  claim 8  wherein said cancer is a carcinoma.  
     
     
         13 . A method according to  claim 8  wherein said cancer is leukemia.  
     
     
         14 . A method according to  claim 8  wherein said cancer is melanoma.  
     
     
         15 . A method according to  claim 8  wherein said cancer is colon cancer.  
     
     
         16 . A method according to  claim 8  wherein said cancer is breast cancer.  
     
     
         17 . A method according to  claim 8  wherein said cancer is lung cancer.  
     
     
         18 . A method according to  claim 8  wherein said cancer is pancreatic cancer.  
     
     
         19 . A method according to  claim 8  wherein said cancer is ovarian cancer.  
     
     
         20 . A method according to  claim 8  wherein said cancer is prostate cancer.