Compounds and methods for use thereof in the treatment of viral infections

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 a viral infection in a warm-blooded animal comprising administering to the warm-blooded animal a therapeutically effective amount of a compound of the following formula A-1:  
       
         
           
           
               
               
           
         
         wherein,  
         R is —CONR 1 R 2 , —OCOR 1  or —NHCOR 1 ;  
         R 1  is alkyl, haloalkyl, hydroxyalkyl, alkenyl, haloalkenyl, cycloalkyl, cycloalkalkyl, heterocycloalkyl, heterocycloalkalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenylamino, substituted or unsubstituted benzyl, alkoxyalkyl, poly(alkoxy)alkyl, hydroxyalkoxyalkyl, hydroxypoly(alkoxy)alkyl, haloalkoxyalkyl, halopoly(alkoxy)alkyl, or aminoalkyl; and  
         R 2  is hydrogen or alkyl, a prodrug thereof, or a pharmaceutically acceptable salt thereof.  
       
     
     
         2 . A method according to  claim 1  wherein the compound is in the form of a pharmaceutically acceptable salt thereof.  
     
     
         3 . A method according to  claim 2  wherein said pharmaceutically acceptable salt is a hydrochloride salt.  
     
     
         4 . A method according to  claim 1  wherein the compound is in the form of a prodrug thereof.  
     
     
         5 . A method according to  claim 11  wherein the carrier is a liposome delivery system.  
     
     
         6 . A method according to  claim 1  wherein R is —OCOR 1 .  
     
     
         7 . A method according to  claim 6  wherein R 1  is alkyl or substituted or unsubstituted phenyl.  
     
     
         8 . A method according to  claim 1  wherein said compound is micronized and is suitable for administering to said warm-blooded animal by injection.  
     
     
         9 . A method according to  claim 1  wherein said compound is administered in an amount of from 10 mg/kg body weight to 10,000 mg/kg body weight.  
     
     
         10 . A method according to  claim 1  wherein said compound is administered orally, enterically, intravenously, peritoneally, or by injection.  
     
     
         11 . A method according to  claim 1  wherein said compound is administered in a pharmaceutically acceptable carrier.  
     
     
         12 . A method according to  claim 1  wherein the method is for treating a retroviral infection.  
     
     
         13 . A method according to  claim 1  wherein the method is for treating a DNA virus infection.  
     
     
         14 . A method for treating an HIV viral infection in a warm-blooded animal comprising administering to the warm-blooded animal a therapeutically effective amount of a compound of the following formula A-1:  
       
         
           
           
               
               
           
         
         wherein,  
         R is —CONR 1 R 2 , —OCOR 1  or —NHCOR 1 ;  
         R 1  is alkyl, haloalkyl, hydroxyalkyl, alkenyl, haloalkenyl, cycloalkyl, cycloalkalkyl, heterocycloalkyl, heterocycloalkalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenylamino, substituted or unsubstituted benzyl, alkoxyalkyl, poly(alkoxy)alkyl, hydroxyalkoxyalkyl, hydroxypoly(alkoxy)alkyl, haloalkoxyalkyl, halopoly(alkoxy)alkyl, or aminoalkyl; and  
         R 2  is hydrogen or alkyl.  
       
     
     
         15 . A method according to  claim 14  wherein said compound is administered in a pharmaceutically acceptable carrier.  
     
     
         16 . A method according to  claim 14  wherein R 1  is alkyl or substituted or unsubstituted phenyl.  
     
     
         17 . A method according to  claim 14  wherein said compound is micronized and is suitable for administering to said warm-blooded animal by injection.  
     
     
         18 . A method according to  claim 14  wherein said compound is administered in an amount of from 10 mg/kg body weight to 10,000 mg/kg body weight.  
     
     
         19 . A method according to  claim 14  wherein said compound is administered orally, enterically, intravenously, peritoneally, or by injection.  
     
     
         20 . A method for treating an HIV viral infection in a warm-blooded animal comprising administering to the warm-blooded animal a therapeutically effective amount of a compound of the following formula A-1:  
       
         
           
           
               
               
           
         
         wherein,  
         R is —CONR 1 R 2 , —OCOR 1  or —NHCOR 1 ;  
         R 1  is alkyl, and  
         R 2  is hydrogen or alkyl.