Antiviral Drugs for Treatment of Arenvirus Infection

Abstract

Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by the Arenavirus family is disclosed.

1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the following general Formula I or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein B, D, E, G, B′, D′, E′ and G′ are independently N; 
         R is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, aryl, heteroaryl, hydroxy, alkyloxy, aryloxy, heteroaryloxy, acyloxy, arylacyloxy, heteroarylacyloxy, alkylsulfonyloxy, arylsulfonyloxy, thio, alkylthio, amino, alkylamino, dialkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, acylamino, arylacylamino, heteroarylacylamino, alkylsulfonylamino, arylsulfonylamino, acyl, arylacyl, heteroarylacyl, alkylsulfinyl, arylsulfinyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, substituted aminosulfonyl, carboxy, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, carbamoyl, substituted carbamoyl, halogen, cyano, isocyano and nitro; and 
         X and X′ are independently selected from the group consisting of O and S. 
       
     
     
         2 . The composition of  claim 1 , wherein that at least one of B, D, E, G, B′, D′, E′ and G′ is C—Y, wherein Y is halogen. 
     
     
         3 . (canceled) 
     
     
         4 . The composition of  claim 1 , wherein R is selected from the group consisting of hydrogen, alkyl, amino and halogen. 
     
     
         5 . The composition of  claim 1 , wherein, R is hydrogen or methyl. 
     
     
         6 . The composition of  claim 1 , wherein each of X and X′ is N—R′. 
     
     
         7 . The composition of  claim 6 , wherein R′ is hydrogen or alkyl. 
     
     
         8 . The composition of  claim 1 , wherein the compound of Formula I is selected from the group consisting of 1H,1′H-[2,2′]Bibenzoimidazolyl; 5,6,5′,6′-Tetramethyl-1H,1′H-[2,2′]bibenzoimidazolyl; 1,1′-Dimethyl-1H,1′H-[2,2′]bibenzoimidazolyl; 1,1′-Diethyl-1H,1′H-[2,2′]bibenzoimidazolyl; 6,6′-Dinitro-1H,1′H-[2,2′]bibenzoimidazolyl; 4,4′-Difluoro-1H,1′H-[2,2′]bibenzoimidazolyl; 5,5′-Difluoro-1H,1′H-[2,2′]bibenzoimidazolyl; 5,5′-Dichloro-1H,1′H-[2,2′]bibenzoimidazolyl; 5,5′-Dibromo-1H,1′H-[2,2′]bibenzoimidazolyl; 4,4′-Dimethyl-1H,1′H-[2,2′]bibenzoimidazolyl; 5,5′-Dimethyl-1H,1′H-[2,2′]bibenzoimidazolyl; 4,4′-Dimethoxy-1H,1′H-[2,2′]bibenzoimidazolyl; 5,5′-Dimethoxy-1H,1′H-[2,2′]bibenzoimidazolyl; 1H,1′H-[2,2′]Bibenzoimidazolyl-4,4′-dicarboxylic acid dimethyl ester; 1H,1′H-[2,2′]Bibenzoimidazolyl-5,5′-dicarboxylic acid dimethyl ester; 4,4′-Diphenyl-1H,1′H-[2,2′]bibenzoimidazolyl; 4,5,4′,5′-Tetrafluoro-1H,1′H-[2,2′]bibenzoimidazolyl; 4,6,4′,6′-Tetrafluoro-1H,1′H-[2,2′]bibenzoimidazolyl; 5,6,5′,6′-Tetrafluoro-1H,1′H-[2,2′]bibenzoimidazolyl; 1H,1′H-[2,2′]Bi[imidazo[4,5-b]pyridinyl]; 3H,3′H-[2,2′]Bi[imidazo[4,5-c]pyridinyl]; 4,7,4′,7′-Tetrafluoro-1H,1′H-[2,2′]bibenzoimidazolyl; and 4,4′-Dichloro-1H,1′H-[2,2′]bibenzoimidazolyl. 
     
     
         9 . The composition of  claim 1 , wherein the compound of Formula I is selected from the group consisting 1H,1′H-[2,2′]Bibenzoimidazolyl; 4,4′-Difluoro-1H,1′H-[2,2′]bibenzoimidazolyl; 5,5′-Difluoro-1H,1′H-[2,2′]bibenzoimidazolyl; and 4,6,4′,6′-Tetrafluoro-1H,1′H-[2,2′]bibenzoimidazolyl. 
     
     
         10 . (canceled) 
     
     
         11 . The compound of  claim 10 , wherein the compound of Formula I is selected from the group consisting of 4,4′-Difluoro-1H,1′H-[2,2′]bibenzoimidazolyl; 5,5′-Dibromo-1H,1′H-[2,2′]bibenzoimidazolyl; 4,5,4′,5′-Tetrafluoro-1H,1′H-[2,2′]bibenzoimidazolyl; 4,6,4′,6′-Tetrafluoro-1H,1′H-[2,2′]bibenzoimidazolyl; 5,6,5′,6′-Tetrafluoro-1H,1′H-[2,2′]bibenzoimidazolyl; 4,7,4′,7′-Tetrafluoro-1H,1′H-[2,2′]bibenzoimidazolyl; and 4,4′-Dichloro-1H,1′H-[2,2′]bibenzoimidazolyl. 
     
     
         12 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of  claim 1 . 
     
     
         13 . A compound or a pharmaceutically acceptable salt thereof selected from the group consisting of 4,4′-Dimethoxy-1H,1′H-[2,2′]bibenzoimidazolyl; 1H,1′H-[2,2′]Bibenzoimidazolyl-4,4′-dicarboxylic acid dimethyl ester; 1H,1′H-[2,2′]Bibenzoimidazolyl-5,5′-dicarboxylic acid dimethyl ester; and 4,4′-Diphenyl-1H,1′H-[2,2′]bibenzoimidazolyl. 
     
     
         14 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of  claim 13 . 
     
     
         15 .- 36 . (canceled)