Antiviral compounds

Abstract

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

1 . A compound of formula (I):
   E 1a -V 1a —C(═O)—P 1a —W 1a —P 1b —C(═O)—V 1b -E 1b    (I)
   
       wherein:
 W 1a  is 
 
       
         
           
           
               
               
           
         
       
       and W 1a  is optionally substituted with one or more halo, alkyl, haloalkyl, optionally substituted aryl, optionally substituted heterocycle, or cyano;
 Y 5  is —O—CH 2 —, —CH 2 —O—, —O—C(═O)—, or —C(═O)—O—; 
 X 5  is —CH 2 —CH 2 —, or —CH═CH—; 
 P 1a  and P 1b  are each independently: 
 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         V 1a  and V 1b  are each independently: 
       
       
         
           
           
               
               
           
         
         provided that at least one of V 1a  and V 1b  is 
       
       
         
           
           
               
               
           
         
         E 1a  and E 1b  are each independently —N(H)(alkoxycarbonyl), —N(H)(cycloalkylcarbonyl), or —N(H)(cycloalkyloxycarbonyl); or E 1a -V 1a  taken together are R 9a ; or E 1b -V 1b  taken together are R 9b ; and 
         R 9a  and R 9b  are each independently: 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or prodrug thereof. 
       
     
     
         2 . The compound of  claim 1 , which has the formula: 
       
         
           
           
               
               
           
         
       
       wherein the imidazole ring shown in formula A2 and A4 is optionally substituted with one or more halo, haloalkyl, cyano, or alkyl;
 or a pharmaceutically acceptable salt or prodrug thereof. 
 
     
     
         3 . The compound of  claim 1 , wherein P 1a  and P 1b  are each independently: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 1 , wherein:
 W 1a  is   
       
         
           
           
               
               
           
         
       
       and W 1a  is optionally substituted with one or more halo, alkyl, haloalkyl, or cyano;
 Y 5  is —O—CH 2 —, or —CH 2 —O—; 
 X 5  is —CH 2 —CH 2 —, or —CH═CH—; 
 P 1a  and P 1b  are each independently: 
 
       
         
           
           
               
               
           
         
         V 1a  and V 1b  are each independently: 
       
       
         
           
           
               
               
           
         
         provided that at least one of V 1a  and V 1b  is 
       
       
         
           
           
               
               
           
         
         E 1a  and E 1b  are each independently —N(H)(alkoxycarbonyl), —N(H)(cycloalkylcarbonyl), or —N(H)(cycloalkyloxycarbonyl); or E 1a -V 1a  taken together are R 9a ; or E 1b V 1b  taken together are R 9b ; and 
         R 9a  and R 9b  are each independently: 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or prodrug thereof. 
       
     
     
         5 . The compound of  claim 1 , wherein one of V 1a  and V 1b  is: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 1 , wherein both of V 1a  and V 1b  are: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 1 , wherein one of V 1a  and V 1b  is: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 1 , wherein both of V 1a  and V 1b  are: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 1 , wherein one of P 1a  and P 1b  is: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 1 , wherein one of P 1a  and P 1b  is: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound of  claim 1 , wherein both of P 1a  and P 1b  are: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound of  claim 1  wherein —V 1a —C(═O)—P 1a — and —P 1b —C(═O)—V 1b — are each independently: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       provided that at least one of V 1a  and V 1b  is 
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound of  claim 1  selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or prodrug thereof. 
     
     
         14 . The compound of  claim 1  selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or prodrug thereof. 
     
     
         15 . A pharmaceutical composition comprising the compound as described in  claim 1  or a pharmaceutically acceptable salt, or prodrug thereof; and at least one pharmaceutically acceptable carrier. 
     
     
         16 . The pharmaceutical composition of  claim 15 , further comprising at least one additional therapeutic agent for treating HCV. 
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein said at least one additional therapeutic agent is selected from ribavirin, an NS3 protease inhibitor, a nucleoside or nucleotide inhibitor of HCV NSSB polymerase, an alpha-glucosidase 1 inhibitor, a hepatoprotectant, a non-nucleoside inhibitor of HCV polymerase, andcombinations thereof. 
     
     
         18 . A method of treating hepatitis C, said method comprising administering to a human patient a pharmaceutical composition which comprises a therapeutically effective amount of the compound as described in  claim 1  or a pharmaceutically acceptable salt, or prodrug thereof. 
     
     
         19 . The method according to  claim 18 , further comprising administering at least one additional for treating HCV to the patient. 
     
     
         20 . The method according to  claim 19 , wherein said at least one additional therapeutic agent is selected from ribavirin, an NS3 protease inhibitor, a nucleoside or nucleotide inhibitor of HCV NSSB polymerase, an alpha-glucosidase 1 inhibitor, a hepatoprotectant, a non-nucleoside inhibitor of HCV polymerase, and combinations thereof.