Methods for treating hepatitis c

Abstract

In accordance with the present invention, compounds that can inhibit viral replication, preferably Hepatitis C Virus (HCV) replication, have been identified, and methods for their use provided. In one aspect of the invention, compounds useful in the treatment or prevention of a viral infection are provided. In another aspect of the invention, compounds useful in the treatment or prevention of HCV infection are provided.

1 - 34 . (canceled) 
   
   
       35 . A compound having the following formula: 
     
       
         
         
             
             
         
       
       wherein: 
       X is: 
       hydrogen; 
       a cyano group; 
       an amino group; 
       a 
     
     
       
         
         
             
             
         
       
       a 5- or 6-membered heteroaryl; 
       a C 6  to C 8  aryl, optionally substituted with: 
       an alkoxy group, 
       a cyano group, or 
       a halogen; 
       Y is: 
       a halogen; 
       an amino group; 
       a 
     
     
       
         
         
             
             
         
       
       a —SO 2 R x , where R x  is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or cyclohexyl; 
       a —COOR x  group, where R x  is n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, or cyclohexyl; 
       a C 6  aryl, optionally substituted with:
 an alkoxy, or 
 a cyano group; 
 
       a —COR a  group, where R a  is:
 an amino substituted with one or two C 1  to C 6  alkyls, where the alkyls are optionally substituted with a C 6  aryl; 
 a —NHR b  group where R b  is:
 a C 6  aryl optionally substituted with:
 a haloalkyl, 
 a halogen, or 
 a haloalkoxy; 
 
 
 a 5- or 6-membered heterocycle optionally substituted with a C i  to C 6  alkyl; 
 a C 1  to C 6  alkyl; or 
 a —SR x  group, where R x  is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or cyclohexyl; 
 
       a 5 or 6 membered heteroaryl substituted with:
 a C 6  aryl optionally substituted with:
 an alkoxy, 
 a halogen, or 
 
 a C 1  to C 6  alkyl; or 
 a 5- or 6-membered heteroaryl optionally substituted with:
 an alkoxy, 
 a halogen, or 
 a C 1  to C 6  alkyl; 
 
 
       a C 1  to C 6  alkyl, optionally substituted with a —OR c , where R c  is a C 6  aryl optionally substituted with one or more halogens; 
       a nitro group; 
       a —NHR d  group, where R d  is a C 6  aryl optionally substituted with an alkoxy; 
       a —NHCOR e  group where R e  is:
 a C 6  aryl optionally substituted with a haloalkyl, or 
 a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, cyclopentyl or cyclohexyl; 
 
       R is: 
       a hydrogen; 
       a haloalkyl; 
       a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or cyclohexyl optionally substituted with hydroxyl; 
       or R together with R 1  forms: 
     
     
       
         
         
             
             
         
       
       R 1  is: 
       a C 6  aryl; 
       a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or cyclohexyl; 
       a OCOR f  where R f  is a 5- or 6-membered heterocycle; 
       an alkoxy optionally substituted with an amino group, wherein the amino group is optionally substituted with one or two C i  to C 6  alkyls, where the alkyls are optionally substituted with an amino optionally substituted with one or two C 1  to C 6  alkyls; 
       an alkoxy optionally substituted with a 5 to 8 membered heterocycle optionally substituted with a C 1  to C 6  alkyl, which is optionally substituted with:
 an alkoxy; or 
 an amino, optionally substituted with one or two C 1  to C 6  alkyls; 
 
       or R 1  together with R 2  forms: 
     
     
       
         
         
             
             
         
       
       or R 1  together with R forms: 
     
     
       
         
         
             
             
         
       
     
     and
 R 2  is: 
 a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or cyclohexyl; 
 a 5- or 6-membered heterocycle; 
 an amino optionally substituted with a C 1  to C 6  alkyl; 
 or R 1  together with R 2  forms: 
 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof 
   
   
       36 . The compound of  claim 35 , wherein X is an amino group. 
   
   
       37 . The compound of  claim 35 , wherein Y is
 an amino group;   a —SO 2 R x , where R x  is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or cyclohexyl;   a —COOR x  group, where R x  is n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, or cyclohexyl;   a —COR a  group, where R a  is:
 an amino substituted with one or two C 1  to C 6  alkyls, where the alkyls are optionally substituted with a C 6  aryl; 
 a —NHR b  group where R b  is—a C 6  aryl optionally substituted with a haloalkyl, 
 a 5- or 6-membered heterocycle optionally substituted with a C 1  to C 6  alkyl; 
   a C 1  to C 6  alkyl; or
 a —SR x  group, where R x  is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or cyclohexyl; 
   a 5 or 6 membered heteroaryl substituted with—a C 6  aryl; or   a —NHCOR e  group where R e  is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, cyclopentyl or cyclohexyl.   
   
   
       38 . The compound of  claim 35 , wherein R, R 1  and R 2  are independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or cyclohexyl. 
   
   
       39 . The compound of  claim 35 , wherein said C 1  to C 6  alkyl in R, R 1  and R 2  is independently a methyl or an ethyl. 
   
   
       40 . The compound of  claim 39 , wherein R 1  is selected from the group consisting of
 a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or cyclohexyl; and   an alkoxy optionally substituted with an amino group, wherein the amino group is optionally substituted with one or two C 1  to C 6  alkyls, where the alkyls are optionally substituted with an amino optionally substituted with one or two C 1  to C 6  alkyls; and   an alkoxy optionally substituted with a 5 to 8 membered heterocycle optionally substituted with a C 1  to C 6  alkyl, which is optionally substituted with:
 an alkoxy; or 
 an amino, optionally substituted with one or two C 1  to C 6  alkyls. 
   
   
   
       41 . The compound of  claim 35 , wherein said compound is selected from the group consisting of: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof 
   
   
       42 . A pharmaceutical composition comprising a compound of  claim 35 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient. 
   
   
       43 . A pharmaceutical composition comprising a compound of  claim 37 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient. 
   
   
       44 . A pharmaceutical composition comprising a compound of  claim 41 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient. 
   
   
       45 . A method of preventing or treating Hepatitis C viral infection comprising administering a compound of  claim 35 , or a pharmaceutical composition comprising a compound of  claim 42 . 
   
   
       46 . A method of preventing or treating Hepatitis C viral infection comprising administering a compound of  claim 37 , or a pharmaceutical composition comprising a compound of  claim 43 . 
   
   
       47 . A method of preventing or treating Hepatitis C viral infection comprising administering a compound of  claim 41 , or a pharmaceutical composition comprising a compound of  claim 41 .