Inhibitors of human immunodeficiency virus replication

Abstract

Compounds of formula I: wherein R 4 , R 6 and R 7 are defined herein, are useful as inhibitors of HIV replication.

1 - 38 . (canceled) 
     
     
         39 . A method of treating an HIV infection in a mammal having or at risk of having the infection, the method comprising administering to the mammal a therapeutically effective amount of a combination of a compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein:
 R 4  is Het, wherein Het is optionally substituted with 1 to 3 substituents each independently selected from halo, (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )haloalkyl, (C 3-7 )cycloalkyl, —OH, —O(C 1-6 )alkyl, —SH, —S(C 1-6 )alkyl, —NH 2 , —NH(C 1-6 )alkyl and —N((C 1-6 )alkyl) 2 , wherein (C 1-6 )alkyl is optionally substituted with hydroxy, cyano or oxo; 
 R 6  and R 7  are each independently selected from H, halo, (C 1-6 )alkyl and (C 1-6 )haloalkyl; and 
 Het is a 4- to 7-membered saturated, unsaturated or aromatic heterocycle having 1 to 4 heteroatoms each independently selected from O, N and S, or a 7- to 14-membered saturated, unsaturated or aromatic heteropolycycle having wherever possible 1 to 5 heteroatoms, each independently selected from O, N and S; 
 or a salt thereof; and 
 
         at least one other antiviral agent. 
       
     
     
         40 . The method according to  claim 39  wherein R 4  is Het optionally substituted with 1 to 2 substituents each independently selected from halo, (C 1-3 )alkyl and —O(C 1-3 )alkyl. 
     
     
         41 . The method according to  claim 40  wherein R 4  is Het optionally substituted with 1 to 2 substituents each independently selected from Cl, F, CH 3  and CH 2 CH 3  wherein Het is a 7- to 14-membered saturated, unsaturated or aromatic heteropolycycle having wherever possible 1 to 2 heteroatoms, each independently selected from O, N and S. 
     
     
         42 . The method according to  claim 39  wherein R 4  is selected from: 
       
         
           
           
               
               
           
         
         optionally substituted with 1 to 3 substituents each independently selected from halo, (C 1-3 )alkyl and —O(C 1-3 )alkyl. 
       
     
     
         43 . The method according to  claim 42  wherein R 4  is selected from: 
       
         
           
           
               
               
           
         
         optionally substituted with 1 to 2 substituents each independently selected from halo, (C 1-3 )alkyl and —O(C 1-3 )alkyl. 
       
     
     
         44 . The method according to  claim 39  wherein R 6  is H, F, Cl or (C 1-2 )alkyl. 
     
     
         45 . The method according to  claim 44  wherein R 6  is H or CH 3 . 
     
     
         46 . The method according to  claim 39  wherein R 7  is H, F, Cl or CH 3 . 
     
     
         47 . The method according to  claim 46  wherein R 7  is H or CH 3 . 
     
     
         48 . The method according to  claim 39  wherein the compound of formula (I) has following formula: 
       
         
           
           
               
               
           
         
         wherein R 4 , R 6  and R 7  are defined as: 
       
       
         
           
                 
                 
                 
               
                     
                 
                   R 4   
                   R 6   
                   R 7   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   H 
                   H. 
                 
                     
                 
             
                
                
                
               
               
                
                
               
            
           
         
       
     
     
         49 . The method according to  claim 39  wherein the at least one other antiviral agent comprises at least one NNRTI. 
     
     
         50 . The method according to  claim 39  wherein the at least one other antiviral agent comprises at least one NRTI. 
     
     
         51 . The method according to  claim 39  wherein the at least one other antiviral agent comprises at least one protease inhibitor. 
     
     
         52 . The method according to  claim 39  wherein the at least one other antiviral agent comprises at least one entry inhibitor. 
     
     
         53 . The method according to  claim 39  wherein the at least one other antiviral agent comprises at least one integrase inhibitor.