Cyclopropyl Fused Indolobenzazepine HCV NS5B Inhibitors

Abstract

The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.

1 . A composition comprising a compound of formula I, a pharmaceutically acceptable carrier, and at least one additional compound having therapeutic benefits for HCV 
     
       
         
         
             
             
         
       
     
     where:
 R 1  is CO 2 R 5  or CONR 6 R 7 ; 
 
     
       
         
         
             
             
         
       
       R 3  is hydrogen, halo, alkyl, alkenyl, hydroxy, benzyloxy, alkoxy, or haloalkoxy; 
       R 4  is cycloalkyl; 
       R 5  is hydrogen or alkyl; 
       R 6  is hydrogen, alkyl, alkylSO 2 , cycloalkylSO 2 , haloalkylSO 2 , (R 9 ) 2 NSO 2 , or (R 10 )SO 2 ; 
       R 7  is hydrogen or alkyl; 
       R 8  is hydrogen, alkyl, cycloalkyl, (cycloalkyl)alkyl, alkylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, alkylSO 2 , cycloalkylSO 2 , haloalkylSO 2 , aminocarbonyl, (alkylamino)carbonyl, (dialkylamino)carbonyl, benzyl, benzyloxycarbonyl, or pyridinyl; 
       R 9  is hydrogen, alkyl, or cycloalkyl; and 
       R 10  is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperidinyl, or homomorpholinyl and is substituted with 0-3 alkyl substituents; 
       or a pharmaceutically acceptable salt thereof; 
       and where the additional compound having therapeutic benefits for HCV is selected from the group consisting of interferons, cyclosporins, interleukins, HCV metalloprotease inhibitors, HCV serine protease inhibitors, HCV polymerase inhibitors, HCV helicase inhibitors, HCV NS4B protein inhibitors, HCV entry inhibitors, HCV assembly inhibitors, HCV egress inhibitors, HCV NS5A protein inhibitors, HCV NS5B protein inhibitors, and HCV replicon inhibitors. 
     
   
   
       2 . A method of treating hepatitis C infection comprising administering a therapeutically effective amount of a compound of formula I and at least one additional compound having therapeutic benefits for HCV to a patient 
     
       
         
         
             
             
         
       
     
     where:
 R 1  is CO 2 R 5  or CONR 6 R 7 ; 
 
     
       
         
         
             
             
         
       
       R 3  is hydrogen, halo, alkyl, alkenyl, hydroxy, benzyloxy, alkoxy, or haloalkoxy; 
       R 4  is cycloalkyl; 
       R 5  is hydrogen or alkyl; 
       R 6  is hydrogen, alkyl, alkylSO 2 , cycloalkylSO 2 , haloalkylSO 2 , (R 9 ) 2 NSO 2 , or (R 10 )SO 2 ; 
       R 7  is hydrogen or alkyl; 
       R 3  is hydrogen, alkyl, cycloalkyl, (cycloalkyl)alkyl, alkylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, alkylSO 2 , cycloalkylSO 2 , haloalkylSO 2 , aminocarbonyl, (alkylamino)carbonyl, (dialkylamino)carbonyl, benzyl, benzyloxycarbonyl, or pyridinyl; 
       R 9  is hydrogen, alkyl, or cycloalkyl; and 
       R 10  is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperidinyl, or homomorpholinyl and is substituted with 0-3 alkyl substituents; 
       or a pharmaceutically acceptable salt thereof, 
       and where the additional compound having therapeutic benefits for HCV is selected from the group consisting of interferons, cyclosporins, interleukins, HCV metalloprotease inhibitors, HCV serine protease inhibitors, HCV polymerase inhibitors, HCV helicase inhibitors, HCV NS4B protein inhibitors, HCV entry inhibitors, HCV assembly inhibitors, HCV egress inhibitors, HCV NS5A protein inhibitors, HCV NS5B protein inhibitors, and HCV replicon inhibitors.