Hcv protease inhibitors and uses thereof

Abstract

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

1 - 45 . (canceled) 
     
     
         46 . A method for inhibiting HCV protease, or a mutant thereof, activity comprising administering to a patient in need thereof a compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         47 . The method according to  claim 46 , wherein the HCV protease, or a mutant thereof, activity is inhibited irreversibly. 
     
     
         48 . The method according to  claim 47 , wherein the HCV protease, or a mutant thereof, activity is inhibited irreversibly by covalently modifying a cysteine residue conserved at an equivalent position to Cys159 of HCV protease subtype 1b. 
     
     
         49 . The method of  claim 48 , wherein the HCV protease genotype or subtype is selected from the group consisting of 1a, 1b, 1c, 2a, 2b, 2c, 2i, 2k, 3a, 3b, 3k, 4a, 4d, 4f, 5a, 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h, 6i, 6j, 6k, 6l, 6m, 6n, 6o, 6p, 6q, 6t, and 7a. 
     
     
         50 . The method of  claim 49 , wherein the HCV protease genotype or subtype is 1a, 1b, 2a, or 3a. 
     
     
         51 . The method according to  claim 47 , wherein the HCV protease, or a mutant thereof, activity is inhibited irreversibly by covalently modifying Cys16. 
     
     
         52 . A method for inhibiting HCV protease, or a mutant thereof, activity in a biological sample comprising the step of contacting said biological sample with a compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         53 . The method according to  claim 52 , wherein the HCV protease, or a mutant thereof, activity is inhibited irreversibly. 
     
     
         54 . The method according to  claim 53 , wherein the HCV protease, or a mutant thereof, activity is inhibited irreversibly by covalently modifying a cysteine residue conserved at an equivalent position to Cys159 of HCV protease subtype 1b. 
     
     
         55 . The method of  claim 54 , wherein the HCV protease genotype or subtype is selected from the group consisting of 1a, 1b, 1c, 2a, 2b, 2c, 2i, 2k, 3a, 3b, 3k, 4a, 4d, 4f, 5a, 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h, 6i, 6j, 6k, 6l, 6m, 6n, 6o, 6p, 6q, 6t, and 7a. 
     
     
         56 . The method of  claim 55 , wherein the HCV protease genotype or subtype is 1a, 1b, 2a, or 3a. 
     
     
         57 . The method according to  claim 53 , wherein the HCV protease, or a mutant thereof, activity is inhibited irreversibly by covalently modifying Cys16. 
     
     
         58 . A method for treating a hepatitis C viral infection, comprising the step of administering to said patient in need thereof a compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         59 . The method of  claim 58 , wherein the step of administering occurs once daily. 
     
     
         60 . The method according to  claim 59 , wherein the HCV protease, or a mutant thereof, activity is inhibited irreversibly. 
     
     
         61 . The method of  claim 60 , wherein the HCV protease, or a mutant thereof, activity is inhibited irreversibly by covalently modifying a cysteine residue conserved at an equivalent position to Cys159 of HCV protease subtype 1b. 
     
     
         62 . The method of  claim 61 , wherein the HCV protease genotype or subtype is selected from the group consisting of 1a, 1b, 1c, 2a, 2b, 2c, 2i, 2k, 3a, 3b, 3k, 4a, 4d, 4f, 5a, 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h, 6i, 6j, 6k, 6l, 6m, 6n, 6o, 6p, 6q, 6t, and 7a. 
     
     
         63 . The method of  claim 62 , wherein the HCV protease genotype or subtype is 1a, 1b, 2a, or 3a. 
     
     
         64 . The method of  claim 60 , wherein the compound irreversibly inhibits HCV protease by covalently modifying Cys16 of HCV protease. 
     
     
         65 . A covalent adduct formed by reacting HCV protease with a compound selected from the group consisting of: