Inhibitors of serine proteases, particularly hcv ns3-ns4a protease

Abstract

The present invention relates to compounds of formula I: or a pharmaceutically acceptable salt or mixtures thereof that inhibit serine protease activity, particularly the activity of hepatitis C virus NS 3 -NS 4 A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection and to processes for preparing the compounds. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

We claim: 
     
         1 . A compound of formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or mixtures thereof wherein:
 z is 0 or 1; 
 V is —C(O)—, —S(O)—, —C(R′) 2 — or —S(O) 2 —; 
 R is —C(O)—, —S(O)—, —S(O) 2 —, —N(R 8 )—, —O—, or a bond; 
 T is:
 (C6-C10)-aryl, 
 (C6-C10)-aryl-(C1-C12)aliphatic, 
 (C3-C10)-cycloalkyl or -cycloalkenyl, 
 [(C3-C10)-cycloalkyl or -cycloalkenyl]-(C1-C12)-aliphatic, 
 (C3-C10)-heterocyclyl, 
 (C3-C10)-heterocyclyl-(C1-C12)-aliphatic, 
 (C5-C10)heteroaryl, or 
 (C5-C10)heteroaryl-(C1-C12)-aliphatic;
 wherein up to 3 aliphatic carbon atoms in T may be optionally replaced with —S—, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; 
 wherein each T may be optionally substituted with up to 3 J substituents; 
 wherein J is halogen, —OR′, —OC(O)N(R′) 2 , —NO 2 , —CN, —CF 3 , —OCF 3 , —R′, oxo, thioxo, 1,2-methylenedioxy, 1,2-ethylenedioxy, —N(R′) 2 , —SR′, —SOR′, —SO 2 R′, —SO 2 N(R′) 2 , —SO 3 R′, —C(O)R′, —C(O)C(O)R′, —C(O)CH 2 C(O)R′, —C(S)R′, —C(O)OR′, —OC(O)R′, —C(O)N(R′) 2 , —OC(O)N(R′) 2 , —C(S)N(R′) 2 , —(CH 2 ) 0-2 NHC(O)R′, —N(R′)N(R′)COR′, —N(R′)N(R′)C(O)OR′, —N(R′)N(R′)CON(R′) 2 , —N(R′)SO 2 R′, —N(R′)SO 2 N(R′) 2 , —N(R′)C(O)OR′, —N(R′)C(O)R′, —N(R′)C(S)R′, —N(R′)C(O)N(R′) 2 , —N(R′)C(S)N(R′) 2 , —N(COR′)COR′, —N(OR′)R′, —C(═NH)N(R′) 2 , —C(O)N(OR′)R′, —C(═NOR′)R′, —OP(O)(OR′) 2 , —P(O) (R′) 2 , —P(O)(OR′) 2 , or —P(O)(H)(OR′), wherein; 
 two R′ groups together with the nitrogen to which they are bound form a 3- to a 20-membered mono-, an 8- to 20-membered bi- or tri-cyclic heterocyclic ring system; 
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 3 substituents selected independently from J 2 ;
 each R′ is independently selected from: 
  hydrogen-, 
  (C1-C12)-aliphatic-, 
  (C3-C10)-cycloalkyl or -cycloalkenyl-, 
  [(C3-C10)-cycloalkyl or -cycloalkenyl]-(C1-C12)-aliphatic-, 
  (C6-C10)-aryl-, 
  (C6-C10)-aryl-(C1-C12)aliphatic-, 
  (C3-C10)-heterocyclyl-, 
  (C6-C10)-heterocyclyl-(C1-C12)aliphatic-, 
  (C5-C10)-heteroaryl-, or 
  (C5-C10)-heteroaryl-(C1-C12)-aliphatic-, 
 wherein R′ is optionally substituted with up to 3 substituents selected independently from J 2 ; 
 
 
 
 wherein J 2  is halogen, —OR′, —OC(O)N(R′) 2 , —NO 2 , —CN, —CF 3 , —OCF 3 , —R′, oxo, thioxo, 1,2-methylenedioxy, —N(R′) 2 , —SR′, —SOR′, —SO 2 R′, —SO 2 N(R′) 2 , —SO 3 R′, —C(O)R′, —C(O)C(O)R′, —C(O)CH 2 C(O)R′, —C(S)R′, —C(O)OR′, —OC(O)R′, —C(O)N(R′) 2 , —OC(O)N(R′) 2 , —C(S)N(R′) 2 , —(CH 2 ) 0-2 NHC(O)R′, —N(R′)N(R′)COR′, —N(R′)N(R′)C(O)OR′, —N(R′)N(R′)CON(R′) 2 , —N(R′)SO 2 R′, —N(R′)SO 2 N(R′) 2 , —N(R′)C(O)OR′, —N(R′)C(O)R′, —N(R′)C(S)R′, —N(R′)C(O)N(R′) 2 , —N(R′)C(S)N(R′) 2 , —N(COR′)COR′, —N(OR′)R′, —C(═NH)N(R′) 2 , —C(O)N(OR′)R′, —C(═NOR′)R′, —OP(O)(OR′) 2 , —P(O)(R′) 2 , —P(O)(OR′) 2 , or —P(O)(H)(OR′); or 
 T is: 
 
       
         
           
           
               
               
           
         
         
           wherein:
 R 10  is:
 hydrogen, 
 (C1-C12)-aliphatic, 
 (C6-C10)-aryl, 
 (C6-C10)-aryl-(C1-C12)aliphatic, 
 (C3-C10)-cycloalkyl or -cycloalkenyl, 
 [(C3-C10)-cycloalkyl or -cycloalkenyl]-(C1-C12)-aliphatic, 
 (C3-C10)-heterocyclyl, 
 (C3-C10)-heterocyclyl-(C1-C12)-aliphatic, 
 (C5-C10)-heteroaryl, or 
 (C5-C10)-heteroaryl-(C1-C12)-aliphatic; 
 
 K is a bond, (C1-C12)-aliphatic, —O—, —S—, —NR 9 —, —C(O)—, or —C(O)—NR 9 —, wherein R 9  is hydrogen or (C1-C12)-aliphatic; 
 n is 1-3; or 
 
         
         T is N(R 17 ) 2 ;
 wherein each R 17  is independently:
 hydrogen-, 
 (C1-C12)-aliphatic-, 
 (C3-C10)-cycloalkyl- or cycloalkenyl-, 
 [(C3-C10)-cycloalkyl- or cycloalkenyl]-(C1-C12)-aliphatic-, 
 (C6-C10)-aryl-, 
 (C6-C10)-aryl-(C1-C12)aliphatic-, 
 (C3-C10)-heterocyclyl-, 
 (C3-C10)-heterocyclyl-(C1-C12)-aliphatic-, 
 (C5-C10)heteroaryl-, or 
 (C5-C10)heteroaryl-(C1-C12)-aliphatic-, or 
 
 two R 17  groups together with the nitrogen to which they are bound form a 3- to a 20-membered mono-, an 8- to 20-membered bi- or tri-cyclic heterocyclic ring system; 
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 3 substituents selected independently from J; 
 
         W is: 
       
       
         
           
           
               
               
           
         
         
           wherein:
 E is selected from N(R 17 ) or a bond; 
 two R 17  groups together with the nitrogen to which they are bound form a 3- to a 20-membered mono- or an 8- to 20-membered bi- or tri-cyclic heterocyclic ring system; 
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 3 substituents selected independently from J; 
 
         
         R 5  and R 5′  are independently:
 hydrogen 
 (C1-C12)-aliphatic, 
 (C6-C10)-aryl, or 
 (C5-C10)-heteroaryl, 
 
         wherein any hydrogen in the (C1-C12)-aliphatic is optionally replaced with halogen; 
         wherein any terminal carbon atom is optionally substituted with sulfhydryl or hydroxy; and 
         wherein up to two aliphatic carbon atoms may be replaced by a heteroatom selected from N, NH, O, S, SO, or SO 2 ; 
         wherein any ring is optionally substituted with up to 3 substituents selected independently from J 2 ; and 
         wherein each heteroatom in the heteroaryl ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; or 
         R 5  and R 5′  together with the atom to which they are bound optionally form a 3- to 6-membered ring having up to 2 heteroatoms selected from N, NH, O, S, SO, or SO 2 ; wherein the ring is optionally substituted with up to 2 substituents selected independently from J; 
         R 1  (if present), R 1′  (if present), R 11 , R 11′ , R 13 , and R 13′  are independently:
 hydrogen-, 
 (C1-C12)-aliphatic-, 
 (C3-C10)-cycloalkyl or -cycloalkenyl-, 
 [(C3-C10)-cycloalkyl or -cycloalkenyl]-(C1-C12)-aliphatic-, 
 (C6-C10)-aryl-, 
 (C6-C10)-aryl-(C1-C12)aliphatic-, 
 (C3-C10)-heterocyclyl-, 
 (C6-C10)-heterocyclyl-(C1-C12)aliphatic, 
 (C5-C10)-heteroaryl-, or 
 (C5-C10)-heteroaryl-(C1-C12)-aliphatic-, 
 
         wherein each of R 1  (if present), R 1′  (if present), R 11 , R 11′ , R 13 , and R 13′  is independently and optionally substituted with up to 3 substituents independently selected from J; 
         wherein any ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; 
         wherein up to 3 aliphatic carbon atoms in each of R 1  (if present), R 1 , (if present), R 11 , R 11′ , R 13 , and R 13′  may be replaced by a heteroatom selected from O, N, NH, S, SO, or SO 2  in a chemically stable arrangement; or 
         R 1  and R 1′  (both if present) together with the atom to which they are bound optionally form a 3- to 6-membered ring having up to 2 heteroatoms selected from N, NH, O, S, SO, or SO 2 ; wherein the ring system is optionally substituted with up to 2 substituents selected independently from J; or 
         R 11  and R 11′  together with the atom to which they are bound optionally form a 3- to 6-membered ring having up to 2 heteroatoms selected from N, NH, O, S, SO, or SO 2 ; wherein the ring is optionally substituted with up to 2 substituents selected independently from J; or 
         R 13  and R 13′  together with the atom to which they are bound is a 3- to 6-membered ring having up to 2 heteroatoms selected from N, NH, O, S, SO, or SO 2 ; wherein the ring is optionally substituted with up to 2 substituents selected independently from J; 
         R 2 , R 4 , R 8  (if present), and R 12  are independently
 hydrogen-, 
 (C1-C12)-aliphatic-, 
 (C3-C10)-cycloalkyl or -cycloalkenyl-, 
 [(C3-C10)-cycloalkyl or -cycloalkenyl]-(C1-C12)-aliphatic-, 
 (C6-C10)-aryl-, 
 (C6-C10)-aryl-(C1-C12)aliphatic-, 
 (C3-C10)-heterocyclyl-, 
 (C6-C10)-heterocyclyl-(C1-C12)aliphatic, 
 (C5-C10)-heteroaryl-, or 
 (C5-C10)-heteroaryl-(C1-C12)-aliphatic-, 
 
         wherein each R 2 , R 4 , R 8  (if present), and R 12  is independently and optionally substituted with up to 3 substituents independently selected from J; 
         wherein up to two aliphatic carbon atoms in R 2 , R 4 , R 8  (if present), and R 12  may be replaced by a heteroatom selected from O, N, NH, S, SO, or SO 2 ; or 
         R 11  and R 12  together with the atoms to which they are bound form a 3- to a 20-membered mono-, an 8- to 20-membered bi- or tri-cyclic carbocyclic or heterocyclic ring system;
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 3 substituents selected independently from J; or 
 
         R 12  and R 13  together with the atoms to which they are bound form a 4- to a 20-membered mono-, an 8- to 20-membered bi- or tri-cyclic carbocyclic or heterocyclic ring system;
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 3 substituents selected independently from J; or 
 
         R 11  and R 13  together with the atoms to which they are bound form a 5- to a 20-membered mono-, an 8- to 20-membered bi- or tri-cyclic carbocyclic or heterocyclic ring system;
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 3 substituents selected independently from J; or 
 
         R 11 , R 12 , and R 13  together with the atoms to which they are bound form an 8- to a 20-membered bi- or tri-cyclic carbocyclic or heterocyclic ring system;
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 3 substituents selected independently from J; or 
 
         R 13′  and R 2  together with the atoms to which they are bound form a 3- to a 20-membered mono-, an 8- to 20-membered bi- or tri-cyclic carbocyclic or heterocyclic ring system;
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 3 substituents selected independently from J; or 
 
         R 5  and R 13  together with the atoms to which they are bound form a 18- to a 23-membered mono-, a 19- to 24-membered bi-, or a 20- to 25-membered tri-cyclic carbocyclic or heterocyclic ring system;
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 6 substituents selected independently from J; or 
 
         R 1  (if present) and R 12  together with the atoms to which they are bound form a 18- to a 23-membered mono-, a 19- to 24-membered bi-, or a 20- to 25-membered tri-cyclic carbocyclic or heterocyclic ring system;
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 6 substituents selected independently from J. 
 
       
     
     
         2 . The compound according to  claim 1 , wherein z is 1. 
     
     
         3 . The compound according to  claim 1 , wherein the 
       
         
           
           
               
               
           
         
       
       radical is: 
       
         
           
           
               
               
           
         
       
       wherein J is as defined in  claim 1 . 
     
     
         4 . The compound according to  claim 1 , wherein the 
       
         
           
           
               
               
           
         
       
       radical is: 
       
         
           
           
               
               
           
         
       
       wherein n is 0 or 1 and Z and Z′ are S or O. 
     
     
         5 . The compound according to  claim 1 , wherein the 
       
         
           
           
               
               
           
         
       
       radical is: 
       
         
           
           
               
               
           
         
         wherein each B independently forms a 3- to a 20-membered carbocyclic or heterocyclic ring system; 
         wherein each ring B is either aromatic or nonaromatic; 
         wherein each heteroatom in the heterocyclic ring system is N, NH, O, S, SO, or SO 2 ; 
         wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
         wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
         wherein each ring is optionally substituted with up to 3 substituents selected independently from J. 
       
     
     
         6 . The compound according to  claim 5 , wherein the 
       
         
           
           
               
               
           
         
       
       radical is: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound according to  claim 6 , wherein wherein the 
       
         
           
           
               
               
           
         
       
       radical is: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound according to  claim 1 , wherein R 5  and R 5′  is: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound according to  claim 1 , wherein R 5  and R 5′  are independently hydrogen or: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound according to  claim 1 , wherein R 13′  is hydrogen and R 13  is:
 (C1-C6)-aliphatic,   (C3-C10)-cycloalkyl,   [(C3-C10)-cycloalkyl]-(C1-C12)-alkyl,   (C6-C10)-aryl,   (C6-C10)-aryl-(C1-C6)alkyl,   (C3-C10)-heterocyclyl,   (C6-C10)-heterocyclyl-(C1-C6)alkyl,   (C5-C10)-heteroaryl, or   (C5-C10)-heteroaryl-(C1-C6)-alkyl;   wherein R 13  is optionally substituted with up to 3 substituents independently selected from J; and   wherein up to 3 aliphatic carbon atoms in R 13  may be replaced by a heteroatom selected from O, NH, S, SO, or SO 2  in a chemically stable arrangement.   
     
     
         11 . The compound according to  claim 10 , wherein R 13′  is hydrogen and R 13  is: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound according to  claim 1 , wherein R 1′ , if present, is hydrogen and R 1 , if present, is:
 (C1-C6)-aliphatic,   (C3-C10)-cycloalkyl,   [(C3-C10)-cycloalkyl]-(C1-C12)-alkyl,   (C6-C10)-aryl,   (C6-C10)-aryl-(C1-C6)alkyl,   (C3-C10)-heterocyclyl,   (C6-C10)-heterocyclyl-(C1-C6)alkyl,   (C5-C10)-heteroaryl, or   (C5-C10)-heteroaryl-(C1-C6)-alkyl;   wherein R 1  is optionally substituted with up to 3 substituents independently selected from J; and   wherein up to 3 aliphatic carbon atoms in R 1  may be replaced by a heteroatom selected from O, NH, S, SO, or SO 2  in a chemically stable arrangement.   
     
     
         13 . The compound according to  claim 12 , wherein R 1′ , if present, is hydrogen and R 1 , if present, is: 
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound according to  claim 1 , wherein T is:
 (C5-C10)heteroaryl, wherein T is optionally substituted with up to 3 J substitutents.   
     
     
         15 . The compound according to  claim 14 , wherein T is: 
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound according to  claim 14 , wherein T is: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound according to  claim 1 , wherein R 2  and R 4  are each H and R 8 , if present, is H. 
     
     
         18 . The compound according to  claim 1 , wherein W is: 
       
         
           
           
               
               
           
         
       
       wherein
 each R 17  is independently:
 hydrogen-, 
 (C1-C12)-aliphatic-, 
 (C3-C10)-cycloalkyl- or cycloalkenyl-, 
 [(C3-C10)-cycloalkyl- or cycloalkenyl]-(C1-C12)-aliphatic-, 
 (C6-C10)-aryl-, 
 (C6-C10)-aryl-(C1-C12)aliphatic-, 
 (C3-C10)-heterocyclyl-, 
 (C3-C10)-heterocyclyl-(C1-C12)-aliphatic-, 
 (C5-C10)heteroaryl-, 
 (C5-C10)heteroaryl-(C1-C12)-aliphatic-, or 
 
 two R 17  groups together with the nitrogen to which they are bound form a 3- to a 20-membered mono-, an 8- to 20-membered bi- or tri-cyclic heterocyclic ring system; 
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 3 substituents selected independently from J. 
 
     
     
         19 . The compound according to  claim 1 , wherein W is: 
       
         
           
           
               
               
           
         
       
       wherein
 each R 17  is independently:
 hydrogen-, 
 (C1-C12)-aliphatic-, 
 (C3-C10)-cycloalkyl- or cycloalkenyl-, 
 [(C3-C10)-cycloalkyl- or cycloalkenyl]-(C1-C12)-aliphatic-, 
 (C6-C10)-aryl-, 
 (C6-C10)-aryl-(C1-C12)aliphatic-, 
 (C3-C10)-heterocyclyl-, 
 (C3-C10)-heterocyclyl-(C1-C12)-aliphatic-, 
 (C5-C10)heteroaryl-, 
 (C5-C10)heteroaryl-(C1-C12)-aliphatic-, or 
 
 two R 17  groups together with the nitrogen to which they are bound form a 3- to a 20-membered mono-, an 8- to 20-membered bi- or tri-cyclic heterocyclic ring system; 
 wherein, in the bi- and tri-cyclic ring system, each ring is linearly fused, bridged, or spirocyclic; 
 wherein each ring is either aromatic or nonaromatic; 
 wherein each heteroatom in the heterocyclic ring system is selected from the group consisting of N, NH, O, S, SO, and SO 2 ; 
 wherein each ring is optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; and 
 wherein each ring is optionally substituted with up to 3 substituents selected independently from J. 
 
     
     
         20 . The compound according to  claim 1 , wherein said compound is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         21 . A pharmaceutical composition comprising a compound according to  claim 1  or a pharmaceutically acceptable salt thereof, in an amount effective to inhibit a serine protease; and a acceptable carrier, adjuvant or vehicle. 
     
     
         22 . The pharmaceutical composition according to  claim 21 , wherein said composition comprises an additional agent selected from an immunomodulatory agent; an antiviral agent; a second inhibitor of HCV protease; an inhibitor of another target in the HCV life cycle; and a cytochrome P-450 inhibitor; or combinations thereof. 
     
     
         23 . A method of inhibiting the activity of a serine protease comprising the step of contacting said serine protease with a compound according to  claim 1 . 
     
     
         24 . A method of treating an HCV infection in a patient comprising the step of administering to said patient a composition according to  claim 21 .