Inhibitors of serine protease, 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 NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are useful as antiviral agents. The invention further relates to pharmaceutically acceptable compositions comprising said compounds either for ex vivo use or for administration to a patient suffering from HCV infection and processes for preparing the compounds. The invention also relates to methods of treating an HCV infection in a patient by administering a pharmaceutical composition comprising a compound of this invention.

1 . A compound of formula I: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, or mixtures thereof, wherein:
 W is: 
 
     
       
         
         
             
             
         
       
       
         wherein each R 6  is independently:
 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-, or 
 wherein up to 3 aliphatic carbon atoms in each R 6  may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)— in a chemically stable arrangement; 
 wherein R 6  may be optionally substituted with up to 3 J substituents; or 
 two R 6  groups, together with the nitrogen atom to which they are bound, may optionally form a 5- to 6-membered aromatic or a 3- to 7-membered saturated or partially unsaturated ring system wherein up to 3 ring atoms may be optionally replaced with N, NH, O, S, SO, and SO 2 , wherein said ring system may be optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or a (C3-C10)heterocyclyl, wherein any ring has up to 3 substituents selected independently from J; 
 wherein each R 8  is independently —OR′; or the R 8  groups together with the boron atom, may optionally form a (C3-C10)-membered heterocyclic ring wherein each R 8  is independently —OR′; or the R 8  groups together with the boron atom, may optionally form a (C3-C10)-membered heterocyclic ring having, in addition to the boron, up to 3 ring atoms optionally replaced with N, NH, O, S, SO, and SO 2 ; 
 
       
       J is halogen, —OR′, —NO 2 , —CN, —CF 3 , —OCF 3 , —R′, oxo, thioxo, ═N(R′), ═N(OR′), 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)C(O)OR′, —C(O)C(O)NR′, —C(O)CH 2 C(O)R′, —C(S)R′, —C(S)OR′, —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;
 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-, 
 (C3-C10)-heterocyclyl-(C1-C12)aliphatic-, 
 (C5-C10)-heteroaryl-, and 
 (C5-C10)-heteroaryl-(C1-C12)-aliphatic-; 
 wherein up to 5 atoms in R′ may be optionally and independently substituted with J; 
 wherein two R′ groups bound to the same atom may optionally form a 5- to 6-membered aromatic or a 3- to 7-membered saturated or partially unsaturated ring system wherein up to 3 ring atoms may be optionally replaced with a heteroatom independently selected from N, NH, O, S, SO, and SO 2 , wherein said ring system may be optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or a (C3-C10)heterocyclyl, wherein any ring has up to 3 substituents selected independently from J; 
 
       R 5  and R 5′  are each independently hydrogen or (C1-C12)-aliphatic, wherein any hydrogen may be optionally replaced with halogen; wherein any terminal carbon atom of R 5  may be optionally substituted with sulfhydryl or hydroxy; or R 5  is Ph or —CH 2 Ph and R 5′  is H, wherein said Ph or —CH 2 Ph group may be optionally substituted with up to 3 substituents independently selected from J; or 
       R 5  and R 5′  together with the atom to which they are bound may optionally form a 3- to 6-membered saturated or partially unsaturated ring system wherein up to 2 ring atoms may be optionally replaced with N, NH, O, SO, or SO 2 ; wherein said ring system has up to 2 substituents selected independently from J; 
       R 2 , R 4 , and R 7  are each independently:
 hydrogen-, 
 (C1-C12)-aliphatic-, 
 (C3-C10)-cycloalkyl-(C1-C12)-aliphatic-, or 
 (C6-C10)-aryl-(C1-C12)-aliphatic-;
 wherein up to two aliphatic carbon atoms in each of R 2 , R 4 , and R 7  may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)— in a chemically stable arrangement; 
 wherein each of R 2 , R 4 , and R 7  may be independently and optionally substituted with up to 3 substituents independently selected from J; 
 
 
       R 1  and R 3  are each independently:
 (C1-C12)-aliphatic-, 
 (C3-C10)-cycloalkyl- or -cycloalkenyl-, 
 [(C3-C10)-cycloalkyl- or -cycloalkenyl]-(C1-C12)-aliphatic-, 
 (C6-C10)-aryl-(C1-C12)aliphatic-, or 
 (C5-C10)-heteroaryl-(C1-C12)-aliphatic-;
 wherein up to 3 aliphatic carbon atoms in each of R 1  and R 3  may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)— in a chemically stable arrangement; 
 wherein each of R 1  and R 3  may be independently and optionally substituted with up to 3 substituents independently selected from J; 
 
 
       R 9 , R 9′ , R 10 , and R 10′  are each independently —X—Y-Z; 
       X is a bond, —C(H)(R 6 )—, —O—, —S—, or —N(R 11 )—; 
       R 11  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-,
 wherein up to 3 aliphatic carbon atoms in each R 11  may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)— in a chemically stable arrangement; 
 wherein R 11  may be optionally substituted with up to 3 J substituents; or 
 wherein R 11  and Z together with the atoms to which they are bound, optionally form a nitrogen containing 5-7-membered mono- or 6-11-membered bicyclic ring system optionally substituted with up to 3 J substitutents, wherein up to 3 ring atoms in said ring system may be optionally replaced with O, NH, S, SO, or SO 2  in a chemically stable arrangement; 
 
 
       Y is a bond, —CH 2 —, —C(O)—, —C(O)C(O)—, —S(O)—, S(O) 2 —, or —S(O)(NR 12 )—; 
       R 12  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-,
 wherein up to 3 aliphatic carbon atoms in each R 12  may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; 
 wherein R 12  may be optionally substituted with up to 3 J substituents; 
 
 
       Z is:
 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-;
 wherein up to three aliphatic carbon atoms in Z may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; 
 wherein any ring may be optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; 
 wherein Z may be independently and optionally substituted with up to 3 substituents independently selected from J; 
 
 
       V is —C(O)—, —S(O)—, or —S(O) 2 —; 
       R is —C(O)—, —S(O)—, —S(O) 2 —, —N(R 12 )—, —O—, or a bond; 
       T is:
 (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-;
 wherein up to 3 aliphatic carbon atoms in T may be 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; or 
 
 
       T is selected from —N(R 6 )(R 6′ ); and 
       R 6′  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-, or
 wherein up to 3 aliphatic carbon atoms in each R 6′  may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)— in a chemically stable arrangement; 
 wherein R 6′  may be optionally substituted with up to 3 J substituents; or 
 R 6  and R 6′ , together with the nitrogen atom to which they are bound, may optionally form a (C3-C10)-heterocyclic ring system wherein said ring system may be optionally substituted with up to 3 substituents independently selected from J. 
 
 
     
   
   
       2 . The compound according to  claim 1 , wherein the 
     
       
         
         
             
             
         
       
     
     radical is, 
     
       
         
         
             
             
         
       
     
     wherein;
 in R′, R 10 , and R 10′ , X and Y are both a bond and Z is hydrogen; and in R 9′ ; 
 X is a bond; 
 Y is a bond, —CH 2 —, or —C(O)—; and 
 Z is (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-;
 wherein up to three aliphatic carbon atoms in Z may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; 
 wherein any ring may be optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; 
 wherein Z may be independently and optionally substituted with up to 3 substituents independently selected from J. 
 
 
 
   
   
       3 . The compound according to  claim 2 , wherein in R 9′ ;
 X is a bond;   Y is a bond; and   Z is (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-, 
 (C5-C10)-heteroaryl-, or 
 (C5-C10)-heteroaryl-(C1-C12)-aliphatic-;
 wherein up to three aliphatic carbon atoms in Z may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; 
 wherein any ring may be optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; 
 wherein Z may be independently and optionally substituted with up to 3 substituents independently selected from J. 
 
   
   
   
       4 . The compound according to  claim 3 , wherein in
 R 9′ ;   X is a bond;   Y is a bond; and   Z is (C1-C12)-aliphatic-,
 (C3-C10)-cycloalkyl- or -cycloalkenyl-, 
 [(C3-C10)-cycloalkyl or -cycloalkenyl]-(C1-C12)-aliphatic-, or 
 (C6-C10)-aryl-(C1-C12)aliphatic-,
 wherein up to three aliphatic carbon atoms in Z may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; 
 wherein Z may be independently and optionally substituted with up to 3 substituents independently selected from J. 
 
   
   
   
       5 . The compound according to  claim 4 , wherein R 9′  is 
     
       
         
         
             
             
         
       
     
   
   
       6 . The compound according to  claim 5 , wherein R 9′  is 
     
       
         
         
             
             
         
       
     
   
   
       7 . The compound according to  claim 6 , wherein R 9′  is
 ethyl.   
   
   
       8 . The compound according to  claim 1 , wherein in
 R 9 , R 10 , and R 10′ , X and Y are both a bond and Z is hydrogen;   and in R 9′ ;   X is a bond;   Y is —C(O)—; and   Z is (C1-C12)-aliphatic-, or
 (C3-C10)-heterocyclyl-(C1-C12)aliphatic-;
 wherein up to three aliphatic carbon atoms in Z may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; 
 wherein any ring may be optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; 
 wherein Z may be independently and optionally substituted with up to 3 substituents independently selected from J. 
 
   
   
   
       9 . The compound according to  claim 8 , wherein Z is —O—(C1-C6)-aliphatic or —N(R′) 2 , wherein the two R′ groups bound to the nitrogen atom may optionally form a 3- to 7-membered saturated or partially unsaturated ring system wherein up to 3 ring atoms may be optionally replaced with a heteroatom independently selected from N, NH, O, S, SO, and SO 2 , wherein said ring system may be optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or a (C3-C10)heterocyclyl, wherein any ring has up to 3 substituents selected independently from J. 
   
   
       10 . The compound according to  claim 8 , wherein Z is —N(R′) 2 , wherein the two R′ groups bound to the nitrogen atom may optionally form a 3- to 7-membered saturated or partially unsaturated ring system wherein up to 3 ring atoms may be optionally replaced with a heteroatom independently selected from N, NH, O, S, SO, and SO 2 , wherein said ring system may be optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or a (C3-C10)heterocyclyl, wherein any ring has up to 3 substituents selected independently from J. 
   
   
       11 . The compound according to  claim 1 , wherein in
 R′, and R 10 , X and Y are a bond and Z is hydrogen; and in each of R 9  and R 10′  independently;   X is a bond;   Y is a bond; and   Z is (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-;
 wherein up to three aliphatic carbon atoms in Z may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; 
 wherein any ring may be optionally fused to a (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C10)cycloalkyl, or (C3-C10)heterocyclyl; 
 wherein Z may be independently and optionally substituted with up to 3 substituents independently selected from J. 
 
   
   
   
       12 . The compound according to  claim 11 , wherein Z, in each of R 9′  and R 10′  independently, is
 (C1-C12)-aliphatic-,   (C3-C10)-cycloalkyl- or -cycloalkenyl-, or   [(C3-C10)-cycloalkyl or -cycloalkenyl]-(C1-C12)-aliphatic-;
 wherein up to three aliphatic carbon atoms in Z may be optionally replaced with S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; 
 wherein Z may be independently and optionally substituted with up to 3 substituents independently selected from J. 
   
   
   
       13 . The compound according to  claim 12 , wherein Z, in each of R 9′  and R 10′  independently, is (C1-C6)-aliphatic-. 
   
   
       14 . The compound according to  claim 1 , wherein in
 R 10 , and R 10′ , X and Y are a bond and Z is hydrogen; and in each of R 9  and R 9′ ;   X is a bond,   Y is a bond, and   Z is (C1-C6)-aliphatic-,
 wherein Z may be independently and optionally substituted with up to 3 substituents independently selected from J. 
   
   
   
       15 . The compound according to  claim 1 , wherein W is: 
     
       
         
         
             
             
         
       
     
     wherein in the W, the NR 6 R 6  is selected from —NH—(C1-C6 aliphatic), —NH— (C3-C6 cycloalkyl), —NH—CH(CH 3 )-aryl, or —NH—CH(CH 3 )-heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with up to 3 halogens. 
   
   
       16 . The compound according to  claim 15 , wherein in the W, the NR 6 R 6  is: 
     
       
         
         
             
             
         
       
     
   
   
       17 . The compound according to  claim 16 , wherein in the W, the NR 6 R 6  is: 
     
       
         
         
             
             
         
       
     
   
   
       18 . The compound according to  claim 17 , wherein in the W, the NR 6 R 6  is: 
     
       
         
         
             
             
         
       
     
   
   
       19 . The compound according to  claim 18 , wherein in the W, the NR 6 R 6  is: 
     
       
         
         
             
             
         
       
     
   
   
       20 . The compound according to  claim 1 , wherein R 5′  is hydrogen and R 5  is: 
     
       
         
         
             
             
         
       
     
   
   
       21 . The compound according to  claim 20 , wherein R 5′  is hydrogen and R 5  is: 
     
       
         
         
             
             
         
       
     
   
   
       22 . The compound according to  claim 1 , wherein R 2 , R 4 , and R 7  are each independently H, methyl, ethyl, or propyl. 
   
   
       23 . The compound according to  claim 22 , wherein R 2 , R 4 , and R 7  are each hydrogen. 
   
   
       24 . The compound according to  claim 1 , wherein R 3  is: 
     
       
         
         
             
             
         
       
     
   
   
       25 . The compound according to  claim 24 , wherein R 3  is: 
     
       
         
         
             
             
         
       
     
   
   
       26 . The compound according to  claim 25 , wherein R 3  is: 
     
       
         
         
             
             
         
       
     
   
   
       27 . The compound according to  claim 1 , wherein R 1  is: 
     
       
         
         
             
             
         
       
     
   
   
       28 . The compound according to  claim 27 , wherein R 1  is: 
     
       
         
         
             
             
         
       
     
   
   
       29 . The compound according to  claim 18 , wherein R 1  is isopropyl or cyclohexyl. 
   
   
       30 . The compound according to  claim 1 , wherein the 
     
       
         
         
             
             
         
       
     
     radical is: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 6 , R 6′ , R 7 , and R 12 , are as defined in  claim 1 . 
 
   
   
       31 . The compound according to  claim 30 , wherein
 in the   
     
       
         
         
             
             
         
       
       radical;
 R 6′  and R 7  are both hydrogen; 
 R 6  is: 
 (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-;
 wherein up to 3 aliphatic carbon atoms in R 6  may be optionally replaced by S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; and 
 wherein R 6  may be optionally substituted with up to 3 substituents independently selected from J; and 
 
 
       R 12  is as defined in  claim 1 . 
     
   
   
       32 . The compound according to  claim 31 , wherein;
 R 6  is:
 (C1-C12)-aliphatic-; 
 (C6-C10)-aryl-(C1-C12)aliphatic-, or 
 (C3-C10)-cycloalkyl or -cycloalkenyl-;
 wherein up to 3 aliphatic carbon atoms in R 6  may be optionally replaced by S, —S(O)—, —S(O) 2 —, —O—, —N—, or —N(H)—, in a chemically stable arrangement; 
 wherein R 6  may be optionally substituted with up to 3 substituents independently selected from J; and 
 
   R 12  is as defined in  claim 1 .   
   
   
       33 . The compound according to  claim 32 , wherein the
 radical is:   
     
       
         
         
             
             
         
       
     
   
   
       34 . The compound according to  claim 33 , wherein the 
     
       
         
         
             
             
         
       
     
     radical is: 
     
       
         
         
             
             
         
       
     
   
   
       35 . The compound according to  claim 1 , wherein;
 V is —C(O)—; and   R is a bond.   
   
   
       36 . The compound according to  claim 1 , wherein;
 V is —C(O)—;   R is a bond; and   T is:
 (C3-C10)-heterocyclyl- or (C5-C10)heteroaryl-;
 wherein each T is optionally substituted with up to 3 J substituents. 
 
   
   
   
       37 . The compound according to  claim 36 , wherein T is (C5-C6)heterocyclyl- or (C5-C6)heteroaryl-;
 wherein each T is optionally substituted with up to 3 J substituents.   
   
   
       38 . The compound according to  claim 37 , wherein T is: 
     
       
         
         
             
             
         
       
     
     wherein:
 Z′ is independently O, S, NR′, or C(R′) 2 . 
 
   
   
       39 . The compound according to  claim 38 , wherein T is: 
     
       
         
         
             
             
         
       
     
   
   
       40 . The compound according to  claim 1 , wherein the compound is: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       41 . A pharmaceutical composition comprising a compound according to  claim 1  or a pharmaceutically acceptable salt or mixtures thereof in an amount effective to inhibit a serine protease; and a acceptable carrier, adjuvant or vehicle. 
   
   
       42 .- 45 . (canceled) 
   
   
       46 . 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 . 
   
   
       47 . (canceled) 
   
   
       48 . A method of treating an HCV infection in a patient comprising the step of administering to said patient a composition according to claim  42 . 
   
   
       49 .- 50 . (canceled) 
   
   
       51 . A method of eliminating or reducing HCV contamination of a biological sample or medical or laboratory equipment, comprising the step of contacting said biological sample or medical or laboratory equipment with a composition according to  claim 41 . 
   
   
       52 .- 53 . (canceled)