US2005090450A1PendingUtilityA1
Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
Priority: Apr 11, 2003Filed: Apr 9, 2004Published: Apr 28, 2005
Est. expiryApr 11, 2023(expired)· nominal 20-yr term from priority
A61P 43/00C07K 5/0812C07K 5/0808A61P 31/14C07D 417/12A61P 31/12A61K 38/00C07D 403/12C07K 5/0804
56
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Claims
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.
Claims
exact text as granted — not AI-modified1 . 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)—, —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 S O 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 0, 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 (C 3 -C 10 )-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 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 a bond, —CH 2 —, or —C(O)—; and
Z is (C1-C12)-aliphatic-,
(C3-C10)-cycloalkyl- or -cycloalkenyl-,
[C(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 9 , 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 any one of claims 1 - 14 , 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 . (original) 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:
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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 . The composition according to claim 41 , wherein said composition is formulated for administration to a patient.
43 . The composition according to claim 42 , 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.
44 . The composition according to claim 41 , wherein said immunomodulatory agent is α-, β-, or γ-interferon or thymosin; said antiviral agent is ribavirin, amantadine, or telbivudine; or said inhibitor of another target in the HCV life cycle is an inhibitor of HCV helicase, polymerase, or metalloprotease.
45 . The composition according to claim 43 , wherein said cytochrome P-450 inhibitor is ritonavir.
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 . The method according to claim 46 , wherein said serine protease is an HCV NS3 protease.
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 . The method according to claim 48 , comprising the additional step of administering to said patient 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; or combinations thereof; wherein said additional agent is administered to said patient as part of said composition according to claim 42 or as a separate dosage form.
50 . The method according to claim 49 , wherein said immunomodulatory agent is α-, β-, or γ-interferon or thymosin; said antiviral agent is ribavarin or amantadine; or said inhibitor of another target in the HCV life cycle is an inhibitor of HCV helicase, polymerase, or metalloprotease.
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 . The method according to claim 51 , wherein said sample or equipment is selected from blood, other body fluids, biological tissue, a surgical instrument, a surgical garment, a laboratory instrument, a laboratory garment, a blood or other body fluid collection apparatus; a blood or other body fluid storage material.
53 . The method according to claim 52 , wherein said body fluid is blood.Join the waitlist — get patent alerts
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