US2010028300A1PendingUtilityA1
Macrocyclic peptides active against the hepatitis c virus
Est. expirySep 22, 2023(expired)· nominal 20-yr term from priority
Inventors:Montse Llinas-BrunetMurray D. BaileyPunit BhardwajPasquale ForgioneElise GhiroNathalie GoudreauTeddy HalmosJean Rancourt
A61P 43/00A61P 31/12A61P 31/14C07K 5/0827C07K 5/0802C07K 5/0812A61K 38/00C07K 5/08C07K 5/00Y02A50/30
60
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Claims
Abstract
Compounds of formula I: wherein D, R 4 , R 3 , L 0 , L 1 , L 2 , R 2 and R C are defined herein; or a pharmaceutically acceptable salt thereof, useful as inhibitors of the HCV NS3 protease.
Claims
exact text as granted — not AI-modified1 . A compound of formula I:
wherein W is CH or N,
L 0 is H;
L 1 , L 2 are each independently halogen, (C 1-4 )alkyl, (C 2-4 )alkynyl, —O—(C 1-4 )alkyl, —S—(C 1-4 )alkyl, —SO—(C 1-4 )alkyl, or —SO 2 —(C 1-4 )alkyl; and
either L 1 or L 2 (but not both at the same time) may also be H; or
R 2 is (C 6 or 10 )aryl or Het, wherein Het is a five-, six-, or seven-membered, saturated or unsaturated (including aromatic) heterocycle, containing from one to four heteroatoms each independently selected from nitrogen, oxygen and sulfur, said aryl or Het being substituted with R 24 ,
wherein R 24 is H, halo, (C 1-6 )alkoxy, (C 3-6 )cycloalkoxy or NO 2 ; or
R 24 is R 20 —NHCOR 20 , —NHCOOR 20 , —NHR 21 or —NHCONR 21 R 22 , wherein
R 20 is selected from (C 1-8 )alkyl, (C 3-7 )cycloalkyl and (C 1-4 )alkyl-(C 3-7 )cycloalkyl, wherein said cycloalkyl and alkyl-cycloalkyl may be mono-, di- or tri-substituted with (C 1-3 )alkyl;
R 21 is H or R 20 as defined above; and
R 22 is H or methyl;
R 3 is hydroxy, NH 2 , or a group of formula —NH—R 31 , wherein R 31 is (C 6 or 10 )aryl, heteroaryl, —C(O)—B, —C(O)—OB, or —C(O)—NH—B, wherein B is (C 1-10 )alkyl, (C 3-7 ) cycloalkyl or (C 1-4 )alkyl-(C 3-7 )cycloalkyl,
a) wherein each said alkyl, cycloalkyl, and alkyl-cycloalkyl may be mono-, di- or tri-substituted with (C 1-3 )alkyl; and
b) wherein each said alkyl, cycloalkyl, and alkyl-cycloalkyl may be mono- or di-substituted with substituents each independently selected from hydroxy and O—(C 1-6 )alkyl; and
c) wherein each of said alkyl groups may be mono-, di- or tri-substituted with halogen; and
d) wherein in each of said cycloalkyl groups being 5-, 6- or 7-membered, one or two —CH 2 -groups not being directly linked to each other may be replaced by —O—;
D is a 5 to 10-atom saturated or unsaturated alkylene chain optionally containing one to three heteroatoms each independently selected from: O, S, and N—R 41 , wherein
R 41 is H, (C 1-6 )alkyl, (C 3-6 )cycloalkyl, or —C(O)—R 42 , wherein R 42 is (C 1-6 )alkyl, (C 3-6 )cycloalkyl or (C 6 or 10 )aryl;
R 4 is H or from one to three substituents at any carbon atom of said chain D, said substituents each independently selected from the group consisting of: (C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 1-6 )alkoxy, hydroxy, halo, amino, oxo, thio, and (C 1-6 )alkylthio;
and
R C is hydroxy or —NHSO 2 R S wherein R S is (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 3-7 )cycloalkyl, (C 1-6 )alkyl-(C 3-7 )cycloalkyl, phenyl, naphthyl, pyridinyl, (C 1-4 )alkyl-phenyl, (C 1-4 )alkyl-naphthyl or (C 1-4 )alkyl-pyridinyl; each of which optionally being monosubstituted with nitro; and each of which optionally being mono-, di- or tri-substituted with substituents each independently selected from halogen, hydroxy, cyano, (C 1-6 )alkyl, (C 2-6 )alkenyl, O—(C 1-6 )alkyl, —CO—NH 2 , —CO—NH(C 1-4 )alkyl, —CO—N((C 1-4 )alkyl) 2 , —NH 2 , —NH(C 1-4 )alkyl and —N((C 1-4 )alkyl) 2 , wherein (C 1-6 )alkyl and O—(C 1-6 )alkyl are optionally substituted with one to three halogen atoms;
or R S is —N(R N2 )(R N1 ), wherein R N1 and R N2 are each independently selected from H, (C 1-6 )alkyl, (C 3-7 )cycloalkyl, (C 1-6 )alkyl-(C 3-7 )cycloalkyl, aryl and (C 1-6 )alkyl-aryl; wherein said (C 1-6 )alkyl, (C 3-7 )cycloalkyl, (C 1-6 )alkyl-(C 3-7 )cycloalkyl, aryl and (C 1-6 )alkyl-aryl are each optionally substituted with one or more substituents each independently selected from halogen, (C 1-6 )alkyl, hydroxy, cyano, O—(C 1-6 )alkyl, —NH 2 , —NH(C 1-4 )alkyl, —N((C 1-4 )alkyl) 2 , —CO—NH 2 , —CO—NH(C 1-4 )alkyl, —CO—N((C 1-4 )alkyl) 2 , —COOH, and —COO(C 1-6 )alkyl; or
R N2 and R N1 are linked, together with the nitrogen to which they are bonded, to form a 3- to 7-membered monocyclic saturated or unsaturated heterocycle or a 9- or 10-membered bicyclic saturated or unsaturated heterocycle, each of which optionally containing from one to three further heteroatoms each independently selected from N, S and O, and each of which being optionally substituted with one or more substituents each independently selected from halogen, (C 1-6 )alkyl, hydroxy, cyano, O—(C 1-6 )alkyl, —NH 2 , —NH(C 1-4 )alkyl, —N((C 1-4 )alkyl) 2 , —CO—NH 2 , —CO—NH(C 1-4 )alkyl, —CO—N((C 1-4 )alkyl) 2 , —COOH, and —COO(C 1-6 )alkyl;
or a pharmaceutically acceptable salt or ester thereof;
with the proviso that
when W is N; one of L 1 or L 2 is H and the other L 2 or L 1 is halo or —O—(C 1-4 )alkyl; and
R 2 is (C 6 or 10 )aryl or Het, wherein Het is a five-, six-, or seven-membered, saturated or unsaturated (including aromatic) heterocycle, containing from one to four heteroatoms each independently selected from nitrogen, oxygen and sulfur, said aryl or Het being substituted with R 24
wherein R 24 is selected from H, halo, (C 1-6 )alkyl, —NH 2 , —NH(C 1-6 )alkyl, —NH(C 3-6 )cycloalkyl, —NHCOO(C 1-6 )alkyl, —NHCOO(C 3-6 )cycloalkyl, —NHCO(C 1-6 )alkyl, —NHCO(C 3-6 )cycloalkyl, and —NHCONR 21 R 22 wherein R 21 is selected from H, (C 1-6 )alkyl and (C 3-6 )cycloalkyl and R 22 is selected from H and methyl; and
R 3 is NH 2 , or a group of formula —NH—R 31 , wherein R 31 is —C(O)—B, —C(O)—OB, or —C(O)—NH—B, wherein B is (C 1-6 )alkyl optionally substituted with halo, or B is —(CH 2 ) p —(C 3-7 )cycloalkyl wherein p is 0-4, or B is a tetrahydrofuran ring linked through the C3 or C4 position of the ring; and
D is a 5 to 9-atom saturated or unsaturated alkylene chain optionally containing one to three heteroatoms each independently selected from O and S; and R 4 is H;
then R C is not —NHSO 2 R S , wherein R S is (C 1-6 )alkyl or unsubstituted (C 3-7 )cycloalkyl.
2 . The compound according to claim 1 wherein R 3 is selected from NH—C(O)—B, NH—C(O)—NH—B, and NH—C(O)—O—B, wherein B is defined as in claim 1 .
3 . The compound according to claim 1 wherein D is a 7-carbon alkylene chain containing one cis double bond at position 13, 14 of the chain.
4 . The compound according to claim 1 of formula (I′)
wherein:
X is O or NH; and B, L 0 , L 1 , L 2 , R 2 and R C are defined as in claim 1 ;
with the proviso that:
when one of L 1 or L 2 is H and the other L 2 or L 1 is halo or —O—(C 1-4 )alkyl; and
R 2 is (C 6 or 10 )aryl or Het, wherein Het is a five-, six-, or seven-membered, saturated or unsaturated (including aromatic) heterocycle, containing from one to four heteroatoms each independently selected from nitrogen, oxygen and sulfur, said aryl or Het being substituted with R 24
wherein R 24 is selected from H, halo, (C 1-6 )alkyl, —NH 2 , —NH(C 1-6 )alkyl, —NH(C 3-6 )cycloalkyl, —NHCOO(C 1-6 )alkyl, —NHCOO(C 3-6 )cycloalkyl, —NHCO(C 1-6 )alkyl, —NHCO(C 3-6 )cycloalkyl, and —NHCONR 21 R 22 wherein R 21 is selected from H, (C 1-6 )alkyl and (C 3-6 )cycloalkyl and R 22 is selected from H and methyl; and
B is (C 1-6 )alkyl optionally substituted with halo, or B is —(CH 2 ) p —(C 3-7 )cycloalkyl wherein p is 0-4, or B is a tetrahydrofuran ring linked through the C3 or C4 position of the ring;
then R C is not —NHSO 2 R S , wherein R S is (C 1-6 )alkyl or unsubstituted (C 3-7 )cycloalkyl.
5 . The compound according to claim 1 wherein R 2 is phenyl or Het, wherein said Het is selected from the group consisting of:
wherein R 24 is defined as in claim 1 .
6 . The compound according to claim 5 wherein R 2 is Het, wherein said Het is selected from the group consisting of:
7 . The compound according to claim 1 of formula IA
wherein
B is (C 1-10 )alkyl, (C 3-7 )cycloalkyl or (C 1-4 )alkyl-(C 3-7 )cycloalkyl,
a) wherein each said alkyl, cycloalkyl, and alkyl-cycloalkyl may be mono-, di- or tri-substituted with (C 1-3 )alkyl; and
b) wherein each said alkyl, cycloalkyl, and alkyl-cycloalkyl may be mono- or di-substituted with substituents each independently selected from hydroxy and O—(C 1-6 )alkyl; and
c) wherein each of said alkyl groups may be mono-, di- or tri-substituted with halogen; and
d) wherein in each of said cycloalkyl groups being 5-, 6- or 7-membered, one or two —CH 2 -groups not being directly linked to each other may be replaced by —O—;
X is O or NH;
L 0 is H;
L 1 , L 2 are each independently halogen, (C 1-4 )alkyl, (C 2-4 )alkynyl, —O—(C 1-4 )alkyl, —S—(C 1-4 )alkyl, —SO—(C 1-4 )alkyl, or —SO 2 —(C 1-4 )alkyl; and
either L 1 or L 2 (but not both at the same time) may also be H; or
R 24 is R 20 —NHCOR 20 , —NHCOOR 20 , —NHR 21 or —NHCONR 21 R 22 , wherein
R 20 is selected from (C 1-8 )alkyl, (C 3-7 )cycloalkyl and (C 1-4 )alkyl-(C 3-7 )cycloalkyl, wherein said cycloalkyl and alkyl-cycloalkyl may be mono-, di- or tri-substituted with (C 1-3 )alkyl;
R 21 is H or R 20 as defined above; and
R 22 is H or methyl; and
R C is hydroxy or —NHSO 2 R S wherein R S is (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 3-7 )cycloalkyl, (C 1-6 )alkyl-(C 3-7 )cycloalkyl, phenyl, naphthyl, pyridinyl, (C 1-4 )alkyl-phenyl, (C 1-4 )alkyl-naphthyl or (C 1-4 )alkyl-pyridinyl; each of which optionally being monosubstituted with nitro; and each of which optionally being mono-, di- or tri-substituted with substituents each independently selected from halogen, hydroxy, cyano, (C 1-6 )alkyl, (C 2-6 )alkenyl, O—(C 1-6 )alkyl, —CO—NH 2 , —CO—NH(C 1-4 )alkyl, —CO—N((C 1-4 )alkyl) 2 , —NH 2 , —NH(C 1-4 )alkyl and —N((C 1-4 )alkyl) 2 , wherein (C 1-6 )alkyl and O—(C 1-6 )alkyl are optionally substituted with one to three halogen atoms;
or R S is —N(R N2 )(R N1 ), wherein R N1 and R N2 are each independently selected from H, (C 1-6 )alkyl, (C 3-7 )cycloalkyl, (C 1-6 )alkyl-(C 3-7 )cycloalkyl, aryl and (C 1-6 )alkyl-aryl; wherein said (C 1-6 )alkyl, (C 3-7 )cycloalkyl, (C 1-6 )alkyl-(C 3-7 )cycloalkyl, aryl and (C 1-6 )alkyl-aryl are each optionally substituted with one or more substituents each independently selected from halogen, (C 1-6 )alkyl, hydroxy, cyano, O—(C 1-6 )alkyl, —NH 2 , —NH(C 1-4 )alkyl, —N((C 1-4 )alkyl) 2 , —CO—NH 2 , —CO—NH(C 1-4 )alkyl, —CO—N((C 1-4 )alkyl) 2 , —COOH, and —COO(C 1-6 )alkyl; or
R N2 and R N1 are linked, together with the nitrogen to which they are bonded, to form a 3- to 7-membered monocyclic saturated or unsaturated heterocycle or a 9- or 10-membered bicyclic saturated or unsaturated heterocycle, each of which optionally containing from one to three further heteroatoms each independently selected from N, S and O, and each of which being optionally substituted with one or more substituents each independently selected from halogen, (C 1-6 )alkyl, hydroxy, cyano, O—(C 1-6 )alkyl, —NH 2 , —NH(C 1-4 )alkyl, —N((C 1-4 )alkyl) 2 , —CO—NH 2 , —CO—NH(C 1-4 )alkyl, —CO—N((C 1-4 )alkyl) 2 , —COOH, and —COO(C 1-6 )alkyl;
or a pharmaceutically acceptable salt or ester thereof;
with the proviso that
when one of L 1 or L 2 is H and the other L 2 or L 1 is halo or —O—(C 1-4 )alkyl; and
R 24 is selected from H, halo, (C 1-6 )alkyl, —NH 2 , —NH(C 1-6 )alkyl, —NH(C 3-6 )cycloalkyl, —NHCOO(C 1-6 )alkyl, —NHCOO(C 3-6 )cycloalkyl, —NHCO(C 1-6 )alkyl, —NHCO(C 3-6 )cycloalkyl, and —NHCONR 21 R 22 wherein R 21 is selected from H, (C 1-6 )alkyl and (C 3-6 )cycloalkyl and R 22 is selected from H and methyl; and
B is (C 1-6 )alkyl optionally substituted with halo, or B is —(CH 2 ) p —(C 3-7 )cycloalkyl wherein p is 0-4, or B is a tetrahydrofuran ring linked through the C3 or C4 position of the ring;
then R C is not —NHSO 2 R S , wherein R S is (C 1-6 )alkyl or unsubstituted (C 3-7 )cycloalkyl.
8 . The compound according to claim 1 wherein B is selected from tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-methylcyclopentyl and 1-methylcyclohexyl.
9 . The compound according to claim 1 wherein B is cyclopentyl.
10 . The compound according to claim 4 wherein X is O.
11 . The compound according to claim 4 wherein X is NH.
12 . The compound according to claim 1 wherein L 1 and L 2 are each independently selected from: halogen, —CH 3 , —C≡CH, —OCH 3 , —OC 2 H 5 , —SMe, —SOMe, and SO 2 Me whereby either L 1 or L 2 , but not both at the same time, may be H.
13 . The compound according to claim 12 wherein L 1 is CH 3 , —C≡CH, —F, —Cl, —Br, —OMe, —SMe, or —SO 2 Me and L 2 is H.
14 . The compound according to claim 1 wherein R 24 is selected from R 20 , NHCOR 20 , —NHCOOR 20 , —NHR 21 and —NHCONR 21 R 22 , wherein
R 20 is selected from (C 1-8 )alkyl, (C 3-7 )cycloalkyl, and (C 1-3 )alkyl-(C 3-7 )cycloalkyl, wherein said cycloalkyl and alkyl-cycloalkyl may be mono-, di- or tri-substituted with (C 1-3 )alkyl; and R 21 is H or R 20 as defined above; and R 22 is H or methyl.
15 . The compound according to claim 14 wherein R 24 is —NHCOR 20 , —NHCOOR 20 , or —NHR 21 .
16 . The compound according to claim 1 wherein R 20 and R 21 are each independently selected from: methyl, ethyl, n-propyl, i-propyl, n-butyl, 1-methylpropyl, 2-methylpropyl, tert-butyl, 2,2-dimethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1,2,2-trimethylpropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl, each of said cycloalkyl or alkyl-cycloalkyl groups optionally being mono- or di-substituted with methyl or ethyl.
17 . The compound according to claim 16 wherein R 20 and R 21 are each independently selected from: methyl, ethyl, n-propyl, i-propyl, 2,2-dimethylpropyl and cyclopentylmethyl.
18 . The compound according to claim 1 wherein R C is hydroxy.
19 . The compound according to claim 1 wherein R C is —NHSO 2 R S wherein R S is methyl, ethyl, n-propyl, i-propyl, n-butyl, 1-methylpropyl, 2-methylpropyl, tert-butyl, ethenyl, 1-propenyl, 2-propenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, phenyl, naphthyl, pyridinyl, phenylmethyl, naphthylmethyl or pyridinylmethyl;
a) each of which optionally being mono-, di- or tri-substituted with substituents each independently selected from fluorine, methyl, ethyl and propyl; and b) each of which optionally being mono- or disubstituted with substituents each independently selected from hydroxy, trifluoromethyl, methoxy and trifluoromethoxy; and c) each of which optionally being monosubstituted with a substituent selected from chlorine, bromine, cyano, nitro, ethenyl, 1-propenyl, 2-propenyl, —CO—NH 2 , —CO—NHCH 3 , —CO—N(CH 3 ) 2 , —NH 2 , —NH(CH 3 ) and —N(CH 3 ) 2 ; or R S is —N(R N2 )(R N1 ),
wherein R N1 and R N2 are each independently selected from H, (C 1-4 )alkyl, (C 3-7 )cycloalkyl, (C 1-3 )alkyl-(C 3-7 )cycloalkyl, phenyl, and (C 1-3 )alkyl-phenyl; wherein said (C 1-4 )alkyl, (C 3-7 )cycloalkyl, (C 1-3 )alkyl-(C 3-7 )cycloalkyl, phenyl and (C 1-3 )alkyl-phenyl are optionally substituted with one, two or three substituents each independently selected from halogen, (C 1-6 )alkyl, hydroxy, cyano, O—(C 1-6 )alkyl, —NH 2 , —NH(C 1-4 )alkyl, —N((C 1-4 )alkyl) 2 , —CO—NH 2 , —CO—NH(C 1-4 )alkyl, —CO—N((C 1-4 )alkyl) 2 , —COOH, and —COO(C 1-6 )alkyl; or
R N2 and R N1 are linked, together with the nitrogen to which they are bonded, to form a 5 or 6-membered monocyclic heterocycle which may be saturated or unsaturated, optionally containing from one to three further heteroatoms each independently selected from N, S and O, and optionally substituted with one, two or three substituents each independently selected from halogen, (C 1-6 )alkyl, hydroxy, cyano, O—(C 1-6 )alkyl, —NH 2 , —NH(C 1-4 )alkyl, —N((C 1-4 )alkyl) 2 , —CO—NH 2 , —CO—NH(C 1-4 )alkyl, —CO—N((C 1-4 )alkyl) 2 , —COOH, and —COO(C 1-6 )alkyl.
20 . The compound according to claim 19 wherein R C is selected from —NHSO 2 -methyl, —NHSO 2 -ethyl, —NHSO 2 -(1-methyl)ethyl, —NHSO 2 -propyl, —NHSO 2 -cyclopropyl, —NHSO 2 —CH 2 -cyclopropyl, —NHSO 2 -(1-methylcyclopropyl), —NHSO 2 -cyclobutyl, —NHSO 2 -cyclopentyl, —NHSO 2 -phenyl and —NHSO 2 N(CH 3 ) 2 .
21 . The compound according to claim 20 wherein R C is selected from —NHSO 2 -cyclopropyl, —NHSO 2 -(1-methylcyclopropyl) and —NHSO 2 N(CH 3 ) 2 .
22 . The compound according to claim 1 of formula IA:
wherein
B is cyclopentyl;
X is or NH;
L 0 is H; L 1 is CH 3 , —C≡CH, —F, —Cl, —Br, —OMe, —SMe, or —SO 2 Me; and L 2 is H;
R 24 is —NHCOR 20 , —NHCOOR 20 , or —NHR 21 , wherein R 20 and R 21 are each independently selected from: methyl, ethyl, n-propyl, i-propyl, 2,2-dimethylpropyl and cyclopentylmethyl; and
R C is hydroxy.
23 . The compound according to claim 1 of formula IA:
wherein
B is cyclopentyl;
X is O or NH;
L 0 is H; L 1 is CH 3 , —C≡CH, —F, —Cl, —Br, —OMe, —SMe, or —SO 2 Me; and L 2 is H;
R 24 is —NHCOR 20 , —NHCOOR 20 , or —NHR 21 , wherein R 20 and R 21 are each independently selected from: methyl, ethyl, n-propyl, i-propyl, 2,2-dimethylpropyl and cyclopentylmethyl; and
R C is —NHSO 2 -cyclopropyl, —NHSO 2 -(1-methylcyclopropyl) or —NHSO 2 N(CH 3 ) 2 ;
with the proviso that
when L 1 is —F, —Cl, —Br or —OMe; and
R 24 is —NHCOR 20 , —NHCOOR 20 , or —NHR 21 , wherein R 20 and R 21 are each independently selected from: methyl, ethyl, n-propyl, i-propyl and 2,2-dimethylpropyl;
then R C is not —NHSO 2 -cyclopropyl.
24 . The compound according to claim 1 of the formula
wherein R 24 and L 1 are defined as in the table below
Cpd #
L 1
R 24
201
—SMe
202
—SMe
203
—SMe
204
—SMe
205
—SMe
206
—SMe
207
—SMe
208
—SO 2 Me
209
—SO 2 Me
210
—SO 2 Me
211
—SO 2 Me
212
—Me
213
—Me
214
—Me
215
—Me
216
—Me
217
218
219
220
25 . A pharmaceutical composition comprising an anti-hepatitis C virally effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, and a pharmaceutically acceptable carrier medium or auxiliary agent.
26 . The pharmaceutical composition according to claim 25 further comprising a therapeutically effective amount of at least one other antiviral agent.
27 . The pharmaceutical composition according to claim 26 , wherein said antiviral agent is ribavirin.
28 . The pharmaceutical composition according to claim 26 , wherein said antiviral agent is selected from another anti-HCV agent, HIV inhibitor, HAV inhibitor and HBV inhibitor.
29 . The pharmaceutical composition according to claim 28 , wherein said anti-HCV agent is selected from the group consisting of immunomodulatory agents, other inhibitors of HCV NS3 protease, inhibitors of HCV polymerase and inhibitors of another target in the HCV life cycle.
30 . The pharmaceutical composition according to claim 29 , wherein said immunomodulatory agent is selected from α-interferon and pegylated α-interferon.
31 . The pharmaceutical composition according to claim 29 , wherein said inhibitor of another target in the HCV life cycle is selected from inhibitors of: helicase, NS2/3 protease and internal ribosome entry site (IRES).
32 . A method for treating or preventing a hepatitis C viral infection in a mammal comprising administering to the mammal an anti-hepatitis C virally effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof.
33 . A method for treating or preventing a hepatitis C viral infection in a mammal comprising administering to the mammal an anti-hepatitis C virally effective amount of a combination of a compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, and at least one other antiviral agent.
34 . The method according to claim 33 , wherein said antiviral agent is ribavirin.
35 . The method according to claim 33 , wherein said antiviral agent is selected from another anti-HCV agent, HIV inhibitor, HAV inhibitor and HBV inhibitor.
36 . The method according to claim 35 , wherein said anti-HCV agent is selected from immunomodulatory agents, other inhibitors of HCV NS3 protease, inhibitors of HCV polymerase and inhibitors of another target in the HCV life cycle.
37 . The method according to claim 36 , wherein said immunomodulatory agent is selected from α-interferon and pegylated α-interferon.
38 . The method according to claim 36 , wherein said inhibitor of another target in the HCV life cycle is selected from inhibitors of: helicase, NS2/3 protease and internal ribosome entry site (IRES).
39 . A method of inhibiting the replication of hepatitis C virus comprising exposing the virus to a hepatitis C viral NS3 protease inhibiting amount of a compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof.
40 . An article of manufacture comprising
a composition effective to treat an HCV infection or to inhibit the NS3 protease of HCV and packaging material comprising a label which indicates that the composition can be used to treat infection by the hepatitis C virus, wherein said composition comprises a compound according to claim 1 or a pharmaceutically acceptable salt or ester thereof.Join the waitlist — get patent alerts
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