Glycine α-ketoamides as HCVNS3 protease inhibitors

被引：40

作者：

Han, W ^{[1
]}

Hu, ZL ^{[1
]}

Jiang, XJ ^{[1
]}

Wasserman, ZR ^{[1
]}

Decicco, CP ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Discovery Chem, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 06期

关键词：

D O I：

10.1016/S0960-894X(03)00031-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using a tetrapeptide-based alpha-ketoamide template, various amines and amino acids were incorporated to explore the prime side of the HCV NS3 protease catalytic site. Glycine carboxylic acid was found to be the most effective prime group. Further optimization yielded an inhibitor with IC50 of 0.060 muM. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：1111 / 1114

页数：4

共 22 条

[1] The NS3/4A proteinase of the hepatitis C virus: unravelling structure and function of an unusual enzyme and a prime target for antiviral therapy
Bartenschlager, R
[J]. JOURNAL OF VIRAL HEPATITIS, 1999, 6 (03) : 165 - 181
[2] Molecular targets in inhibition of hepatitis C virus replication
Bartenschlager, R
[J]. ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1997, 8 (04) : 281 - 301
[3] The identification of α-ketoamides as potent inhibitors of hepatitis C virus NS3-4A proteinase
Bennett, JM
Campbell, AD
Campbell, AJ
Carr, MG
Dunsdon, RM
Greening, JR
Hurst, DN
Jennings, NS
Jones, PS
Jordan, S
Kay, PB
O'Brien, MA
King-Underwood, J
Raynham, TM
Wilkinson, CS
Wilkinson, TCI
Wilson, FX
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (03) : 355 - 357
[4] Evolution, synthesis and SAR of tripeptide α-ketoacid inhibitors of the hepatitis C virus NS3/NS4A serine protease
Colarusso, S
Gerlach, B
Koch, U
Muraglia, E
Conte, I
Stansfield, I
Matassa, VG
Narjes, F
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (04) : 705 - 708
[5] Inhibition of the hepatitis C virus NS3/4A protease - The crystal structures of two protease-inhibitor complexes
Di Marco, S
Rizzi, M
Volpari, C
Walsh, MA
Narjes, F
Colarusso, S
De Francesco, R
Matassa, VG
Sollazzo, M
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (10) : 7152 - 7157
[6] α-ketoamides, α-ketoesters and α-diketones as HCVNS3 protease inhibitors
Han, W
Hu, ZL
Jiang, XJ
Decicco, CP
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (08) : 711 - 713
[7] HAN W, 2001, NAT M AM CHEM SOC SA, DOI UNSP MEDI-121
[8] HAN W, 2001, NAT M AM CHEM SOC SA, DOI UNSP MEDI-119
[9] Houghton M., 1996, FIELDS VIROLOGY, P1035
[10] Prime site binding inhibitors of a serine protease:: NS3/4A of hepatitis C virus
Ingallinella, P
Fattori, D
Altamura, S
Steinkühler, C
Koch, U
Cicero, D
Bazzo, R
Cortese, R
Bianchi, E
Pessi, A
[J]. BIOCHEMISTRY, 2002, 41 (17) : 5483 - 5492

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