A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCVNS3 protease

被引：172

作者：

Narjes, F

Koehler, KF

Koch, U

Gerlach, B

Colarusso, S

Steinkuhler, C

Brunetti, M

Altamura, S

De Francesco, R

Matassa, VG

机构：

[1] IRBM, MRL Rome, Dept Chem, I-00040 Rome, Italy

[2] IRBM, MRL Rome, Dept Biochem, I-00040 Rome, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 04期

关键词：

D O I：

10.1016/S0960-894X(01)00842-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The difluoromethyl group was designed by computational chemistry methods as a mimetic of the canonical P-1 cysteine thiol for inhibitors of the hepatitis C virus NS3 protease. This modification led to the development of competitive, non-covalent inhibitor 4 (K-i 30 nM) and reversible covalent inhibitors (6, K-i 0.5 nM; and 8 K-i* 10 pM). (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：701 / 704

页数：4

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