The design of potent, non-peptidic inhibitors of hepatitis C protease

被引：13

作者：

Andrews, DM ^{[1
]}

Chaignot, HM ^{[1
]}

Coomber, BA ^{[1
]}

Dowle, MD ^{[1
]}

Hind, SL ^{[1
]}

Johnson, MR ^{[1
]}

Jones, PS ^{[1
]}

Mills, G ^{[1
]}

Patikis, A ^{[1
]}

Pateman, TJ ^{[1
]}

Robinson, JE ^{[1
]}

Slater, MJ ^{[1
]}

Trivedi, N ^{[1
]}

机构：

[1] GlaxoSmithKline Med Res Ctr, Dept Med Chem, Stevenage SG1 2NY, Herts, England

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 38卷 / 04期

关键词：

hepatitis C; NS3; 4A protease; 5,5-trans-lactam; replicon; mechanism-based; serine protease;

D O I：

10.1016/S0223-5234(03)00050-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The pyrrolidine-5,5-trans-lactam template was used to design small, neutral, mechanism-based inhibitors of hepatitis C NS3/4A protease displaying potent activity in the replicon cell-based assay. The activity of this series is not dependent upon its chemical reactivity and molecules have been synthesised which combine enhanced biochemical potency with improved plasma stability. promising initial pharmacokinetic data indicating the potential for further optimisation of this series into low molecular weight, drug-like inhibitors is presented. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

引用

页码：339 / 343

页数：5

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