Design and synthesis of depeptidized macrocyclic inhibitors of hepatitis C NS3-4A protease using structure-based drug design

被引：30

作者：

Venkatraman, S ^{[1
]}

Njoroge, FG ^{[1
]}

Girijavallabhan, VM ^{[1
]}

Madison, VS ^{[1
]}

Yao, NH ^{[1
]}

Prongay, AJ ^{[1
]}

Butkiewicz, N ^{[1
]}

Pichardo, J ^{[1
]}

机构：

[1] Schering Plough Res Inst, Kenilworth, NJ 07033 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 16期

关键词：

D O I：

10.1021/jm0489556

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Hepatitus C virus (HCV) NS3, when bound to NS-4A cofactor, facilitates development of mature virons by catalyzing cleavage of a polyprotein to form functional and structural proteins of HCV. The enzyme has a shallow binding pocket at the catalytic site, making development of inhibitors difficult. We have designed, preorganized, and depeptidized macrocyclic inhibitors from P-4 to P-2' and optimized binding to 0.1 mu M. The structure of an inhibitor bound to the enzyme was also solved.

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收藏

页码：5088 / 5091

页数：4

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