Binding mode determination of benzimidazole inhibitors of the hepatitis C virus RNA polymerase by a structure and dynamics strategy

被引：43

作者：

LaPlante, SR

Jakalian, A

Aubry, N

Bousquet, Y

Ferland, JM

Gillard, J

Lefebvre, S

Poirier, M

Tsantrizos, YS

Kukolj, G

Beaulieu, PL

机构：

[1] Boehringer Ingelheim Canada Ltd, Dept Chem, Res & Dev, Laval, PQ H7S 2G5, Canada

[2] Boehringer Ingelheim Canada Ltd, Dept Biol Sci, Res & Dev, Laval, PQ H7S 2G5, Canada

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2004年 / 43卷 / 33期

关键词：

drug design; hepatitis C virus; molecular modeling; NMR spectroscopy; structure-activity relationships;

D O I：

10.1002/anie.200460326

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A novel strategy involving NMR, medicinal chemistry, and molecular modeling is described for determining the binding mode of ligands and the binding roles of their substituents. The first solution structure of an inhibitor bound to hepatitis C virus (HCV) polymerase (see picture) provides practical information for the rational design of potential therapeutics against HCV infections.

引用

页码：4306 / 4311

页数：6

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