Potent inhibitors of the hepatitis C virus NS3 protease:: Design and synthesis of macrocyclic substrate-based β-strand mimics

被引：55

作者：

Goudreau, N ^{[1
]}

Brochu, C ^{[1
]}

Cameron, DR ^{[1
]}

Duceppe, JS ^{[1
]}

Faucher, AM ^{[1
]}

Ferland, JM ^{[1
]}

Grand-Maître, C ^{[1
]}

Poirier, M ^{[1
]}

Simoneau, B ^{[1
]}

Tsantrizos, YS ^{[1
]}

机构：

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

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2004年 / 69卷 / 19期

关键词：

D O I：

10.1021/jo049288r

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. The design and synthesis of 15-membered ring beta-strand mimics which are capable of inhibiting the interactions between the HCV NS3 protease enzyme and its polyprotein substrate will be described. The binding interactions between a macrocyclic ligand and the enzyme were explored by NMR and molecular dynamics, and a model of the ligand/enzyme complex was developed.

引用

页码：6185 / 6201

页数：17

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