Synthesis and antiviral activity of HCV NS3/4A peptidomimetic boronic acid inhibitors

被引：16

作者：

Boloor, Amogh ^{[1
]}

Hanway, Denise ^{[1
]}

Joshi, Maria ^{[1
]}

Winn, David T. ^{[1
]}

Mendez, Gabriel ^{[1
]}

Walls, Marlena ^{[1
]}

Wei, Ping ^{[1
]}

Qian, Fuxin ^{[2
]}

Zhang, Xiaoli ^{[2
]}

Zhang, Yuliang ^{[2
]}

Hepperle, Michael E. ^{[1
]}

Li, Xinqiang ^{[1
]}

Campbell, David A. ^{[1
]}

Betancort, Juan M. ^{[1
]}

机构：

[1] Phenomix Corp, San Diego, CA 92121 USA

[2] Beijing Honghui Meditech Co, Beijing 102600, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 19期

关键词：

Hepatitis C; HCV; NS3/4A; Boronic acids; HEPATITIS-C; PROTEASE INHIBITORS; SERINE-PROTEASE; MACROCYCLIC INHIBITORS; VIRUS; DISCOVERY; REPLICATION; THERAPIES; POTENT;

D O I：

10.1016/j.bmcl.2009.08.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of NS3/4A protease boronic acid inhibitors is described. The compounds show good biochemical potency and cellular activity. The peptidomimetic inhibitors were evaluated against proteases from different HCV genotypes and clinically relevant NS3/4A mutants. Compound 28 displayed subnanomolar to single digit nanomolar potencies in the enzymatic assays and an EC50 of 25 nM in the replicon cell-based assay. (C) 2009 Elsevier Ltd. All rights reserved.

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收藏

页码：5708 / 5711

页数：4

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