Novel, potent, and orally bioavailable phosphinic acid inhibitors of the hepatitis C virus NS3 protease

被引：23

作者：

Clarke, Michael O. ^{[1
]}

Chen, Xiaowu ^{[1
]}

Cho, Aesop ^{[1
]}

Delaney, William E. ^{[1
]}

Doerffler, Edward ^{[1
]}

Fardis, Maria ^{[1
]}

Ji, Mingzhe ^{[1
]}

Mertzman, Michael ^{[1
]}

Pakdaman, Rowchanak ^{[1
]}

Pyun, Hyun-Jun ^{[1
]}

Rowe, Tanisha ^{[1
]}

Yang, Cheng Y. ^{[1
]}

Sheng, X. Christopher ^{[1
]}

Kim, Choung U. ^{[1
]}

机构：

[1] Gilead Sci Inc, Foster City, CA 94404 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 12期

关键词：

HCV; NS3; protease; Phosphinic acid; Carboxylate isostere; METATHESIS; INFECTION; RNA;

D O I：

10.1016/j.bmcl.2011.04.125

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationally constraining these compounds through macrocyclization. The syntheses and preliminary biological evaluation of these phosphinic acids is described. (C) 2011 Elsevier Ltd. All rights reserved.

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收藏

页码：3568 / 3572

页数：5

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