Discovery of 2-(4-sulfonamidophenyl)-indole 3-carboxamides as potent and selective inhibitors with broad hepatitis C virus genotype activity targeting HCV NS4B

被引：9

作者：

Zhang, Nanjing ^{[1
]}

Turpoff, Anthony ^{[1
]}

Zhang, Xiaoyan ^{[1
]}

Huang, Song ^{[1
]}

Liu, Yalei ^{[1
]}

Almstead, Neil ^{[1
]}

Njoroge, F. George ^{[2
]}

Gu, Zhengxian ^{[1
]}

Graci, Jason ^{[1
]}

Jung, Stephen P. ^{[1
]}

Pichardo, John ^{[1
]}

Colacino, Joseph ^{[1
]}

Lahser, Fred ^{[2
]}

Ingravallo, Paul ^{[2
]}

Weetall, Marla ^{[1
]}

Nomeir, Amin ^{[2
]}

Karp, Gary M. ^{[1
]}

机构：

[1] PTC Therapeut Inc, South Plainfield, NJ 07080 USA

[2] Merck Res Labs, Kenilworth, NJ 07033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 02期

关键词：

HCV inhibitor; Replicon; 2-(4-Sulfonamidophenyl)-indole; 3-carboxamides; NS4B; HUMAN HEPATOMA-CELLS; PROTEASE INHIBITOR; SMALL-MOLECULE; IN-VITRO; IDENTIFICATION; REPLICATION; INFECTION; INDOLES; NS5A; SAR;

D O I：

10.1016/j.bmcl.2015.11.065

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of 2-(4-sulfonamidophenyl)-indole 3-carboxamides was identified and optimized for activity against the HCV genotype 1b replicon resulting in compounds with potent and selective activity. Further evaluation of this series demonstrated potent activity across HCV genotypes 1a, 2a and 3a. Compound 4z had reduced activity against HCV genotype 1b replicons containing single mutations in the NS4B coding sequence (F98C and V105M) indicating that NS4B is the target. This novel series of 2-(4-sulfonamidophenyl)-indole 3-carboxamides serves as a promising starting point for a pan-genotype HCV discovery program. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：594 / 601

页数：8

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