Parallel synthesis of pteridine derivatives as potent inhibitors for hepatitis C virus NS5B RNA-dependent RNA polymerase

被引：38

作者：

Ding, Y ^{[1
]}

Girardet, JL ^{[1
]}

Smith, KL ^{[1
]}

Larson, G ^{[1
]}

Prigaro, B ^{[1
]}

Lai, VCH ^{[1
]}

Zhong, WD ^{[1
]}

Wu, JZ ^{[1
]}

机构：

[1] Valeant Pharmaceut Int, Costa Mesa, CA 92626 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 03期

关键词：

HCV; inhibitor; NS5B; pteridine;

D O I：

10.1016/j.bmcl.2004.11.028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

From compound library screening using an HCV NS5B RNA-dependent RNA polymerase enzymatic assay, we identified a pteridine hit compound with an IC50 of 15 muM. Our SAR studies were focused on the different groups at the 6- and 7-positions. substitutions at the 4-position, and replacement of N-1 or N-3 with carbon in the pteridine ring. We found that NH or OH at 4-position is critical for the inhibitory activity. Furthermore, a hydrophobic substituent at the 4-position may help compounds permeate through the cell membrane. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：675 / 678

页数：4

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