Synthesis and SAR of novel isoquinoline CXCR4 antagonists with potent anti-HIV activity

被引：38

作者：

Miller, John F. ^{[1
]}

Gudmundsson, Kristjan S. ^{[1
]}

Richardson, Leah D'Aurora ^{[1
]}

Jenkinson, Stephen ^{[4
]}

Spaltenstein, Andrew ^{[1
]}

Thomson, Michael ^{[2
]}

Wheelan, Pat ^{[3
]}

机构：

[1] GlaxoSmithKline Res & Dev Ltd, Dept Med Chem, Infect Dis Ctr Excellence Drug Discovery, Res Triangle Pk, NC 27709 USA

[2] GlaxoSmithKline Res & Dev Ltd, Dept Virol, Infect Dis Ctr Excellence Drug Discovery, Res Triangle Pk, NC 27709 USA

[3] GlaxoSmithKline Res & Dev Ltd, Dept DMPK, Infect Dis Ctr Excellence Drug Discovery, Res Triangle Pk, NC 27709 USA

[4] GlaxoSmithKline Res & Dev Ltd, Dept Biochem & Analyt Pharmacol, Infect Dis Ctr Excellence Drug Discovery, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 10期

关键词：

CXCR4; Isoquinoline; Tetrahydroquinoline; AMD070; HIV; Antiviral; ENTRY INHIBITORS; THERAPY; CORECEPTOR; TYPE-1;

D O I：

10.1016/j.bmcl.2010.03.118

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using AMD070 as a starting point for structural modification, a novel series of isoquinoline CXCR4 antagonists was developed. A structure-activity scan of alternate lower heterocycles led to the 3-isoquinolinyl moiety as an attractive replacement for benzimidazole. Side chain optimization in the isoquinoline series led to a number of compounds with low nanomolar anti-HIV activities and promising rat PK properties. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：3026 / 3030

页数：5

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