Inhibitors of HIV-1 attachment. Part 4: A study of the effect of piperazine substitution patterns on antiviral potency in the context of indole-based derivatives

被引：51

作者：

Wang, Tao ^{[1
]}

Kadow, John F. ^{[1
]}

Zhang, Zhongxing ^{[1
]}

Yin, Zhiwei ^{[1
]}

Gao, Qi ^{[2
]}

Wu, Dedong ^{[2
]}

Parker, Dawn DiGiugno ^{[3
]}

Yang, Zheng ^{[4
]}

Zadjura, Lisa ^{[4
]}

Robinson, Brett A. ^{[5
]}

Gong, Yi-Fei ^{[5
]}

Blair, Wade S. ^{[5
]}

Shi, Pei-Yong ^{[5
]}

Yamanaka, Gregory ^{[5
]}

Lin, Pin-Fang ^{[5
]}

Meanwell, Nicholas A. ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Res & Dev, Dept Chem, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Co, Res & Dev, Dept Analyt Res & Dev, Wallingford, CT 06492 USA

[3] Bristol Myers Squibb Co, Res & Dev, Dept Pharmaceut, Wallingford, CT 06492 USA

[4] Bristol Myers Squibb Co, Res & Dev, Dept Metab & Pharmacokinet, Wallingford, CT 06492 USA

[5] Bristol Myers Squibb Co, Res & Dev, Dept Virol, Wallingford, CT 06492 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 17期

关键词：

HIV; HIV attachment; gp120; Piperazine; A(1,3) strain; VIRUS ENTRY INHIBITORS; CD4; RECEPTOR-BINDING; CONFORMATIONAL-CHANGES; VIRAL ENVELOPE; CRYSTAL; BMS-378806; DISCOVERY; DIAMINES; TARGETS; GP120;

D O I：

10.1016/j.bmcl.2009.07.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

4-Fluoro- and 4-methoxy-1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl) ethane-1,2-dione (2 and 3, respectively) have been characterized as potent inhibitors of HIV-1 attachment that interfere with the interaction of viral gp120 with the host cell receptor CD4. As part of an effort to understand fundamental aspects of this pharmacophore, discovered originally using a high throughput cell-based screen, modification and substitution of the piperazine ring was examined in the context of compounds 6a-ah. The piperazine ring was shown to be a critical element of the HIV-1 attachment inhibiting pharmacophore, acting as a scaffold to deploy the indole glyoxamide and benzamide in a topographical relationship that complements the binding site on gp120. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5140 / 5145

页数：6

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