Combining symmetry elements results in potent naphthyridinone (NTD) HIV-1 integrase inhibitors

被引：6

作者：

Johns, Brian A. ^{[1
]}

Kawasuji, Takashi ^{[2
]}

Weatherhead, Jason G. ^{[1
]}

Boros, Eric E. ^{[1
]}

Thompson, James B. ^{[1
]}

Garvey, Edward P. ^{[1
]}

Foster, Scott A. ^{[1
]}

Jeffrey, Jerry L. ^{[1
]}

Miller, Wayne H. ^{[1
]}

Kurose, Noriyuki ^{[2
]}

Matsumura, Kenichi ^{[2
]}

Fujiwara, Tamio ^{[2
]}

机构：

[1] GlaxoSmithKline Res & Dev Ltd, Infect Dis Therapeut Area Unit, Res Triangle Pk, NC 27709 USA

[2] Shionogi & Co Ltd, Shionogi Res Labs, Fukushima Ku, Osaka 5530002, Japan

来源：

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

关键词：

HIV Integrase; Naphthyridinone; Antiviral; HAART;

D O I：

10.1016/j.bmcl.2011.08.082

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of naphthyridinone HIV-1 integrase strand-transfer inhibitors have been designed based on a psdeudo-C2 symmetry element present in the two-metal chelation pharmacophore. A combination of two distinct inhibitor binding modes resulted in potent inhibition of the integrase strand-transfer reaction in the low nM range. Effects of aryl and N1 substitutions are disclosed including the impact on protein binding adjusted antiviral activity. (C) 2011 Published by Elsevier Ltd.

引用

页码：6461 / 6464

页数：4

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