Thiotetrazole alkynylacetanilides as potent and bioavailable non-nucleoside inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases

被引：56

作者：

Gagnon, Alexandre ^{[1
]}

Amad, Ma'an H. ^{[1
]}

Bonneau, Pierre R. ^{[1
]}

Coulombe, Rene ^{[1
]}

Deroy, Patrick L. ^{[1
]}

Doyon, Louise ^{[1
]}

Duan, Jianmin ^{[1
]}

Garneau, Michel ^{[1
]}

Guse, Ingrid ^{[1
]}

Jakalian, Araz ^{[1
]}

Jolicoeur, Eric ^{[1
]}

Landry, Serge ^{[1
]}

Malenfant, Eric ^{[1
]}

Simoneau, Bruno ^{[1
]}

Yoakirn, Christiane ^{[1
]}

机构：

[1] Boehringer Ingelheim Canada Ltd, Res & Dev, Laval, PQ H7S 2G5, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 16期

关键词：

thiotetrazoles; alkynes; non-nucleoside reverse transcriplase; inhibitor (NNRTI); SAR; pharmacokinetics; molecular modeling; double mutant reverse transcriptase;

D O I：

10.1016/j.bmcl.2007.06.012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of aryl thiotetrazolylacetanilides were synthesized and found to be potent inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. The incorporation of an alkynyl fragment on the aniline provided inhibitors with excellent cellular activity and extensive SAR led to the identification of one inhibitor having good oral bioavailability in rats. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：4437 / 4441

页数：5

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