Anti-HIV activity of aromatic and heterocyclic thiazolyl thiourea compounds

被引：96

作者：

Venkatachalam, TK

Sudbeck, EA

Mao, C

Uckun, FM ^{[1
]}

机构：

[1] Parker Hughes Inst, Drug Discovery Program, St Paul, MN 55113 USA

[2] Parker Hughes Inst, Dept Chem, St Paul, MN 55113 USA

[3] Parker Hughes Inst, Dept Biol Struct, St Paul, MN 55113 USA

[4] Parker Hughes Inst, Dept Virol, St Paul, MN 55113 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 04期

关键词：

D O I：

10.1016/S0960-894X(01)00011-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several thiazolyl thiourea derivatives were designed and synthesized as non-nucleoside inhibitors (NNRTI) of HIV-1 reverse transcriptase. Six lead compounds were identified that showed subnanomolar IC50 values for the inhibition of HIV replication, were minimally toxic to human peripheral blood mononuclear cells (PBMC) with CC50 values ranging from 28 to >100 muM, and showed remarkably high selectivity indices ranging from 28,000 to >100,000. The most promising compound was N-[1-(1-furoylmethyl)]-N'-[2-(thiazolyl)]thiourea (compound 6), which showed potency against two NNRTI-resistant HIV-1 isolates (A17 and A17 variant) at nanomolar to low micromolar concentrations, exhibited much greater potency against both wild-type as well as NNRTI-resistant HIV-1 than nevirapine, delavirdine, HI-443, and HI-244, was minimally toxic to PBMC, and had a selectivity index of >100,000. The potency and minimal cytotoxicity of these aromatic/heterocyclic thiourea compounds suggest that they may be potentially useful as anti-AIDS drugs. (C) 2001 Published by Elsevier Science Ltd.

引用

页码：523 / 528

页数：6

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