Structure-based design of novel dihydroalkoxybenzyloxopyrimidine derivatives as potent nonnucleoside inhibitors of the human immunodeficiency virus reverse transcriptase

被引：54

作者：

Sudbeck, EA

Mao, C

Vig, R

Venkatachalam, TK

Tuel-Ahlgren, L

Uckun, FM ^{[1
]}

机构：

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

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

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

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

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 1998年 / 42卷 / 12期

关键词：

D O I：

10.1128/AAC.42.12.3225

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Two highly potent dihydroalkoxybenzyloxopyrimidine (DABO) derivatives targeting the nonnucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been designed based on the structure of the NNI binding pocket and tested for anti-HIV activity. Our lead DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-one, elicited potent inhibitory activity against purified recombinant HIV RT and abrogated HIV replication in peripheral blood mononuclear cells at nanomolar concentrations (50% inhibitory concentration, <1 nM) but showed no detectable cytotoxicity at concentrations as high as 100 mu M.

引用

页码：3225 / 3233

页数：9

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