Inhibition of clinically relevant mutant variants of HIV-1 by quinazolinone non-nucleoside reverse transcriptase inhibitors

被引：298

作者：

Corbett, JW ^{[1
]}

Ko, SS ^{[1
]}

Rodgers, JD ^{[1
]}

Gearhart, LA ^{[1
]}

Magnus, NA ^{[1
]}

Bacheler, LT ^{[1
]}

Diamond, S ^{[1
]}

Jeffrey, S ^{[1
]}

Klabe, RM ^{[1
]}

Cordova, BC ^{[1
]}

Garber, S ^{[1
]}

Logue, K ^{[1
]}

Trainor, GL ^{[1
]}

Anderson, PS ^{[1
]}

Erickson-Viitanen, SK ^{[1
]}

机构：

[1] Dupont Pharmaceut Co, Expt Stn, Wilmington, DE 19880 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2000年 / 43卷 / 10期

关键词：

D O I：

10.1021/jm990580e

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4-alkenyl and 4-alkynyl-3,4-dihydro-4-(trifluoromethyl)-2-(1H)-quinazolinones were found to be potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) of human immunodeficiency virus type-1 (HIV-1). The 4-alkenyl-3,4-dihydro-4-(trifluoromethyl) quinazolinones DPC 082 and DPC 083 and the 4-alkynyl-3,4-dihydro-4-(trifluoromethyl) (LK)-quinazolinones DPC 961 and DPC 963 were found to exhibit low nanomolar potency toward wild-type RF virus (IC90 = 2.0, 2.1, 2.0, and 1.3 nM, respectively) and various single and many multiple amino acid substituted HIV-1 mutant viruses.-The increased potency is combined with favorable plasma serum protein binding as demonstrated by improvements in the percent free drug in human plasma when compared to efavirenz: 3.0%, 2.0%, 1.5% 2.8%, and 0.2- 0.5% for DPC 082, DPC 083, DPC 961, DPC 963, and efavirenz, respectively.

引用

页码：2019 / 2030

页数：12

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