Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells

被引：272

作者：

Zhuang, LC

Wai, JS

Embrey, MW

Fisher, TE

Egbertson, MS

Payne, LS

Guare, JP

Vacca, JP

Hazuda, DJ

Felock, PJ

Wolfe, AL

Stillmock, KA

Witmer, MV

Moyer, G

Schleif, WA

Gabryelski, LJ

Leonard, YM

Lynch, JJ

Michelson, SR

Young, SD

机构：

[1] Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA

[2] Merck Res Labs, Dept Antiviral Res, W Point, PA 19486 USA

[3] Merck Res Labs, Dept Pharmacol, W Point, PA 19486 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 04期

关键词：

D O I：

10.1021/jm025553u

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Naphthyridine 7 inhibits the strand transfer of the integration process catalyzed by integrase with an IC50 of 10 nM and inhibits 95% of the spread of HIV-1 infection in cell culture at 0.39 muM. It does not exhibit cytotoxicity in cell culture at less than or equal to 12.5 muM and shows a good pharmacokinetic profile when dosed orally to rats. The antiviral activity of 7 and its effect on integration were confirmed using viruses with specific integrase mutations.

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页码：453 / 456

页数：4

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