A series of 5-(5,6)-dihydrouracil substituted 8-hydroxy-[1,6]naphthyridine-7-carboxylic acid 4-fluorobenzylamide inhibitors of HIV-1 integrase and viral replication in cells

被引：56

作者：

Embrey, MW ^{[1
]}

Wai, JS

Funk, TW

Homnick, CF

Perlow, DS

Young, SD

Vacca, JP

Hazuda, DJ

Felock, PJ

Stillmock, KA

Witmer, MV

Moyer, G

Schleif, WA

Gabryelski, LJ

Jin, LX

Chen, IW

Ellis, JD

Wong, BK

Lin, JH

Leonard, YM

Tsou, NN

Zhuang, LH

机构：

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

[2] Merck Res Labs, Dept Biol Chem, West Point, PA 19486 USA

[3] Merck Res Labs, Dept Vaccine & Biol Res, West Point, PA 19486 USA

[4] Merck Res Labs, Dept Drug Metab & Pharmacol, West Point, PA 19486 USA

[5] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 20期

关键词：

HIV-1 integrase inhibitors; naphthyridine;

D O I：

10.1016/j.bmcl.2005.06.105

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Introduction of a 5,6-dihydrouracil functionality in the 5-position of N-(4-fluorobenzyl)-8-hydroxy-[1,6]naphthyridine-7-carboxamide I led to a series of highly active HIV-1 integrase inhibitors. These compounds displayed low nanomolar activity in inhibiting both the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 11 is a 150-fold more potent antiviral agent than 1, with a CIC95 of 40 nM in the presence of human serum. It displays good pharmacokinetics when dosed in rats and dogs. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：4550 / 4554

页数：5

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