HIV protease inhibitors with picomolar potency against PI-resistant HIV-1 by extension of the P3 substituent

被引：11

作者：

Duffy, JL ^{[1
]}

Rano, TA

Kevin, NJ

Chapman, KT

Schleif, WA

Olsen, DB

Stahlhut, M

Rutkowski, CA

Kuo, LC

Jin, LX

Lin, JH

Emini, EA

Tata, JR

机构：

[1] Merck Res Labs, Dept Basic Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Virus & Cell Biol, W Point, PA 19486 USA

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

[4] Merck Res Labs, Dept Biol Struct, W Point, PA 19486 USA

[5] Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(03)00475-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A biaryl pyridylfuran P-3 substituent on the hydroxyethylene isostere scaffold affords HIV protease inhibitors (PI's) with picomolar (IC50) potency against the protease enzymes from PI-resistant HIV-1 strains. Inclusion of a gem-dimethyl substituent afforded compound 3 with 100% oral bioavailability (dogs) and more than double the t(1/2) of indinavir. Inhibition of multiple P450 isoforms is dependent on the regiochemistry of the pyridyl nitrogen in these compounds. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：2569 / 2572

页数：4

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