HIV-1 protease inhibitors with picomolar potency against PI-resistant HIV-1 by modification of the P1′ substituent

被引：9

作者：

Duffy, JL ^{[1
]}

Kirk, BA

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 / 19期

关键词：

D O I：

10.1016/S0960-894X(03)00680-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Transposition of the pyridyl nitrogen from the P-3 substituent to the P-1' substituent in HIV-1 protease inhibitors (PI) affords compounds such as 3 with an improved inhibitory profile against multiple P450 isoforms. These compounds also displayed increased potency, with 3 inhibiting viral spread (CIC95) at <8 nM for every strain of PI-resistant HIV-1 tested. The poor to modest bioavailability of these compounds may correlate in part to their aqueous solubility. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：3323 / 3326

页数：4

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