Synthesis and activity of novel HIV protease inhibitors with improved potency against multiple PI-resistant viral strains

被引：12

作者：

Duffy, JL ^{[1
]}

Kevin, NJ

Kirk, BA

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 | 2002年 / 12卷 / 17期

关键词：

D O I：

10.1016/S0960-894X(02)00425-0

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Substitution of the t-butylcarboxamide substituent in analogues of the HIV protease inhibitor (PI) Indinavir with a trifluoroethylamide moiety confers greater potency against both the wild-type (NL4-3) virus and PI-resistant HIV. The trifluoroethyl substituent also affords a slower clearance rate in vivo (dogs); however, this may be due to more potent inhibition of at least two P450 isoforms. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：2423 / 2426

页数：4

共 16 条

[11] DIASTEREOSELECTIVE SYN-EPOXIDATION OF 2-ALKYL-4-ENAMIDES TO EPOXYAMIDES - SYNTHESIS OF THE MERCK HIV-1 PROTEASE INHIBITOR EPOXIDE INTERMEDIATE [J].