Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: The discovery of GW0385

被引：71

作者：

Miller, JF

Andrews, CW

Brieger, M

Furfine, ES

Hale, MR

Hanlon, MH

Hazen, RJ

Kaldor, I

McLean, EW

Reynolds, D

Sarnmond, DM

Spaltenstein, A

Tung, R

Turner, EM

Xu, RX

Sherrill, RG

机构：

[1] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA

[2] Vertex Pharmaceut, Cambridge, MA 02139 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 07期

关键词：

antiviral; antiretroviral; arylsulfonamide; brecanavir; drug resistance; GW0385; HIV protease;

D O I：

10.1016/j.bmcl.2006.01.035

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385. (C) 2006 Elsevier Ltd. All rights reserved.

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收藏

页码：1788 / 1794

页数：7

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