Metal mediated protease inhibition: Design and synthesis of inhibitors of the human cytomegalovirus (hCMV) protease

被引：10

作者：

Dhanak, D

Burton, G

Christmann, LT

Darcy, MG

Elrod, KC

Kaura, A

Keenan, RM

Link, JO

Peishoff, CE

Shah, DH

机构：

[1] SmithKline Beecham Pharmaceut, Collegeville, PA 19426 USA

[2] Axys Pharmaceut, S San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(00)00462-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A versatile synthetic route to a novel series of bis-imidazolemethanes designed to inhibit the hCMV protease has been developed and a series of potential metal binding inhibitors has been identified. In selectivity assays, the compounds were highly specific for CMV protease and showed no inhibition (IC50 >100 muM) Of Other prototypical serine proteases such as trypsin, elastase, and chymotrypsin. Although the presence of free zinc ions was found to be an absolute requirement for the in vitro biological activity of this class of inhibitor, the potency of the inhibitors could not be improved beyond the micromolar level. (C) 2000 Elsevier Science Ltd. All rights reserved.

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页码：2279 / 2282

页数：4

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