Structure-based design of irreversible, tripeptidyl human rhinovirus 3C protease inhibitors containing N-methyl amino acids

被引：23

作者：

Dragovich, PS ^{[1
]}

Webber, SE ^{[1
]}

Prins, TJ ^{[1
]}

Zhou, R ^{[1
]}

Marakovits, JT ^{[1
]}

Tikhe, JG ^{[1
]}

Fuhrman, SA ^{[1
]}

Patick, AK ^{[1
]}

Matthews, DA ^{[1
]}

Ford, CE ^{[1
]}

Brown, EL ^{[1
]}

Binford, SL ^{[1
]}

Meador, JW ^{[1
]}

Ferre, RA ^{[1
]}

Worland, ST ^{[1
]}

机构：

[1] Agouron Pharmaceut Inc, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(99)00368-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tripeptide-derived molecules incorporating N-methyl amino acid residues and C-terminal Michael acceptor moieties were evaluated as irreversible inhibitors of the cysteine-containing human rhinovirus 3C protease (3CP). Such compounds displayed good 3CP inhibition activity (k(obs)/[I] up to 610,000 M(-1)s(-1)) and potent in vitro antiviral properties (EC50 approaching 0.03 mu M) when tested against HRV serotype-14. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：2189 / 2194

页数：6

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