Design and synthesis of dipeptidyl nitriles as potent, selective, and reversible inhibitors of cathepsin C

被引：39

作者：

Guay, Daniel ^{[2
]}

Beaulieu, Christian ^{[2
]}

Reddy, T. Jagadeeswar ^{[2
]}

Zamboni, Robert ^{[2
]}

Methot, Nathalie ^{[1
]}

Rubin, Joel ^{[1
]}

Ethier, Diane ^{[1
]}

Percival, M. David ^{[1
]}

机构：

[1] Merck Frosst Canada & Co, Dept Biochem, Kirkland, PQ H9H 3L1, Canada

[2] Merck Frosst Canada & Co, Dept Med Chem, Kirkland, PQ H9H 3L1, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 18期

关键词：

Dipeptide nitrile; Cathepsin C; Dipeptidyl peptidase I; PEPTIDASE-I; SERINE PROTEASES; ACTIVATION; IDENTIFICATION; PROTEINASES; REQUIRES; VIVO;

D O I：

10.1016/j.bmcl.2009.07.114

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of dipeptide nitriles with a thienyl alanine in P2 were identified as potent and selective cathepsin C inhibitors. Incorporation of a substituted cyclopropyl moiety in PI effectively protects these derivatives against hydrolase activity in whole blood. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5392 / 5396

页数：5

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