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
收藏
页码：5392 / 5396
页数：5
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