Identification of a novel class of succinyl-nitrile-based Cathepsin S inhibitors

被引：14

作者：

Bekkali, Younes ^{[1
]}

Thomson, David S. ^{[1
]}

Betageri, Raj ^{[1
]}

Emmanuel, Michel J. ^{[1
]}

Hao, Ming-Hong ^{[1
]}

Hickey, Eugene ^{[1
]}

Liu, Weimin ^{[1
]}

Patel, Usha ^{[1
]}

Ward, Yancey D. ^{[1
]}

Young, Erick R. R. ^{[1
]}

Nelson, Richard ^{[1
]}

Kukulka, Alison ^{[1
]}

Brown, Maryanne L. ^{[1
]}

Crane, Kathy ^{[1
]}

White, Della ^{[1
]}

Freeman, Dorothy M. ^{[1
]}

Labadia, Mark E. ^{[1
]}

Wildeson, Jessi ^{[1
]}

Spero, Denice M. ^{[1
]}

机构：

[1] Boehringer Ingelheim Pharmaceut Inc, Dept Med Chem, Ridgefield, CT 06877 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 09期

关键词：

cathepsin S; cat S; nitrile; succinyl;

D O I：

10.1016/j.bmcl.2007.02.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and in vitro activities of a series of suceinyl-nitrile-based inhibitors of Cathepsin S are described. Several members of this class show nanomolar inhibition of the target enzyme as well as cellular potency. The inhibitors displaying the greatest potency contain N-alkyl substituted piperidine and pyrrolidine rings spiro-fused to the alpha-carbon of the P1 residue. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：2465 / 2469

页数：5

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