Keto-1,3,4-oxadiazoles as cathepsin K inhibitors

被引：60

作者：

Palmer, JT

Hirschbein, BL

Cheung, H

McCarter, J

Janc, JW

Yu, ZW

Wesolowski, G

机构：

[1] Celera Genom Inc, San Francisco, CA 94080 USA

[2] Merck Res Labs, Dept Bone Biol & Osteoporosis, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 11期

基金：

美国国家卫生研究院;

关键词：

osteoporosis; cathepsin; cysteine protease; inhibitor; ketoheterocycle; reversible; selective; potent;

D O I：

10.1016/j.bmcl.2006.03.001

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have prepared a series of cathepsin K inhibitors bearing the keto-1,3,4-oxadiazole warhead capable of forming a hemithioketal complex with the target enzyme. By modifying binding moieties at the P-1, P-2, and prime side positions of the inhibitors, we have achieved selectivity over cathepsins B, L, and S, and have achieved sub-nanomolar potency against cathepsin K. This series thus represents a promising chemotype that could be used in diseases implicated by imbalances in cathepsin K activity such as osteoporosis. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：2909 / 2914

页数：6

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