Acyclic cyanamide-based inhibitors of cathepsin K

被引：26

作者：

Barrett, DG ^{[1
]}

Deaton, DN

Hassell, AM

McFadyen, RB

Miller, AB

Miller, LR

Payne, JA

Shewchuk, LM

Willard, DH

Wright, LL

机构：

[1] GlaxoSmithKline, Dept Med Chem, Res Triangle Pk, NC 27709 USA

[2] GlaxoSmithKline, Discovery Res Computat Analyt & Struct Sci, Res Triangle Pk, NC 27709 USA

[3] GlaxoSmithKline, Dept Mol Pharmacol, Res Triangle Pk, NC 27709 USA

[4] GlaxoSmithKline, Dept Gene Express & Prot Purificat, Res Triangle Pk, NC 27709 USA

[5] GlaxoSmithKline, Discovery Res Biol, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 12期

关键词：

cyanamide; cathepsin K; cysteine protease inhibitor;

D O I：

10.1016/j.bmcl.2005.04.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Conversion of the proline-derived cyanamide lead to an acyclic cyanamide capable of forming an additional hydrogen bond with cathepsin K resulted in a large increase in inhibitory activity. An X-ray structure of a co-crystal of a cyanamide with cathepsin K confirmed the enzyme interaction. Furthermore, a representative acyclic cyanamide inhibitor 6r was able to attenuate bone resorption in the rat calvarial model. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：3039 / 3043

页数：5

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