5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5

被引：62

作者：

Gilbert, Adam M.

Bursavich, Matthew G.

Lombardi, Sabrina

Georgiadis, Katy E.

Reifenberg, Erica

Flannery, Carl R.

Morris, Elisabeth A.

机构：

[1] Wyeth Res, Exploratory Med Chem, Chem & Screening Sci, Pearl River, NY 10965 USA

[2] Wyeth Res, Womens Hlth & Musculoskeletal Biol, Cambridge, MA 02140 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 05期

关键词：

ADAMTS-5; aggrecanase-2; thioxothiazolidin-4-ones; osteoporosis;

D O I：

10.1016/j.bmcl.2006.12.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

A series of 5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5 (aggrecanase-2) is described. These compounds show mu M functional inhibition of ADAMTS-5, and represent a new class of agents with the potential of inhibiting degradation of aggrecan, a major component of cartilage which is lost in osteoporosis. Compound 12 is noteworthy in that it has an ADAMTS-5 IC50: 1.1 mu M and shows > 40-fold functional selectivity over ADAMTS-4 (aggrecanase-1). (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1189 / 1192

页数：4

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