5'-Phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2)

被引：45

作者：

Bursavich, Matthew G.

Gilbert, Adam M.

Lombardi, Sabrina

Georgiadis, Katy E.

Reifenberg, Erica

Flannery, Carl R.

Morris, Elisabeth A.

机构：

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 20期

关键词：

ADAMTS-5; aggrecanase-2; metalloprotease inhibitors; Osteoarthritis; thiadiazoles;

D O I：

10.1016/j.bmcl.2007.07.048

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

5'-Phenyl-3' H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared via commercially available starting materials. Selected compounds 23, 33-35 show sub-micromolar ADAMTS-5 potency and strong SAR trends with selectivity over the related metalloproteases ADAMTS-4 (Aggrecanase-1), MMP12, and MMP13. This series of compounds represents progress toward a selective ADAMTS-5 inhibitor as a disease modifying osteoarthritis drug. (c) 2007 Elsevier Ltd. All rights reserved.

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页码：5630 / 5633

页数：4

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