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.
引用
收藏
页码：5630 / 5633
页数：4
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