5'-Phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (aggrecanase-2) |
| |
| Authors: | Bursavich Matthew G Gilbert Adam M Lombardi Sabrina Georgiadis Katy E Reifenberg Erica Flannery Carl R Morris Elisabeth A |
| |
| Institution: | Exploratory Medicinal Chemistry, Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA. Bursavm@wyeth.com |
| |
| Abstract: | 5'-Phenyl-3'H-spiroindoline-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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
