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ID: ALA1137466

Journal: Bioorg Med Chem Lett

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

Authors: Bursavich MG, Gilbert AM, Lombardi S, Georgiadis KE, Reifenberg E, Flannery CR, Morris EA.

Abstract: 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.

CiteXplore: 17804234

DOI: 10.1016/j.bmcl.2007.07.048