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

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

  • Bioorg Med Chem Lett. 2007 Oct 15;17(20):5630-3. doi: 10.1016/j.bmcl.2007.07.048.
Matthew G Bursavich 1,  Adam M Gilbert,  Sabrina Lombardi,  Katy E Georgiadis,  Erica Reifenberg,  Carl R Flannery,  Elisabeth A Morris
Affiliations

Affiliation

  • 1 Exploratory Medicinal Chemistry, Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA. [email protected]
PMID: 17804234 DOI: 10.1016/j.bmcl.2007.07.048
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.

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