2. Academic Validation
  3. 5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5

5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5

  • Bioorg Med Chem Lett. 2007 Mar 1;17(5):1189-92. doi: 10.1016/j.bmcl.2006.12.020.
Adam M Gilbert 1,  Matthew G Bursavich,  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. gilbera@wyeth.com
PMID: 17210252 DOI: 10.1016/j.bmcl.2006.12.020
Abstract

A series of 5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5 (aggrecanase-2) is described. These compounds show microM functional inhibition of ADAMTS-5, and represent a new class of agents with the potential of inhibiting degradation of aggrecan, a major component of cartilage which is lost in osteoporosis. Compound 12 is noteworthy in that it has an ADAMTS-5 IC50: 1.1 microM and shows >40-fold functional selectivity over ADAMTS-4 (aggrecanase-1).

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