Synthesis and evaluation of aryl thioxothiazolidinone inhibitors of ADAMTS-5 (Aggrecanase-2)

…, S Lombardi, KE Georgiadis, E Reifenberg…

Index: Bursavich, Matthew G.; Gilbert, Adam M.; Lombardi, Sabrina; Georgiadis, Katy E.; Reifenberg, Erica; Flannery, Carl R.; Morris, Elisabeth A. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 5 p. 1185 - 1188

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Citation Number: 53

Abstract

5-Benzylidene-2-thioxo-thiazolidin-4-one inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared via commercially available starting materials. The identified compounds show micromolar ADAMTS-5 potency and demonstrate SAR trends for both the aryl group and thioxothiazolidinone zinc chelator. This series of compounds represents steps toward a metalloprotease inhibitor as a disease-modifying osteoarthritis drug.