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

…, S Lombardi, KE Georgiadis, E Reifenberg…

Index: Gilbert, Adam M.; Bursavich, Matthew G.; Lombardi, Sabrina; Georgiadis, Katy E.; Reifenberg, Erica; Flannery, Carl R.; Morris, Elisabeth A. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 5 p. 1189 - 1192

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Citation Number: 55

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 μM 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 μM and shows> 40-fold functional ...