Document Report Card

ID: ALA1127463

Journal: J Med Chem

Title: Heteroaryl-fused 2-phenylisothiazolone inhibitors of cartilage breakdown.

Authors: Wright SW, Petraitis JJ, Abelman MM, Batt DG, Bostrom LL, Corbett RL, Decicco CP, Di Meo SV, Freimark B, Giannaras JV.

Abstract: The synthesis, biological evaluation, and structure-activity relationships of a series of N-phenyl heteroaryl-fused isothiazolones are described. These isothiazolones have been shown to exhibit potent, dose-dependent inhibition of IL-1 beta-induced breakdown of proteoglycan in a cartilage organ culture assay. This effect is likely due to inhibition of MMP activation and a consequent reduction in MMP activity following IL-1 beta stimulation. Thus these compounds potentially represent simple, non-peptidic disease-modifying agents for the treatment of arthritic diseases. To examine the effects of structure on in vitro activity, three general features of the molecules were varied, substituents on the pendant N-phenyl group, the position of ring fusion to the isothiazolone, and substituents on the fused ring peri to the isothiazolone sulfur.

CiteXplore: 7932530

DOI: 10.1021/jm00045a012