1027016-73-4Relevant articles and documents
Heteroaryl-Fused 2-Phenylisothiazolone Inhibitors of Cartilage Breakdown
Wright, Stephen W.,Petraitis, Joseph J.,Abelman, Matthew M.,Batt, Douglas G.,Bostrom, Lori L.,et al.
, p. 3071 - 3078 (2007/10/02)
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-1β-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-1β 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.
