Heteroaryl-fused 2-phenylisothiazolone inhibitors of cartilage breakdown

SW Wright, JJ Petraitis, MM Abelman…

Index: Wright, Stephen W.; Petraitis, Joseph J.; Abelman, Matthew M.; Batt, Douglas G.; Bostrom, Lori L.; et al. Journal of Medicinal Chemistry, 1994 , vol. 37, # 19 p. 3071 - 3078

Full Text: HTML

Citation Number: 21

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-1/3-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-la stimulation. Thus ...