Stephen W. Wright

Benzyl and t-butyl sulfoxides as sulfenyl halide equivalents: a convenient preparation of benzisothiazolones

Abstract A new methodology is described for the synthesis of benzisothiazolones from benzylsulfinyl or t-buthylsulfinyl substituted carboxamides that provides a mild alternative to conventional cyclization methods that employ halogens.

A synthesis of 2-aryl-3-hydroxybenzothiophenes and analogs by the base promoted cyclization of N-phenyl-2-(benzylthio)benzamides

Abstract A new methodology is described for the synthesis of 3-hydroxybenzothiophenes, 3-hydroxypyridothiophenes, and the corresponding selenophene analogs by the base promoted cyclization of corresponding 2-(benzylthio)arenecarboxanilides. The starting materials are readily prepared using directed metalation of the corresponding arenecarboxanilides.

Metabolism resistant isothiazolone inhibitors of cartilage breakdown

A series of 2-(arylmethyl)pyridoisothiazolones is reported that inhibit the IL-1 beta induced breakdown of bovine nasal septum cartilage in an organ culture assay. The synthesis and preliminary SAR of these compounds are described. These compounds represent a novel, non-peptide lead series approach to the mediation of the chronic cartilage breakdown associated with arthritic disease. These compounds are relatively resistant to reductive metabolism by liver microsomal preparations and appear to inhibit cartilage breakdown by interfering with the proteolytic activation of matrix metalloproteinases.

2,5-Diarylisothiazolone: novel inhibitors of cytokine-induced cartilage destruction

A series of 2,5-diarylisothiazolones is reported that inhibit the IL-1 beta-induced breakdown of bovine nasal septum cartilage in an organ culture assay. The synthesis and preliminary SAR of these compounds are described. These compounds represent a novel, nonpeptide lead series approach to the mediation of the chronic cartilage breakdown associated with arthritic disease. These compounds are relatively resistant to reductive metabolism by liver microsomal preparations and appear to inhibit cartilage breakdown by interfering with the proteolytic activation of matrix metalloproteinases.

Inhibition of cartilage breakdown by isothiazolones

Abstract Isothiazolones and isoselenazolones have been found to inhibit IL-1β induced breakdown of bovine nasal cartilage in an organ culture assay. The synthesis and preliminary SAR of these compounds are described. These compounds represent a novel, non-peptide lead series approach to the mediation of the chronic cartilage breakdown associated with arthritic disease.

Episulfide inhibitors of lipoxygenase

Abstract A set of epoxide and episulfide substrate mimics were synthesized as inhibitors of soybean lipoxygenase. Enzyme inhibition was observed exclusively with the 12,13-episulfides (1a and 4a), with a high degree of regio- and chemoselectivity. Inhibition by 1a was shown to occur with reduction of the enzyme active site iron from the catalytically active Fe(III) to the inactive Fe(II).

Vinylogous hydroxamic acids: 5-lipoxygenase inhibitors

Abstract Vinylogous hydroxamic acids were prepared as inhibitors of 5-lipoxygenase. The synthesis and preliminary SAR of these relatively unexplored compounds are described. These compounds are potent 5-lipoxygenase inhibitors which do not inhibit other enzymes of the arachidonic acid cascade.