Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates

A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing propargylic ether P1′ groups, was explored. In particular, compound 5h has excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-α production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA.

Compound 5h with excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-α production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA.Figure optionsDownload as PowerPoint slide