Solid-phase synthesis of benzisothiazolones as serine protease inhibitors

An efficient solid-phase synthesis of benzisothiazolone-1,1-dioxide-based serine protease inhibitors involving alkylation of carboxylic acids with N-(bromomethyl)benzisothiazolone-1,1-dioxide has been developed. An example using this procedure for preparation of a library of human mast cell tryptase inhibitors is described. An efficient solid-phase synthesis of benzisothiazolone protease inhibitors involving the alkylation of carboxylic acids with N-(bromomethyl)-benzisothiazolone-1,1-dioxide is described.