Synthesis and elastase-inhibiting activity of 2-pyridinyl-isothiazol-3(2 H)-one 1,1-dioxides

The synthesis of a series of new isothiazol-3(2 H)-one 1,1-dioxides with halogenated (mostly fluorinated) pyridinyl and pentafluorophenyl substituents at 2-position is reported. These compounds ( 18– 24) became easily accessible from 2-thiocyanato-1-carboxaldehydes and aminopyridines, pentafluoroaniline, respectively, by an isothiazolium cyclization–oxidation route. Compound 21 exhibited an IC 50 value of 3.1 μM toward human leukocyte elastase. The proteases cathepsin G, trypsin, cathepsin L, and angiotensin-converting enzyme, and the serine esterases acetylcholinesterase and cholesterol esterase were not inhibited by 21.