CARBONIC-ANHYDRASE INHIBITORS - INHIBITION OF ISOZYME-I, ISOZYME-II AND ISOZYME-IV WITH N-HYDROXYSULFONAMIDES - A NOVEL CLASS OF INTRAOCULAR-PRESSURE LOWERING AGENTS

A series of N-hydroxy sulfonamides has been prepared by reaction of al kyl-, arylalkyl- and arylsulfonyl halides or sulfonic acid anhydrides with hydroxylamine. Structurally related inhibitors were also obtained from acyl chlorides and hydroxylamine, as well as by reaction of tosy l isocyanate with hydroxylamine, sulfamic acid and sulfamide. Inhibiti on of three carbonic anhydrase (CA) isozymes, hCA I, hCA II and bCA IV (h = human; b = bovine) with the prepared compounds has been investig ated. Good inhibitors, as well as compounds with moderate activity aga inst these isozymes were detected, depending on the R group to which t he SO2NHOH or CONHOH moieties were attached. Susceptibility to inhibit ion sv as generally: hCA II > bCA IV much greater than hCA I. Some of the new inhibitors showed very good antiglaucoma action when administe red directly into the eye in experimental animals, acting as more effi cient intraocular pressure lowering agents as compared to the clinical drug dorzolamide. This constitutes an encouraging result for obtainin g novel antiglaucoma drugs from this class of CA inhibitors.