Carbonic anhydrase inhibitors: Synthesis of sulfonamides incorporating dtpa tails and of their zinc complexes with powerful topical antiglaucoma properties

Reaction of diethylenetriamino pentaacetic acid (dtpa) dianhydride with aro matic/heterocyclic sulfonamides possessing a free amino/imino/hydrazino/hyd roxy group afforded bis-sulfonamides containing metal-complexing, polyamino -polycarboxylic acid moieties in their molecule. The corresponding mono-sul fonamide derivatives of dtpa were also obtained by an alternative method, f rom the free acid. Zn(II) complexes of these new sulfonamides were then pre pared. Many of these derivatives showed nanomolar affinity towards isozymes I, II and IV of carbonic anhydrase (CA). Some of the best inhibitors were applied as 2% water solutions/suspensions into the eye of normotensive or g laucomatous albino rabbits, when strong and long-lasting intraocular pressu re (IOP) lowering was observed. (C) 2001 Elsevier Science Ltd. All rights r eserved.