Carbonic anhydrase inhibitors: 4-sulfamoyl-benzenecarboxamides and 4-chloro-3-sulfamoyl-benzenecarboxamides with strong topical antiglaucoma properties

Reaction of 4-carboxy-benzenesulfonamide or 3-chloro-3-sulfamoyl benzoic acid with carboxy-protected amino acids' dipeptides, or aromatic/heterocyclic sulfonamides:mercaptans afforded the corresponding benzene-carboxamide derivatives. These were tested as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II and IV. Some of the new derivatives showed affinity in the low nanomolar range for isozymes CA II and IV. involved in aqueous humor secretion within the eye, and were tested as topically acting anti-glaucoma agents, in normotensive and glaucomatoous rabbits. Good in vivo activity and prolonged duration of action has been observed for some of these derivatives. as compared to the clinically used drugs dorzolamide and brinzolamide. Some of the 4-chloro-3-sulfamoyl benzenecarboxamides reported here showed higher affinity for CA I than for the sulfonamide avid isozyme CA II. (C) 2001 Elsevier Science Ltd. All rights reserved.