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 ac id with carboxy-protected amino acids' dipeptides, or aromatic/heterocyclic sulfonamides:mercaptans afforded the corresponding benzene-carboxamide der ivatives. These were tested as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II and IV. Some of the new derivatives showed affinity in t he low nanomolar range for isozymes CA II and IV. involved in aqueous humor secretion within the eye, and were tested as topically acting anti-glaucom a agents, in normotensive and glaucomatoous rabbits. Good in vivo activity and prolonged duration of action has been observed for some of these deriva tives. as compared to the clinically used drugs dorzolamide and brinzolamid e. Some of the 4-chloro-3-sulfamoyl benzenecarboxamides reported here showe d higher affinity for CA I than for the sulfonamide avid isozyme CA II. (C) 2001 Elsevier Science Ltd. All rights reserved.