title: Carbonic anhydrase inhibitors: 4-sulfamoyl-benzenecarboxamides and 4-chloro-3-sulfamoyl-benzenecarboxamides with strong topical antiglaucoma properties.
abstract: Reaction of 4-carboxy-benzenesulfonamide or 4-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 glaucomatous 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.
authors: Università degli Studi, Istituto Oculistico, Viale Morgagni 85, I-50134, Firenze, Italy.
authors: F
authors: F
authors: Mincione
authors: M
authors: M
authors: Starnotti
authors: L
authors: L
authors: Menabuoni
authors: A
authors: A
authors: Scozzafava
authors: A
authors: A
authors: Casini
authors: C T
authors: CT
authors: Supuran
mesh_terms: D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005901:Glaucoma / Q000188:drug therapy*; D007429:Intraocular Pressure / Q000187:drug effects; D011817:Rabbits; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C434649:4-chloro-3-sulfamoyl-benzenecarboxamide; C434648:4-sulfamoyl-benzenecarboxamide; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides