title: Carbonic anhydrase inhibitors: topically acting antiglaucoma sulfonamides incorporating esters and amides of 3- and 4-carboxybenzolamide.
abstract: Reaction of 3- and 4-carboxybenzenesulfonyl chloride with 5-amino-1,3,4-thiadiazole-2-sulfonamide/5-imino-4-methyl-delta(2)-1,3,4-thiadiazoline-2-sulfonamide afforded two series of benzolamide analogues to which the carboxyl moiety has been derivatized as esters or amides, in order to reduce their very polar character. The new derivatives showed low nanomolar affinity for three carbonic anhydrase (CA) isozymes, CA I, II and IV, and were effective as topical antiglaucoma agents in normotensive rabbits. Efficacy of several of the new sulfonamides reported was better than that of the standard drugs dorzolamide and brinzolamide, whereas their duration of action was prolonged as compared to that of the clinically used drugs.
authors: Università degli Studi, Laboratorio di Chimica Inorganica e Bioinorganica, Via della Lastruccia 3, Rm. 188; 50019 Sesto Fiorentino, Florence, Italy.
authors: Angela
authors: A
authors: Casini
authors: Andrea
authors: A
authors: Scozzafava
authors: Francesco
authors: F
authors: Mincione
authors: Luca
authors: L
authors: Menabuoni
authors: Michele
authors: M
authors: Starnotti
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001574:Benzolamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors; D030741:Carbonic Anhydrase IV / Q000037:antagonists & inhibitors; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D005901:Glaucoma / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D004952:Esters; D013449:Sulfonamides; D013843:Thiazines; D013876:Thiophenes; C111827:brinzolamide; C062765:dorzolamide; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D030741:Carbonic Anhydrase IV; D001574:Benzolamide