Carbonic anhydrase inhibitors: topically acting antiglaucoma sulfonamides incorporating esters and amides of 3- and 4-carboxybenzolamide.
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.
Casini
Angela
A
Università degli Studi, Laboratorio di Chimica Inorganica e Bioinorganica, Via della Lastruccia 3, Rm. 188; 50019 Sesto Fiorentino, Florence, Italy.
Scozzafava
Andrea
A
Mincione
Francesco
F
Menabuoni
Luca
L
Starnotti
Michele
M
Supuran
Claudiu T
CT
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
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