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Abstract #8064 Published in IGR 4-3
Carbonic anhydrase inhibitors with strong topical antiglaucoma properties incorporating a 4-(2-amino-pyrimidin-4-yl-amino)-benzene-sulfonamide scaffold
Casini A; Mincione F; Vullo D; Menabuoni L; Scozzafava A; Supuran CTJournal of Enzyme Inhibition and Medicinal Chemistry 2002; 17: 9-18
The reaction of 4-(2-amino-pyrimidin-4-yl-amino)-benzene-sulfonamide with alkyl/aryl-sulfonyl halides, acyl halides or arysulfonyl isocyanates afforded a series of derivatives which were tested for inhibition of three carbonic anhydrase (CA) isozymes. These compounds were designed in such a way as to (i) strongly inhibit several CA isozymes involved in aqueous humor secretion within the eye (such as CA II and CA IV), and (ii) to possess a pharmacological profile that allows easy penetration through the cornea, when administered as eye drops in solution or suspension, thus constituting a valuable therapeutic approach for glaucoma. Several of the inhibitors obtained showed low nanomolar affinities for the two isozymes involved in aqueous humor secretion, CA II and CA IV. Furthermore, in normotensive and hypertensive rabbits, some of them showed effective and prolonged intraocular pressure (IOP) lowering when administered topically, as 2% suspensions/solutions.
C.T. Supuran, MD, Universita degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Florence, Italy. claudiu.supuran@unifi.it
Classification:
11.5.2 Topical (Part of: 11 Medical treatment > 11.5 Carbonic anhydrase inhibitors)
