Topically active carbonic anhydrase inhibitors. 1. O-Acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide
| Autor: | P. Gautheron, Otto W. Woltersdorf, Harvey Schwam, S J deSolms, Jacob M. Hoffman, Samuel L. Graham, Fishman Dr, Larson Rd, John B. Bicking, Brown Sl |
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| Rok vydání: | 1989 |
| Předmět: |
Chemical Phenomena
medicine.drug_class Guinea Pigs Cornea Carbonic anhydrase Drug Discovery medicine Animals Humans Prodrugs Carbonic anhydrase inhibitor Benzothiazoles Ethoxzolamide Carbonic Anhydrase Inhibitors Intraocular Pressure chemistry.chemical_classification biology Bicyclic molecule Biological activity Prodrug eye diseases In vitro Sulfonamide Chemistry Thiazoles chemistry Biochemistry Enzyme inhibitor biology.protein Molecular Medicine Rabbits sense organs Ophthalmic Solutions |
| Zdroj: | Journal of Medicinal Chemistry. 32:2486-2492 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00131a011 |
| Popis: | A series of O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide (4, L-643,799) was prepared and the potential utility of each series member as a topically active inhibitor of ocular carbonic anhydrase was determined. In vitro studies showed these esters to be substrates for ocular esterases which liberate 4 during corneal translocation. The most interesting series member, 2-sulfamoyl-6-benzothiazolyl 2,2-dimethylpropionate (22, L-645,151), acting as a prodrug form of 4, was found to enhance delivery through the isolated albino rabbit cornea by 40-fold when compared to the parent phenol 4. Studies in rabbits revealed that 22 is a potent topically active ocular hypotensive carbonic anhydrase inhibitor. |
| Databáze: | OpenAIRE |
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