2 H -Thieno[3,2- e ]- and [2,3- e ]-1,2-thiazine-6-sulfonamide 1,1-dioxides as ocular hypotensive agents: synthesis, carbonic anhydrase inhibition and evaluation in the rabbit
| Autor: | Sharon Gross, William S. Sly, Hwang-Hsing Chen, Marsha A. McLaughlin, Jesse A. May, Thomas R. Dean, John B. Liao |
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| Rok vydání: | 2000 |
| Předmět: |
Magnetic Resonance Spectroscopy
Stereochemistry Carbonic anhydrase II Clinical Biochemistry Brinzolamide Pharmaceutical Science Pharmacology Biochemistry Chemical synthesis chemistry.chemical_compound Thiazine Carbonic anhydrase Drug Discovery medicine Animals Humans Carbonic Anhydrase Inhibitors Molecular Biology Antihypertensive Agents Intraocular Pressure Carbonic Anhydrases chemistry.chemical_classification Sulfonamides biology Bicyclic molecule Chemistry Organic Chemistry Sulfonamide (medicine) Glaucoma Enzyme biology.protein Drug Evaluation Molecular Medicine Rabbits medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 8:957-975 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(00)00026-2 |
| Popis: | Novel non-chiral 2H-thieno[3,2-e]- and [2,3-e]-1,2-thiazine-6-sulfonamide 1,1-dioxides were synthesized for evaluation as potential candidates for the treatment of glaucoma. All of the compounds prepared were potent high affinity inhibitors of human carbonic anhydrase II, Ki0.5 nM. Additionally, inhibition of recombinant human carbonic anhydrase IV was determined for selected compounds; these were shown to be moderate to potent inhibitors of this isozyme with IC50 values ranging from 4.25 to 73.6 nM. Of the compounds evaluated for their ability to lower intraocular pressure in naturally hypertensive Dutch-belted rabbits, 5a, 17a3, 17b1, 17b2, 17h2 and 17i1 showed significant efficacy (20% decrease) in this model following topical ocular administration. |
| Databáze: | OpenAIRE |
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