| Autor: |
de Tullio P; Centre de Recherche en Pharmacochimie des Substances Naturelles et Synthétiques, Laboratoire de Chimie Pharmaceutique, Université de Liège, 1 Avenue de l'Hôpital, B-4000 Liège, Belgium. P.deTullio@ulg.ac.be, Boverie S, Becker B, Antoine MH, Nguyen QA, Francotte P, Counerotte S, Sebille S, Pirotte B, Lebrun P |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2005 Jul 28; Vol. 48 (15), pp. 4990-5000. |
| DOI: |
10.1021/jm0580050 |
| Abstrakt: |
A series of 6,7-disubstituted 4H-1,2,4-benzothiadiazine 1,1-dioxides bearing a short alkylamino side chain in the 3-position were synthesized. These compounds were tested on rat pancreatic islets and on rat aorta rings. In vitro data indicated that in most cases substitution in the 6 and the 7 positions increased their activity as inhibitors of insulin secretion, while the myorelaxant potency of the drugs was maintained or enhanced according to the nature of the substituent in the 7-position. The presence of either chlorine or bromine atoms in the 6 and 7 positions did not improve the apparent selectivity of the drugs for the pancreatic tissue. By contrast, the introduction of one or two fluorine atoms, as well as the presence of a methoxy group in the 7-position, generated potent and selective inhibitors of insulin release. Radioisotopic and fluorimetric experiments performed with the most potent compound inhibiting insulin release (34, BPDZ 259, 6-chloro-7-fluoro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide) confirmed that the drug activated K(ATP) channels. 34 was found to be one of the most potent and selective pancreatic potassium channel openers yet described. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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