BENZOFURAZANYL-1,4-DIHYDROPYRIDINES AND BENZOFUROXANYL-1,4-DIHYDROPYRIDINES - SYNTHESIS, STRUCTURE AND CALCIUM-ENTRY BLOCKER ACTIVITY

The synthesis, structural characterization and calcium blocking activi ty of a series of benzofurazanyl-1,4-dihydropyridines (18 and 19) and benzofuroxanyl analogues (20 and 21) are reported. H-1-NMR showed that all the benzofuroxan derivatives exist in solution as tautomeric mixt ures. The predominant tautomeric form in solution of the derivative 20 (dimethyl yl-4-(4-benzofuroxanyl)-3,5-pyridinedicarboxylate) is also the one preferred in the solid state as shown by X-ray analysis. The c onformation in the solid state of the benzofurazanyl analogue is also reported. Calcium entry blocker activity of the dihydropyridine deriva tives 18-21 has been evaluated in isolated rabbit basilar artery as re laxation of calcium-induced contractions in high K+-depolarizing solut ion. All the compounds displayed high potency. The activity of benzofu razan derivatives was not changed by the N-oxidation. The two most act ive compounds 18 and 20 were as potent as Nifedipine.