Benzofurazanyl- and benzofuroxanyl-1,4-dihydropyridines: synthesis, structure and calcium entry blocker activity

Abstract

The synthesis, structural characterization and calcium blocking activity of a series of benzofurazanyl-1,4-dihydropyridines ( 18 and 19) and benzofuroxanyl analogues ( 20 and 21) are reported. 1H-NMR showed that all the benzofuroxan derivatives exist in solution as tautomeric mixtures. The predominant tautomeric form in solution of the derivative 20 (dimethyl 1,4-dihydro-2,6-dimethyl-4-(4-benzofuroxanyl)-3,5-pyridinedicarboxylate) is also the one preferred in the solid state as shown by X-ray analysis. The conformation in the solid state of the benzofurazanyl analogue is also reported. Calcium entry blocker activity of the dihydropyridine derivatives 18–21 has been evaluated in isolated rabbit basilar artery as relaxation of calcium-induced contractions in high K +-depolarizing solution. All the compounds displayed high potency. The activity of benzofurazan derivatives was not changed by the N-oxidation. The two most active compounds 18 and 20 were as potent as Nifedipine.