Synthesis and smooth muscle calcium channel antagonist effects of new derivatives of 1, 4 - dihydropyridine containing nitroimidazolyl substituent

ABSTRACT

A group of racemic 3-[[2-hydroxyethyl], [2-Methoxyethyl], [2-acetylethyl] or [2-cyanoethyl]], 5- methyl, ethyl or isopropyl-1, 4-dihydro-2, 6-dimethyl-4-[1-methyl-5-nitro-2-imidazolyl]-3, 5-pyridinedicarboxylates [XIV-XXV] were prepared by the reaction of 1-methyl-5-nitroimidazol-2-carboxaldehyde [X] with acetoacetic esters [VI-IX] and alkys 3-aminocrotonate [XI-XIII]. In vitro calcium channel antagonist activities of the tested compounds were determined by their effects on contraction of Guinea Pig Ileal Longitudinal Smooth Muscle [GPILSM] which was induced by carbacol [1.67 calcium channel antagonist activity [IC50=10 -12 to 10 -13 M range] comparable to nifedipine as reference drug [IC50=1.07 +/- 0.12x 10 -11 M]