"Synthesis and smooth muscle Calcium channel antagonist effects of new derivatives of 1,4-Dihydropyridine containing Nitroimidazol 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 χ 10^-7 M). All compounds exhibited 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).