Design and syntheses of 4-[3-(1-methoxycarbonyl-1,6-dihydropyridyl)]- and 4-[3-(1-methoxycarbonyl-4-substituted-1,4-dihydropyridyl)]- derivatives of alkyl 1,4-dihydro-2,6-dimethyl-3-nitro-5-pyridine-carboxylates with calcium channel modulating activities

Abstract

A group of 4-[3-(1-methoxycarbonyl-1,6-dihydropyridyl)]-derivatives of alkyl 1,4-dihydro-2,6-dimethyl-3-nitro-5-pyridinecarboxylates 8a-e were synthesized by the regioselective reduction of the corresponding 4-(3-pyridyl)-analogs in the presence of methyl chloroformate using Li(tBuO)3AlH. Alternatively, a related group of 4-[3-(1-methoxycarbonyl-4-substituted-1,4-dihydropyridyl)]-compounds 14-18 were prepared using a modified Hantzsch reaction involving the condensation of 1-methoxycarbonyl-4-substituted-1,4-dihydropyridyl-3-carboxaldehydes 11a-c with an alkyl 3-aminocrotonate 12 and nitroacetone 13. In contrast to the 4-(3-pyridyl)-compound 2b, which exhibits an undesirable calcium channel agonist smooth muscle failure.