Synthesis and Pharmacological Effects of Optically Active 2-[4-(4-Benzhydryl-1-piperazinyl)phenyl]-ethyl Methyl 1, 4-Dihydro-2, 6-dimethyl-4-(3-nitrophenyl-3, 5-pyridinedicarboxylate Hydrochloride

Abstract

Optically active 2-[4-(4-banzhydryl-1-piperazinyl)phenyl]ethyl methyl 1, 4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylate [(S)-(+)-1 and (R)-(-)-1] hydrochlorides were synthesized with high optical purities from (R)-(-)- and (S)-(+)-1, 4-dihydro-5-methoxycarbonyl-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylic acids [(R)-(-)-6 and (S)-(+)-6], which are availabel from (±)-6 by optical resolution using quinidine and cinchonidine, respectively. From pharmacological investigations of (S)-(+)-1 and (R)-(-)-1 such as the antihypertensive effect on spontaneously hypertensive rats and inhibition of [³H]nimodipine binding to rat cardiac mambrane homogenate, the active form of 1 was defined to be the (4S)-(+)-enantiomer of 1.