Synthesis and Biological Activities of Optical Isomers of 2-(4-Diphenylmethyl-1-piperazinyl)ethyl Methyl 1, 4-Dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylate (Manidipine) Dihydrochloride

Abstract

Enantiomeric (+)- and (-)-manidipine (1) dihydrochlorides were synthesized by the esterification of the optically active monocarboxylic acids (-)-6 and (+)-6, respectively. The absolute configurations, (S)-(+)-1 and (R)-(-)-1, were unambiguously determined by X-ray crystallographic analysis of (+)-7 derived from (-)-6. The (S)-(+)-1 was about 30 and 80 times as potent as the (R)-(-)-isomer in antihypertensive activity in spontaneously hypertensive rats (SHR), and in the radioligand binding assay using [³H]nitrendipine, respectively.