Synthesis and biological activity of the calcium modulator (R) and (S)-3-methyl 5-pentyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.
An efficient total synthesis of (R) and (S)-3-methyl 5-pentyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate in high optical purities is reported. The useful step is the resolution of racemic 2, 6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid by using commercially available Cinchona alkaloids cinchonidine and quinidine as the resolving agents. Under the optimum conditions, the optical purities for R- and S-enantiomers are extremely high (ee>99.5%). The further dihydropyridine receptor binding activity assay shows that the S-enantiomer is more potent than R-enantiomer both in rat cardiac (approximately 19 times) and cerebral cortex membrane (12 times).
Zhang
Bang-le
BL
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. blezhang@fmmu.edu.cn
He
Wei
W
Shi
Xin
X
Huan
Meng-Lei
ML
Huang
Qiu-Ju
QJ
Zhou
Si-Yuan
SY
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013237:Stereoisomerism
D020746:Calcium Channels, L-Type; D003998:Dicarboxylic Acids; D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D002118:Calcium