Studies on nilvadipine. IV. Synthesis of deuteriated and optically active isopropyl 2-cyano-3-methoxycarbonyl-4-(3-nitrophenyl)-6-methyl-1,4- dihydropyridine-5-carboxylate (nilvadipine).
Nilvadipine, I, has already entered clinical use for the treatment of hypertension. In the process of the developing nilvadipine, we prepared the deuteriated analogue of I as an internal standard for the determination of I in human plasma by capillary column gas chromatography-negative-ion chemical-ionization mass spectrometer. Nilvadipine has an asymmetric center at the C-4 position of the dihydropyridine ring, and characterization of the optical isomers with regard to their activity and bioavailability is of interest. Thus, we synthesized both the enantiomers of I by optical resolution via the 5-carboxy derivative (3), which was previously prepared as one of the metabolites of I.
Satoh
Y
Y
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan.
Okumura
K
K
Shiokawa
Y
Y
D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D003903:Deuterium; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013237:Stereoisomerism
D000959:Antihypertensive Agents; C035100:nilvadipine; D003903:Deuterium; D009543:Nifedipine