Synthesis of expected metabolites of benidipine hydrochloride.
(+/-)-(R*)-2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049, 1), a highly potent and long-acting calcium antagonistic 1,4-dihydropyridine derivative, is now under clinical study as an antihypertensive and as an antianginal agent. In order to confirm the structures of the metabolites of KW-3049, 19 compounds were prepared. Among them 11 compounds were found to be metabolites (the compounds 2, 3, 6, 8, 14, 15, 16, 28, 31, 32 and 34) of KW-3049 in rats and/or dogs.
Muto
K
K
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Kuroda
T
T
Kawato
H
H
Nishikawa
H
H
Nakamizo
N
N
D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D002121:Calcium Channel Blockers / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D015394:Molecular Structure; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D009543:Nifedipine