The structure-activity relationship study on 2-, 5-, and 6-position of the water soluble 1,4-dihydropyridine derivatives blocking N-type calcium channels.
In order to find an injectable and selective N-type calcium channel blocker, we have performed the structure-activity relationship (SAR) study on the 2-, 5-, and 6-position of 1,4-dihydropyridine-3-carboxylate derivative APJ2708 (2), which is a derivative of Cilnidipine and has L/N-type calcium channel dual inhibitory activities. As a consequence of the optimization, 6-dimethylacetal derivative 7 was found to have an effective inhibitory activity against N-type calcium channels with more than 170-fold lower activity for L-type channel compared to that of APJ2708.
Yamamoto
Takashi
T
Pharmaceutical Research Laboratory, Ajinomoto company Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi, Japan.
Niwa
Seiji
S
Ohno
Seiji
S
Tokumasu
Munetaka
M
Masuzawa
Yoko
Y
Nakanishi
Chika
C
Nakajo
Akira
A
Onishi
Tomoyuki
T
Koganei
Hajime
H
Fujita
Shin-Ichi
S
Takeda
Tomoko
T
Kito
Morikazu
M
Ono
Yukitsugu
Y
Saitou
Yuki
Y
Takahara
Akira
A
Iwata
Seinosuke
S
Shoji
Masataka
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D014867:Water; C038806:1,4-dihydropyridine; C065927:cilnidipine