title: The structure-activity relationship study on 2-, 5-, and 6-position of the water soluble 1,4-dihydropyridine derivatives blocking N-type calcium channels.
abstract: 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.
authors.affiliation: Pharmaceutical Research Laboratory, Ajinomoto company Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Niwa
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohno
authors.forename: Munetaka
authors.initials: M
authors.lastname: Tokumasu
authors.forename: Yoko
authors.initials: Y
authors.lastname: Masuzawa
authors.forename: Chika
authors.initials: C
authors.lastname: Nakanishi
authors.forename: Akira
authors.initials: A
authors.lastname: Nakajo
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Onishi
authors.forename: Hajime
authors.initials: H
authors.lastname: Koganei
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Fujita
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takeda
authors.forename: Morikazu
authors.initials: M
authors.lastname: Kito
authors.forename: Yukitsugu
authors.initials: Y
authors.lastname: Ono
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saitou
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Iwata
authors.forename: Masataka
authors.initials: M
authors.lastname: Shoji
mesh_terms: 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
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D014867:Water; C038806:1,4-dihydropyridine; C065927:cilnidipine