Structure-activity relationship study of 1,4-dihydropyridine derivatives blocking N-type calcium channels.
Cilnidipine is a 1,4-dihydropyridine derived L/N-type calcium channel dual blocker possessing neuroprotective and analgesic effects which are related to its N-type calcium channel inhibitory activity. In order to find specific N-type calcium channel blockers with the least effects on cardiovascular system, we performed structure-activity relationship study on APJ2708, which is a derivative of cilnidipine, and found a promising N-type calcium channel blocker 21b possessing analgesic effect in vivo with a 1600-fold lower activity against L-type calcium channels than that of cilnidipine.
Yamamoto
Takashi
T
Pharmaceutical Research Laboratory, Ajinomoto company Inc., Kawasaki-ku, Kawasaki-shi, Japan.
Niwa
Seiji
S
Ohno
Seiji
S
Onishi
Tomoyuki
T
Matsueda
Hiroyuki
H
Koganei
Hajime
H
Uneyama
Hisayuki
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 / Q000187:drug effects*; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005557:Formaldehyde / Q000737:chemistry; D015394:Molecular Structure; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D005557:Formaldehyde; C038806:1,4-dihydropyridine; C065927:cilnidipine