Structure-activity study of L-cysteine-based N-type calcium channel blockers: optimization of N- and C-terminal substituents.
Synthesis and structure-activity relationship (SAR) studies of L-cysteine-based N-type calcium channel blockers are described. In the course of exploring SAR of the N- and C-terminal substituents, the L-cysteine derivative was found to be a potent N-type calcium channel blocker with an IC(50) value of 0.14 microM on IMR-32 assay. Compound showed 12-fold selectivity for N-type over L-type calcium channels on AtT-20 assay.
Seko
Takuya
T
Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, 618-8585, Osaka, Japan. seko@ono.co.jp
Kato
Masashi
M
Kohno
Hiroshi
H
Ono
Shizuka
S
Hashimura
Kazuya
K
Takimizu
Hideyuki
H
Nakai
Katsuhiko
K
Maegawa
Hitoshi
H
Katsube
Nobuo
N
Toda
Masaaki
M
D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D003545:Cysteine / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D020960:omega-Conotoxins / Q000737:chemistry / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020960:omega-Conotoxins; D003545:Cysteine