title: Structure-activity study of L-cysteine-based N-type calcium channel blockers: optimization of N- and C-terminal substituents.
abstract: 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.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, 618-8585, Osaka, Japan. seko@ono.co.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Seko
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kohno
authors.forename: Shizuka
authors.initials: S
authors.lastname: Ono
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hashimura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takimizu
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nakai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Maegawa
authors.forename: Nobuo
authors.initials: N
authors.lastname: Katsube
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: 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
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020960:omega-Conotoxins; D003545:Cysteine