title: Discovery and evaluation of selective N-type calcium channel blockers: 6-unsubstituted-1,4-dihydropyridine-5-carboxylic acid derivatives.
abstract: A structure-activity relationship study of 6-unsubstituted-1,4-dihydropyridine and 2,6-unsubstituted-1,4-dihydropyridine derivatives was conducted in an attempt to discover N-type calcium channel blockers that were highly selective over L-type calcium channel blockers. Among the tested compounds, (+)-4-(3,5-dichloro-4-methoxy-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-cinnamyl ester was found to be an effective and selective N-type calcium channel blocker with oral analgesic potential.
authors.affiliation: Exploratory Research Laboratories, Ajinomoto Pharmaceuticals Co. Ltd, Kawasaki-ku, Kawasaki-shi, Kanagawa, Japan. takashia_yamamoto@ajinomoto.com
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Niwa
authors.forename: Munetaka
authors.initials: M
authors.lastname: Tokumasu
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Onishi
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohno
authors.forename: Masako
authors.initials: M
authors.lastname: Hagihara
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: Yuki
authors.initials: Y
authors.lastname: Saitou
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iwayama
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: D000284:Administration, Oral; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000737:chemistry* / Q000378:metabolism; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004095:Dihydropyridines / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D005557:Formaldehyde / Q000633:toxicity; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D002264:Carboxylic Acids; D004095:Dihydropyridines; D005557:Formaldehyde; C038806:1,4-dihydropyridine