Discovery and evaluation of selective N-type calcium channel blockers: 6-Unsubstituted-1,4-dihydropyridine-5-carboxylic acid derivatives

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 11; pp. 3639 - 3642
• Main Authors: Yamamoto, Takashi, Niwa, Seiji, Tokumasu, Munetaka, Onishi, Tomoyuki, Ohno, Seiji, Hagihara, Masako, Koganei, Hajime, Fujita, Shin-ichi, Takeda, Tomoko, Saitou, Yuki, Iwayama, Satoshi, Takahara, Akira, Iwata, Seinosuke, Shoji, Masataka
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-06-2012; Elsevier
• Subjects: 1,4-Dihydropyridine derivative; Administration, Oral; Analgesics; Analgesics - chemical synthesis; Analgesics - chemistry; Analgesics - pharmacology; Animals; Biological and medical sciences; calcium channel blockers; Calcium Channel Blockers - chemical synthesis; Calcium Channel Blockers - chemistry; Calcium Channel Blockers - pharmacology; calcium channels; Calcium Channels, N-Type - chemistry; Calcium Channels, N-Type - metabolism; Carboxylic Acids - chemical synthesis; Carboxylic Acids - chemistry; Carboxylic Acids - pharmacology; Dihydropyridines - chemistry; Drug Evaluation, Preclinical; Formaldehyde - toxicity; Medical sciences; N-Type calcium channel blocker; Pain Measurement - drug effects; Pharmacology. Drug treatments; Rats; Structure-Activity Relationship; Structure–activity relationships; N-Type calcium channel blocker; 1,4-Dihydropyridine derivative; Structure–activity relationships; Evaluation; Structure activity relation; Carboxylic acid; N-type calcium channel; Ionic channel; Dihydropyridine derivatives; Selectivity; Antagonist; Structure-activity relationships
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.04.051

The structure–activity relationship study on 6-unsubstituted-1,4-dihydropyridine derivatives and 2,6-dihydro-1,4-dihydropyridine derivatives are reported as selective N-type calcium channel blockers over L-type calcium channel.
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.