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

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.

Graphical abstractThe 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.Figure optionsDownload full-size imageDownload as PowerPoint slide