The structure–activity relationship study on 2-, 5-, and 6-position of the water soluble 1,4-dihydropyridine derivatives blocking N-type calcium channels

In order to find an injectable and selective N-type calcium channel blocker, we have performed the structure–activity relationship (SAR) study on the 2-, 5-, and 6-position of 1,4-dihydropyridine-3-carboxylate derivative APJ2708 (2), which is a derivative of Cilnidipine and has L/N-type calcium channel dual inhibitory activities. As a consequence of the optimization, 6-dimethylacetal derivative 7 was found to have an effective inhibitory activity against N-type calcium channels with more than 170-fold lower activity for L-type channel compared to that of APJ2708.

Graphical abstractThe structure–activity relationship of the 2-, 5-, and 6-position of 1,4-dihydropyridine-3-carboxylic acid-derived N-type calcium channel blockers is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide