Title of article :
The structure–activity relationship study on 2-, 5-, and 6-position of the water soluble 1,4-dihydropyridine derivatives blocking N-type calcium channels
Author/Authors :
Takashi Yamamoto، نويسنده , , Seiji Niwa، نويسنده , , Seiji Ohno، نويسنده , , Munetaka Tokumasu، نويسنده , , Yoko Masuzawa، نويسنده , , Chika Nakanishi، نويسنده , , Akira Nakajo، نويسنده , , Tomoyuki Onishi، نويسنده , , Hajime Koganei، نويسنده , , Shin-ichi Fujita، نويسنده , , Tomoko Takeda، نويسنده , , Morikazu Kito، نويسنده , , Yukitsugu Ono، نويسنده , , Yuki Saitou، نويسنده , , Akira Takahara، نويسنده , , Seinosuke Iwata، نويسنده , , Masataka Shoji، نويسنده ,
Abstract :
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.
Keywords :
1 , N-type calcium channel blocker , Structure–activity relationships , 4-dihydropyridine derivative
