Structure-activity relationship study of 1,4-dihydropyridine derivatives blocking N-type calcium channels

  • Bioorg Med Chem Lett. 2006 Feb 15;16(4):798-802. doi: 10.1016/j.bmcl.2005.11.021.
Takashi Yamamoto  1 ,  Seiji Niwa ,  Seiji Ohno ,  Tomoyuki Onishi ,  Hiroyuki Matsueda ,  Hajime Koganei ,  Hisayuki Uneyama ,  Shin-ichi Fujita ,  Tomoko Takeda ,  Morikazu Kito ,  Yukitsugu Ono ,  Yuki Saitou ,  Akira Takahara ,  Seinosuke Iwata ,  Masataka Shoji
Affiliations
  • 1. Pharmaceutical Research Laboratory, Ajinomoto company Inc., Kawasaki-ku, Kawasaki-shi, Japan.
PMID: 16309909 DOI: 10.1016/j.bmcl.2005.11.021
Abstract

Cilnidipine is a 1,4-dihydropyridine derived L/N-type calcium channel dual blocker possessing neuroprotective and analgesic effects which are related to its N-type calcium channel inhibitory activity. In order to find specific N-type calcium channel blockers with the least effects on cardiovascular system, we performed structure-activity relationship study on APJ2708, which is a derivative of cilnidipine, and found a promising N-type calcium channel blocker 21b possessing analgesic effect in vivo with a 1600-fold lower activity against L-type calcium channels than that of cilnidipine.