Yamamoto Takashi, Niwa Seiji, Ohno Seiji, Onishi Tomoyuki, Matsueda Hiroyuki, Koganei Hajime, Uneyama Hisayuki, Fujita Shin-ichi, Takeda Tomoko, Kito Morikazu, Ono Yukitsugu, Saitou Yuki, Takahara Akira, Iwata Seinosuke, Shoji Masataka
Pharmaceutical Research Laboratory, Ajinomoto company Inc., Kawasaki-ku, Kawasaki-shi, Japan.
Bioorg Med Chem Lett. 2006 Feb 15;16(4):798-802. doi: 10.1016/j.bmcl.2005.11.021. Epub 2005 Nov 23.
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.
西尼地平是一种1,4-二氢吡啶类L/N型钙通道双重阻滞剂，具有神经保护和镇痛作用，这些作用与其N型钙通道抑制活性有关。为了找到对心血管系统影响最小的特异性N型钙通道阻滞剂，我们对西尼地平的衍生物APJ2708进行了构效关系研究，发现了一种有前景的N型钙通道阻滞剂21b，它在体内具有镇痛作用，对L型钙通道的活性比西尼地平低1600倍。
