Structure-activity relationship study of 1,4-dihydropyridine derivatives blocking N-type calcium channels.
Bioorganic & medicinal chemistry letters 2006 Feb 15; 16(4):798-802
Yamamoto T T, Niwa S S, Ohno S S, Onishi T T, Matsueda H H, Koganei H H, Uneyama H H, Fujita S S, Takeda T T, Kito M M, Ono Y Y, Saitou Y Y, Takahara A A, Iwata S S, Shoji M M
Pharmaceutical Research Laboratory, Ajinomoto company Inc., Kawasaki-ku, Kawasaki-shi, Japan.
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.