Channelpedia

PubMed 15139767


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , Kv7.2



Title: Synthesis and structure-activity relationship of acrylamides as KCNQ2 potassium channel openers.

Authors: Yong-Jin Wu, Huan He, Li-Qiang Sun, Alexandre L'Heureux, Jie Chen, Pierre Dextraze, John E Starrett, Christopher G Boissard, Valentin K Gribkoff, Joanne Natale, Steven I Dworetzky

Journal, date & volume: J. Med. Chem., 2004 May 20 , 47, 2887-96

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15139767


Abstract
A new class of acrylamides was synthesized, and the effects of these analogues on outward potassium current were evaluated by using two electrode voltage clamp recordings from Xenopus laevis oocytes expressing cloned mKCNQ2 channels. SAR studies indicated that the pharmacophore of the acrylamide series includes the (S) absolute configuration at the (1-phenyl)ethyl moiety and the alpha,beta-unsaturated acrylamide functionality with a free NH. This study identified (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide ((S)-1) and (S)-N-[1-(4-fluoro-3-morpholin-4-yl-phenyl)-ethyl]-3-(4-fluoro-phenyl)-acrylamide ((S)-2) as KCNQ2 openers for further electrophysiological evaluations. These two acrylamides demonstrated significant activity in the cortical spreading depression model of migraine as we reported previously.