Document Report Card

ID: ALA1149174

Journal: J Med Chem

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

Authors: Wu YJ, He H, Sun LQ, L'Heureux A, Chen J, Dextraze P, Starrett JE, Boissard CG, Gribkoff VK, Natale J, Dworetzky SI.

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.

CiteXplore: 15139767

DOI: 10.1021/jm0305826