Synthesis and KCNQ2 opener activity of N-(1-benzo [1, 3] dioxol-5-yl-ethyl, N-[1-(2, 3-dihydro-benzofuran-5-yl)-ethyl, and N-[1-(2, 3-dihydro-1H-indol-5-yl)-ethyl …

…, CG Boissard, RL Pieschl, VK Gribkoff, J Natale…

Index: Wu, Yong-Jin; Sun, Li-Qiang; He, Huan; Chen, Jie; Starrett Jr., John E.; Dextraze, Pierre; Daris, Jean-Paul; Boissard, Christopher G.; Pieschl, Rick L.; Gribkoff, Valentin K.; Natale, Joanne; Knox, Ronald J.; Harden, David G.; Thompson, Mark W.; Fitzpatrick, William; Weaver, David; Wu, Dedong; Gao, Qi; Dworetzky, Steven I. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 17 p. 4533 - 4537

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Citation Number: 20

Abstract

Bioisosteric replacement studies led to the identification of N-(1-benzo [1, 3] dioxol-5-yl- ethyl)-3-(2-chloro-phenyl)-acrylamide ((S)-3) as a highly potent KCNQ2 opener, and 3-(2, 6- difluoro-phenyl)-N-[1-(2, 3-dihydro-benzofuran-5-yl)-ethyl]-acrylamide ((S)-4), and N-[1-(2, 3- dihydro-1H-indol-5-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide ((S)-5) as highly efficacious KCNQ2 openers. In contrast, their respective R enantiomers showed significantly less or ...