Bioorganic & Medicinal Chemistry Letters 2004-04-19

(S)-N-[1-(4-cyclopropylmethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide is a potent and efficacious KCNQ2 opener which inhibits induced hyperexcitability of rat hippocampal neurons.

Yong-Jin Wu, Christopher G Boissard, Jie Chen, William Fitzpatrick, Qi Gao, Valentin K Gribkoff, David G Harden, Huan He, Ronald J Knox, Joanne Natale, Rick L Pieschl, John E Starrett, Li-Qiang Sun, Mark Thompson, David Weaver, Dedong Wu, Steven I Dworetzky

Index: Bioorg. Med. Chem. Lett. 14 , 1991, (2004)

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Abstract

(S)-N-[1-(4-Cyclopropylmethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide ((S)-2) was identified as a potent and efficacious KCNQ2 opener. This compound demonstrated significant activity in reducing neuronal hyperexcitability in rat hippocampal slices, and the inhibition mediated by (S)-2 was reversed by the KCNQ blocker linopirdine.