title: (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.
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.
authors.affiliation: Department of Neuroscience Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. yong-jin.wu@bms.com
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Wu
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Boissard
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: William
authors.initials: W
authors.lastname: Fitzpatrick
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: Valentin K
authors.initials: VK
authors.lastname: Gribkoff
authors.forename: David G
authors.initials: DG
authors.lastname: Harden
authors.forename: Huan
authors.initials: H
authors.lastname: He
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Knox
authors.forename: Joanne
authors.initials: J
authors.lastname: Natale
authors.forename: Rick L
authors.initials: RL
authors.lastname: Pieschl
authors.forename: John E
authors.initials: JE
authors.lastname: Starrett
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Sun
authors.forename: Mark
authors.initials: M
authors.lastname: Thompson
authors.forename: David
authors.initials: D
authors.lastname: Weaver
authors.forename: Dedong
authors.initials: D
authors.lastname: Wu
authors.forename: Steven I
authors.initials: SI
authors.lastname: Dworetzky
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051658:KCNQ2 Potassium Channel; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010078:Oxazines / Q000138:chemical synthesis / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000178:Acrylamides; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; C496915:Kcnq2 protein, rat; C492891:N-(1-(4-cyclopropylmethyl-3,4-dihydro-2H-benzo(1,4)oxazin-6-yl)ethyl)-3-(2-fluorophenyl)acrylamide; D010078:Oxazines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated