title: (S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide: an orally bioavailable KCNQ2 opener with significant activity in a cortical spreading depression model of migraine.
abstract: (S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut 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: Corinne
authors.initials: C
authors.lastname: Greco
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: Alexandre
authors.initials: A
authors.lastname: L'Heureux
authors.forename: Shing Hong
authors.initials: SH
authors.lastname: Kang
authors.forename: Gene G
authors.initials: GG
authors.lastname: Kinney
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Knox
authors.forename: Joanne
authors.initials: J
authors.lastname: Natale
authors.forename: Amy E
authors.initials: AE
authors.lastname: Newton
authors.forename: Sanna
authors.initials: S
authors.lastname: Lehtinen-Oboma
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sinz
authors.forename: Digavalli V
authors.initials: DV
authors.lastname: Sivarao
authors.forename: John E
authors.initials: JE
authors.lastname: Starrett
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Sun
authors.forename: Svetlana
authors.initials: S
authors.lastname: Tertyshnikova
authors.forename: Mark W
authors.initials: MW
authors.lastname: Thompson
authors.forename: David
authors.initials: D
authors.lastname: Weaver
authors.forename: Henry S
authors.initials: HS
authors.lastname: Wong
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Steven I
authors.initials: SI
authors.lastname: Dworetzky
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D015640:Ion Channel Gating; D051658:KCNQ2 Potassium Channel; D008881:Migraine Disorders / Q000378:metabolism / Q000503:physiopathology*; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D000178:Acrylamides; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; C496915:Kcnq2 protein, rat; D009025:Morpholines; C476437:N-(1-(3-morpholin-4-ylphenyl)ethyl)-3-phenylacrylamide; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated