title: (S,E)-N-[1-(3-heteroarylphenyl)ethyl]-3-(2-fluorophenyl)acrylamides: synthesis and KCNQ2 potassium channel opener activity.
abstract: Replacement of the morpholinyl moiety in (S,E)-N-[1-(3-morpholinophenyl)ethyl]-3-phenylacrylamide (1) with heteroaryl groups led to the identification of (S,E)-N-1-[3-(6-fluoropyridin-3-yl)phenyl]ethyl-3-(2-fluorophenyl)acrylamide (5) as a potent KCNQ2 potassium channel opener. Among this series of heteroaryl substituted acrylamides, (S,E)-N-1-[3-(1H-pyrazol-1-yl)phenyl]ethyl-3-(2-fluorophenyl)acrylamide (9) exhibits balanced potency and efficacy. The syntheses and the KCNQ2 opener activity of this series of acrylamides are described.
authors.affiliation: Department of Medicinal Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 100 de l'Industrie Blvd., Candiac, Quebec, Canada, J5R 1J1.
authors.forename: Alexandre
authors.initials: A
authors.lastname: L'Heureux
authors.forename: Alain
authors.initials: A
authors.lastname: Martel
authors.forename: Huan
authors.initials: H
authors.lastname: He
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Sun
authors.forename: John E
authors.initials: JE
authors.lastname: Starrett
authors.forename: Joanne
authors.initials: J
authors.lastname: Natale
authors.forename: Steven I
authors.initials: SI
authors.lastname: Dworetzky
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Knox
authors.forename: David G
authors.initials: DG
authors.lastname: Harden
authors.forename: David
authors.initials: D
authors.lastname: Weaver
authors.forename: Mark W
authors.initials: MW
authors.lastname: Thompson
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051658:KCNQ2 Potassium Channel; D015394:Molecular Structure; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*
chemical_list: D000178:Acrylamides; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D024642:Potassium Channels, Voltage-Gated