title: The synthesis and structure-activity relationships of 3-amino-4-benzylquinolin-2-ones; discovery of novel KCNQ2 channel openers.
abstract: 3-amino-4-benzylquinolin-2-ones have been identified as a novel class of KCNQ2 channel openers. Synthesis and SAR is described along with their electrophysiological evaluation as activators of the cloned mKCNQ2 channel expressed in Xenopus laevis oocytes. The preliminary SAR data suggest the importance of both the trifluoromethylsulfonamido group and electron-withdrawing substituents on the quinolone nucleus for expression of KCNQ2 channel opening properties.
authors.affiliation: Department of Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. hewawasp@bms.com
authors.forename: Piyasena
authors.initials: P
authors.lastname: Hewawasam
authors.forename: Nathan
authors.initials: N
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Ding
authors.forename: Joanne T
authors.initials: JT
authors.lastname: Natale
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Boissard
authors.forename: Sarita
authors.initials: S
authors.lastname: Yeola
authors.forename: Valentin K
authors.initials: VK
authors.lastname: Gribkoff
authors.forename: John
authors.initials: J
authors.lastname: Starrett
authors.forename: Steven I
authors.initials: SI
authors.lastname: Dworetzky
mesh_terms: D000818:Animals; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D051658:KCNQ2 Potassium Channel; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D051658:KCNQ2 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015363:Quinolones