The synthesis and structure-activity relationships of 3-amino-4-benzylquinolin-2-ones; discovery of novel KCNQ2 channel openers.
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.
Hewawasam
Piyasena
P
Department of Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. hewawasp@bms.com
Chen
Nathan
N
Ding
Min
M
Natale
Joanne T
JT
Boissard
Christopher G
CG
Yeola
Sarita
S
Gribkoff
Valentin K
VK
Starrett
John
J
Dworetzky
Steven I
SI
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
D051658:KCNQ2 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015363:Quinolones