title: 3-Amino-1,5-benzodiazepinones: potent, state-dependent sodium channel blockers with anti-epileptic activity.
abstract: A series of 3-amino-1,5-benzodiazepinones were synthesized and evaluated as potential sodium channel blockers in a functional, membrane potential-based assay. One member of this series displayed subnanomolar, state-dependent sodium channel block, and was orally efficacious in a mouse model of epilepsy.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, RY 123-236, Rahway, NJ 07065-0900, USA.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Hoyt
authors.forename: Clare
authors.initials: C
authors.lastname: London
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wyvratt
authors.forename: Michael H
authors.initials: MH
authors.lastname: Fisher
authors.forename: Doreen E
authors.initials: DE
authors.lastname: Cashen
authors.forename: John P
authors.initials: JP
authors.lastname: Felix
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Li
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: D
authors.initials: D
authors.lastname: Euan MacIntyre
authors.forename: William J
authors.initials: WJ
authors.lastname: Martin
authors.forename: Birgit T
authors.initials: BT
authors.lastname: Priest
authors.forename: McHardy M
authors.initials: MM
authors.lastname: Smith
authors.forename: Vivien A
authors.initials: VA
authors.lastname: Warren
authors.forename: Brande S
authors.initials: BS
authors.lastname: Williams
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kaczorowski
authors.forename: William H
authors.initials: WH
authors.lastname: Parsons
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D004594:Electrophysiology; D004597:Electroshock; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D026941:Sodium Channel Blockers / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D001570:Benzodiazepinones; D051638:Ether-A-Go-Go Potassium Channels; D026941:Sodium Channel Blockers