3-Amino-1,5-benzodiazepinones: potent, state-dependent sodium channel blockers with anti-epileptic activity.
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.
Hoyt
Scott B
SB
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, RY 123-236, Rahway, NJ 07065-0900, USA.
London
Clare
C
Wyvratt
Matthew J
MJ
Fisher
Michael H
MH
Cashen
Doreen E
DE
Felix
John P
JP
Garcia
Maria L
ML
Li
Xiaohua
X
Lyons
Kathryn A
KA
Euan MacIntyre
D
D
Martin
William J
WJ
Priest
Birgit T
BT
Smith
McHardy M
MM
Warren
Vivien A
VA
Williams
Brande S
BS
Kaczorowski
Gregory J
GJ
Parsons
William H
WH
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*
D000927:Anticonvulsants; D001570:Benzodiazepinones; D051638:Ether-A-Go-Go Potassium Channels; D026941:Sodium Channel Blockers