Discovery of a novel class of benzazepinone Na(v)1.7 blockers: potential treatments for neuropathic pain.
A series of benzodiazepines and benzazepinones were synthesized and evaluated as potential sodium channel blockers in a functional, membrane potential-based assay. One member of the benzazepinone series, compound 47, displayed potent, state-dependent block of hNa(v)1.7, and was orally efficacious in a rat model of neuropathic pain.
Hoyt
Scott B
SB
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. scott_hoyt@merck.com
London
Clare
C
Gorin
David
D
Wyvratt
Matthew J
MJ
Fisher
Michael H
MH
Abbadie
Catherine
C
Felix
John P
JP
Garcia
Maria L
ML
Li
Xiaohua
X
Lyons
Kathryn A
KA
McGowan
Erin
E
MacIntyre
D Euan
DE
Martin
William J
WJ
Priest
Birgit T
BT
Ritter
Amy
A
Smith
McHardy M
MM
Warren
Vivien A
VA
Williams
Brande S
BS
Kaczorowski
Gregory J
GJ
Parsons
William H
WH
D000818:Animals; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D015394:Molecular Structure; D062556:NAV1.7 Voltage-Gated Sodium Channel; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000145:classification* / Q000494:pharmacology* / Q000627:therapeutic use; D015222:Sodium Channels / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006575:Heterocyclic Compounds, 3-Ring; D062556:NAV1.7 Voltage-Gated Sodium Channel; C503480:Scn9a protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels