title: Discovery of a novel class of benzazepinone Na(v)1.7 blockers: potential treatments for neuropathic pain.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. scott_hoyt@merck.com
authors.forename: Scott B
authors.initials: SB
authors.lastname: Hoyt
authors.forename: Clare
authors.initials: C
authors.lastname: London
authors.forename: David
authors.initials: D
authors.lastname: Gorin
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wyvratt
authors.forename: Michael H
authors.initials: MH
authors.lastname: Fisher
authors.forename: Catherine
authors.initials: C
authors.lastname: Abbadie
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: Erin
authors.initials: E
authors.lastname: McGowan
authors.forename: D Euan
authors.initials: DE
authors.lastname: MacIntyre
authors.forename: William J
authors.initials: WJ
authors.lastname: Martin
authors.forename: Birgit T
authors.initials: BT
authors.lastname: Priest
authors.forename: Amy
authors.initials: A
authors.lastname: Ritter
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; 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
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D062556:NAV1.7 Voltage-Gated Sodium Channel; C503480:Scn9a protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels