title: Discovery of potent and use-dependent sodium channel blockers for treatment of chronic pain.
abstract: A new series of voltage-gated sodium channel blockers with potential for treatment of chronic pain is reported. Systematic structure-activity relationship studies, starting with compound 1, led to identification of potent analogs that displayed use-dependent block of sodium channels, were efficacious in pain models in vivo, and most importantly, were devoid of activity against the cardiac potassium channel hERG.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. jun_liang@merck.com
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Brochu
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Cohen
authors.forename: Ivy E
authors.initials: IE
authors.lastname: Dick
authors.forename: John P
authors.initials: JP
authors.lastname: Felix
authors.forename: Michael H
authors.initials: MH
authors.lastname: Fisher
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kaczorowski
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: Peter T
authors.initials: PT
authors.lastname: Meinke
authors.forename: Birgit T
authors.initials: BT
authors.lastname: Priest
authors.forename: William A
authors.initials: WA
authors.lastname: Schmalhofer
authors.forename: McHardy M
authors.initials: MM
authors.lastname: Smith
authors.forename: Jason W
authors.initials: JW
authors.lastname: Tarpley
authors.forename: Brande S
authors.initials: BS
authors.lastname: Williams
authors.forename: William J
authors.initials: WJ
authors.lastname: Martin
authors.forename: William H
authors.initials: WH
authors.lastname: Parsons
mesh_terms: D002908:Chronic Disease; D006801:Humans; D008968:Molecular Conformation; D015335:Molecular Probes; D010146:Pain / Q000188:drug therapy*; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D015335:Molecular Probes; D026941:Sodium Channel Blockers