title: Subtype-selective Na(v)1.8 sodium channel blockers: identification of potent, orally active nicotinamide derivatives.
abstract: A series of aryl-substituted nicotinamide derivatives with selective inhibitory activity against the Na(v)1.8 sodium channel is reported. Replacement of the furan nucleus and homologation of the anilide linker in subtype-selective blocker A-803467 (1) provided potent, selective derivatives with improved aqueous solubility and oral bioavailability. Representative compounds from this series displayed efficacy in rat models of inflammatory and neuropathic pain.
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. michael.e.kort@abbott.com
authors.forename: Michael E
authors.initials: ME
authors.lastname: Kort
authors.forename: Robert N
authors.initials: RN
authors.lastname: Atkinson
authors.forename: James B
authors.initials: JB
authors.lastname: Thomas
authors.forename: Irene
authors.initials: I
authors.lastname: Drizin
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Johnson
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Secrest
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gregg
authors.forename: Marc J C
authors.initials: MJ
authors.lastname: Scanio
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Hakeem
authors.forename: Mark A
authors.initials: MA
authors.lastname: Matulenko
authors.forename: Mark L
authors.initials: ML
authors.lastname: Chapman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Krambis
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Char-Chang
authors.initials: CC
authors.lastname: Shieh
authors.forename: XuFeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Gricelda
authors.initials: G
authors.lastname: Simler
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mikusa
authors.forename: Chengmin
authors.initials: C
authors.lastname: Zhong
authors.forename: Shailen
authors.initials: S
authors.lastname: Joshi
authors.forename: Prisca
authors.initials: P
authors.lastname: Honore
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Roeloffs
authors.forename: Stephen
authors.initials: S
authors.lastname: Werness
authors.forename: Brett
authors.initials: B
authors.lastname: Antonio
authors.forename: Kennan C
authors.initials: KC
authors.lastname: Marsh
authors.forename: Connie R
authors.initials: CR
authors.lastname: Faltynek
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Krafte
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
authors.forename: Brian E
authors.initials: BE
authors.lastname: Marron
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D009536:Niacinamide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D026941:Sodium Channel Blockers; D009536:Niacinamide