title: N-Aryl azacycles as novel sodium channel blockers.
abstract: We have identified a new series of N-aryl azacycles as sodium channel blockers, which showed good potency on Nav1.7 in FLIPR-based and electrophysiological functional assays. Analogs from this series possessed selectivity over hERG, reasonable oral exposure in rat PK studies and are predicted to have limited CNS penetration.
authors.affiliation: Discovery Research, Purdue Pharma L.P., 6 Cedarbrook Drive, Cranbury, NJ 08512, United States.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lynch
authors.affiliation: Discovery Research, Purdue Pharma L.P., 6 Cedarbrook Drive, Cranbury, NJ 08512, United States. Electronic address: laykea.tafesse@pharma.com.
authors.forename: Laykea
authors.initials: L
authors.lastname: Tafesse
authors.affiliation: Discovery Research, Purdue Pharma L.P., 6 Cedarbrook Drive, Cranbury, NJ 08512, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Carlin
authors.affiliation: Discovery Research, Purdue Pharma L.P., 6 Cedarbrook Drive, Cranbury, NJ 08512, United States.
authors.forename: Parijat
authors.initials: P
authors.lastname: Ghatak
authors.affiliation: Discovery Research, Purdue Pharma L.P., 6 Cedarbrook Drive, Cranbury, NJ 08512, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Shao
authors.affiliation: Discovery Research, Purdue Pharma L.P., 6 Cedarbrook Drive, Cranbury, NJ 08512, United States.
authors.forename: Haissam
authors.initials: H
authors.lastname: Abdelhamid
authors.affiliation: Discovery Research, Purdue Pharma L.P., 6 Cedarbrook Drive, Cranbury, NJ 08512, United States.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Kyle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D061985:Madin Darby Canine Kidney Cells; D008969:Molecular Sequence Data; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000502:physiology*; D051381:Rats; D026941:Sodium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; C503480:Scn9a protein, rat; D026941:Sodium Channel Blockers
keywords: Azacycle; Na(v)1.7; Neuropathic pain; Sodium channel