title: 5-(1H-Benzimidazol-1-yl)-3-alkoxy-2-thiophenecarbonitriles as potent, selective, inhibitors of IKK-epsilon kinase.
abstract: The identification and hit-to-lead exploration of a novel, potent and selective series of substituted benzimidazole-thiophene carbonitrile inhibitors of IKK-epsilon kinase is described. Compound 12e was identified with an IKK-epsilon enzyme potency of pIC(50) 7.4, and has a highly encouraging wider selectivity profile, including selectivity within the IKK kinase family.
authors.affiliation: GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Bamborough
authors.forename: John A
authors.initials: JA
authors.lastname: Christopher
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Cutler
authors.forename: Marion C
authors.initials: MC
authors.lastname: Dickson
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Mellor
authors.forename: James V
authors.initials: JV
authors.lastname: Morey
authors.forename: Champa B
authors.initials: CB
authors.lastname: Patel
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Shewchuk
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D001562:Benzimidazoles; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D013876:Thiophenes; D051550:I-kappa B Kinase