title: The discovery of 2-amino-3,5-diarylbenzamide inhibitors of IKK-alpha and IKK-beta kinases.
abstract: A potent and selective series of 2-amino-3,5-diarylbenzamide inhibitors of IKK-alpha and IKK-beta is described. The most potent compounds are 8h, 8r and 8v, with IKK-beta inhibitory potencies of pIC(50) 7.0, 6.8 and 6.8, respectively. The series has excellent selectivity, both within the IKK family over IKK-epsilon, and across a wide variety of kinase assays. The potency of 8h in the IKK-beta enzyme assay translates to significant cellular activity (pIC(50) 5.7-6.1) in assays of functional and mechanistic relevance.
authors.affiliation: GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. John.A.Christopher@gsk.com
authors.forename: John A
authors.initials: JA
authors.lastname: Christopher
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Avitabile
authors.forename: Paul
authors.initials: P
authors.lastname: Bamborough
authors.forename: Aurelie C
authors.initials: AC
authors.lastname: Champigny
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Cutler
authors.forename: Susan L
authors.initials: SL
authors.lastname: Dyos
authors.forename: Ken G
authors.initials: KG
authors.lastname: Grace
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Kerns
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Kitson
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Mellor
authors.forename: James V
authors.initials: JV
authors.lastname: Morey
authors.forename: Mary A
authors.initials: MA
authors.lastname: Morse
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: O'Malley
authors.forename: Champa B
authors.initials: CB
authors.lastname: Patel
authors.forename: Nicholas
authors.initials: N
authors.lastname: Probst
authors.forename: William
authors.initials: W
authors.lastname: Rumsey
authors.forename: Clive A
authors.initials: CA
authors.lastname: Smith
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wilson
mesh_terms: D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D051550:I-kappa B Kinase