5-(1H-Benzimidazol-1-yl)-3-alkoxy-2-thiophenecarbonitriles as potent, selective, inhibitors of IKK-epsilon kinase.
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.
Bamborough
Paul
P
GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Christopher
John A
JA
Cutler
Geoffrey J
GJ
Dickson
Marion C
MC
Mellor
Geoffrey W
GW
Morey
James V
JV
Patel
Champa B
CB
Shewchuk
Lisa M
LM
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
D001562:Benzimidazoles; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D013876:Thiophenes; D051550:I-kappa B Kinase