5-(1H-Benzimidazol-1-yl)-3-alkoxy-2-thiophenecarbonitriles as potent, selective, inhibitors of IKK-epsilon kinase

Paul Bamborough; John A Christopher; Geoffrey J Cutler; Marion C Dickson; Geoffrey W Mellor; James V Morey; Champa B Patel; Lisa M Shewchuk

doi:10.1016/j.bmcl.2006.09.018

5-(1H-Benzimidazol-1-yl)-3-alkoxy-2-thiophenecarbonitriles as potent, selective, inhibitors of IKK-epsilon kinase

Bioorg Med Chem Lett. 2006 Dec 15;16(24):6236-40. doi: 10.1016/j.bmcl.2006.09.018. Epub 2006 Sep 25.

Authors

Paul Bamborough¹, John A Christopher, Geoffrey J Cutler, Marion C Dickson, Geoffrey W Mellor, James V Morey, Champa B Patel, Lisa M Shewchuk

Affiliation

¹ GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.

PMID: 16997559
DOI: 10.1016/j.bmcl.2006.09.018

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.

MeSH terms

Benzimidazoles / chemical synthesis*
Benzimidazoles / pharmacology*
Hydrogen Bonding
I-kappa B Kinase / antagonists & inhibitors*
Kinetics
Models, Molecular
Nitriles / chemical synthesis*
Nitriles / pharmacology*
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / pharmacology*
Thiophenes / chemical synthesis*
Thiophenes / chemistry
Thiophenes / pharmacology*
X-Ray Diffraction

Substances

Benzimidazoles
Nitriles
Protein Kinase Inhibitors
Thiophenes
I-kappa B Kinase