The discovery of 2-amino-3,5-diarylbenzamide inhibitors of IKK-alpha and IKK-beta kinases

  • Bioorg Med Chem Lett. 2007 Jul 15;17(14):3972-7. doi: 10.1016/j.bmcl.2007.04.088.
John A Christopher  1 ,  Barbara G Avitabile ,  Paul Bamborough ,  Aurelie C Champigny ,  Geoffrey J Cutler ,  Susan L Dyos ,  Ken G Grace ,  Jeffrey K Kerns ,  Jeremy D Kitson ,  Geoffrey W Mellor ,  James V Morey ,  Mary A Morse ,  Carolyn F O'Malley ,  Champa B Patel ,  Nicholas Probst ,  William Rumsey ,  Clive A Smith ,  Michael J Wilson
Affiliations
  • 1. GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. [email protected]
PMID: 17502144 DOI: 10.1016/j.bmcl.2007.04.088
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.

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