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

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

Affiliation

  • 1 GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. John.A.Christopher@gsk.com
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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