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. Epub 2007 Apr 29.

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.

MeSH terms

  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hydrogen Bonding
  • I-kappa B Kinase / antagonists & inhibitors*
  • Models, Molecular

Substances

  • Benzamides
  • Enzyme Inhibitors
  • I-kappa B Kinase