Synthesis, initial SAR and biological evaluation of 1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine derived inhibitors of IkappaB kinase

Bioorg Med Chem Lett. 2009 May 15;19(10):2646-9. doi: 10.1016/j.bmcl.2009.03.159. Epub 2009 Apr 5.

Abstract

A new series of tricyclic-based inhibitors of IKK have been derived from an earlier lead compound. The synthesis and structure-activity relationships (SAR) are described. Compound 4k inhibited TNF production in rats stimulated with LPS.

MeSH terms

  • Animals
  • I-kappa B Kinase / antagonists & inhibitors*
  • I-kappa B Kinase / metabolism
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Lipopolysaccharides / pharmacology
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Rats
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Imidazoles
  • Lipopolysaccharides
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Tumor Necrosis Factor-alpha
  • I-kappa B Kinase