Synthesis and biological evaluation of 4-amino derivatives of benzimidazoquinoxaline, benzimidazoquinoline, and benzopyrazoloquinazoline as potent IKK inhibitors

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1233-7. doi: 10.1016/j.bmcl.2006.12.017. Epub 2006 Dec 9.

Abstract

We have recently identified BMS-345541 (1) as a highly selective and potent inhibitor of IKK-2 (IC50 = 0.30 microM), which however was considerably less potent against IKK-1 (IC50 = 4.0 microM). In order to further explore the SAR around the imidazoquinoxaline tricyclic structure of 1, we prepared a series of tetracyclic analogues (7, 13, and 18). The synthesis and biological activities of these potent IKK inhibitors are described.

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / pharmacology
  • Cell Line
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Humans
  • I-kappa B Kinase / antagonists & inhibitors*
  • Inhibitory Concentration 50
  • Quinazolines / chemical synthesis
  • Quinazolines / pharmacology
  • Quinolines / chemical synthesis
  • Quinolines / pharmacology
  • Quinoxalines / chemical synthesis
  • Quinoxalines / pharmacology
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Benzimidazoles
  • Heterocyclic Compounds, 4 or More Rings
  • Quinazolines
  • Quinolines
  • Quinoxalines
  • I-kappa B Kinase