Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents

Bioorg Med Chem Lett. 2002 Oct 21;12(20):2893-7. doi: 10.1016/s0960-894x(02)00598-x.

Abstract

The syntheses and biological evaluations of 4-anilinoquinoline-3-carbonitrile analogues of the three clinical lead 4-anilinoquinazolines Iressa, Tarceva, and CI-1033 are described. The EGFR and HER-2 kinase inhibitory activities and the cell growth inhibition of the two series are compared with each other and with the clinical lead EKB-569. Similar activities are observed between these two series.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cyclization
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • ErbB Receptors / antagonists & inhibitors*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Conformation
  • Nitriles / chemical synthesis*
  • Nitriles / pharmacology*
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology*
  • Receptor, ErbB-2 / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Nitriles
  • Quinolines
  • ErbB Receptors
  • Receptor, ErbB-2