Synthesis and biological evaluation of crown ether fused quinazoline analogues as potent EGFR inhibitors

Bioorg Med Chem Lett. 2012 Oct 1;22(19):6301-5. doi: 10.1016/j.bmcl.2012.06.067. Epub 2012 Jun 28.

Abstract

Crown ether fused anilinoquinazoline analogues were synthesized as novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Representative compounds showed potent and selective EGFR inhibitory activities in an in vitro EGFR kinase assay and an EGFR-mediated intracellular tyrosine phosphorylation assay. The synthesis and preliminary biological, physical, and pharmacokinetic evaluation of these fused quinazoline compounds is reported.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Crown Ethers / chemistry*
  • Dose-Response Relationship, Drug
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology*
  • Quinazolines / administration & dosage
  • Quinazolines / chemical synthesis
  • Quinazolines / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Crown Ethers
  • Protein Kinase Inhibitors
  • Quinazolines
  • ErbB Receptors