Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as epidermal growth factor receptor (EGFR) kinase inhibitors

Bioorg Med Chem Lett. 2013 Oct 1;23(19):5385-8. doi: 10.1016/j.bmcl.2013.07.049. Epub 2013 Jul 31.

Abstract

We report herein the design and synthesis of novel azaspirocycle or azetidine substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and in vitro antitumor potency of these newly synthesized compounds against two lung cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6-azaspiro[3.4]octane substituent was found to possess higher EGFR inhibitory activities and similar antitumor potency comparing to the lead compound gefitinib with improved water solubility.

Keywords: Anilinoquinazolines; Anti-tumor agents; EGFR inhibitors; Four-membered heterocycles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology
  • Azetidines / chemical synthesis*
  • Azetidines / chemistry
  • Azetidines / pharmacology
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • ErbB Receptors / antagonists & inhibitors*
  • Gefitinib
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Molecular Structure
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology

Substances

  • Aza Compounds
  • Azetidines
  • Heterocyclic Compounds
  • Quinazolines
  • azetidine
  • ErbB Receptors
  • Gefitinib