Allene as an alternative functional group for drug design: effect of C--C multiple bonds conjugated with quinazolines on the inhibition of EGFR tyrosine kinase

ChemMedChem. 2008 Jul;3(7):1094-103. doi: 10.1002/cmdc.200800073.

Abstract

A series of allenic quinazolines were synthesized as receptor tyrosine kinase inhibitors by using a simple protocol for palladium-catalyzed allene transformation. Among the compounds synthesized, two allenic 4-anilinoquinazolines selectively suppressed epidermal growth factor receptor (EGFR) tyrosine kinase activity in vitro. According to immunoblot analysis, the allenic quinazolines inhibited the EGF-mediated phosphorylation of EGFR and its downstream kinases in A431 cells. Furthermore, one of these allenic quinazolines decreased the proliferation of A431 cells through the induction of cell-cycle arrest and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkadienes / chemistry
  • Alkadienes / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Catalysis
  • Cell Cycle / drug effects*
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Drug Design
  • ErbB Receptors / antagonists & inhibitors*
  • Humans
  • Palladium / chemistry
  • Phosphorylation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / pharmacology*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Alkadienes
  • Protein Kinase Inhibitors
  • Quinazolines
  • Palladium
  • ErbB Receptors