Design and synthesis of a series of novel bisquinazoline glycosides as epidermal growth factor receptor inhibitors

Chem Biol Drug Des. 2011 Dec;78(6):1006-13. doi: 10.1111/j.1747-0285.2011.01209.x. Epub 2011 Sep 29.

Abstract

A new series of potential epidermal growth factor receptor inhibitors possessing bisquinazoline and saccharide moieties were designed and synthesized. The biological results demonstrated that the synthetic derivatives significantly inhibited epidermal growth factor receptor enzymatic activity in vitro. Of them, compound 14b showed the highest inhibitory rate toward epidermal growth factor receptor protein tyrosine kinase (81.36%) at a concentration of 1 μM. Further molecular simulation predicted that 14b offered its saccharide moieties hydrogen bonding to ATP-binding pocket.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Binding Sites
  • ErbB Receptors / antagonists & inhibitors*
  • Glycosides / chemistry
  • Phenyl Ethers / chemical synthesis*
  • Phenyl Ethers / chemistry
  • Phenyl Ethers / pharmacology*
  • Phosphorylation
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 6,6'-(2,2'-(4,4'-(4,4'-oxybis(4,1-phenylene)bis(azanediyl))bis(7-methoxyquinazoline-6,4-diyl))bis(oxy)bis(ethane-2,1-diyl))bis(oxy)bis(2-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol)
  • Glycosides
  • Phenyl Ethers
  • Protein Kinase Inhibitors
  • Quinazolines
  • Adenosine Triphosphate
  • ErbB Receptors