Novel 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitrile derivatives as dual cyclin-dependent kinase 1 (CDK1)/glycogen synthase kinase-3 (GSK-3) inhibitors: synthesis, biological evaluation and molecular modeling studies

Eur J Med Chem. 2008 Jul;43(7):1469-77. doi: 10.1016/j.ejmech.2007.09.020. Epub 2007 Sep 29.


Continuous efforts in microwave-assisted synthesis and the structure-activity relationships' (SARs) studies of novel modified 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitriles, allowed identification of new amidine and imidate derivatives as potent and dual CDK1/GSK-3 inhibitors. Combination of lead optimization and molecular modeling studies allowed identification of a dual CDK1/GSK-3 inhibitor (compound 13d) with submicromolar values.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC2 Protein Kinase / antagonists & inhibitors*
  • Enzyme Inhibitors / pharmacology*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular*
  • Nitriles / chemical synthesis*
  • Nitriles / pharmacology*
  • Quinazolines / chemical synthesis*
  • Quinazolines / pharmacology*
  • Spectrophotometry, Infrared


  • 9-oxo-thiazolo(5,4-f)quinazoline-2-carbonitrile
  • Enzyme Inhibitors
  • Nitriles
  • Quinazolines
  • CDC2 Protein Kinase
  • Glycogen Synthase Kinase 3