Development of Kinase Inhibitors via Metal-Catalyzed C⁻H Arylation of 8-Alkyl-thiazolo[5,4- f]-quinazolin-9-ones Designed by Fragment-Growing Studies

Molecules. 2018 Aug 29;23(9):2181. doi: 10.3390/molecules23092181.


Efficient metal catalyzed C⁻H arylation of 8-alkyl-thiazolo[5,4-f]-quinazolin-9-ones was explored for SAR studies. Application of this powerful chemical tool at the last stage of the synthesis of kinase inhibitors allowed the synthesis of arrays of molecules inspired by fragment-growing studies generated by molecular modeling calculations. Among the potentially active compounds designed through this strategy, FC162 (4c) exhibits nanomolar IC50 values against some kinases, and is the best candidate for the development as a DYRK kinase inhibitor.

Keywords: CDK5; CK1; CLK1; C–H arylation; DYRK1A; GSK-3; microwave-assisted synthesis; protein kinases; thiazolo[5,4-f]quinazolin-9(8H)-ones.

MeSH terms

  • Microwaves
  • Models, Molecular
  • Molecular Docking Simulation
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Structure-Activity Relationship


  • Protein Kinase Inhibitors
  • Quinazolines
  • Dyrk kinase
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases