Synthesis of Thiazolo[5,4-f]quinazolin-9(8H)-ones as Multi-Target Directed Ligands of Ser/Thr Kinases

Molecules. 2016 Apr 30;21(5):578. doi: 10.3390/molecules21050578.

Abstract

A library of thirty novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives belonging to four series designated as 12, 13, 14 and 15 was efficiently prepared, helped by microwave-assisted technology when required. The efficient multistep synthesis of methyl 6-amino-2-cyano- benzo[d]thiazole-7-carboxylate (1) has been reinvestigated and performed on a multigram scale. The inhibitory potency of the final products against five kinases involved in Alzheimer's disease was evaluated. This study demonstrates that some molecules of the 12 and 13 series described in this paper are particularly promising for the development of new multi-target inhibitors of kinases.

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

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Animals
  • Humans
  • Ligands
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein-Serine-Threonine Kinases / metabolism
  • Quinazolinones / chemical synthesis*
  • Quinazolinones / metabolism
  • Quinazolinones / therapeutic use
  • Swine
  • Thiazoles / chemical synthesis*
  • Thiazoles / metabolism
  • Thiazoles / therapeutic use

Substances

  • Ligands
  • Protein Kinase Inhibitors
  • Quinazolinones
  • Thiazoles
  • Protein-Serine-Threonine Kinases