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

Damien Hédou (1) , Julien Godeau (1) , N. Loaëc (2, 3) , L. Meijer (3) , Corinne Fruit (1) , Thierry Besson (1)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
2 P3H - Phophorylation de protéines et Pathologies Humaines
3 ManRos Therapeutics

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

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

Domaines: Chimie

Damien Hédou, Julien Godeau, N. Loaëc, L. Meijer, Corinne Fruit, et al.. Synthesis of Thiazolo[5,4-f]quinazolin-9(8H)-ones as Multi-Target Directed Ligands of Ser/Thr Kinases. Molecules, 2016, 21 (5), pp.578. ⟨10.3390/molecules21050578⟩. ⟨hal-02046213⟩