title: Synthesis of Thiazolo[5,4-f]quinazolin-9(8H)-ones as Multi-Target Directed Ligands of Ser/Thr Kinases.
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.
authors.affiliation: Normandie Univ; Uni Rouen; INSA; CNRS, COBRA, UMR 6014, 76000 Rouen, France. d.hedou@laposte.net.
authors.forename: Damien
authors.initials: D
authors.lastname: Hédou
authors.affiliation: Normandie Univ; Uni Rouen; INSA; CNRS, COBRA, UMR 6014, 76000 Rouen, France. juliengoorga@hotmail.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Godeau
authors.affiliation: Protein Phosphorylation &amp; Human Disease group, Station Biologique, 29680 Roscoff, France. Nadege.Loaec@univ-brest.fr.|Manros Therapeutics, Centre de Perharidy, 29680 Roscoff, France. Nadege.Loaec@univ-brest.fr.
authors.forename: Nadège
authors.initials: N
authors.lastname: Loaëc
authors.affiliation: Manros Therapeutics, Centre de Perharidy, 29680 Roscoff, France. meijer@manros-therapeutics.com.
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.affiliation: Normandie Univ; Uni Rouen; INSA; CNRS, COBRA, UMR 6014, 76000 Rouen, France. corinne.fruit@univ-rouen.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Fruit
authors.affiliation: Normandie Univ; Uni Rouen; INSA; CNRS, COBRA, UMR 6014, 76000 Rouen, France. thierry.besson@univ-rouen.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Besson
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D013552:Swine; D013844:Thiazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D008024:Ligands; D047428:Protein Kinase Inhibitors; D052999:Quinazolinones; D013844:Thiazoles; D017346:Protein Serine-Threonine 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