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.
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.
Logé
Cédric
C
Université de Nantes, Nantes Atlantique Universités, Biomolécules et Cibles Thérapeutiques, Département de Pharmacochimie, BioCiT, UPRES EA 1155, UFR Sciences Pharmaceutiques, Nantes Cedex 1, France. cedric.loge@univ-nantes.fr
Testard
Alexandra
A
Thiéry
Valérie
V
Lozach
Olivier
O
Blairvacq
Mélina
M
Robert
Jean-Michel
JM
Meijer
Laurent
L
Besson
Thierry
T
D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
C532280:9-oxo-thiazolo(5,4-f)quinazoline-2-carbonitrile; D004791:Enzyme Inhibitors; D009570:Nitriles; D011799:Quinazolines; D016203:CDC2 Protein Kinase; D038362:Glycogen Synthase Kinase 3