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

Autor: Alexandra Testard, Cédric Logé, Olivier Lozach, Laurent Meijer, Mélina Blairvacq, Thierry Besson, Jean-Michel Robert, Valérie Thiéry
Přispěvatelé: Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Génie Protéique et Cellulaire (LGPC), Université de La Rochelle (ULR), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2008
Předmět:
Models
Molecular
Magnetic Resonance Spectroscopy
Spectrophotometry
Infrared
Stereochemistry
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
01 natural sciences
Chemical synthesis
Amidine
Glycogen Synthase Kinase 3
03 medical and health sciences
chemistry.chemical_compound
[CHIM.ANAL]Chemical Sciences/Analytical chemistry
Cyclin-dependent kinase
GSK-3
CDC2 Protein Kinase
Nitriles
Drug Discovery
Quinazoline
Enzyme Inhibitors
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Pharmacology
0303 health sciences
Cyclin-dependent kinase 1
biology
[CHIM.ORGA]Chemical Sciences/Organic chemistry
010405 organic chemistry
Chemistry
Organic Chemistry
[CHIM.CATA]Chemical Sciences/Catalysis
General Medicine
3. Good health
0104 chemical sciences
Biochemistry
Quinazolines
biology.protein
Tau-protein kinase
Zdroj: European Journal of Medicinal Chemistry
European Journal of Medicinal Chemistry, Elsevier, 2008, 43 (7), pp.1469-1477. ⟨10.1016/j.ejmech.2007.09.020⟩
ISSN: 0223-5234
1768-3254
DOI: 10.1016/j.ejmech.2007.09.020
Popis: 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.
Databáze: OpenAIRE
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