Abstract
New pyrido[3,4-g]quinazoline derivatives were prepared and evaluated for their inhibitory potency toward 5 protein kinases (CLK1, DYRK1A, GSK3, CDK5, CK1). A related pyrido[4,3-h]quinazoline scaffold with an angular structure was also synthesized and its potency against the same protein kinase panel was compared to the analogous pyrido[3,4-g]quinazoline. Best results were obtained for 10-nitropyrido[3,4-g]quinazoline 4 toward CLK1 with nanomolar activities.
Keywords:
CLK1; Protein kinase inhibition; Pyrido[3,4-g]quinazolines; Pyrido[4,3-h]quinazoline.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cyclin-Dependent Kinase 5 / antagonists & inhibitors
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Cyclin-Dependent Kinase 5 / metabolism
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Glycogen Synthase Kinase 3 / antagonists & inhibitors
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Glycogen Synthase Kinase 3 / metabolism
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Humans
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Molecular Docking Simulation
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / metabolism
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Protein Kinases / chemistry
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Pyridines / chemistry*
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Quinazolines / chemistry*
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Quinazolines / metabolism
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Structure-Activity Relationship
Substances
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Protein Kinase Inhibitors
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Pyridines
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Quinazolines
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Protein Kinases
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Clk dual-specificity kinases
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Protein-Tyrosine Kinases
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Cyclin-Dependent Kinase 5
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Protein Serine-Threonine Kinases
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Glycogen Synthase Kinase 3