Abstract
The discovery of a series of 6-(4-pyridyl)pyrimidin-4(3H)-ones derived from a hit compound with low molecular weight and sufficient chemical space is reported. Transformation of substituents led to subnanomolar potent inhibitors with in vivo tau phoshorylation lowering activity.
Keywords:
Alzheimer’s disease; Glycogen synthase kinase 3β; Hyperphoshorylation; Pyrimidin-4(3H)-one; Tau protein.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Binding Sites
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Enzyme Activation
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Glycogen Synthase Kinase 3 / antagonists & inhibitors*
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Molecular Docking Simulation
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Protein Binding / drug effects
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / metabolism
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Protein Kinase Inhibitors / pharmacology
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Protein Structure, Tertiary
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Pyrimidinones / chemical synthesis
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Pyrimidinones / chemistry*
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Pyrimidinones / metabolism
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Pyrimidinones / pharmacology
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Structure-Activity Relationship
Substances
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Protein Kinase Inhibitors
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Pyrimidinones
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3