Abstract
A series of novel 4-anilinoquinazoline derivatives (3a-3j) has been synthesized and evaluated as potential inhibitors for protein kinases implicated in Alzheimer's disease. Among all the synthesized compounds, compound 3e (N-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinazolin-4-amine) exhibited the most potent inhibitory activity against CLK1 and GSK-3α/β kinase with IC₅₀ values of 1.5 μM and 3 μM, respectively. Docking studies were performed to elucidate the binding mode of the compounds to the active site of CLK1 and GSK-3β. The results of our study suggest that compound 3e may serve as a valuable template for the design and development of dual inhibitors of CLK1 and GSK-3α/β enzymes with potential therapeutic application in Alzheimer's disease.
Keywords:
Anilino quinazolines; CLK1 kinase; Docking studies; Protein kinase inhibitor.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aniline Compounds / chemical synthesis
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Aniline Compounds / chemistry
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Aniline Compounds / pharmacology*
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Dose-Response Relationship, Drug
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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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Models, Molecular
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Protein-Tyrosine Kinases / metabolism
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Quinazolines / chemical synthesis
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Quinazolines / chemistry
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Quinazolines / pharmacology*
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Structure-Activity Relationship
Substances
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Aniline Compounds
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Protein Kinase Inhibitors
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Quinazolines
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Clk dual-specificity kinases
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Glycogen Synthase Kinase 3