Abstract
A series of 7-azaindazolyl-indolyl-maleimides were designed, synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited potent activity against GSK-3β. Among them, compounds 17a, 17b, 17g, 17i, 29a and 30 significantly reduced Aβ-induced Tau hyperphosphorylation, showin;g the inhibition of GSK-3β at the cell level. Preliminary structure-activity relationships were discussed based on the experimental data obtained.
Keywords:
7-Azaindazolyl-indolyl-maleimides; Cellular activity; Enzymatic activity; GSK-3β inhibitors.
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Aza Compounds / chemical synthesis
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Aza Compounds / chemistry
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Aza Compounds / pharmacology
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Blotting, Western
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Cell Line, Tumor
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Drug Design*
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Enzyme Activation / drug effects
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Glycogen Synthase Kinase 3 / antagonists & inhibitors*
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry
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Indoles / pharmacology
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Inhibitory Concentration 50
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Maleimides* / chemical synthesis
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Maleimides* / chemistry
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Maleimides* / pharmacology
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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
Substances
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Aza Compounds
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Indoles
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Maleimides
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Protein Kinase Inhibitors
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Glycogen Synthase Kinase 3