Abstract
Individuals with Down syndrome (DS) suffer from mental retardation. Overexpression and the resulting increased specific activity of Dyrk1A kinase located on chromosome 21 cause a learning and memory deficit in Dyrk1A transgenic mice. To search for therapeutic agents with Dyrk1A inhibition activity, previously we obtained HCD160 as a new hit compound for Dyrk1A inhibition. In the present study, we synthesized 34 HCD160 derivatives to investigate the quantitative structure-activity relationship (QSAR). This analysis could provide important information for novel drug discovery for treatment of DS related learning and memory deficits.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding, Competitive / drug effects
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Dyrk Kinases
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Mice
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Phosphorylation / drug effects
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Phosphorylation / physiology
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Protein Binding / drug effects
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / metabolism
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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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Pyrazoles / chemistry*
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Pyrazoles / metabolism
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Pyrazoles / pharmacology
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Quantitative Structure-Activity Relationship*
Substances
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Protein Kinase Inhibitors
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Pyrazoles
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pyrazolidine-3,5-dione
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases