Abstract
Since Alzheimer disease (AD) is a multifactorial disease, recent therapeutical approaches concentrate on the development of a multitargeting drug. Various protein kinases are known to be involved in the progression of AD. A first series of 3-ethoxycarbonyl-1-aza-9-oxafluorenes has been synthesized and biologically evaluated as AD-relevant protein kinase inhibitors. A concentration-dependent inhibition of important AD-relevant kinases has been characterized after the selectivity of kinase inhibition had been demonstrated. Structure-activity relationships of protein kinase inhibition are discussed and first multitargeting inhibitors have been identified.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / drug therapy
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Alzheimer Disease / enzymology*
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Animals
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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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Biological Assay
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CDC2 Protein Kinase / metabolism*
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Cyclin-Dependent Kinase 5 / metabolism*
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Drug Delivery Systems
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Drug Design*
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Drug Evaluation, Preclinical
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Enzyme Activation / drug effects
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Fluorenes / chemical synthesis
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Fluorenes / chemistry*
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Fluorenes / pharmacology*
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Glycogen Synthase Kinase 3 / metabolism*
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Glycogen Synthase Kinase 3 beta
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Humans
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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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Sf9 Cells
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Structure-Activity Relationship
Substances
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Aza Compounds
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Fluorenes
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Protein Kinase Inhibitors
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Cyclin-Dependent Kinase 5
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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CDC2 Protein Kinase
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Glycogen Synthase Kinase 3