Abstract
The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multifunctional compounds to combat causes and symptoms of such neurodegeneration. To this aim we designed, synthesized, and tested a series of compounds by introducing halophenylalkylamidic functions on the scaffold of AP2238, which is a dual binding site acetylcholinesterase inhibitor. The inhibitory activity was successfully extended to the beta-site amyloid precursor protein cleavage enzyme, leading to the discovery of a potent inhibitor of this enzyme (3) and affording multifunctional compounds (2, 6, 8) for the treatment of AD.
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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Amides / chemical synthesis
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Amides / chemistry
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Amides / pharmacology
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Cholinesterase Inhibitors / chemical synthesis
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Cholinesterase Inhibitors / chemistry*
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Cholinesterase Inhibitors / pharmacology
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Coumarins / chemical synthesis
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Coumarins / chemistry
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Coumarins / pharmacology*
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Drug Design
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Humans
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Models, Molecular
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / chemistry*
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Protease Inhibitors / pharmacology
Substances
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Amides
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Cholinesterase Inhibitors
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Coumarins
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Protease Inhibitors
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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BACE1 protein, human