Abstract
A novel 5-membered iminocyclitol derivative was found to be a potent and selective inhibitor of the glycoprotein-processing alpha-glucosidase with a Ki value of 53 nM. This compound was further derivatized to antiviral agents against Japanese encephalitis virus, dengue virus serotype 2 (DEN-2), human SARS coronavirus, and human beta-hexosaminidase (Ki = 2.6 nM), a new target for the development of osteoarthritis therapeutics.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiviral Agents / chemical synthesis
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Cell Line
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Cell Proliferation / drug effects
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Combinatorial Chemistry Techniques
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Dengue Virus / drug effects
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Encephalitis Virus, Japanese / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Glycoside Hydrolases / antagonists & inhibitors*
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Heterocyclic Compounds, 1-Ring / chemical synthesis
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Heterocyclic Compounds, 1-Ring / chemistry
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Heterocyclic Compounds, 1-Ring / pharmacology*
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Humans
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Imino Pyranoses* / chemical synthesis
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Imino Pyranoses* / chemistry
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Imino Pyranoses* / pharmacology
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Microbial Sensitivity Tests
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Models, Biological
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Models, Molecular
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Osteoarthritis / enzymology*
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Severe acute respiratory syndrome-related coronavirus / drug effects
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Structure-Activity Relationship
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Substrate Specificity
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beta-N-Acetylhexosaminidases / antagonists & inhibitors
Substances
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Antiviral Agents
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Enzyme Inhibitors
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Heterocyclic Compounds, 1-Ring
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Imino Pyranoses
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Glycoside Hydrolases
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beta-N-Acetylhexosaminidases