Abstract
Polyhydroxylated quinolizidines bearing a hydroxymethyl group at the ring junction were synthesized from a readily available l-sorbose-derived ketonitrone. Evaluated as glycoside hydrolase inhibitors, these quinolizidines revealed to be potent and selective α-glucosidase inhibitors. Quinolizidine 9a is the first quinolizidine-scaffolded iminosugar exhibiting nanomolar inhibition of a glycoenzyme.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Dose-Response Relationship, Drug
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Glycoside Hydrolase Inhibitors / chemical synthesis
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Glycoside Hydrolase Inhibitors / chemistry
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Glycoside Hydrolase Inhibitors / pharmacology*
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Humans
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Hydroxylation
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Imino Sugars / chemistry
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Imino Sugars / pharmacology*
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Molecular Structure
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Quinolizidines / chemistry
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Quinolizidines / pharmacology*
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Structure-Activity Relationship
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alpha-Glucosidases / metabolism*
Substances
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Glycoside Hydrolase Inhibitors
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Imino Sugars
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Quinolizidines
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alpha-Glucosidases