Abstract
The synthesis, selectivity, rat pharmacokinetic profile, and drug metabolism profiles of a series of potent fluoroolefin-derived DPP-4 inhibitors (4) are reported. A radiolabeled fluoroolefin 33 was shown to possess a high propensity to form reactive metabolites, thus revealing a potential liability for this class of DPP-4 inhibitors.
MeSH terms
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Alkenes / chemical synthesis
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Alkenes / pharmacokinetics*
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Amides / chemistry*
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Animals
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Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis
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Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics*
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Hydrocarbons, Fluorinated / chemical synthesis
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Hydrocarbons, Fluorinated / pharmacokinetics*
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Hypoglycemic Agents / chemical synthesis
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Hypoglycemic Agents / pharmacokinetics*
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Microsomes, Liver / drug effects*
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Microsomes, Liver / pathology
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Models, Chemical
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Molecular Mimicry
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Rats
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Stereoisomerism
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Alkenes
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Amides
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Dipeptidyl-Peptidase IV Inhibitors
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Hydrocarbons, Fluorinated
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Hypoglycemic Agents