Abstract
In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.
MeSH terms
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Animals
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Diabetes Mellitus, Type 2 / drug therapy*
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Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis
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Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics
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Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
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Dipeptidyl-Peptidase IV Inhibitors / toxicity
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Heterocyclic Compounds, 2-Ring / chemical synthesis
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Heterocyclic Compounds, 2-Ring / pharmacokinetics
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Heterocyclic Compounds, 2-Ring / pharmacology*
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Heterocyclic Compounds, 2-Ring / toxicity
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Humans
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Hypoglycemic Agents / chemical synthesis
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Hypoglycemic Agents / pharmacokinetics
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Hypoglycemic Agents / pharmacology*
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Hypoglycemic Agents / toxicity
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Pyrans / chemical synthesis
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Pyrans / pharmacokinetics
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Pyrans / pharmacology*
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Pyrans / toxicity
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Structure-Activity Relationship
Substances
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2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine
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Dipeptidyl-Peptidase IV Inhibitors
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Heterocyclic Compounds, 2-Ring
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Hypoglycemic Agents
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Pyrans