Abstract
For a series of beta-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes.
MeSH terms
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Amides / antagonists & inhibitors
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Amides / chemistry*
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Aminobutyrates / chemistry*
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Caco-2 Cells
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Cell Line, Tumor
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Chemistry, Pharmaceutical
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Diabetes Mellitus, Type 2 / drug therapy
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Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
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Drug Design
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Humans
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Hypoglycemic Agents / antagonists & inhibitors
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Hypoglycemic Agents / therapeutic use
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Protease Inhibitors / pharmacokinetics
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Protease Inhibitors / pharmacology
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Sodium Channels / metabolism
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Structure-Activity Relationship*
Substances
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Amides
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Aminobutyrates
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Dipeptidyl-Peptidase IV Inhibitors
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Hypoglycemic Agents
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Protease Inhibitors
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Sodium Channels
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2-amino-4-phenylbutyric acid