Abstract
Inhibitors of dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes. A series of beta-aminoacyl-containing cyclic hydrazine derivatives were synthesized and evaluated as DPP-IV inhibitors. One member of this series, (R)-3-amino-1-(2-benzoyl-1,2-diazepan-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one (10f), showed potent in vitro activity, good selectivity and in vivo efficacy in mouse models. Also, the binding mode of compound 10f was determined by X-ray crystallography.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Chemistry, Pharmaceutical / methods*
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Crystallography, X-Ray
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Dipeptidyl-Peptidase IV Inhibitors*
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Glucagon-Like Peptide 1 / metabolism
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Hydrazines / chemical synthesis*
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Hydrazines / pharmacology
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Inhibitory Concentration 50
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Kinetics
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Mice
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Mice, Inbred C57BL
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Models, Chemical
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Molecular Conformation
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Protein Structure, Tertiary
Substances
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Dipeptidyl-Peptidase IV Inhibitors
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Enzyme Inhibitors
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Hydrazines
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hydrazine
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Glucagon-Like Peptide 1