Abstract
Cyclohexylglycine amides of various fluorinated pyrrolidines and azetidines were prepared and tested for activity against dipeptidyl peptidase IV and in vivo in the KK mouse model of type 2 diabetes. The tetrafluoropyrrolidide, cis-3,4-difluoropyrrolidide and the fluorinated azetidides displayed unexpectedly strong activity.
MeSH terms
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Adenosine Deaminase Inhibitors*
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Amides / chemical synthesis*
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Amides / pharmacology
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Animals
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Azetidines
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Diabetes Mellitus, Type 2 / drug therapy
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Dipeptidyl Peptidase 4
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Disease Models, Animal
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Fluorine
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Glucose Tolerance Test
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Glycoproteins / antagonists & inhibitors*
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Inhibitory Concentration 50
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Mice
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / pharmacology
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Serine Proteinase Inhibitors / chemical synthesis*
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Serine Proteinase Inhibitors / pharmacology
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Structure-Activity Relationship
Substances
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Adenosine Deaminase Inhibitors
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Amides
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Azetidines
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Glycoproteins
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Pyrrolidines
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Serine Proteinase Inhibitors
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Fluorine
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azetidine
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DPP4 protein, human
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Dipeptidyl Peptidase 4