Abstract
Dipeptide derivatives bearing various P2 residues and pyrrolidine derivatives as P1 mimics were evaluated in order to identify lead structures for the development of DPP8 and DPP9 inhibitors. Structure-activity-relationship data obtained in this way led to the preparation of a series of alpha-aminoacyl ((2S, 4S)-4-azido-2-cyanopyrrolidines). These compounds were shown to be nanomolar DPP8/9 inhibitors with modest overall selectivity toward DPP IV and DPP II.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Chemistry, Pharmaceutical / methods
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Dipeptidases / antagonists & inhibitors*
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Dipeptides / chemistry
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors*
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Lysine
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Models, Chemical
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Molecular Structure
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Nitriles / chemistry
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Peptides / chemistry
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Pyrrolidines / chemistry
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Structure-Activity Relationship
Substances
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Dipeptides
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Enzyme Inhibitors
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Nitriles
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Peptides
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Pyrrolidines
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Dipeptidases
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DPP9 protein, human
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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DPP8 protein, human
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Lysine