Abstract
We report the synthesis and in vitro activity of a series of novel pyrrolidinyl pyridones and pyrazinones as potent inhibitors of prolyl oligopeptidase (POP). Within this series, compound 39 was co-crystallized within the catalytic site of a human chimeric POP protein which provided a more detailed understanding of how these inhibitors interacted with the key residues within the catalytic pocket.
MeSH terms
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Brain / drug effects
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Brain / metabolism
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Combinatorial Chemistry Techniques
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Crystallography, X-Ray
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Drug Design
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Humans
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Molecular Conformation
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Molecular Structure
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Prolyl Oligopeptidases
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Pyridones / blood
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Pyridones / chemical synthesis*
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Pyridones / chemistry
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Pyridones / pharmacology*
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Pyrrolidines / blood
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / chemistry
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Pyrrolidines / pharmacology*
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Serine Endopeptidases / drug effects*
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Serine Proteinase Inhibitors / blood
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Serine Proteinase Inhibitors / chemical synthesis*
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Serine Proteinase Inhibitors / chemistry
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Serine Proteinase Inhibitors / pharmacology*
Substances
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Pyridones
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Pyrrolidines
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Serine Proteinase Inhibitors
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Serine Endopeptidases
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PREPL protein, human
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Prolyl Oligopeptidases