Abstract
The synthesis, SAR, binding affinities and pharmacokinetic profiles are described for a series of cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors discovered by high throughput screening. Compounds show high levels of ex vivo target engagement in mouse plasma 20 h post oral dose.
Keywords:
Inhibitor; Obesity; PrCP; Prolylcarboxypeptidase; Serine protease.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Carboxypeptidases / antagonists & inhibitors*
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Cyclohexanes / chemistry*
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Cyclohexanes / pharmacokinetics
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Cyclohexanes / pharmacology*
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Drug Discovery
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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Male
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Mice
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Mice, Inbred C57BL
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Molecular Structure
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Obesity / drug therapy
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Structure-Activity Relationship
Substances
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Cyclohexanes
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Enzyme Inhibitors
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Carboxypeptidases
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lysosomal Pro-X carboxypeptidase