Abstract
To improve the pharmacokinetics of a previously reported series of dipeptidyl nitrile cathepsin B inhibitors, the P(2)-P(3) amide group was replaced with an arylamine. Further optimization of this template resulted in highly potent and selective inhibitors with excellent oral availability.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Cathepsin B / antagonists & inhibitors*
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Dipeptides / administration & dosage
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Dipeptides / chemical synthesis
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Dipeptides / pharmacokinetics*
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Dipeptides / pharmacology
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacokinetics*
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Enzyme Inhibitors / pharmacology
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Models, Molecular
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Molecular Conformation
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Rats
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X-Ray Diffraction
Substances
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Dipeptides
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Enzyme Inhibitors
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Cathepsin B