Abstract
A series of Nalpha-acyl-alpha-amino acid-(arylaminoethyl)amides were found to be potent and noncovalent cathepsin S inhibitors. Compound 20 possessed high cathepsin S affinity (Ki=3.3 nM) and showed excellent selectivity over cathepsin K, L, F, and V. Molecular modeling, design, synthesis, and in vitro activity are described.
MeSH terms
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Amides / chemical synthesis
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Amides / chemistry*
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Amination
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Binding Sites
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Cathepsin K
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Cathepsin L
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Cathepsins / antagonists & inhibitors*
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Cathepsins / chemistry
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Cathepsins / metabolism
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Cysteine Endopeptidases / chemistry
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Cysteine Endopeptidases / metabolism
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Drug Design*
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Ethanol / chemistry*
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Models, Molecular
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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Protein Structure, Tertiary
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Structure-Activity Relationship
Substances
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Amides
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Protease Inhibitors
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Ethanol
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Cathepsins
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Cysteine Endopeptidases
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Cathepsin L
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cathepsin S
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Cathepsin K