Abstract
A series of N(alpha)-2-benzoxazolyl-alpha-amino acid-(arylaminoethyl)amides were identified as potent, selective, and noncovalent inhibitors of cathepsin S. Structure-activity relationships including strategies for modulating the selectivities among cathepsins S, K, and L, and in vivo pharmacokinetics are discussed. A X-ray structure of compound 3 bound to the active site of cathepsin S is also reported.
MeSH terms
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Amides / chemistry
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Amides / pharmacology*
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Animals
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Cathepsins / antagonists & inhibitors*
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Cathepsins / chemistry
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Cathepsins / genetics
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Cathepsins / physiology
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Crystallography, X-Ray
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Heterocyclic Compounds / chemistry
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Heterocyclic Compounds / pharmacology*
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Mice
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Mice, Knockout
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Models, Molecular
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Rats
Substances
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Amides
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Enzyme Inhibitors
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Heterocyclic Compounds
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Cathepsins
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cathepsin S