Abstract
We report a novel series of noncovalent inhibitors of cathepsin S. The synthesis of the peptidomimetic scaffold is described and structure-activity relationships of P3, P1, and P1' subunits are discussed. Lead optimization to a non-peptidic scaffold has resulted in a new class of potent, highly selective, and orally bioavailable cathepsin S inhibitors.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Carbamates / chemical synthesis*
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Carbamates / pharmacokinetics
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Carbamates / pharmacology*
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Cathepsins / antagonists & inhibitors*
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Humans
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Male
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Molecular Mimicry
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Oligopeptides / chemical synthesis*
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Oligopeptides / pharmacology
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / pharmacokinetics
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Protease Inhibitors / pharmacology
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Rats
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Rats, Wistar
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Structure-Activity Relationship
Substances
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Carbamates
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Oligopeptides
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Protease Inhibitors
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Cathepsins
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cathepsin S