Abstract
Nonpeptidic, selective, and potent cathepsin S inhibitors were derived from an in-house pyrrolopyrimidine cathepsin K inhibitor by modification of the P2 and P3 moieties. The pyrrolopyrimidine-based inhibitors show nanomolar inhibition of cathepsin S with over 100-fold selectivity against other cysteine proteases, including cathepsin K and L. Some of the inhibitors showed cellular activities in mouse splenocytes as well as oral bioavailabilities in rats.
MeSH terms
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Biological Availability
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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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Chemistry, Pharmaceutical
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Cysteine Endopeptidases / chemical synthesis*
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Cysteine Endopeptidases / chemistry
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Cysteine Proteinase Inhibitors / chemical synthesis*
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Cysteine Proteinase Inhibitors / pharmacology
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Drug Design
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Humans
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Inhibitory Concentration 50
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Models, Chemical
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Molecular Conformation
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Molecular Structure
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Pyridines / chemistry
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Structure-Activity Relationship
Substances
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Cysteine Proteinase Inhibitors
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Pyridines
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Cathepsins
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Cysteine Endopeptidases
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CTSL protein, human
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Cathepsin L
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Ctsl protein, mouse
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Ctsl protein, rat
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cathepsin S
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CTSK protein, human
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Cathepsin K
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Ctsk protein, mouse
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Ctsk protein, rat