Abstract
A series of constrained ketone-based inhibitors has been developed that show low nanomolar Ki values. These ketone inhibitors showed promising activity towards cruzain, the cysteine protease implicated in Chagas' disease. This series of constrained inhibitors, which can be accessed quickly and efficiently using a solid-phase combinatorial strategy, should be applicable to other members of the cysteine protease class.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cathepsin B / antagonists & inhibitors
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Cathepsin L
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Cathepsins / antagonists & inhibitors
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Chemical Phenomena
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Chemistry, Physical
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Cysteine Endopeptidases
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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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Ketones / chemical synthesis
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Ketones / pharmacology
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Kinetics
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Molecular Conformation
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Protozoan Proteins / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Cysteine Proteinase Inhibitors
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Ketones
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Protozoan Proteins
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Cathepsins
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Cysteine Endopeptidases
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cruzain, Trypanosoma cruzi
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Cathepsin B
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CTSL protein, human
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Cathepsin L