Abstract
We have identified a new class of chymase inhibitor through a substituent analysis of MWP00965, which we previously discovered by in silico screening. TY-51076 (7) showed high potency (IC(50)=56 nM) and excellent selectivity for chymase compared to chymotrypsin and cathepsin G (>400-fold). The synthesis and structure-activity relationship of this class are described.
MeSH terms
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Chymases
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Drug Design
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Humans
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / pharmacology*
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Serine Endopeptidases / drug effects
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Serine Endopeptidases / metabolism*
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / pharmacology*
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Thiophenes / chemical synthesis
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Thiophenes / pharmacology
Substances
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Protease Inhibitors
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Sulfonamides
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Thiophenes
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benzothiophene
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Serine Endopeptidases
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Chymases