Abstract
A series of coumarin types MMP inhibitors were designed based on gelastatin hydroxamates (1) and evaluated for TACE, cellular TNF-alpha, and NO inhibitory activities. Among them, compounds 9b had potent inhibitory activities in enzymatic and cellular assays and good selectivity to MMP-2 and MMP-9. Further investigation of 9b will be carried out for its efficacy in RA animal model system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADAM Proteins / antagonists & inhibitors
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ADAM17 Protein
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Coumarins*
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Hydroxamic Acids
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Matrix Metalloproteinase Inhibitors
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Metalloendopeptidases / antagonists & inhibitors*
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Nitric Oxide / antagonists & inhibitors
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / pharmacology
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
Substances
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Coumarins
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Hydroxamic Acids
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Matrix Metalloproteinase Inhibitors
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Protease Inhibitors
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Tumor Necrosis Factor-alpha
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Nitric Oxide
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ADAM Proteins
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Metalloendopeptidases
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ADAM17 Protein