Abstract
A novel series of phosphonamide-based inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) was discovered by structural modification of tetrahydroisoquinoline derivative 1b, which was extremely weak inhibitor of TACE. (S)-Isomer at the phosphorus atom (7b) displayed potent inhibition for TACE, while selectivity sparing MMP-1, -3, and -9.
MeSH terms
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ADAM Proteins
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ADAM17 Protein
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Amides / chemistry*
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Amides / pharmacology*
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Binding Sites
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Drug Design
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Isomerism
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Matrix Metalloproteinase Inhibitors
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Matrix Metalloproteinases / metabolism
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Metalloendopeptidases / antagonists & inhibitors*
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Models, Molecular
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Organophosphonates / chemistry*
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Organophosphonates / pharmacology*
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Structure-Activity Relationship
Substances
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Amides
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Enzyme Inhibitors
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Matrix Metalloproteinase Inhibitors
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Organophosphonates
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ADAM Proteins
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Matrix Metalloproteinases
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Metalloendopeptidases
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ADAM17 Protein