Abstract
The structural requirements of sulfonamide-based hydroxamic acid 1 for inhibition of macrophage metalloelastase (MME) were investigated. A short aliphatic group at the R2 position together with an aromatic group at the R3 position significantly improved the inhibitory activity. Compounds 32, 34, and 40 were the most potent inhibitors of MME with IC50 values between 5 and 6 nM.
MeSH terms
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Animals
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology
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Indicators and Reagents
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Kinetics
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Macrophages / enzymology
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Matrix Metalloproteinase 12
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Metalloendopeptidases / antagonists & inhibitors*
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Mice
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Molecular Structure
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
Substances
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Enzyme Inhibitors
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Hydroxamic Acids
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Indicators and Reagents
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Sulfonamides
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Metalloendopeptidases
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Matrix Metalloproteinase 12