Sulfonamide-based hydroxamic acids as potent inhibitors of mouse macrophage metalloelastase.
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.
Jeng
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Metabolic and Cardiovascular Diseases Research, Novartis Pharmaceuticals, Summit, NJ 07901, USA.
Chou
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Parker
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D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D007700:Kinetics; D008264:Macrophages / Q000201:enzymology; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007202:Indicators and Reagents; D013449:Sulfonamides; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12