1. N-Acyl and N-sulfonyloxazolidine-2,4-diones are pseudo-irreversible inhibitors of serine proteases.
- Author
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Santana AB, Lucas SD, Gonçalves LM, Correia HF, Cardote TA, Guedes RC, Iley J, and Moreira R
- Subjects
- Animals, Anti-Inflammatory Agents pharmacology, Cathepsin G antagonists & inhibitors, Cathepsin G metabolism, Humans, Kinetics, Leukocyte Elastase metabolism, Oxazolidinones pharmacology, Pancreatic Elastase metabolism, Serine Proteinase Inhibitors pharmacology, Structure-Activity Relationship, Swine, Anti-Inflammatory Agents chemical synthesis, Leukocyte Elastase antagonists & inhibitors, Oxazolidinones chemical synthesis, Pancreatic Elastase antagonists & inhibitors, Serine Proteinase Inhibitors chemical synthesis
- Abstract
The synthesis, inhibitory activity and mode of action of oxazolidine-2,4-diones against porcine pancreatic elastase, here used as a model for human neutrophil elastase, are reported. The nature of N-substitution at the oxazolidine-2,4-dione scaffold has large effect on the inhibitory potency against elastase. N-Acyl and N-sulfonyloxazolidine-2,4-diones emerged as potent pseudo-irreversible inhibitors, displaying high second-order rate constants for PPE inactivation. The title compounds were also shown to be potent inhibitors of human neutrophil elastase (HNE) and proteinase-3, and weak inhibitors of human cathepsin G. The results herein presented show that the oxazolidine-2,4-diones represent a new promising class of serine protease inhibitors., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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