1-Alkoxycarbonyl-3-halogenoazetidin-2-ones as elastase (PPE) inhibitors.
A series of 1-alkoxycarbonyl-3-halogenoazetidin-2-ones, designed as potential suicide inhibitors of serine proteases, has been synthesized and evaluated against porcine pancreatic elastase (PPE). All the compounds were transient inhibitors, their activity depending mainly on the nature of the halogen substituent: bromo- and iodo- derivatives are more active (K(i) approximately 2-22 microM) than 3-chloroazetidinones (K(i) approximately 20-150 microM). The lipophilicity of the N-1 substituent appeared to exert a slightly positive effect.
Gérard
Stéphane
S
Unité de Chimie Organique et Médicinale, Université catholique de Louvain, Bâtiment Lavoisier, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium.
Nollet
Gaëtan
G
Vande Put
Jennifer
J
Marchand-Brynaert
Jacqueline
J
D000818:Animals; D001384:Azetidines / Q000138:chemical synthesis / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013552:Swine
D001384:Azetidines; D015842:Serine Proteinase Inhibitors; D010196:Pancreatic Elastase