1-Alkoxycarbonyl-3-halogenoazetidin-2-ones as elastase (PPE) inhibitors Original Research Article

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 (Ki ∼2–22 μM) than 3-chloroazetidinones (Ki ∼20–150 μM). The lipophilicity of the N-1 substituent appeared to exert a slightly positive effect.