243143-32-0Relevant academic research and scientific papers
1-Alkoxycarbonyl-3-halogenoazetidin-2-ones as elastase (PPE) inhibitors
Gerard, Stephane,Nollet, Gaetan,Vande Put, Jennifer,Marchand-Brynaert, Jacqueline
, p. 3955 - 3964 (2007/10/03)
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.
1-Alkoxycarbonyl-3-bromoazetidin-2-ones as potential elastase inhibitors
Beauve, Cecile,Tjoens, Gregory,Touillaux, Roland,Lamotte-Brasseur, Josette,Marchand-Brynaert, Jacqueline,Fastrez, Jacques
, p. 1441 - 1447 (2007/10/03)
Three 1-alkoxycarbonyl-3-bromoazetidin-2-ones have been prepared by reaction of (3S)-3-(tert-butoxycarbonyl)amino-azetidin-2-one with benzyl, trichloroethyl, and trifluoroethyl chloroformates followed by tBoc deprotection, diazotation of the exocyclic amino function and its substitution with potassium bromide. The 3-bromoazetidin-2-ones were obtained as racemic mixtures. Their hydroxide-catalyzed hydrolysis exclusively affords ring-opening products. Porcine pancreatic elastase (PPE) catalyzes the same reaction stereospecifically. Model building suggests that it is the (R) isomer that is enzymatically hydrolysed. The PPE-catalyzed hydrolysis is characterised by low k(cat) and K(m) values. Accordingly, these compounds behave as transient inhibitors of the enzyme.
