β-Lactam derivatives as enzyme inhibitors:: halogenated β-lactams and related compounds

Different modifications of the imine - acyl chloride reaction were used for the synthesis of 3-mono- and 3,3-dihalogenated 1,4-diaryl substituted beta-lactams. Furthermore, these beta-lactams were modified by halogen substitution either at the aryl at position 1 or at the aryl substituent at position 4, or at both positions. The influence of the halogen atoms on the reactivity of the beta-lactam ring, visible by the carbonyl frequence in their IR spectra, was studied. A selection of compounds was tested as inhibitors of the serin protease porcine pancreatic elastase. No simple correlation between IR frequence and biological activity was found. Finally, the base induced rearrangement of N-benzyl beta-lactams was used for the synthesis of 4,5-diaryl substituted pyrrolidinones.