N-Aryl 3-halogenated azetidin-2-ones and benzocarbacephems, inhibitors of .beta.-lactamases

Abstract

N-(3-Carboxy-6-methylphenyl)-3-fluoroazetidin-2-one and a series of related N-aryl-3-halo- and -3,3-dihaloazetidinones 3, in which the halo substituent is a fluorine or a bromine atom, were prepared by using the Wasserman procedure of cyclization of beta-bromopropionamides as a key step. Their affinities for the TEM-1 beta-lactamase were determined and compared with those of a series of tricyclic azetidinones, the benzocarbacephems 2, and known beta-lactamase inhibitors. The beta-lactams 2 and 3 behave as competitive inhibitors and not as substrates of the enzyme; neither halogen substitution (series 3) nor ring strain (series 2) induces enzymatic hydrolysis.