N-Aryl 3-halogenated azetidin-2-ones and benzocarbacephems, inhibitors of .beta.-lactamases
- 1 February 1988
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 31 (2) , 370-374
- https://doi.org/10.1021/jm00397a018
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.This publication has 1 reference indexed in Scilit:
- Substituent effects on reactivity and spectral parameters of cephalosporinsJournal of Medicinal Chemistry, 1984