N-aryl 3-halogenated azetidin-2-ones and benzocarbacephems, inhibitors of beta-lactamases.
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.
Joyeau
R
R
CNRS-CERCOA, Thiais, France.
Molines
H
H
Labia
R
R
Wakselman
M
M
D001384:Azetidines / Q000494:pharmacology*; D001385:Azetines / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors
D001384:Azetidines; D001385:Azetines; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors