Structure-activity relations of 4-fluoromethyl monobactams.
New monobactam compounds with fluoromethyl side chains at the 4-position were synthesized. These compounds showed strong antibacterial activity against Gram-negative bacteria including Pseudomonas aeruginosa and good stability to various beta-lactamases. The effect of replacement of the 1-carboxy-1-methylethoxyimino residue of aztreonam with various substituted groups, and of the configuration of the 3- and 4-position were examined. Substitution of a carboxycyclopropoxy group in the oxyimino moiety effected the most potent antibacterial activity. The cis congeners were not hydrolysed by any types of beta-lactamases including the oxyiminocephalosporin hydrolysing enzyme. Introduction of a fluorine atom in the methyl group at the 4-position increased the beta-lactamase stability of monobactams.
D001419:Bacteria / Q000187:drug effects; D006868:Hydrolysis; D008997:Monobactams / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000494:pharmacology
D008997:Monobactams; D001618:beta-Lactamases