Structure-activity relations of 4-fluoromethyl monobactams

J Antimicrob Chemother. 1987 Jun;19(6):753-60. doi: 10.1093/jac/19.6.753.

Abstract

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.

MeSH terms

  • Bacteria / drug effects
  • Hydrolysis
  • Monobactams / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • beta-Lactamases / pharmacology

Substances

  • Monobactams
  • beta-Lactamases