Structure-based design of beta-lactamase inhibitors. 2. Synthesis and evaluation of bridged sulfactams and oxamazins

J Med Chem. 1998 Oct 8;41(21):3972-5. doi: 10.1021/jm9800245.

Abstract

A series of bridged monocyclic beta-lactams activated by various groups on the beta-lactam nitrogen (X = OCH2CO2H, OSO3H) has been synthesized and evaluated. Among them, the bridged sulfactams (X = OSO3H) were found to be effective beta-lactamase inhibitors. They inhibit both class A and class C beta-lactamases.

MeSH terms

  • Acetates / chemical synthesis*
  • Acetates / chemistry
  • Acetates / pharmacology
  • Ceftriaxone / pharmacology
  • Cephalosporins / pharmacology
  • Citrobacter freundii / drug effects
  • Citrobacter freundii / enzymology
  • Drug Design*
  • Drug Synergism
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Kinetics
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / enzymology
  • Sulfonic Acids / chemical synthesis*
  • Sulfonic Acids / chemistry
  • Sulfonic Acids / pharmacology
  • beta-Lactamase Inhibitors*
  • beta-Lactams / chemical synthesis*
  • beta-Lactams / chemistry
  • beta-Lactams / pharmacology

Substances

  • Acetates
  • Cephalosporins
  • Enzyme Inhibitors
  • Sulfonic Acids
  • beta-Lactamase Inhibitors
  • beta-Lactams
  • Ceftriaxone