Synthesis and biological evaluation of 6-bromo-6-substituted penicillanic acid derivatives as beta-lactamase inhibitors

Farmaco. 2002 Aug;57(8):663-9. doi: 10.1016/s0014-827x(02)01261-2.

Abstract

The synthesis of a selected set of 6-bromopenicillanic acid derivatives with an additional C6 substituent is reported. All these substances were tested as inhibitors of class A and C beta-lactamase enzymes derived from Escherichia coli (TEM-1) and E. cloacae (P99). As 6-(1-hydroxyethyl) derivatives 4c and 6c were found to be weak beta-lactamase inhibitors, they were further investigated in combination with amoxicillin against a series of beta-lactamase-producing bacterial strains. Some structure-activity relationships are discussed.

MeSH terms

  • Drug Evaluation, Preclinical / methods
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / chemical synthesis*
  • Penicillanic Acid / chemistry
  • Penicillanic Acid / pharmacology*
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / metabolism

Substances

  • Enzyme Inhibitors
  • beta-Lactamase Inhibitors
  • brobactam
  • Penicillanic Acid
  • beta-Lactamases