Synthesis and antibacterial activity of novel 3-O-carbamoyl derivatives of clarithromycin and 11,12-cyclic carbonate azithromycin

Eur J Med Chem. 2010 Mar;45(3):915-22. doi: 10.1016/j.ejmech.2009.11.032. Epub 2009 Nov 28.

Abstract

Two series of novel 3-O-carbamoyl derivatives of clarithromycin and 11,12-cyclic carbonate azithromycin were designed, synthesized and evaluated for their in vitro antibacterial activities. Compounds 4j and 4k were the most potent activity against erythromycin-susceptible Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, which were comparable to those of clarithromycin and azithromycin. Compounds 4d, 4h and 4i showed potent activity against erythromycin-resistant S. pneumoniae encoded by the mef gene and compounds 4h and 4i displayed greatly improved activity against erythromycin-resistant S. pneumoniae encoded by the erm gene. Compound 7c exhibited improved activity against erythromycin-resistant S. pneumoniae encoded by the erm and mef genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents* / chemical synthesis
  • Anti-Bacterial Agents* / pharmacology
  • Azithromycin / analogs & derivatives
  • Azithromycin / chemical synthesis*
  • Azithromycin / pharmacology*
  • Clarithromycin / analogs & derivatives
  • Clarithromycin / chemical synthesis*
  • Clarithromycin / pharmacology*
  • Drug Evaluation, Preclinical
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / drug effects*

Substances

  • Anti-Bacterial Agents
  • Azithromycin
  • Clarithromycin