Design at the atomic level: generation of novel hybrid biaryloxazolidinones as promising new antibiotics

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6179-83. doi: 10.1016/j.bmcl.2008.10.014. Epub 2008 Oct 7.

Abstract

From the X-ray crystal structures of linezolid and the non-selective antibiotic sparsomycin, we have derived a new family of hybrid oxazolidinones. From this initial compound set we have developed a new biaryloxazolidinone scaffold that shows both potent antimicrobial activity as well as selective inhibition of ribosomal translation. The synthesis of these compounds is outlined.

MeSH terms

  • Acetamides / pharmacology
  • Administration, Oral
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Crystallography, X-Ray
  • Drug Design
  • Escherichia coli / drug effects
  • Haemophilus influenzae / drug effects
  • Linezolid
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Molecular Structure
  • Moraxella catarrhalis / drug effects
  • Oxazolidinones / chemical synthesis*
  • Oxazolidinones / chemistry
  • Oxazolidinones / pharmacology*
  • Protein Biosynthesis / drug effects
  • Sparsomycin / pharmacology
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Oxazolidinones
  • Sparsomycin
  • Linezolid