New carbon-linked azole oxazolidinones with improved potency and pharmacokinetics

Bioorg Med Chem Lett. 2007 Jan 15;17(2):337-40. doi: 10.1016/j.bmcl.2006.10.063. Epub 2006 Oct 26.

Abstract

Substitution of phenyl oxazolidinones with carbon-linked azoles resulted in the discovery of a new class of potent oxazolidinones that have excellent Gram-positive activity. In addition, replacement of the C-5 acetamide side chains with a 4-methyl triazole diminished monoamine oxidase activity. The synthesis and biological evaluation of these compounds are reported.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology*
  • Biological Availability
  • Colony Count, Microbial
  • Female
  • Gram-Positive Bacteria / drug effects
  • Half-Life
  • Humans
  • Liver / enzymology
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / pharmacology
  • Oxazolidinones / chemical synthesis*
  • Oxazolidinones / pharmacology*
  • Pneumococcal Infections / drug therapy
  • Pneumococcal Infections / microbiology
  • Rats
  • Streptococcus pneumoniae / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Monoamine Oxidase Inhibitors
  • Oxazolidinones