Synthesis and antibacterial activity of novel 6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-4-oxoquinoline-3-carboxylic acids bearing cyclopropane-fused 2-amino-8-azabicyclo[4.3.0]nonan-8-yl substituents at the C-7 position

Bioorg Med Chem Lett. 2004 Oct 18;14(20):5193-8. doi: 10.1016/j.bmcl.2004.07.064.

Abstract

A series of novel 6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-4-oxoquinoline-3-carboxylic acids bearing cyclopropane-fused 2-amino-8-azabicyclo[4.3.0]nonan-8-yl substituents at the C-7 position were synthesized to obtain potent drugs for the treatment of Gram-positive infections. Some compounds exhibited excellent antibacterial activity, and potent inhibitory activity against bacterial DNA topoisomerase IV. In addition, some of the potent compounds showed reduced inhibitory activity against human DNA topoisomerase II compared with the corresponding noncyclopropane-fused compounds.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology
  • DNA Topoisomerase IV / antagonists & inhibitors
  • Gram-Positive Bacteria / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors

Substances

  • Anti-Infective Agents
  • Cyclopropanes
  • Quinolones
  • Topoisomerase II Inhibitors
  • DNA Topoisomerase IV