Synthesis and antibacterial activities of new quinolone derivatives utilizing 1-azabicyclo[1.1.0]butane

Bioorg Med Chem Lett. 2007 Feb 15;17(4):942-5. doi: 10.1016/j.bmcl.2006.11.048. Epub 2006 Nov 18.

Abstract

The ring-opening reactions of 1-azabicyclo[1.1.0]butane 3 with thiols 6a-f gave 3-sulfenylazetidine derivatives 7a-f in 50-92% yields. Treatment of 3 with aromatic amines 11a-e and dibenzylamine 11f in the presence of Mg(ClO(4))(2) afforded the corresponding 3-aminoazetidine derivatives 12a-f in 24-53% yields. These azetidine derivatives were introduced into the C7 position of a quinolone nucleus 8 to afford the corresponding fluoroquinolones 9a-f and 13a-f in 21-83% yields. Some of them exhibited superior antibacterial activity against quinolone-susceptible MRSA in comparison with clinically used fluoroquinolones, such as levofloxacin, ciprofloxacin, and gatifloxacin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Aza Compounds / chemistry*
  • Bridged Bicyclo Compounds / chemistry*
  • Crystallography, X-Ray
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Methicillin Resistance
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Pseudomonas aeruginosa / drug effects
  • Quinolones / chemical synthesis*
  • Quinolones / pharmacology*
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship

Substances

  • 1-azabicyclo(1,1,0)butane
  • Anti-Bacterial Agents
  • Aza Compounds
  • Bridged Bicyclo Compounds
  • Indicators and Reagents
  • Quinolones