Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase

Bioorg Med Chem Lett. 2010 May 1;20(9):2828-31. doi: 10.1016/j.bmcl.2010.03.052. Epub 2010 Mar 15.


Bacterial DNA gyrase is an attractive target for the investigation of new antibacterial agents. Inhibitors of the GyrB subunit, which contains the ATP-binding site, are described in this communication. Novel, substituted 5-(1H-pyrazol-3-yl)thiazole compounds were identified as inhibitors of bacterial gyrase. Structure-guided optimization led to greater enzymatic potency and moderate antibacterial potency. Data are presented for the demonstration of selective enzyme inhibition of Escherichia coli GyrB over Staphylococcus aureus GyrB.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Binding Sites
  • Crystallography, X-Ray
  • DNA Gyrase / metabolism
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology
  • Topoisomerase II Inhibitors*


  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Thiazoles
  • Topoisomerase II Inhibitors
  • DNA Gyrase