Structure-activity relationships of 3-aminoquinazolinediones, a new class of bacterial type-2 topoisomerase (DNA gyrase and topo IV) inhibitors

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1312-20. doi: 10.1016/j.bmcl.2006.12.005. Epub 2006 Dec 15.

Abstract

A series of 3-aminoquinazolinediones was synthesized and evaluated for its antibacterial and DNA gyrase activity. The SAR around the quinazolinedione core was explored and the optimal substitutions were combined to give two compounds, 2r and 2s, with exceptional enzyme potency (IC50 = 0.2 microM) and activity against gram-positive organisms (MIC's = 0.015-0.06 microg/mL).

MeSH terms

  • Amines / chemistry
  • Amines / pharmacology
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • DNA Gyrase
  • Gram-Positive Bacteria / drug effects
  • Inhibitory Concentration 50
  • Quinazolinones / chemical synthesis*
  • Quinazolinones / chemistry
  • Quinazolinones / pharmacology*
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors*

Substances

  • Amines
  • Anti-Bacterial Agents
  • Quinazolinones
  • Topoisomerase II Inhibitors
  • DNA Gyrase