Novel amino-piperidines as potent antibacterials targeting bacterial type IIA topoisomerases

Bioorg Med Chem Lett. 2011 Dec 15;21(24):7489-95. doi: 10.1016/j.bmcl.2011.09.117. Epub 2011 Oct 10.

Abstract

We have identified a series of amino-piperidine antibacterials with a good broad spectrum potency. We report the investigation of various subunits in this series and advanced studies on compound 8. Compound 8 possesses good pharmacokinetics, broad spectrum antibacterial activity and demonstrates oral efficacy in a rat lung infection model.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • DNA Topoisomerases, Type II / chemistry*
  • DNA Topoisomerases, Type II / metabolism
  • Dioxanes / chemistry*
  • Dioxanes / pharmacology*
  • Dioxanes / therapeutic use
  • Disease Models, Animal
  • Dogs
  • Haplorhini
  • Humans
  • Lung Diseases / drug therapy
  • Microbial Sensitivity Tests
  • Naphthyridines / chemistry*
  • Naphthyridines / pharmacology*
  • Naphthyridines / therapeutic use
  • Piperidines / chemistry*
  • Piperidines / pharmacology
  • Piperidines / therapeutic use
  • Rats
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors / chemistry*
  • Topoisomerase II Inhibitors / pharmacology
  • Topoisomerase II Inhibitors / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Dioxanes
  • Naphthyridines
  • Piperidines
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type II