Synthesis and antibacterial activity of C6-carbazate ketolides

Bioorg Med Chem Lett. 2006 Dec 15;16(24):6231-5. doi: 10.1016/j.bmcl.2006.09.036. Epub 2006 Sep 25.

Abstract

A novel series of ketolides containing heteroaryl groups that are linked to the erythronolide ring via a C6-carbazate functionality has been successfully synthesized. Careful modulation of the heteroaryl groups, the length and degree of saturation of the C6-carbazate linker, and the substituents present on each of the carbazate nitrogens led to compounds with potent activity against key bacterial respiratory pathogens. The best analogs of this series had in vitro and in vivo (sc dosing) profiles that were comparable to telithromycin.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Hydrazines*
  • Ketolides / chemical synthesis*
  • Ketolides / pharmacology*
  • Microbial Sensitivity Tests
  • Staphylococcus / drug effects*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Hydrazines
  • Ketolides
  • carbazic acid