Synthesis and antibacterial activity of novel ketolides with 11,12-quinoylalkyl side chains

Bioorg Med Chem Lett. 2018 Aug 1;28(14):2358-2363. doi: 10.1016/j.bmcl.2018.06.039. Epub 2018 Jun 19.

Abstract

A series of quinoylalkyl side chains was designed and synthesized, followed by introduction into ketolides by coupling with building block 6 or 32. The corresponding targets 7a-n, 33b, and 33e were tested for their in vitro activities against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed a similar antibacterial spectrum and comparable activity to telithromycin. Among them, two C2-F ketolides, compounds 33b and 33e, displayed excellent activities against macrolide-sensitive and macrolide-resistant pathogens.

Keywords: Antibacterial activity; Arylalkyl side chain; Ketolides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Azithromycin / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Resistance, Bacterial
  • Haemophilus influenzae / drug effects*
  • Ketolides / chemical synthesis
  • Ketolides / chemistry
  • Ketolides / pharmacology*
  • Methicillin Resistance
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Staphylococcus / drug effects*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Ketolides
  • Quinolines
  • Azithromycin
  • quinoline