Cefiderocol (S-649266), A new siderophore cephalosporin exhibiting potent activities against Pseudomonas aeruginosa and other gram-negative pathogens including multi-drug resistant bacteria: Structure activity relationship

Eur J Med Chem. 2018 Jul 15:155:847-868. doi: 10.1016/j.ejmech.2018.06.014. Epub 2018 Jun 8.

Abstract

The structure-activity relationship (SAR) for a novel series of catechol conjugated siderophore cephalosporins is described with their in vitro activities against multi-drug resistant Gram-negative pathogens including Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Enterobacteriaceae. Cefiderocol (3) was one of the best molecules which displayed well-balanced and potent activities against multi-drug resistant Gram-negative pathogens including carbapenem resistant bacteria among the prepared compounds with the modified C-7 side chain and the modified C-3 side chain. Cefiderocol (3) is a highly promising parenteral cephalosporin for the treatment of multi-drug resistant Gram-negative infection.

Keywords: Cefiderocol; Multi-drug resistant Gram-negative pathogens; Siderophore; Siderophore cephalosporin.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cefiderocol
  • Cephalosporins / chemical synthesis
  • Cephalosporins / chemistry
  • Cephalosporins / pharmacology*
  • Dose-Response Relationship, Drug
  • Gram-Negative Bacteria / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Cephalosporins