The discovery of a novel siderophore cephalosporin Cefiderocol

Abstract

The threat of carbapenem resistant Gram-negative pathogens e.g. Enterobacterales, P. aeruginosa and A. baumannii is expanding worldwide. One strategy to discover a new antibacterial to be active against these resistant pathogens is to utilize the bacterial iron acquisition system by attaching a siderophore-mimicking molecule to the parent molecule. In 1980’s, our team identified a siderophore cephalosporin A-2, which displayed a potent activity against P. aeruginosa. We restarted the SAR study of siderophore cephalosporin to increase the in vitro and in vivo antimicrobial activity against various carbapenemase-producing resistant strains by the modification of the C-3 and C-7 side chains of A-2. Here, we report the SAR results about the several siderophore cephalosporins that led to the discovery of Cefiderocol.