Synthesis and SAR of novel parenteral anti-pseudomonal cephalosporins: Discovery of FR264205

We describe herein the synthesis and biological evaluation of a series of novel cephalosporins with potent activity against Pseudomonas aeruginosa. Introduction of various amino groups to the 4-position of a 3-amino-2-methylpyrazole cephalosporin 3-side chain resulted in enhanced MIC values against multiple Pseudomonas aeruginosa strains and ultimately led to the discovery of FR264205 (15) with excellent anti-bacterial activity and weak convulsion effect by direct intracerebroventricular injection assay.

Graphical abstractSynthesis and biological evaluation of novel cephalosporins with excellent anti-pseudomonal activity are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide