Design, synthesis and structure–activity relationships of new phosphinate inhibitors of MurD

A series of new phosphinate compounds were designed and synthesized as inhibitors of the d-glutamic acid-adding enzyme (MurD) involved in peptidoglycan biosynthesis. They were tested against the MurD enzyme from Escherichia coli, allowing initial structure–activity relationships to be deduced. Two compounds had IC50 values near 100 μM and constitute a promising starting point for further development.

Graphical abstractA series of new inhibitors of the d-glutamic acid-adding enzyme (MurD) is presented. Two compounds (12g and 12c) had IC50 values near 100 μM and constitute a promising starting point for further development.Figure optionsDownload full-size imageDownload as PowerPoint slide