Pleuromutilin derivatives having a purine ring. Part 3: Synthesis and antibacterial activity of novel compounds possessing a piperazine ring spacer

SAR studies on the water-soluble thioether pleuromutilin analogue 6, which has excellent in vitro and in vivo antibacterial activities, led to discovery of the novel pleuromutilin derivatives having a piperazine ring spacer. These derivatives displayed potent and well-balanced in vitro antibacterial activity against various drug-susceptible and -resistant Gram-positive bacteria. In particular, the promising pleuromutilin analogues 37 and 40 were found to exhibit strong in vivo efficacy against Staphylococcus aureus Smith.

Graphical abstractIn the course of our research aimed at the discovery of metabolically stable pleuromutilin analogues with potent in vitro antibacterial activity against Gram-positive pathogens, the synthesis and antibacterial activity of novel compounds bearing a piperazine ring spacer are described.Figure optionsDownload full-size imageDownload as PowerPoint slide