Synthesis and antibacterial activity of dihydro-1,2-oxazine and 2-pyrazoline oxazolidinones: novel analogs of linezolid

The synthesis and antibacterial activity of oxazolidinones containing dihydro-1,2-oxazine and 2-pyrazoline ring systems are described. Linezolid analogs utilizing dihydro-1,2-oxazines as morpholine mimics were prepared utilizing a nitrosoamine/diene 4+2 cycloaddition strategy. Pyrazolidine, hexahydro-pyridazine, and 2-pyrazoline analogs more closely related to eperezolid were also prepared. The most active of these new oxazolidinones were the dihydro-1,2-oxazine 6 and the 2-pyrazoline 20 both of which had potency similar to linezolid against a panel of Gram-positive bacteria.

Graphical abstractThe synthesis and antibacterial activity of dihydro-1,2-oxazine and 2-pyrazoline oxazolidinones are reported. Dihydro-1,2-oxazine 6 and 2-pyrazoline 20 were found to have in vitro potencies rivaling linezolid.Figure optionsDownload full-size imageDownload as PowerPoint slide