Biaryl isoxazolinone antibacterial agents

In an era of increasing resistance to classical antibacterial agents, the synthetic oxazolidinone series of antibiotics has attracted much interest. Zyvox™ was the first oxazolidinone to be approved for clinical use against infections caused by multi-drug resistant Gram-positive bacteria. In the course of studies directed toward the discovery of novel antibacterial agents, a new series of synthetic phenyl-isoxazolinone agents that displayed potent activity against Gram-positive bacterial strains was recently discovered at Bristol-Myers Squibb. Extensive investigation of various substitutions on the phenyl ring was then undertaken. We report here, the synthesis and antibacterial activity of a series of biaryl isoxazolinone compounds.

Graphical abstractThe synthesis and SAR of potent isoxazolinone analogs as antibacterial agents is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide