Novel and potent oxazolidinone antibacterials featuring 3-indolylglyoxamide substituents

The synthesis and antibacterial activity of novel oxazolidinones possessing indolylglyoxamide moiety on piperazine scaffold have been disclosed. Novel oxazolidinone antibacterials bearing a variety of 3-indolylglyoxamide substituents have been explored in an effort to improve the spectrum and potency of this class of agents. A subclass of this series was also made with the diversity at C-5 terminus. These derivatives have been screened against a panel of clinically relevant Gram-positive pathogens and fastidious Gram-negative organisms. Several analogs in this series were identified with in vitro activity superior to linezolid (MIC = 0.25–2 μg/mL). Compounds 10a, 10c, 10e and 10f displayed activity against linezolid resistant Gram-positive organisms (MIC = 2–4 μg/mL). Selected oxazolidinones were evaluated for in vivo efficacy against a mouse systemic infection model.