Novel piperidinyloxy oxazolidinone antibacterial agents. Diversification of the N-Substituent.
Oxazolidinone antibacterial agents, where the morpholino group of linezolid was replaced with an N-substituted piperidinyloxy moiety, were synthesized and shown to be active against a variety of resistant and susceptible Gram-positive organisms. The functionality attached to the piperidine nitrogen was varied extensively to determine the SAR for this series. One of the most potent compounds, 11, showed in vivo efficacy upon subcutaneous administration in a Staphylococcus aureus Smith murine systemic infection.
Weidner-Wells
Michele A
MA
Antimicrobial Agents Research Team, Johnson and Johnson Pharmaceutical Research and Development, LLC, 1000 Route 202, Raritan, NJ 08869, USA. mwells@prdus.jnj.com
Boggs
Christine M
CM
Foleno
Barbara D
BD
Melton
John
J
Bush
Karen
K
Goldschmidt
Raul M
RM
Hlasta
Dennis J
DJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023303:Oxazolidinones