Synthesis and In Vitro Evaluation of Substituted Phenyl‐Piperazinyl‐Phenyl Oxazolidinones Against Gram‐positive Bacteria

Abstract

With the incidence of linezolid-resistant Enterococcus faecalis, E. faecium and Staphylococcus aureus, modification of linezolid at the 5- and/or 3-positions led to the development of a series of 3-(methoxyl-phenyl)-piperazinyl-phenyl oxazolidinone analogues. These compounds were tested in vitro against six gram-positive standard organisms (S. aureus, S. epidermidis, S. pneumoniae, S. albus, Streptococcus enteridis and S. nonhemolyticus). 5-acetylaminomethyl oxazolidinones bearing fluorine at 3'-position of phenyl ring showed activities against several gram-positive bacteria (MIC: 3.13-6.25 mug/mL). The position of methoxyl group on the phenyl ring of piperazine group affected antibacterial spectrum. 3-(4'- (para-methoxyl-phenyl)-piperazinyl)-(3'-fluoro)-phenyl-5-acetylaminomethyl oxazolidinone was found active against 5 gram-positive organisms except S. nonhemolyticus, whereas 3-(4'-(ortho-methoxyl-phenyl)-piperazinyl)-(3'-fluoro)-phenyl-5-acetylaminomethyl oxazolidinone was found active only against 2 gram-positive organisms, namely S. albus, S. enteridis.