Synthesis and in vitro evaluation of substituted phenyl-piperazinyl-phenyl oxazolidinones against Gram-positive bacteria.
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.
Liu
Jidong
J
The Innovation Center of Drugs, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China. liujd_1018@yahoo.com
He
Baoyuan
B
Yu
Aizhen
A
Zhou
Weicheng
W
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010879:Piperazines / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D010879:Piperazines; C031503:phenylpiperazine