[Synthesis and antibacterial activity of (S) -5-acetylaminomethyl-3-[(4-substituted-aminomethyl) phenyl] -2-oxazolindinone derivatives].
OBJECTIVE
To synthesize oxazolindinone derivatives and test their antibacterial activities.


METHODS
3-Halo-4-methylaniline was acylated with benzyl chloroformate, followed by cyclization with (R)-glycidyl butyrate, acylation with methanesulfonyl chloride, substitution with NaN3, reduction with H2 + Pd/C or P(OMe)3 + HCl, acylation with Ac2O, and bromination with NBS to form bromides VIIIa and VIIIb, Substitution of the bromides with various amines including aliphatic amine and aromatic amine provided the target compounds IXa and IXb. The in vitro antibacterial activity of the target compounds was tested.


RESULTS
Fifty one new compounds were designed and synthesized. And their structures were confirmed by 1H NMR and elemental analyses or MS. Some physical constants such as [alpha]D25 were reported also. Compounds VIIb, IXa1, IXa2, IXa7, IXb1, IXb3, IXb10, IXb16 and IXb23 had moderate in vitro antibacterial activity against G+ bacteria but they were less active than linezolid or norfloxacin.


CONCLUSIONS
Insertion of methylene group between 4-position of phenyl and morpholinyl group in linezolid derivatives can not increase the antibacterial activity.
Li
Rong-Po
RP
Shanghai Institute of Pharmaceutical Industry, Shanghai 200237, China.
Zhou
Wei-Cheng
WC
Zhou
Wei-Liang
WL
D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013210:Staphylococcus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid