Linezolid And 3,5 - Replaced By A New Oxazolidinone Synthesis And Antibacterial Activity Was Measured With Tricyclic Key Intermediate Of Synthesis

The rapid development of antibiotic-resistant strains such as MRSA, MRSE, PRSP, multi-drug resistant M. tuberculosis and VRE have caused difficulty to clinical treatment in recent years. Drugs being used are difficult to control diseases infected by these strains.All the pharmaceutists are seeking new antibiotics which have new structure.Linezolid is a newly synthetic antibiotic which inhibits bacterial protein synthesis in early stage while other antibiotic in last stage. It mainly inhibit gram-positive bacteria (resistant and susceptible) such as MRSA, MRSE, VRE, etc. Linezolid reduced side effect and was appreciated to be a potent and safe oral antibiotic.Linezolid has been successfully synthesized through three new synthetic routes. Based on the literature method the first route made modification on three steps and other two new routes have not been reported in literatures now. The third route was testified to be a good method to the synthesis of Linezolid and its analogues. In order to seek new oxazolidinones that have better activity and study the structure-activity relationship(SAR), 3, 5-disubstituted new oxazolidinones have been synthesized. New substituting groups on 5-methylane: acetylamino, camphormide, succinimide, 1, 3, 4-1H-triazole and other aromatic heterocycles, etc. Substituting groups on N-3 include 3 ' -fluoro⁴-(4 " -aromatic groups substituted piperazine-1-yl), 3 ' -fluoro-4 ' -(4" -(un)substituted piperadine -1-yl) and 3 ' -substituted(H, Cl,CF₃)-4 ' -morphiliyl benzene.In vitro antibacterial activities of 28 new compounds have been measured. Most compounds are 4-250 times better than Vancomycin, 16-2000 times better than Sultamicilin, 32-2000 times better than...