Antibacterials. Synthesis and structure-activity studies of 2-aryl-2-oxooxazolidines. Multiply-substituted aryl derivatives

The synthesis and structure-activity relationship (SAR) studies of the effect of different polysubstitution patterns in the aromatic ring of 5-(acetamidomethyl) oxazolidinone antibacterials (I) on antibacterial activity are presented. Compounds I were prepared by the six-step synthesis described previously. Antibacterial evaluation of compounds I against Staphylococcus aureus and Enterococcus faecalis gave the following results. The 2,4- and 2,5-disubstituted derivatives have weak or no antibacterial activity. Antibacterial activities of 3,4-disubstituted compounds are comparable to those of the 4-monosubstituted analogues for small 3-substituents (smaller than Br), but decline rapidly for larger 3-substituents. 3,4-Annulated derivatives are comparable in activity to their open-chain analogues. 3,5-Disubstituted and 3,4,5- and 2,4,6-trisubstituted derivatives are devoid of antibacterial activity.