(Fig. 1)For the in vitro tests, stock solutions were prepared by dissolving the compounds in water, except for ampicillin, which was dissolved in 0.1 M phosphate buffer (pH 8); DuP 721, chloramphenicol, and erythromycin, which were dissolved in dimethyl sulfoxide; ciprofloxacin, which was dissolved in 0.1 N NaOH solution; and griseofulvin, which was

The synthesis and structure/activity studies of the effect of varying the "B" group in a series of oxazolidinone antibacterials (I) are described. Two synthetic routes were used: (1) alkylation of aniline with glycidol followed by dialkyl carbonate heterocyclization to afford I (A = H, B = OH), whose arene ring was further elaborated by using electrophilic aromatic substitution methodology; (2) cycloaddition of substituted aryl isocyanates with epoxides to give A and B with a variety of values. I with B = OH or Br were converted to other "B" functionalities by using SN2 methodology. Antibacterial evaluation of compounds I with A = acetyl, isopropyl, methylthio, methylsulfinyl, methylsulfonyl, and sulfonamido and a variety of different "B" groups against Staphylococcus aureus and Enterococcus faecalis concluded that the compounds with B = aminoacyl, and particularly acetamido, were the most active of those examined in each A series, possessing MICs in the range of 0.5-4 micrograms/mL for the most active compounds described.

While anti-human blood group B agglutinins are present in the majority of ordinary White Leghorn chicks by the age of 30 days, none could be demonstrated in germfree chicks up to the age of 60 days. Anti-B agglutinins in trace amounts were first found in germfree chicks 66 days old and increased to an average titer of about 1:2 by 91 days of age. This titer amounts to about 10 per cent of that found in ordinary chicks. The appearance of antibody in low titer is attributed to trace amounts of non-living antigenic contaminants penetrating the germfree barrier. The necessity of appropriate absorption in order to obtain well defined specificities was pointed out. Several means commonly used to differentiate between normal and immune antibodies were employed in this investigation. None showed a difference between anti-B agglutinins from ordinary chicks and from germfree chicks intentionally immunized with blood group B active E. coli O86 or with B active preparations from human meconium. The implications of these findings on the origin of natural agglutinins are discussed. It is concluded, that measurable anti-human blood group B agglutinins in White Leghorn chicks are acquired early in life and are not inherited. The possibilities as well as limitations of present day germfree technique for this kind of immunological research have been considered.

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 (Gregory, W. A.; et al. J. Med. Chem. [formula: see text] 1989, 32, 1673), electrophilic aromatic substitution reactions of 3-substituted compounds, and functional-group interchange reactions of 3,4-disubstituted compounds. 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.