ORALLY ACTIVE CEPHALOSPORINS .3. SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF NEW 3-HETEROCYCLICTHIOMETHYLTHIO-7-BETA-[(Z)-2-(2-AMINOTHIAZOL-4-YL)-2-HYDROXYIMINOACETAMIDO]-3-CEPHEM-4-CARBOXYLIC ACIDS

3-Heterocyclicthiomethylthio-7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-cephem-4-carboxylic acids (2) were synthesized. Their antibacterial activity and oral absorbability were much influenced by the structure of heteroaromatic moiety in the side chain at the 3-position of a cephem nucleus. In this cephalosporin series, 3-thiadiazolylthiomethylthiocephalosporins (2k, 21 and 2m) exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria, whereas 3-(2-methyl-1,2,3-triazol-4-yl)thiomethylthiocephalosporin (2b) and 3-(pyridin-2-yl)thiomethylthiocephalosporin (2n) showed better oral absorption in mice than the other cephalosporins prepared. The structure-activity relationships of 2 are presented.