STUDIES ON CEPHALOSPORIN ANTIBIOTICS

III. SYNTHESIS, ANTIBACTERIAL ACTIVITY AND ORAL ABSORPTION OF NEW3-(SUBSTITUTED-ALKYLTHIO)-7β-[(Z)-2-(2-AMINOTHIAZOL-4-YL)-2-(CARBOXYMETHOXYIMINO)ACETAMIDO]CEPHALOSPORINS

Abstract

The synthesis, antibacterial activity and oral absorption in rats of new 7β-[(Z)-2-(2-aminothiazol4-yl)-2-(carboxymethoxyimino)acetamido]cephalosporins (1) having various substituted-alkylthio groups at the C-3 position of the cephem nucleus are described. Of these, the cephalosporins with a cyanomethylthio group (1d) and fluoroethylthio group (1p) at the C-3 position showed a potent in vitro antibacterial activity against Gram-positive and Gram-negative bacteria as well as good oral absorption in rats. When administered orally to mice infected with Klebsiella pneumoniae, 1d had stronger protective effect than 1p. The structure-activity relationships of 1 are also presented.