STUDIES ON β-LACTAM ANTIBIOTICS

X. SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF 7β-[(Z)-2-(2-AMINO-4-THIA ZOLYL)-2-(CARBOYMETHOXYIMINO) ACETAMIDO]CEPHALOSPORIN DERIVATIVES

Abstract

The synthesis of 7β-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino)acetamido]-cephalosporins (2a-h) modified at the C-3 position of a cephem nucleus and the effect of the C-3 substituents on the antibacterial activity, oral absorptivity and therapeutic activity are discussed. The cephems (2a and 2b) having a C-3 substituent such as hydrogen or vinyl were more potent than other cephalosporins against Gram-negative bacteria. However, the cephalosporin (2f) having methylthio group at the 3-position showed the highest absorption rate in rats. These three cephalosporins (2a, b and f) exhibited equally good protective activities in mice infected. Furthermore, the serum levels of these cephalosporins (2a, b and f) were examined in dogs, and 2b and 2f showed outstanding high and prolonged serum levels.