Studies on beta-lactam antibiotics. X. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino)acetamido] cephalosporin derivatives.
The synthesis of 7 beta-([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.
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D047090:beta-Lactams