Studies on cephalosporin antibiotics. III. Synthesis, antibacterial activity and oral absorption of new 3-(substituted-alkylthio)-7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2- (carboxymethoxyimino)acetamido]cephalosporins.
The synthesis, antibacterial activity and oral absorption in rats of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(carboxymethoxyimino)ace tamido] 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.
Yokoo
C
C
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Goi
M
M
Onodera
A
A
Murata
M
M
Nagate
T
T
Watanabe
Y
Y
D000284:Administration, Oral; D000818:Animals; D002511:Cephalosporins / Q000096:biosynthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D007408:Intestinal Absorption; D008297:Male; D008826:Microbial Sensitivity Tests; D051381:Rats; D011919:Rats, Inbred Strains
D002511:Cephalosporins