Studies on cephalosporin antibiotics. VI. Synthesis, antibacterial activity and oral efficacy in mice of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino)-acetamido]-3- (substituted alkylthio)cephalosporins.
A series of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetamido] cephalosporins (1) having various substituted alkylthio groups at the C-3 position of the cephem nucleus were prepared and evaluated for antibacterial activity and oral absorption in rats. Of these, the cephalosporin with a cyanomethylthio group (1a) showed the greatest activity against Staphylococcus aureus and Gram-negative bacteria. Its pivaloyloxymethyl ester (6a), a representative prodrug, exhibited good in vivo efficacy in mice by oral administration. The structure-activity relationships of 1 are also presented.
Yokoo
C
C
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Onodera
A
A
Fukushima
H
H
Numata
K
K
Nagate
T
T
D000284:Administration, Oral; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D001798:Blood Proteins; D002511:Cephalosporins