Orally active cephalosporins. III. Synthesis and structure-activity relationships of new 3-heterocyclicthiomethylthio-7 beta-[(Z)- 2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-cephem-4 -carboxylic acids.
3-Heterocyclicthiomethylthio-7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2- hydroxyiminoacetamido]-3-cephem-4-carboxylic acids (2) were synthesized. Their antibacterial activity and oral absorbability were much influenced by the structure of heteroaromatic moiety in the side chain at the 3-position of a cephem nucleus. In this cephalosporin series, 3-thiadiazolylthiomethylthiocephalosporins (2k, 2l and 2m) exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria, whereas 3-(2-methyl-1,2,3-triazol-4-yl)thiomethylthiocephalosporin (2b) and 3-(pyridin-2-yl)thiomethylthiocephalosporin (2n) showed better oral absorption in mice than the other cephalosporins prepared. The structure-activity relationships of 2 are presented.
Kume
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Kubota
T
T
Kimura
Y
Y
Nakashimizu
H
H
Motokawa
K
K
D000284:Administration, Oral; D000818:Animals; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007408:Intestinal Absorption; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D002511:Cephalosporins; D013844:Thiazoles