Orally active cephalosporins. II. Synthesis and structure-activity relationships of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-cephalospori ns with 1,2,3-triazole in C-3 side chain.
The synthesis, antibacterial activity and oral absorbability of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3 -(1H-1,2, 3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid (1g) and related compounds are described. Their oral absorbability was influenced by the spacer length between C-3 of a cephem nucleus and C-4' of 1,2,3-triazole. The SCH2S structure was also found to contribute to their good oral absorption. The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a-1n) is discussed.
Kume
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Kubota
T
T
Kimura
Y
Y
Nakashimizu
H
H
Motokawa
K
K
Nakano
M
M
D000042:Absorption; D000818:Animals; D001419:Bacteria / Q000187:drug effects; D001682:Biological Availability; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005260:Female; D008252:Macaca fascicularis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009061:Mouth Mucosa / Q000378:metabolism*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D002511:Cephalosporins