Studies on beta-lactam antibiotics. XIX. Structure-activity relationships of cephalosporins having a thiadiazolylthiomethyl group at the C-3 side chain.
The synthesis and antibacterial activity of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(hydroxy or alkoxy)iminoacetamido]cephalosporins with various thiadiazolylthiomethyl moieties at the 3-position are discussed. Of the compounds (1a-1e, 7a-7d), 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-hydroxyiminoacetamido]-3-[(1,2 ,4- thiadiazol-5-yl)thiomethyl]cephalosporin (1d: FK312) exhibited the highest activity against Gram-positive and Gram-negative bacteria, especially, against methicillin-resistant Staphylococcus aureus. Furthermore, the pharmacokinetic profiles of the compound 1d showed longer serum levels than that of ceftriaxone in rats.
Inamoto
Y
Y
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Goto
J
J
Sakane
K
K
Kamimura
T
T
Takaya
T
T
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015296:Ceftizoxime / Q000031:analogs & derivatives / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C069639:FK 312; C049934:cefuzonam; D015296:Ceftizoxime; C045693:flomoxef