Studies on 3'-quaternary ammonium cephalosporins--IV. Synthesis and antibacterial activity of 3'-(2-alkyl-3-aminopyrazolium) cephalosporins related to FK037.
The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido] cephalosporins bearing various 2-alkyl-3-aminopyrazolium groups at the 3-position are described. Antibacterial activity against MRSA was affected by the nature of the substituent at the 2-position on the 3'-aminopyrazolium groups. Among the cephalosporins prepared in this study, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[3-am ino-2-(2 -hydroxyethyl)-pyrazolio]methyl-3-cephem-4-carboxylate sulfate (23e, FK037) showed extremely potent broad-spectrum activity against both Gram-positive bacteria including MRSA, and Gram-negative bacteria including Pseudomonas aeruginosa. In particular, the in vivo activity against MRSA of FK037 was the highest of all the beta-lactam antibiotics tested.
Ohki
H
H
New Drug Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
Kawabata
K
K
Inamoto
Y
Y
Okuda
S
S
Kamimura
T
T
Sakane
K
K
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C079769:cefoselis; D015296:Ceftizoxime