S-3578, a new broad spectrum parenteral cephalosporin exhibiting potent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Synthesis and structure-activity relationships.
A series of 7-aminothiadiazolylcephalosporins having a 1-(substituted)-1H-imidazo[4,5-b]pyridinium group at the C-3' position of the cephem nucleus were synthesized and evaluated for in vitro antibacterial activities. Among the cephalosporins prepared in this study, 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-ethoxyiminoacetamido]-3-[1-(3-methylaminopropyl)-1H-imidazo[4,5-b]pyridinium-4-yl]methyl-3-cephem-4-carboxylate sulfate (S-3578) showed extremely potent broad spectrum activity against both gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative bacteria including Pseudomonas aeruginosa, and good water solubility.
Yoshizawa
Hidenori
H
Shionogi Research Laboratories, Shionogi & Co., Ltd., Fukushima-ku, Osaka 553, Japan. hidenori.yoshizawa@shionogi.co.jp
Itani
Hikaru
H
Ishikura
Koji
K
Irie
Tadashi
T
Yokoo
Katsuki
K
Kubota
Tadatoshi
T
Minami
Kyoji
K
Iwaki
Tsutomu
T
Miwa
Hideaki
H
Nishitani
Yasuhiro
Y
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
C471249:7-(2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido)-3-(1-(3-methylaminopropyl)-1H-imidazo(4,5-b)pyridinium-4-yl)methyl-3-cephem-4-carboxylate; D000900:Anti-Bacterial Agents; D002511:Cephalosporins