title: 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.
abstract: 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.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd., Fukushima-ku, Osaka 553, Japan. hidenori.yoshizawa@shionogi.co.jp
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yoshizawa
authors.forename: Hikaru
authors.initials: H
authors.lastname: Itani
authors.forename: Koji
authors.initials: K
authors.lastname: Ishikura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Irie
authors.forename: Katsuki
authors.initials: K
authors.lastname: Yokoo
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Kubota
authors.forename: Kyoji
authors.initials: K
authors.lastname: Minami
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Iwaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miwa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishitani
mesh_terms: 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
chemical_list: 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