title: A novel series of parenteral cephalosporins exhibiting potent activities against Pseudomonas aeruginosa and other Gram-negative pathogens: synthesis and structure-activity relationships.
abstract: A series of 7beta-[2-(2-aminothiazol-4-yl)-2-(Z)-(carboxymethoxyimino)acetamido]cephalosporins bearing a 1-(substituted)-1H-pyrrolo[3,2-b]pyridinium group at C-3' position was synthesized and their in vitro antibacterial activities against Pseudomonas aeruginosa and other Gram-negative pathogens were evaluated. Among the cephalosporins prepared, 7beta-[2-(2-amino-5-chlorothiazol-4yl)-2(Z)-((S)-1-carboxyethoxyimino)acetamido]cephalosporins (42d) showed potent antibacterial activities against P. aeruginosa and other Gram-negative pathogens including the strains which produce class C beta-lactamase and extended spectrum beta-lactamase (ESBL). These results imply that both the Cl atom on the C-7 aminothiazole moiety and the alpha-substituent at the iminoether moiety are essential for the stability against beta-lactamase and the potent activity against Gram-negative bacteria including P. aeruginosa.
authors.affiliation: Discovery Research Laboratories, Shionogi & Co Ltd, 12-4, Sagisu 5-Chome, Osaka, Japan. kenji.yamawaki@shionogi.co.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamawaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomura
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Yasukata
authors.forename: Koichi
authors.initials: K
authors.lastname: Uotani
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miwa
authors.forename: Kei
authors.initials: K
authors.lastname: Takeda
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*; D004333:Drug Administration Routes; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins