title: Synthesis and biological evaluation of a series of new parenteral optically active 3-[[(N-alkylpyridinium-4'-yl)thio]methyl]-2-oxaisocephems.
abstract: The preparation and biological evaluation of a series of 7-[2-(2-aminothiazol-4-yl)-2-(Z)-[(cyclopentyloxy)imino]acetamido] optically active 2-oxaisocephems, substituted at the 3-position with [(N-alkylpyridinium-4'-yl)thio]methyl groups, are described. The resulting family of parenteral compounds displays a broad spectrum of in vitro antibacterial activity. These compounds exhibit increased activity against Gram-positive organisms including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis which are resistant to most cephalosporins with a similar level of Gram-negative activity to that of the third-generation antibiotics. In vivo efficacy of new antibacterial agents in this investigation is excellent against both Gram-positive and Gram-negative bacteria as compared with reference compounds. The in vitro and in vivo antimicrobial activity and the structure-activity relationships are presented.
authors.affiliation: Microbiological Research Institute, Otsuka Pharmaceutical Company, Ltd., Tokushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsubouchi
authors.forename: K
authors.initials: K
authors.lastname: Tsuji
authors.forename: K
authors.initials: K
authors.lastname: Yasumura
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Shitsuta
authors.forename: H
authors.initials: H
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins