title: Structure-activity relationships of cephalosporins having a (dimethylisoxazolidinio)vinyl moiety at their 3-position.
abstract: A series of cephalosporins having a (dimethylisoxazolidinio)vinyl group at their 3-position were synthesized to investigate their structure-activity relationships. With regard to the olefin geometry, the (E)-vinyl compound exhibited higher in vitro activity than the (Z)-compound. Regarding the C-7 substituents, the replacement of 2-aminothiazole with 5-amino-1,2,4-thiadiazole increased the anti-pseudomonal activity. Determination of the absolute configuration of the C-3 substituent is also presented. Among the compounds synthesized, we selected 7 beta-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(fluoromethoxyimi no)acetamido]-3-[(E)-2-((S)-2,2-dimethyl-5-isoxazolidinio)vinyl ]-3-cephem-4-carboxylate (YM-40220), which showed well-balanced in vitro activity and an excellent in vivo efficacy against Staphylococcus aureus Smith, as a candidate for further development.
authors.affiliation: Infectious Disease & Immunology Research Labs, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Hara
authors.forename: K
authors.initials: K
authors.lastname: Sakamoto
authors.forename: H
authors.initials: H
authors.lastname: Hisamichi
authors.forename: N
authors.initials: N
authors.lastname: Nagano
mesh_terms: D000818:Animals; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D002511:Cephalosporins