title: Synthesis and structure-activity relationships of new cephalosporins with aminoimidazoles at C-7. Effect of the pKa of the C-7 aminoimidazole on antibacterial spectrum and beta-lactamase stability.
abstract: Cephalosporins with new aminoimidazole heterocycles at C-7 have been synthesized by reaction of anti-alpha-aminooximes with C-7 dihaloisocyanocephalosporins esters or by direct condensation of 2-fluoroimidazoles with C-7 aminocephalosporins esters. These compounds combine a broad spectrum of antibacterial activity, including Gram-negative and Gram-positive organisms with a good beta-lactamase stability. Activity is discussed in terms of its relationship to the pKa of the C-7 aminoimidazole heterocycle, basic C-7 aminoimidazole residues gave cephalosporins with the best beta-lactamase stability but the poorest activity against Gram-positive organisms. An additional interesting property of the C-7 imidazolylaminocephalosporins is the oral activity present in some compounds of this series.
authors.affiliation: ZENECA Pharma, Centre de Recherches, Zone Industrielle La Pompelle, REIMS, France.
authors.forename: F
authors.initials: F
authors.lastname: Jung
authors.forename: D
authors.initials: D
authors.lastname: Boucherot
authors.forename: C
authors.initials: C
authors.lastname: Delvare
authors.forename: A
authors.initials: A
authors.lastname: Olivier
authors.forename: G M
authors.initials: GM
authors.lastname: Davies
authors.forename: M J
authors.initials: MJ
authors.lastname: Betts
authors.forename: R
authors.initials: R
authors.lastname: Brown
authors.forename: R
authors.initials: R
authors.lastname: Stevenson
authors.forename: M
authors.initials: M
authors.lastname: Joseph
authors.forename: J F
authors.initials: JF
authors.lastname: Kingston
mesh_terms: D000818:Animals; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology*; D004795:Enzyme Stability / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000737:chemistry* / Q000187:drug effects
chemical_list: D002511:Cephalosporins; D007093:Imidazoles; D001618:beta-Lactamases