title: Synthesis and biological evaluation of a series of parenteral 3'-quaternary ammonium cephalosporins.
abstract: The preparation and biological evaluation of a series of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoximinoacetamido]cep halosporins, substituted at the 3'-position with monocyclic or bicyclic nitrogen-containing heterocycles are described. The resulting family of parenteral compounds displays a broad spectrum of antibacterial activity. Some compounds exhibit a similar level of Gram-negative activity to that of the "third-generation" cephalosporins with increased staphylococcal activity. The in vitro and in vivo antimicrobial activity, structure-activity relationships, beta-lactamase stability, and in vitro and in vivo pharmacological evaluations are presented.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285.
authors.forename: R F
authors.initials: RF
authors.lastname: Brown
authors.forename: M D
authors.initials: MD
authors.lastname: Kinnick
authors.forename: J M
authors.initials: JM
authors.lastname: Morin
authors.forename: R T
authors.initials: RT
authors.lastname: Vasileff
authors.forename: F T
authors.initials: FT
authors.lastname: Counter
authors.forename: E O
authors.initials: EO
authors.lastname: Davidson
authors.forename: P W
authors.initials: PW
authors.lastname: Ensminger
authors.forename: J A
authors.initials: JA
authors.lastname: Eudaly
authors.forename: J S
authors.initials: JS
authors.lastname: Kasher
authors.forename: A S
authors.initials: AS
authors.lastname: Katner
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002511:Cephalosporins / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004754:Enterobacter / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010276:Parasympatholytics / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D012706:Serratia marcescens / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D002511:Cephalosporins; D010276:Parasympatholytics; D001618:beta-Lactamases