The synthesis of 6-alkyloxapenems bearing hydroxy, fluorine, amino, acylamino and sulfonamido substituents in the 1'-position is described. Several of the compounds are potent inhibitors of β-lactamases from Staphylococcus aureus and Proteus vulgaris and have an appreciable stability against chemical hydrolysis.

BAY Y3118, 1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8- chloro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid hydrochloride, is a new fluoroquinolone with antibacterial activity against an expanded spectrum of species including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus pyogenes, and also anaerobes such as Bacteriodes fragilis and Clostridium perfringens. MIC90s for S. aureus, S. epidermidis, E. faecalis, and S. pneumoniae clinical isolates were 0.125, 0.25, 0.125 and 0.25 micrograms/ml, respectively. Against methicillin- and/or quinolone-resistant S. aureus, MIC50 levels of BAY Y3118 were 10- to 100-fold lower than those of tosufloxacin, sparfloxacin, or ciprofloxacin. The potency of BAY Y3118 against all members of the Enterobacteriaceae generally was equal to or 2-fold greater than that of ciprofloxacin or tosufloxacin. BAY Y3118 was also highly active against Haemophilus influenzae, Moraxella catarrhalis, Acinetobacter spp. and Pseudomonas aeruginosa. Increasing inoculum concentrations had a minimal effect on MIC determinations. The drug was determined to be bactericidal based upon reference MBCs and time-kill curves. From the results presented here, it was concluded that this new compound surpasses other known 4-quinolones both in spectrum and activity and that its further evaluation by in vitro, in vivo, and clinical studies seems warranted.

Chemischer InformationsdienstVolume 17, Issue 38 Reviews ChemInform Abstract: Development of Acylureido Penicillins H. B. KOENIG, H. B. KOENIGSearch for more papers by this authorK. G. METZGER, K. G. METZGERSearch for more papers by this authorW. SCHROECK, W. SCHROECKSearch for more papers by this author H. B. KOENIG, H. B. KOENIGSearch for more papers by this authorK. G. METZGER, K. G. METZGERSearch for more papers by this authorW. SCHROECK, W. SCHROECKSearch for more papers by this author First published: September 23, 1986 https://doi.org/10.1002/chin.198638361Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume17, Issue38September 23, 1986 RelatedInformation

The bactericidal activity of ciprofloxacin in active human serum was investigated using serum-resistant Escherichia coli C14 and Pseudomonas aeruginosa 220 as test organisms. In 100% or 80% human serum the growth rate of E. coli C14 was lower than in broth. This also influenced the killing rate of ciprofloxacin. Ciprofloxacin was more active in serum than norfloxacin or ofloxacin and killed Pseudomonas aeruginosa 220 much more rapidly than azlocillin or tobramycin. Rapid killing was also observed in vivo in the blood of intraperitoneally infected mice, ciprofloxacin being superior to norfloxacin, ofloxacin and sisomicin. In mouse protection studies with E. coli Neumann as infecting organism, the dose-effect ratio showed that, despite extremely low blood concentrations, ciprofloxacin had a full therapeutic effect at a dose of 2.5 mg/kg p.o. or less than or equal to 0.5 mg/kg s.c., whereas cefotaxime, despite similar low MIC values in vitro, had to be administered at a dose of 20 mg/kg s.c. in order to achieve 100% survival. These data indicate that ciprofloxacin is effective at low concentrations both in vitro and in vivo.

AbstractDurch Acylierung von Ampicillin (II) mit dem Chlorcarbonylimidazolidinon (Ic) erhält man die Mezlocillinsäure (IIIa), aus der das Mezlocillin‐natrium‐ Salz (IIIb) hergestellt wird.

Mezlocillin, 6-[D-2-(2-Oxo-3-mesyl-imidazolidine-1-carboxamido)- 2-phenylacetamido]-penicillanic acid, is a new semisynthetic acylureido-penicillin with a broad spectrum of antibacterial activity. The synthesis of mezlocillin from ampicillin and from 6-aminopenicillanic acid and the physicochemical properties are described. Mezlocillin is cleaved by penicillinase to the penicilloate which is degraded further by acids to the penilloate.

Azlocillin (Securopen®) ist ein neues parenterales Acylureidopenicillin mit besonders guter Wirkung gegen Pseudomonas aeruginosa und andere gramnegative Bakterien. Im Wirkungsspektrum liegen auch Enterokokken und Bacteroides fragilis. Azlocillin ist sehr gut verträglich. Die gute Verträglichkeit ergibt zusammen mit der im Vergleich zu Carbenicillin vier- bis achtfach besseren Wirkung gegen P. aeruginosa einen erweiterten Therapiebereich.