Karl Georg Metzger

Synthesis and antibacterial activity of (1′R,5R,6R)-2-tert-butyl-6-(1′-hydroxyethyl)oxapenem-3-carboxylic acid

Abstract As with the oxapenems, the 2-tert-butyl substituents substantially increased the hydrolytic stability of penems. The corresponding penems 1 and 2 were prepared and found to be extremely stable compounds. 2 showed good in vitro activity against gram-positive bacteria.

A short synthesis of (±) 7-oxo-3-oxa-1-azabicyclo[3.2.0] heptane-2-carboxylic acid.

Abstract A short 4-step synthesis of the title compound 3 , an inhibitor of β-lactamases, is presented. The essential step utilizes the palladium(O)-catalyzed deprotection of an allyl ester.

In vitro Evaluation of BAY Y3118, a New Full-Spectrum Fluoroquinolone

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.