Studies on antibacterial agents. I. Synthesis of substituted 6,7-dihydro-1-oxo-1H,5H-benzo(i,j)-quinolizine-2-carboxylic acids.

Abstract

A series of substituted 6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acids was synthesized and tested for antibacterial activities. Among them, 9-fluoro-6,7-dihydro-5-methyl-8-(4-methyl-1-piperazinyl)-1-oxo-1H,5H- benzo[i,j]quinolizine-2-carboxylic acid (OPC-7241) exhibited potent antibacterial activity against gram-positive and -negative bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa, and 9-fluoro-6,7-dihydro-8-(4-hydroxy-1-piperidyl)-5-methyl-1-oxo-1H, 5H-benzo[i,j]quinolizine-2-carboxylic acid (OPC-7251) showed potent activity characteristically against Propionibacterium acnes.

Nadifloxacin downmodulates antigen-presenting functions of epidermal Langerhans cells and keratinocytes

“…The attenuation of the antigen-presenting or accessory ability of these cells is thought to result from NDFX downregulation of MHC class II or costimulatory molecules, because these molecules are essential for the presentation of hapten or superantigen to Tcells. The minimal concentration of NDFX suppressive for these cells was 10 or 30 mg/ml, which is higher than the dose necessary for anti-bacterial activity against P. acnes [11]. However, since the concentration in the rat skin measured 4 h after a single application of NDFX is approximately 30 mg/ml [11], these suppressive effects are considered to occur clinically.…”

“…These findings have put forward antigen-dependent and independent mechanisms in the immunological aspect of inflammatory acne. Nadifloxacin (NDFX) is a fluorinated quinolone derivative widely used in Japan and European countries as a topical anti-microbial agent for the treatment of acne [11]. In addition to this bacteriocidal action, NDFX has been known to possess anti-inflammatory properties, as it inhibits migration of neutrophils and generation of reactive oxygen species [12].…”

Amide-transforming activity of Streptomyces: possible application to the formation of hydroxy amides and aminoalcohols

“…Aminoalcohols and their derivatives are important building blocks of many pharmaceuticals and other biologically active molecules (Ichikawa et al 1988;Collins et al 2004;Okamoto et al 2007) (Fig. 1).…”

In vitro activity of nadifloxacin against several Gram-positive bacteria and analysis of the possible evolution of resistance after 2 years of use in Germany

“…Nadifloxacin is considered to belong to the thirdgeneration quinolones and is used for topical dermatological use [2], having little systemic side effects since only a limited amount of drug is absorbed through the skin [3,4].…”