A complement inhibitor, K-76 , was isolated and purified from the

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.

The antibacterial activity of OPC-17116, a new fluoroquinolone antibacterial agent, against important pathogens that cause respiratory tract infections was evaluated in vitro and in vivo and compared with those of ciprofloxacin, ofloxacin, and norfloxacin. The pharmacokinetic profiles of OPC-17116 were studied in both mice and rats given the drug orally at doses of 50 and 40 mg/kg of body weight, respectively. OPC-17116 showed a high degree of distribution in the lung tissues of both species, with maximum concentrations of 29.6 and 32.0 micrograms/g, respectively. Furthermore, the drug concentrations in lung tissue were about 10 to 15 times greater than the concentrations in plasma. OPC-17116 showed potent antibacterial activity against such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, and Moraxella catarrhalis. The MICs of this compound for 90% of these organisms except methicillin-resistant S. aureus and P. aeruginosa ranged from < or = 0.006 to 0.78 microgram/ml. The in vitro antibacterial activity of OPC-17116 was reflected by the efficacy of a single oral dose against systemic bacterial infections in mice. OPC-17116 showed a superior effect against gram-positive bacteria, H. influenzae, and M. catarrhalis. In comparison with the other reference compounds, the efficacy of OPC-17116 was less than that of ciprofloxacin against K. pneumoniae and P. aeruginosa. OPC-17116 showed a greater therapeutic effect than the other drugs against experimental acute pneumonia caused by these organisms in mice or rats. This excellent therapeutic effect against respiratory tract infections may be a result of its high level of distribution in lung tissue.