In vitro and in vivo antibacterial activities of OPC-20011, a novel parenteral broad-spectrum 2-oxaisocephem antibiotic.

OPC-20011, a new parenteral 2-oxaisocephem antibiotic, has an oxygen atom at the 2- position of the cephalosporin frame. OPC-20011 had the best antibacterial activities against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae: MICs at which 90% of the isolates were inhibited were 6.25, 6.

Synthesis and biological properties of substituted 1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic acids.

A series of substituted 1-cyclopropyl-6-fluoro-1, 4-dihydro-5-methyl-4-oxo-3-quinoline carboxylic acids was synthesized and tested for their in vitro and in vivo antibacterial activity. The introduction of a methyl group at the 5-position of quinoline nucleus enhanced characteristically the antibacterial activity against Gram-positive bacteria, including Streptococcus pneumoniae, which is a major pathogen in the respiratory tract infection, while retaining Gram-negative activity. Among them, 1-cyclopropyl-6-fluoro-1, 4-dihydro-5-methyl-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxyli c acid hydrochloride (grepafloxacin) exhibited potent in vitro antibacterial activity against Gram-positive bacteria such as Streptococcus pneumoniae and high in vivo efficacy on the experimental systemic infections caused by the Gram-positive and -negative bacteria tested.

Evaluation of OPC-17116 against important pathogens that cause respiratory tract infections.

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.

Studies on antibacterial agents. II. Synthesis and antibacterial activities of substituted 1,2-dihydro-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids.

A series of substituted 1,2-dihydro-6-oxo-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids for the treatment of systemic infections was synthesized via 7-bromo-3-ethylthio-4,5-difluoro-2-methylindole (3), which was prepared by Gassman's indole synthesis in excellent yield. The synthesized pyrroloquinolines were tested for their antibacterial activities. 8-Fluoro-1,2-dihydro-2-methyl-9-(4-methyl-1-piperazinyl)-6-oxo-6H- pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid showed a potent antibacterial activity against gram-positive and gram-negative bacteria.