Pyridone-carboxylic Acid Derivative Research Articles

ChemInform Abstract: Syntheses of New Pyridonecarboxylic Acid Derivatives Containing 1‐ or 2‐Naphthyl Substituents at N‐1 and Their anti‐HIV‐RT Activities.

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Syntheses of new pyridonecarboxylic acid derivatives containing 3‐,5‐ or 6‐quinolyl substituents at N‐1 and their anti‐HIV‐RT activities

AbstractA series of new pyridonecarboxylic acid derivatives containing 3‐, 5‐ or 6‐quinolyl substituents at N‐1 were synthesized and their in vitro anti‐HIV‐RT activities were evaluated. Several compounds in this series showed better activity than Atevirdine.

Syntheses of new pyridonecarboxylic acid derivatives containing 1‐ or 2‐naphthyl substituents at n‐1 and their anti‐hiv‐rt activities

AbstractA series of new pyridonecarboxylic acid derivatives containing 1‐ or 2‐naphthyl substituents at N‐1 were synthesized and their in vitro anti‐HIV‐RT activities were evaluated. Several compounds in this series showed better activity than Atevirdine.

耳鼻咽喉科感染症におけるＴＦＬＸ使用経験

Tosufloxacin a new pyridone-carboxylic acid derivative, was used to treat 110 patients with otorhinolaryngological infections. They were 43 with otitis media, 38 with sinusitis and 29 with tonsillitis.The clinical efficacy rate was assessed as excellent in 27 patients, good in 68 patients, fair in 13 patients and poor in 2 patients, the clinical efficacy rate being 85.5%. The bacterial examinations revealed an excellent eradication rate. No adverse events or abnormal laboratory finding were observed.

エノキサシンの慢性中耳炎組織内移行の検討

The serum and middle ear tissue concentration of enoxacin, a pyridone carboxylic acid derivative, was measured in 20 patients with chronic otitis media. The drug was given orally in a dose of 600mg 3 times a day for one to 24 days (average 6.3 days) on an average of 13.1 hours before the serum and tissue samples were obtained during tympanoplasty. In the 14 patients, for whom data of both serum and tissue concentrations were obtained, the concentrations were 0.90±0.66μg/ml and 3.32±3.50μg/kg, respectively. The tissue concentration was 384±236% times the serum concentration.

Aminoglycosides enhance the adherence of Staphylococcus aureus to HeLa cells.

Sub-lethal concentrations of aminoglycosides enhanced the adherence of Staphylococcus aureus FDA 209P to HeLa cells, whereas beta-lactams, pyridone carboxylic acid derivatives and chloramphenicol did not. Treatment with aminoglycosides also enhanced the bacterial adherence of these cells to immobilized fibronectin and laminin, and changed the bacterial cell surface to a more hydrophilic state than exists in non-treated cells. The adherence of S. aureus was not inhibited by lipoteichoic acid, extracted from the same strain, regardless of whether the bacterial cells were treated with an aminoglycoside or not. No correlation was observed between the adherence and zeta-potential of S. aureus.

Utilisation du fluorure de tetrabutylammonium comme de cyclisation dans la synthese d'antibacterines derives d'acide pyridone-4-carboxylique-3

Resume It has been found that the Bu4NF/THF base/solvent couple is very efficient in the key cyclisation step of ( 2 ) to ( 5 ) in the synthesis of antibacterial pyridonecarboxylic acid derivatives. In particular chiral intermediate ( 2d ) is directly converted in one step to ( 4d ), a key intermediate in the synthesis of (S)-Ofloxacin.

Chemotherapeutic efficacy of ofloxacin on renal and subcutaneous infection models with Staphylococcus aureus in mice.

Ofloxacin, a new pyridone-carboxylic acid derivative, was evaluated in descending nephritis and subcutaneous abscess models with Staphylococcus aureus in mice in comparison with norfloxacin. Descending nephritis was produced by intravenous injection of S. aureus 39 (MIC 0.78 microgram/ml for ofloxacin and 3.13 micrograms/ml for norfloxacin). Subcutaneous abscess was established by subcutaneous injection of soft agar containing S. aureus 56230 (MIC 0.39 microgram/ml for ofloxacin and 1.56 micrograms/ml for norfloxacin). Three days after infection, the lesions of both models were characterized by purulent inflammation accompanied with massive infiltration of neutrophils and bacterial multiplication. The animals were treated twice a day orally with each compound for 4 consecutive days, and subjected to bacteriological examination 18 h later. In the renal model, the 50% effective doses calculated on the basis of clearance of bacteria from kidneys were 38.4 mg/kg for ofloxacin and greater than 100 mg/kg for norfloxacin. In the subcutaneous model, the 50% effective doses based upon 90% reduction of viable bacteria as compared with untreated controls were 25.2 mg/kg for ofloxacin and greater than 100 mg/kg for norfloxacin. The excellent efficacies of ofloxacin in both infection models are attributed to its high oral absorbability and tissue distribution.

Effects of norfloxacin on DNA metabolism in Pseudomonas aeruginosa.

Norfloxacin is a quinolone (pyridonecarboxylic acid derivative) effective against Pseudomonas aeruginosa infections. We studied the effects of this drug on DNA metabolism in P. aeruginosa. Norfloxacin inhibits DNA replication immediately on its addition to a logarithmically growing culture of P. aeruginosa. It inhibits the ability of P. aeruginosa DNA gyrase to supercoil relaxed, closed circular DNA in vitro. At intermediate concentrations of the drug, inhibition of DNA replication in vivo is followed by secondary (recovery) synthesis. Both recovery synthesis and the bactericidal effects of norfloxacin are dependent on continued protein synthesis, suggesting that these are inducible functions. Neither norfloxacin nor nalidixic acid induces Weigle-reactivation (inducible DNA repair) or mutagenesis in P. aeruginosa.

In vitro antibacterial properties of AT-2266, a new pyridonecarboxylic acid.

AT-2266, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3 -carboxylic acid, is a new pyridonecarboxylic acid derivative with broad and potent antibacterial activity. It inhibited some gram-positive bacteria, such as staphylococci and Bacillus subtilis, and most gram-negative bacteria, including Serratia marcescens, Pseudomonas aeruginosa, Haemophilus influenzae, and Campylobacter jejuni, at concentrations of 0.1 to 0.78 microgram/ml, and most gram-positive bacteria, glucose-nonfermenters, and Mycoplasma pneumoniae at concentrations of 1.56 to 12.5 micrograms/ml. Most of the clinical isolates tested were as susceptible to AT-2266 as were laboratory strains. The antibacterial potency of AT-2266 was higher than those of pipemidic acid and nalidixic acid and similar to that of norfloxacin. AT-2266 was not cross-resistant with antibiotics and inhibited most highly nalidixic acid-resistant bacteria at concentrations of 1.56 to 3.13 micrograms/ml. Its activity was barely affected by the addition of horse serum or sodium cholate but weakened by lowering the medium pH or increasing the inoculum size. AT-2266 was bactericidal at concentrations near its minimal inhibitory concentrations. Frequencies of mutants resistant to 10 micrograms of AT-2266 per ml were lower than 4.0 x 10(-9).