Pyridonecarboxylic Acids Research Articles

Pyridonecarboxylic acid antibacterial agents. Part XV. Synthesis of 7-thio-substituted 4-oxoquinoline-3-carboxylic acids with antibacterial activity.

A series of C-7 thio-substituted 1-cyclopropyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were prepared and tested for their antibacterial activity. Structure-activity relationships associated with the C-5 and C-7 substituents were discussed. Among the C-7 substituents including alkylthio, arylthio, heteroarylthio, and cyclic aminothio groups, a 2-aminoethylthio group was the best for enhancing in vitro antibacterial activity. The C-5 variants increased activity in the order OH less than F less than H less than NH2. Of compounds prepared in this work, 5-amino-7-(2-aminoethyl)thio-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4 -oxo-quinoline-3-carboxylic acid (18) was the most active.

Fluorinated pyrido(2,3-c)pyridazines. II. Synthesis and antibacterial activity of 1,7-disubstituted 6-fluoro-4(1H)-oxopyrido(2,3-c)pyridazine-3-carboxylic acids.

Chemical modification of pyridonecarboxylic acid antibacterials with a 1,8-naphthyridine ring, such as enoxacin and tosufloxacin, to their 2-aza derivatives was studied. A new series of 1,7-disubstituted 6-fluoro-4(1H)-oxopyrido[2,3-c]pridazine-3-carboxylic acids (25-27) was prepared by a route involving either alkylation of ethyl 6-fluoro-4(1H)-oxo-7-(p-tolylthio)pyrido[2,3-c]pyridazine-3-carbox ylate (7) or intramolecular cyclization of ethyl 2-(2,6-dichloro-5-fluoronicotinoyl)-2-[2-(p-fluorophenyl)hydraz ono]acetate, (20), followed by displacement reaction with cyclic amines at C-7; the N-1 substituent in these compounds included of ethyl, 2-fluoroethyl and p-fluorophenyl groups, and the C-7 functional group comprised variously-substituted piperazines and pyrrolidines. Antibacterial activities of these compounds were markedly inferior to those of enoxacin and tosufloxacin.

ChemInform Abstract: Synthesis of Antimicrobial Agents. Part 4. Synthesis of 1‐Hydroxypiperazine (V) Dihydrochloride and Its Applications to Pyridone Carboxylic Acid Antibacterial Agents (VII).

AbstractThe cyclopropyl derivative (VII) shows the most potent antibacterial activity.

Synthesis of antimicrobial agents. IV. synthesis of 1‐hydroxypiperazine dihydrochloride and its applications to pyridone carboxylic acid antibacterial agents

Abstract1‐Hydroxypiperazine dihydrochloride 7 was prepared and it was applied to the syntheses of new pyridone carboxylic acid antibacterial agents (PCA‐antibacterial agents). 1‐Cyclopropyl‐6,8‐difluoro‐1,4‐dihydro‐7‐(4‐hydroxypiperazin‐1‐yl)‐4‐oxoquinoline‐3‐carboxylic acid 13 showed the most potent antibacterial activity.

In Vitro Antimicrobial Activity of Pyridonecarboxylic Acids against Fish Pathogens

Abstract New pyridonecarboxylic acids (PCAs) were evaluated for in vitro antibacterial activity against Pasteurella piscicida, Vibrio anguillarum, Edwardsiella tarda, and Streptococcus sp., which were pathogens isolated from diseased fish in Japan. The minimal inhibitory concentrations of 11 PCAs, nalidixic acid, oxolinic acid, piromidic acid, pipemidic acid, miloxacin, flumequine, enoxacin, ofloxacin, norfloxacin, ciprofloxacin, and FR77040, were determined with the serial twofold agar dilution method. Newer PCAs, enoxacin, ofloxacin, norfloxacin, ciprofloxacin, and FR77040, showed the strongest antibacterial activity against all the fish pathogens. Oxolinic acid, miloxacin, and flumequine were highly active against the tested fish pathogens except Streptococcus sp. The remaining PCAs, nalidixic, piromidic, and pipemidic acids, were also effective against gram-negative pathogens, but the level of activity was even lower than that of the previous three. The frequency of spontaneous mutation of the pathoge...

Adverse drug interactions between pyridonecarboxylic acids and nonsteroidal antiinflammatory drugs: convulsion after oral or intracerebral administration in mice

Comparing with other pyridonecarboxylic acids (PCAs), the neurotoxicity of (+/-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)-1,4- dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262), which is a new PCA, was investigated in mice in a combination with fenbufen (FBF). T-3262, ofloxacin (OFLX) and nalidixic acid (NA) did not produce convulsion, but enoxacin (ENX) and norfloxacin (NFLX) produced it after an oral administration with FBF. The intracerebral injection of drugs alone to mice revealed that both FBF and 4-biphenylacetic acid (BPAA), which is principally responsible for FBF's antiinflammatory action, scarcely had convulsant activity. While all the PCAs had convulsant activity and the order of potency was as follows; NFLX greater than ENX greater than OFLX greater than penicillin G potassium greater than the free base of T-3262 (T-3262 base) greater than or equal to NA. When orally pretreated with BPAA, the convulsive threshold was scarcely lowered for T-3262 base and OFLX, but for ENX and NFLX it was lowered to about 1/300 and 1/100 of the respective activity. As the result, convulsant activities of ENX and NFLX were greatly potentiated, and their potencies became almost equal. The adverse drug interactions between T-3262 and FBF were scarcely observed in mice.

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.

STUDY ON METABOLISM OF PYRIDONECARBOXYLIC ACID I

STUDY ON METABOLISM OF PYRIDONECARBOXYLIC ACID I

ChemInform Abstract: Pyridonecarboxylic Acids as Antibacterial Agents. Part 10. Synthesis and Reactions of 7‐Substituted 1‐Cyclopropyl‐6‐fluoro‐1,4‐dihydro‐4‐ oxo‐1,8‐naphthyridine‐3‐carboxylic Acids as an Antibacterial Agent.

AbstractStarting with 3‐cyano‐2,6‐dichloro‐5‐fluoropyridine (I), the p‐tolylthio derivatives (III) are prepared.

ChemInform Abstract: Pyridonecarboxylic Acids as Antibacterial Agents. Part 9. Synthesis and Antibacterial Activity of 1‐Substituted 6‐Fluoro‐1,4‐dihydro‐4‐oxo‐7‐ (4‐pyridyl)‐1,8‐naphthyridine‐3‐carboxylic Acids.

AbstractCoupling of the amine (I) with the malonate (II) gives the vinylic amine (III) which produces the pyridone (IV) on heating.

Pyridonecarboxylic acids as antibacterial agents. XII. Synthesis and antibacterial activity of enoxacin analogues with a variant at position 1.

Syntheses par alkylation d'[ethyl-4 piperidino]-7 dihydro-1,4 fluoro-6 oxo-4 naphtyridine-1,8 carboxylates-3 d'ethyle en position 1

Separation of pyridone carboxylic acid enantiomers by high-performance liquid chromatography using copper(II)- l-amino acid as the eluent

Separation of pyridone carboxylic acid enantiomers by high-performance liquid chromatography using copper(II)- l-amino acid as the eluent

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.

ChemInform Abstract: Pyridonecarboxylic Acids as Antibacterial Agents. Part 8. An Alternative Synthesis of Enoxacin (I) via Fluoronicotinic Acid Derivatives.

ChemInform Abstract: Pyridonecarboxylic Acids as Antibacterial Agents. Part 8. An Alternative Synthesis of Enoxacin (I) via Fluoronicotinic Acid Derivatives.

Pyridonecarboxylic acids as antibacterial agents. 9. Synthesis and antibacterial activity of 1-substituted 6-fluoro-1,4-dihydro-4-oxo-7-(4-pyridyl)-1,8-naphthyridine-3- carboxylic acids.

The title compounds (7a-e) with ethyl, 2-fluoroethyl, 2-hydroxyethyl, vinyl, or cyclopropyl groups, respectively, at C-1 were prepared by the method involving the Balz-Schiemann reaction of 2-(4-pyridyl)pyridine- and 7-(4-pyridyl)-1,8-naphthyridinediazonium tetrafluoroborates (15 and 27). The 1-ethyl, 1-(2-fluoroethyl), and 1-vinyl derivatives showed in vitro activities as potent as the corresponding 7-(1-piperazinyl) analogues against Staphylococcus aureus 209P JC-1 and Escherichia coli NIHJ JC-2 but were less active against Pseudomonas aeruginosa 12. Among the 7-(4-pyridyl) derivatives having the different C-1 substituent, 1-cyclopropyl derivative 7e was found to be the most active. In vivo efficacy of 7e was superior to that of enoxacin against experimental infections due to S. aureus 50774. Some aspects of structure-activity relationships associated with the C-1, C-6, and C-7 substituents were discussed.

ChemInform Abstract: Pyridonecarboxylic Acids as Antibacterial Agents. Part 4. Synthesis and Structure‐Activity Relationship of 7‐Amino‐1‐aryl‐6‐fluoro‐4‐quinolone‐ 3‐carboxylic Acids. Pyridonecarboxylic Acids as Antibacterial Agents. Part 5. Synthesis and Structure‐Activity Relationship of 7‐Amino‐6‐ fluoro‐1‐(fluorophenyl)‐4‐oxo‐1,8‐naphthyridine‐3‐carboxylic Acids.

AbstractThe quinolone carboxylic acids (VI) are synthesized and their antibacterial activity in mice is evaluated.

ChemInform Abstract: Pyridonecarboxylic Acids as Antibacterial Agents. Part 2. Synthesis and Structure‐Activity Relationship of 1‐(4‐Hydroxyphenyl)‐6‐substituted‐4‐ pyridone‐3‐carboxylic Acids. Pyridonecarboxylic Acids as Antibacterial Agents. Part 3. Synthesis and Structure‐Activity Relationship of 1‐(4‐ Fluorophenyl)‐ and 1‐(2,4‐Difluorophenyl)‐6‐substituted‐4‐pyridone‐3‐ carboxylic Acids.

AbstractThe 4‐pyridone‐3‐carboxylic acids (VII) are prepared by Wittig reaction, coupling of the olefins (III) with the acetal (IV) and the anilines (V), followed by cyclization.

ChemInform Abstract: Pyridonecarboxylic Acids as Antibacterial Agents. Part 1. Synthesis and Structure‐Activity Relationship of 1‐Aryl‐6‐(4‐dimethylaminophenyl)‐4‐ pyridone‐3‐carboxylic Acids.

AbstractThe 1‐aryl‐6‐(4‐dimethylaminophenyl)‐4‐pyridones (VII) are synthesized as shown in the reaction scheme.

Application of o-hydroxyhydroquinonephthalein-iron(III) complex to determination of pyridone carboxylic acids.

A simple spectrophotometric method for the determination of pyridone carboxylic acids (PCA) using ο-hydroxyhydroquinonephthalein (Qnph) -iron (III) complex was developed. The present method is based on the ternary complex formation among Qnph, iron (III) and PCA in the presence of sodium dodecylbenzenesulfonate in weakly basic media. In the determination of nalidixic acid (NA), Beer's law held up to ca. 20 μg of NA in the final volume of 10 ml, with an apparent molar absorptivity of 1.3 × 105 l mol-1 cm-1 for NA {1.8 × 105 l mol-1 cm-1 for piromidic acid (PA), 6.6 × 104 l mol-1 cm-1 for pipemidic acid}. The proposed method was applied to the assay of NA or PA in pharmaceutical preparations and calf serum. The use of a membrane filter preconcentration technique was also investigated in an attempt to improve the proposed method.

Pyridonecarboxylic acids as antibacterial agents. VIII. An alternative synthesis of enoxacin via fluoronicotinic acid derivatives.

An alternative synthesis of enoxacin, a 1, 8-naphthyridine antibacterial agent, was developed. The present method involves 1, 8-naphthyridine ring construction by the Dieckmann type cyclization of ethyl 5-fluoronicotinate having a 2-ethoxycarbonylethylamino moiety at C-2. This nicotinate was prepared in 7 steps from ethyl fluoroacetate via ethyl 2, 6-dichloro-5-fluoronicotinate.