68077-26-9

Usage

Uses

Used in Pharmaceutical Industry:
1-Ethyl-7-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid is used as an intermediate in the synthesis of Norfloxacin, a fluoroquinolone antibiotic. It is utilized for its antimicrobial properties, which are effective against a broad range of bacterial infections, including urinary tract infections, respiratory infections, and skin infections.
Used in Quality Control:
1-Ethyl-7-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid is used as a reference compound in the quality control and standardization of Norfloxacin products. It helps ensure the purity, potency, and safety of the final drug product by serving as a benchmark for comparison during various analytical tests and assays.

InChI:InChI=1/C12H9ClFNO3/c1-2-15-5-7(12(17)18)11(16)6-3-9(14)8(13)4-10(6)15/h3-5H,2H2,1H3,(H,17,18)/p-1

Synthetic route

1-ethyl-6-fluoro-7-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (70458-94-5) → 7-chloro-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (68077-26-9)

Conditions	Yield
Stage #1: 1-ethyl-6-fluoro-7-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester With water; sodium hydroxide In ethanol at 90℃; for 1.5h; Stage #2: With hydrogenchloride In ethanol; water pH=2;	92%
With sulfuric acid In water; acetic acid for 1.5h; Heating;	91%
With water; sodium hydroxide In ethanol for 2.5h; Reflux;	91%

Upstream product

• 70032-30-3 diethyl 2-[(3-chloro-4-fluorophenylamino)methylene]malonate 
• 70458-94-5 1-ethyl-6-fluoro-7-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 
• 105392-20-9 ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-(dimethylamino)acrylate 
• 75073-15-3 ethyl 7-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline 3-carboxylate 
• 106648-05-9 2-(2,4-Dichlor-5-fluorbenzoyl)-3-ethylaminoacrylsaeure-ethylester 
• 86393-34-2 2,4-dichloro-5-fluorobenzoyl chloride 
• 55330-56-8 ethyl 3-(ethylamino)-2-propenoate 
• 367-21-5 3-chloro-4-fluorophenylamine 
• 70458-93-4 7-Chloro-6-fluoro-4-hydroxy-3-quinolinecarboxylic acid ethyl ester 
• 149859-18-7 2-(4-morpholinylcarbonyl)ethanoic acid methyl ester 
• 136491-18-4 N-(3-Chlor-4-fluor-phenyl)-N-ethyl-aminomethylen-meldrumsaeure 

Downstream Products

• 70458-96-7 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid 
• 70458-92-3 Pefloxacin 
• 74011-42-0 Oxonorfloxacin 
• 75001-78-4 7-chloro-1-ethyl-1,4-dihydro-4-oxo-6-(1-piperazinyl)quinoline-3-carboxylic acid 
• 5654-94-4 2,8-diazabicyclo-[4.3.0]-nonane 
• 727664-15-5 AS 1842856 
• 68077-27-0 Norfloxacin hydrochloride 
• 70458-99-0 1-ethyl-6-fluoro-7-(4-benzylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 
• 74011-41-9 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-<4-(p-aminobenzyl)-1-piperazinyl>quinoline-3-carboxylic acid 
• 70458-97-8 7-(4-allylpiperazin-1-yl)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 
• 74011-39-5 1-ethyl-1,4-dihydro-6-fluoro-7-[4-(p-nitrobenzyl)-1-piperazinyl]-4-oxoquinoline-3-carboxylic acid 
• 75001-81-9 7-(4-Benzoyl-piperazin-1-yl)-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid 
• 75001-82-0 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)quinoline 
• 74011-56-6 N-acetylnorfloxacin 

Relevant academic research and scientific papers

A New Short and Efficient Strategy for the Synthesis of Quinolone Antibiotics

A simple protocol for the synthesis of quinolone antibiotics is exemplified for the synthesis of norfloxacin; 3-chloro-4-fluoroaniline with triethyl orthoformate is transformed into its N-ethyl-N-formyl derivative which reacts with methyl malonyl morpholide and phosphoryl chloride at 100 deg C to give 6-fluoro-7-chloro-1-ethylquinol-4-one-3-carboxylic acid, which has previously been converted into norfloxacin by the action of piperazine.

Synthesis of 6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid derivatives as potential antimicrobial agents

In the present study, a series of 1-ethyl/benzyl-6-fluoro-7-(substituted piperazin-1-yl)1,4-dihydro-4-oxo-quinoline-3-carboxylic acid were synthesized and characterized by IR, 1H-NMR, mass spectral and elemental analysis. The in vitro antibacterial and antifungal activities of the compounds were evaluated by paper disc diffusion method. The minimum inhibitory concentrations (MIC) of the compounds were also determined by agar streak dilution method. The in vivo antibacterial activity of the compounds against Escherichia coli was also evaluated by mouse protection test. All the compounds exhibited significant antibacterial and weak antifungal activities. The in vivo antibacterial activity (ED50) against E. coli was 50-160 mg kg -1 in the order of 7100 μg mL-1 against Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, Bacillus cereus, E. coli, Klebsiella pneumoniae, Candida albicans and Aspergillus niger.

Developing ciprofloxacin analogues against plant DNA gyrase: A novel herbicide mode of action

Ciprofloxacin has been shown to exhibit potent herbicidal activity through action against plant DNA gyrase, presenting a novel mode of action. Analogues of ciprofloxacin have been prepared with increased herbicidal activity and diminished antibacterial activity, compared to ciprofloxacin, as demonstrated using model systems.

Chemical synthesis method for norfloxacin

The invention discloses a chemical synthesis method for norfloxacin. The chemical synthesis method comprises the following steps: (1) synthesis of a compound ethyl quinolinate: 3-ethylamino-2-(2,4-dichloro-5-fluorobenzoyl) ethyl acrylate is dissolved in DMF, potassium carbonate is added, the mixture is heated to 50-80 DEG C, reacts and stands overnight, a product is cooled and poured into cold water, produced solids are filtered, solids are washed with a large amount of water, and the product ethyl quinolinate is obtained; (2) synthesis of a compound quinolinic acid: ethyl quinolinate is dissolved in methanol, hydrochloric acid is added in a ratio being 1:1, reflux is performed for 2 h, white solids are precipitated and filtered, a filter product is washed with water and dried in a vacuum oven for 2 h, and the product quinolinic acid is obtained. The design is reasonable, and one novel norfloxacin synthesis method is selected and has good market application value.

An operational transformation of 3-carboxy-4-quinolones into 3-nitro-4-quinolones via ipso-nitration using polysaccharide supported copper nanoparticles: Synthesis of 3-tetrazolyl bioisosteres of 3-carboxy-4-quinolones as antibacterial agents

Chitosan supported Cu nano-particles have been synthesized, and utilized for the synthesis of 3-nitro-4-quinolones from 3-carboxy-4-quinolones via ipso nitration. The synthesized 3-nitro derivatives of 4-quinolones were successfully converted into their 3-tetrazolyl bioisosteres which showed increased antibacterial activity as compared to the standard ciprofloxacin.

MONOCARBOXYLATE TRANSPORT MODULATORS AND USES THEREOF

The invention generally relates to the field of monocarboxylate transport modulators, e.g., monocarboxylate transport inhibitors, and more particularly to new substituted-quinolone compounds, the synthesis and use of these compounds and their pharmaceutical compositions, e.g., in treating, modulating, forestalling and/or reducing physiological conditions associated with monocarboxylate transport activity such as in treating cancer and other neoplastic disorders, inflammatory diseases, disorders of abnormal tissue growth and fibrosis including cardiomyopathy, obesity, diabetes, cardiovascular diseases, tissue and organ transplant rejection, and malaria.

Operative conversions of 3-carboxy-4-quinolones into 3-nitro-4-quinolones via ipso-nitration: Potential antifilarial agents as inhibitors of Brugia malayi thymidylate kinase

An efficient, cost effective and green methodology for ipso nitration in the synthesis of the 3-nitro derivative of 3-carboxy 4-quinolones has been developed by the quantitative use of copper acetate and silver nitrate in water. The observed regioselectivity of nitration is explained by the DFT calculations. Three of these compounds with IC50 values (2.9-3.4 μmol) against Brugia malayi thymidylate kinase may be good antifilarial agents as also evidenced by molecular docking studies.

ANTIVIRAL AND ANTIMICROBIAL COMPOUNDS

Disclosed are guanidine and biguanidine derivatives which have anti-viral and antibacterial activity. Also disclosed are pharmaceutical compositions containing such compounds as an active ingredient, and anti-viral and anti-bacterial methods utilizing such compounds. Methods of treating infections using the guanidine and biguanidine derivatives are also disclosed.

Mechanism and synthesis of pharmacologically active quinolones from Morita-Baylis-Hillman adducts

The synthesis of quinolones from Morita-Baylis-Hillman (MBH) adducts is reported. The quinolone skeleton is formed via a TFA-mediated cyclization of the MBH adduct, and a mechanism study using ESI(+)-MS(/MS) has indicated the role played by TFA in this key reaction step. The total syntheses of Norfloxacin and a benzyl quinolone carboxylic acid (BQCA) derivative are described. Norfloxacin is a fluoroquinolonic antibacterial drug whereas BQCA is M1 receptor positive allosteric modulator and seem to provide access to new potential drugs for Alzheimer disease, pain, and sleep disorders. The syntheses of these two important quinolones exemplify the versatility and potentiality of the approach.

A small-molecule inhibitor of nipah virus envelope protein-mediated membrane fusion

Nipah virus (NiV), a highly pathogenic paramyxovirus, causes respiratory disease in pigs and severe febrile encephalitis in humans with high mortality rates. On the basis of the structural similarity of viral fusion (F) proteins within the family Paramyxoviridae, we designed and tested 18 quinolone derivatives in a NiV and measles virus (MV) envelope protein-based fusion assay beside evaluation of cytotoxicity. We found five compounds successfully inhibiting NiV envelope protein-induced cell fusion. The most active molecules (19 and 20), which also inhibit the syncytium formation induced by infectious NiV and show a low cytotoxicity in Vero cells, represent a promising lead quinolone-type compound structure. Molecular modeling indicated that compound 19 fits well into a particular protein cavity present on the NiV F protein that is important for the fusion process. 2009 American Chemical Society.