607-40-9

Usage

Uses

Used in Pharmaceutical Industry:
6-Fluoro-2-hydroxyquinoline-4-carboxylic acid is used as a key intermediate in the synthesis of antimalarial drugs. Its unique chemical structure allows it to be incorporated into drug molecules that target and inhibit the growth of Plasmodium parasites, which are responsible for causing malaria. 6-FLUORO-2-HYDROXYQUINOLINE-4-CARBOXYLIC ACID contributes to the development of effective treatments against malaria, a disease that affects millions of people worldwide and can lead to severe health complications and death if left untreated.

InChI:InChI=1/C10H6FNO3/c11-5-1-2-8-6(3-5)7(10(14)15)4-9(13)12-8/h1-4H,(H,12,13)(H,14,15)

Upstream product

• 715-88-8 1-acetyl-5-fluoro-1H-indole-2,3-dione 
• 351-09-7 N-(4-fluorophenyl)-2-(hydroxyimino) acetamide 
• 443-69-6 5-fluoro-1H-indole-2,3-dione 
• 108-24-7 acetic anhydride 
• 141-82-2 malonic acid 
• 15912-69-3 6-fluoro-2-hydroxy-4-methylquinoline 
• 2713-85-1 N-(4-fluorophenyl)-3-oxobutanamide 
• 371-40-4 4-fluoroaniline 

Downstream Products

• 1469439-69-7 6-fluoro-2-[4-(morpholinomethyl)phenyl]-N-(2-pyrrolidin-1-ylethyl)quinoline-4-carboxamide 
• 436096-52-5 2-chloro-6-fluoro-4-quinolinecarboxylic acid 
• 1388844-25-4 6-fluoro-2-oxo-1,2-dihydroquinoline-4-carbohydrazide 
• 1388844-20-9 ethyl 6-fluoro-2-oxo-1,2-dihydroquinoline-4-carboxylate 

Relevant academic research and scientific papers

Discovery, synthesis and molecular substantiation of N-(benzo[d]thiazol-2-yl)-2-hydroxyquinoline-4-carboxamides as anticancer agents

The effort was taken to develop a series of benzothiazole and quinoline fused bioactive compounds obtained through a four-step synthetic route using a range of substituted acetoacetanilides. Achieved N-(benzo[d]thiazol-2-yl)-2-hydroxyquinoline-4-carboxamides (6a-l) were produced up to 96% of yield while the eco-friendly p-TSA used as a catalyst. Further, the anticancer activity of these compounds was determined using a range of cancer cell lines starting from MCF-7 (Breast cancer), HCT-116 (Colon cancer), PC-3 & LNCaP (Prostate) and SK-HEP-1 (Liver cancer). Present study compounds were also testified for antioxidant properties prior to anticancer studies since the Reactive Oxygen Species (ROS) being vital in cancer development. To determine the cell membrane stability effects of the compounds, human red blood cells (HRBC) based membrane protection assay was determined. In the results, compounds 6a-l were able to produce a dominated result values over PC3 cell lines (Prostate cancer) than the other cell lines used in this study. Since the connectivity of human germ cell alkaline phosphatase (hGC-ALP) in the development of prostate cancer is known, the most active compounds were evaluated for the hGC-ALP inhibition in order to ensure a mechanism of anticancer action of these compounds. The mode of interaction and binding affinity of these compounds was also investigated by a molecular docking study. In the results, 6d, 6i, 6k, and 6l were found with least IC50 values 0.075 μM and highest relative activity of 92%, 90%, and 96% respectively. The need for further animal model evaluation and pre-clinical studies recognized.

Discovery of Quinoline Analogues as Potent Antivirals against Enterovirus D68 (EV-D68)

Enterovirus D68 (EV-D68) is an atypical nonpolio enterovirus that mainly infects the respiratory system of humans, leading to moderate-to-severe respiratory diseases. In rare cases, EV-D68 can spread to the central nervous system and cause paralysis in infected patients, especially young children and immunocompromised individuals. There is currently no approved vaccine or antiviral available for the prevention and treatment of EV-D68. In this study, we aimed to improve the antiviral potency and selectivity of a previously reported EV-D68 inhibitor, dibucaine, through structure-activity relationship studies. In total, 60 compounds were synthesized and tested against EV-D68 using the viral cytopathic effect assay. Three compounds 10a, 12a, and 12c were identified to have significantly improved potency (EC50 180) compared with dibucaine against five different strains of EV-D68 viruses. These compounds also showed potent antiviral activity in neuronal cells, such as A172 and SH-SY5Y cells, suggesting they might be further developed for the treatment of both respiratory infection as well as neuronal infection.

Synthesis and Pharmacological Evaluation of [11C]Granisetron and [18F]Fluoropalonosetron as PET Probes for 5-HT3 Receptor Imaging

Serotonin-gated ionotropic 5-HT3 receptors are the major pharmacological targets for antiemetic compounds. Furthermore, they have become a focus for the treatment of irritable bowel syndrome (IBS) and there is some evidence that pharmacological modulation of 5-HT3 receptors might alleviate symptoms of other neurological disorders. Highly selective, high-affinity antagonists, such as granisetron (Kytril) and palonosetron (Aloxi), belong to a family of drugs (the "setrons") that are well established for clinical use. To enable us to better understand the actions of these drugs in vivo, we report the synthesis of 8-fluoropalonosetron (15) that has a binding affinity (Ki = 0.26 ± 0.05 nM) similar to the parent drug (Ki = 0.21 ± 0.03 nM). We radiolabeled 15 by nucleophilic 18F-fluorination of an unsymmetrical diaryliodonium palonosetron precursor and achieved the radiosynthesis of 1-(methyl-11C)-N-granisetron ([11C]2) through N-alkylation with [11C]CH3I, respectively. Both compounds [18F]15 (chemical and radiochemical purity >95%, specific activity 41 GBq/μmol) and [11C]2 (chemical and radiochemical purity ≥99%, specific activity 170 GBq/μmol) were evaluated for their utility as positron emission tomography (PET) probes. Using mouse and rat brain slices, in vitro autoradiography with both [18F]15 and [11C]2 revealed a heterogeneous and displaceable binding in cortical and hippocampal regions that are known to express 5-HT3 receptors at significant levels. Subsequent PET experiments suggested that [18F]15 and [11C]2 are of limited utility for the PET imaging of brain 5-HT3 receptors in vivo.

Discovery of a Quinoline-4-carboxamide Derivative with a Novel Mechanism of Action, Multistage Antimalarial Activity, and Potent in Vivo Efficacy

The antiplasmodial activity, DMPK properties, and efficacy of a series of quinoline-4-carboxamides are described. This series was identified from a phenotypic screen against the blood stage of Plasmodium falciparum (3D7) and displayed moderate potency but with suboptimal physicochemical properties and poor microsomal stability. The screening hit (1, EC50 = 120 nM) was optimized to lead molecules with low nanomolar in vitro potency. Improvement of the pharmacokinetic profile led to several compounds showing excellent oral efficacy in the P. berghei malaria mouse model with ED90 values below 1 mg/kg when dosed orally for 4 days. The favorable potency, selectivity, DMPK properties, and efficacy coupled with a novel mechanism of action, inhibition of translation elongation factor 2 (PfEF2), led to progression of 2 (DDD107498) to preclinical development.

Anti-Malarial Agents

The present invention relates to a novel class of quinolone-4-carboxamide Pf3D7 inhibitors of general formula (I) (Formula (I)) wherein R1, R2, R3, R4, R5, R6, R7, R8 and X are as defined herein, to their use in medicine, and in the treatment of malaria in particular, to compositions containing them, to processes for their preparation and to intermediates used in such processes.

ANTI-MALARIAL AGENTS

The present invention relates to a novel class of quinolone-4-carboxamide Pf3D7 inhibitors of general formula (I) (Formula (I)) wherein R1, R2, R3, R4, R5, R6, R7, R8 and X are as defined herein, to their use in medicine, and in the treatment of malaria in particular, to compositions containing them, to processes for their preparation and to intermediates used in such processes.

Construction and functionalization of fused pyridine ring leading to novel compounds as potential antitubercular agents

A series of fused and functionalized pyridine derivatives were designed, synthesized and tested for their potential antitubercular properties. All these novel compounds were prepared by using multistep methods involving the construction of pyridine ring as a key synthetic step. Some of these compounds were found to be interesting when tested for their antitubercular properties in vitro and one of them appeared as an attractive and potential antitubercular agent.

Use of imidazo?1,5-a!quinolones as neuroprotective agents

The imidazo?1,5-a!quinolines (I) are useful in treating neurological diseases/conditions or chronic neurodegenerative diseases/conditions.

Imidazo[1,5-A]quinolines for treatment of anxiety and sleep disorders

Imidazo[1,5-a]quinolines of formula (I) which are useful pharmaceutical agents for the treatment of anxiety, sleep disorders, panic states, convulsions and muscle disorders. STR1