83012-13-9

Usage

Uses

Used in Pharmaceutical Industry:
2,8-BIS(TRIFLUOROMETHYL)-4-CHLOROQUINOLINE is used as a key intermediate in the synthesis of various quinoline-based pharmaceutical compounds for the development of new drugs with potential therapeutic applications.
Used in Chemical Research:
2,8-BIS(TRIFLUOROMETHYL)-4-CHLOROQUINOLINE is also utilized in chemical research for studying the properties and reactions of quinoline derivatives, which can contribute to the advancement of organic chemistry and the discovery of novel chemical entities with diverse applications.

InChI:InChI=1/C8H5BrF4O/c9-5-3-1-2-4-6(5)14-8(12,13)7(10)11/h1-4,7H

Upstream product

• 35853-41-9 2,8-bis(trifluoromethyl)quinolin-4-ol 
• 91991-88-7 2,8-bis-(Trichloromethyl)-4-chloro-quinoline 
• 150785-70-9 2,8-bis(trifluoromethyl)quinolin-4-yl 4-methylbenzenesulfonate 
• 88-17-5 2-(trifluoromethyl)benzenamine 

Downstream Products

• 83012-12-8 α-(2-Pyridyl)-2,8-bis(trifluoromethyl)-4-quinolylacetonitrile 
• 1187471-85-7 4-(2,4,6-trimethoxyphenyl)-2,8-bis-trifluoromethylquinoline 
• 1187471-83-5 4-(2,4-dimethoxyphenyl)-2,8-bis-trifluoromethylquinoline 
• 1236921-61-1 4-hydrazinyl-2,8-bis(trifluoromethyl)quinoline 
• 49752-90-1 (+/-)-mefloquine 
• 401567-76-8 4-(piperazin-1-yl)-2,8-bis(trifluoromethyl)quinoline 

Relevant academic research and scientific papers

New hybrid trifluoromethylquinolines as antiplasmodium agents

Malaria remains a major public health problem worldwide, and it is responsible for high rates of morbidity and mortality. Resistance to current antimalarial drugs has been identified, and new drugs are urgently needed. In this study, we designed and synthesized seventeen novel quinolines based on the structures of mefloquine ((2,8-bis(trifluoromethyl)quinolin-4-yl)(piperidin-2-yl)methanol) and amodiaquine (4-((7-chloroquinolin-4-yl)amino)-2-((diethylamino)methyl)phenol) using ring bioisosteric replacement and molecular hybridization of the functional groups. The compounds were evaluated in vitro against Plasmodium falciparum and in vivo in mice infected with P. berghei. All derivatives presented anti-P. falciparum activity with IC50 values ranging from 0.083 to 33.0 μM. The compound with the best anti-P. falciparum activity was N-(5-methyl-4H-1,2,4-triazol-3-yl)-2,8-bis(trifluoromethyl)quinolin-4-amine (12) which showed an IC50 of 0.083 μM. The three most active compounds were selected for antimalarial activity tests against P. berghei-infected mice. Compound 12 was the most active on the 5th day after infection, reducing parasitemia by 66%, which is consistent with its in vitro activity. This is an important result as 12, a simpler molecule than mefloquine, does not contain the stereogenic center, and consequently, its synthesis in the laboratory is easier and less expensive. This system proved promising for the design of potential antimalarial compounds.

Design, Synthesis, and Antifungal Evaluation of Novel Quinoline Derivatives Inspired from Natural Quinine Alkaloids

Inspired by quinine and its analogues, we designed, synthesized, and evaluated two series of quinoline small molecular compounds (a and 2a) and six series of quinoline derivatives (3a-f) for their antifungal activities. The results showed that compounds 3e and 3f series exhibited significant fungicidal activities. Significantly, compounds 3f-4 (EC50 = 0.41 μg/mL) and 3f-28 (EC50 = 0.55 μg/mL) displayed the superior in vitro fungicidal activity and the potent in vivo curative effect against Sclerotinia sclerotiorum. Preliminary mechanism studies showed that compounds 3f-4 and 3f-28 could cause changes in the cell membrane permeability, accumulation of reactive oxygen species, loss of mitochondrial membrane potential, and effective inhibition of germination and formation of S. sclerotiorum sclerotia. These results indicate that compounds 3f-4 and 3f-28 are novel potential fungicidal candidates against S. sclerotiorum derived from natural products.

Application of 2,8-bis(trifluoromethyl)quinoline 4-modified derivatives in prevention and treatment of plant diseases

The invention discloses 2,8-bis(trifluoromethyl)quinoline 4-modified derivatives, a preparation method thereof and an application of the derivatives in prevention and treatment of plant diseases. Thetest results show that the compounds have excellent control effect on sclerotiniasclerotiorum, rhizoctonia solani, wheat phytoalexin, pyriculariaoryzae, phyllostictazeae, botrytis cinerea, watermelongummy stem blight and cotton fusarium wilt. The derivatives of the invention are simple in preparation process, low in price and easy to obtain raw materials, high in product purity and wide in bactericidal spectrum, and are expected to be developed into a new bactericide.

Design, synthesis and biological evaluation of 4-aminoquinoline-guanylthiourea derivatives as antimalarial agents

Guanylthiourea (GTU) has been identified as an important antifolate antimalarial pharmacophore unit, whereas, 4-amino quinolones are already known for antimalarial activity. In the present work molecules carrying 4-aminoquinoline and GTU moiety have been designed using molecular docking analysis with PfDHFR enzyme and heme unit. The docking results indicated that the necessary interactions (Asp54 and Ile14) and docking score (?9.63 to ?7.36 kcal/mmol) were comparable to WR99210 (?9.89 kcal/mol). From these results nine molecules were selected for synthesis. In vitro analysis of these synthesized compounds reveal that out of the nine molecules, eight show antimalarial activity in the range of 0.61–7.55 μM for PfD6 strain and 0.43–8.04 μM for PfW2 strain. Further, molecular dynamics simulations were performed on the most active molecule to establish comparative binding interactions of these compounds and reference ligand with Plasmodium falciparum dihydrofolate reductase (PfDHFR).

Investigations into the flexibility of the 3D structure and rigid backbone of quinoline by fluorine addition to enhance its blue emission

Achieving the desired structures of organic molecules for targeted applications is vital. Folding caused by weak intermolecular forces plays an important part in their 3D structure. Powerful tools which enable us to do this are currently under investigation by researchers across the globe. On this account, quinoline was chosen as a model scaffold because of its rigid 3D structure. Addition of fluorine was found to result in increased flexibility of the structure with a decrease in the number of intermolecular interactions. This resulted in improvement of their photophysics and blue emission. A total of 19 novel fluoroquinoline molecules were synthesised in order to carry out this study. Of these, grown crystals of 10 compounds were successfully achieved and used. In addition, characterisation techniques such as NMR, HRMS, UV-vis and computational techniques were used to explore the 3D structure of these molecules.

Synthesis of novel triazole-linked mefloquine derivatives: Biological evaluation against Plasmodium falciparum

Using 2,8-bis(trifluoromethyl)quinoline, the pharmacophore of mefloquine, as scaffold, eleven novel triazole-linked compounds have been synthesised by the application of CuAAC chemistry. The in vitro biological activity of the compounds on the Plasmodium falciparum chloroquine-sensitive strain NF54 was then determined. The compounds all showed IC50s in the lower μM range with (1R,3S,5R)-N-{[1-(2,8-bis(trifluoromethyl)quinoline-4-yl)-1H-1,2,3-triazol-4-yl]methyl}adamantan-2-amine (29) exhibiting the best activity of 1.00 μM.

New quinoline derivatives: Synthesis and investigation of antibacterial and antituberculosis properties

Four new series of quinoline derivatives were synthesized starting from 2-trifluoromethyl aniline through multi-step reactions. In the reaction sequence,substituted aniline was cyclized to 4-hydroxy quinoline 1,which was then transformed to 4-chloro-2,8-bis(trifluoromethyl)quinoline 2. The key scaffold 4-hydrazinyl-2,8-bis(trifluoromethyl)quinoline 3,obtained from the compound 2,was successfully converted to target quinoline derivatives,viz. hydrazones 4aet,ureas 5aee,thioureas 6aec and pyrazoles 7aed,in good yields. The newly synthesized title compounds were evaluated for their in vitro antibacterial activity against Escherichia coli,Staphylococcus aureus,Pseudomonas aeruginosa and Klebsiella pneumoniae (recultured) and antituberculosis activity against Mycobacterium tuberculosis H37Rv and MDR-TB. Preliminary results indicated that most of the hydrazone derivatives demonstrated very good antibacterial and antituberculosis activities while other derivatives showed moderate activity.

Synthesis of quinoline analogs: Search for antimalarial agents

Novel synthesis routes for the promising antimalarial agents 4(3-hydroxypyrrolidin-1-yl) and 4(3-hydroxypiperidine-1-yl)-2,8- bis(trifluoromethyl)quinoline have been developed.

A straightforward mid high yielding synthesis of mefloquine - II

A new practical and high yielding synthesis of mefloquine (1) is described. Heteroarylation of 2-pyridylacetonitrile (2) gave the key intermediate 2-pyridyl-4-quinolylacetonitrile 4, which, on reaction with m-chloroperbenzoic acid, gave unexpectedly the cyanhydrine 5 The later, after base treatment afforded quantitatively the ketone 6.

Process for the preparation of fluoromethyl-quinoline derivatives

A process is disclosed for preparing a compound of the Formula (I) STR1 wherein R2 is trifluoromethyl or chloro; R3 is hydrogen or chloro; and X is halogen; wherein a compound of the Formula (II) STR2 wherein R5 is --CFCl2, --CF2 Cl, or --CCl3 ; and R6 is chloro or trichloromethyl; is fluoroinated either with a mixture of antimony (III) fluoride and antimony (V) chloride or bromide; or with antimony (V) fluoride; or with antimony (V) chloride and hydrogen fluoride.