4295-06-1

Basic information

• Product Name: 4-CHLORO-2-METHYLQUINOLINE
• Synonyms: TIMTEC-BB SBB005362;AKOS BBS-00000956;4-CHLOROQUINALDINE;4-CHLORO-2-METHYLQUINOLINE;Quinaldine, 4-chloro-;Quinoline, 4-chloro-2-methyl-;2-Methyl-4-chloroquinoline;4-Chloroquinaldine 99%
• CAS NO: 4295-06-1
• Molecular Formula: C₁₀H₈ClN
• Molecular Weight: 177.63
• EINECS: 224-300-8
• Product Categories: Halides;Quinolines, Isoquinolines & Quinoxalines;Quinolines;Quinolines, Isoquinolines & Quinoxalines;QuinaldinesHeterocyclic Building Blocks;Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Quinaldines
• Mol File: 4295-06-1.mol

Chemical Properties

• Melting Point: 39 °C
• Boiling Point: 269-270 °C(lit.)
• Flash Point: >230 °F
• Appearance: /
• Density: 0.881 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.012mmHg at 25°C
• Refractive Index: n20/D 1.622(lit.)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 4.40±0.50(Predicted)
• Water Solubility: Slightly soluble in water.
• BRN: 3522
• CAS DataBase Reference: 4-CHLORO-2-METHYLQUINOLINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-CHLORO-2-METHYLQUINOLINE(4295-06-1)
• EPA Substance Registry System: 4-CHLORO-2-METHYLQUINOLINE(4295-06-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39
• WGK Germany: 3
• Hazardous Substances Data: 4295-06-1(Hazardous Substances Data)

Usage

Uses

4-Chloroquinaldine is used in the preparation of 4-phenyl-hydrazinoquinaldine

InChI:InChI=1/C10H8ClN/c1-7-6-9(11)8-4-2-3-5-10(8)12-7/h2-6H,1H3

Upstream product

• 1076-28-4 2-methylquinoline N-oxide 
• 5660-24-2 2-methyl-1H-quinolin-4-one 
• 7791-25-5 sulfuryl dichloride 
• 10026-13-8 phosphorus pentachloride 
• 10025-87-3 trichlorophosphate 
• 90924-22-4 1-hydroxy-2-methylquinolin-4(1H)-one 
• 7719-12-2 phosphorus trichloride 
• 607-67-0 4-hydroxy-2-methylquinoline 
• 68-12-2 N,N-dimethyl-formamide 
• 611-35-8 4-chloroquinoline 
• 917-54-4 methyllithium 
• 17469-23-7 (E)-ethyl 3-(phenylamino)but-2-enoate 
• 62-53-3 aniline 
• 497-19-8 sodium carbonate 

Downstream Products

• 57599-96-9 bis(quinaldinylamino)hexane 
• 19056-26-9 N,N'-bis-(2-methyl-[4]quinolyl)-decanediyldiamine 
• 856093-76-0 2-methyl-4-(3-nitro-phenoxy)-quinoline 
• 858451-94-2 2-methyl-4-(4-methyl-3-nitro-phenoxy)-quinoline 
• 31835-53-7 4-methoxy-2-methyl-quinoline 
• 82241-22-3 2-methyl-4-(piperazin-1-yl)quinoline 
• 113798-28-0 4-chloro-2-[(1E)-2-phenylethenyl]quinoline 
• 6907-56-8 (4-methoxyphenyl)-(2-methylquinolin-4-yl)-amine 
• 116289-37-3 2-(2-methyl-[4]quinolylamino)-ethanol 
• 219528-34-4 4-(4-methoxy-phenoxy)-2-methyl-quinoline 
• 97739-99-6 N-(2-methyl-[4]quinolyl)-sulfanilic acid amide 
• 51336-03-9 (2-methylquinolin-4-yl)-phenylamine 

Relevant articles and documents

Facile syntheses of disubstituted bis(vinylquinolinium)benzene derivatives as G-quadruplex DNA binders

Abstract A series of disubstituted bis(vinylquinolinium)benzene derivatives were designed, which were prepared through a facile three-component one-pot reaction in good yield. FRET results showed that 1,3-disubstituted benzene derivatives had much stronger stabilization effect on G-quadruplex DNA than that of 1,4-disubstituted benzene derivatives. The introduction of substituted amine side chain at quinolinium obviously increased the binding affinity of compounds to G-quadruplex DNA. It was also found that 1,3-disubstituted benzene derivatives and 1,4-disubstituted benzene derivatives had different effects on the conformation of G-quadruplex DNA by CD spectroscopy analysis. The differences for the interactions of these two classes of compounds with G-quadruplex were further studied and elaborated through molecular modeling experiments.

Development of a light-up fluorescent probe for HRAS G-quadruplex DNA

The development of small-molecule G-quadruplex DNA probes has attracted significant attention in recent years. However, G-quadruplexes can display a wide variety of topologies, which process different structures and functions. Therefore, selective discrimination one G-quadruplex structure over another is promising. Herein, we reported the design, synthesis and biological evaluation of a long-chain fatty amine functionalized triphenylamine-quinolinium conjugate 1b. Significant enhancement of the fluorescence intensity (over 180 fold) was observed when 1b bound with HRAS G-quadruplex DNA, while much weaker enhancements were presented in the presence of other G-quadruplexes (45–90-fold) and single/double-stranded DNAs (less than 20-fold), indicating 1b had an excellent selectivity to HRAS. The details of the interactions were investigated by UV–Vis, FID and CD analysis. The results show 1b could interact and stabilize HRAS structure mainly by π-π stacking binding mode. The introduced amine chain of the structure core was found to be better in the terms of inducing selectivity toward G-quadruplex structure. In addition, the application of 1b as a fluorescent agent for living cell imaging was also demonstrated.

A triphenylamine derivative as a naked-eye and light-up fluorescent probe for G-quadruplex DNA

G-quadruplex (G4) DNAs have attracted considerable interest because of their important biological functions and medical applications. Searching for highly specific binding molecules is important for the basic research of G4 DNA, as well as the design of novel anticancer drugs. Previous, we have developed a quinolone-substituted triphenylamine probe (TPA-2b) with selectivity to G4 DNAs. Herein, we further designed and synthesized a hydroxyethyl functionalized derivative (TPA-3) and investigated the interactions with G4 DNAs and living cells. TPA-3 was found to express significant fluorescence enhancement upon its interaction with G4 DNAs while shows almost no response to non-quadruplex DNAs. The distinction can even be easily distinguished by the naked eye under UV light. The spectral analysis showed TPA-3 bound to G4 DNAs mainly through intercalative binding mode. CD study results indicated TPA-3 did not disturb the conformation of G4 structure. Cellular uptake assay suggested that TPA-3 could pass through membrane and enter living cells. Our results suggested the side chain of core structure could change the binding affinity to G4 DNAs, as well as the interaction with living cells. Thus, this study gives some clues to design new G4 DNA probes with high selectivity, sensitivity, and biological imaging applications.

Development of an engineered carbazole/thiazole orange conjugating probe for G-quadruplexes

The development of selective and sensitive probes for sensing G-quadruplexes either in vitro or in cellulo has been the focus of investigation for a long time. Of those investigated, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) is a promising fluorescent probe utilized in many studies investigating G-quadruplex structures. However, its shortcomings, including similar fluorescence responses for G-quadruplex and duplex DNA and green but not red fluorescent emission, might restrict the further application of BMVC. In this study, in order to improve the selectivity and optical properties of BMVC, we engineered a new probe (TO-CZ) by incorporating thiazole orange (TO) into the structure of BMVC. We next found that TO-CZ can act as a colorimetric and red-emitting fluorescent dual probe selective for G-quadruplexes without affecting the G-quadruplex topology. Further experiments showed that a 2:1 binding model involving the external binding of TO-CZ to both ends of the G-quadruplex is the most possible binding mode. Furthermore, we applied TO-CZ in sensing G-quadruplexes both in vitro and in cellulo, and found that TO-CZ can selectively and sensitively visualize G-quadruplexes. Notably, TO-CZ might be used to map DNA and RNA G-quadruplexes in cellulo, showing its great potential in investigating intracellular G-quadruplex structures.

Preparation of 4-flexible amino-2-arylethenyl-quinoline derivatives as multi-target agents for the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is a complex and multifactorial neurodegenerative disorder of aged people. The development of multitarget-directed ligands (MTDLs) to act as multifunctional agents to treat this disease is the mainstream of current research. As a continuation of our previous studies, a series of 4-flexible amino-2-arylethenylquinoline derivatives as multi-target agents was efficiently synthesized and evaluated for the treatment of AD. Among these synthesized derivatives, some compounds exhibited strong self-induced Aβ1–42 aggregation inhibition and antioxidant activity. The structure-activity relationship was summarized, which confirmed that the introduction of a flexible amino group featuring a N,N-dimethylaminoalkylamino moiety at the 4-position increased the Aβ1–42 aggregation inhibition activity, with an inhibition ratio of 95.3% at 20 μM concentration. Compound 6b1, the optimal compound, was able to selectively chelate copper (II), and inhibit Cu2+-induced Aβ aggregation effectively. It also could disassemble the self-induced Aβ1–42 aggregation fibrils with a ratio of 64.3% at 20 μM concentration. Moreover, compound 6b1 showed low toxicity and a good neuroprotective effect against Aβ1–42-induced toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated compound 6b1 significantly reversed scopolamine-induced memory deficit in mice. Taken together, these results suggested that compound 6b1 was a promising multi-target compound worthy of further study for AD.

Discovery of 4-anilinoquinolinylchalcone derivatives as potential NRF2 activators

Activation of nuclear factor erythroid-2-related factor 2 (NRF2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent NRF2 activator and cancer chemopreventive agent. In this study, we have synthesized a series of 4-anilinoquinolinylchalcone derivatives, and used a NRF2 promoter-driven firefly luciferase reporter stable cell line, the HaCaT/ARE cells, to screen a panel of these compounds. Among them, (E)-3-{4-[(4-acetylphenyl)amino]quinolin-2-yl}-1-(4-fluorophenyl)prop-2-en-1-one (13b) significantly increased NRF2 activity in the HaCaT cell with a half maximal effective concentration (EC50) value of 1.95 μM. Treatment of compound 13b upregulated HaCaT cell NRF2 expression at the protein level. Moreover, the mRNA level of NRF2 target genes, heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glucose-6-phosphate dehydrogenase (G6PD) were significantly increased in HaCaT cells upon the compound 13b treatment. The molecular docking results exhibited that the small molecule 13b is well accommodated by the bound region of Kelch-like ECH-associated protein 1 (Keap1)-Kelch and NRF2 through stable hydrogen bonds and hydrophobic interaction, which contributed to the enhancement of affinity and stability between the ligand and receptor. Compound 13b has been identified as the lead compound for further structural optimization.

Synthesis, Structure-Activity Relationship, and Antimalarial Efficacy of 6-Chloro-2-arylvinylquinolines

There is an urgent need to develop new efficacious antimalarials to address the emerging drug-resistant clinical cases. Our previous phenotypic screening identified styrylquinoline UCF501 as a promising antimalarial compound. To optimize UCF501, we herein report a detailed structure-activity relationship study of 2-arylvinylquinolines, leading to the discovery of potent, low nanomolar antiplasmodial compounds against a Plasmodium falciparum CQ-resistant Dd2 strain, with excellent selectivity profiles (resistance index 200). Several metabolically stable 2-arylvinylquinolines are identified as fast-acting agents that kill asexual blood-stage parasites at the trophozoite phase, and the most promising compound 24 also demonstrates transmission blocking potential. Additionally, the monophosphate salt of 24 exhibits excellent in vivo antimalarial efficacy in the murine model without noticeable toxicity. Thus, the 2-arylvinylquinolines represent a promising class of antimalarial drug leads.

A ortho position alkylation method of organic compound containg pyridine

A process for introducing alkyl at ortho positions of organic compounds containing pyridine. The method is not affected by the kind of substituent bonded to the pyridine and can be alkylated with high positional selectivity and high yield at N-based ortho-position of pyridine without being affected by the kind of substituent introduced to pyridine ortho position (pyridine N-based) can be advantageously used for the preparation of a compound containing an alkyl-introduced pyridine structure.

Triphenylamine - quinoline derivatives and adopts its modification for detecting the oncogene related G - quadruplex optical fiber sensor

The invention belongs to the field of molecular biology, in particular to triphenylamine - quinoline derivatives and adopts its modification for detecting the oncogene related G - quadruplex optical fiber sensor, the present invention provides a new structure of the triphenylamine - quinoline derivatives, the quinoline derivative by the method of the present invention modified with activated hydroxyl of the surface layer of the optical fiber sensor of the optical fiber, the optical fiber sensor can be quickly specific detection HRAS G - quadruplex and HTG - 21 G - quadruplex, makes up for the optical fiber DNA sensor detecting G4 - DNA vacancies of the chain, since many of the cancer disease is due to the initiation of the cells in vivo G4 - DNA over-expression of the chain, the invention is specific detection G4 DNA offers a high-efficient and swift sensor, the sensor is expected to be applied to the biological and clinical analysis.

Design, synthesis, biological evaluation, and molecular modeling studies of quinoline-ferulic acid hybrids as cholinesterase inhibitors

A series of quinoline-ferulic acid hybrids has been designed, synthesized, and evaluated as cholinesterase inhibitors. Most of the compounds showed good inhibitory activities toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, 10f was found to be the most potent inhibitor against AChE (IC50 = 0.62 ± 0.17 μM), and 14 was the most potent inhibitor against BChE (IC50 = 0.10 ± 0.01 μM). Representative compounds, such as 10f and 12g, act in a competitive manner when they inhibit AChE or BChE. Molecular docking and dynamic simulation revealed that the synthesized compounds bind to the target by simultaneously interacting with the catalytic active site (CAS) and the peripheral anionic site (PAS) of both AChE and BChE. The U-shaped confirmation was preferred when 12g bound to BChE, which was different from the linear conformation of 10f bound to AChE. Cell-based assays have confirmed the moderate neuroprotective effects of compounds 10f and 12g against H2O2-induced oxidative damage towards PC12 cells. Moreover, the hepatotoxicity of 12g was lower than that of tacrine, indicating its potential safety as an anti-Alzheimer's agent. In summary, we report a new chemotype of multifunctional hybrid, which may be further modified to develop new anti-Alzheimer's agents.