21168-41-2

Basic information

• Product Name: ETHYL 4,6-DICHLORO-3-QUINOLINECARBOXYLATE
• Synonyms: ETHYL 4,6-DICHLOROQUINOLINE-3-CARBOXYLATE;ETHYL 4,6-DICHLORO-3-QUINOLINECARBOXYLATE;4,6-dichloroquinoline-3-carboxylate;4,6-Dichloroquinoline-3-carboxylic acid ethyl ester;Ethyl 4,6-dichloro-quinolin-3-carboxylate
• CAS NO: 21168-41-2
• Molecular Formula: C₁₂H₉Cl₂NO₂
• Molecular Weight: 270.11
• Mol File: 21168-41-2.mol

Chemical Properties

• Melting Point: 90-91℃
• Boiling Point: 351.3 °C at 760 mmHg
• Flash Point: 166.3 °C
• Appearance: /
• Density: 1.384±0.06 g/cm3 (20 ºC 760 Torr)
• Vapor Pressure: 4.15E-05mmHg at 25°C
• Refractive Index: 1.618
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: ETHYL 4,6-DICHLORO-3-QUINOLINECARBOXYLATE(CAS DataBase Reference)
• NIST Chemistry Reference: ETHYL 4,6-DICHLORO-3-QUINOLINECARBOXYLATE(21168-41-2)
• EPA Substance Registry System: ETHYL 4,6-DICHLORO-3-QUINOLINECARBOXYLATE(21168-41-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26
• Hazardous Substances Data: 21168-41-2(Hazardous Substances Data)

Usage

Uses

It is used as a pharmaceutical intermediate.

InChI:InChI=1/C12H9Cl2NO2/c1-2-17-12(16)9-6-15-10-4-3-7(13)5-8(10)11(9)14/h3-6H,2H2,1H3

Upstream product

• 106-47-8 4-chloro-aniline 
• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 79607-22-0 6-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 
• 19056-79-2 diethyl 4-chloroanilinomethylenemalonate 
• 70271-77-1 6-chloro-4-hydroxyquinoline-3-carboxylic acid ethyl ester 

Downstream Products

• 1223002-96-7 ethyl 4-(4-benzylphenylamino)-6-chloroquinoline-3-carboxylate 
• 1223003-25-5 ethyl 6-chloro-4-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)quinoline-3-carboxylate 
• 1307300-91-9 9-chloro-2-phenylbenzo[h][1,6]naphthyridine 
• 1307300-92-0 9-chloro-3-methyl-2-phenylbenzo[h][1,6]naphthyridine 
• 1307300-93-1 9-chloro-2-(2-chlorophenyl)benzo[h][1,6]naphthyridine 
• 1307300-94-2 9-chloro-2-(4-chlorophenyl)benzo[h][1,6]naphthyridine 
• 1307300-95-3 9-chloro-2-(4-fluorophenyl)benzo[h][1,6]naphthyridine 
• 1307300-96-4 9-chloro-2-(4-bromophenyl)benzo[h][1,6]naphthyridine 
• 1307300-97-5 9-chloro-2-(3,4-dimethoxyphenyl)benzo[h][1,6]naphthyridine 
• 1307300-98-6 9-chloro-2-(2,6-dimethoxyphenyl)benzo[h][1,6]naphthyridine 
• 1307300-99-7 9-chloro-2-p-tolylbenzo[h][1,6]naphthyridine 
• 1307301-00-3 2-(3,5-bis(trifluoromethyl)phenyl)-9-chlorobenzo[h][1,6]naphthyridine 
• 1307301-02-5 9-chloro-2-methyl-3-phenylbenzo[h][1,6]naphthyridine 
• 1307301-03-6 9-chloro-2-(4-chlorophenyl)benzo[h][1,6]naphthyridine-3-carbonitrile 

Relevant articles and documents

Interaction of a Triantennary Quinoline Glycoconjugate with the Asialoglycoprotein Receptor

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GABAa receptor ligands often interact with binding sites in the transmembrane domain and in the extracellular domain—can the promiscuity code be cracked?

Many allosteric binding sites that modulate gamma aminobutyric acid (GABA) effects have been described in heteropentameric GABA type A (GABAA) receptors, among them sites for benzodiazepines, pyrazoloquinolinones and etomidate. Diazepam not only binds at the high affinity extracellular “canonical” site, but also at sites in the transmembrane domain. Many ligands of the benzodiazepine binding site interact also with homologous sites in the extracellular domain, among them the pyrazoloquinolinones that exert modulation at extracellular α+/β? sites. Additional interaction of this chemotype with the sites for etomidate has also been described. We have recently described a new indole‐based scaffold with pharmacophore features highly similar to pyrazoloquinolinones as a novel class of GABAA receptor modulators. Contrary to what the pharmacophore overlap suggests, the ligand presented here behaves very differently from the identically substituted pyrazoloquinolinone. Structural evidence demonstrates that small changes in pharmacophore features can induce radical changes in ligand binding properties. Analysis of published data reveals that many chemotypes display a strong tendency to interact promiscuously with binding sites in the transmembrane domain and others in the extracellular domain of the same receptor. Further structural investigations of this phenomenon should enable a more targeted path to less promiscuous ligands, potentially reducing side effect liabilities.

Design and Synthesis of Novel Deuterated Ligands Functionally Selective for the γ-Aminobutyric Acid Type A Receptor (GABAAR) α6 Subtype with Improved Metabolic Stability and Enhanced Bioavailability

Recent reports indicate that α6β2/3γ2 GABAAR selective ligands may be important for the treatment of trigeminal activation-related pain and neuropsychiatric disorders with sensori-motor gating deficits. Based on 3 functionally α6β2/3γ2 GABAAR selective pyrazoloquinolinones, 42 novel analogs were synthesized, and their in vitro metabolic stability and cytotoxicity as well as their in vivo pharmacokinetics, basic behavioral pharmacology, and effects on locomotion were investigated. Incorporation of deuterium into the methoxy substituents of the ligands increased their duration of action via improved metabolic stability and bioavailability, while their selectivity for the GABAAR α6 subtype was retained. 8b was identified as the lead compound with a substantially improved pharmacokinetic profile. The ligands allosterically modulated diazepam insensitive α6β2/3γ2 GABAARs and were functionally silent at diazepam sensitive α1β2/3γ2 GABAARs, thus no sedation was detected. In addition, these analogs were not cytotoxic, which render them interesting candidates for treatment of CNS disorders mediated by GABAAR α6β2/3γ2 subtypes.

Synthesis and preliminary structure-activity relationship study of 2-aryl-2H-pyrazolo[4,3-c]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors

The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour efficacy of cytotoxic chemotherapeutic agents. In the search for new Chk1 inhibitors, a congeneric series of 2-aryl-2 H-pyrazolo[4,3-c]quinolin-3-one (PQ) was evaluated by in-vitro and in-silico approaches for the first time. A total of 30 PQ structures were synthesised in good to excellent yields using conventional or microwave heating, highlighting that 14 of them are new chemical entities. Noteworthy, in this preliminary study two compounds 4e2 and 4h2 have shown a modest but significant reduction in the basal activity of the Chk1 kinase. Starting from these preliminary results, we have designed the second generation of analogous in this class and further studies are in progress in our laboratories.

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SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF

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Structure-activity relationship investigations of the modulating effect of core substituents on the affinity of pyrazoloquinolinone congeners for the benzodiazepine receptor

A series of 6- and 7-substituted-2-arylpyrazolo [4,3-c] quinolin-3-ones was synthesized and tested in vitro for binding with the benzodiazepine receptor in competition with [3H]flunitrazepam. Electronic parameters (molecular electrostatic potential (MEP), charge distribution on the nitrogen atoms, dipole moment μ, and ionization potential (IP) were calculated for the compounds by semi-empirical quantum chemistry methods. Lipophilicity of the compounds, expressed as logarithm of the octanol-water partition coefficient (log P), was calculated by the program Pallas. A quantitative correlation of the biological data with molecular parameters revealed a significant dependence (r = 0.95) of the activity on hydrophobic constants of the substituents, log P, and magnitude of the MEP minimum associated with the carbonyl oxygen atom.