19056-78-1

Usage

Uses

Used in Organic Synthesis:
2-((2-CHLOROPHENYLAMINO)METHYLENE)MALONIC ACID DIETHYL ESTER is used as a building block in organic synthesis for its ability to contribute to the formation of various complex organic molecules. Its reactive methylene group allows for versatile chemical reactions, making it a valuable component in the creation of new compounds.
Used in Pharmaceutical Research:
In the pharmaceutical industry, 2-((2-CHLOROPHENYLAMINO)METHYLENE)MALONIC ACID DIETHYL ESTER is used as a precursor in the development of new drugs. Its unique structure and reactivity can be harnessed to create pharmaceutical agents with potential therapeutic applications. Researchers leverage its properties to explore its efficacy in treating various medical conditions, although further studies are required to fully understand its potential impact on human health.

InChI:InChI=1/C14H16ClNO4/c1-3-19-13(17)10(14(18)20-4-2)9-16-12-8-6-5-7-11(12)15/h5-9,16H,3-4H2,1-2H3

Upstream product

• 95-51-2 o-chloroaniline 
• 87-13-8 diethyl 2-ethoxymethylenemalonate 

Downstream Products

• 73987-37-8 8-chloro-4-hydroxy-quinoline-3-carboxylic acid ethyl ester 
• 52980-27-5 8-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 
• 874764-65-5 8-chloro-4-hydroxy-quinoline-3-carboxylic acid hydrazide 
• 95-51-2 o-chloroaniline 
• 1415327-28-4 2-[(2-chloro-phenylamino)-methylene]-malonic acid monoethyl ester 
• 21617-12-9 4,8-dichloroquinoline 
• 57797-97-4 4-hydroxy-8-chloroquinoline 
• 35975-71-4 8-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 

Relevant academic research and scientific papers

Crystal Packing Modulation of the Strength of Resonance-Assisted Hydrogen Bonds and the Role of Resonance-Assisted Pseudoring Stacking in Geminal Amido Esters: Study Based on Crystallography and Theoretical Calculations

A detailed experimental and theoretical investigation of a series of substituted geminal amido esters (ethyl (2E)-3-(arylamino)-2-(arylcarbamoyl)prop-2-enoate, AME-1-8) leading to the identification of a unique angularly fused pseudotricyclic (S(6),S(6),S(6)) ring system stabilized by an intramolecular resonance-assisted hydrogen bond (RAHB) and a non-RAHB are presented in addition to weak intermolecular interactions. An analysis of X-ray and theoretical models reveals that the strength of the intramolecular RAHB (N1-H1N···O1) varies in a wide range (6.9-11.4 kcal mol-1) due to crystal-packing constraints arising from different aromatic ring substitutions. However, the effect is less significant and the strength differs only in a narrow range (8.2-9.9 kcal mol-1) in the case of non-RAHB. The downfield shift (δ～12.3) observed for the N-Haniline signal in 1H NMR spectra of AME-1-8 is due to the presence of intramolecular RAHB. A PIXEL energy analysis suggests that the molecular dimer formed by stacking of RAHB pseudorings is found to be strong (Etot = -14.4 to -17.9 kcal mol-1), and this dimer forms the basic motif in most of the structures reported herein. A detailed analysis of the isostructurality suggests that the basic motif exists in most of the structural combinations. The weak intermolecular C-H···O, C-H···Cl, and C-H···πinteractions play a vital role in the stabilization of these crystal structures, as evaluated by PIXEL and Bader's quantum theory of atoms in molecules approach (QTAIM). A lattice energy analysis suggests that the Coulombic contribution and total lattice energies are higher in the para-substituted compounds (AME-2, AME-5, and AME-8) in comparison to the other isomeric compounds. Further, the crystal packing of these compounds is analyzed on the basis of the energy frameworks. It shows that most of the crystals show similar 3D topologies, suggesting that these compounds may have similar mechanical behavior.

3-(Benzo[: D] thiazol-2-yl)-4-aminoquinoline derivatives as novel scaffold topoisomerase i inhibitor via DNA intercalation: Design, synthesis, and antitumor activities

Twenty-seven 3-(benzo[d]thiazol-2-yl)-4-aminoquinoline derivatives have been designed and synthesized as topoisomerase I inhibitors. The in vitro anti-proliferation evaluation against four human cancer cell lines (MGC-803, HepG-2, T24, and NCI-H460) and one normal cell line (HL-7702) indicated that most of them exhibited potent cytotoxicity. Among them, 5a was identified as the most promising candidate with a low IC50 value of about 2.20 ± 0.14 and was selected for further exploration. Spectroscopic analyses and agarose-gel electrophoresis assays indicated that 5a could interact with DNA and strongly inhibit topoisomerase I (Topo I). Further screening of the Topo I activity of compounds 5b, 5c, 5e, 5f, 5h, 5i, 5j, 5l, and 5n suggested that some of the compounds might exert quite a different cytotoxicity profile to that of 5a. Molecular modeling studies confirmed that 5a adopts a unique mode to interact with DNA and Topo I. Other molecular mechanistic studies suggested that the treatment of MGC-803 cells with 5a induces S phase arrest, up-regulates the pro-apoptotic protein, down-regulates the anti-apoptotic protein, activates caspase-3, and subsequently induces mitochondrial dysfunction so as to induce cell apoptosis. The in vivo efficiency of 5a was also evaluated on MGC-803 xenograft nude mice and the relative tumor growth inhibition was 42.4percent at 12 mg kg-1 without an obvious loss in the body weight. This journal is

2,2-Bis(ethoxycarbonyl)vinyl (BECV) as a versatile amine protecting group for selective functional-group transformations

A 2,2-Bis(ethoxycarbonyl) vinyl- (BECV) group was used for the selective protection of amines at room temperature in the presence of potentially interfering functional groups such as OH, SH, COOH as well as other NH 2 groups. Several functional group transformations such as esterification, O-alkylation, O-acylation, N-alkylation, N-acylation, S-alkylation can selectively be carried out in the presence of the BECV group. The selective deprotection of the BECV group was achieved in a short time using ethylenediamine at room temperature while several other functional groups such as benzoate, aliphatic esters, amides and ethers remain intact. The BECV group shows orthogonal stability against the common protecting groups such as Fmoc, Cbz and Boc.

Quinoline-3-carboxamide containing sulfones as liver X receptor (LXR) agonists with binding selectivity for LXRβ and low blood-brain penetration

A series of quinoline-3-carboxamide containing sulfones was prepared and found to have good binding affinity for LXRβ and moderate binding selectivity over LXRα. The 8-Cl quinoline analog 33 with a high TPSA score, displayed 34-fold binding selectivity for LXRβ over LXRα (LXRβ IC50 = 16 nM), good activity for inducing ABCA1 gene expression in a THP macrophage cell line, desired weak potency in the LXRα Gal4 functional assay, and low blood-brain barrier penetration in rat.

Design, synthesis, and biological evaluation of novel quinoline derivatives as HIV-1 Tat-TAR interaction inhibitors

Thirty-two quinoline derivatives were designed and synthesized as HIV-1 Tat-TAR interaction inhibitors. All the compounds showed high antiviral activities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Nine of them with low cytotoxicities were evaluated by Tat dependent HIV-1 LTR-driven CAT gene expression colorimetric enzyme assay in human 293T cells, indicating effective inhibitory activities of blocking the Tat-TAR interaction. Molecular modeling experiments indicated that these compounds may inhibit Tat-TAR interaction by binding to Tat protein instead of TAR RNA.

Pharmacomodulations around the 4-oxo-1,4-dihydroquinoline-3-carboxamides, a class of potent CB2-selective cannabinoid receptor ligands: Consequences in receptor affinity and functionality

CB2 receptor selective ligands are becoming increasingly attractive drugs due to the potential role of this receptor in several physiopathological processes. Thus, the development of our previously described series of 4-oxo-1,4-dihydroquinoline-3-carboxamides was pursued with the aim to further characterize the structure-affinity and structure-functionality relationships of these derivatives. The influence of the side chain was investigated by synthesizing compounds bearing various carboxamido and keto substituents. On the other hand, the role of the quinoline central scaffold was studied by synthesizing several 6-, 7-, or 8-chloro-4-oxo-1,4-dihydroquinolines, as well as 4-oxo-1,4-dihydronaphthyridine and 4-oxo-1,4-dihydrocinnoline derivatives. The effect of these modifications on the affinity and functionality at the CB2 receptor was studied and allowed for the characterization of new selective CB2 receptor ligands.

TRIAZOLE COMPOUNDS AS LIPOXYGENASE INHIBITORS

There is provided compounds of formula (I) wherein W is an optionally substituted aryl or heteroaryl group, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a lipoxygenase (e.g. 15- lipoxygenase) is desired and/or required, and particularly in the treatment of inflammation.

Evaluation of 3-carboxy-4(1H)-quinolones as inhibitors of human protein kinase CK2

Due to the emerging role of protein kinase CK2 as a molecule that participates not only in the development of some cancers but also in viral infections and inflammatory failures, small organic inhibitors of CK2, besides application in scientific research, may have therapeutic significance. In this paper, we present a new class of CK2 inhibitors-3-carboxy-4(1H)-quinolones. This class of inhibitors has been selected via receptor-based virtual screening of the Otava compound library. It was revealed that the most active compounds, 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (7) (IC 50 = 0.3 μM) and 4-oxo-1,4-dihydrobenzo[h]quinoline-3-carboxylic acid (9) (IC50 = 1 μM), are ATP competitive (Ki values are 0.06 and 0.28 μM, respectively). Evaluation of the inhibitors on seven protein kinases shows considerable selectivity toward CK2. According to theoretical calculations and experimental data, a structural model describing the key features of 3-carboxy-4(1H)-quinolones responsible for tight binding to CK2 active site has been developed.

Antimalarials: Synthesis of 4-aminoquinolines that circumvent drug resistance in malaria parasites

The strategies described here have permitted the synthesis of a series of 4-aminoquinoline antimalarials. Substantive improvements over previous syntheses include nucleophilic substitution with neat amine rather than in phenol, regioselective reductive alkylation to convert the terminal primary amine (12a-20a) on the diaminoalkane side chain to a diethylamino group, and purification by column chromatography with basic alumina. The 1H nmr spectra obtained after regioselective reductive alkylation with sodium borodeuteride (in comparison with sodium borohydride) demonstrated that this reductive alkylation proceeds via formation and subsequent reduction of the corresponding diamides in situ.

An NMR study of halogenated 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylates

Ethyl 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylate and 29 of its mono-, di-and tri-fluoro and/or -chloro derivatives were synthesized and their 1H, 13C and 19F NMR spectra were recorded. 1H, 13C and 19F chemical shifts, JHH, JFH, JCF and JFF coupling constants are reported. The 13C substituent chemical shift values of the chloro and fluoro substituents were calculated by linear multiple regression.