19056-79-2

Usage

Uses

Used in Organic Synthesis:
2-((4-CHLOROPHENYLAMINO)METHYLENE)MALONIC ACID DIETHYL ESTER is used as a reagent for the formation of heterocycles, which are important structural components in many biologically active compounds and materials.
Used in Pharmaceutical Synthesis:
In the pharmaceutical industry, 2-((4-CHLOROPHENYLAMINO)METHYLENE)MALONIC ACID DIETHYL ESTER is used as a starting material for the synthesis of various drugs, contributing to the development of new therapeutic agents.
Used in Agrochemical Synthesis:
Similarly, in agrochemical applications, 2-((4-CHLOROPHENYLAMINO)METHYLENE)MALONIC ACID DIETHYL ESTER is utilized as a starting material for the synthesis of agrochemicals, aiding in the creation of compounds for crop protection and enhancement of agricultural productivity.

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

Upstream product

• 106-47-8 4-chloro-aniline 
• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 105-53-3 diethyl malonate 
• 27971-92-2 diethyl 2,2,2-trichloroethylidenepropanedioate 

Downstream Products

• 70271-77-1 6-chloro-4-hydroxyquinoline-3-carboxylic acid ethyl ester 
• 302965-43-1 6-chloro-4-hydroxy-quinoline-3-carboxylic acid hydrazide 
• 1456629-64-3 6-chloro-1-ethyl-4-oxo-1,4-dihydro-3-[1-oxo-2-hydrazino-3-{p-toluenesulfon}]quinoline 
• 955314-37-1 6-chloro-4-oxo-N'-(2,5-dimethoxyphenyl)-1,4-dihydroquinoline-3-carboxamide 
• 1636164-11-8 6-chloro-4-oxo-N'-(2,5-dichlorophenyl)-1,4-dihydroquinoline-3-carboxamide 
• 955314-03-1 6-chloro-4-oxo-N'-(p-tolyl)-1,4-dihydroquinoline-3-carboxamide 
• 914658-49-4 6-chloro-4-oxo-N'-phenyl-1,4-dihydroquinoline-3-carboxamide 
• 860205-71-6 6-chloro-4-oxo-N'-(4-chlorophenyl)-1,4-dihydroquinoline-3-carboxamide 
• 228725-53-9 6-chloro-4-oxo-N'-(4-chlorobenzyl)-1,4-dihydroquinoline-3-carboxamide 
• 1185869-39-9 6-chloro-1,4-dihydro-4-oxoquinoline-3-carbohydrazide 
• 1462359-44-9 6-chloro-4-oxo-1,4-dihydro-3-[1-oxo-2-hydrazino-3-{p-toluenesulfonyl}]quinoline 
• 1415327-27-3 2-[(4-chlorophenylamino)-methylene]-malonic acid monoethyl ester 

Relevant academic research and scientific papers

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.

Insights into supramolecular assembly formation of diethyl aryl amino methylene malonate (DAM)derivatives assisted via non-covalent interactions

The crystal structures of four derivatives of diethyl 2-(((aryl)amino)methylene)malonate (DAM)have been studied by single crystal X-ray diffraction. The molecular structures of all the four derivatives were found to be in co-planar conformation. The detailed analysis of molecular conformation in four derivatives reveals the presence of a common strong intramolecular N–H?O hydrogen bonding, forming a ring of graph-set motif S1 1 (6). The effect of chloro and nitro substitution on their relative strengths of hydrogen bonding are analyzed here. Particularly, in compound 1, additional intramolecular hydrogen bonding between –NO2 and N–H was observed that results in the formation of another six-membered chelate ring. On the other hand in case of compound 3, we have observed type-I Cl?Cl interaction for the first time in this class of compounds. Further, Hirshfeld surface has been generated that is mapped with dnorm shape index and curvedness to summarize the weak interactions and examine the molecular shapes in all four derivatives. Effect of nitro (1 and 2)and chloro (3 and 4)substitution on the C?H, N?O and C?O interaction is highlighted in molecular contour and 2D fingerprint plots.

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.

Interaction of a Triantennary Quinoline Glycoconjugate with the Asialoglycoprotein Receptor

Targeted intracellular delivery is an efficient strategy for developing therapeutics against cancer and other intracellular infections. Nonspecific drug delivery shows limited clinical applications owing to high dosage, cytotoxicity, nonspecific action, h

Design, synthesis, in vitro and in silico studies of novel 4-oxoquinoline ribonucleoside derivatives as HIV-1 reverse transcriptase inhibitors

Human immunodeficiency virus type 1 (HIV-1) is a public health problem that affects over 38 million people worldwide. Although there are highly active antiretroviral therapies, emergence of antiviral resistant strains is a problem which leads to almost a million death annually. Thus, the development of new drugs is necessary. The viral enzyme reverse transcriptase (RT) represents a validated therapeutic target. Because the oxoquinolinic scaffold has substantial biological activities, including antiretroviral, a new series of 4-oxoquinoline ribonucleoside derivatives obtained by molecular hybridization were studied here. All synthesized compounds were tested against human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT), and 9a and 9d displayed the highest antiviral activities, with IC50 values of 1.4 and 1.6 μM, respectively. These compounds were less cytotoxic than AZT and showed CC50 values of 1486 and 1394 μM, respectively. Molecular docking studies showed that the most active compounds bound to the allosteric site of the enzyme, suggesting a low susceptibility to the development of antiviral resistance. In silico pharmacokinetic and toxicological evaluations reinforced the potential of the active compounds as anti-HIV candidates for further exploration. Overall, this work showed that compounds 9a and 9d are promising scaffold for future anti-HIV-1 RT drug design.

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

Design, synthesis and 2D QSAR study of novel pyridine and quinolone hydrazone derivatives as potential antimicrobial and antitubercular agents

The increased development of highly resistant bacterial strains and tuberculosis, constitute a serious public health threat, highlighting the urgent need of novel antibacterial agents. In this work, two novel series of nicotinic acid hydrazone derivatives (6a-r) and quinolone hydrazide derivatives (12a-l) were synthesized and evaluated as antimicrobial and antitubercular agents. The synthesized compounds were evaluated in vitro for their antibacterial, antifungal and antimycobacterial activities. Compounds 6f and 6p bearing the 3,4,5- (OCH3)3 and 2,5-(OCH3)2 benzylidene motifs were the most potent and as antibacterial, antifungal (MIC: 0.49–1.95 μg/mL) and (MIC: 0.49–0.98 μg/mL) respectively and antimycobacterial activity (MIC = 0.76 and 0.39 μg/mL) respectively. Besides, several derivatives, 6e, 6h, 6l-6o, 6q, 6r, 12a, 12b, 12e, 12h, 12k and 12l, exhibited significant antibacterial and antifungal activities with MIC values ranging from 1.95 to 7.81 μg/mL, they also displayed excellent to good activity against Mycobacterium tuberculosis with MIC range from 0.39 to 3.12 μg/mL. In addition, some of the most active compounds were tested for cytotoxic activities against human lung fibroblast normal cells (WI-38) and displayed low toxicity. Moreover, 2D-QSAR models to characterize the descriptors controlling the observed activities, were generated and validated.

6-substituted-1-((1-substituted phenyl-1,2,3-triazole-4-yl)methyl)-4-carbonylquinoline-3-ethyl formate compound, and preparation and application thereof

The invention specifically discloses a 6-substituted-1-((1-substituted phenyl-1,2,3-triazole-4-yl)methyl)-4-carbonylquinoline-3-ethyl formate compound, and preparation and application thereof, belonging to the technical field of organic synthesis. The com

6-substituted-1-((1-substituted phenyl-1,2,3-triazole-4-yl)methyl)-4-carbonylquinoline-3-carboxylic acid or pharmaceutical salt, preparation and application

The present invention belongs to the technical field of organic synthesis, and specifically discloses 6-substituted-1-((1-substituted phenyl-1,2,3-triazole-4-yl)methyl)-4-carbonylquinoline-3-carboxylic compounds or a pharmaceutical salt thereof, and prepa

Invariant and variable intermolecular interactions in functionalized malonic acid half-esters: X-ray, Hirshfeld surface and PIXEL energy analyses

A series of functionalized malonic acid half-ester derivatives (parent compound MHE-1), with variations in functional groups at different positions on the aromatic ring, have been synthesized and crystal structures are determined at room temperature (296