83507-70-4

Usage

Uses

Used in Pharmaceutical Industry:
2-((4-Methoxyphenylamino)methylene)malonic acid diethyl ester is used as a reagent or building block for the synthesis of various pharmaceuticals. Its unique structure allows for the creation of a wide range of medicinal compounds with potential therapeutic applications.
Used in Agrochemical Industry:
In the agrochemical industry, 2-((4-Methoxyphenylamino)methylene)malonic acid diethyl ester is used as a precursor in the production of various agrochemicals. Its versatility in organic synthesis enables the development of new compounds with improved properties for agricultural use.
Used in Materials Science:
2-((4-Methoxyphenylamino)methylene)malonic acid diethyl ester is also utilized in materials science for the development of new materials with specific properties. Its ability to form a variety of chemical structures makes it a valuable component in the creation of advanced materials for various applications.

InChI:InChI=1/C15H19NO5/c1-4-20-14(17)13(15(18)21-5-2)10-16-11-6-8-12(19-3)9-7-11/h6-10,16H,4-5H2,1-3H3

Upstream product

• 104-94-9 4-methoxy-aniline 
• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 122-51-0 orthoformic acid triethyl ester 
• 105-53-3 diethyl malonate 
• 10349-38-9 p-methoxyphenylisonitrile 
• 27971-92-2 diethyl 2,2,2-trichloroethylidenepropanedioate 
• 226881-95-4 2-[2,2,2-trichloro-1-(4-methoxy-phenylamino)-ethyl]-malonic acid diethyl ester 

Downstream Products

• 77156-78-6 ethyl 4-hydroxy-6-methoxyquinoline-3-carboxylate 
• 22931-71-1 ethyl 4-chloro-6-methoxyquinolin-3-carboxylate 
• 148018-29-5 4-chloro-quinolin-6-ol 
• 23432-39-5 4-hydroxy-6-methoxyquinoline 
• 28027-16-9 4-hydroxy-6-methoxy-3-quinoline carboxylic acid 
• 104-94-9 4-methoxy-aniline 
• 1415327-23-9 (2E)-2-(ethoxycarbonyl)-3-[(4-methoxyphenyl)amino]prop-2-enoic acid 
• 13788-72-2 6-methoxy-4(1H)-quinolinone 
• 1598416-84-2 6-methoxy-4-(2-(4-(4-nitrobenzylamino)piperidin-1-yl)ethyl)quinoline-3-carbonitrile 
• 1598416-85-3 4-(2-(4-(4-hydroxy-3-methoxybenzylamino)piperidin-1-yl)ethyl)-6-methoxyquinoline-3-carbonitrile 
• 1598416-86-4 4-(2-(4-(4-fluoro-3-nitrobenzylamino)piperidin-1-yl)ethyl)-6-methoxyquinoline-3-carbonitrile 
• 1598416-87-5 6-methoxy-4-(2-(4-(3-nitrobenzylamino)piperidin-1-yl)ethyl)quinoline-3-carbonitrile 
• 1598416-88-6 4-(2-(4-(2-fluoro-5-nitrobenzylamino)piperidin-1-yl)ethyl)-6-methoxyquinoline-3-carbonitrile 
• 1598416-92-2 4-(2-(4-(3-fluoro-4-nitrobenzylamino)piperidin-1-yl)ethyl)-6-methoxyquinoline-3-carbonitrile 

Relevant academic research and scientific papers

Improved fluorescence assays to measure the defects associated with F508del-CFTR allow identification of new active compounds

Background and Purpose: Cystic fibrosis (CF) is a debilitating disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which codes for a Clˉ/HCO3ˉ channel. F508del, the most common CF-associated mutat

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.

Synthesis and biological evaluation of small molecule modulators of CDK8/Cyclin C complex with phenylaminoquinoline scaffold

Background. CDK8/CycC complex has kinase activity towards the carboxyterminal domain of RNA polymerase II, and contributes to the regulation of transcription via association with the mediator complex. Different human malignancies, mainly colorectal and gastric cancers, were produced as a result of overexpression of CDK8/CycC in the mediator complex. Therefore, CDK8/CycC complex represents as a cancer oncogene and it has become a potential target for developing CDK8/CycC modulators. Methods. A series of nine 4-phenylaminoquinoline scaffold-based compounds 5a-i was synthesized, and biologically evaluated as potential CDK8/CycC complex inhibitors. Results. The scaffold substituent effects on the intrinsic inhibitory activity toward CDK8/CycC complex are addressed trying to present a novel outlook of CDK8/CycC Complex inhibitors with 4-phenylaminoquinoline scaffold in cancer therapy. The secondary benzenesulfonamide analogues proved to be the most potent compounds in suppressing CDK8/CycC enzyme, whereas, their primary benzenesulfonamide analogues showed inferior activity. Moreover, the benzene reversed sulfonamide analogues were totally inactive. Discussion. The titled scaffold showed promising inhibitory activity data and there is a crucial role of un/substituted sulfonamido group for CDK8/CycC complex inhibitory activity. Compound 5d showed submicromolar potency against CDK8/CycC (IC50 = 0.639 μM) and it can be used for further investigations and to design another larger library of phenylaminoquinoline scaffold-based analogues in order to establish detailed SARs.

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

Structural development of a type-1 ryanodine receptor (RyR1) Ca2+-release channel inhibitor guided by endoplasmic reticulum Ca2+ assay

Type-1 ryanodine receptor (RyR1) is a calcium-release channel localized on sarcoplasmic reticulum (SR) of the skeletal muscle, and mediates muscle contraction by releasing Ca2+ from the SR. Genetic mutations of RyR1 are associated with skeletal muscle diseases such as malignant hyperthermia and central core diseases, in which over-activation of RyR1 causes leakage of Ca2+ from the SR. We recently developed an efficient high-throughput screening system based on the measurement of Ca2+ in endoplasmic reticulum, and used it to identify oxolinic acid (1) as a novel RyR1 channel inhibitor. Here, we designed and synthesized a series of quinolone derivatives based on 1 as a lead compound. Derivatives bearing a long alkyl chain at the nitrogen atom of the quinolone ring and having a suitable substituent at the 7-position of quinolone exhibited potent RyR1 channel-inhibitory activity. Among the synthesized compounds, 14h showed more potent activity than dantrolene, a known RyR1 inhibitor, and exhibited high RyR1 selectivity over RyR2 and RyR3. These compounds may be promising leads for clinically applicable RyR1 channel inhibitors.

Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamidesAQ3 as carbonic anhydrase isoforms I and II inhibitors

Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial metalloenzymes that are involved in diverse bioprocesses. We report the synthesis and biological evaluation of novel series of benzenesulfonamides incorporating un/substituted ethyl quinoline-3-carboxylate moieties. The newly synthesised compounds were in vitro evaluated as inhibitors of the cytosolic human (h) isoforms hCA I and II. Both isoforms hCA I and II were inhibited by the quinolines reported here in variable degrees: hCA I was inhibited with KIs in the range of 0.966–9.091 μM, whereas hCA II in the range of 0.083–3.594 μM. The primary 7-chloro-6-flouro substituted sulphfonamide derivative 6e (KI = 0.083 μM) proved to be the most active quinoline in inhibiting hCA II, whereas, its secondary sulfonamide analog failed to inhibit the hCA II up to 10 μM, confirming the crucial role of the primary sulphfonamide group, as a zinc-binding group for CA inhibitory activity.

SAR-Guided Scoring Function and Mutational Validation Reveal the Binding Mode of CGS-8216 at the α1+/γ2- Benzodiazepine Site

The structural resolution of a bound ligand-receptor complex is a key asset to efficiently drive lead optimization in drug design. However, structural resolution of many drug targets still remains a challenging endeavor. In the absence of structural knowl

Synthesis and pharmacological evaluation of pyrazolo[4,3-c]quinolinones as high affinity GABAA-R ligands and potential anxiolytics

The synthesis, in vitro ligand binding study and in vivo Elevated Plus Maze test (EPM) of a series of pyrazolo[4,3-c]quinolin-3-ones (PQs) are reported. Multistep synthesis of PQs started from anilines and diethyl 2-(ethoxymethylene)malonate to give the q

Synthesis of novel 3,4,6-trisubstituted quinolines enabled by a Gould-Jacobs cyclization

A Gould-Jacobs cyclization enabled the synthesis of several novel, so far undescribed 3,4,6-trisubstituted quinoline derivatives. They all bear substituents which are well-suited for further transformations, e.g. carboxylic acid or ester functions, haloge

Structural investigation of (2E)-2-(ethoxycarbonyl)-3-[(4-methoxyphenyl)amino]prop-2-enoic acid: X-ray crystal structure, spectroscopy and DFT

The title compound, (2E)-2-(ethoxycarbonyl)-3-[(4-methoxyphenyl)amino]prop-2-enoic acid is characterized by means of X-ray crystallography, spectroscopic methods and quantum chemical calculations. The title compound crystallizes in centrosymmetric space g