Awesome and Easy Science Experiments about Quinoxaline-2,3(1H,4H)-dione

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First coordination polymer of 1,4-dihydro-2,3-quinoxalinedione in ketoamine tautomeric form

The first coordination compound of 1,4-dihydro-2,3-quinoxalinedione in ketoamine tautomeric form (denoted as H2qdione) was reported. H 2qdione was obtained by a solid-state reaction of o-phenylenediamine and oxalic acid. Reaction of this ligand with CdCl2 solvothermally yielded a coordination polymer [Cd(H2qdione)Cl2] n, which was structurally characterized by X-ray diffraction and IR spectroscopy. Continuous Cd2Cl2 diamonds form a double-sided comb with terminal H2qdione-kappa2O,O’ as the comb teeth. Interaction of these combs through very extensive pi-pi stacking, C-HA…Cl, and N-HA…Cl hydrogen bonds leads to a novel 3D architecture and significant enhancement of solid-state luminescence of about 10 times compared to the free H2qdione ligand.

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Reference:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N397 | ChemSpider

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Heterocycles as Nonclassical Bioisosteres of alpha-Amino Acids

Bioisosterism of alpha-amino acids is often accomplished by replacing the alpha-carboxylate with one of the many known carboxylic acid bioisosteres. However, bioisosterism of the whole alpha-amino acid moiety is accomplished with heterocyclic bioisosteres that often display an acidic function. In this Minireview, we summarized the reported heterocycles as nonclassical bioisosteres of alpha-amino acids, which include quinoxaline-2,4(1H)-dione, quinoxaline-2,3(1H)-dione and quinolin-2(1H)-one, azagrevellin and azepine-derived structures. The binding mode of the crystalized bioisosteres were compared with those of the crystalized alpha-amino acids that bind in the same domain, and where no data on the crystal structure were available, the displacement studies of known orthosteric ligands were used. The reported bioisosteres share the following essential structural features for mimicking alpha-amino acids: an aromatic ring system joined to a lactam ring system with an acidic feature next to the lactam carbonyl, where this acidic feature together with the lactam carbonyl can mimic the alpha-carboxylate, and the lactam nitrogen together with the aromatic ring system can mimic the alpha-ammonium. The majority of these heterocycles can be prepared from three common corresponding starting materials: the corresponding anilines, isatins or anthranilic esters. The data collected here show the potential of this class of bioisosteres in the design of glutamate receptor ligands and beyond.

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Quinoxaline – Wikipedia,
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Design and discovery of novel quinoxaline derivatives as dual DNA intercalators and topoisomerase II inhibitors

Backgroun/Methods: In attempt to develop new potent anti-tumor agents, a series of quinoxaline derivatives was designed and synthesized. The novel compounds were tested in vitro for their anti-proliferative activities against HePG-2, MCF-7 and HCT-116 cell lines. Additionally, DNA binding affinities as well as DNA-top II inhibitory activities of the synthesized compounds were investigated as potential mechanism for anticancer activity. Compounds 13, 15, 16 and 19 exhibited good cytotoxicity activities against the three cell lines (IC50 ranging from 7.6 to 32.4 muM) comparable to that of doxorubicin (IC50 = 9.8 muM). Results: Interestingly, the results of DNA binding and DNA-top II inhibition assays were in agreement with those of the cytotoxicity tests, where the most potent anticancer compounds showed good DNA binding affinities (IC50 ranging from 25.1 to 32.4 muM) and DNA-top II inhibitory activities (IC50 ranging from 6.4 to 15.3 muM) comparable to those of doxorubicin (IC50 = 28.1 and 3.8 muM, respectively). Furthermore, molecular docking studies were carried out for the new compounds in order to investigate their binding pattern with the prospective target, DNA-top II complex (PDB-code: 3qx3).

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N313 | ChemSpider

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An efficient and versatile synthesis of 2, 2?-(alkanediyl)-bis-1H- benzimidazoles employing aqueous fluoroboric acid as catalyst: Density functional theory calculations and fluorescence studies

2,2?-(Alkanediyl)-bis-1H-benzimidazoles (simple and mixed) with variable methylene spacers were synthesized in excellent yields with aqueous fluoroboric acid (45%) (0.1 ml) as catalyst under solvent-free conditions. Their optimized structures were obtained using DFT calculations where it was seen that the s-trans orientation of the two imidazole rings was preferred for all types of bis-benzimidazole systems. The X-ray crystal structure of one such bis-benzimidazole further corroborated this fact. Finally, photophysical studies were carried out to get insight into the fluorescence characteristics of the newly synthesized bis-1H-benzimidazoles. ARKAT USA, Inc.

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Quinoxaline – Wikipedia,
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Kynurenic Acid Derivatives. Structure-Activity Relationships for Excitatory Amino Acid Antagonism and Identification of Potent and Selective Antagonists at the Glycine Site of the N-Methyl-D-aspartate Receptor

Derivatives of the nonselective excitatory amino acid antagonist kynurenic acid (4-oxo-1,4-dihydroquinoline-2-carboxylic acid, 1) have been synthesized and evaluated for in vitro antagonist activity at the excitatory amino acid receptors sensitive to N-methyl-D-aspartic acid (NMDA), quisqualic acid (QUIS or AMPA), and kainic acid (KA).Introduction of substituents at the 5-, 7-, and 5,7-positions resulted in analogues having selective NMDA antagonist action, as a result of blockade of the glycine modulatory (or coagonist) site on the NMDA receptor.Regression analysis suggested a requirement for op timally sized, hydrophobic 5- and 7-substituents, with bulk tolerance being greater at the 5-position.Optimization led to the 5-iodo-7-chloro derivative (53), which is the most potent and selective glycine/NMDA antagonist to date (IC50 vs <3H>glycine binding, 32 nM; IC50’s for other excitatory amino acid receptor sites, >100 muM).Substitution of 1 at the 6-position resulted in compounds having selective non-NMDA antagonism and 8-substituted compounds were inactive at all receptors.The retention of glycine/NMDA antagonist activity in heterocyclic ring modified analogues, such as the oxanilide 69 and the 2-carboxybenzimidazole 70, suggests that the 4-oxo tautomer of 1 and its derivatives is required for activity.Structurally related quinoxaline-2,3-diones are also glycine/NMDA antagonists, but are not selective and are less potent than the 1 derivatives, and additionally show different structure-activity requirements for aromatic ring substitution.On the basis of these results, a model accounting for glycine receptor binding of the 1 derived antagonists is proposed, comprising (a) size-limited, hydrophobic binding of the benzene ring, (b) hydrogen- bond acceptance by the 4-oxo group, (c) hydrogen-bond donation by the 1-amino group, and (d) a Coulombic attraction of the 2-carboxylate.The model can also account for the binding of quinoxaline-2,3-diones, quinoxalic acids, and 2-carboxybenzimidazoles.

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Design, synthesis and photoinduced DNA cleavage studies of [1,2,4]-triazolo[4,3-a]quinoxalin-4(5H)-ones

An expedient and eco-friendly synthesis of 1-aryl/heteroaryl-[1,2,4]-triazolo[4,3-a]quinoxalin-4(5H)-ones (4) has been accomplished via iodobenzene diacetate mediated oxidative intramolecular cyclization of 3-(2-(aryl/heteroarylidene)hydrazinyl)-quinoxalin-2(1H)-ones (3). Ten synthesized compounds 3 and 4 (10?40 mug) on irradiation with UV light at lambdamax 312 nm could lead to cleavage of supercoiled pMaxGFP DNA (Form I) into the relaxed DNA (Form II) without any additive. Further, DNA cleaving ability of triazoles was quantitatively evaluated and was found to be dependent on its structure, concentration, and strictly on photoirradiation time. Mechanistic investigations using several additives as potential inhibitors/activator revealed that the DNA photocleavage reaction involves Type-I pathway leading to formation of superoxide anion radicals (O2 ? [rad]) as the major reactive oxygen species responsible for photocleavage process.

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Reference:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N401 | ChemSpider

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A series of ?drug-like? compounds based on quinoxaline scaffold with arylsulfonyl hydrazinyl, arylformyl hydrazinyl or arylsulfonyl groups at C-2 and aryloxy groups at C-3, were synthesized in 4 or 5 steps involving cyclization, chlorination and coupling reactions. Cellular anti-proliferative activities of these quinoxaline derivatives in vitro were determined, which revealed that the inhibitory potency and selectivity of 6f was comparable to that of the positive control.

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Top Picks: new discover of Quinoxaline-2,3(1H,4H)-dione

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The oxidation reaction of a series of quinoxaline derivatives, using KMnO4 in the presence or absence of NaOH, are described.Neutral oxidation of 2-chloro- and 2,3-dichlorodioxalines 2-4 afforded the corresponding chloro- and dichloropyrazinedicarboxilic acids 13 and 14 in good yield.On the other hand, oxidation of quinoxalin-2(1H)-one and 1,4-dihydroquinoxaline-2,3-dione derivatives in alkaline medium gave different products, with the quinoxalin-2(1H)-one (5) forming 1,4-dihydroquinoxaline-2,3-dione (9), while various substituted quinoxalin-2,3-dione derivatives (see 9-11) gave a new type of dimeric products.The structural assignments for the new compounds were based on spectroscopic data.

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Structure-Activity Relationships of Quinoxaline-Based 5-HT3A and 5-HT3AB Receptor-Selective Ligands

Until recently, discriminating between homomeric 5-HT3A and heteromeric 5-HT3AB receptors was only possible with ligands that bind in the receptor pore. This study describes the first series of ligands that can discriminate between these receptor types at the level of the orthosteric binding site. During a recent fragment screen, 2-chloro-3-(4-methylpiperazin-1-yl)quinoxaline (VUF10166) was identified as a ligand that displays an 83-fold difference in [3H]granisetron binding affinity between 5-HT3A and 5-HT3AB receptors. Fragment hit exploration, initiated from VUF10166 and 3-(4-methylpiperazin-1-yl)quinoxalin-2-ol, resulted in a series of compounds with higher affinity at either 5-HT3A or 5-HT3AB receptors. These ligands reveal that a single atom is sufficient to change the selectivity profile of a compound. At the extremes of the new compounds were 2-amino-3-(4-methylpiperazin-1-yl)quinoxaline, which showed 11-fold selectivity for the 5-HT3A receptor, and 2-(4-methylpiperazin-1-yl)quinoxaline, which showed an 8.3-fold selectivity for the 5-HT3AB receptor. These compounds represent novel molecular tools for studying 5-HT3 receptor subtypes and could help elucidate their physiological roles.

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Quinoxaline – Wikipedia,
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Extracurricular laboratory:new discovery of Quinoxaline-2,3(1H,4H)-dione

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A series of inhibitors of the derivative, preparation method and use thereof (by machine translation)

The present invention provides a compound of formula I shown in structure, synthesis method, and its pharmaceutically acceptable salt or their mixture in the preparation of the prevention and/or treating diabetes complications in the use of the medicament, such compounds as aldose reductase inhibitor and antioxidant, by inhibiting aldose reductase activity, while at the same time effectively eliminating free radical and inhibiting lipid peroxide generation, thereby preventing and/or treating diabetes complication. The invention also provides comprising such compounds with the prevention and/or treating diabetes complication effects of the pharmaceutical composition. (by machine translation)

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