2474-50-2

Usage

Chemical Properties

Pink powder

InChI:InChI=1/C10H10N2O2/c1-5-3-7-8(4-6(5)2)12-10(14)9(13)11-7/h3-4H,1-2H3,(H,11,13)(H,12,14)

Upstream product

• 144-62-7 oxalic acid 
• 3171-45-7 4,5-dimethyl-1,2-phenylenediamine 
• 95-92-1 oxalic acid diethyl ester 
• 7732-18-5 water 

Downstream Products

• 63810-80-0 2,3-dichloro-6,7-dimethylquinoxaline 
• 82083-16-7 6,7-Dimethyl-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2,3(1H,4H)-chinoxalindion 
• 130064-16-3 2,3-dimethoxy-6,7-dimethylquinoxaline 

Relevant academic research and scientific papers

Unravelling the Selectivity of 6,7-Dimethyl Quinoxaline Analogs for Kinase Inhibition: An Insight towards the Development of Alzheimer's Therapeutics

Untangling the most selective kinase inhibitors via pharmacological intervention remains one of the challenging affairs to date. In accordance to this drift, herein we describe the design and synthesis of a set of new heterocyclic analogs consisting of 6,7-dimethyl Quinoxaline, appended to a connector, employing Schiff base strategy (Compounds I–IX). The compounds were characterized by various spectroscopic techniques and the kinase inhibition assay were performed on few prime members of the CMGC family namely the GSK3β, DYRK1A and CLK1 receptors, respectively, that have been known to be directly involved in hyperphosphorylation of Tau. Interestingly the biological evaluation results revealed that Compounds IV and V, with bromo/chloro functionalities in the aromatic core were advantaged of being highly selective towards the target GSK3β over others. To strengthen our analysis, we adopted molecular modelling studies, where compounds IV/V were redocked in the same grid 4AFJ, as that of the reference ligand, 5-aryl-4-carboxamide-1,3-oxazole. Surprisingly, our investigation underpinned that for both the compounds IV/V, a primary H-bonding existed between the designed molecules (IV/V) and Val 135 residue in the receptor GSK3β, in line with the reference ligand. We attribute this interaction to instigate potency in the compounds. Indeed the other non-covalent interaction, between the derivative's aromatic nucleus and Arg 141/Thr 138 in the receptor GSK3β, might have been responsible for enhancing the selectivity in the targets. Overall, we feel that the present work depicts a logical demonstration towards fine tuning the efficacy of the inhibitors through systematic adjustment of electron density at appropriate positions in the aromatic ring be it the main quinoxaline or the other aromatic nucleus. Thus this pathway offers a convenient strategy for the development of efficient therapeutics for diversified neurodegenerative diseases like that of Alzheimer's.

Novel molecular targeting anti-tumor aza-steroid derivative based on lipid toxicity and preparation and application thereof

The invention provides a novel molecular targeting anti-tumor aza-steroid derivative based on lipid toxicity and a preparation method and application thereof, and belongs to the field of chemical medicines. The derivative is a compound as shown in a formula I, or a salt thereof, or a stereoisomer thereof. The compound is low in toxicity or basically non-toxic to normal cells, has an obvious inhibition effect to tumor cell lines, particularly has good lipid toxicity selectivity to tumor cells such as liver cancer, lung cancer and the like in vivo, and has an obvious inhibition effect; meanwhile, the compound can effectively activate SREBP1 and PPAR gamma, inhibit lipid transport MTTP, cause lipid aggregation in tumor cells and cause lipid toxicity of the tumor cells. The compound can be used for treating liver cancer, lung cancer and the like in a molecular targeting manner, is low in toxicity or even non-toxic, and has a good application prospect.

A One-pot Facile Synthesis of 2,3-Dihydroxyquinoxaline and 2,3-Dichloroquinoxaline Derivatives Using Silica Gel as an Efficient Catalyst

An efficient one-pot reaction has been developed for the synthesis of 2,3-dichloroquinoxaline derivatives 3a–n. The reaction was performed in two steps via a silica gel catalyzed tandem process from o-phenylenediamine and oxalic acid, followed by addition of phosphorus oxychloride (POCl3). A variety of 2,3-dichloroquinoxalines have been obtained in good to excellent overall yields. Eight known compounds 3a–3h were characterized by IR, 1H-NMR, and mass spectroscopies. Compounds 3i–3n without spectroscopic data were characterized by IR, 1H-NMR, 13C-NMR, and mass spectroscopies.

Rationalization of benzazole-2-carboxylate versus benzazine-3-one/ benzazine-2,3-dione selectivity switch during cyclocondensation of 2-aminothiophenols/phenols/anilines with 1,2-biselectrophiles in aqueous medium

The cyclocondensation reaction of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyoxalate and diethyl oxalate in aqueous medium leads to the formation of benzothiazole-2-carboxylates via the 5-endo-trig process contrary to Baldwin's rule. On the other hand, the reaction of 2-aminophenols/anilines produced the corresponding benzazine-3-ones or benzazine-2,3-diones via the 6-exo-trig process in compliance with Baldwin's rule. The mechanistic insights of these cyclocondensation reactions using the hard-soft acid-base principle, quantum chemical calculations (density functional theory), and orbital interaction studies rationalize the selectivity switch of benzothiazole-2-carboxylates versus benzazine-3-ones/ benzazine-2,3-diones. The presence of water facilitates these cyclocondensation reactions by lowering of the energy barrier.

SUBSTITUTED IMIDAZOQUINOXALINES

The present invention relates to substituted imidazoquinoxaline compounds of general formula (I) as inhibitors of Mps-1 Kinase or TTK, and being active against inflammation and cancer

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.

Water superstructures within organic arrays; hydrogen-bonded water sheets, chains and clusters

A strategy for encouraging the formation of extended water arrays is presented, in which molecules that contain a 1,4-dihydroquinoxaline-2,3-dione core are used as supramolecular hosts for the accommodation of guest water molecules and arrays. These molecules were selected as they contain a hydrophilic oxalamide-based "terminus" that allows water molecules to hydrogen-bond to the host organic molecules as well as to each other. The host molecules also contain a hydrophobic "end" based upon an aromatic ring, which serves to encourage the formation of discrete water clusters in preference to three-dimensional networks, as the water molecules cannot form strong hydrogen bonds with this part of the molecule. A systematic study of several hydrated structures of four organic molecules based on 1,4-dihydroquinoxaline-2,3-dione (qd) is discussed. The organic molecules, qd, 6-methyl-1,4-dihydroquinoxaline-2,3-dione (mqd), 6,7-dimethyl-1,4- dihydroquinoxaline-2,3-dione (dmqd) and 1,4-dihydrobenzo[g]-quinoxaline-2,3- dione (Phqd), act as supramolecular crystal hosts for the clusters of water, with zero-, one- and two-dimensional arrays of water being observed. The hydrogen bonding in the structures, both within the water clusters and between the clusters and organic molecules, is examined. In particular, the structure of dmqd·6H2O contains a two-dimensional water sheet composed of pentagonal and octagonal units. Phqd·3H2O forms a hydrophilic extended structure encouraging the formation of one-dimensional chains consisting entirely of water. Both qd·2H2O and dmqd·2H2O can be considered to form one-dimensional chains, but only by utilising bridging carbonyl groups of the oxalamide moieties to form the extended array; if only the water is considered, zero-dimensional water tetramers are observed. The remaining hydrated structures, [Na+ dmqd-]dmqd·H2O, dmqd·1/3H2O and mqd·1/2H2O, all contain discrete water molecules but do not form extended water structures.

The syntheses of pyrazino-containing sultines and their application in Diels-Alder reactions with electron-poor olefins and [60]fullerene

The Diels-Alder reactions of heterocyclic o-quinodimethanes, generated in situ from 6,7-disubstituted quinoxalino[2,3-d]-[1,2λ4]oxathiine 2-oxides (6a-c), 2,3-disubstituted-8,9-dihydro-6H-8λ 4-[1,2]oxathiino[4,5-g]quinoxalin-8-one (7a-c) (sultines), and pyrazinosultine (22), with electron-poor olefins and [60]fullerene are described. The heterocyclic-fused sultines 7a-c and 22 are readily prepared from the corresponding dibromides 9a-c and 24 with the commercially available Rongalite (sodium formaldehyde sulfoxylate). When heated in the presence of electron-poor dienophiles and [60]fullerene, all of the sultines underwent extrusion of SO2, and the resulting heterocyclic o-quinodimethanes (3a-d, 4a-c, and 25) were intercepted as the 1:1 adducts in good to excellent yields. The temperature-dependent 1H NMR spectra of fullerene derivatives 31-38 show a dynamic process for the methylene protons. The activation free energies (ΔGc?) determined for the boat-to-boat inversion of these pyrazino-containing C60 compounds (31-34 and 38) are found to be in the range of 14.1-14.8 kcal/mol, but they are in the range of 15.2 to >17.1 kcal/mol for adducts 35-37. The activation free energies (ΔGC?) are significantly affected by (1) the orientations and (2) the substituents of the quinoxaline rings and (3) the extended benzannulation in the arenes of C60 adducts (see Table 2), which implies that both electronic interactions and steric effects between the aromatic addends and C60 are important. Tautomerization of methylquinoxaline to its enamine is invoked as a rationalization for the lowering of ΔGC? in some of the fulleroadducts.

1,4-Dihydro-2,3-quinoxalinediones as potential flavin metabolites and excitatory amino acid receptor ligands. Part 1: Synthesis and pharmacological evaluation of the benzylic oxidation series of 1,4-dihydro-6,7-dimethyl-2,3- quinoxalinedione

A series of five 6,7-disubstituted 1,4-dihydro-2,3-quinoxalinediones was prepared, two of which are known microbial flavin metabolites and three of which are potential flavin metabolites. Four of the five compounds inhibited specific binding of [3H]-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic acid ([3H]AMPA), [3H]kainic acid, and [3H]6-cyano-1,4-dihydro-7-nitro-2,3- quinoxalinedione ([3H]CNQX) in rat brain homogenate fractions, with IC50 values in the low micromolar range (the fifth compound competed only with [3H]CNQX). Two of the compounds were moderately potent AMPA antagonists in an in vitro functional test.

Alkyl, azido, alkoxy, and fluoro-substituted and fused quinoxalinediones

Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia, and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, and inducing anesthesia are disclosed by administering to an animal in need of such treatment an alkyl or azido-substituted 1,4-dihydroquinoxaline-2,3-dione or pharmaceutically acceptable salts thereof, which have high binding to the glycine receptor.