103977-08-8Relevant articles and documents
Catalytic application of recyclable silica-supported bismuth(III) chloride in the benzo[N,N]-heterocyclic condensation
Aghapoor, Kioumars,Mohsenzadeh, Farshid,Shakeri, Atena,Darabi, Hossein Reza,Ghassemzadeh, Mitra,Neumüller, Bernhard
, p. 170 - 178 (2013)
Silica-supported bismuth(III) chloride (BiCl3/SiO2) has been successfully employed in the condensation of 1,2-dicarbonyls with a variety of arene-1,2-diamines bearing either electron withdrawing or donating functional groups. The catalyzed reaction proceeded smoothly under ambient temperature in methanol to give the corresponding quinoxaline and pyrido[2,3-b]pyrazine compounds in good to excellent yields. The catalyst exhibited remarkable reusable activity and higher catalytic performance than homogeneous BiCl3. A plausible mechanism for the catalytic action of BiCl3/SiO2 has been introduced. Moreover, the crystal structure of the prepared unsymmetrical benzo[N,N]-heterocycles has been determined by single crystal X-ray diffraction.
New 6-Aminoquinoxaline Derivatives with Neuroprotective Effect on Dopaminergic Neurons in Cellular and Animal Parkinson Disease Models
Le Douaron, Gael,Ferrié, Laurent,Sepulveda-Diaz, Julia E.,Amar, Majid,Harfouche, Abha,Séon-Méniel, Blandine,Raisman-Vozari, Rita,Michel, Patrick P.,Figadère, Bruno
, p. 6169 - 6186 (2016)
Parkinson's disease (PD) is a neurodegenerative disorder of aging characterized by motor symptoms that result from the loss of midbrain dopamine neurons and the disruption of dopamine-mediated neurotransmission. There is currently no curative treatment for this disorder. To discover druggable neuroprotective compounds for dopamine neurons, we have designed and synthesized a second-generation of quinoxaline-derived molecules based on structure-activity relationship studies, which led previously to the discovery of our first neuroprotective brain penetrant hit compound MPAQ (5c). Neuroprotection assessment in PD cellular models of our newly synthesized quinoxaline-derived compounds has led to the selection of a better hit compound, PAQ (4c). Extensive in vitro characterization of 4c showed that its neuroprotective action is partially attributable to the activation of reticulum endoplasmic ryanodine receptor channels. Most interestingly, 4c was able to attenuate neurodegeneration in a mouse model of PD, making this compound an interesting drug candidate for the treatment of this disorder.
Unexpected approach to the synthesis of 2-phenylquinoxalines and pyrido[2,3-b]pyrazines via a regioselective reaction
Alizadeh, Abdolali,Mokhtari, Javad
, p. 124 - 129 (2013)
An unexpected approach to the preparation of quinoxaline and pyrido[2,3-b]pyrazine derivatives 5 is described. The reaction between 1H-indole-2,3-diones 1, 1-phenyl-2-(triphenylphosphoranylidene)ethanone (2), and benzene-1,2- or pyridine-2,3-diamines 3 proceeds in MeOH under reflux in good to excellent yields (Scheme 1 and Table). No co-catalyst or activator is required for this multi-component reaction (MCR), and the reaction is, from an experimental point of view, simple to perform. The structures of 5, 5′, and 6 were corroborated spectroscopically (IR, 1H- and 13C-NMR, and EI-MS) and were confirmed by comparison with reference compounds. A plausible mechanism for this type of reaction is proposed (Scheme 2). Copyright
Synthesis, biological evaluation, and in silico studies of new acetylcholinesterase inhibitors based on quinoxaline scaffold
Khongkow, Pasarat,Lomlim, Luelak,Nualnoi, Teerapat,Saetang, Jirakrit,Suwanhom, Paptawan,Tipmanee, Varomyalin
, (2021/08/20)
A quinoxaline scaffold exhibits various bioactivities in pharmacotherapeutic interests. In this research, twelve quinoxaline derivatives were synthesized and evaluated as new acetyl-cholinesterase inhibitors. We found all compounds showed potent inhibitory activity against acetyl-cholinesterase (AChE) with IC50 values of 0.077 to 50.080 μM, along with promising predicted drug-likeness and blood–brain barrier (BBB) permeation. In addition, potent butyrylcholinesterase (BChE) inhibitory activity with IC50 values of 14.91 to 60.95 μM was observed in some compounds. Enzyme kinetic study revealed the most potent compound (6c) as a mixed-type AChE inhibitor. No cytotoxicity from the quinoxaline derivatives was noticed in the human neuroblastoma cell line (SHSY5Y). In silico study suggested the compounds preferred the peripheral anionic site (PAS) to the catalytic anionic site (CAS), which was different from AChE inhibitors (tacrine and galanthamine). We had proposed the molecular design guided for quinoxaline derivatives targeting the PAS site. Therefore, the quinoxaline derivatives could offer the lead for the newly developed candidate as potential acetylcholinesterase inhibitors.
Copper-catalyzed aerobic oxidative coupling of o-phenylenediamines with 2-aryl/heteroarylethylamines: direct access to construct quinoxalines
Gopalaiah, Kovuru,Saini, Anupama,Chandrudu, Sankala Naga,Rao, Devarapalli Chenna,Yadav, Harsh,Kumar, Binay
, p. 2259 - 2268 (2017/03/20)
A copper-catalyzed oxidative coupling reaction of o-phenylenediamines with 2-aryl/heteroarylethylamines using molecular oxygen as an oxidant has been developed. This approach provides a practical and direct access to construct quinoxalines in excellent yields at room temperature. The reaction has a broad substrate scope and exhibits excellent functional-group tolerance. This method could be easily scaled up and applied to the synthesis of biologically active molecules bearing a quinoxaline structural scaffold.
Metal free synthesis of quinoxalines from alkynes via a cascade process using TsNBr2
Hazarika, Debojit,Phukan, Prodeep
, p. 1374 - 1379 (2017/02/15)
A metal free protocol for the synthesis of quinoxalines from alkynes has been developed. The reaction was carried out by treating alkynes with TsNBr2in presence of O-phenylenediamines in a mixture of acetonitrile and water (9:1). This one-pot reaction proceeds via an oxidative transformation of alkynes to α,α-dibromoketones in presence of TsNBr2and eventually to quinoxalines in presence of 1,2-diamines in a cascade process.
One-Pot Protocol for the Synthesis of Imidazoles and Quinoxalines using N-Bromosuccinimide
Pardeshi, Sachin D.,Sathe, Pratima A.,Vadagaonkar, Kamlesh S.,Chaskar, Atul C.
supporting information, p. 4217 - 4226 (2017/12/07)
N-bromosuccinimide (NBS)-mediated one-pot, green, efficient and practical synthesis of substituted imidazoles and quinoxalines has been achieved by the reaction of styrenes with N-arylbenzamidines and o-phenylenediamines, respectively, in a water:1,4-dioxane mixture. The reaction involves formation of an α-bromo ketone as an intermediate in the presence of NBS and water, followed by condensation with the N-arylbenzamidine and o-phenylenediamine. Use of an inexpensive NBS as a bromine source as well as an oxidant, water as a solvent and readily available starting materials makes this protocol environmentally benign and economically viable. Substituted imidazoles and quinoxalines were obtained in good to excellent yields with wide functional group compatibility. (Figure presented.).
I2 catalyzed tandem protocol for synthesis of quinoxalines via sp3, sp2 and sp C-H functionalization
Vadagaonkar, Kamlesh S.,Kalmode, Hanuman P.,Murugan, Kaliyappan,Chaskar, Atul C.
, p. 5580 - 5590 (2015/02/05)
One-pot, atom-economic synthesis of quinoxalines has been achieved through generation of arylglyoxal from easily available ethylarenes, ethylenearenes and ethynearenes, and subsequent condensation with o-phenylenediamines. Catalytic I2 with TBHP as an oxidant in DMSO is the system of choice for this domino reaction involving C-H functionalization/oxidative cyclization. This metal-free, mechanistically distinct and functional group tolerant tandem approach could be a powerful complement to traditional approaches for the synthesis of quinoxalines. This journal is
Design, synthesis, and enzyme kinetics of novel benzimidazole and quinoxaline derivatives as methionine synthase inhibitors
Elshihawy, Hosam,Helal, Mohamed A.,Said, Mohamed,Hammad, Mohamed A.
, p. 550 - 558 (2014/01/17)
Methionine synthase catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine, producing methionine and tetrahydrofolate. Benzimidazole and deazatetrahydrofolates derivatives have been shown to inhibit methionine synthase by competing with the substrate 5-methyltetrahydrofolate. In this study, a novel series of substituted benzimidazoles and quinoxalines were designed and assessed for inhibitory activity against purified rat liver methionine synthase using a radiometric enzyme assay. Compounds 3g, 3j, and 5c showed the highest activity against methionine synthase (IC50: 20 μM, 18 μM, 9 μM, respectively). Kinetic analysis of these compounds using Lineweaver-Burk plots revealed characteristics of mixed inhibition for 3g and 5c; and uncompetitive inhibition for 3j. Docking study into a homology model of the rat methionine synthase gave insights into the molecular determinants of the activity of this class of compounds. The identification of these drug-like inhibitors could lead the design of the next generation modulators of methionine synthase.
One-pot copper-catalyzed three-component synthesis of quinoxalines by condensation and C-N bond formation
Yuan, Hua,Li, Kangning,Chen, Yongxin,Wang, Yu,Cui, Jiaojiao,Chen, Baohua
supporting information, p. 2315 - 2319 (2013/11/06)
A novel way of synthesizing quinoxalines has been developed that involves condensation and C-N bond formation in a copper-catalyzed, one-pot, three-component reaction. The reaction was optimized when 2-iodoanilines (1.0 equiv), arylacetaldehydes (2.0 equiv), sodium azide (1.2 equiv), CuI (10 mol%), DMEDA (10 mol%), and K2CO3 (1.0 equiv) were reacted in DMSO at 80 °C for 20 hours. This approach was used to directly synthesize a variety of quinoxalines in moderate to good yields. Georg Thieme Verlag KG Stuttgart.
