- Solid-Phase Synthesis of 3,4-Dihydroquinoxalin-2(1H)-ones via the Cyclative Cleavage of N-Arylated Carboxamides
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We describe a practical (time-efficient, with commercially available building blocks, user friendly reaction conditions, high purity of products) synthesis of pharmacologically relevant quinoxalinones with three points of diversification that takes advantage of solid-phase synthesis and cyclative cleavage. Resin-bound (S)-2-(N-alkyl-2-nitrophenyl)sulfonamide-3-alkyl-N-(2-hydroxyethyl)propanamides, which are accessible from Fmoc-protected α-amino acids, 2-nitrobenzenesulfonyl chloride and alcohols, underwent base-mediated N-arylation. The reduction of the nitro group produced acyclic intermediates that were subjected to acid-mediated cyclative cleavage to yield 3,4-dihydroquinoxalin-2(1H)-ones.
- Carbain, Benoit,Schütznerová, Eva,P?ibylka, Adam,Krchňák, Viktor
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- Multicomponent synthesis of substituted 3-styryl-1H-quinoxalin-2-ones in an aqueous medium
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A multicomponent synthesis of substituted 3-styryl-1H-quinoxalin-2-ones is described. Sequential reactions of o-phenylenediamine with sodium pyruvate and aldehydes in 20% aqueous acetic acid containing sodium acetate provided the target products in good to high yields. The reaction is proposed to proceed via initial condensation of the diamine and pyruvate partners followed by an aldol condensation-type mechanism.
- da Costa, Erivaldo P.,Coelho, Sara E.,de Oliveira, André H.,Araújo, Renata M.,Cavalcanti, Livia N.,Domingos, Josiel B.,Menezes, Fabrício G.
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- Design, synthesis, biological evaluation and molecular docking study on peptidomimetic analogues of XK469
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XK469 is identified as a potent quinoxaline antineoplastic agent based on its significant clinical efficacy. It probably exerts its activity via DNA topoisomerase II (topo II) inhibition. To obtain more effective antineoplastic agents, a spectrum of peptidomimetic-type quinoxaline analogues of XK469 was herein designed, synthesized, and evaluated. Few compounds (e.g. 13a and 13b) exhibited obvious cytotoxicity indicated by in?vitro anti-proliferative assay. SAR investigation revealed that introducing of hydrophobic tert-butylamine or dodecylamine moiety at the 3-position of quinoxaline core is favorable for achieving a better anti-proliferative potency, while peptidomimetic derivatives only yielded moderate cytotoxicity. Compounds with improved anti-proliferative activities also demonstrated decent anti-metastatic potencies comparable with that of doxorubicin (Doxo) based on in?vivo mouse model study. The topo II-mediated kinetoplast DNA (kDNA) decatenation assay as well as molecular docking studies implicated that these compounds tend to be potent topo II inhibitors. Overall, compounds 13a and 13b, 13b in particular, standed out from various assessments and might be promising candidates for further chemical optimization.
- Xia, Qiao-Hong,Hu, Wei,Li, Chen,Wu, Ji-Feng,Yang, Liang,Han, Xue-Mei,Shen, Yue-Mao,Li, Zhi-Yu,Li, Xun
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- A newly synthesized nitrogen-rich derivative of bicyclic quinoxaline—Structural and conceptual DFT reactivity study
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Novel nitrogen-rich compound featured bicyclic quinoxaline as a basic core structure has been synthesized, 1-{[1-(3-azido-2-hydroxypropyl)-1H-1,2,3-triazol-4-yl]methyl}-3-methyl-1,2-dihydroquinoxalin-2-one with formula C15H16N8O2, and their structural and chemical reactivity aspects have been comprehensively discussed. Nature, role, and relative contribution of weak noncovalent interactions in supramolecular assembly have been assessed through single-crystal analysis and computational approaches. Useful information about the global and local reactivity were obtained from Conceptual Density Functional Theory at wB97X-D/cc-pVDZ level. Studied system could act as strong electrophile and/or moderate nucleophile in polar organic reactions. We hope this study will provide deeper insight in the knowledge of the synthesis and chemistry of the quinoxaline and quinoxaline derivatives.
- Abad, Nadeem,Hajji, Melek,Ramli, Youssef,Belkhiria, Marwa,Moftah H. Elmgirhi, Salima,A. Habib, Mohamed,Guerfel, Taha,T. Mague, Joel,Essassi, El Mokhtar
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- Reaction-Based Color-Convertible Fluorescent Probe for Ferroptosis Identification
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Ferroptosis is an iron-mediated, caspase-independent pathway of cell death that is accompanied with the accumulations of reactive oxygen species (ROS) and oxygenases, as well as being involved in many other pathophysiological procedures. However, specific and rapid monitoring of ferroptosis in living cells or tissues has not been achieved so far. Herein, a quinoxalinone-based fluorescent probe (termed as Quinos-4, or QS-4) with a reactive aromatic thioether moiety was designed for ferroptosis identification. Upon exposing it to high levels of ROS and hemeoxygenase-1 (HO-1), which are considered as the biochemical characteristics of ferroptosis, QS-4 could be oxidized into a sulfoxide derivative (QSO-4) and its original aggregation-induced enhanced red fluorescence emission could be converted to green fluorescence emission sharply. On the basis of this unique reaction-induced color conversion, this molecular probe can be employed for identifying the occurrence of ferroptosis both in vitro and in vivo.
- Shi, Leilei,Guan, Qinghua,Gao, Xihui,Jin, Xin,Xu, Li,Shen, Jian,Wu, Chenwei,Zhu, Xinyuan,Zhang, Chuan
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- Docking of disordered independent molecules of novel crystal structure of (N-(4-methoxyphenyl)-2-(3-methyl-2-oxo-3,4-dihydroquinoxalin-1(2H)-yl)acetamide as anti-COVID-19 and anti-Alzheimer's disease. Crystal structure, HSA/DFT/XRD
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New quinoxaline derivative, N-(4-methyl-2-nitrophenyl)-2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide (NMPOQA= disordered molecules NMPOQAa(50.3% and NMPOQAb(49.7%)) has been synthesized and characterized by ESI-MS, IR, 1H &13C NMR. The geometric parameters of NMPOQA compound which crystallographic structure has been defined by X-ray diffraction have been calculated by Density Functional Theory (DFT), B3LYP, 6-311++G(d,p) basis set. The correlation between experimental and theoretical structure was checked by superimposing the experimental and theoretical structure. Frontier Molecular Orbitals (FMO's) have been created and the gap energy between High Occupied Molecular Orbital (HOMO) and Low Unoccupied Molecular Orbital (LUMO) has been calculated. Additionally, Molecular Electrostatic Potential (MEP) and Hirshfeld studies have been conducted to analyze intermolecular interactions. Interesting molecular docking of NMPOQA and Remdesivir drug with 6M03 was conducted using the same parameters for a fair comparison. A low binding affinity of the NMPOQA (?6.9 kcal/mol) compared to the Remdesivir drug, (?7.1 kcal/mol) and other good reasons make NMPOQA a good candidate against COVID-19. A similar study was calculated with 1EVE producing evidences that suggest NMPOQA may serve as a potential drug for developing Alzheimer's disease (AD) treatment
- Demirta?, Güne?,Mague, Joel T.,Missioui, Mohcine,Ramli, Youssef,Said, Musa A.
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- Revisiting the Hinsberg reaction: Facile and expeditious synthesis of 3-substituted quinoxalin-2(1H)-ones under catalyst-free conditions in water
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Substituted benzene-1,2-diamine reacted with various α-keto esters at 50° under mild conditions for 15 min using H2O as reaction medium, providing a variety of 3-substituted quinoxalinone derivatives in excellent yields. The reaction was instantaneous, and products were isolated by simple filtration.
- Murthy, Sabbavarapu Narayana,Madhav, Bandaru,Nageswar, Yadavalli Venkata Durga
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- Synthesis and Biological Evaluation of 2-Oxo/Thioxoquinoxaline and 2-Oxo/Thioxoquinoxaline-Based Nucleoside Analogues
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Several O-and S-quinoxaline glycosides have been prepared by glycosidation of 3-methyl-2-oxo(thioxo)-1,2-dihydroquinoxalines 1a,b with α-D-glucopyranosyl, α-D-galactopyranosyl, and α-D-lactosyl bromide in the presence of K2CO3 followed by deacetylation with Et3N/H2O. Furthermore, alkylation of 1a,b with 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 3-chloropropanol afforded the corresponding O-and S-acycloquinoxaline nucleosides. Reaction of 1b with chloroacetic acid followed by condensation with sulfacetamide and sulfadiazine in the presence of Et3N/THF and ethyl chloroformate gave the corresponding sulfonamide derivatives 14 and 15, respectively. The structures of new compounds were confirmed by using IR, 1H, 13C NMR spectra and microanalysis. Some of these compounds were screened in vitro for antitumor and antifungal activities.
- El-Sayed, Hassan A.,Said, Said A.,Moustafa, Ahmed H.,Baraka, Mohamed M.,Abdel-Kader, Rimaa T.
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- Synthesis, crystal structure and calculation of oxides of 2-methylamino-3-methyl quinoxaline
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Monoxide and dioxide of animo quinoxaline were synthesized and characterized by 1H NMR, 13C NMR and HRMS. The result shows that monoxide is main product. 1H NMR analysis, quantum calculation and crystal structure all indicate that the monoxide is 4-oxide structure but not 1-oxide structure. The subsequent discussions of electronic effect and steric effect of 1-oxide and 4-oxide support the conclusion that 4-oxide is dominant product, which is consistent with 1H NMR analysis and crystal structure. At last, the calculated structure is in good agreement with the crystal structure in this paper, which indicates that the calculation result in this paper is credible.
- Li, Junjian,Wang, Rui,Wang, Wenfeng,Wang, Xucheng,Yuan, Yaofeng,Zhang, Min
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- Crystal structures of 3-methyl-2(1H)-quinoxalinone and three substituted derivatives
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3-Methyl-2(1H)-quinoxalinone and three derivatives (3,7-dimethyl-2(1H)- quinoxalinone, 3-methyl-6,7-dichloro-2(1H)-quinoxalinone and 3-methyl-7-nitro-2(1H)-quinoxalinone) have been synthesised and analysed by 1H NMR and IR spectral spectroscopies. The crystal structures have been determined at room temperature from X-ray single crystal diffraction data for three of them and from powder diffraction data for the nitro derivative. 3-Methyl-2(1H)-quinoxalinone crystallises in the P21/c monoclinic system, 3,7-dimethyl-2(1H)-quinoxalinone in the Pbca orthorhombic system and the two others compounds in the P1 triclinic system. For the nitro derivative, C-H..N short contacts are established between the carbon of the methyl and the double bounded nitrogen of the ring. For the three other compounds N-H..O hydrogen bonds involve the atoms of the heterocyclic ring. Copyright
- Mondieig, Denise,Negrier, Philippe,Massip, Stephane,Leger, Jean Michel,Jarmoumi, Chakir,Lakhrissi, Brahim
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- Cyclisation reaction between 3-methylquinoxaline-2-thione and benzaldehydes into 3-benzyl-2-aryl-thieno[2,3-b] quinoxaline promoted by Br?nsted acids
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2,3-Disubstituted thieno[2,3-b]quinoxaline derivatives have been synthetized through the condensation of commercially available benzaldehydes with 3-methylquinoxaline-2-thione in EtOH using Br?nsted acids, namely sulfuric or hydrochloric acids. A wide range of substituted benzaldehydes has been used, allowing the formation of 3-(substituted)benzyl-2-arylthieno[2,3-b]quinoxalines in high yields in only one step.
- Saoudi, Besma,Teniou, Abderrahmane,Debache, Adbelmadjid,Roisnel, Thierry,Soulé, Jean-Fran?ois,Doucet, Henri
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- Qualitative Profiling of Polyglucose Degradation Products in Peritoneal Dialysis Fluids
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Heat sterilization of peritoneal dialysis (PD) fluids leads to partial degradation of the osmotic agent to form reactive carbonyl structures, which significantly reduce the biocompatibility of PD fluids and impair long-term PD therapy. Hence, it is important to know the exact composition of the degradation products to improve biocompatibility of PD fluids. Our study conducted targeted screening for degradation products in polyglucose (icodextrin)-containing PD fluids (pGDPs) by applying o-phenylenediamine (OPD) to form stable derivatives, which were analyzed by ultrahigh-performance liquid chromatography with hyphenated diode array tandem mass spectrometry (UHPLC-DAD-MS/MS). For the first time, specific degradation products of polyglucose, namely, 4-deoxyglucosone (4-DG) and 3,4-dideoxypentosone (3,4-DDPS), could be identified in PD fluids. Further, a reaction product of 5-hydroxymethylfurfural (5-HMF) and OPD could be characterized to be (5-(1H-benzo[d]imidazol-2-yl)furan-2-yl)methanol. Additionally, 3-deoxyglucosone (3-DG) and 3-deoxygalactosone (3-DGal), both known to be present in glucose-based PD fluids, were also detected in polyglucose-containing fluids. Trapping a hitherto unknown degradation product with OPD yielded 1,4-bis(1H-benzo[d]imidazol-2-yl)-3,4-dihydroxybutan-1-one, which was present in heat- as well as filter-sterilized PD fluids.
- Gensberger, Sabrina,Knabner, Carina,Waibel, Reiner,Huppert, Jochen,Pischetsrieder, Monika
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- Quinoxalinone (Part II). Discovery of (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates as potent VEGFR-2 kinase inhibitors
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Inhibition of VEGFR-2 kinase has been highlighted as one of the well-defined strategies to suppress tumor growth via blockade of angiogenesis. Guided by the principles of bioisosteric replacement and pharmacophoric fragment migration, a series of novel quinoxalinone derivates were designed, synthesized and evaluated for their VEGFR-2 inhibitory potencies. Among them, compounds 7c, 8b, 8c, 8e and 10b displayed antiangiogenic abilities via the in vitro tube formation assay (cellular level) and ex vivo rat aortic ring assay (tissue level) at a low concentration (0.1 μM). By means of in vivo zebrafish embryo model, two (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates 8c and 8e showed significant antiangiogenesis effects, suggesting they have potentials to be developed into antiangiogenesis agents via further structural optimization. Moreover, these two compounds also demonstrated potent inhibition toward VEGFR-2 and B-raf kinases in a low concentration (1 μM). A possible interpretation of our evaluation result has been presented by a molecular docking study by docking representative compound 8c with VEGFR-2.
- Shi, Leilei,Zhou, Jianfeng,Wu, Jifeng,Cao, Junya,Shen, Yuemao,Zhou, Hua,Li, Xun
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- Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of novel quinoxaline derivatives as potential PPARγ and SUR agonists
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In our effort to develop potent anti-hyperglycemic agents with potential agonistic activities toward PPARγ and SUR, three novel series of quinoxaline derivatives bearing sulfonylurea or sulfonylthiourea moieties with different linkers were designed and synthesized. Some of the newly synthesized compounds were evaluated in vivo for their anti-hyperglycemic activities in STZ-induced hyperglycemic rats. Compounds 15a, 15e, 19band 24aexhibited the highest anti-hyperglycemic activities with % reduction in blood glucose level of (50.58, 43.84, 45.10 and 49.62, respectively). Additionally, eight compounds revealed potent anti-hyperglycemic activities were further evaluated in vitro for their PPARγ binding affinity and insulin-secreting ability as potential mechanisms for anti-hyperglycemic activity. Four compounds (15a, 15b, 15dand 15e) significantly bound to PPARγ with IC50values of 0.482, 0.491, 0.350 and 0.369 μM, respectively. Moreover, Compounds 15aand 15bhave demonstrated induction of insulin-secretion with EC50values of 0.92 and 0.98 μM, respectively. Furthermore, molecular docking and pharmacophore generation techniques were carried out to investigate binding patterns and fit values of the designed compounds with PPARγ and SUR, respectively.
- Ibrahim, Mohammed K.,Eissa, Ibrahim H.,Abdallah, Abdallah E.,Metwaly, Ahmed M.,Radwan,ElSohly
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- Pyrazolo[4′,3′:5,6]pyrano[2,3-b]quinoxalin-4(1H)-one: Synthesis and characterization of a novel tetracyclic ring system
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(Chemical Equation Presented) Derivatives of the hitherto unknown ring system, pyrazolo[4′,3′:5,6]pyrano[2,3-b]quinoxalin-4(1H)-one, are synthesized in one step from the corresponding 1-substuituted or 1,3-disubstituted 2-pyrazolin-5-ones and 3-chloroquinoxaline-2-carbonyl chloride using calcium hydroxide in boiling 1,4-dioxane. The parent system carrying no substituent in positions 1 and 3 is obtained upon treatment of the 1-PMB (p-methoxybenzyl) protected congener with trifluoroacetic acid. Detailed NMR spectroscopic investigations including unambiguous chemical shift assignments of all 1H, 13C, and 15N resonances of the obtained tetracycles are reported.
- Eller, Gernot A.,Datterl, Barbara,Holzer, Wolfgang
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- Novel antioxidant quinoxaline derivative: Synthesis, crystal structure, theoretical studies, antidiabetic activity and molecular docking study
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New quinoxaline derivative, N-(4-methyl-2-nitrophenyl)-2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide (NPOQA) has been synthesized and characterized by IR, 1H &13C NMR, ESI-MS and single crystal X-ray diffraction analysis using exper
- Missioui, Mohcine,Mortada, Salma,Guerrab, Walid,Serdaro?lu, Goncagül,Kaya, Sava?,Mague, Joel T.,Essassi, El Mokhtar,Faouzi, My El Abbes,Ramli, Youssef
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- Discovery of new quinoxaline-2(1H)-one-based anticancer agents targeting VEGFR-2 as inhibitors: Design, synthesis, and anti-proliferative evaluation
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VEGF/VEGFR2 pathway is the crucial therapeutic target in the treatment of cancer. So that, a new series of quinoxaline-2(1H)-one derivatives were designed and synthesized. The synthesized compounds were tested against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) aiming to evaluate its anti-proliferative activities. Doxorubicin as a universal anticancer drug and sorafenib as a potent VEGFR-2 inhibitor were used as positive controls. The data obtained from biological activity were found highly correlated with that obtained from molecular modeling studies. The most sensitive cell line to the influence of our new derivatives was HCT-116. Compounds 13b, 15, 16e and 17b exert the highest cytotoxic activities against the tested cell lines. Overall, compound 15 was the most active member with IC50 values of 5.30, 2.20, 5.50 μM against HepG-2, MCF-7 and HCT-116, respectively. Compounds 15 and 17b showed better anti-proliferative activities than doxorubicin and sorafenib against the three cancer cell lines. Additionally, compound 16e showed better anti-proliferative activities than doxorubicin and sorafenib against HepG-2 and HCT-116 but exhibited lower activity against MCF-7 cell line. In addition, the most promising members were further evaluated for their inhibitory activities against VEGFR-2. Compounds 15 and 17b potently inhibited VEGFR-2 at lower IC50 values of 1.09 and 1.19 μM, respectively, compared to sorafenib (IC50 = 1.27 μM). Moreover, docking studies were conducted to investigate the binding pattern of the synthesized compounds against the prospective molecular target VEGFR-2.
- Abulkhair, Hamada S.,Eissa, Ibrahim H.,El-Adl, Khaled,ElSohly, Mahmoud A.,Elhendawy, Mostafa A.,Mehany, Ahmed B. M.,Metwaly, Ahmed M.,Radwan, Mohamed M.,Sakr, Helmy M.,Yousef, Reda G.
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- New quinoxaline-2(1H)-ones as potential VEGFR-2 inhibitors: design, synthesis, molecular docking, ADMET profile and anti-proliferative evaluations
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Eleven new quinoxaline derivatives were designed and synthesized as modified VEGFR-2 inhibitors of our previous work. The synthesized compounds were tested against three human cancer cell lines (HepG-2, MCF-7 and HCT-116). Compounds11g,11eand11cwere the most potent members against the tested cells. Compound11g(IC50= 4.50, 2.40, and 5.90 μM) was the most potent member compared to doxorubicin (IC50= 8.29, 9.65, and 7.68 μM) and sorafenib (IC50= 7.33, 9.41, and 7.23 μM) against HepG-2 and HCT-116, and MCF-7 cell lines, respectively. Compound11eshowed better anti-proliferative activities than doxorubicin and sorafenib with IC50values of 5.34, 4.19, and 6.06 μM, against HepG-2 and HCT-116 and MCF-7 cell lines, respectively. In addition, the most active anti-proliferative derivatives11c,11e,11f, and11gwere selected to evaluate their inhibitory activities against VEGFR-2. The tested compounds displayed good inhibitory activity with IC50values ranging from 0.75 to 1.36 μM. Among them, compound11gwas the most active member with an IC50value of 0.75 μM, compared to the reference drug; sorafenib (IC50= 1.29 μM). Moreover, docking studies revealed that the synthesized compounds have good binding patterns against the prospective molecular target; VEGFR-2. In addition,in silico, ADMET and toxicity studies showed a high level of drug likeness for the synthesized compounds.
- Abulkhair, Hamada S.,Eissa, Ibrahim H.,El-Adl, Khaled,ElSohly, Mahmoud A.,Elhendawy, Mostafa A.,Mehany, Ahmed. B. M.,Metwaly, Ahmed M.,Radwan, Mohamed M.,Sakr, Helmy M.,Yousef, Reda G.
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p. 16949 - 16964
(2021/09/27)
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- New quinoxaline-based VEGFR-2 inhibitors: Design, synthesis, and antiproliferative evaluation with: In silico docking, ADMET, toxicity, and DFT studies
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A new series of 3-methylquinoxaline-based derivatives having the same essential pharmacophoric features as VEGFR-2 inhibitors have been synthesized and evaluated for their antiproliferative activities against two human cancer cell lines, MCF-7 and HepG-2. Compounds 15b and 17b demonstrated a significant antiproliferative effect with IC50 ranging from 2.3 to 5.8 μM. An enzymatic assay was carried out for all the tested candidates against VEGFR-2. Compound 17b was the most potent VEGFR-2 inhibitor (IC50 = 2.7 nM). Mechanistic investigation including cell cycle arrest and apoptosis was performed for compound 17b against HepG-2 cells, and the results revealed that 17b induced cell apoptosis and arrested cell cycle in the G2/M phase. Moreover, apoptosis analyses were conducted for compound 17b to evaluate its apoptotic potential. The results showed upregulation in caspase-3 and caspase-9 levels, and improving the Bax/Bcl-2 ratio by more than 10-fold. Docking studies were performed to determine the possible interaction with the VEGFR-2 active site. Further docking studies were carried out for compound 17b against cytochrome P450 to present such compounds as non-inhibitors. In silico ADMET, toxicity, and physico-chemical properties revealed that most of the synthesized members have acceptable values of drug-likeness. Finally, DFT studies were carried out to calculate the thermodynamic, molecular orbital and electrostatic potential properties.
- Alanazi, Manal M.,Alanazi, Mohammed M.,Alharbi, Madhawi A.,Alkahtani, Hamad M.,Alsaif, Nawaf A.,Dahab, Mohammed A.,Eissa, Ibrahim H.,Elkady, Hazem,Obaidullah, Ahmad J.
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p. 30315 - 30328
(2021/10/25)
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- Small molecule compound bonded with alpha-synuclein aggregate, and preparation method and application thereof
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The invention belongs to the technical field of medicine, and relates to a compound capable of being bonded with alpha-synuclein aggregate, and a preparation method and application thereof. The structural general formula of the compound is shown in the formula I, wherein m is a positive integer selected from 1 to 3, R1 is respectively selected from phenyl, substituted phenyl, naphthyl, biphenyl, 5-6-membered aromatic heterocycle and substituted 5-6-membered aromatic heterocycle, and R2 is selected from benzyl, C1-3 alkyl naphthyl, C1-3 alkyl, phenyl, substituted phenyl, 5-6-membered heteroaromatic ring and substituted 5-6-membered heteroaromatic ring. The compound disclosed by the invention can be strongly bonded with alpha-synuclein aggregate, can be used as an imaging tracer agent required by image examination technologies such as PET (Polyethylene Terephthalate) and SPECT (Single Photon Emission Computed Tomography) for clinical disease diagnosis or used for preparing the imaging tracer agent and preparing a composition comprising the imaging tracer agent, and used for detecting diseases related to alpha-synuclein misfolding and abnormal aggregation, such as Parkinson's disease, and has a remarkable good application prospect.
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Paragraph 0024
(2021/04/14)
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- Antiplasmodial 2-thiophenoxy-3-trichloromethyl quinoxalines target the apicoplast of Plasmodium falciparum
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The identification of a plant-like Achille's Heel relict, i.e. the apicoplast, that is essential for Plasmodium spp., the causative agent of malaria lead to an attractive drug target for new antimalarials with original mechanism of action. Although it is not photosynthetic, the apicoplast retains several anabolic pathways that are indispensable for the parasite. Based on previously identified antiplasmodial hit-molecules belonging to the 2-trichloromethylquinazoline and 3-trichloromethylquinoxaline series, we report herein an antiplasmodial Structure-Activity Relationships (SAR) study at position two of the quinoxaline ring of 16 newly synthesized compounds. Evaluation of their activity toward the multi-resistant K1 Plasmodium falciparum strain and cytotoxicity on the human hepatocyte HepG2 cell line revealed a hit compound (3k) with a PfK1 EC50 value of 0.3 μM and a HepG2 CC50 value of 56.0 μM (selectivity index = 175). Moreover, hit-compound 3k was not cytotoxic on VERO or CHO cell lines and was not genotoxic in the in vitro comet assay. Activity cliffs were observed when the trichloromethyl group was replaced by CH3, CF3 or H, showing that this group played a key role in the antiplasmodial activity. Biological investigations performed to determine the target and mechanism of action of the compound 3k strongly suggest that the apicoplast is the putative target as showed by severe alteration of apicoplaste biogenesis and delayed death response. Considering that there are very few molecules that affect the Plasmodium apicoplast, our work provides, for the first time, evidence of the biological target of trichloromethylated derivatives.
- Amanzougaghene, Nadia,Amrane, Dyhia,Azas, Nadine,Azqueta, Amaya,Mazier, Dominique,Primas, Nicolas,Sanz-Serrano, Julen,Tajeri, Shahin,Vanelle, Patrice,Verhaeghe, Pierre,Arnold, Christophe-Sébastien,Botté, Cyrille,Hutter, Sébastien,Louis, Béatrice
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- Aggregation-induced emission photosensitizer, preparation method and application
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The invention provides an aggregation-induced emission photosensitizer based on a quinoxaline ketone skeleton, and a preparation method and application thereof. A photosensitizer molecule is prepared from o-phenylenediamine and a derivative thereof through cyclization, nucleophilic substitution, aldol condensation and Suzuki coupling reaction. The compound provided by the invention has strong near-infrared fluorescence emission in an aggregation state, generates a large amount of reactive oxygen free radicals under the radiation of a 530 nm laser, and can be used as a potential photosensitizer. The compound provided by the invention can be directly added into a culture medium for photodynamic therapy of tumor cells, and can also be prepared into nano particles for intravenous injection to perform in-vivo photodynamic therapy.
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Paragraph 0033-0034
(2021/06/23)
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- Active photosensitizer and preparation method and application thereof
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The invention provides a quinoxalinone active photosensitizer based on histone deacetylase as a target and a preparation method and application thereof. Nucleophilic substitution, aldol condensation The reaction is obtained by a hydroxylamine solution or the like. The compounds of the invention can significantly inhibit HDAC1, 6, 8 activity, IC50 respectively 89 ±4.6, 34 ±2.7 and 852 ± 6 . 3nM, and the compound generates a large amount of active oxygen radicals under irradiation of 450 nm lasers, and can be used as a potential active photosensitizer. The compound can be directly added into a culture medium and then used for photodynamic binding molecule targeted therapy of breast cancer cells (MCF-7), and can also be used for intravenous injection after nano particles. Power therapy.
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Paragraph 0011; 0036-0038
(2021/10/16)
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- Metal-Free Tandem One-Pot Construction of 3,3-Disubsituted 3,4-Dihydroquinoxalin-2(1H)-Ones under Visible-Light Photoredox Catalysis
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Visible-light photoredox-catalyzed metal-free tandem one-pot synthesis of 3,3-disubstituted 3,4-dihydroquinoxalin-2(1H)-ones from easily accessible 1,2-diaminobenzenes, α-ketoesters and 4-alkyl Hantzsch esters has been described. This mild transformation affords the desired products in 47–93% yields for diversely decorated substrates, and can proceed on a gram-scale. The efficacy of the current catalysis arises from the use of organic 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) as the photocatalyst and CF3CO2H as the additive. (Figure presented.).
- Li, Bohan,Luo, Zhenli,Pan, Yixiao,Shi, Qian,Wang, Peng,Xu, Lijin,Yao, Zhen,Zhang, Xin
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supporting information
(2021/12/01)
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- Alkylation of quinoxalin-2(1H)-ones using phosphonium ylides as alkylating reagents
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A practical and efficient methodology for the construction of 3-alkylquinoxalinones through base promoted direct alkylation of quinoxalin-2(1H)-ones with phosphonium ylides as alkylating reagents under metal- and oxidant-free conditions was developed. Various 3-alkylquinoxalin-2(1H)-ones were easily obtained in good to excellent yields. Tentative mechanistic studies suggest that this reaction is likely to involve a nucleophilic addition-elimination process.
- Liu, Jun-Jia,Peng, Sha,Yang, Luo
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supporting information
p. 9705 - 9710
(2021/11/30)
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- N, N, N', N'-Tetramethylethylenediamine-Enabled Photoredox-Catalyzed C-H Methylation of N-Heteroarenes
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Aiming at the valuable methylation process, readily available and inexpensive N,N,N′,N′-tetramethylethylenediamine (TMEDA) was first identified as a new methyl source in photoredox-catalyzed transformation in this work. By virtue of this simple methylating reagent, a facile and practical protocol for the direct C-H methylation of N-heteroarenes was developed, featuring mild reaction conditions, broad substrate scope, and scalability. Mechanistic studies disclosed that a sequential photoredox, base-assisted proton shift, fragmentation, and tautomerization process was essentially involved.
- Liu, Fang,Ye, Zhi-Peng,Hu, Yuan-Zhuo,Gao, Jie,Zheng, Lan,Chen, Kai,Xiang, Hao-Yue,Chen, Xiao-Qing,Yang, Hua
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p. 11905 - 11914
(2021/08/24)
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- Direct functionalization of quinoxalin-2(1H)-one with alkanes: C(sp2)-H/C(sp3)-H cross coupling in transition metal-free mode
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Considering the significance of pharmaceutically important heterocycles, efficient and highly versatile protocols for the functionalization of diverse heterocycles with easily accessible feedstock are crucial. Here, we have reported selective alkylation of quinoxalin-2(1H)-one with a broad class of hydrocarbons having different C(sp3)-H bonds with varying bond strengths using di-tert-butyl peroxide (DTBP) as an alkoxyl radical mediator for hydrogen atom transfer (HAT). This dehydrogenative coupling approach utilizes feedstock chemicals such as cycloalkanes, cyclic ethers and alkyl arenes as coupling partners. This protocol exhibits good functional group compatibility and selectivity regarding both heterocycles and unactivated alkanes. Moreover, this methodology allows functionalization of relatively strong C-H bonds of adamantane and exclusive selectivity towards 3° C(sp3)-H bonds is observed. We also illustrate the applicability of this C(sp2)-H/C(sp3)-H cross-coupling for practical access to bioactive pharmaceuticals.
- Dagar, Neha,Raha Roy, Sudipta,Singh, Swati
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p. 5383 - 5394
(2021/06/28)
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- Design, synthesis and biological evaluation of quinoxaline compounds as anti-HIV agents targeting reverse transcriptase enzyme
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Infection by human immunodeficiency virus still represents a continuous serious concern and a global threat to human health. Due to appearance of multi-resistant virus strains and the serious adverse side effects of the antiretroviral therapy administered, there is an urgent need for the development of new treatment agents, more active, less toxic and with increased tolerability to mutations. Quinoxaline derivatives are an emergent class of heterocyclic compounds with a wide spectrum of biological activities and therapeutic applications. These types of compounds have also shown high potency in the inhibition of HIV reverse transcriptase and HIV replication in cell culture. For these reasons we propose, in this work, the design, synthesis and biological evaluation of quinoxaline derivatives targeting HIV reverse transcriptase enzyme. For this, we first carried out a structure-based development of target-specific compound virtual chemical library of quinoxaline derivatives. The rational construction of the virtual chemical library was based on previously assigned pharmacophore features. This library was processed by a virtual screening protocol employing molecular docking and 3D-QSAR. Twenty-five quinoxaline compounds were selected for synthesis in the basis of their docking and 3D-QSAR scores and chemical synthetic simplicity. They were evaluated as inhibitors of the recombinant wild-type reverse transcriptase enzyme. Finally, the anti-HIV activity and cytotoxicity of the synthesized quinoxaline compounds with highest reverse transcriptase inhibitory capabilities was evaluated. This simple screening strategy led to the discovery of two selective and potent quinoxaline reverse transcriptase inhibitors with high selectivity index.
- Estrin, Darío,Fabian, Lucas,Gómez, Natalia,Moglioni, Albertina,Salvatori, Melina,Taverna Porro, Marisa,Turk, Gabriela
-
-
- Preparation method of 3-methylquinoxaline-2-(1H)-one derivative
-
The invention discloses a preparation method of a 3-methylquinoxaline-2-(1H)-one derivative. The preparation method comprises the following steps: by taking elemental iodine as an oxidizing agent, sodium sulfite as an additive and tert-butyl hydroperoxide (TBHP) as a methyl source, carrying out a direct methylation reaction on carbon No. 3 on a quinoxaline-2-(1H)-one compound in an organic solvent, and after the reaction is completed, carrying out aftertreatment to obtain the 3-methylquinoxaline-2-(1H)-one derivative. The preparation method uses cheap and easily available reaction raw materials and is simple.
- -
-
Paragraph 0130-0135
(2020/05/30)
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- Peroxide-mediated site-specific C-H methylation of imidazo[1,2-: A] pyridines and quinoxalin-2(1 H)-ones under metal-free conditions
-
An effective approach to realize the direct methylation of imidazo[1,2-a]pyridines and quinoxalin-2(1H)-ones with peroxides under metal-free conditions is described. In this protocol, peroxides serve as both the radical initiator and methyl source. Methylated imidazopyridines and quinoxalin-2(1H)-ones were smoothly synthesized in moderate to good yields. A free radical reaction mechanism was proposed to describe the methylation process.
- Jin, Shengzhou,Yao, Hua,Lin, Sen,You, Xiaoqing,Yang, Yao,Yan, Zhaohua
-
supporting information
p. 205 - 210
(2020/01/13)
-
- Design, synthesis,: In silico docking studies and biological evaluation of novel quinoxaline-hydrazide hydrazone-1,2,3-triazole hybrids as α-glucosidase inhibitors and antioxidants
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A new series of quinoxaline-hydrazidehydrazone-1,2,3-triazole hybrids, 14a-j, 15a-j and 16a-e, was designed, synthesized and screened for in vitro α-glucosidase and antioxidant activities. For the synthesis of the target compounds, quinoxaline hydrazides were condensed with benzaldehyde triazoles in the presence of AcOH (cat) in ethanol. The key step in the preparation of compounds 8a-j was the Cu(i)-catalyzed [3+2] cycloaddition reaction (CuAAC) with appropriate alkynes (6, 7) and azides, and 13a-j were prepared from simple aldehydes utilizing the same click reaction as the final step. Quinoxaline hydrazides (3, 3a) were synthesized from o-phenylenediamine and pyruvic acid via three-step reactions comprising cyclization, alkylation and hydrazidation. Among these hybrids, 14a (IC50 = 21.92 μg mL-1), 14b (IC50 = 22.32 μg mL-1), 14c (IC50 = 23.58 μg mL-1) and 15a (IC50 = 24.50 μg mL-1) showed good α-glucosidase inhibition compared with the standard acarbose (IC50 = 22.32 μg mL-1). Further, the scavenging abilities of the synthesized compounds as antioxidants were studied using the DPPH, H2O2, and NO methods; as per the obtained results, compounds 14a, 14b, 14c and 15a displayed good antioxidant activity. Docking studies of the active compounds and acarbose as a standard with α-glucosidase (PDB ID: 2ZEO) were performed to determine the molecular interactions between the inhibitors and the active site of the enzyme. Better binding energies of the active compounds than of the standard acarbose were observed. Therefore, our new hybrid molecules may be useful for further optimization in developing new lead molecules with both α-glucosidase inhibition and antioxidant activities.
- Settypalli, Triloknadh,Chunduri, Venkata Rao,Maddineni, Aruna Kumari,Begari, Nagaraju,Allagadda, Rajasekhar,Kotha, Peddanna,Chippada, Appa Rao
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p. 15435 - 15452
(2019/10/08)
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- Quinoxaline-PABA bipartite hybrid derivatization approach: Design and search for antimicrobial agents
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In an attempt to find a new class of antimicrobial agents, in the present study we report the synthesis of bipartite hybrid styryl derivatives of quinoxaline containing para-aminobenzoic acid (PABA) and their biological evaluation as antimicrobial agents. The series of new substituted styryl based derivatives 5(a–k) were evaluated for antimicrobial potential against various bacteria including Staphylococcus aureus, Vibrio cholerae, Escherichia coli, Bacillus subtilis, Escherichia coli, Mycobacterium smegmatis, Pseudomonas aeruginosa and fungi; C. albicans, with ampicillin and amphotericin B as standards. Similarly these compounds were also screened for anti-cancer activity using MCF-7 cell line. Among the synthesized compounds, 5(c) was observed to be the most active compound against various strains with MIC in a range of 7.9–31 μM of the series and compound 5i came out with significant anti-cancer activity with IC50 value of 7 μM.
- Patel, Harun M.,Bhardwaj, Varun,Sharma, Poonam,Noolvi, Malleshappa N.,Lohan, Sandeep,Bansal, Sumit,Sharma, Amit
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p. 562 - 568
(2019/03/06)
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- Design and synthesis of new quinoxaline derivatives as anticancer agents and apoptotic inducers
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The quinoxaline scaffold is a promising platform for the discovery of active chemotherapeutic agents. Three series of quinoxaline derivatives were synthesized and biologically evaluated against three tumor cell lines (HCT116 human colon carcinoma, HepG2, liver hepatocellular carcinoma and MCF-7, human breast adenocarcinoma cell line), in addition to VEGFR-2 enzyme inhibition activity. Compounds VIId, VIIIa, VIIIc, VIIIe and XVa exhibited promising activity against the tested cell lines and weak activity against VEGFR-2. Compound VIIIc induced a significant disruption in the cell cycle profile and cell cycle arrest at the G2/M phase boundary. In further assays, the cytotoxic effect of the highly active compounds was determined using a normal Caucasian fibroblast-like fetal lung cell line (WI-38). Compound VIIIc could be considered as a lead compound that merits further optimization and development as an anti-cancer and an apoptotic inducing candidate against the HCT116 cell line.
- El Newahie, Aliya M.S.,Nissan, Yassin M.,Ismail, Nasser S.M.,Abou El Ella, Dalal A.,Khojah, Sohair M.,Abouzid, Khaled A.M.
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-
- Visible-light induced decarboxylative alkylation of quinoxalin-2(1H)-ones at the C3-position
-
A simple and efficient method for the visible light induced direct carbon alkylation of quinoxalin-2(1H)-ones at the C3 position is described. This protocol employs cheap and readily available phenyliodine(iii) dicarboxylates as the alkylation reagents to conduct decarboxylative radical coupling reaction with quinoxalin-2(1H)-ones. The process exhibits excellent compatibility to functional groups and provides a convenient and selective access to various 3-alkylquinoxalin-2(1H)-ones in good yields.
- Xue, Wenxuan,Su, Yingpeng,Wang, Ke-Hu,Zhang, Rong,Feng, Yawei,Cao, Lindan,Huang, Dangfeng,Hu, Yulai
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p. 6654 - 6661
(2019/07/16)
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- A Catalyst-Free Minisci-Type Reaction: the C–H Alkylation of Quinoxalinones with Sodium Alkylsulfinates and Phenyliodine(III) Dicarboxylates
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A direct C–H alkylation of quinoxalinones at the C-3 position with sodium alkylsulfinates and phenyliodine(III) dicarboxylates has been developed under catalyst-free conditions. A series of 3-alkylquinoxalinones were afforded in moderate to excellent yields in this protocol, which offers a practical and efficient access to biologically interesting 3-alkylquinoxalin-2(1H)-one derivatives.
- Wang, Liping,Zhao, Jiquan,Sun, Yuting,Zhang, Hong-Yu,Zhang, Yuecheng
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p. 6935 - 6944
(2019/11/11)
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- Act on the FGFR - 1 of 3 - vinyl - quinoxaline -2 (1 H) - one derivatives and its preparation and use
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The present invention discloses 3-vinyl-quinoxaline-2(1H)-one derivative acting on FGFR-1, a preparation method and uses thereof, and belongs to the field of pharmaceutical chemistry. According to the present invention, o-phenylenediamine and pyruvic acid are adopted as raw materials and are subjected to cyclization to obtain 3-methyl quinoxaline-2(1H)-one, the 3-methyl quinoxaline-2(1H)-one reacts with different substituted aldehydes to obtain 3-substituted quinoxaline derivatives, and the 3-substituted quinoxaline derivatives are adopted as the intermediate products and are subjected to substitution to obtain other types of the target compounds, wherein the 6 new compounds are prepared; and the 3-vinyl-quinoxaline-2(1H)-one derivatives of the present invention have a certain inhibition effect for experiment cells, show a certain anti-tumor activity, and further have characteristics of cell selectively, good safety, and kinase inhibition activity.
- -
-
Paragraph 0039; 0040
(2018/07/06)
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- Method for preparing ethylene glycol compounds
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The invention provides a method for preparing ethylene glycol compounds. The preparation method is short in route, the yield is high, and the operation is simple, Compounds VIII and IX serve as intermediates for preparing the ethylene glycol compounds in the invention, and the ethylene glycol compounds disclosed by the invention are prepared by taking the compounds VIII and IX as the intermediates. The method is high in yield, high in purity and suitable for industrial production.
- -
-
Paragraph 0163; 0164; 0165; 0166
(2018/12/02)
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- Fluorescent probe based on quinoxalinone aryl sulfides as well as preparation method and application thereof
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The invention provides a fluorescent probe based on quinoxalinone aryl sulfides as well as a preparation method and application thereof. A chemical structure of a fluorescent probe molecule is shown in formula (I) (shown in the specification), wherein R is selected from allyl and derivatives thereof, benzyl and derivatives thereof, fatty acid ester groups with the carbon atom number of 1-8 or fatty acid with the carbon atom number of 1-8; R1 is selected from alkoxy with the carbon atom number of 1-8, halogen or alkyl with the carbon atom number of 1-8; and R2 is aryl sulfides. The fluorescentprobe molecule is obtained by cyclizing o-phenylenediamine and derivatives thereof, carrying out nucleophilic substitution and carrying out aldol condensation reaction. The quinoxalinone derivative compound turns red fluorescence into green fluorescene after thioether is oxidized into sulfoxide in the presence of up-regulated heme oxidase and active oxygen in ferroptosis cells. The fluorescent probe provided by the invention can be directly added into a culture medium, then acts on cells and carries out detection, and also can be directly injected intravenously or intratumorally and play a role of animal in vivo detection.
- -
-
Paragraph 0074; 0075; 0076
(2018/06/16)
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- DNA topoisomerase II inhibition has the activity of modulating kui analogue and its preparation method and application
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The invention discloses a quinoxalinone analog with DNA (deoxyribonucleic acid) topoismerase II inhibiting activity, an optical isomer, diastereoisomer or racemic mixture, or pharmaceutically acceptable salt, solvate, prodrug, intermediate or metabolite thereof. The structural general formula is disclosed as Formula (I), wherein R1, R2, R3, R4, R5 and Ar are defined in the specification. The invention also discloses a preparation method of the compounds and application of the compounds as drugs and in treating tumors. The compounds have the advantages of definite curative effect and small toxic and side effects, enriches the varieties of inhibitors of drugs for treating diseases caused by topoismerase II expression abnormity in the prior art, and is hopeful to become clinical drugs with higher therapeutic index.
- -
-
Paragraph 0129; 0130; 0131
(2018/08/03)
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- Metal-free tandem cyclization/hydrosilylation to construct tetrahydroquinoxalines
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A one-pot tandem procedure involving cyclization and sequential hydrosilylation of imines and amides under the catalysis of B(C6F5)3 has been developed for the step-economical construction of 1,2,3,4-tetrahydroquinoxalines directly from readily available 1,2-diaminobenzenes, α-ketoesters and low-cost, safe polymethylhydrosiloxane (PMHS). This metal-free approach provides various products in good to excellent yields, and displays a wide range of substrate scope and a high degree of functional group tolerance even to reduction-sensitive moieties. The choice of hydrosilanes is critical to the catalysis, and PMHS has proved to be optimal. Decreasing the amount of PMHS could enable the reaction to stop at the 3,4-dihydroquinoxalin-2(1H)-one stage. The procedure is convenient and scalable, and neither a dried solvent nor an inert atmosphere is required. Moreover, the enantioselective construction of these products was explored, and promising results were achieved.
- Pan, Yixiao,Chen, Changjun,Xu, Xin,Zhao, Haoqiang,Han, Jiahong,Li, Huanrong,Xu, Lijin,Fan, Qinghua,Xiao, Jianliang
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supporting information
p. 403 - 411
(2018/02/07)
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- A new solvent for the reaction of chlorination of hydroxyquinoxaline derivatives with vilsmeier reagent
-
A new efficient procedure for the chlorination of hydroxyquinoxaline derivatives into the corresponding chlorides is described. It has been found that the use of 1-chlorobutane produces the highest yield, reduces the time of reaction and facilitates direct formation of crystals without any purification.
- Bouanane, Zohra,Bounekhel, Mahmoud,Elkolli, Meriem,Takfaoui, Abdelilah
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p. 903 - 906
(2018/04/09)
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- Synthesis and in vivo diuretic activity of some new benzothiazole sulfonamides containing quinoxaline ring system
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A series of new 6-substituted-N-[3-{2-(substituted phenyl)-ethenyl} quinoxaline-2(1H)-ylidene]-1,3-benzothiazole-2-amine (4a–f) were designed and synthesized by condensing 2-amino-benzothiazole-6-sulfonic acid amide (1) with chalcones of quinoxaline-2-one (3a–f) in a hope to obtain promising and a new class of diuretic agents. Structures of all the newly synthesized compounds were characterized by spectral data and elemental analysis. The pharmacological studies in experimental rats indicates that compound 4c possesses excellent in vivo diuretic activity of 1.13 and appears to be a better diuretic agent than the reference drugs, acetazolamide (1.0) and urea (0.88). Insight of the binding mode of the synthesized compounds (ligand) into the binding sites of carbonic anhydrase enzyme (PDF code: 4KUV) was provided by docking studies, performed with the help of Maestro 9.0 docking software. Further pharmacokinetic and toxicological studies are needed to confirm the safety of compound 4c which emerged as a lead diuretic compound.
- Husain, Asif,Madhesia, Diwakar,Rashid, Mohd,Ahmad, Aftab,Khan, Shah Alam
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p. 1682 - 1689
(2016/10/09)
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- Quinoxalinone diaryl urea having VEGFR-2 and B-raf dual inhibition effect, derivative, preparation method and applications thereof
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The present invention discloses quinoxalinone diaryl urea having a VEGFR-2/B-raf dual inhibition effect, a derivative, a pharmacologically acceptable salt, a solvate, a prodrug, an intermediate, a metabolite thereof or a pharmaceutical composition containing the quinoxalinone diaryl urea, wherein the structure general formula is represented by a formula (I), and R1, R2, R, Q, Y and Ar are defined in the specification. The invention further provides preparation methods of the compounds, and applications of the compounds as drugs and applications of the compounds in tumor treatment. According to the present invention, the compound has advantages of exact treatment effect and low toxic-side effect, wherein the types of the drug inhibitors for treatment of diseases caused by abnormal expression of VEGFR-2 and/or B-Raf are enriched, and the quinoxalinone diaryl urea is expected to be the clinical medicine having the high therapeutic index. The formula (I) is defined in the specification.
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-
Paragraph 0128; 0129
(2017/08/25)
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- 3-(cis)-vinyl aryl quinoxalinone analogue, and preparation method and application thereof
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The invention discloses a 3-(cis)-vinyl aryl quinoxalinone analogue with VEGFR-2 inhibitory activity, a pharmaceutically acceptable salt thereof, and pharmaceutical compositions using solvate, prodrug, intermediate and metabolite thereof as an active substance or containing the compound. The compound has general structural formula (I) and formula (II) shown as below, wherein R1, R2 and Ar are as defined in the specification. The present invention also describes a preparation method of the analogue and application thereof as medicaments in the treatment of tumors. The compound of the present invention has effective effect and less toxic or side effect, enriches the medicament inhibitors for diseases caused by VEGFR-2 abnormal expression in the prior art, and is expected to become a clinical medicine with higher therapeutic index.
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-
Paragraph 0128; 0129
(2016/12/22)
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- Chemoselective synthesis of 3,6,7-trisubstituted 2-(2,3:5,6-di-O-isopropylidene-β-D-mannofuranosyloxy]- and 2-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyloxy)quinoxaline derivatives
-
[Figure not available: see fulltext.] A series of quinoxaline O-nucleosides, 3,6,7-trisubstituted 2-(2,3:5,6-di-O-isopropylidene-β-D-mannofuranosyl-1-yl)quinoxalines and 2-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-β-D-glucopyranosyl)quinoxalines, was prepared by the reaction of 3,6,7-trisubstituted quinoxalin-2(1H)-ones with the corresponding protected α-chlorosugars in the presence of NaH. The reaction proceeded chemoselectively to give products of O-substitution with β-configuration at anomeric carbon, as proved by NMR data. The deprotection of the 1-(2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-β-D-glucopyranosyl)quinoxalines was achieved by stirring in ammonia-methanol mixture to afford free O-quinoxaline nucleoside analogs.
- Fathalla, Walid
-
-
- Reaction of 5-methylene-hydantoins and their chemical modification to twin-drug type symmeteical molecules
-
We report chemical modifications of 5-methylenehydantoins (3a-e) with various amine nucleophiles to 5-substitutedhydantoins and transformations the obtained hydantoins to new symmetrical twin-drug type bivalent molecules 12 and 13. We also report 5-methyl
- Fujisaki, Fumiko,Fujiwara, Ryou,Okabe, Miriko,Naito, Ayumi,Fukami, Enko,Aki, Hatsumi,Kashige, Nobuhiro,Miake, Fumio,Sumoto, Kunihiro
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p. 2745 - 2759
(2015/02/19)
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- A new facile, efficient synthesis and structure peculiarity of quinoxaline derivatives with two benzimidazole fragments
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A highly efficient and versatile method for the synthesis of quinoxaline derivatives with two benzimidazole fragments have been developed on the basis of the ring contraction of 3-(benzimidazo-2-yl)quinoxalin-2(1H)-one with 1,2-diaminobenzene and its various types of substituted and condensed derivatives. Owing to the inter- and intramolecular processes, involving self association, proton exchange, conformational, and/or tautomeric exchanges between several forms for most of the bis-benzimidazolylquinoxalines signals of bridged and neighboring carbon atoms and the hydrogen atoms of the neighboring carbon atoms of benzimidazole fragments in the NMR spectra are broadened. The conjugation between the benzimidazole fragments and the quinoxaline core of the molecules is increased from the quinoxaline derivative (10c) to its thiadiazol[f]- (17) and pyrrolo[a]-(19) annulated derivatives, resulting in a greater planarity of the molecule as a whole.
- Mamedov, Vakhid A.,Zhukova, Nataliya A.,Syakaev, Victor V.,Gubaidullin, Aidar T.,Beschastnova, Tat'Yana N.,Adgamova, Dil'Bar I.,Samigullina, Aida I.,Latypov, Shamil K.
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supporting information
p. 1403 - 1416
(2013/02/23)
-
- Synthesis of 2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide-based azetidinone derivatives as potent antibacterial and antifungal agents
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Twelve compounds belonging to series N-[3-chloro-2-oxo-4-(substituted) phenylazetidin-1-yl]-2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide (5a-l) were synthesized. These compounds were evaluated for their in vitro antibacterial against E. coli, S. aureus, K. pneumoniae, P. aeruginosa and antifungal activity against C. albicans, A. niger and A. flavus by cup-plate method. Structures of all the newly synthesized compounds were confirmed by their spectral data interpretation. Compound 5g having p-dimethylaminophenyl group on 4-position of azetidinone ring attached to N-atom of acetamido group on 1-position of 3-methyl-1H-quinoxaline-2-one, was found to be active against all the bacterial and fungal strains under investigation.
- Kumar, Shiv,Kumar, Nitin,Drabu, Sushma,Minhaj, Md. Akram
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p. 129 - 139
(2013/04/24)
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- TRIAZOLOPYRAZINE DERIVATIVES AND THEIR USE FOR TREATING NEUROLOGICAL AND PSYCHIATRIC DISORDERS
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The present invention is directed to triazolopyrazine compounds of Formula (I). Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds as therapeutic agents treating neurological and psychiatric disorders.
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-
Page/Page column 17
(2013/03/26)
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- Unexpected imidazoquinoxalinone annulation products in the photoinitiated reaction of substituted-3-methyl-quinoxalin-2-ones with N-phenylglycine
-
Photoinduced electron transfer between N-phenylglycine (NPG) and electronically excited triplets of 7-substituted-3-methyl-quinoxalin-2-ones in acetonitrile generate the respective ion radical pair, where by decarboxylation the phenyl-amino-alkyl radical, PhNHCH2?, is generated. This radical reacts with the 3-methyl-quinoxalin-2-ones ground states, leading to the product 2. Other, unexpected, 7-substituted-1,2,3,3a-tetrahydro-3a-methyl-2- phenylimidazo[1,5-a]quinoxalin-4(5H)-ones, annulation products, 3a-f, were generated; likely by the addition of two PhNHCH2? radicals, to positions 3 and 4 of the quinoxalin-2-ones. The reaction mechanism includes a photoinduced one electron transfer initiation step, propagation steps involving radical intermediates and NPG with radical chain termination steps that lead to the respective products 2a-f and 3a-f and NPG by-products. The proposed mechanism accounts for the strong dependency found for the initial photoconsumption quantum yields on the electron-withdrawing power of the substituent. Therefore, photolysis of common reactants widely used such as NPG and substituted quinoxalin-2-ones may provide a simple synthetic way to the unusual, unreported tetrahydro-imidazoquinoxalinones 3a-f.
- De La Fuente, Julio R.,Canete, Alvaro,Jullian, Carolina,Saitz, Claudio,Aliaga, Christian
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p. 1335 - 1345
(2013/11/19)
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- A thienoquinoxaline and a styryl-quinoxaline as new fluorescent probes for amyloid-β fibrils
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Simple and easy to prepare quinoxaline derivatives proved able to stain amyloid fibers such as aggregated lysozyme and Aβ(1-40)-peptide by a fluorescence "turn on" mechanism. Thienoquinoxaline 1 allowed the detection of lysozyme and Aβ(1-40) fibers at λ = 555 and 532 nm, respectively, with excitation at λ = 450 nm. Styryl-quinoxaline 2 stained lysozyme and Aβ(1-40) fibers with fluorescence at λ = 579 and 567 nm, respectively, upon excitation at λ = 453 nm. The apparent K d values for Aβ(1-40) fibers were 77 and 294 nM for 1 and 2, respectively. The sensitivity of the aggregates detection assay with these new dyes was higher than that of thioflavin T. Considering their unique fluorescence properties compared to other dyes reported in the field, they can be considered as additional staining tools for the detection and studies of peptide/protein aggregation.
- Benzeid, Hanane,Mothes, Emmanuelle,Essassi, El Mokhtar,Faller, Peter,Pratviel, Genevive
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experimental part
p. 79 - 85
(2012/04/23)
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- Microwave induced synthesis of quinoxalines and their antitubercular and antiinflammatory activities
-
Quinoxaline incorporated Schiff bases (4a-j) were synthesized by the condensation of 2-[(3-methylquinoxalin-2-yl)oxy] acetohydrazide (3) with indole-3-carbaldehyde, furfuraldehyde, 5-(4-nitrophenyl)-2-furfuraldehyde and substituted benzaldehydes under conventional and microwave irradiation methods. The microwave method was found to be remarkably successful with higher yields, less reaction time and environmental friendly compared to conventional heating method. The chemical structures of the synthesized compounds have been confirmeu: IR, 1H NMR and Mass spectral data. All the compounds have been evaluated for antitubercular and antiinflammatory activities.
- Achutha,Madhava Reddy,Ravikiran,Harinadha Babu
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p. 293 - 296
(2013/09/24)
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- RING-opening reactions of 2-phenyl-1'H,5H-spiro-[oxazole-4,2'-quinoxalin]- 3'(4'H)-ones?
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Several simple quinoxaline derivatives were prepared by ring-opening reactions of 2-phenyl-1'H,5H-spiro[oxazole-4,2'-quinoxalin]-3'(4'H)-one and its N-alkyl derivatives under various reaction conditions.
- Music, Irena,Vercek, Bojan
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p. 719 - 725
(2013/08/23)
-
