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Dissertations / Theses on the topic 'Quinoxaline'
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1
Coez, Arnaud. "Synthèse de quinoxaline-2,3-dione." Paris 5, 1992. http://www.theses.fr/1992PA05P117.
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Guillon, Jean. "Contribution à l'étude de nouvelles pyrrolo [1,2-α] quinoxalines : potentiels antagonistes non-peptidiques du récepteur au glucagon." Caen, 1996. http://www.theses.fr/1996CAEN4058.
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Blache, Yves. "Hétérocyclisation en séries quinoxalinique et pyrido[2,3-b]pyrazinique : synthèse, structure, réactivité." Montpellier 1, 1991. http://www.theses.fr/1991MON13508.
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Horton, Aaron Michael. "Novel Reactive Dyes Based on Pyrimidine and Quinoxaline Systems." NCSU, 2009. http://www.lib.ncsu.edu/theses/available/etd-04302009-143537/.
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Fitzsimmons, Sara Ann. "Enzymology and structure-activity relationships of quinoxaline bioreductive cytotoxins." Thesis, University of Glasgow, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295320.
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Ihara, Eiji. "Synthesis and Structure Analysis of Poly (2,3-quinoxaline)s." Kyoto University, 1992. http://hdl.handle.net/2433/74625.
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Desvignes, Nicole. "Etude physico-chimique et diélectrique de polymères thermostables pour condensateurs." Dijon, 1988. http://www.theses.fr/1988DIJOS017.
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Etude des propriétés physicochimiques et diélectriques de deux polymères thermostables solubles: les polyphénylquinoxalines et les polyhydantoïnes dans le but de les utiliser comme diélectriques pour condensateurs à haute capacité volumique et a haute stabilité thermique
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Ahmad, Abid Rafiq. "Studies of novel diazanaphthoquinones and ion-responsive fluorescent quinoxaline derivatives." Thesis, Brunel University, 1994. http://bura.brunel.ac.uk/handle/2438/7130.
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The work reported is divided into two parts: fIrstly a section dealing with the preparation of some novel diazanaphthoquinones and their reactions, especially the Diels-Alder reaction, and secondly an account of some quinoxaline derivatives and their fluorescence properties. Quinoxaline quinones containing electron-donating groups at both the 2- and 3- position have shown a difference in their stability and their behaviour in the Diels-Alder reaction compared to the stability and the reactions of quinoxaline quinone. Symmetrical dienes in the Diels-Alder reaction yielded the initial addition products, which were resistant to oxidation, whereas unsymmetrical dienes produced fully aromatized products. Crown ether derivatives of 5,8-dimethoxyquinoxaline and the corresponding quinoxaline quinones were prepared. An improved method for the preparation of a fluorescent derivatising reagent is described. This compound was then used to prepare ion-responsive fluoroionophores containing monoazacrown ethers of different cavity sizes. The complexation of these fluoroionophores, in dichloromethane, was achieved by using perchlorates of alkali and alkaline earth metals. A strong correlation between the size of the metal ion and the cavity size of the crown ether was seen in the fluorescence quantum yields of the complex, and a fluoroionophore containing a diazacrown ether gave particularly noteworthy results. A bathochromic shift with a strong hyperchromic effect was the most important feature caused by complexation with metal ions for these fluoroionophores. Fluorescent open chain ethers (podands) were also prepared and their complexation with metal ions was studied. A strong bathochromic shift and a hypochromic effect was observed especially in their excitation spectra. A further novel fluorescent derivatising reagent was prepared by extending the conjugated system. This gave the expected improved results upon the preparation of the derivatives including fluoroionophores having crown ethers of different cavity sizes. However, the changes in fluorescence did not correlate with the relationship between the sizes of the metals ion and the cavity of the crown ether. Nevertheless, a large bathochromic shift was observed on complexation with metal ions.
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Vieira, Mónica Andreia Almeida. "Monitoring antibiotics in the environment. Study of Quinoxaline derivatives bioactivity." Doctoral thesis, Faculdade de Ciências e Tecnologia, 2013. http://hdl.handle.net/10362/11350.
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Dissertação para obtenção do Grau de Doutor em
Química SustentávelAntimicrobial agents have revolutionized medicine and promoted an increase in average life expectancy of human populations worldwide. These drugs are used not only in human medicine but also in veterinary practice, in the treatment and prevention of infections, and in some regions in the world, as well as growth promoters, ensuring a greater and better animal production. The use of antimicrobial agents in animal production causes contamination of the final product with drug residues that are eventually distributed in human food chain. Residues of antimicrobial agents provenient from human and animal consumption are also present in sewage, surface water or ground water. It is still unknown all the consequences of this contamination, but there are indications of changes in indigenous microbiota. The use of these drugs was quickly followed by the emergence of resistance, which led to decreased efficacy and compounds available. Therefore, the spread of antimicrobial agents in the environment is also associated with increased resistance to such drugs. The presented work intended to establish methods for monitoring the presence of antibiotics in animal foods, evaluate if the presence of antimicrobial agents in the environment at sub-inhibitory concentrations can contribute to the selection of resistant bacteria and characterize the biological activity of a number of compounds of the quinoxaline family as potential new antimicrobial agents. In order to achieve these objectives, chromatographic techniques were used for detection and quantification of antimicrobial agents, methods of microbiology and molecular biology to evaluate the behavior of bacteria under selective pressure. Various strains of prokaryotes and eukaryotes microorganisms were also used to evaluate the antimicrobial activity of N-oxide derivatives of quinoxaline. We used, also, cell cultures to assess the potential toxicity of these new antibiotics. A new chromatographic method was developed to quantify the reduced and oxidized forms of glutathione, in order to infer the cellular oxidative stress induced by exposure to the quinoxaline derivative compounds with proven antimicrobial activity. The results confirm that the chromatographic HPLC-DAD methods are powerful tools in monitoring food quality. They also indicate that the presence of subinhibitory amounts of ciprofloxacin in water may influence the dynamic of susceptible and resistant to ciprofloxacin Escherichia coli population. An assessment of the biological activity of quinoxaline derivatives indicated the compounds studied as potential new antimicrobial agents who have shown low toxicity in cell lines and oxidative cell damage in small extent.
Fundação para a Ciência e Tecnologia - bolsa de doutoramento SFRH / BD /48116 / 2008
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Poola, Bhaskar. "Synthesis and characterization of quinoxaline-functionalized, cage-annulated oxa- and thiacrown ethers and reaction chemistry of the diphosphine ligand 2,3-bis(diphenylphosphino)-N-p-tolylmaleimide (bmi) at triosmium carbonyl clusters." Thesis, University of North Texas, 2006. https://digital.library.unt.edu/ark:/67531/metadc5608/.
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Quinoxaline-functionalized, cage-annulated oxa- and thiacrown ethers have been synthesized as possible specific metal host systems. The synthesis and characterization of quinoxaline-functionalized, cage-annulated oxa- and thiacrown ethers have been described. The characterization of these host systems have been fully achieved in solution by using various techniques such as IR, 1H NMR, and 13C NMR spectroscopic methods, high-resolution mass spectrometry (HRMS), elemental microanalysis, and X-ray crystallographic analysis in case of one quinoxaline-functionalized, cage-annulated oxacrown ether compound. The synthesis of the diphosphine ligand 2,3-bis(diphenylphosphino)-N-p-tolylmaleimide (bmi) is described. The substitution of the MeCN ligands in the activated cluster 1,2-Os3(CO)10(MeCN)2 by the diphosphine ligand bmi proceeds rapidly at room temperature to furnish a mixture of bridging and chelating Os3(CO)10(bmi) isomers and the ortho-metalated product HOs3(CO)9[μ-(PPh2)C=C{PPh(C6H4)}C(O)N(tolyl-p)C(O)]. Thermolysis of the bridging isomer 1,2-Os3(CO)10(bmi) under mild conditions gives the chelating isomer 1,1-Os3(CO)10(bmi), whose molecular structure has been determined by X-ray crystallography. The kinetics for the ligand isomerization have been investigated by UV-vis and 1H NMR spectroscopy in toluene solution over the temperature range of 318-348 K. On the basis of kinetic data conducted in the presence of added CO and the Eyring activation parameters, a non-dissociative phosphine migration across one of the Os-Os bonds is proposed. Orthometalation of one of the phenyl groups associated with the bmi ligand is triggered by near-UV photolysis of the chelating cluster 1,1- Os3(CO)10(bmi).
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Kolay, Merve. "Dibenzophenazine And Quinoxaline Derivatives As Novel Visible Photosensitizers For Diaryliodonium Salts." Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613419/index.pdf.
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This study is focused on the use of visible light in photoinitiated cationic polymerization. Photoinitiated polymerization of oxiranes, vinyl ethers, and other vinyl monomers was achieved. In doing so, (2-(2,3 dihydrobenzo [b][1,4]dioxin-6-yl)-3-(2,3-dihydrobenzo[b]-[1,4]dioxin-7-yl)-5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-8-(2,3-dihydrothieno[3,4-b][1,4]dioxin-7yl) quinoxaline) (DBQEd) and poly(2,3,5,8-tetra(thiophen-2-yl)quinoxaline) (TTQ), two dibenzo[a,c]phenazine derivatives10,13-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)dibenzo[a,c] phenazine (PHED) and 10,13-bis(4-hexylthiophen-2-yl)dibenzo[a,c]phenazine (PHEHT) were utilized as the photosensitizers for diaryliodonium salt photoinitiators. Novel dyes based on the dibenzo[a,c]phenazine and quinoxaline skeleton were shown to be efficient in carrying out the cationic photopolymerizations of a wide variety of epoxide, oxetane, and vinyl monomers at room temperature upon irradiation with long-wavelength UV and visible light. The polymerizations were initiated at room temperature in the presence of diphenyliodonium hexafluorophosphate (Ph2I+PF-6) and monitored by optical pyrometry (OP). The photopolymerization of an epoxide monomer via solar irradiation was also demonstrated.
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Breton, Anne-Catherine. "Synthèse et caractérisation de copolymères dérivés de quinoxaline et de carbazole." Thesis, Université Laval, 2012. http://www.theses.ulaval.ca/2012/28992/28992.pdf.
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En raison de la demande croissante pour de nouvelles formes d'énergie renouvelable au cours des dernières années, la recherche sur les matériaux organiques pour d'éventuelles applications en photovoltaïque a rapidement progressé. Ainsi, tout récemment, des performances intéressantes ont été obtenues à partir de dispositifs dont la couche active était constituée d'un mélange de [6,6]-phényl-C61-butyrate de méthyle (PCBM) et d’un polymère semi-conducteur. Puis, dans le dessein d’améliorer les performances des matériaux organiques, les chercheurs ont ensuite tenté de moduler les niveaux d'énergie et la largeur de bande interdite des polymères conjugués. Une façon de parvenir à moduler les propriétés électroniques de ces molécules est d'utiliser une séquence de donneurs-accepteurs dans la chaîne du polymère.
Le groupe de recherche du Dr Leclerc participe aussi activement à cette quête de nouvelles sources d'énergie. Entre autre, nous synthétisons et caractérisons des copolymères contenant des unités hautement déficientes en électrons, les quinoxalines, et des unités riches en électrons, les carbazoles. La polymérisation de plusieurs unités de quinoxaline portant des groupements substituants de nature différente nous a ainsi permis d’élaborer une famille complète de co-polymères semi-conducteurs. Nous évaluons ensuite l'impact de l'ajout de ces substituants par les propriétés électroniques et optiques afin d'identifier parmi les polymères synthétisés, ceux qui possèdent des propriétés adéquates pour des applications en cellules photovoltaïques. Pour terminer, les polymères sont testés en les incorporant dans la couche active des cellules photovoltaïques pour évaluer leurs performances. Des taux de conversion énergétique variant entre 1,24% et 3,37% ont ainsi été obtenus. Pour ces polymères, nous avons aussi réalisé plusieurs essais sur le type de solvant, le ratio polymère :PCBM, la nature de l’électrode ou, encore, sur l’ajout d’additifs pouvant permettre d’optimiser leur utilisation dans la fabrication des cellules photovoltaïques.
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Breton, Anne-Catherine, and Anne-Catherine Breton. "Synthèse et caractérisation de copolymères dérivés de quinoxaline et de carbazole." Master's thesis, Université Laval, 2012. http://hdl.handle.net/20.500.11794/23503.
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En raison de la demande croissante pour de nouvelles formes d'énergie renouvelable au cours des dernières années, la recherche sur les matériaux organiques pour d'éventuelles applications en photovoltaïque a rapidement progressé. Ainsi, tout récemment, des performances intéressantes ont été obtenues à partir de dispositifs dont la couche active était constituée d'un mélange de [6,6]-phényl-C₆₁-butyrate de méthyle (PCBM) et d’un polymère semi-conducteur. Puis, dans le dessein d’améliorer les performances des matériaux organiques, les chercheurs ont ensuite tenté de moduler les niveaux d'énergie et la largeur de bande interdite des polymères conjugués. Une façon de parvenir à moduler les propriétés électroniques de ces molécules est d'utiliser une séquence de donneurs-accepteurs dans la chaîne du polymère. Le groupe de recherche du Dr Leclerc participe aussi activement à cette quête de nouvelles sources d'énergie. Entre autre, nous synthétisons et caractérisons des copolymères contenant des unités hautement déficientes en électrons, les quinoxalines, et des unités riches en électrons, les carbazoles. La polymérisation de plusieurs unités de quinoxaline portant des groupements substituants de nature différente nous a ainsi permis d’élaborer une famille complète de co-polymères semi-conducteurs. Nous évaluons ensuite l'impact de l'ajout de ces substituants par les propriétés électroniques et optiques afin d'identifier parmi les polymères synthétisés, ceux qui possèdent des propriétés adéquates pour des applications en cellules photovoltaïques. Pour terminer, les polymères sont testés en les incorporant dans la couche active des cellules photovoltaïques pour évaluer leurs performances. Des taux de conversion énergétique variant entre 1,24% et 3,37% ont ainsi été obtenus. Pour ces polymères, nous avons aussi réalisé plusieurs essais sur le type de solvant, le ratio polymère :PCBM, la nature de l’électrode ou, encore, sur l’ajout d’additifs pouvant permettre d’optimiser leur utilisation dans la fabrication des cellules photovoltaïques.En raison de la demande croissante pour de nouvelles formes d'énergie renouvelable au cours des dernières années, la recherche sur les matériaux organiques pour d'éventuelles applications en photovoltaïque a rapidement progressé. Ainsi, tout récemment, des performances intéressantes ont été obtenues à partir de dispositifs dont la couche active était constituée d'un mélange de [6,6]-phényl-C₆₁-butyrate de méthyle (PCBM) et d’un polymère semi-conducteur. Puis, dans le dessein d’améliorer les performances des matériaux organiques, les chercheurs ont ensuite tenté de moduler les niveaux d'énergie et la largeur de bande interdite des polymères conjugués. Une façon de parvenir à moduler les propriétés électroniques de ces molécules est d'utiliser une séquence de donneurs-accepteurs dans la chaîne du polymère. Le groupe de recherche du Dr Leclerc participe aussi activement à cette quête de nouvelles sources d'énergie. Entre autre, nous synthétisons et caractérisons des copolymères contenant des unités hautement déficientes en électrons, les quinoxalines, et des unités riches en électrons, les carbazoles. La polymérisation de plusieurs unités de quinoxaline portant des groupements substituants de nature différente nous a ainsi permis d’élaborer une famille complète de co-polymères semi-conducteurs. Nous évaluons ensuite l'impact de l'ajout de ces substituants par les propriétés électroniques et optiques afin d'identifier parmi les polymères synthétisés, ceux qui possèdent des propriétés adéquates pour des applications en cellules photovoltaïques. Pour terminer, les polymères sont testés en les incorporant dans la couche active des cellules photovoltaïques pour évaluer leurs performances. Des taux de conversion énergétique variant entre 1,24% et 3,37% ont ainsi été obtenus. Pour ces polymères, nous avons aussi réalisé plusieurs essais sur le type de solvant, le ratio polymère :PCBM, la nature de l’électrode ou, encore, sur l’ajout d’additifs pouvant permettre d’optimiser leur utilisation dans la fabrication des cellules photovoltaïques.
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Estevez, Yannick. "Activité leishmanicide de plantes issues de la pharmacopée traditionnelle Péruvienne et de molécules de synthèse : étude relation structure activité." Phd thesis, Université Paul Sabatier - Toulouse III, 2009. http://tel.archives-ouvertes.fr/tel-00519174.
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Les Leishmanioses du nouveau monde sont des parasitoses aux conséquences socio-économiques lourdes. En effet les traitements disponibles requièrent pour la plus part des administrations parentérales et sont coûteux pour les populations concernées. La recherche de nouvelles molécules actives est donc une nécessité. Pour contribuer à l'effort de recherche d'alternative thérapeutiques, nous nous sommes intéressés d'une part aux pharmacopées traditionnelles de populations vivant en zone d'endémie (deux ethnies de l'Amazonie péruvienne : Chayahuita et Yanesha) et d'autre part, nous avons également étudiés l'activité de drogues synthétisées sur la base de molécules ayant un certain degré d'activité antiparasitaire. Nous avons également contribué à l'amélioration éthique de nos modèles biologiques afin d'optimiser le criblage de composés leishmanicides potentiels en développant un modèle remplaçant l'utilisation de souris pour l'extraction de macrophages par des cellules Thp1.
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Zamudio, Vázquez Rubí. "Synthesis, Biological Evaluation and Insights into the Mode of Action of Quinoxaline Containing Peptides." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/132249.
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Triostins are members of the quinoxaline antibiotic family, together with the "prototypical bisintercalator" echinomycin. These molecules display interesting antitumour activities as they inhibit transcription through insertion of their two planar quinoxaline rings into the DNA double helix, spanning two base pairs, while the peptide backbone is placed in the minor groove.
The main objective of this Doctoral Thesis has been the design, synthesis and characterization of novel compounds with antitumoral activity, taking as basis the chemical structure of the natural bisintercalator triostin A.
Synthetically challenging peptides bearing consecutive N-methyl and beta-branched amino acids were obtained after careful selection of a suitable coupling system for the solid-phase synthesis of the peptidic scaffolds. The introduction of the heterocycles and side-chains deprotection were carried out in solution as final stages. At the end, a small library of twelve peptides, fifteen quinoxaline-containing peptides and three fluorescent versions were obtained in excellent purities and employed in further biological evaluations.
The synthesized compounds were evaluated for their antitumoral activity using the MTT assay, performing preliminar determinations of the detection limits of the assay, the lenght of the exponential phase of the cell lines tested and their doubling times.
The most active compound was RZ2, with low micromolar cytotoxic activities, being in all cases more active than the natural parent compound triostin A, and with better cytotoxic activity than the commercial drug doxorubicin against cervical and breast adenocarcinoma cells. Unfortunatelly, compound RZ2 was also cytotoxic against non-tumor endotelial cells. However, this same compound resulted also active against the parasite Plasmodium falciparum.
The stability of RZ2 in human serum and in presence of two overexpressed tumor proteases, MMP2 and cathepsin B, was studied. A little percentage of degradation was observed from 24 hours, with a maximum degradation of 30% in presence of serum at 48 hours. These data indicate that the peptide is advantageous in terms of proteolytic stability in vivo. Moreover, RZ2 is not hemolytic ex vivo, pointing out the great potential of this compound in antiplasmodial treatment without nocive effects on human erythrocytes.
Furthermore, a liposomal formulation of compound RZ2 was prepared using egg phosphatidylcholine and cholesterol so as to obtain small unilamellar vesicles and improve the solubility of the quinoxaline-containing peptide.
In regard of the mode of action of the synthesized compounds, it was demonstrated through circular dichroism, band-shift and DNase I footprinting experiments that there is no interaction with the genetic material. Molecular dynamics simulations showed that the analogues do adopt the predicted antiparallel beta-sheet conformation, but the separation between the quinoxaline moieties is too little to allow the sandwitching of two DNA base pairs.
Non-synchronized HeLa cells cultures treated with compound RZ2 resulted in S phase-arrest. PI permeability assays coupled to annexin V labeling in HeLa cells showed increased PI/annexin V labeling in response to RZ2 in a time-dependant manner. Induction of apoptosis was confirmed by an increase in the sub-G1 DNA fragmentation in response to the compound over time. Furthermore, cells treated with RZ2 for 48 hours showed increase in active caspase 3 and poly(ADP-ribose) polymerase levels, confirming that HeLa cells die as a result of apoptosis when exposed to RZ2.
Internalization into the cytosol was studied using a fluorescent version of RZ2 that displayed similar cytotoxicity. It was observed that the compound accumulates in acidic compartments and may inhibit the autophagic responsed triggering apoptosis.
Changes in gene expression before the apoptotic pathway activation were studied using a gene expression microarray. Results suggest that RZ2 induces metabolic stress in HeLa cells.
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Low, C. M. L. "Sequence-selective binding of quinoxaline antibiotics to DNA and nucleosome core particles." Thesis, University of Cambridge, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355258.
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Sadiq, Samina. "Studies of some fused-ring heterocycles and 2,6-Diarylpyridine derivatives." Thesis, Brunel University, 1999. http://bura.brunel.ac.uk/handle/2438/7281.
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This work reported is divided into two parts: the first part deals with quinoxaline derivatives and includes the preparation and characterisation of novel linear tricyclic quinones 1,4-diazanthracen-9,10-diones, (54) and (55). The reaction of diazanaphthoquinones and 1-acetyl-1,3-butadiene are used to produce these quinones through the Diels-Alder reaction. In addition hexaazapentacyclic 5,6,7,12,13, 14-hexaazapentacene was prepared by the reaction ofbis(2-chloroquinoxalin-3-yl)sulfide with thioxamide and the reaction of the sulfide with amines was investigated. Two different approaches to 6,13-dibutyl-5,6,7,12,13,14-hexaazapentacene are given. Derivatives of the pentacyclic, 6-thia- 5,7,12,13,14-pentaazapentacene and the unsubstituted 6,13 -dihydro compound are described. The novel N-(2,5-dimethoxy-6-nitrophenyl)guanidine is used to obtain 3-amino-5,6-dimethoxy-1 ,2,4-benzotriazine-1-oxide and 4,7 -dimethoxy-1 ,2,3 -benzotriazole is shown to be second product. Second part of the work is concerned with the development of a preparative route to 2,6-diphenylpyridines substituted with different groups on the phenyl nuclei. Several approaches were attempted. Finally, success was achieved and a series of compounds having basic chains of different length on the phenyl groups was prepared. One chain in each case had a terminal primary amine. The binding constants of the primary amines and their N-acetyl derivatives with DNA were determined using fluorescence spectroscopy.
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Dahbi, Samir. "Chimie innovante en série dioxyde de quinoxaline : vers de nouveaux antituberculeux, inhibiteurs de la biosynthèse des mycobactines." Thesis, Mulhouse, 2012. http://www.theses.fr/2012MULH4078.
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Afin d'internaliser le fer, un micronutriment essentiel pour sa survie, Mycobacterium tuberculosis, la mycobactérie responsable de la tuberculose, biosynthétise des composés ayant une très grande affinité pour Fe3+ appelés les mycobactines. Ces sidérophores sont biosynthétisés par voie non ribosomale, la synthèse débutant par l'activation d'une molécule d'acide salicylique par l'enzyme d'adénylation mbtA sous la forme d'un dérivé ester d'adénosylmonophosphate (salicyl-AMP). Notre laboratoire a déjà préparé des analogues stables de salicyl-AMP, inhibiteurs potentiels de la biosynthèse des mycobactines. Durant la thèse, nous nous sommes attachés à la préparation de phosphonamidates et de sulfonamides porteurs d'un motif dioxyde de quinoxaline en tant qu'analogues de salicyl-AMP, qui devraient présenter une excellente affinité avec le site actif de l'enzyme mbtA. Nous avons développé une extension à la réaction de Beirut, permettant la préparation, pour la première fois, de phosphonates de dioxyde de quinoxaline, précurseurs de nos analogues phosphonamidates. Lorsque le dioxyde de quinoxaline était substitué par un groupement aryle en position 3, un réarrangement du phosphonate en phosphate de monoxyde de quinoxaline a été observé. Des études RMN ont permis de mettre en évidence le caractère intramoléculaire de ce réarrangement, inédit en série N-oxyde d'aryle. La suite de la synthèse pour accéder à nos analogues phosphonamidate s'est en revanche avérée difficile. D'autre part, afin d'accéder à nos analogues sulfonamides, nous avons développé une voie de synthèse utilisant des conditions douces, et qui nous a permis de préparer les premiers exemples de sulfonamide en série dioxyde de quinoxaline. Ces derniers devraient être testés afm d'évaluer l'influence du motif dioxyde de quinoxaline sur l'activité antituberculeuse, et ainsi confirmer le potentiel de nos analogues-cibles, dont la synthèse est à terminer. Enfin, en parallèle de la synthèse des analogues sulfonamides, nous avons développé avec succès une nouvelle préparation de dioxydes de quinoxaline 2,3-disubstituée via un couplage de type Liebeskind-Srogl, qui représente le premier exemple de couplage organométallique en série dioxyde de quinoxalineIn order to intemalize iron, a vital micronutriment, Mycobacterium tuberculosis, the causative agent of tuberculosis, biosynthesizes compounds with extremely Fe (III) affinity, called mycobactins. The biosynthesis of these compounds is a non ribosomal process initiated by the adenylation enzyme mbtA, which activates a molecule of salicylic acid to the corresponding adenosylmonophosphate ester (salicyl-AMP). Our laboratory has already prepared various hydrolytically-stable analogues of salicyl-AMP as potential inhibitors of mycobactin biosynthesis. Lately, we have been working on the preparation of phosphonamidate and sulfonamide analogues with a quinoxaline 1,4-dioxide moiety, which should display a very good affinity with the active site of the enzyme mbtA. We successfully developed an extension to the Beirut reaction to access the first phosphonates of quinoxaline 1,4-dioxides, precursors of our phosphonamidates analogues. When the phopshonylated quinoxaline 1,4-dioxide was substituted with an aryl group on position 3, a rearrangement of the phosphonate into a phosphate of quinoxaline 1-monoxide was observed. NMR studies of this rearrangement, new in the N-aryl oxide series, suggested that it was intramolecular. The end of the synthesis to get our phosphonamidate analogues, however, proved difficult. Also, in order to prepare our sulfonamide analogues, we developed a synthesis that uses mild conditions and allowed us to access the first examples of sulfonamide in the quinoxaline 1,4-dioxide series, which should be tested to evaluate the influence of the quinoxaline 1,4-dioxide moiety on the antitubercular activity and confirm the potency of our targeted sulfonamide analogues, which have yet to be synthesized. Finally, while working on the synthesis of our sulfonamide analogues, we successfully developed a new preparation of 2,3-disubstituted quinoxaline 1,4-dioxide via a Liebeskind-Srogl-like cross-coupling reaction, which represents the first example of organometallic cross-coupling reaction in the quinoxaline 1,4-dioxide series
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Ozdemir, Serife. "Synthesis Of New Ferrocenyl Substituted Quinoxaline Derivative Monomers, Their Polymerization And Electrochemical Behaviors." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/12612390/index.pdf.
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5,8-Bis(2,3-dihydrothieno[3,4b][1,4]dioxin-5-yl)-2-(naphthalen-2-yl)-3-ferrocenyl-4a,8a-dihydroquinoxaline (DEFNQ), 5,8-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-2-(phenyl)-3 ferrocenylquinoxaline (DEFPQ) and 5,8-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-2,3-di(naphthalen-2-yl)quinoxaline (DEDNQ) were synthesized, electrochemically polymerized and electrochromic properties of resultant polymers were investigated. For the characterization of the monomers Nuclear Magnetic Resonance (1H-NMR, 13C-NMR) were used. Cyclic Voltammetry (CV) and Ultraviolet&ndashVisible Spectroscopy were used to investigate electrochemical behavior of the monomers and redox reactions of conducting polymers. After electrochemical polymerizations, the electrochromic properties of the conducting polymers were investigated via spectroelectrochemistry, kinetic and colorimetry studies to explore the one of most important property of conducting polymers, the ability to switch reversibly between the two states of different optical properties, &lsquo
electrochromism&rsquo
. Cyclic Voltammetry and Spectroelectrochemistry studies for PDEFNQ, PDEFPQ and PDEDNQ showed that ferrocenyl (Fc) group containing derivatives are multichromic green to transmissive polymer with high tendency to be both p and n doped. PDEDNQ which was not functionalized with ferrocenyl group does not show multichromism. According to the electrochemical and spectroscopic results each polymer is a potential candidate for optoelectronic applications.
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Dawson, Simon Jonathon. "Solid-Phase-based Synthesis and Biological Evaluation of Quinoxaline Antibiotics and Structural Analogues." Thesis, University College London (University of London), 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509309.
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Caffy, Florent. "Copolymères à grande largeur de bande interdite contenant des quinoxalines : nouveaux matériaux pour les cellules solaires organiques à hétérojonction." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAV021/document.
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Une alternative aux énergies fossiles est le domaine du photovoltaïque organique qui a récemment commencé son transfert technologique des laboratoires de recherche vers l’industrie. De nombreux efforts de recherche sont réalisés sur les matériaux et les procédés pour augmenter les performances des cellules solaires organiques. Dans ce contexte, ce travail présente une étude complète allant de la conception de nouveaux polymères donneurs d’électrons à grande largeur de bande interdite à leur caractérisation en dispositifs photovoltaïques. La principale caractéristique recherchée a été de diminuer le niveau énergétique HOMO des polymères pour augmenter la tension en circuit ouvert des dispositifs photovoltaïques. L’approche « donneur-accepteur » a été utilisée pour obtenir les propriétés désirées. Des polymères comportant des unités pauvres en électrons, quinoxaline ou dithienoquinoxaline, et des unités riches en électrons, dibenzosilole ou carbazole, ont été synthétisés par couplage de Suzuki ou par hétéroarylation directe. Des masses molaires allant jusqu’à 56 kg.mol-1 ont été obtenues. Le motif quinoxaline a été décliné sous forme de plusieurs molécules substituées par des atomes de fluor sur le benzène ou par des groupements thiophènes, bithiophènes et terthiophènes sur la partie pyrazine. Des espaceurs thiophènes ou thiazoles ont été utilisés pour relier l’unité riche en électrons et l’unité pauvre en électrons. Les relations entre les modifications structurales et les propriétés structurales et optoélectroniques des polymères ont été analysées. Les propriétés optiques ont été étudiées par spectroscopie UV-visible et par spectroscopie de fluorescence et ont montré une absorption allant jusqu’à 550 nm pour les polymères à motifs dithienoquinoxaline-dibenzosilole, 650 nm pour les polymères à motifs quinoxaline-dibenzosilole et 700 nm pour la famille quinoxaline-carbazole. Ces valeurs correspondent à des largeurs de bande interdite comprises entre 1,8 eV et 2,3 eV. Les niveaux énergétiques HOMO et LUMO des polymères ont été déterminés par électrochimie. Tous les polymères possèdent des niveaux énergétiques HOMO inférieurs à -5,0 eV. Les atomes de fluor et les espaceurs thiazoles ont permis d’abaisser les niveaux énergétiques HOMO des polymères jusqu’à -5,69 eV. Les structures des polymères ont été modélisées par DFT et étudiées par diffraction des rayons X. Les mobilités des trous des polymères ont été mesurées en transistor organique à effet de champ, des valeurs atteignant 9,0. 10 3 cm.V 1.s 1 ont été atteintes. Les polymères ont été testés en dispositifs photovoltaïques selon une architecture standard à hétérojonction volumique en mélange binaire et en mélange ternaire. En mélange avec le PC71BM ou l’IC61BA, ces polymères ont permis d’atteindre des tensions en circuit ouvert entre 0,65 V et 1,05 V et des rendements de conversion photovoltaïque jusqu’à 5,14 % sur une surface active de 0,28 cm2. Les morphologies des couches actives ont été étudiées par AFM afin de comprendre en détail les paramètres de fonctionnement des cellules obtenues. Les polymères présentés dans cette étude ont été utilisés dans des cellules solaires à mélange ternaire présentant de bonnes performances. Certains polymères ont été testés dans des photocathodes pour la production d’hydrogène et ont permis d’obtenir une amélioration du potentiel de réduction par rapport à celui obtenu avec les photocathodes à base de P3HT. Enfin, compte tenu de leurs propriétés optoélectroniques et de leurs performances photovoltaïques certains de ces polymères devraient pouvoir être employés de manière avantageuse en sous cellules de dispositifs tandem en remplacement du P3HT par exempleAn alternative to fossil fuels are the organic photovoltaic cells which have recently started their technological transfer from research laboratories to industry. Many research efforts have been made on the modification of materials and processes to increase the performance of organic solar cells. In this context, this work presents a comprehensive study from the design of new electron-donor high band gap polymers to their characterisation in photovoltaic devices. The main requirement was to decrease the HOMO energy level of the polymers in order to increase the open circuit voltage of the solar cells. The "push-pull" approach was used to obtain the desired properties. Polymers with quinoxaline or dithienoquinoxaline as electron-deficient units and dibenzosilole or carbazole as electron-rich units were synthesized by Suzuki coupling or by direct heteroarylation. Molecular weights up to 56 kg.mol 1 were obtained. The electron-withdrawing unit quinoxaline was substituted by fluorine atoms on the benzene moiety and by thiophene, bithiophene and terthiophene group on the pyrazine moiety. Thiophenes or thiazoles were used as spacers to link the electron-donating and the electron-withdrawing units. The relationship between the structural modification of the polymers and their optoelectronic properties were analysed. The optical properties were studied by UV-visible spectroscopy and fluorescence spectroscopy. Whereby it appears that polymers with dithienoquinoxaline-dibenzosilole units showed an absorption up to 550 nm and polymers with both quinoxaline-dibenzosilole units and quinoxaline-carbazole units showed an absorption up to 650-700 nm respectively. The corresponding optical band gaps were found to range from 1.8 eV to 2.3 eV. The HOMO and LUMO energy levels of the polymers were determined by electrochemistry. All polymers exhibited HOMO energy levels below -5.0 eV. Fluorine atoms and thiazole spacers significantly lowered the HOMO energy levels of the polymers up to -5.69 eV. DFT was used to model the polymer structures. X-ray diffraction was used to analyse the distances between the polymer chains. Hole mobilities were measured in organic field effect transistors and values of up to 9.0 x 10 3 cm2.V-1.s-1 were obtained. The polymers were tested in organic photovoltaic devices according to a standard bulk heterojunction structure in binary and ternary mixtures. In a blend with PC71BM or IC61BA, these polymers have led to open circuit voltages ranging from 0.65 V to 1.05 V and to power conversion efficiencies of up to 5.14 % on a surface area of 0.28 cm2. The active layer morphologies were studied by AFM. The polymers presented in this work were used in ternary blend solar cells. Some polymers were tested in photocathodes for hydrogen evolution and showed an improvement of the reduction potential compared to that of the photocathodes based on P3HT. Owing to their optoelectronic properties and their photovoltaic properties in standard device configurations, some of the materials developed in this study appear as valuable materials for future developments of organic tandem solar cells
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Lavesa, Curto Manuel. "New strategies for assessing the sequence selective binding of small molecules to DNA." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390604.
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Le, Douaron Gael. "Synthèse et évaluation biologique de molécules neuroprotectrices pour le traitement de la maladie de parkinson." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114841.
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Ce manuscrit détaille la stratégie utilisée par nos laboratoires pour identifier de nouvelles molécules neuroprotectrices pour le traitement curatif de la maladie de Parkinson (MP). La MP est une maladie neurodégénérative caractérisée par des symptômes moteurs invalidants qui résultent de la dégénérescence des neurones dopaminergiques (DA) des noyaux gris centraux. Précédemment, nos laboratoires ont synthétisé et identifié au cours d’un criblage 3 molécules chefs de file qui possèdent un effet neurotrophique sur les neurones DA embryonnaires. Des études préliminaires d’ADMEtox nous ont permis de sélectionner la molécule SF41, un dérivé 6-aminoquinoxaline, pour une première évaluation de l’effet neuroprotecteur in vivo de nos molécules. En effet, cette molécule est bien tolérée chez l’animal et, administrée par voie orale, elle est capable de traverser la BHE. SF41 a montré un faible effet protecteur vis-à-vis des fibres DA dans un modèle animal de la MP. Dans le but d’augmenter l’activité neurotrophique de cette molécule, une 50ène de dérivés de seconde génération ont été synthètisés et criblés in vitro dans un modèle de mort spontanée des neurones DA. Ce criblage nous a permis d’identifier 5 molécules lead plus puisssantes et efficaces que SF41. Ces molécules, qui possédent les mêmes propriétés physico-chimiques que SF41, pourraient également atteindre le système nerveux central et ainsi conduire à un effet neuroprotecteur marqué dans un modèle animal de la MP. De plus, ces molécules possèdent un profil pharmacologique intéressant car elles sont capables d’empêcher la mise en place de mécanismes qui peuvent potentiellement contribuer à la mort des neurones DA dans la MP (stress oxydant, stress médié par les astrocytes, dyshoméostasie calcique, stress médié par la diminution en facteur trophique…). Une étude préliminaire avec la molécule PAQ, l’une de ces 5 molécules, a permis d’obtenir un effet neuroprotecteur dans un modèle in vivo de la MP qui semble supérieur à celui de la molécule SF41. Ces résultats encourageants nous donnent bon espoir d’obtenir la preuve de concept de l’activité neuroprotectrice de nos dérivés 6-aminoquinoxalineThis manuscript describes the strategy used by our laboratories to identify new neuroprotective molecules for the therapy of Parkinson disease (PD). PD is a neurodegenerative disease characterized by disabling motor symptoms resulting from the degeneration of dopaminergic (DA) neurons of the basal ganglia. Previously, our laboratories have synthesized and identified in a screening 3 lead compound which exhibited a neurotrophic effect on embryonic midbrain DA neurons. Preliminary ADMEtox studies allowed us to select the molecule SF41, a 6-aminoquinoxaline derivative, for a first in vivo evaluation of the neuroprotective effect of our molecules in an animal model of PD. Indeed, SF41 is well tolerated in animals and is able of crossing the BBB after oral treatment. SF41 showed a weak protective effect on DA fibers in an animal model of PD.In order to increase the neurotrophic activity of this molecule, around fifty second generation derivatives were synthesized and screened in vitro in a model of spontaneous death of DA neurons. This screening allowed us to identify five lead compounds more powerful and effective than SF41. These molecules, which possess the same physico-chemical properties that SF41, could also reach the central nervous system and lead to a marked neuroprotective effect in an animal model of PD. In addition, these molecules have an interesting pharmacological profile because they are able to prevent the establishment of mechanisms that can potentially contribute to the death of DA neurons in PD (oxidative stress, stress mediated by astrocytes, calcium dyshomeostasis, stress mediated by trophic factor deprivation...).A preliminary study with the molecule PAQ, one of these five molecules, yielded a neuroprotective effect in animal model of PD that seems higher than with SF41. These encouraging results give us hope to achieve proof of concept of the neuroprotective activity of our 6-aminoquinoxaline derivatives
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Benakli, Kamel. "Synthèse de nouveaux agents pharmacologiques par réactions de transfert monoélectronique en série 5-nitroimidazole et quinoxaline." Aix-Marseille 3, 1999. http://www.theses.fr/1999AIX30043.
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Ce travail est consacre a la synthese par reactions de transfert monoelectronique de nouveaux agents pharmacologiques. La premiere partie decrit la preparation de nouveaux derives bis-alkylants nitroaromatiques et heterocycliques et l'etude de leur reactivite dans des reactions de c-alkylation avec l'anion du 2-nitropropane. La sensibilite de ces reactions aux inhibiteurs des reactions de substitution par transfert monoelectronique a permis de definir un mecanisme radicalaire en chaine bis-s#r#n1 en series 5-nitroimidazole, p-nitrobenzyle et quinoxaline. L'extension a divers anions nitronates, de nitroesters et malonates a donne a ces reactions un caractere general. En vue d'obtenir de nouveaux 5-nitroimidazoles avec une plus grande delocalisation du systeme , de nouvelles molecules monoalkylantes ont ete preparees et l'etude de leur reactivite avec divers anions a permis d'etablir un nouveau concept de reaction s#r#n1 a longue distance ou ld-s#r#n1 et d'en etablir les limites. Nous presentons ensuite la synthese d'un agent tris-alkylant 5-nitroimidazolique et les resultats obtenus par reactions avec divers anions nitronates qui font intervenir un processus d'elimination radicalaire e#r#c1 consecutif a une reaction s#r#n1. Enfin, les 5-nitroimidazoles ainsi synthetises ont fait l'objet d'une evaluation antiparasitaire et genotoxique et presentent pour certains d'entre eux une activite trichomonacide et leishmanicide superieure ou egale a celle des produits de reference.
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Yamada, Tetsuya. "Nickel-Mediated Asymmetric Synthesis and Screw-Sense Control of Helical Poly(quinoxaline-2,3-diyl)s." 京都大学 (Kyoto University), 2013. http://hdl.handle.net/2433/174968.
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Heilporn, Sylvie. "Etude des réactions de Meisenheimer et de Reissert sur des dérivés du quinoxaline-N-oxyde." Doctoral thesis, Universite Libre de Bruxelles, 1989. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/213262.
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Zanzoul, Asmae. "Synthèse de ligands hétérocycliques polyaromatiques dérivés de quinoxaline pour le ciblage de l'ADN G-quadruplex." Toulouse 3, 2014. http://thesesups.ups-tlse.fr/2425/.
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Ce travail sur la synthèse de ligands hétérocycliques polyaromatiques dérivés de quinoxaline pour le ciblage de l'ADN G-quadruplex télomèrique s'inscrit dans le cadre de la recherche de nouveaux agents anti-cancéreux. L'objectif du travail est la conception des molécules capables d'inhiber la télomérase par stabilisation des G-quadruplex au niveau des télomères. Trois familles de composés polyaromatiques dérivés de quinoxaline ont été synthétisées : (i) la famille benzymidazopyridoquinoxaline, (ii) la famille indoloquinoxaline et (iii) la famille triazoloquinoxaline. Ces macrocycles ont été ensuite quaternarisés pour améliorer la solubilité dans l'eau et l'affinité vers l'ADN quadruplex. Nous décrivons la synthèse d'un noyau pentacyclique dérivé du benzimidazole à partir de la sérine et l'o-phénylènediamine non substituée dans un milieu acide. La quaternarisation de cette molécule avec le triflate de méthyle donne un produit méthylé soluble dans l'eau. Puis nous décrivons la synthèse de quatre noyaux tetracyclique dérivés du 6H-indolo[2,3- b]quinoxaline en deux étapes : une alkylation d'indole-2,3-dione suivie d'une condensation isatines substituées avec l'o-phénylènediamine dans un milieu acide. La quaternarisation de ces composés a été effectuée avec le sulfate de diméthyle pour obtenir des produits solubles dans l'eau. Enfin nous avons préparé quelques molécules polycycliques de la famille triazoloquinoxaline, ainsi qu'un produit de forme ouverte que nous avons isolé sous forme cristalline. Dans une dernière partie l'étude des interactions des ligands de la famille de benzymidazopyridoquinoxaline et d'indoloquinoxaline avec l'ADN G-quadruplex télomérique par la méthode de FRET a été réalisée. Cette étude a montré que le composé aromatique et cationique de la série benzimidazopyridoquinoxaline, décrite dans le chapitre II, est apparu comme un ligand de l'ADN G-quadruplex modeste mais sélectif pour l'ADN quadruplex. Le composé pentacyclique sous forme de croissant semble plus prometteur que les aromatiques linéaires plus classiques comme les dérivés d'ellipticine ou d'indoloquinoxaline décrits dans le chapitre III. Certains composés ont été également testés comme inhibiteurs de l'enzyme InhA de Mycobacterium tuberculosis. Le composé 6(diéthylaminoéthyl)indoloquinoxaline que nous avons synthétisés au chapitre III peut être considéré comme une molécule " lead" pour la conception de nouveaux inhibiteurs d'INhAThis work on the synthesis of polyaromatic heterocyclic ligands quinoxaline derivatives for targeting G-quadruplex telomeric DNA be part of the search for new anti-cancer agents. The objective of the work is the design of molecules capable of inhibiting telomerase by stabilizing G-quadruplex at the telomeres. Three families of polyaromatic compounds quinoxaline derivatives were synthesized: (i) benzymidazopyridoquinoxaline family, (ii) the indoloquinoxaline family and (iii) triazoloquinoxaline family. These macrocycles were then quaternized to improve the water solubility and the affinity to the quadruplex DNA. We describe the synthesis of a pentacyclic ring of the benzimidazole derivative from serine and unsubstituted o-phenylenediamine in an acidic medium. The quaternization of this molecule with methyl triflate gives a methylated product soluble in water. Then we describe the synthesis of four tetracyclic cores derivatives 6H-indolo [2,3-b] quinoxaline in two steps: alkylating a indole-2,3-dione followed by condensation isatins with substituted o-phenylenediamine in an acidic medium. The quaternization of these compounds was carried out with dimethyl sulfate to obtain water-soluble products. Finally we have prepared some polycyclic molecules triazoloquinoxaline family and a product of open form that we isolated in crystalline form. The last part of the study of the interactions of ligands family benzymidazopyridoquinoxaline and indoloquinoxaline with G-quadruplex telomeric DNA by the method of FRET was performed. This study showed that the aromatic compound and the cationic benzimidazopyridoquinoxaline series, described in Chapter II, has emerged as a ligand G-quadruplex DNA modest but selective for DNA quadruplex. The pentacyclic compound crescent looks brighter than most conventional linear aromatic as ellipticine derivatives or indoloquinoxaline described in Chapter III. Some compounds were also tested as inhibitors of the enzyme InhA of Mycobacterium tuberculosis. Compound 6 (diethylaminoethyl) indoloquinoxaline we synthesized in Chapter III can be considered a "lead" molecule for designing new Inha inhibitors
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Corakci, Bengisu. "Substituted Quinoxaline And Benzimidazole Containing Monomers As Long Wavelength Photosensitizers For Diaryliodonium Salt Initiators In Photopolymerization." Master's thesis, METU, 2013. http://etd.lib.metu.edu.tr/upload/12615458/index.pdf.
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In this studyferrocenyl and naphthalenyl substituted quinoxaline derivatives
5,8- bis (2,3- dihydrothieno [3,4-b] [1,4] dioxin-5-yl)-2- (naphthalen-2-yl)- 3- ferrocenyl- 4a,8a-dihydroquinoxaline
5,8- bis (2,3-dihydrothieno [3,4-b] [1,4]dioxin-5-yl) -2- (phenyl) -3-ferrocenylquinoxaline
5,8-bis (2,3-dihydrothieno [3,4-b] [1,4]dioxin-5-yl) -2,3- di(naphthalen-2-yl)quinoxaline and trihexylthiophene and thiophene coupled benzimidazole derivatives
4-(tert-butyl)-4,7-bis(4-hexylthiophen-2-yl)spiro[benzo[d]imidazole-2,1-cyclohexane] and 4-(tert-butyl)-4, 7-bis(thiophenyl)spiro[benzo[d]imidazole-2,1-cyclohexane] were used as photosensitizers to broaden the active area of diaryliodonium salts. Both quinoxaline and benzimidazole derivatives are expected to be efficient in cationic photopolymerization with a variety of vinyl and oxide monomers at room temperature upon long wavelength UV irradiation. Photopolymerization will be initiated by diphenyliodonium salts and monitored with Optical Pyrometry. Characterization will be completed with optical absorption, flourescence studies and photopolymerization under solar irradiation.
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Zheng, Hui. "Stereoselective pharmacokinetics and metabolism of XK469, a new quinoxaline topoisomerase II beta poison, in the rat." Columbus, Ohio : Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1080257372.
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Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xxi, 190 p.; also includes graphics. Includes abstract and vita. Advisor: Kenneth K. Chan, Dept. of Pharmacy. Includes bibliographical references (p. 182-190).
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Montana, Marc. "Réactions par transfert monoélectronique initiées par le TDAE en série azahétérocyclique." Aix-Marseille 2, 2006. http://www.theses.fr/2006AIX22961.
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Szydlo, Florence. "Synthèses et caratérisations de macrocycles oligopyrroliques incorporant l'entité quinoxaline pour la complexation des métaux et la reconnaissance moléculaire." Paris 6, 2006. http://www.theses.fr/2006PA066091.
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Tallon, Valérie. "Fonctionnalisation des quinoxalines et des cinnolines par réaction d'ortho-métallation." Rouen, 1996. http://www.theses.fr/1996ROUES041.
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La préparation de plusieurs quinoxalines et cinnolines, et en particulier une nouvelle synthèse de la 4-hydroxycinnoline ont été réalisées. Ce travail décrit la fonctionnalisation de la partie hétérocyclique de diverses quinoxalines et cinnolines par la réaction de métallation. La possibilité de métallation sur le cycle benzénique, en péri de l'azote, a aussi été montrée sur les cinnolines, avec l'iode et le chlorure de triméthylsilyle comme électrophiles. Enfin l'interêt de cette réaction de métallation est illustré par la préparation de xanthones et de diazépines.
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Vidaillac, Céline. "Pharmacomodulations en série pyrrolo[1,2-a]quinoxaline : application à la mise au point d'inhibiteurs de pompes d'efflux." Bordeaux 2, 2007. http://www.theses.fr/2007BOR21439.
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Les systèmes d'efflux sont des transporteurs transmembranaires impliqués dans la résistance aux antibiotiques et aux anticancéreux. La découverte d'inhibiteurs (EPIs, Efflux Pump Inhibitors) est une voie de recherche essentielle en chimiothérapie. Le projet de cette thèse était de synthétiser et d'évaluer l'activité in vitro de nouveaux EPIs. Trois séries de dérivés pyrrolo [1,2-a]quinoxalines ont été élaborées sur la base de critères structuraux d'EPIs" de référence" (oméprazole, dérivés quinolines et INF) et évaluées en tant qu'inhibiteurs de systèmes bactériens. Une stratégie d'évaluation a été définie dans un modèle utilisant NorA de Staphylococcus aureus, prototype des systèmes MDR (MultiDrug Resistance) des Gram positif. Elle comprend des tests de screening, la mise en évidence de la synergie d'activité EPI-antibiotique, et l'étude du mécanisme d'inhibition. Dans chaque série, plusieurs molécules se sont révélées plus actives que les EPIs de référence. Les premières études de relation structure-activité ont permis de préciser l'influence de certains motifs chimiques (hétérocycle, atome de soufre, fonctions protonables) sur l'activité EPI. Certaines molécules (1e, 11g, 11m e 17) pourraient servir de base au développement de molécules utilisables en thérapeutique. Cependant, la troisième série, comparée à 8 EPIs de référence sur 10 pompes d'efflux représentatives des 5 classes de transporteurs, confirme que l'hypothèse d'un EPI à large spectre est peu probable. Enfin, deux autres séries de dérivés pyrrolo [1, 2-a] quinoxalines on,t été conçues sur la base du MS-073 et du MS-207 et des dérivés pyrrolopyrimidines, pour élargir l'application biologique à la cancérologieEfflux systems are transmembrane transporters, involved in antibiotic and anticancer resistances. The discovery of efflux pump inhibitors (EPIs) is an essential way of research in chemotherapy. The aim of this thesis was to synthesize and evaluate the in vitro activity of new EPIs. Three series of pyrrolo [1,2a]quinoxaline molecules have been elaborated on the basis of structural criteria of reference EPIs (omeprazole, quinoline derivatives and INF), and have been assessed as inhibitors of bacterial efflux systems. A strategy of evaluation has been defined using NorA of Staphylococcus aureus, which is considered as the prototype of Gram positive MDR (MultiDrug Resistance) systems. This strategy included screening tests, evidence of EPI-antibiotic synergy, and investigation of the inhibition lechanism. Among each series, several molecules were more active than reference EPIs. Preliminary structure-activity relationship studies highlighted the influence of particular chemical elements (heterocycle, sulphur atom, protonable functions) on the EPI activity. Some molecules (1e, 11g, 11m and 17) might provide the basis for further pharmacomodulation to obtain therapeutically useful drugs. However, the third series, compared to 8 reference EPIs on 10 efflux systems representative of the 5 classes of transporters, has confirmed that the hypothesis of a very wide-spectrum EPI is unlikely. Finally, two other series of pyrrolo [1,2-a] quinoxaline molecules have been designed on the basis of the chemical structures of MS-073 and MS-207 and pyrrolopyrimidine derivatives, in order to broaden the biological application to cancerology
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Miyake, Toshiyuki. "Asymmetric Synthesis of Helical Poly(quinoxaline-2,3-diyl)s by Palladium-Mediated Polymerization of 1, 2-Diisocyanobenzenes." Kyoto University, 2000. http://hdl.handle.net/2433/180987.
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Ramakadi, Tselane Geneva. "Buchwald coupling of quinoxaline-o-sulfonates leading to the heterocyclic compounds with potential medicinal properties against TB." Thesis, University of Limpopo, 2018. http://hdl.handle.net/10386/2341.
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Thesis (M. Sc. (Chemistry)) --University of Limpopo, 2018The dissertation describes the use of 2-benzenesulfonyloxyquinoxaline as a good coupling partner for different amine substrates. The palladium-mediated cross- coupling of aryl electrophiles and amines has become a widely used method of constructing arylamine frameworks. The formation of carbon-nitrogen bonds was accomplished via palladium-catalysed Buchwald-Hartwig amination employing different amine substrates to yield substituted quinoxaline-2-amines compounds in good to moderate yields. Buchwald ligands (Xphos, tButylxphos and BrettPhos), were varied with different amine substrates in an attempt of improving the yields. Compounds 81a N-phenylquinoxalin-2-amine and 82b, N-benzylquinoxalin-2-amine were obtained with the yield over 70 % employing Xphos as the ligand. Significant attention has also been given to the application of cross coupling reaction protocols in substrates bearing electron withdrawing substituents. The presence of deactivating groups on the arylamine such as fluoro, nitro and iodo proved to be a challenge as only few compounds were synthesised in moderate yields. Compound 81b, N-(4-fluorophenyl)quinoxalin-2-amine which has electronegative atom attached, showed significant improvement when employing tButyl-Xphos ligand rather than XPhos since the yield improved from 10 % to 71 %. Furthermore, nucleophilic substitution on Buchwald-Hartwig coupled compounds by treating them with alkyl iodides was successful when using methyl and ethyl electrophiles on the N-H group of 81a 2-quinoxalineamine. The synthesised quinoxaline derivatives comprised 7 novel compounds. The in vitro analysis on anti-tubercular screening against H37RvMA strains of Mycobacterium tuberculosis was conducted on 9 compounds. The results revealed none of the compounds to have promising inhibition percentages against Mycobacterium tuberculosis when compared with rifampicin which was used as a positive control. Screening against malaria with chloroquine as the control also did not yield any active compounds.
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Vincenzi, Marian. "Interactions protéines-molécules biotechnologiques originales : une approche intégrée de RMN et de modélisation moléculaire." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0042/document.
Full textAbstract:
Ce travail de thèse PhD concerne l'application d'une approche intégrée pour obtenir une meilleure compréhension des mécanismes d'action de Akt et CXCR4, surexprimées dans différents cancers humains. Efforts récents dans le développement et l'évaluation biologique (activité antiproliférative) de petites entités moléculaires inhibitrices d’Akt, une sérine/thréonine protéine-kinase, ont conduit à l'identification de nouveaux inhibiteurs pyrrolo[1,2-a]quinoxaline, conçus et préparés via une stratégie multi-étapes. Certains des composés synthétisés ont montré une activité contre les lignées cellulaires leucémiques testées (Jurkat, U266, K562, U937 et HL60) supérieure à celle de composé de référence A6730. En outre, des résultats préliminaires menés sur Akt puis sur le domaine de PH isolé d’Akt, ont montré que ils peuvent être considérés comme des inhibiteurs allostériques potentiels. La seconde partie des travaux concerne la conception et la synthèse de deux nouvelles séquences peptidiques contenant quelques acides aminés "disorder promoting" et une unité CPC. Les études CD, RMN et MD ont fait ressortir leur flexibilité et ont démontré leurs capacités à assumer des ensembles de conformations stabilisées par un réseau de liaisons hydrogène. Ensuite, nous avons étudié l'effet de la chaîne alkyle reliée sur la conformation des peptides. Des études de fluorescence et DLS ont été réalisées pour évaluer les CMC et la dimension des agrégats supramoléculaires. Les tests biologiques ont souligné que ces édifices moléculaires (peptides amphiphiles nommés, PAs) montrent ainsi des activités prometteuses, voire plus que la molécule de référence (AMD3100)This PhD thesis work has been covered in the application of an integrated approach to get a better understanding about the mechanism of action of two systems: Akt and CXCR4, proteins overexpressed in different human cancers. On the basis of previous results obtained on the antiproliferative activities of small molecule inhibitors of Akt, a serine/threonine protein kinase, a novel series of pyrrolo[1,2-a]quinoxaline derivatives have been designed and synthesized via multistep heterocyclization process. Some compounds showed promising activities against all leukemia cell lines tested (Jurkat, U266, K562, U937 and HL60), even better than the reference compound (A6730) one. In addition, docking results, conducted on the isolated PH domain, showed that these new compounds could be considered as allosteric inhibitors. The second workpackage reports on the design and the synthesis of two new peptidic sequences containing a few amino acids “disorder promoting” and a CPC unit, the CXCL12 binding motif towards CXCR4. The peptide structural preferences were analysed by CD, NMR and MD techniques that highlighted their flexibility and demonstrated the ability of these peptides to assume conformational ensembles stabilized by a network of transient and dynamic H-bonds. Afterwards we studied the alkyl chain effect on the conformation of the peptide portion. Solution fluorescence and DLS studies have been performed to evaluate CMC and the dimension of supramolecular aggregates (named peptide amphiphiles, PAs). Biological tests pointed out that these molecular buildings show promising activities, even higher than the reference molecule (AMD3100) one
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Amrane, Dyhia. "Pharmacomodulation d'hétérocycles α-trichlorométhylés ciblant l'apicoplaste chez P. falciparum." Electronic Thesis or Diss., Aix-Marseille, 2021. http://www.theses.fr/2021AIXM0379.
Full textAbstract:
Le paludisme est la première parasitose en termes de mortalité à l’échelle mondiale. Les thérapies combinées à base d'artémisinine, traitement de première ligne du paludisme à Plasmodium falciparum, font face à des échecs dûs à l’apparition de résistances. Il est donc nécessaire de développer de nouvelles molécules antiplasmodiales possédant un mécanisme d’action novateur. Dans cet objectif, notre laboratoire a précédemment décrit la synthèse et les activités biologiques d'une chimiothèque de molécules azahétérocycliques α-trichlorométhylées, dont une molécule hit en série quinazoline qui présente le meilleur profil biologique.Une première partie de ce travail s’est intéressée à la pharmacomodulation en série 4-carboxamidoquinazoline. Afin de compléter l’étude RSA, la stratégie de scaffold hopping a permis l’obtention de nouvelles molécules en séries quinoxaline et phtalazine. Par simplification structurale, de nouveaux composés en séries pyrimidine, pyridazine et pyrazine ont été obtenus. Enfin, dans le but de moduler la partie benzénique des noyaux quinazoline et quinoxaline, des dérivés en série thiénopyrimidine et pyrido[2,3-b]pyrazine ont été synthétisés. Parmi plus de 110 nouvelles molécules originales synthétisées, plusieurs nouvelles molécules hit ont pu être identifiées. Leurs propriétés physicochimiques et pharmacocinétiques in vitro ont été déterminées en vue d’identifier une molécule candidate pour l’évaluation in vivo. De plus, afin d’élucider le mécanisme d’action de ces composés qui diffère de ceux des antipaludiques commerciaux, nous avons récemment identifié par immunofluorescence que ces molécules possèdent une action sur l’apicoplaste de P. falciparumMalaria remains the leading cause of death among parasitic infections worldwide. Currently, there are major concerns about the spread of resistance to artemisinin derivatives that are the basis of first-line antimalarial treatment. Therefore, there is an urgent need to develop new antiplasmodial molecules with a novel mechanism of action. For this purpose, our laboratory has previously described the synthesis and biological activities of a chemical library of α-trichloromethylated azaheterocycles including a hit molecule in the quinazoline series which presents the best biological profile.The first part of this work focused on 4-carboxamide quinazoline pharmacomodulation. In order to complete the SARs, scaffold hopping strategies allowed us to obtain new compounds in the quinoxaline and phthalazine series. By structural simplification, new compounds in the pyrimidine, pyridazine and pyrazine series were obtained. Finally, in order to explore the benzene part of the quinazoline and quinoxaline rings, new thienopyrimidine and pyrido[2,3-b]pyrazine derivatives were also synthesized. More than 110 new original molecules were obtained, among them several new hit molecules were obtained. The physicochemical and in vitro pharmacokinetic properties were determined in order to initiate the study of their in vivo activity on Plasmodium berghei. In addition, in order to elucidate the mechanism of action of these compounds, which differs from those of commercial antimalarials, we have recently identified by immunofluorescence that these molecules target the apicoplast of P. falciparum, an organelle essential to parasite survival
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Vegytė, Agnė. "Chinoksalino darinių antimikrobinio ir priešvėžinio aktyvumo tyrimas bei jų toksiškumo, farmakokinetinių savybių ir struktūros-aktyvumo ryšio įvertinimas." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140630_134439-47628.
Full textAbstract:
Tikslas: Įvertinti chinoksalino darinių struktūros įtaką jų antimikrobiniam ir priešvėžiniam aktyvumui ir atrinkti perspektyviausius junginius tolimesniems tyrimams.
Darbo uždaviniai:
1. Ištirti chinoksalino darinių antimikrobinį (priešgrybelinį ir antibakterinį) aktyvumą in vitro.
2. Ištirti chinoksalino darinių priešvėžinį aktyvumą in vitro.
3. Nustatyti chinoksalino darinių antimikrobinio ir priešvėžinio aktyvumo bei cheminės struktūros ryšio dėsningumus.
4. Įvertinti chinoksalino darinių toksiškumą ir farmakokinetines savybes in silico.
5. Remiantis gautais rezultatais, atrinkti perspektyviausius chinoksalino darinius.
Tyrimo metodai. Antimikrobiniam aktyvumui nustatyti naudoti in vitro metodai: skiedimo standžioje ir skystoje terpėse bei difuzijos į agarą metodas. Priešvėžinis aktyvumas įvertintas tiriant ląstelių gyvybingumo slopinimą MTT metodu. Struktūros-aktyvumo ryšys įvertintas analizuojant eksperimentinius duomenis. Junginių toksiškumas ir farmakokinetinės savybės įvertintos in silico, remiantis kompiuterinės programos ACD/I-Lab duomenimis.
Tyrimo rezultatai. Aktyviausi chinoksalino dariniai Bacillus ir Staphylococcus genties bakterijų augimą slopino 16 μM koncentracija, grybelio Candida albicans – 22 μM koncentracija. Aktyviausi chinoksalino dariniai žmogaus plaučių karcinomos A549 ir glioblastomos U87 ląsteles veikė 0,5-10 μM koncentracijomis. Nustatyti antimikrobinio poveikio struktūros ryšio dėsningumai: aktyviausi junginiai chinoksalino žiedo antroje padėtyje... [toliau žr. visą tekstą]The Aim of the Research: To evaluate the structure influence on antimicrobial and anticancer activity of quinoxaline derivatives and identify the most promising compounds for the further development. Objectives: 1. To test antimicrobial (antibacterial and antifungal) activity of quinoxaline derivatives in vitro. 2. To test anticancer activity of quinoxaline derivatives in vitro. 3. To establish relationship between structure and antimicrobial, also anticancer activity. 4. To evaluate toxicity and pharmacokinetic properties of quinoxaline derivatives in silico. 5. To identify the most promising quinoxaline derivatives with reference to experimental results. Methods. Antimicrobial activity was tested in vitro using three different methods: serial dilution in agar, in liquid broth, and diffusion into agar. Anticancer activity was investigated by evaluating cell viability using MTT assay. Structure-activity relationship was evaluated from analysis of experimental data. Toxicity and pharmacokinetic properties were predicted by using ACD/I-Lab program. Results. The most promising quinoxaline derivatives inhibited growth of Bacillus and Staphylococcus genus bacteria with 16 μM concentration, fungus Candida albicans with 22 μM concentration. The most active quinoxaline derivatives were active against human lung carcinoma A549 and glioblastoma U87 cell lines with concentrations of 0.5-10 μM. Some principles of structure – antimicrobial activity relationship were established: the most... [to full text]
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Erdem, Haci Bayram. "Synthesis and Characterization of Thermoplastic Polyphenoxyquinoxalines." University of Akron / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=akron1207147171.
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Sendur, Merve. "Combination Of Donor Characters In Donor-acceptor-donor Type Polymers Containing Benzothiadiazole And Quinoxaline As The Acceptor Units." Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613990/index.pdf.
Full textAbstract:
Donor-acceptor-donor approach is one of the effective ways to synthesize low band gap polymers. The monomers that will be designed with respect to donor-acceptor-donor approach have low band gap achieved by the coupling of a strong donor with high HOMO level to a strong acceptor with low LUMO level. Thus, the new donor-acceptor material will have a reduced bandgap (Eg) relative to either of its parent components. Due to this point of view, in this study, new electroactive benzothiadiazole and 2,3-bis(4-(tert-butyl)phenyl)quinoxaline monomers substituted with different donor groups (3,4-ethylenedioxythiophene and thiophene) were synthesized to explain the effect of different donor groups on the electronic and optical properties of DAD type polymers. The characterizations of the monomers were performed by 1H and 13C NMR techniques. Electrochemical behavior of both monomers and polymers were studied by cyclic voltammetry. The electrochromic properties of the synthesized conducting polymers were investigated by several methods like spectroelectrochemistry, kinetic and colorimetry studies. The polymers have two different donor units may behave as a copolymer of the symmetric monomer having the same donor groups. Hence, the properties of copolymers were investigated with the co-monomers having either thiophene or 3,4-ethylenedioxythiophene as the donor group.
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Nishikawa, Tsuyoshi. "Screw-sense Control of Helical Poly(quinoxaline-2,3-diyl)s for Chirality-switchable Asymmetric Catalysts and Luminescent Materials." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225637.
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Takeda, Ryohei. "Effect of Chiral Solvent and Pressure on the Dynamic Screw-Sense Induction to Poly(quinoxaline-2,3-diyl)s." Kyoto University, 2017. http://hdl.handle.net/2433/227637.
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Van, Heerden Lezanne. "Synthesis and in vitro antimalarial activity of series of bisquinoline and bispyrrolo[1,2a]quinoxaline compounds / Lezanne van Heerden." Thesis, North-West University, 2012. http://hdl.handle.net/10394/8518.
Full textAbstract:
Every year an estimated 1 million people die of malaria, with the majority of these deaths
reported in Africa. The disease caused by Plasmodium falciparum affects an approximate
250 million people annually and with the emergence of monodrug and multidrug resistance it
has seen resurgence in the last decade. The decline in effectiveness of chloroquine in the
treatment of drug resistant malaria has contributed to the doubling of malaria specific
mortality in the last fifteen years. Since the quinoline drug family represents the basis of
malaria chemotherapy for much of the past 50 years. This spread of resistance to existing
antimalarial drugs such as chloroquine, mefloquine, sulfadoxine and pyrimethamine has
driven the search for new drugs that might circumvent parasite resistance mechanisms. The
mechanism of chloroquine resistance is associated with reduced accumulation of the drug
inside the digestive vacuole, which is connected to a Plasmodium falciparum chloroquine
resistance transporter (PfCRT) or ATP-dependant P-glycoprotein efflux pump (Pgh1). The
PfCRT protein demonstrates a structural specificity for the chloroquine side chain, which
allows for changes in the structures of drugs to have different affinities for the transporter.
New drugs with structural modifications that result in reduced affinity for PfCRT may be able
to avoid reduced drug accumulation. Despite resistance, the aminoquinoline pharmacophore
remains an attractive scaffold in the design of new drugs, since it demonstrates a unique
affinity for haematin. This is a desirable feature since the quinoline antimalarial drugs inhibit
conversion of haematin to hemozoin. The 4-aminoquinoline antimalarial drugs are also weak
bases which traverse down the pH gradient to concentrate inside the acidic food vacuole.
The protonation of these drugs inside the vacuole makes them membrane impermeable and
increases their accumulation, which allows for the high concentrations required for hemozoin
inhibition.
The aim of this study was to synthesise a series of bisquinoline and
bispyrrolo[1,2a]quinoxaline compounds containing various polyamines, which may act as
potential protonation sites in the hope of increasing their accumulation via pH-trapping. In
order to achieve this aim twelve bisquinolines 4 - 15 and five bispyrrolo[1,2a]quinoxalines 16
- 20 were synthesised and their structures confirmed by nuclear magnetic resonance
spectroscopy (NMR) and mass spectroscopy (MS). The aqueous solubility (Sw) and
distribution coefficients (logD) were experimentally determined in phosphate buffered saline
(pH 5.5) to mimic the parasitic digestive vacuole environment. The compounds were
screened for antimalarial activity alongside chloroquine (CQ) against chloroquine-sensitive
(CQS) D10 and the moderately chloroquine-resistant (CQR) Dd2 strains of P. falciparum.
The series were also tested for cytotoxicity against Chinese Hamster Ovarian (CHO) cells, using emetine as reference drug. The most active compounds against P. falciparum were
screened for anticancer activity against the TK10 (renal), UACC62 (melanoma) and MCF7
(breast) cancer cells.
The bisquinoline- and bispyrrolo[1,2a]quinoxaline compounds were found to be more
hydrophilic than chloroquine (SW = 0.033 mM) itself with aqueous solubility varying in the
18.94 - 38.86 mM range. Irrespective of the series, the aqueous solubility increases with the
increase in potential protonation sites (N atoms) in the polyamine bridge. However, this
effect is overruled if the carbon-carbon chain separating two nitrogen atoms in the polyamine
also increases.
The in vitro data revealed seven of the twelve bisquinoline compounds to be significantly
more potent against the CQR (Dd2) strain compared to chloroquine. Compounds 8 (7-
chloro-4-[10-(7-chloroquinolin-4-yl)-1,4,7,10-tetraazadecan-1-yl]quinoline) (IC50 = 35.49 nM)
and 9 (7-chloro-4-[12-(7-chloroquinolin-4-yl)-1,5,8,12-tetraazadodecan-1-yl]quinoline) (IC50 =
49.48 nM) featuring the triethylenetetramine or N,N’-bis(3-aminopropyl)ethylenediamine
linkers respectively, were the most active of all synthesised compounds. They were found
significantly more potent than CQ (IC50 = 242.3 nM) against the Dd2 strain. However, they
were as potent as CQ (IC50 = 48.35 nM) against the D10 strain. This potent activity against
the CQR strain could possibly be as result of enhanced pH-trapping inside the digestive
vacuole, since they contain increased protonation sites that also enhance their hydrophilicity.
These compounds also displayed the best drug profile based on toxicity and antimalarial
activity, both demonstrating good selectivity towards parasitic cells with a selectivity index of
greater than 90.
The bis-(7-chloroquinoline)-series displayed the most potent antimalarial activity and were
subsequently screened for potential anticancer activity. The series showed potent growth
inhibitory activity against all 3 cancer cell lines. Presumably the polyamine bridges of
bisquinoline compounds provide increased ionisation of structures that allows for increased
van der Waals interactions with the highly polar phosphate backbone of the parasite DNA.
These interactions possibly interfere with cell replication and cause DNA strand scission,
since bisquinolines are known to bind by external attachment to the AT-rich sequences of
DNA, which is less stable and easier to pull apart. Compound 4 (7-chloro-N-[2-({2-[(7-
chloroquinolin-4-yl)amino]ethyl}amino)ethyl]quinolin-4-amine), 6 (7-chloro-N-[3-({3-[(7-
chloroquinolin-4-yl)amino]propyl}amino)propyl]quinolin-4-amine) and 7 (bis({3-[(7-
chloroquinolin-4-yl)amino]propyl})(methyl)amine) showed significantly more potent growth
inhibition efficacy against breast (MCF7) cancer cells compared to etoposide (TGI > 100 μM) with TGI-values in the range of 0.55 - 0.69 μM. Compounds 4, 6 and 7 were also the most
potent against TK10 (renal) and melanoma (UACC62) cancer cells with TGI-values of 0.6,
2.05 and 1 μM against TK10 cells respectively, compared to etoposide (TGI = 43.33 μM).
Against melanoma cells the TGI values were 0.59 for 4, 0.74 for 6 and 0.64 μM for 7,
compared to 4 μM for etoposide. The results reveal that a two C-C chain, and a three C-C
chain with or without methyl substitution is the optimal linker to separate the identical nonintercalating
pharmacophores for potent anticancer activity. All of the compounds in the
series warrant further investigation in search of more potent anticancer agents.Thesis (MSc (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2012
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Moagi, Kgotso Herbet. "Reaction Mechanism of 2-monosubstituted Quinoxalines with Organolithium Compounds : a Theoretical Study." Diss., University of Pretoria, 2020. http://hdl.handle.net/2263/75182.
Full textAbstract:
This dissertation describes the density functional theory (DFT) computational modelling of reactions between organolithium nucleophiles and various substituted quinoxalines. These reactions result in the functionalisation of the C (sp2)–H bond, thus substituting the sigma-hydrogen. The reactions are known as nucleophilic substitution of hydrogen (SNH) and are used by experimental chemists to form new C–C bonds. The SNH reactions are very important in various industries, e.g. in designing and manufacturing of pharmaceuticals. Quinoxaline is widely used in medicinal chemistry due to its various biological activities; these reactions play a crucial role in the synthesis of new classes of compounds.
The reactions of 2-phenyl- (A), 2-butyl- (B), and 6-nitro-2-phenyl- (C) quinoxaline with lithiofuran (a) and lithiothiophene (b) involves a direct (1) nucleophilic attack on an activated electron-deficient system, leading to the intermediate sigma^H-complex. This is followed by hydrolysis (2), where an sp2-type nitrogen is changed to an sp3 while forming Li---OH as a by-product. The presence of Li---OH then allows the departure of an sigma-proton via oxidation reaction, concomitantly forming H2O2 as the second by-product. All approaches to functionalise the C(sp2)–H bond involve elimination of a proton, and an oxidant is needed for the departure of the sigma-hydrogen. Although the sequence of steps and mechanisms of these C–H transformations are the same, various factors have shown to affect the reactions differently.
The theoretical study of this catalytic-free transformation, shows that the formation of sigma^H-adducts is not easily reversible, and that their formation is spontaneous. The reaction does not just require an oxidant to eliminate the sigma-hydrogen with the pair of electrons, but rather requires the presence of water for hydrolysis prior to oxidation. We must stress the crucial role of the oxidant since the key problem of the SNH reactions is associated with the elimination of sigma-hydrogen. However, the main objective of this study is to present a correct and complete mechanistic picture of oxidative nucleophilic substitution of hydrogen (ONSH).
Previous reports indicated that the presence of an electron donating/withdrawing group on the quinoxaline ring had a significant influence on the yield and selectivity. This is between reactions A+a, A+b, and B+a. These experimental observations correlated well with the modelling results when the potential energy surfaces (PES) of the reactions were compared.Dissertation (MSc)--University of Pretoria, 2020.
National Research Foundation (NRF)
Chemistry
MSc
Unrestricted
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Ishow, Eléna. "Synthese modulaire et caracterisation de complexes polyquinoxaliniques d'osmium et de ruthenium." Toulouse 3, 1997. http://www.theses.fr/1997TOU30204.
Full textAbstract:
Des sytemes polyquinoxaliniques, retenus pour jouer le role de fils moleculaires ont ete construits a partir de complexes precurseurs d'osmium et de ruthenium. Cette voie de synthese, dite modulaire, a permis de pallier l'insolubilite des polyquinoxalines et de generer de facon univoque des complexes mono- et heterodinucleaires de taille et de forme variees. Des etudes spectroscopiques, electrochimiques et photophysiques portant notamment sur les complexes dinucleaires lineaires et leurs especes a valence mixte, ont revele l'absence de toute interaction electronique et/ou optique des deux metaux au travers du ligand pontant polyquinoxalinique en raison d'une localisation elevee de la densite electronique. Les proprietes physiques qui en resultent ont ete mises a profit pour demontrer et evaluer les potentialites de sonde luminescente du complexe monoculeaire (bpy)#2rup(1,0)#2#+ par intercalation entre les nucleobases.
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Zhou, Mengqi. "Synthesis of [1,2,5]Thiadiazolo[3,4-g]Quinoxaline Based Donor-Acceptor-Donor Type Small Molecules For Bulk-Heterojunction Photovoltaic Device." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1385465422.
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Murakami, Ryo. "Helical Poly(quinoxaline-2, 3-diyl)s Bearing Boronyl Pendants as a Platform of New Chiral Catalysts and Ligands." Kyoto University, 2018. http://hdl.handle.net/2433/232488.
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Bou, Karroum Nour. "Synthèse et développement de nouvelles molécules hétérocycliques tricycliques : étude de leurs propriétés immunomodulatrices." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT014/document.
Full textAbstract:
Les récepteurs Toll-like 7 et 8 jouent un rôle important dans l’activation de la réponse immunitaire innée et adaptative. Leur stimulation conduit à la production des cytokines pro-inflammatoires et d’interférons de type I. L’imiquimod et son dérivé le résiquimod sont les premières molécules de faible poids moléculaire décrites comme agonistes du TLR7 et TLR8. Ces deux molécules ont montré des activités anticancéreuses et adjuvantes très importantes. Récemment, les TLR 7 et 8 ont fait l’objet de plusieurs publications visant à développer de nouveaux agonistes TLR7 et/ou TLR8 dans la perspective d’être utilisés comme adjuvants vaccinaux. Malgré les rôles essentiels de TLR7 et TLR8 dans la stimulation du système immunitaire, une activation immunitaire chronique peut être responsable de plusieurs maladies infectieuses et auto-immunes. D’où l’importance de développer également des antagonistes TLR7 et/ou TLR8.Ce travail de thèse est consacré à la synthèse et le développement de nouvelles molécules hétérocycliques, analogues de l’imiquimod et de résiquimod, dans le but d’identifier de nouveaux ligands TLR7 et/ou TLR8. Des voies de synthèse innovantes, permettant une modulation chimique importante grâce à des couplages croisés pallado-catalysés, ont été mises au point et ont permis d’obtenir une cinquantaine de molécules appartenant à trois séries chimiques différentes de type imidazo[1,2-a]pyrazine, imidazo[1,5-a]quinoxaline et pyrazolo[1,5-a]quinoxaline. De nombreux essais d’alkylation ont été tentés sur ces trois séries chimiques afin d’introduire une large variété de substituants sur le cycle à cinq sommets. L’application du couplage croisé de Sonogashira nous a permis d’établir une liaison C-C et introduire diverses chaines alkyles. Ces composés ont été testés pour leur activité agoniste et antagoniste TLR7 et 8. Aucun des composés cibles n'a présenté d’activité agoniste TLR7 et TLR8, dans l'intervalle des concentrations testées. Par contre, tous les composés ont montré une activité antagoniste sélective du TLR7. Les composés les plus actifs, 5.35a et 5.35b, membres de la série pyrazolo[1,5-a]quinoxaline ont montré des IC50 de l’ordre de 10 μM. Ces résultats prometteurs nous ont permis la découverte d’une activité antagoniste TLR7 importante pour la série pyrazolo[1,5-a]quinoxaline, une série très peu développée dans la littérature. La modulation chimique des molécules actives nous permet de donner naissance à de nouveaux leaders, qui peuvent jouer un rôle important dans la thérapie de plusieurs maladies infectieuses et auto-immunesToll-like receptors 7 and 8 play an important role in immune system activation. Their stimulation leads to the production of pro-inflammatory cytokines and type I interferons. Both receptors recognize viral ssRNA, as well as synthetic tricyclic imidazoquinoline derivatives such as imiquimod (TLR7 agonist) and resiquimod (TLR7/8 agonist). These two molecules showed significative anti-cancer and adjuvant activities. Many reports in the literature have been focused on the development of new TLR7/8 agonists belonging to different chemical series. These agonists strongly induce the production of T helper 1-polarizing cytokines and may therefore serve as promising candidate vaccine adjuvants. Despite the essential roles of TLR7 and TLR8 in the immune system stimulation, chronic immune activation may be responsible for several infectious and autoimmune diseases. Consequently, the development of TLR7 inhibitors may play an important role in the therapy of these diseases.In this study, we are interested in the synthesis and development of new heterocyclic molecules, analogs of imiquimod and resiquimod, in order to identify new TLR7 and/or TLR8 ligands. Different synthetic pathways have been developed, using cross coupling reactions, in order to obtain a wide variety of molecules belonging to three chemical series: imidazo[1,2-a]pyrazine, imidazo[1,5-a]quinoxaline et pyrazolo[1,5-a]quinoxaline. Various alkylation reactions were attempted on these three chemical series in order to introduce a wide variety of substituents on the five-membered ring. The application of Sonogashira's cross-coupling allowed us to establish a C-C bond and introduce various alkyl chains. All compounds have been tested for their TLR7/8 agonistic and antagonistic activity using HEK-Blue™-hTLR7/8 cells. The synthesized compounds are completely inactive as TLR7/8 agonists and are selective TLR7 antagonists. Two compounds of the pyrazolo[1,5-a]quinoxaline series, compound 5.35a and 5.35b, bearing butyl and isobutyl chain respectively, are potent and selective TLR7 antagonists with low micromolar IC50. Results allowed us to discover significative activity for the pyrazolo[1,5-a]quinoxaline series as selective TLR7 antagonists, which may therefore play an important role in the therapy of several infectious or autoimmune diseases
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Franco, Márcia Silvana Freire. "Síntese de biblioteca de derivados quinoidais e quinoxalínicos visando à atividade biológica." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/60/60138/tde-22052018-155948/.
Full textAbstract:
Nesta tese são apresentados, em dois capítulos, os resultados da reatividade química de quinoxalinas e os estudos visando à síntese de quinona natural, a vegfrecina. Modificações específicas em estruturas privilegiadas, padrões estruturais relevantes para bioatividade, representam uma alternativa viável na busca de novos ligantes para alvos macromoleculares. Neste cenário, as quinoxalinas apresentam destacada importância no âmbito da química medicinal, sendo assim é de grande importância o desenvolvimento de metodologias de funcionalização que conduzam a diversidade molecular deste núcleo. Neste contexto, foram realizadas reações de ativação C - H, como uma estratégia para a síntese de derivados vinil quinoxalinicos, com base na abordagem de Fujiwara-Moritani. Os resultados obtidos com este estudo indicaram que a densidade eletrônica das olefinas utilizadas neste estudo foi determinante para o rendimento reacional. Assim, as reações envolvendo olefinas ricas em elétrons, resultaram em maior rendimento do produto alquenilado, alcançando 89%. A deoxidação ocorreu em rendimentos de 43 - 54%, levando a ampliação da coleção de compostos desenvolvidos neste projeto. Os compostos aqui desenvolvidos foram testados quanto à atividade antimicobacteriana, entretanto, nenhum deles apresentou resultados promissores. O segundo capítulo desta tese abordou a síntese da Vegfrecina, que possui seletividade de inibição dos receptores do fator de crescimento endotelial vascular (VEGFR), bloqueando a ativação de VEGFR-1 e VEGFR-2 e, consequentemente, interferindo na vascularização, proliferação e metástase tumoral. Nossa estratégia utilizou o intermediário chave 6-Bromo-5,8-dimetoxi-2,2-dimetil-2,3-dihidroquinazolin-4(1H)-ona em reações de aminação de Buchwald Hartwig com três anilinas diferentes. Embora tenhamos obtido três intermediários sintéticos inéditos, em bons rendimentos, a etapa de oxidação não foi promissora, impossibilitando a obtenção da Vegfrecina e de seus análogos.The study of chemistry reactivity of quinoxalines and the study aiming total syntheses of natural quinone, vegfrecine, are shown in this thesis in two chapters. The specific modifications privileged scaffold represents a promising way following for new macromolecular ligands targets. Considering the great importance of quinoxaline core in medicinal chemistry, the development of efficient methodologies in orther to obtain molecular diversity have attracted large attention. In this context, using Fujiwara-Moritani approach the C-H activation reactions were performed as good strategy in synthesis of vinyl- quinoxaline derivatives. Our results indicated the importance of olefin electron density in the reaction yields. In this way, reactions involving high electron density olefines, results in the high alkenilated products, achieving 89% of yield. The deoxygenation process occurred in yields of 43 until 54. The compounds obtained were tested against Mycobacterium tuberculosis, however no primissing results were observed. The second chapter in this thesis show our attempt to total synthesis of Vegfrecine, that have inhibitory activity of vascular endothelial growth factor receptor (VEGFR), Our strategy used the 6-bromo-5,8-dimethoxy-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-one in Buchwald Hartwig reaction with three different olefins. Although these new synthetic intermediates were obtained with good yield, the last step of oxidation didn\'t work. Therefore, it was not possible to obtain the Vegfrecine and its analogous.
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Machnik, David. "Réactions de couplage hétéroaryl-hétéroaryle et aryl-hétéroaryle catalysées par le palladium, le nickel ou le manganèse permettant d'accéder à des composés hétérocycliques d'intérêt biologique." Cergy-Pontoise, 2001. http://www.theses.fr/2001CERG0120.
Full textAbstract:
Les reactions de couplage catalysees par un metal de transition entre un compose organometallique aromatique et un halogenure ou un triflate aromatique, permettent d'obtenir rapidement des molecules elaborees. De nombreux composes de structure polyheterocyclique possedent des proprietes biologiques et interessent vivement l'industrie pharmaceutique. Au cours de ce travail, nous avons etudie diverses reactions de couplage en serie heteroaromatique. Dans le cas de derives de la pyridine et du thiophene, la reaction entre un halogenure d'heteroarylmanganese et un bromure d'heteroaryle, en presence d'un complexe du palladium (pdcl 2dppp) dans le thf, conduit aux produits de couplage avec de bons rendements. Dans le cas de pyrazoles, nous avons mis au point une nouvelle methode de synthese regioselective de pyrazoles 3,5-disubstitues basee sur des couplages de suzuki et de negishi a partir d'un 3-bromopyrazole convenablement n-protege. Les pyrazoles ainsi prepares ont ete fonctionnalises et ont permis d'obtenir une librairie de composes originaux qui presentent une activite biologique potentielle. Enfin, dans la deuxieme partie de ce travail, nous avons montre qu'en presence de chlorure de manganese (20%), les composes organomagnesiens reagissent avec de bons rendements et dans des conditions douces avec des chlorures et des bromures d'heteroaryle actives. Cette nouvelle methode de couplage etudiee dans le cas de derives de l'isoquinoleine a ete etendue avec succes a un chloropyrazole ainsi qu'a des halogenoquinoxalines (x = cl, br).