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1
Horner, Katherine A. "Synthesis and applications of triazole- and triazine-containing amino acids." Thesis, University of Leeds, 2015. http://etheses.whiterose.ac.uk/11024/.
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Through their use as mimics of post-translational modifications (PTMs) and in bioorthogonal chemical reporting strategies, unnatural amino acids (UAAs) are vital tools for studying biological systems. τ-Phosphotriazolylalanine I can act as a non-hydrolysable analogue of phosphohistidine and is compatible with the Fmoc-strategy for peptide synthesis. Peptides containing either I or an alternative phosphoamino acid were synthesised and used to demonstrate the selectivity of the SH2 domain of the growth factor receptor-bound 2 protein (a phosphotyrosine binding protein) towards τ-phosphohistidine. In addition, peptides containing I were ineffectively used to study the binding interaction between a histidine-phosphorylated protein, phosphoenolpyruvate synthase and its cognate regulatory protein, YdiA. It was concluded that mimicking the primary structure of one protein through peptide generation was not sufficient to study this protein-protein interaction. As a result, third generation τ phosphotriazolylalanine II was synthesised, which has the potential to be genetically incorporated into proteins using amber suppression. Bioorthogonal reactions can be used to selectively derivatise probes onto biomolecules. Although there are a number of chemical reactions that have been used for this purpose, many are limited in terms of biocompatibility and synthetic accessibility of bioorthogonal reagents. Therefore, a novel bioorthogonal reaction was developed based on the cycloaddition of 1,2,4-triazines to strained dienophiles. An accessible and robust synthesis to novel 1,2,4-triazin-3-yl-linked amino acid III was devised and its reactivity towards a range of strained dienophiles was investigated. It was determined that III reacted readily with bicyclononyne at 37 °C with a second order rate constant between 0.3 - 0.5 ×10-3 M-1 s-1, depending on solvent mix. The utility of III towards late stage functionalisation of probe molecules was also demonstrated through generation of a fluorescent probe containing III. This triazine probe was used to demonstrate cycloaddition of triazine to a strained dienophile in vitro.
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Vieira, Andreia Sofia da Costa. "Rethinking Triazoles as Antifungals: Synthesis and Evaluation of New Triazole Derivatives." Master's thesis, Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica António Xavier, 2017. http://hdl.handle.net/10362/81407.
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"In the last decades, fungal infections have become a serious problem, mainly due to the excessive use of this reduced number of drugs, leading to an increase of acquired resistances1. Therefore, it is urgent to develop new and more effective antifungal medicines.
The main objective of this master's thesis was the development of novel antifungal drugs, based on triazoles and pyrimidines, combining two groups with antifungal properties, known to be active in combinatorial therapies, in a single molecule. For the synthesis of these compounds, Huisgen's 1,3-dipolar cycloaddition methodologies, catalyzed by copper2 or ruthenium3 were employed. 1,4- and 1,5-triazoles derived from AZT (azidothymidine) were synthesized successfully as well as their methylated triazolium salts. Similarly, 1,4-triazoles derived from 5-fluorouracil were synthesized, as well as one methylated derivative. In general, the synthesis of the azidothymidine derivatives presented higher yields than those of 5-fluorouracil.(...)"N/A
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Khaldi, Zineb. "Elaboration et évaluation biologique de nouveaux matériaux lignocellulosiques antibactériens." Thesis, Limoges, 2018. http://www.theses.fr/2018LIMO0090/document.
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La contamination des surfaces par des bactéries et l’émergence de souches résistantes aux antimicrobiens sont des problèmes très préoccupants dans différents domaines tel que les domaines hospitalier et alimentaire. Cette contamination commence par l’adhésion de bactéries pathogènes sur une surface jusqu’à la formation de biofilms. Ces derniers contribuent à l’émergence de résistances de certaines souches bactériennes aux traitements conventionnels. Pour répondre à ces problèmes de contamination des surfaces, ces travaux de thèse portent sur le développement de nouveaux matériaux antibactériens à base de fibres de pâte à papier. Nous nous sommes intéressés, dans une première partie, à l’élaboration d’un papier antibactérien par le greffage, via un lien triazine, de deux composés d’huiles essentielles, le thymol et le carvacrol, connus pour leurs activités antibactériennes. L’évaluation microbiologique des matériaux élaborés, sur les deux souches bactériennes testées, E.coli et S.aureus, a montré un effet bactériostatique. Ces matériaux bloquent donc la croissance bactérienne empêchant ainsi la formation des biofilms. Une synergie entre le thymol et le carvacrol lorsqu’ils sont greffés sur les fibres de pâte à papier a également été montré. Dans une deuxième partie, notre étude s’est focalisée sur l’élaboration d’un papier antibactérien qui n’acquière son activité qu’après greffage et formation du motif actif « aryl-1,2,3-triazole ». Le greffage est réalisé par une réaction de « Click Chemistry », la cycloaddition de Huisguen catalysée par le cuivre I. Les tests antibactériens révèlent l’importance du substituant de l’aryle, l’influence du temps de contact et la pertinence d’utiliser des mélanges de matériaux. L’activité antibactérienne observée sur les fibres de la pâte thermomécanique est meilleure dans les deux parties. Les différents résultats obtenus sont décrits dans ce manuscritThe contamination of surfaces by bacteria and the emergence of antimicrobial resistant strains are very worrying problems in different areas such as hospital and food. This contamination begins with the adhesion of pathogenic bacteria on a surface until the formation of biofilms. These biofilms contribute to the emergence of resistances of certain bacterial strains to conventional treatments. To answer these problems of surface contamination, this thesis work focuses on the development of new antibacterial materials based on pulp fibers. In the first part, we focused on the development of an antibacterial paper by grafting, via triazine link, two essential oil compounds, thymol and carvacrol, known for their antibacterial activities. The microbiological evaluation of the developed materials against the two bacterial strains tested, E. coli and S. aureus, showed a bacteriostatic effect. These materials block the bacterial growth thus preventing the biofilms formation. Synergy between thymol and carvacrol grafted onto paper has also been shown. In a second part, our study focused on the development of an antibacterial paper that acquires its activity only after the grafting and formation of "aryl-1,2,3-triazole", the active motif. The grafting is carried out by a reaction of "Click Chemistry", the copper (I)-catalyzed Azide Alkyne Cycloaddition. The antibacterial tests reveal the importance of the aryl substituent, the influence of the contact time and the relevance of using mixtures of materials. The antibacterial activity observed on the thermomechanical pulp fibers is better in both parts. The different results obtained are described in this manuscript
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Fiscus, David Michael. "The chemistry of 3-diazo-3H̲-1,4-triazole and 3H̲-1,2,4- triazol-3-ylidene /." The Ohio State University, 1985. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487260135358319.
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Canduzini, Hugo Antonio. "Síntese e funcionalização de 1,2,3-triazóis via reação de cicloadição [3+2] de azidas e acetilenos terminais." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-07032013-094439/.
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O objetivo deste trabalho é explorar a síntese e funcionalização de 1,2,3- triazóis empregando o uso de reações do tipo \"Click-chemistry\", que é uma abordagem para a síntese de diversos compostos com base em reações de formação de ligação carbono-heteroátomo, onde a reação é estereoespecífica, altamente eficiente e geralmente com elevados rendimentos e em alguns casos ausência de subprodutos. O composto 1,2,3-triazol, sendo o material de partida para a continuidade do projeto foi preparado a partir do álcool propargílico (4) em presença de uma azida orgânica (1) e utilizando cobre(I) como agente promotor. Após a obtenção de uma série de compostos 1,2,3-triazólicos (2), procedeu-se a etapa de tosilação da hidroxila e posterior cicloadição multicomponente de um novo 1,2,3-triazol formando compostos bis-triazólicos. Os bis-triazóis (5) obtidos foram testados frente a cepas fúngicas, responsáveis por dermatites, com resultados satisfatórios. Ainda essas estruturas poderão ser empregados como blocos construtores para a síntese de estruturas mais complexas.The aim of this work has been exploring the synthesis and functionalization of 1,2,3-triazoles employing the use of \"click-chemistry\" concept, which is defined as an approach for synthesis of various compounds based on reactions of carbon-heteroatom bond formation, which the reaction is stereospecific, high-efficiently, commonly gives high yields and in some cases no by-products are formed. The compound 1,2,3-triazole, which is the main starting material for the next steps was prepared from propargyl alcohol (4) in the presence of an organic azide (1) and copper(I) as a reaction promoter. Subsequently with a series of 1,2,3-triazole (2n) prepared we proceeded to the next step which is the substitution of hydroxyl for a tosyl group and after that a multicomponent cycloaddition of a new 1,2,3-triazole compound forming bis-triazoles. Bis-triazoles (5) were tested against fungal strains, responsible for dermatitis, with delighted results, furhtermore this class of strutures can be used as building blocks to improve efficiency in some other more complex structure.
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Cong, Mei. "Design, synthesis and characterization of novel triazole nucleoside analogues." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM4018.
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Les analogues de nucléosides sont d'une importance considérable dans la recherche de nouveaux candidats médicaments antiviraux et anticancéreux. La ribavirine est en effet le premier nucléoside triazole antiviral synthétique. Elle est toujours activement utilisée en milieu hospitalier pour le traitement de l'hépatite C et celui des pandémies virales émergentes. Récemment, le besoin de nouveaux agents thérapeutiques efficaces dotés de nouveaux mécanismes d'action a donc créé un regain d'intérêt dans la création de nouvelles entités structurelles de nucléosides triazoles. Au cours de mon doctorat, j’ai été activement engagée dans l’élaboration de nouvelles structures O-arylées et S-arylées de nucléosides triazoles. Les nucléosides triazoles O-arylés ont été obtenus par substitution nucléophile aromatique initiée par micro-ondes, tandis que les nucléosides triazoles S-arylés ont été synthétisés par réaction de couplage C-S en utilisant un catalyseur palladié possédant des ligands mixtes nouvellement mis au point dans notre laboratoire. Le concept du système de catalyseur à ligands mixtes est extrêmement avantageux et enrichissant puisqu’il permet de combiner de façon rationnelle des ligands possédant des fonctionnalités complémentaires afin de promouvoir des réactions avec des substrats pour lesquels ces réactions sont très compliquées. Enfin, afin d'améliorer la solubilité dans l'eau des analogues nucléosidiques triazoles actifs que nous avons identifiés, j’ai tenté de conjuguer le nucléoside triazole à un dendrimère amphiphile dans le but d'élaborer un système de délivrance efficace des médicaments et ainsi d’améliorer leur biodisponibilitéNucleoside mimics are of considerable importance in the search of antiviral and anticancer drug candidates. One noteworthy example is ribavirin, the first synthetic antiviral triazole nucleoside discovered 40 years ago, which is still actively in clinic use for treating hepatitis C infection and emerging viral pandemics. Recently, ribavirin has been also reported to demonstrate apoptosis-related anticancer effects and is in clinical trial for treating leukemia. Consequently, there is a renewed interest in creating new structural entities of triazole nucleosides with the aim of developing potent therapeutic agents with novel mechanisms of action. During my PhD program, I have been actively engaged in constructing structurally novel O-arylated and S-arylated triazole nucleosides. The O-arylated triazole nucleosides were obtained via microwave promoted aromatic nucleophilic substitution, whereas the S-arylated triazole nucleosides were synthesized via C-S coupling reaction using our newly developed mixed ligand Pd catalyst (Pd2(dba)3/Xantphos/CyPF-tBu). The concept of the mixed ligand catalyst system is extremely advantageous and rewarding, offering a unique opportunity to rationally combine ligands with complementary features in order to promote the reactions with challenging substrates which are otherwise difficult to proceed. Finally, in order to improve bioavailability of the active triazole nucleoside analogues identified in our group, I have attempted to conjugate the triazole nucleoside to an amphiphilic dendrimer in the view to establishing an effective drug delivery system and offering a better bioavailability
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REDENTI, SARA. "DESIGN, SYNTHESIS AND CHARACTERIZATION OF GSK-3β AND CK-1δ INHIBITORS." Doctoral thesis, Università degli Studi di Trieste, 2017. http://hdl.handle.net/11368/2908172.
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Glycogen Synthase Kinase 3-β (GSK-3β) and Casein Kinase 1-δ (CK-1δ) are both highly conserved serine/threonine protein kinases that seem to be involved in neuroinflammation and in the development and progression of several disorders of the central nervous system (CNS), such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). In particular, both are related to the hyperphosphorylation of tau-protein, one of the major hallmark of AD and other taupathies. So, the inhibition of GSK-3β and or CK-1δ could represent a strategy for the treatment of these unmet diseases. The main purpose of this thesis is the synthesis of new chemical entities as GSK-3β and/or CK-1δ inhibitors as potential therapeutic agents for neurodegenerative disorders. Since all kinases present an ATP-binding site, we can deduce that adenine-like nuclei could be suitable scaffolds to design novel ATP-competitive inhibitors. In particular, we focused our attention on fused 5 and 6 membered rings: [1,2,4]triazolo[1,5-a]triazines (TT) and [1,2,4]triazolo[1,5-c]pyrimidines (TP), two classes of heterocyclic derivatives well known in literature. Both TT and TP scaffolds were obtained following the synthetic pathways reported in literature. Computational studies helped us to decide the pattern of substitutions to introduce on the above-mentioned nuclei: in particular, we modified positions 2, 5 and 7 of the TT nucleus and 2, 5, 7 and 8 of the TP one. After chemical characterization through 1H-NMR, 13C-NMR and ESI-MS, all the synthetized derivatives were assayed against GSK-3β and/or CK-1δ. On the most promising compounds, kinetic experiments, to investigate the inhibitory mechanism towards the kinases, and PAMPA assay for predicting the brain permeability were performed. Different substituents were inserted in both TT and TP nuclei and good inhibitors of GSK-3β and/or CK-1δ were obtained with IC50 values in the submicromolar range. Moreover, the insertion of a Michael acceptor moiety (eg. cyanacrylamide) in position 2 of the TT scaffold led to a potent GSK-3β irreversible inhibitor (IC50=0.17 μM) that inhibited also CK-1δ in an ATP competitive manner with an IC50 value of 0.68 μM, and for these reasons it could be considered a good dual inhibitor of GSK-3β and CK-1δ. Its reactivity in front of thiols was evaluated through UV-spectrometry and HPLC-MS methodology and its binding mode to GSK-3β has been investigated, both theoretically and experimentally. In fact, kinetic assays showed a mixed ATP-competitive/non-ATP-competitive behavior of the TT derivative; on the other hand, time-dependent experiments confirmed that a covalent interaction with GSK-3β took place. Interestingly, despite the dual inhibitor has not shown an optimal BBB-permeability, it resulted able to increase the survival of cells treated with 6-OHDA or MPTP, two models of Parkinson’s disease (PD), and also to enhance β-catenin expression.
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Wareman, P. J. "Regioselectivity of 1,2,4-triazole." Thesis, Swansea University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.639348.
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The project investigated the regioselectivity of 1,2,4-triazole with 1,1-diphenylepoxide. Typically N1 substitution was favoured over N4 substitution resulting in isomer ratios of 85-90/15-10. The kinetic factors affecting the regioselectivity were investigated and showed the importance of the 1,2,4-triazole anion. When 1,2,4-triazole reacted in the form of its ambident anion greater preference for the 1-isomer was observed. The use of low reactant concentrations and dipolar aprotic solvents were shown to increase the formation of the ambident anion. Under these favourable conditions the isomer ratio obtained was 95/5. Synthesis of new epoxides and subsequent reaction with 1,2,4-triazole had no effect on the regioselectivity. Thermodynamic control of the regioselectivity was then observed with the 1-alkyl-1,2,4-triazole being the thermally more stable isomer. The mechanism was shown to occur through the nucleophilic displacement of the triazole anion and formation of the epoxide. The 1-isomer was also seen to be the thermally more stable isomer regardless of the alkyl group and that it is formed in a ratio with the 4-isomer approaching the ratio found in the prototropic tautomer equilibrium of 1,2,4-triazole. Under thermodynamic control the equilibrium mixture was shown to be 99.3/0.7 by both experimental and theoretical (free energy diagrams) methods. From the literature other azoles are seen to exhibit thermodynamically controlled regioselectivity and are therefore also open to the predictive approach to their equilibrium isomer ratios from their respective prototropic tautomer equilibriums.
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Obszynski, Julie. "Conception et synthèse d'aminoglycosides guidées par l'ARN." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAF018.
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Le développement de nouveaux antibiotiques est un enjeu majeur de santé publique. Etant donné, le fort potentiel des aminoglycosides en tant qu’antibiotique, ces composés ont attisé l’intérêt de plusieurs groupes de recherche. Cependant, leur usage est encore très limité, malgré leur ancienneté, du fait de leur toxicité et du développement toujours croissant des mécanismes de résistances aux aminoglycosides. Afin de mieux appréhender les problèmes inhérents à leur utilisation, il est crucial de mieux comprendre leur action sur les différentes cibles cellulaires, et d’étudier leur interaction avec leur cible moléculaire (ARN et protéine). En plus de leur pouvoir antibiotique, les aminoglycosides sont également des ligands universels pour des ARN, capables d’interagir spécifiquement avec notamment les ARN du VIH-1 suivants : DIS, TAR, RRE. L’élaboration d’aminoglycosides modifiés présente un énorme avantage car le domaine d’application, et en conséquence les retombées, sont grandes. Néanmoins, la complexité structurale de ces molécules est un frein majeur, la fonctionnalisation chimiosélective est indispensable mais malheureusement peu décrite dans la littérature. Dans le cadre de ce travail, nous avons développé deux types d’approches pour cibler le DIS et/ou le site A du ribosome bactérien. La première originale, mais risquée se base sur le concept de click in situ. La seconde approche est traditionnelle et est basée sur la fonctionnalisation sélective de certaines positions clés des aminoglycosidesThe development of new antibiotics is a major public health issue. Given the high potential of aminoglycosides as antibiotics, these compounds have aroused great interest in many research groups. However, despite their maturity, their use is still limited because of their toxicity and the increasing development of resistance mechanisms to aminoglycosides. To better understand the problems inherent to their use, it is crucial to understand their action a cellular level, and to study the interactions with their molecular targets (RNA and protein). In addition to their antibiotic power, aminoglycosides are also universal ligands for several RNAs, capable of specific interactions with RNAs of HIV-1: DIS, TAR and RRE. The elaboration of modified aminoglycosides presents a huge advantage because the domain of application, and therefore the benefits, are important. Nevertheless, the structural complexity of these molecules is a major constraint, chemoselective functionalization is essential but unfortunately poorly described in the literature.In this work, we developed two approaches to target the DIS and/or the A site of the bacterialribosome. The first one, unique but challenging is based on the concept of in situ click chemistry. The second approach is conventional and is based on the selective functionalization of some keypositions of aminoglycosides
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Small, A. "Regiospecific reactions of 1,2,4-triazole." Thesis, Swansea University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.639059.
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An in-depth study on the alkylation of the ambident 1,2,4-triazole nucleophile has been made. Typical alkylations of 1,2,4-trizole with alkyl halides or epoxides in the presence of base, yield both the 1-isomer and small quantitities (ca 5-30%) of the 4-isomer. Subsequent research enabled three novel regiospecific 1,2,4-triazole alkylations to be developed. Firstly, it was found that 1-alkyl-1,2,4-triazole derivatives can be obtained regiospecifically upon the reaction of 1,2,4-triazole with alkyl halide at elevated temperatures in the absence of base. The reactions proceed through the intermediacy of a quaternary salt which breaks down in heat to give only the thermodynamically stable 1-isomer. Knowledge of this quaternary salt mechanism enabled a novel isomerisation process to be developed. It was found that on heating with a catalytic quantity of corresponding alkyl or phenacyl halide, 4-alkyl- or 4-phenacyl-1,2,4-triazoles isomerise via quaternary salts to their 1-substituted isomers. The reactions of 1,2,4-triazole with aldehydes offered another regiospecific route to the 1-isomer. The initially obtained hemi-aminal was readily converted to the α-methanesulphonate ester (mesyl) leaving group. Nucleophilic substitution upon this reactive ester then allowed the formation of various α-substituted-1-alkyl-1,2,4-triazole derivatives, many of which are commercially important. The above alkylation via the hemi-aminal was unsuccessful for aromatic aldehydes where hemi-aminal formation does not occur. An alternative process was developed which utilised the reaction of 1-trifluoroacetyl-1,2,4-triazole with aldehyde to form the 1-(1-trifluoroacetoxyalkyl)-1,2,4-triazole derivative. Subsequent nucleophilic substitution of the trifluoroacetoxy group again allowed the formation of various α-substituted-1-alkyl-1,2,4-triazole derivatives.
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Salem, Omar. "Photophysics and applications of triazole complexes." Thesis, University of Huddersfield, 2018. http://eprints.hud.ac.uk/id/eprint/34637/.
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1,2,3-Triazoles have proven to be highly successful in ligand design due to their facile synthesis owing to the advent of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The Cu(I) species necessary for the CuAAC reaction can be generated in situ with simple purification of the resulting 1,4-disubstituted products and has proven to be an outstanding method to prepare triazole-containing ligands. The present work focuses on the synthesis, characterization and photophysical investigation of triazole-containing transition metal complexes and their possible use in applications, such as LECs and biological cell imaging. To explore this wide topic different types of 1,2,3-triazole containing ligands including 2-(1-benzyl-1H-1,2,3-triazol-4-yl)pyridine as a bidentate ligand, 2,6-bis(1-phenyl-1H-1,2,3-triazol-4-yl)pyridine as a tridentate ligand and 1,4-bis((4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl)benzene as a bridging ligand. were prepared and used with Re(I), Os(II), Ru(II) and Ir(III) transition metals. Chapter 2 deals with rhenium complexes [Re(CO)3(Bn-pytz)(X)]+/0 (X = Cl or substituted pyridine). The photophysical investigation indicates that the emission can be further shifted towards the blue by replacing the Cl- ligand with pyridine. Two of these complexes were utilised in preliminary tests as the phosphor in light-emitting electrochemical cell LEC devices. In Chapter 3 a series of osmium(II) complexes [Os(bpy)3−n(Bn-pytz)n](PF6)2 (where bpy = bipyridine, n = 1, 2, 3) were prepared and characterised. The progressive replacement of bpy by Bn-pytz leads to blue-shifted UV-visible electronic absorption and emission spectra. Successful separation of the fac and mer isomers of [Os(Bn-pytz)3](PF6)2 complexes was achieved, which exhibits phosphorescence (λem = 615 nm, in degassed acetonitrile). [Os(Bn-pytz)3][PF6]2 was shown to exhibit significant quenching of luminescence intensity in the presence of oxygen (Ksv = 83 atm-1). The water soluble chloride form of the complexes were prepared and were subjected to preliminary cellular uptake and luminescence imaging microscopy studies. The results from these studies reveal that the [Os(Bn-pytz)3]2+ is successfully taken up by two cancer cell lines. Bright emission from [Os(Bn-pytz)3]2+ can be seen by confocal microscopy with localisation at the lysosomes, however, no photodynamic therapy (PDT) activity is observed. Described in Chapter 4 is the synthesis, characterisation and photophysical investigation of an osmium(II) 2,6-bis(1-phenyl-1H-1,2,3-triazol-4-yl)pyridine (btzpy) complex. From photophysical investigations [Os(btzpy)2](PF6)2 exhibits phosphorescence (λem = 595 nm, τ = 937 ns, φem = 9.3% in degassed acetonitrile). The complex undergoes significant oxygen-dependent quenching of emission with a 43-fold reduction in luminescence intensity between degassed and aerated acetonitrile solutions (Ksv = 110 atm-1), demonstrating its capability as a singlet oxygen sensitiser. The water soluble chloride form of the complex was prepared on the basis of the photophysical properties and was subject to preliminary cellular uptake and luminescence microscopy imaging studies. The complex easily entered the HeLa and U2OS cancer cell lines with mitochondrial localisation observed with intense emission permitting imaging at reduced concentrations up to 1 μM. Long-term dose toxicity results show low toxicity in HeLa cells with LD50 >100 μM. Described in Chapter 5 is the synthesis and characterisation of a range of dinuclear supramolecular complexes, containing a bridging ligand incorporating the 1,2,3-triazole moiety. The homonuclear complexes ([Ir(ppy)2-L-Ir(ppy)2](PF6)2, [Ru(bpy)2-L-Ru(bpy)2](PF6)4, [Os(bpy)2-L-Os(bpy)2](PF6)4 and [Os(Bn-pytz)2-L-Os(Bn-pytz)2](PF6)4 and heteronuclear complex ([Ru(bpy)2-L-Ir(ppy)2](PF6)3 (where L = 1,4-{bis-4-(pyrid-2-yl)-1,2,3-triazol-1-yl methyl}benzene) were prepared. Photophysical studies show that the dinuclear species display greater luminescence intensities than their mononuclear model complexes. The emission spectra of the heteronuclear complex [Ru(bpy)2-L-Ir(ppy)2](PF6)3, exhibits features similar to those observed in the emission spectra of the mononuclear complexes [Ir(ppy)2-L](PF6) and [Ru(bpy)2-L](PF6)2. This indicates dual emission occurs from both the Ir- and Ru-centred chromophores (φem = 0.33% in acetonitrile). Interestingly the emission from the Ru-centred chromophore seems greatly enhanced relative to the emission of the Ru mononuclear analogue. This indicates partial energy transfer from Ir to Ru. The dual emission results in near white light emission and could be used for the devolpment of single component white light emitting phosphors.
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Pereira, Evelin Fornari. "Síntese de compostos α-amino-1,3-dicarbonílicos em microrreator de fluxo contínuo e suas aplicações." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-10082017-114511/.
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Na primeira parte deste trabalho apresentamos uma forma eficiente para sintetizar quinze novos compostos α-amino-1,3-dicarbonílicos através da reação multicomponente de Ugi. Para estas sínteses foi utilizado o microrreator de fluxo contínuo, um aparelho que possibilita uma excelente transferência de calor, de massa e alta relação superfície / volume. Algumas das vantagens em se utilizar um microrreator de fluxo contínuo na síntese são: redução do tempo de reação, aumento de rendimento, seletividade das reações e menor geração de resíduos. Foi possível assim estudar as reações químicas em condições inéditas, variando parâmetros como: temperatura, pressão, tempo de residência e relação estequiométrica. Um comparativo de rendimento da síntese de quatro moléculas foi realizado e pôde-se notar a eficiência do equipamento utilizado, pois os rendimentos obtidos foram superiores quando as mesmas moléculas foram sintetizadas através da reação one-pot. Um scale-up da reação de Ugi também foi realizado e apresentou um resultado satisfatório. Na segunda parte alguns destes compostos foram utilizados como intermediários na formação de uma ligação amídica e também aplicamos a metodologia relacionada à cicloadição catalisada por cobre entre alquinos e azidas na síntese de cinco novos compostos 1,2,3-triazóis. Este foi o primeiro trabalho realizado no Laboratório de Compostos Heterocíclicos da Faculdade de Ciências Farmacêuticas utilizando o microrreator de fluxo contínuo e este equipamento atendeu as necessidades deste trabalho com efetividade.The first part of this work we present an efficient way to synthesize fifteen new α-amino-1,3-dicarbonyl compounds through the multicomponent Ugi reaction. For these syntheses was used the continuous flow micro-reactor, an equipment that allows an excellent transfer of heat, mass and high surface / volume ratio. Some of the advantages of using a continuous flow micro-reactor in the synthesis are: reduction of reaction time, increase of yield, selectivity of reactions and less generation of residues. It was possible to study the chemical reactions under new conditions, varying parameters such as: temperature, pressure, residence time and stoichiometric ratio. A yield comparison of the synthesis of four molecules was carried out and it was possible to note the efficiency of the equipment used, because the obtained yields were superior when the same molecules were synthesized through the one-pot reaction. A scale-up of the Ugi reaction was also performed and presented a satisfactory result. In the second part some of these compounds were used as intermediates in the formation of an amide bond and we also apply the methodology related to the copper catalyzed cycloaddition between alkynes and azides in the synthesis of five new 1,2,3-triazoles compounds. It was the first work performed in the Laboratory of Heterocyclic Compounds of the Faculty of Pharmaceutical Sciences using the continuous flow micro-reactor and this equipment met the needs of this work with effectiveness.
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Nina, Diogo Anthony. "Hétérocycles fluorescents pour la détection des protéines carbonylées associées au vieillissement et à l’inflammation." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS355.
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Les travaux présentés dans ce manuscrit décrivent la synthèse de nouvelles sondes fluorescentes pour le marquage des protéines carbonylées. Dans une première partie, la synthèse de nouvelles molécules fluorescentes à base 1,2,4-triazoles 1,3,5-trisubstitués est décrite à partir des 4H-pyrido[e][1,3]oxazin-4-ones. L’étude photophysique des 1,2,4- triazoles dans plusieurs solvants a permis de mettre en évidence un mécanisme de fluorescence de type ESIPT induisant un large déplacement de Stokes (jusqu’à 250 nm). La deuxième partie de ce manuscrit est consacrée à la synthèse de nouveaux BODIPY avec une fonction hydrazide. Enfin, la dernière partie décrit les applications de ces nouveaux BODIPY en tant que marqueurs des protéines carbonylées, utilisable avec la 2D-Oxi DIGE, la microscopie à fluorescence et la cytométrie en fluxThe works presented in this manuscript describe the synthesis of new fluorescent probes for protein labelling. In a first part, the synthesis of new fluorescent molecules 1,2,4-triazoles based 1,3,5-trisubstituted is described from 4H-pyrido[e][1,3]oxazin-4-ones. The photophysical study of 1,2,4-triazoles in several solvents allowed to highlight a fluorescence ESIPT type mechanism leadingto a wide Stokes’shift (close to 250 nm). The second part of this manuscript is dedicated to the synthesis of new BODIPY with a hydrazide function. Finally, the last part describes the applications of these new BODIPY as fluorescent probes for carbonylated proteins labelling, used in 2D - Oxi DIGE, fluorescence microscopy and flow cytometry
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Abdelhedi, Miladi Imen. "Synthèse et caractérisation de nouveaux polymères à structures norbornadiène et triazolium pour le stockage et la conversion de l'énergie." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10348/document.
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L'objectif de cette thèse est d'appliquer la réaction de cycloaddition-1,3-dipolaire catalysée par le Cu(I) entre un alcyne et un azoture (CuAAC) pour la synthèse de nouveaux polymères utilisables pour le stockage d'énergies alternatives. Dans une première partie, la polyaddition par CuAAC de type AA+BB a été étudiée à partir de plusieurs monomères difonctionnels afin d'obtenir des poly(1,2,3-triazole)s à structures norbornadiènes. Grâce à un réarrangement structural régi par une irradiation photochimique, le norbornadiène au sein du polytriazole est transformé en quadricyclane qui est une molécule capable de stocker l'énergie solaire. Dans une deuxième partie des polymères linéaires à motif 1,2,3-triazole ont été obtenus à partir de monomères hétérofonctionnels α-azoture-ω-alcyne. La modification chimique post-polymérisation de ces poly(1,2,3-triazole)s (quaternisation du noyau 1,2,3-triazole suivie d'un échange anionique) a permis d'obtenir de nouveaux poly(liquide ionique)s à base 1,2,3-triazolium (TPILs). Différents TPILs ont été obtenus et leurs propriétés de conductivité ionique ont été étudiées par spectroscopie diélectrique. Enfin, la synthèse d'un poly(1,2,3- triazolium) photoréticulable a permis, lors d'un processus de photolithographie, de servir en tant que résine photosensible à tonalité négative ce qui a conduit pour la première fois à la structuration d'électrolytes solides à l'échelle du micronThe present work aims at elaborating new polymers by copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) step growth polymerization suited for the storage of alternative energies. In a first part, the AA+BB CuAAC polyaddition has been investigated using several difunctional monomers to prepare norbornadiene-containing poly(1,2,3-triazole)s. The norbornadiene units present in the main chain of these polymers are isomerized after UVirradiation into quadricyclane units able to store solar energy. In a second part, other linear poly(1,2,3-triazole)s were prepared from α-azide-ω-alkyne heterofunctional monomers. The post-polymerization chemical modification of these poly(1,2,3-triazole)s (quaternization of the 1,2,3-triazole units followed by anion metathesis reaction) resulted in new 1,2,3-triazolium-based poly(ionic liquid)s (TPILs). Various TPILs were obtained and their ionic conductivity properties were studied by dielectric spectroscopy. Finally, a UV-crosslinkable poly(1,2,3-triazolium) was synthesized and was used as a negative tone photoresist for lithography thus affording the efficient patterning of solid electrolytes
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Hug, Stephan. "Covalent triazine frameworks." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-185677.
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Reynaud, Patricia. "Analyses des résidus d'une triazole dans l'alimentation." Aix-Marseille 1, 1991. http://www.theses.fr/1991AIX11391.
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L'analyse de la polarite du triadimenol, a permis la selection de solvants et de techniques de purification a tester. Grace a ses capacites de separation, la clhp semi-preparative s'est averee etre la technique la plus appropriee pour la purification des residus de triadimenol au sein de differents vegetaux. Elle a fait preuve de fiabilite et de reproductibilite. Cette methode a ete eprouvee sur une vingtaine de substrats aussi bien frais que cuits. Nous obtenons globalement un rendement de recuperation oscillant entre 90-98% avec une limite de quantification moyenne 155 fois inferieure aux limites maximales de residu en vigueur. Apres adaptations, cette methode a ete eprouvee sur deux autres triazoles: diniconazole et la dichlobutrazol. Les resultats sont similaires a ceux obtenus pour le triadimenol. Par ailleurs, l'etude sur la stabilite thermique du triadimenol nous permet d'affirmer que cette molecule est relativement stable et que l'ordre de la reaction s'ordonne vers un etat d'equilibre. Par comparaison entre les resultats obtenus sur les substrats et sur l'eau, nous avons observe une plus grande disparition dans le premier cas. Outre une degradation plus importante, un phenomene d'adsorption sur le substrat et de formation de metabolites pourraient avoir lieu. S'il reste au sein de notre alimentation des traces de residus de triadimenol, il n'en subsiste plus apres cuisson. En revanche, il serait inquietant de rencontrer de fortes concentrations dans notre alimentation, sachant experimentalement que la possibilite de disparition du triadimenol diminue quand sa concentration augmente
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Журавель, Карина Олегівна. "The ocute toxicity of 1,2,4-triazole derivatives." Thesis, Київський національний університет технологій та дизайну, 2017. https://er.knutd.edu.ua/handle/123456789/7369.
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Barchi, Tobia. "Synthesis and characterization of heteroleptic Cu(I) complexes based on quinolin-yl-1,2,3-triazole and pyridin-yl-1,2,3 triazole." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amslaurea.unibo.it/20680/.
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The present work is part of a research project that involves the study of new copper based complexes to be employed as photosensitizer in carbon dioxide photoreduction reaction. My research project is focused on the synthesis and characterization of 1,2,3 triazoles with a quinoline or pyridine in the lateral chain, which have been successively utilized to synthesize heteroleptic Cu(I) complexes. Redox potential and photophysic properties have been studied.
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Probst, Katrin. "Synthese von neuartigen alpha-Aminosäuren sowie Analytik elektrochemisch erzeugter, trisubstituierter 1,2,4-Triazole." [S.l. : s.n.], 2003. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10790801.
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Yu, Yanhua. "Synthesis and properties of triazole-containing fluorescent molecules." Thesis, Cachan, Ecole normale supérieure, 2013. http://www.theses.fr/2013DENS0028.
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Cette thèse se concentre sur le design et la synthèse de molécules fluorescentes contenant un motif triazole et un squelette benzothiadiazole (BTD), coumarine, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacène (BODIPY) ou dicyanométhylène-4H-pyran (DCM) par chimie "click" et l’étude de leurs propriétés et applications en biologie et en chimie analytique. Dans le but de synthétiser des peptides fluorescents et d'étudier leurs applications, des acides aminés fluorescents contenant BTD, coumarine et BODIPY ont été préparés par réaction "click", et incorporés dans la somatostatine par synthèse peptidique en phase solide. Les peptides fluorescents synthétisés pourront être utilisés pour le développement d'un test de "binding" des analogues de la somatostatine. Des dérivés de BTD et BODIPY ont également été conçus et synthétisés pour servir de mimes de coudes beta- qui conduisent à des peptides courts qui pourraient être facilement détectés et étudiés en utilisant des techniques de fluorescence. La capacité des composés obtenus à former des liaisons hydrogène intramoléculaires a été étudiée par spectroscopie infrarouge. En outre, une série de macrocycles à base de BODIPY contenant un C-glucopyranoside conjugué ou non à des acides aminés tels que glycine, acid aspartique ou méthionine ont été synthétisés avec succès en utilisant une réaction "click" comme étape de macrocyclisation. Certains des composés synthétisés présentent des propriétés de reconnaissance sélective vers Cu2+, Fe3+, F- et CN- dans l'acétonitrile. Enfin, un nouveau capteur fluorescent, qui est capable de reconnaître les cations et anions d'une manière coopérative, a été conçu et synthétisé par chimie "click". Ce composé est très sensible à des combinaisons de Cu2+, F- et / ou Br- d’une manière séquence- et halogénure-dépendanteThis thesis is focused on the design and synthesis of triazole-containing fluorescent molecules based on benzothiadiazole (BTD), coumarin, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) or dicyanomethylene-4H-pyran (DCM) by “click” chemistry and investigation of their properties and applications in biology and analytical chemistry. In the aim to synthesize fluorescent peptides and investigate their applications, fluorescent amino acids containing BTD, coumarin and BODIPY were prepared by “click” reaction, and incorporated into somatostatin through solid phase peptide synthesis. The resulting fluorescent peptides could be used for the development of a binding assay for somatostatin analogues. BTD and BODIPY derivatives have also been designed and synthesized to act as beta-turn mimics which lead to short conformationally restricted peptides that could be easily detected and studied using fluorescence techniques. The ability of the synthesized compounds to form intramolecular hydrogen bond was studied by infrared spectroscopy. Moreover, a series of BODIPY-based macrocycles containing a C-glucopyranoside conjugated or not with various amino acids such as glycine, aspartic acid or methionine have been successfully synthesized by using “click” reaction as the macrocyclization step. Some of the synthesized compounds exhibited selective recognition properties towards Cu2+, Fe3+, F- and CN- in acetonitrile. Finally, a new fluorescent sensor, which has the ability to recognize cations and anions in a cooperative way, was designed and synthesized by “click” chemistry. This compound was highly sensitive to combinations of Cu2+, F– and/or Br– in a sequence- and halide-dependent way
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Maingot, Mathieu. "Conception et synthèse de ligands peptidomimétiques du récepteur de la ghréline." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTS110.
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La ghréline est une hormone de 28 acides aminés, synthétisée principalement par l'estomac. D'abord identifiée comme un sécretagogue de l'hormone de croissance, elle joue également un rôle central dans la prise alimentaire, la glycémie ainsi que dans certains processus liés à l'addiction. Ces effets sont médiés par un récepteur couplé aux protéines G : le GHS-R1a (Growth Hormone Secretagogue Receptor). Ce récepteur possède une activité constitutive élevée et un réseau de signalisation intra-cellulaire relativement complexe via l'activation de β-arrestines et de différentes isoformes de protéines G (Gq, Gi/o, G12/13). Compte tenu de ces multiples effets, les ligands du GHS-R1a présentent un intérêt thérapeutique certain.Cette thèse est consacrée au développement d'antagonistes et d'agonistes inverses du hGHS-R1a, dont la structure est basée sur le motif 1,2,4-triazole 3,4,5-trisubstitué. Grâce à une étude successive des différents substituants de cette plateforme peptido-mimétique nous avons identifié des antagonistes d'affinités nanomolaires ainsi que des agonistes inverses possédant une efficacité significative. Ces composés paraissent donc être des candidats intéressants pour des études in vivo sur des modèles de prise alimentaire ou d'addiction. D'autre part, une étude pharmacologique sophistiquée, menée sur nos composés, a démontré qu'il est possible d'obtenir des ligands biaisés sur la base du motif triazole. Ces résultats fournissent de nouvelles informations sur la sélectivité fonctionnelle du GHS-R1a. Ainsi, associés à des études in vivo complémentaires, ces données pourraient être précieuses pour la conception de nouveaux médicaments possédant des effets secondaires limitésGhrelin is a hormone of 28 amino acids, mostly synthesized in the stomach. Firstly identified as a growth hormone secretagogue, this peptide is also involved in food intake, blood glucose and in some processes related to addiction. Ghrelin effects are mediated by a G protein-coupled receptor: GHS-R1a (Growth Hormone Secretagogue Receptor). This receptor has a high constitutive activity and a complex intra-cellular signaling network via the activation of β-arrestin and different isoforms of G protein (Gq, Gi / o, G12 / 13). Given these multiple effects, ligands of GHS-R1a have a therapeutic interest.This thesis is devoted to the development of antagonists and inverse agonists of hGHS-R1a whose structure is based on the 3,4,5-trisubstituted 1,2,4-triazole scaffold. Thanks to a successive study of the various substituents of the peptidomimetic platform we identified antagonists with nanomolar affinity and inverse agonists with a significant efficiency. These compounds appear to be attractive candidates for in vivo studies on food intake or addiction models. On the other hand, a sophisticated pharmacological study, conducted on our compounds, has demonstrated that it is possible to obtain biased ligands based on the triazole motif. These results provide new informations about the functional selectivity of GHS-R1a. Thus, these data, combined with additional in vivo studies, could be useful for the design of new drugs with limited side effects
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Hartley, David John. "Thieniomidazoles, thieno-extended purines and related triazole systems." Thesis, University of Salford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299149.
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Tazioli, Lia Ashley Maria. "Synthetic approaches to novel, Triazole-containing Oligonucleotide analogues." Thesis, Heriot-Watt University, 2010. http://hdl.handle.net/10399/2442.
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The work reported in this thesis focuses on the development of synthetic approaches to prepare novel triazole-containing nucleic acid (TCNA) monomers for subsequent incorporation into oligomers. The triazole moiety was designed to be prepared using “click chemistry”. Initial studies involved development of viable synthetic pathways for preparation of both the required azide component, derived from L-serine methyl ester and the nucleobase-containing alkyne component. The azide has been successfully synthesised from either protected or unprotected L-serine methyl ester by direct diazotransfer employing the novel ‘diazo donor’, imidazole-1-sulfonyl azide 152. Synthesis of the four protected nucleobase-containing alkyne components has been achieved in overall yields ranging from 55-89%. The key step involved alkylation of the appropriately protected nucleobase with propargyl bromide. A series of model ‘click’ reactions were performed in which it was found that the best yields of triazole products were obtained using CuSO4·5H2O and sodium ascorbate in a 1:2 ratio. These conditions have been applied to the ‘click’ reaction employing the thymine alkyne component 161 and L-serine derived azide 158 to afford the desired thymine-derivatised triazole product 246 in a 44% yield. Preliminary studies into converting the resulting triazole compound into the required phosphoramidite thyminyl TCNA monomer 252 have been undertaken.
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Guérin, Charles. "Synthèse et valorisation de ligands dipyrrométhène bis-triazole." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1254/document.
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Analogues structuraux des porphyrines et des Salens, des ligands de type dipyrrométhène bis-phénol ont été étudiés dans notre groupe, notamment sous forme de complexes pour la catalyse d'oxydation. L'activité catalytique de ces complexes étant faible, il a été proposé de remplacer les phénols par des triazoles. L'objet de cette thèse était d'étudier et de valoriser une nouvelle famille de ligands dipyrrométhène bis-triazole.Plusieurs voies de synthèse ont d'abord été étudiées et optimisées pour accéder à ces nouveaux ligands. Nous nous sommes attachés ensuite à valoriser ces nouveaux ligands selon plusieurs axes.Un de ces ligands a été testé en reconnaissance d'anions, ainsi que les dérivés monotriazolium et bis-triazolium. Les triazoliums ont également permis l'accès à des métallocomplexes carbéniques, qui ont été étudiés.Par ailleurs, les métallocomplexes des dipyrrométhène bis-triazole ont été préparés et caractérisés, y compris par électrochimie. Des essais d'utilisation en oxydation ont été entrepris. Enfin, la synthèse de BODIPYs® liposolubles et hydrosolubles a été réalisée. Les propriétés optiques ont été mesurées puis ces dérivés fluorescents ont été testés pour le marquage fluorescent de cellules HeLaKnown as structural analogues of porphyrins and Salens, dipyrromethene bis-phenol-type ligands have been studied in our group, especially as complexes for oxidation catalysis. Due to the poor catalytic activity of these complexes, it has been proposed to replace the phenol moieties with triazoles. The purpose of this thesis was to study and develop a new family of dipyrromethene bis-triazole ligands.Several synthetic routes were first investigated and optimized to reach these new ligands. We then have endeavoured to add value to these new ligands along several lines.The ligand has been tested in anion recognition, as well as monotriazolium and bis-triazolium derivatives. The triazoliums also allowed access to carbene metallocomplexes that were studied.Furthermore, dipyrromethene bis-triazole metallocomplexes were prepared and characterized, notably by electrochemistry. Oxidation catalysis tests were undertaken.Finally, the synthesis of liposoluble and hydrosoluble BODIPYs® was performed. Their optical properties were measured and these fluorescent derivatives were tested for the fluorescent labeling of HeLa cells
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Iikawa, Shinya. "Conception d'agents antipaludiques autour du motif γ-hydroxy-γ-lactame : synthèses et évaluation biologique." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10172.
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La recherche de nouvelles molécules pour le traitement du paludisme est un domaine de recherche toujours d'actualité. L'émergence de résistance aux différents agents antipaludiques de première génération (chloroquine, quinine, mefloquine) est un grave problème dans les zones endémiques nécessitant un effort soutenu pour pouvoir proposer un nouveau traitement en combinaison avec des dérivés de l'artemisinine. Le présent projet s'inscrit dans cet effort avec comme souci de proposer une nouvelle famille de molécules simple d'accès, à faible coût et si possible avec un mécanisme d'action original. Nous nous sommes plus particulièrement intéressés à des dérivés de type γ-hydroxy-γ-lactame car ce motif n'est que très peu étudié dans la conception d'agents antiparasitaires bien que présent dans un certain nombre de molécules d'origine naturelle et il offre également la possibilité d'un certain nombre de variations structurales. La synthèse de ce type de structures utilise l'acide tétronique comme réactif de départ commercial, permettant dans un premier temps d'accéder en 3-4 étapes à des γ-lactones insaturées en série tétronique; de nombreuses modifications chimiques autour de ce motif ont été proposées à partir d'une séquence alkylation ou benzylation, aldolisation, et déshydratation. L'introduction de motifs halogénés sur ce type de structures permet ensuite d'accéder, après différents couplages catalysées au palladium (Sonogashira, Stille et Suzuki-Miyaura) à une grande diversité de composés ; également une ouverture vers des dérivés d'acides tétroniques possédant un motif 1,2,3-triazole à partir d'une réaction de cycloaddition 1,3-dipolaire catalysée au cuivre est présentée. Les différentes γ-lactones insaturées en série tétronique sont ensuite mises en réaction en présence de différentes amines afin de construire le cycle γ-hydroxy-γ-lactame ; les amines sont soient des dérivés de la 7-chloro-4-amino quinoléine ou des amines aliphatiques, allyliques, propargyliques, benzyliques le plus souvent commerciales. Une famille possédant un motif énaminone trifluorométhylée a également été synthétisée car ce motif peut apporter une diversité supplémentaire et la possibilité d'accéder à des complexes métalliques. Des amines portant le motif ferrocène ont été également utilisées. Plus de 80 molécules ont pu être ainsi obtenues et les activités in vitro sur deux souches de P.falciparum (3D7 et W2) ont révélées que les molécules possédant le motif 7-chloro-4-aminoquinoléine étaient en général aussi actives que la chloroquine, voire même plus actives (CI50 proches de 20 nM) avec des indexes de résistance de l'ordre de 1.0-3.5, ne présentaient pas de cytotoxicité (HUVEC) jusqu'à 50 μM et présentaient une stabilité à pH 5.2 et 7.4 pendant 48 heures. Les molécules ne possédant pas le motif présent dans la chloroquine ont démontré des activités plus élevées que la chloroquine avec pour les meilleures des CI50 proches de 10-50 μM ; les γ-hydroxy-γ- lactame-énaminones possédant un motif redox et les γ-hydroxy-γ-lactame incorporant le motif ferrocène sont, par contre, les molécules les plus actives avec des têtes de séries ayant des CI50 proches de 50 à 600 nM. Elles sont également non-cytotoxiques jusqu'à 50 μM. Le mécanisme d'action des têtes de série n'est pas encore connu, ni d'ailleurs l'efficacité in vivo sur un modèle murinThe search for new molecules for the treatment of malaria is still one of important reserch fields. The emergence of resistance to different first-generation antimalarial agents (chloroquine, quinine, mefloquine) is a serious problem in endemic areas requiring sustained effort to be able to offer new treatments in combination with artemisinin derivatives. This project is part of this effort with concern as to propose a new family of molecules which are easy access, low cost and if possible with a novel mechanism of action. We are particularly interested in type derivatives γ-hydroxy-γ-lactam because this pattern is only very little attention in the design of antiparasitic agents that present in a number of naturally occurring molecules and also offers the possibility of a number of structural variations. The synthesis of this type of structures using commercially available tetronic acid initially starts to access to unsaturated γ-lactones (γ-ylidenetetronates) in 3-4 steps, many structure analogues have been proposed from an alkylation or benzylation sequence, aldol and dehydration. The halogenations on such structures then allows access for various palladium-catalyzed coupling (Sonogashira, Stille and Suzuki-Miyaura) with a wide variety of compounds, also an opening to the tetronic acid derivatives having a 1,2,3-triazole moiety from copper catalyzed 1,3-dipolar cycloaddition is shown. Different unsaturated γ-lactones in tetronic series are then reacted with different amines in order to build γ- hydroxy-γ-lactam ring; amines are either derivatives of 7-chloro-4-amino quinoline, aliphatic, allyl, propargyl, benzyl amines, which are usually commercially available. A family with an enaminone with trifluoromethyl moiety were also synthesized for the reason of these can provide additional diversity and the possibility of accessing metal complexes. Amines with the ferrocene moiety ere also used for the lactamization. Thus, more than 80 molecules have been obtained and in vitro activities of two strains of P. falciparum (3D7 and W2) have revealed that molecules with 7-chloro-4-aminoquinoline pattern were generally as active as chloroquine, even more active (IC50 around 20 nM) with better resistance index (1.0-3.5), showed no cytotoxicity (HUVEC) up to 50 μM and showed stability at pH 5.2 and 7.4 for 48 hours. The molecules do not have chloroquine moiety showed less activity than chloroquine with the best IC50 around 10-50 μM, the γ-hydroxy-γ-lactam-enaminones with a redox motif and γ-hydroxy-γ- lactam having ferrocene moiety are the most active seed molecules with IC50 around 50 to 600 nM. They are also non-cytotoxic up to 50 μM. The mechanism of action of seeds is not yet known, nor in vivo efficacy in a mouse model
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Gonnet, Lori. "Mécanosynthèses organiques : étude cinétique de la réaction de Diels-Alder et synthèses de 1,2,4-triazoles à activités biologiques." Thesis, Ecole nationale des Mines d'Albi-Carmaux, 2019. http://www.theses.fr/2019EMAC0011.
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Ce projet de thèse vise à développer des procédés verts en utilisant la mécanochimie pharmaceutique. Il comporte deux volets imbriqués. Tout d’abord, le mécanisme de la réaction de Diels-Alder par mécanochimie en comparaison avec la réaction en milieu liquide a été étudié. L’impact des paramètres du procédé pour un broyeur vibrant a été évalué. Le matériau, la taille et la masse de la bille de broyage ont été étudiés, ainsi que la température de broyage, ce qui a permis le calcul de l’énergie d’activation apparente (Ea). Par ailleurs, différentes voies de synthèses de dérivés 1,2,4-triazoles par mécanochimie ont été développées. Les activités biologiques de ces composés contre M. Tuberculosis ont été évaluées. Cette thèse vise à poser les bases de futurs changement d’échelle de procédés verts mécanochimiques, en approfondissant les mécanismes, afin d'énoncer des règles de portée générale. Cette thèse bénéficiant d'une aide de la Région Occitanie s'appuie sur la synergie de compétences complémentaires des laboratoires RAPSODEE (Albi) et SPCMIB (Toulouse)This thesis project aims at developing green processes by medicinal mechanochemistry. It contains two parts. First, the Diels-Alder reaction mechanism using mechano-chemistry in comparison with the reaction in solvent medium was studied. The impact of process parameters for a vibratory ball mill was assessed. Grinding material, size and mass of the balls were studied, as well as the temperature of the milling media, providing apparent activation energy (Ea). In addition, different pathways for the synthesis of 1,2,4-triazole derivatives using mechanochemistry were developed. The biological activities of these compounds against M. Tuberculosis were evaluated. This thesis aims to lay the foundations for future scaling-up of green mechanochemical processes, analyzing the mechanisms, in order to formulate rules of general scope. This thesis, supported by the Occitanie Region, is based on the synergy of complementary skills of RAPSODEE (Albi) and SPCMIB (Toulouse) laboratories
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Vasconcelos, Stanley Nunes Siqueira. "Síntese de 5-organoteluro-1H-1,2,3-triazóis-1,4-dissubstituídos, funcionalização via reação de acoplamento cruzado de Sonogashira e síntese one-pot de derivados do indol-3-glioxila e indol-3-glioxil-1,2,3-triazóis." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-16012014-141941/.
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No capítulo 1 apresentamos uma síntese eficiente de compostos 5-organoteluro-1H- 1,2,3-triazóis realizada via reação de cicloadição [3+2] entre azidas orgânicas e alquinos substituídos com organotelúrio. Além disso, os 5-organoteluro-1H-1,2,3-triazóis foram funcionalizados na posição 5 do anel triazólico por reação de acoplamento cruzado de Sonogashira. A regioquímica dos produtos de cicloadição foram descritas com base em experimentos de RMN, cálculos teóricos e cristalografia de raio-x. Apresentamos uma proposta mecanística para a cicloadição mediada por cobre, baseada em experimentos de espectrometria de massas de alta resolução. No capítulo 2, investigamos a eficiência de reações one-pot com indol, cloreto de oxalila e diferentes nucleófilos para obtermos derivados do indol-3-glioxila em condições adequadas. Do mesmo modo, envolvendo a adição de azidas orgânicas, levando à síntese de indol-3-glioxil-1,2,3-triazóis, os produtos foram obtidos com rendimentos que variaram de 59 a 85%.In chapter 1 we present an efficient synthesis of 5-organotelluro-1H-1,2,3-triazole compounds that was accomplished via the [3+2]-cycloaddition reaction of organoazides and organotelluro alkynes. Additionally, 5-organotelluro-1H-1,2,3-triazoles were readily functionalized at the 5-position via the Sonogashira cross-coupling reaction, leading to highly functionalised triazoles. The regiochemistry of the products was assessed by bidimensional NMR experiments, theoretical calculations and x-ray crystallography. We presented a mechanistic proposal for the cycloaddition mediated by copper, based on high resolution mass spectrometry experiments. In chapter 2 we investigated a general and efficient reaction of indole with oxalyl chloride and nucleophiles providing indole-3-glyoxyl derivatives which has been developed in mild conditions. In the same fashion, the other reaction involved the addition of organic azides leading to the synthesis of indole-3-glyoxyl-1,2,3-triazoles, which proceeds smoothly generating the products in moderate to high yields.
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Le, Falher Laetitia. "Préparation et dérivatisation de 4H-pyrido[e][1,3]oxazinones : une contribution à la diversité chimique." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066344.
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Ce manuscrit porte sur la synthèse et les applications d'une nouvelle série de composés hétéroaromatiques : les 4H-pyrido[e][1,3]oxazin-4-ones. La première partie de ce manuscrit présente la préparation de ces squelettes via une réaction d'O-arylation intramoléculaire. La seconde partie du manuscrit repose sur la réactivité de ces entités chimiques et de leur utilisation en tant qu'intermédiaires de synthèse. La fonctionnalisation des 4H-pyrido[e][1,3]oxazin-4-ones, via des réactions de couplage pallado-catalysées, a permis d'obtenir des systèmes polyfonctionnalisés plus complexes. Les pyrido-oxazinones ont également été transformées, en une étape, en divers petits hétérocycles d'intérêt : les 1,3,5-triazines, les 1,2,4-triazoles et les 1,2,4-oxadiazoles. La dernière partie du manuscrit est consacrée à l'utilisation des molécules synthétisées comme potentielles sondes fluorescentes pour la détection de protéines oxydéesThis work focused on the synthesis and applications of a novel series of heteroaromaticcompounds: the 4H-pyrido[e][1,3]oxazin-4-ones. The first part of this thesis presents thepreparation of these pyrido-oxazinones via an intramolecular O-arylation reaction. The secondpart of this work relies on the reactivity of these chemical entities and their use as buildingblocks. The functionalization of the 4H-pyrido[e][1,3]oxazin-4-ones has been studied viacross-coupling reactions to obtain more elaborated structures. The pyrido-oxazinones werealso converted, in one step, into other diverse small molecules of interest: 1,3,5-triazines,1,2,4-triazoles and 1,2,4-oxadiazoles. The last part of this thesis was devoted to the use of theobtained heterocycles as potential fluorescent probes for the detection of carbonylatedproteins
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Angell, Yu Li. "Triazole based peptidomimetics for mimicking protein-protein hot spots." [College Station, Tex. : Texas A&M University, 2007. http://hdl.handle.net/1969.1/ETD-TAMU-1432.
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Ozkal, Erhan. "Triazole-based ligands for click chemistry and asymmetric catalysis." Doctoral thesis, Universitat Rovira i Virgili, 2013. http://hdl.handle.net/10803/128207.
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In this thesis, different approaches for the application of click chemistry to the preparation of catalysts and ligands are developed. Several strategies towards the use of 1,2,3-triazoles from copper-catalyzed azide-alkyne cycloaddition(CuAAC) reaction as click ligands are explored. Mainly, 1,2,3-triazole is used as donor groups for transition metal complexes in metal-catalyzed reactions, following on the simplicity of the synthetic route.
In particular, CuAAC reaction is used to synthesize triazole-based ligands and later, for the first part of the project, tris(triazolyl)methanol•copper(I) chloride complexes are used in order to catalyze CuAAC very efficiently, on water, neat, under microwave irradiation and in organic solvents. Under all optimized conditions excellent yields are obtained. Then, the covalent immobilizations of these ligands are succeeded onto Merrifiled resin with 5 reuses and a broad functional group tolerance.
In the second part of the thesis, triazole-based ligands are further developed for metal-catalyzed asymmetric transformations. Particularly, for molybdenum-catalyzed asymmetric allylicalkylations excellent enantio- nadregio-selectivities are achieved both under conventional and microwave assisted conditions with a very broad scope.
Finally, ligands for enantioselective copper-catalzyed conjugate addition of diethylzinc are established under optimized conditions very good conversion are obtained albeit moderate ee.
In general, the metal/triazole-based ligand complexes are used as catalysts in CuAAC reaction and catalytic asymmetric transformations.En este trabajo se pretende desarrollar diferentes aproximaciones para la aplicación de “clickchemistry” a la preparación de catalizadores y ligandos. Así, se han explorado diferentes estrategias para una ruta sintética “click” que dé acceso a compuestos útiles en este campo, incluyendo cicloadiciones 1,3–dipolares. Principalmente, el 1,2,3-triazol se utiliza como grupo dador para los complejos de metales de transición en reacciones catalizadas por metales. Así, se presenta la ruta más sencilla para la síntesis de cada ligando. En general, los complejos de metal / ligando se utilizan como catalizadores para CuAAC y transformaciones asimétricas catalíticas.
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Radies, Hendrik. "Tetrazole und Triazole als neuartige Oxidationsmittel in IR-Täuschkörpern." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-113956.
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Dippold, Alexander. "Nitrogen-rich energetic materials based on 1,2,4-triazole derivatives." Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-161426.
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Kracker, Oliver [Verfasser]. "Synthesis and Application of Triazole Containing Peptidomimetics / Oliver Kracker." Bielefeld : Universitätsbibliothek Bielefeld, 2019. http://d-nb.info/1191896447/34.
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Merlos, Romain. "Development of Triazole-based Dry Powder Formulations for Inhalation." Doctoral thesis, Universite Libre de Bruxelles, 2019. https://dipot.ulb.ac.be/dspace/bitstream/2013/289299/5/these.pdf.
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Among the different pulmonary fungal infections, aspergillosis, and in particular invasive pulmonary aspergillosis (IPA), are becoming the most worrying diseases in immunocompromised patients. This is due to their high incidence and mortality. Indeed, invasive aspergillosis manifests as invasive pulmonary disease accounting for 50/60% of all cases, with a mortality of 50-90% in severely immunocompromised patients. Triazoles act by inhibiting 14-α demethylase, a fungal cytochrome P450 enzyme implicated in the synthesis of ergosterol, an essential constituent of fungal cell walls. Moreover, they interact with the same cytochrome present in large quantities in the human liver, inducing possible drug-drug interactions in IPA patients. Consequently, interactions resulting from inhibitors, inductors, or substrates of cytochromes can modify the plasmatic concentrations of triazoles or other drugs administered concomitantly. To overcome these important issues, pulmonary delivery of triazoles could be an interesting alternative to conventional routes.The aim of this work was to develop triazole-based dry powders for inhalation able to be deposited adequately in the lungs, with a release of drug and a lung retention that can optimize its pharmacological action. This work focused on two active pharmaceutical ingredients (API): itraconazole (ITZ), for which improved solubility was needed, and voriconazole (VCZ), for which slow release was required.Concerning ITZ, solid dispersions for inhalation (SDIs) comprising ITZ and mannitol were previously developed in our laboratory. The selected SDI showed interesting results in terms of improved dissolution and lung retention in vivo in mice during a pharmacokinetic study. Therefore, this SDI was tested in a murine preclinical model of IPA and showed promising results in terms of prophylaxis efficacy. One aim of this work was to continue the pharmaceutical development of this promising SDI by making a scaling-up study. These methods were intended to improve the SDI’s ecological footprint and productivity by increasing the production yield and decreasing the amount of solvents and time used in its manufacture. During the first step of this study, the obtained SDI showed interesting results obtaining similar powder characteristics (i.e. amorphous content, aerodynamic performance, and dissolution profiles) from concentrated solutions using a laboratory-scale spray-dryer B-290 (Büchi, Switzerland) before using a pilot-scale spray-dryer (GEA Niro, Denmark). Then, the upscaling was performed on the pilot spray-dryer allowing the production of SDIs with increased productivity (yield and process duration). These SDIs had similar powder characteristics than the optimized lab-scale SDIs. During the second part of this work we developed VCZ based dry powder for inhalation. The aim was to slow down the release of this highly permeable and very slightly soluble API and to prolong its lung residence. To this end, various lipidic excipients were chosen. The selection took into account the potential good pulmonary tolerance of the lipids and their hydrophobicity to evaluate their ability to slow down the VCZ release (FPFs 20-25%, slowed release up to 24h, burst effect of ± 58% of VCZ dissolved within 30min). Immediate-release SDIs were also developed to have a comparator reference for the pharmacokinetic and efficacy studies (FPFs of 40%).Then, a pharmacokinetic study in mice was performed following the pulmonary administration of one immediate-release and two sustained-release SDIs (with or without PEG excipient). With an 80-fold higher pulmonary exposure over 24 hours, the slow-release SDIs presented a real interest compared to the immediate-release SDI. Moreover, in accordance with these results, VCZ plasma exposure following the administration of the SDI with PL90-H was more than 1.5-fold higher than its pulmonary exposure (AUC0-24 of 8.70 µg.h/g in the lungs and 14.70 µg.h/mL in the plasma). The slow-release formulations presented plasma exposures at least 15 times lower than their pulmonary exposures (AUC0-24 in lung of 741.40 and 686.85 µg.h/g vs plasmatic AUC0-24 of 37.44 and 42.81 µg.h.mL, respectively with and without PEG excipient). Moreover, the presence of PEG excipient did not influence the residence time and the exposure of the VCZ within the lungs. Finally, the sustained-release SDIs administration by inhalation led to VCZ lung and plasma concentrations higher than the minimal inhibitory concentration (MIC) of VCZ against Aspergillus fumigatus (1 μg/mL) over 24 h. Finally, a murine model of IPA was developed in our lab. The immunosuppression model was fixed and performed by the intraperitoneal (IP) injection of corticosteroids to induce a neutropenia state. Then, different doses of spores (from 1.10^4 to 5.10^6 spores) were inoculated to the neutropenic mice via an endotracheal instillation and the survival rate of each group was observed. Unfortunately, the survival rate resulting from the different infections were not reproducible. Therefore, these models were not suitable to conduct the efficacy study. This underlined the link between the immunosuppressive model and the infection. Indeed, the IPA murine model should be developed according to the immune state of the animal, the Aspergillus conidia species and its concentration to be used.Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie)
info:eu-repo/semantics/nonPublished
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Murrell, Derek, John B. Bossaer, Ronald Carico, Sam Harirforoosh, and David Cluck. "Isavuconazonium Sulfate: A Triazole Prodrug for Invasive Fungal Infections." Digital Commons @ East Tennessee State University, 2016. https://doi.org/10.1111/ijpp.12302.
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Objective: To review the place in therapy of isavuconazole, the active metabolite of isavuconazonium sulfate, via a review of the available literature on drug chemistry, spectrum of activity, pharmacokinetic/pharmacodynamic profile and trials assessing clinical efficacy and safety.
Methods: Relevant data, original research articles and reviews, were gathered primarily through the use of a PubMed database search. The search was conducted without date restrictions in order to collect both historical and recent data regarding isavuconazole.
Key findings: Isavuconazole is a triazole currently approved not only for use in invasive aspergillosis and mucormycosis but also has demonstrable activity against Candida species and other common fungal pathogens. This drug has features which make it more clinically appealing compared to other azoles with similar indications. In specific, isavuconazole does not require a cyclodextrin vehicle due to its water solubility, and at present, does not require therapeutic drug monitoring. Moreover, isavuconazole has displayed improved safety and tolerability compared to voriconazole. Available data from Phase III clinical trials shows isavuconazole to be a possible therapeutic option to currently available therapies for which it is approved; however, clinical conclusions should be reserved until results have been published and more data from clinical use is reported.
Conclusions: Isavuconazole is a new triazole with broad‐spectrum antifungal activity including invasive aspergillosis and mucormycosis.
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Kalenga, J. D. "Studies in 1,2,3-triazine chemistry." Thesis, University of East Anglia, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356612.
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Bastardis, Cristiane Aragão de Souza. "Preparação e Avaliação da Atividade Catalítica de Polímeros de Condensação de Metilpiridinas e Tereftalaldeído em Reações de Nitroaldol e Cicloadição Heterodipolar [3+2]." Universidade do Estado do Rio de Janeiro, 2015. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=8607.
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Nesse estudo, foram preparadas bases poliméricas derivadas de 2,6-dimetilpiridinas e tereftaladeído utilizando a 2,4,6-trimetilpiridina como agente de reticulação. As resinas foram sintetizadas sob aquecimento convencional e purificadas por precipitação em metanol, apresentando rendimentos variando de 59 a 95%. Os copolímeros produzidos foram caracterizados por análise termogravimétrica (TGA), ressonância nuclear magnética de núcleo de hidrogênio (RMN-1H) e espectroscopia na região do infravermelho com técnica de ATR (FTIR - ATR), além de sua atividade básica. A capacidade catalítica do material produzido foi avaliada em reações nitroaldólicas, do tipo Henry, tanto em aquecimento convencional quanto com o uso de reator de micro-ondas. Não sendo observada atividade catalítica significativa para as resinas testadas, nestas reações. O material polimérico produzido também foi testado como suporte para cobre na catálise de reações de cicloadição heterodipolar do tipo [3+2] com benzilazida e propiolato de etila, para a formação de triazóis, processadas em reator de micro-ondas e sob aquecimento convencional. A reação mostrou-se regiosseletiva e processos de reciclo do catalisador se mostrou eficiente em reações consecutivasIn this study, polymeric bases from 2,6-dimethylpyridines and terephthaladehyde using 2,4,6-trimethylpyridine as crosslinking agent were prepared. The resins were synthesized under conventional heating, and purified by precipitation in methanol, with yields ranging 59-95%. The produced copolymers were characterized by thermogravimetric analysis (TGA), proton nuclear magnetic resonance (1H-NMR), infrared spectroscopy by attenuated total reflection (FTIR - ATR) and basic activity. The catalytic ability of the material produced was evaluated in nitroaldol reactions (Henry reactions) as both conventional heating and a microwave reactor. Catalytic activity was not observed for the tested resins in these reactions. The polymeric material produced was also tested as an activator in Heterodipolar [3 + 2] cycloaddition reactions, with benzyl azide and ethyl propiolate to the formation of triazoles, performed in microwave reactor and conventional heating. The reaction proved to be regioselective and recycling processes of the catalyst is efficient in consecutive reactions
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Campagne, Benjamin. "Nouveaux copolymères fluorés porteurs de fonctions azole (imidazole, benzimidazole ou triazole) pour membranes pour piles à combustible (PEMFC) fonctionnant en conditions quasi-anhydres." Thesis, Montpellier, Ecole nationale supérieure de chimie, 2013. http://www.theses.fr/2013ENCM0006.
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Ce travail de thèse s'inscrit dans la continuité des travaux de recherche sur l'utilisation d'hétérocycles azotés pour l'élaboration de membranes échangeuses de protons pour piles à combustible de type PEMFC fonctionnant sous faible taux d'humidité relative (HR < 25 %) et à des températures allant jusqu'à 200 °C pour l'application automobile. Pour cela, trois nouveaux copolymères partiellement fluorés porteurs de trois groupements azole (imidazole, benzimidazole et 1H-1,2,4-triazole) ont été synthétisés et caractérisés. Ils ont ensuite été utilisés pour l'élaboration de membranes polymères (20 µm < épaisseurs < 100 µm) par mélange avec le s-PEEK. Ces membranes sont stables thermiquement jusqu'à 210 °C. Les trois séries de membranes ont été comparées et les meilleurs résultats de conductivité protonique ont été obtenus pour celles contenant le 1H-1,2,4-triazole (σ = 7,0 mS.cm-1, 140 °C, HR < 25 %). Les propriétés mécaniques de ces membranes ont été mesurées et ont montré des valeurs comparables à celles des principales membranes commerciales (de type Nafion®). Afin d'obtenir une meilleure structuration de ces membranes, une stratégie d'élaboration de pseudo réseaux semi-interpénétrés de s-PEEK dans un réseau polymère réticulé a été mise au point. Pour cela, de nouveaux terpolymères porteurs de groupements 1H-1,2,4-triazole et de groupements cyclocarbonate réticulables par la réaction cyclocarbonate / amine ont été synthétisés et caractérisés. Ces terpolymères ont été mélangés à du s-PEEK puis réticulés par une diamine pour former des pseudo réseaux semi-interpénétrés de faibles épaisseurs (20 µm < e < 60 µm) qui ont été caractérisés. Ces membranes à architecture pseudo réseaux semi-interpénétrés ont montré de meilleures propriétés mécaniques mais des valeurs de conductivité protonique légèrement inférieures à celles des membranes non réticulées. Enfin, les membranes réticulées ou non ont été dopées par l'acide phosphorique pour augmenter leurs valeurs de conductivité protonique. Des essais en mono-cellule de PAC de ces membranes dopées ont été effectués et ont montré de bonnes performances. Des estimations par extrapolations des résultats ont ensuite été effectuées à plus hautes températures (140 – 200 °C) et ont montré que les valeurs de conductivité protonique atteignent jusqu'à 210 et 250 mS.cm-1, à 180 et 200 °C, HR < 25 % (valeurs extrapolées). Ces valeurs extrapolées doivent être vérifiées par la réalisation de mesures de conductivité protonique à ces températures (140 – 200 °C)This work concerns the syntheses and characterizations of new proton exchange polymer membranes containing N-heterocyclic compounds for PEMFC working under low relative humidity (HR < 25 %) and temperatures up to 200 °C for automotive applications. Three new partially fluorinated copolymers bearing different azole compounds (imidazole, benzimidazole or 1H-1,2,4-triazole) as pendant groups have been synthesized and characterized. Then, they have been used to synthesize blend polymer membranes with s-PEEK (20 µm < thickness < 100 µm) that showed thermal stabilities up to 210 °C. These new families of membranes have been compared and highest proton conductivity values have been observed for 1H-1,2,4-triazole containing membranes (σ = 7,0 mS.cm-1, 140 °C, HR < 25 %). Mechanical properties and oxidative stability of these membranes have been assessed and showed similar values than main commercially available membranes. To improve membranes structuration, pseudo semi-interpenetrating polymer networks have been synthesized. Thus, original cross-linkable terpolymers bearing 1H-1,2,4-triazole and cyclocabonate functions as pendant groups have been synthesized and blended with s-PEEK as linear polymer to synthesize new polymers membranes (20 µm < thickness < 60 µm). Cross-linking has been carried from the cyclocarbonate/diamine reaction to get pseudo semi-interpenetrated polymer networks. Finally, both pseudo semi-interpenetrated polymer networks and uncross-linked membranes were doped by immersion in phosphoric acid solution to increase proton conductivity of these materials. Single cell fuel cell tests have been carried out and showed good performances. High temperatures (140 – 180 °C) proton conductivity values of these doped membranes have been estimated from extrapolation curves and reached up to 210 and 250 mS.cm-1, at 180 and 200 °C, HR < 25 %, respectively (extrapolated values). Proton conductivity values should be assessed at these targeted temperatures (140 to 200 °C)
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Lima, Milena Moreira. "Síntese de peptídeo modificado contendo grupo 1,2,3-triazol 1,4-dissubstituído." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/60/60138/tde-05092013-135757/.
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Peptídeos são biomoléculas que apresentam extensa variedade estrutural e funcional, atuando em diversos processos biológicos relevantes. Estas moléculas são amplamente utilizadas na terapêutica, constituindo, atualmente, um campo investigativo bastante promissor para o desenvolvimento de novos fármacos, especialmente no desenvolvimento de vacinas sintéticas. Os avanços científicos relacionados às técnicas de identificação, análise e purificação tem estimulado diversas pesquisas na busca por fármacos baseados em peptídeos, os quais podem ser obtidos a partir de fontes naturais ou por métodos químicos (em solução ou em fase sólida), enzimático ou combinação de ambos (semi-síntese) e via tecnologia do DNA recombinante. Entretanto, devido às limitações próprias dos peptídeos naturais, tais como, suscetibilidade proteolítica, toxicidade e baixa biodisponibilidade, torna-se necessária a síntese de peptídeos modificados. Como a função biológica de um peptídeo é definida por sua conformação estrutural, a inserção de modificação em uma estrutura peptídica deve ser capaz de manter ou estabilizar esta conformação estrutural. O desenvolvimento de novas e eficientes rotas de síntese de peptídeos modificados torna-se necessário para superar as limitações relacionadas à suscetibilidade proteolítica, toxicidade e baixa biodisponibilidade, afim de contribuir para novas estratégias terapêuticas, em especial no desenvolvimento de vacinas. Desta forma, a inserção de grupo 1,2,3-triazol tem fornecido propriedades físicoquímicas desejáveis no desenvolvimento de fármacos. O objetivo deste trabalho foi desenvolver um método de síntese de peptídeos contendo grupo 1,2,3-triazol 1,4- dissubstituído, como o peptídeo 1, o qual é constituído por dezesseis resíduos de treonina e um grupo 1,2,3-triazol 1-4-dissubstituído entre os resíduos Thr8 e Thr9 (NH2-(Thr)7-Thr-(ciclo 1,2,3-triazol 1,4-dissubstituído)-Thr-(Thr)7-OH). Adicionalmente, devido à semelhança com mucinas de T. cruzi, as quais apresentam rica composição em resíduos de treonina, 1 poderá ser empregado na preparação de peptideomiméticos destas mucinas e no desenvolvimento de vacinas relacionadas à processos infecciosos causados por T. cruzi. A preparação de 1 envolveu uma associação entre síntese de peptídeo em fase sólida e reações de ciclo-adição azido-alcino 1,3 dipolar catalisada por cobre (I) (CuAAC). Inicialmente, o método utilizado foi padronizado a partir da síntese do modelo dipeptídeo de treonina (8), cuja ligação peptídica foi substituída pelo grupo 1,2,3-triazol 1,4- dissubstituído (NHFmoc-Thr-(ciclo 1,2,3-triazol 1,4 dissubstituído)-Thr-OH). A estratégia via CuAAC conduziu à obtenção do dipeptídeo modificado em excelente rendimento (98%) e permitiu estabelecer as condições a serem empregadas na obtenção do peptídeo mais complexo de cadeia longa 1. A reação de CuAAC gerou o peptídeo 1 com rendimento bruto satisfatório (70%). A obtenção de 1 foi confirmada pela análise de Ressonância Magnética Nuclear de próton (RMN 1H), a qual permitiu identificar a presença do grupo 1,2,3-triazol 1,4-dissubstituído. Adicionalmente, análises posteriores por espectrometria de massas (ESI-MS) sugerem a obtenção do peptídeo 1.Peptides are biomolecules which present great structural and functional variety, acting in several biological processes. These molecules are widely used in therapeutics, and recently represent a very promising field for development of novel drugs, specially on synthetic vaccines. Scientific advances related to identification techniques, analysis and purification stimulate researches in attempt to produce peptides-based drugs, which can be extracted from natural sources or chemically synthesized (in liquid or solid phase), enzymatic process or both (semi-synthesis) and recombinant DNA technology. However, due to limitations concerning natural peptides, such as, proteolytic liability, toxicity and low bioavailability, becomes necessary the synthesis of modified peptides. Being biological function of a peptide defined by its structural conformation, adding a modification in a peptide structure must be able to maintain or stabilize it. The development of novel and efficient synthetic route of modified peptides is necessary to overcome the limitations related to proteolytic liability, toxicity and low bioavailability, to contribute with novel therapeutic strategies, mostly development of vaccines. So, adding a 1,2,3-triazole group can afford desirable chemical-physical properties in drug discovery. The objective was develop a method to synthesize peptides containing 1,4-disubstituted 1,2,3-triazole group, such as peptide 1, which is constituted by sixteen threonine residues and one 1,4 disubstituted 1,2,3-triazole group (NH2-(Thr)7-Thr-(1,4- disubstituted 1,2,3-triazole cycle)-Thr-(Thr)7-OH). Moreover, due to the similarity with T. cruzi mucins that present great composition of threonine, 1 can be employed in development of vaccines related to infectious processes caused by T. cruzi. The preparation of 1 envolved an association between the solid-phase synthesis of peptide and reactions of copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Initially, the method was standardized from synthesis of threonine dipeptide (8), whose peptide bond was replaced by 1,4-disubstituted 1,2,3-triazole group (NHFmoc-Thr-(1,4-disubstituted 1,2,3-triazole cycle)-Thr-OH). The strategy via CuAAC gave the modified dipeptide in good yield (98%) and allowed to establish the conditions to prepare the more complex peptide with long chain 1. The CuAAC reaction gave the peptide 1 with good yield (70%). Compound 1 was confirmed by NMR proton analysis which showed the presence of 1,4-disubstituted 1,2,3-triazole group. Additionally, further analysis of mass spectrometry (ESI-MS) suggest the achievement of peptide 1.
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Acquaah-Harrison, George. "Antibacterial Agents: 1,4-Disubstituted 1,2,3-Triazole Analogs of the Oxazolidinone." Ohio : Ohio University, 2010. http://www.ohiolink.edu/etd/view.cgi?ohiou1273250347.
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Johnson, Sean M. "Toward the Synthesis of Naphthalene-Bridged Bis-Triazole Bimetallic Complexes." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/6872.
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Bimetallic complexes are known to have unique electronic properties and are used in a variety of organic transformations as catalysts. The use of naphthalene-bridged bis- triazoles (NBT) for bimetallic complexes is unknown. NBTs have the unique property of being fluorescent stemming from a twisted intramolecular charge transfer. With the non- coplanar geometry and the distance between the 1,2,3-triazole rings, we hypothesized that 1,8-bis(4-phenyl-2H-1,2,3-triazol-2-yl)naphthalene (12) would be a suitable ligand to synthesize a bimetallic complex. The synthesis of 12 was optimized for large scale synthesis and was synthesized on a 78 mmol scale in 15% total yield. Metal complexation trials were conducted on 12 and several insoluble solids were observed.
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White, Nicholas George. "Macrocyclic, interpenetrated and interlocked triazole and triazolium containing anion receptors." Thesis, University of Oxford, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.669941.
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This thesis describes the synthesis of macrocyclic, interpenetrated, and in particular, interlocked anion receptors containing the triazole and triazolium motifs. Chapter One introduces the field of supramolecular chemistry with a focus on the areas of particular relevance to this thesis, namely anion coordination, anion templation and the synthesis of interlocked structures. Chapter Two describes the preparation of acyclic and macrocyclic neutral bis-triazole receptors, and a study of their anion and transition metal cation recognition properties. The synthesis of an acyclic anion receptor incorporating the novel pyridinium-3,5-bis(triazole) motif is also reported. Chapter Three details the incorporation of the pyridinium bis-triazole motif into pseudorotaxanes, catenanes and rotaxanes. A thorough study of the use of a variety of anions, including oxoanions, to template interpenetrated assemblies is described, and the anion binding a nities of the catenane and rotaxane hosts discussed in comparison to analogous amide based systems. Chapter Four presents research into a series of triazolium containing rotaxanes. A number of structural modifications are made to the interlocked host molecules, and the effect of these changes on the anion recognition properties of the receptors is discussed. Chapter Five investigates the incorporation of two or more cationic triazolium groups into cyclic and interlocked host systems in order to create highly charged receptors capable of anion recognition in aqueous media. Chapter Six describes experimental procedures used in this work, and details the characterization of novel compounds. Chapter Seven summarizes the major conclusions of this thesis. Chapter Eight contains the references cited within Chapters One to Six.
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Wang, Yu Ling. "Mechanisms of triazole and retinoic acid-induced branchial arch malformation." Thesis, St George's, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338915.
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Taleli, Lebusetsa. "Synthesis of triazole-linked chloroquinoline derivatives as novel antimalarial agents." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79827.
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Thesis (MSc)--Stellenbosch University, 2013.Aminoquinolines are important class of drugs that have been used for malaria chemotherapy for centuries. However, long-term exposure to these drugs leads to extensive spread of drug resistance. As such, modified chloroquinoline derivatives are being studied as alternative antimalarial agents with the possibility to overcome drug resistance associated with chloroquine analogues. In this study, 15 aminoquinoline derivatives that are linked by a 1,4-disubstituted 1,2,3-triazole ring to an ethyl and propyl carbon spacer with a distal amine motif were designed and synthesized as novel antimalarial agents using the Cu(I)-promoted Huisgen reaction. The compounds have been synthesized from the 7-chloro-N-(prop-2-yn-1-yl)quinolin-4-amine alkyne precursor and the azides of ethyl and propyl amino moieties using a 1,3-dipolar cycloadditioncoupling in the presence of CuI catalyst to obtain moderate to good yields (53 – 85%). These compounds have been characterized by the combination of NMR, ESI+ HRMS and IR spectroscopic methods. The antiplasmodial activity of the compounds was investigated in vitro against P. falciparum strain NF54 using chloroquine as a reference drug together with a standard antimalarial drug artesunate. Of the 15 novel chloroquinoline derivatives, 11 have demonstrated to possess promising potency by way of the inhibition concentrations less than 250 nM with the lowest being 28 nM. The observed activities have been ascribed to the overall modifications such as the introduction of a triazole linker and changing of carbon chain length as these were the variables. The compounds are accordingly under further biological investigations and only the chloroquine sensitive results are reported in this work.
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Tambo, Yasukazu. "Validierung eines Enzymimmunoassays und Entwicklung von Standardmaterialien für die Analytik freier und gebundener Triazinrückstände." [S.l. : s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=966389441.
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Moreno, Karlos Xavier. "NMR studies of the conformation of a triazine dendrimer and the synthesis of a platinated triazine dendrimer." [College Station, Tex. : Texas A&M University, 2007. http://hdl.handle.net/1969.1/ETD-TAMU-2450.
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Corrales, Roberta Cristina Novaes Reis. "Síntese e avaliação biológica de derivados de 6-mercaptopurina, carboidratos e aminoálcoois." Universidade Federal de Juiz de Fora (UFJF), 2011. https://repositorio.ufjf.br/jspui/handle/ufjf/4290.
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CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A tese de doutorado intitulada Síntese e Avaliação Biológica de Derivados de 6-Mercaptopurina, Carboidratos e Aminoálcoois está apresentada em três capítulos que descrevem a síntese e caracterização de compostos com potencial atividade antiparasitária (Leishmania, Plasmodium berghei), antibacteriana (bactérias Gram positiva e negativa, Mycobacterium tuberculosis) e em macrófagos peritoneais de mamíferos. Foram obtidos 53 compostos neste trabalho, sendo 30 inéditos, a saber: no capitulo 1 foi descrita a síntese de 27 compostos, sendo 14 derivados inéditos de 6mercaptopurina (6-MP); no capítulo 2 foi descrita a síntese de 14 compostos, sendo 6 derivados inéditos da D-glicose e 1 derivado inédito da D-ribonolactona; no capítulo 3 foi descrita a síntese de 14 compostos, sendo 9 aminoálcoois inéditos. O primeiro capítulo mostra a síntese de derivados de 6-MP contendo 1,2,3-triazol e derivados de esteróides. Os derivados triazólicos de 6-MP foram obtidos através de uma reação de cicloadição 1,3-dipolar tipo “click” usando um alcino terminal e um grupo azido. Os derivados de 6-MP contendo esteróides, sem o espaçador triazólico, foram obtidos através de uma reação de substituição nucleofílica entre o sal de 6-MP e mesilatos do ácido cólico e do ácido desoxicólico. Dentre os compostos submetidos à avaliação biológica, os derivados de 6-MP conjugados com esteróides apresentaram melhor atividade em Leishmania e a maioria apresentou importante atividade em P. berghei. Nenhum composto testado apresentou citotoxicidade in vitro para macrófagos peritoneais de camundongos até a máxima concentração de 48 µg/mL. O segundo capítulo mostra a síntese e caracterização de derivados da D-glicose contendo 1,2,3-triazol, obtidos através de reação tipo “click” e de derivados da D-gliconolactona e D-ribonolactona. Apesar dos compostos testados não terem apresentado atividade antiparasitária e antibacteriana efetiva, nenhum apresentou toxidez para os macrófagos de mamíferos. O terceiro capítulo descreve a síntese e caracterização de derivados aminoálcoois aromáticos com variada extensão de cadeia e de função química e apresentaram importante atividade biológica, principalmente em L. major. As estruturas dos produtos obtidos foram elucidadas pelos seus espectros na região do infravermelho, Ressonância Magnética Nuclear de 1H e 13C, Mapa de contornos homonuclear COSY, faixa de fusão e espectros de massas de alta resolução.
The doctoral thesis entitled Synthesis and Biological Evaluation of Derivatives of 6-Mercaptopurine, Carbohydrates and Aminoalcohol is presented in three chapters that describe the synthesis and characterization of compounds with potential antiparasitic activity (Leishmania, Plasmodium berghei), antibacterial (bacteria Gram positive and negative, Mycobacterium tuberculosis) and peritoneal macrophages of mammals. 53 compounds were obtained in this work, with 30 firsts, namely: Chapter 1 was described in the synthesis of compounds 27, 14 novel derivatives of 6-mercaptopurine (6MP), was described in Chapter 2 the synthesis of compounds 14, 6 being derived from unpublished 1 D-glucose and derived novel D-ribonolactona, was described in Chapter 3 the synthesis of compounds 14, 9 amino unpublished. The first chapter shows the synthesis of derivatives of 6-MP containing 1,2,3triazole derivatives and steroids. The triazole derivatives of 6-MP were obtained by a reaction of type 1,3-dipolar cycloaddition "click" using a terminal alkyne and an azide group. Derivatives of 6-MP containing steroids, without the spacer triazole, was obtained through a nucleophilic substitution reaction between the salt of 6-MP and mesylates cholic acid and deoxycholic acid. Among the compounds subjected to biological evaluation, derivatives of 6-MP in conjunction with steroids showed better activity in Leishmania and most showed a significant activity in P. berghei. No compound tested showed cytotoxicity in vitro for mouse peritoneal macrophages to g / mL.µthe maximum concentration of 48 µg/mL. The second chapter shows the synthesis and characterization of D-glucose derivatives containing 1,2,3-triazole, obtained by reaction type "click" derivatives of Dgliconolactona and D-ribonolactona. Although the compounds tested did not show effective antibacterial and antiparasitic activity, showed no toxicity to mammalian macrophages. The third chapter describes the synthesis and characterization of aromatic amino derivatives with varied chain length and chemical function and had significant biological activity, especially in L. Major. The structures of the products obtained were elucidated by their spectra in the infrared, 1H NMR and 13C, homonuclear COSY contour map, melting point and mass spectra with high resolution.
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Bean, Timothy Peter. "Characterisation of Mycosphaerella graminicola isolates with reduced sensitivity to triazole fungicides." Thesis, University of Reading, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506134.
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Evangelista, Fernanda Cristina Gontijo. "Evaluation of in vitro antitumor activity of triazole / azide synthetic chalcones." Instituto Nacional de Pesquisas da Amazônia, 2018. http://bdtd.inpa.gov.br/handle/tede/2639.
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Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP
Many compounds isolated from lichens exhibit biological activity, and a number of them are proven sources of antitumor drugs. Even simple structural changes to these bioactive compounds can lead to potentiation of their activity. The purposes of this study were to evaluate the antiproliferative activity and selectivity of the following compounds isolated from lichens: atranorin; diffractaic, divaricatic, perlatolic, psoromic, norstitic, protocetraric, and fumarprotocetraric acids; and alkyl derivatives. Cytotoxicity tests based on the sulforhodamine B dye were performed on seven lines of neoplastic cells and one line of normal cells (3T3)
Muitas substâncias isoladas de liquens apresentam atividades biológicas, e algumas demonstraram ser fontes promissoras de drogas antitumorais. Modificações estruturais simples a partir dessas substâncias bioativas podem levar a potencialização da atividade apresentada. Os objetivos deste estudo foram avaliar a atividade antiproliferativa e seletividade dos seguintes compostos isolados de liquens: atranorina, ácidos difractaico, divaricático, perlatólico, psorômico, norstítico, protocetrárico e fumarprotocetrárico e derivados alquílicos. O ensaio de citotoxicidade foi realizado com corante sulforrodamina B em sete linhagens de células neoplásicas e uma linhagem de células normais (3T3)
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Blayo, Anne-Laure. "Conception et synthèse d'antagonistes du récepteur de la ghréline basés sur le motif 1,2,4-triazole 3,4,5-trisubstitué." Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20041.
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La ghréline, une hormone peptidique principalement synthétisée au niveau de l'estomac, est le ligand endogène du récepteur des sécrétagogues de l'hormone de croissance appelé GHS-R1a. Elle est impliquée dans de nombreux processus biologiques dont principalement la sécrétion de l'hormone de croissance et la régulation de l'homéostasie énergétique. En raison de ses propriétés orexigènes et adipogènes, la ghréline est un outil puissant pour lutter contre les déséquilibres énergétiques. Développer des antagonistes de son récepteur représente ainsi une stratégie prometteuse pour la découverte de nouvelles pharmacothérapies contre l'obésité.Cette thèse est consacrée au développement d'antagonistes du récepteur de la ghréline dont la structure est basée sur une plateforme peptidomimétique : le 1,2,4-triazole 3,4,5-trisubstitué. Notre objectif est de concilier au mieux l'affinité et l'activité de nos ligands vis-à-vis du GHS-R1a avec des propriétés optimisées permettant de favoriser une bonne biodisponibilité orale. Nous nous sommes basés sur une synthèse rapide et efficace de ces composés pour réaliser des études approfondies de relations structure-activité et structure-propriété. En optimisant successivement les différentes positions autour du motif triazole, des compromis intéressants ont été obtenus. Nous avons ainsi identifié des antagonistes affins du récepteur qui présentent une stabilité microsomale suffisante et une perméabilité membranaire satisfaisante pour envisager des études in vivoGhrelin, a peptidic hormone which is mainly synthesized in the stomach, is the endogenous ligand of the growth hormone secretagogue receptor named GHS-R1a. It is involved in numerous biological processes such as the growth hormone secretion and the control of energy homeostasis. Because of its orexigenic and adipogenic properties, ghrelin is a potent tool to control energy imbalance. Developing ghrelin receptor antagonists represents a promising strategy for the discovery of anti-obesity new drugs.This thesis is devoted to the development of ghrelin receptor antagonists based on a peptidomimetic scaffold: the 3,4,5-trisubstituted 1,2,4-triazole. Our aim is to combine ligand affinity and activity towards GHS-R1a with optimized properties which enable to promote a good oral bioavailability. We based our work on a rapid and efficient synthesis of our compounds to carry out detailed structure-activity and structure-property studies. By successively optimizing the different positions around the triazole scaffold, interesting compounds were obtained. We have thus identified receptor antagonists which exhibit sufficient microsomal stability and satisfactory membrane permeability to consider in vivo studies