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1
Ostache, Nicu-Carmin. "Synthèse et fonctionnalisation de bicycles 5-5 polyazotés : pyrazolo[3,4-d]thiazoles et pyrazolo[3,4-c]pyrazoles." Thesis, Orléans, 2019. http://intranet.univ-orleans.fr/bibliotheques/theses/nicu-cosmin-ostache_3378_vm.pdf/.
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Les structures bicycliques azotées sont parmi les entités les plus utilisées dans le domaine thérapeutique.Les bicycles 5:5 polyazotés sont des structures moins décrites que leurs analogues 6:6 ou6:5. Malgré le potentiel pharmacologique des pyrazolo [3,4-d] thiazoles et des pyrazolo [3,4-c] pyrazoles,deux exemples de ces familles rares, seuls quelques procédés de préparation et de fonctionnalisationdirecte de ces charpentes hétérocycliques sont décrits.De ce fait, l’objectif principal de nos recherches vise à développer de nouvelles voies de synthèse vers cesdeux charpentes bicycliques et ce, à partir de substrats facilement accessibles. Des stratégies efficaces ontété mises au point et s’appuient sur réactions de condensations avec des hydrazines, des N-cyclisationsintramoléculaires, des halogénations chimiosélectives et diverses réactions de couplage-croisé. De surcroît,le motif pyrazolo[3,4-d]thiazole a été fusionné à une structure triazapentalène, afin d’évaluer les propriétésspectroscopiquesNitrogen-rich fused bicyclic structures are undisputedly one of the most used scaffolds for therapeutic use.The 5:5 polynitrogenated bicycles are moieties considerably less documented then their 6:6 or 6:5analogues. Despite the pharmacological potential of the pyrazolo[3,4-d]thiazoles and of thepyrazolo[3,4-c]pyrazoles, two examples of such rare families, only few methods of preparation and directfunctionalization of these heterocyclic moieties have been described.In this context, the main goal of our research aims at exploring new routes towards these bicyclic systemsfrom readily available and affordable starting materials. Efficient strategies were developed relying onhydrazine condensations, on intramolecular N-cyclizations, on chemo-selective halogenation and variouscross-coupling reactions. Moreover, the pyrazolo[3,4-d]thiazole entity was fused to a triazapentalenestructure in order to assess the spectroscopic properties
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Gormen, Meral. "Synthesis Of Ferrocenyl Substituted Pyrazoles." Master's thesis, METU, 2005. http://etd.lib.metu.edu.tr/upload/3/12606358/index.pdf.
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Pyrazoles have been studied for over a century as an important class of heterocyclic compounds and continue to attract considerable interest due to the broad range of biological activities they possess. The incorporation of the essential structural features of pyrazoles with a ferrocene moiety could provide new derivatives with unexpected and/or enhanced biological activities since several ferrocene derivatives have already been shown to be active against a number of tumors. For this reason, we investigated the synthesis of ferrocenyl-substituted pyrazoles, such as 1-alkyl/aryl-5-ferrocenylpyrazoles, by employing the reaction between (2-formyl-1-chlorovinyl)ferrocene and hydrazine derivatives. Although this reaction is known, it was not studied in much detail and the low yields of ferrocenyl pyrazoles were obtained. Thus, we have reinvestigated this reaction and improved the yields of pyrazoles by optimizing the reaction conditions. (2-Formyl-1-chloro vinyl)ferrocene was first reacted with the excess amount (3 equivalents) of hydrazine derivative at 25 0C in dioxane under argon for 2 hours, and the resulting mixture was then heated at 100 0C for 6 hours in the same solvent. Under our optimized conditions, these reactions afforded 1-alkyl/aryl-5-ferrocenylpyrazole derivatives in moderate to good yields as a single or major product of the reaction. In some cases, 1-alkyl/aryl-3-ferrocenylpyrazole derivatives resulted from these reactions as very minor products.
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El, Youssoufi Jawad. "Synthèses de pyrazoles benzocyclohepténiques glycosylés." Limoges, 1997. http://www.theses.fr/1997LIMO0027.
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La synthese des pyrazoles constitue un developpement important dans le domaine de la chimie fine en raison de leur impact en pharmacochimie ou lors de l'elaboration de produits phytosanitaires et insecticides. Dans le present travail nous presentons pour la premiere fois la synthese de dipyrazoles benzocyclohepteniques substitues. Cette synthese passe par deux synthons cles, le 1,5-dioxo-1,2,4,5-tetrahydro-3h-benzocycloheptene-2,4-diaminomethylene et le 1,5-dihydroxy-3h-benzocycloheptene-2,4-dicarbonitrile. Ces deux composes permettent une synthese regioselective de deux series de pyrazoles substitues sur les azotes n-1, n-7 ou sur les azotes n-2, n-6 par des groupements methyles, hydroxyethyles et glycosyles. L'equilibre conformationnel du cycloheptene, mis en evidence par differentes methodes de rmn, revele des structures tridimensionnelles differentes pour chacune des series. Le couplage de ces produits avec le ribose nous a permis d'obtenir des produits hydrosolubles mono et diglycosyles directement sur le pyrazole ou par l'intermediaire d'un bras espaceur. Les methodes presentees pour l'elaboration de ces composes sont suffisamment generales pour permettre des couplages regio et stereoselectifs avec un large eventail de glucides mono ou polysaccharidiques.
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Ervithayasuporn, Vuthichai. "Synthesis and photochemistry of pyrano[2,3-c]pyrazoles." Link to electronic thesis, 2006. http://www.wpi.edu/Pubs/ETD/Available/etd-042006-160619/.
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ERVITHAYASUPORN, VUTHICHAI. "Synthesis and Photochemistry of Pyrano[2,3-c]pyrazoles." Digital WPI, 2006. https://digitalcommons.wpi.edu/etd-theses/228.
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Two different synthetic approaches to the synthesis of pyrano[2,3-c]pyrazoles have been investigated. In one approach, dehydroacetic acid derivatives were treated with phenylhydrazine and methylhydrazine led to the formation of the phenylhydrazones and methylhydrazones, which undergo rearrangement in refluxing acetic acid to diketo-phenylpyrazoles and diketo-methylpyrazoles. Upon treatment with a mixture of acetic and sulfuric acid these compounds isomerize to the phenylpyrano[2,3-c]pyrazol-4-one and methylpyrano[2,3-c]pyrazol-4-one derivatives. In a second approach, phenylhydrazine and methylhydrazine reacted with dimethyl(methoxymethylene)malonate (34) to give phenylpyrazole and methylpyrazole ester derivatives which were converted to phenylpyrazolone and methylpyrazolone by hydrolysis and decarboxylation. C-acylation of these compounds with trans-cinnamoyl chloride gave á,â-unsaturated-4-acetyl-5-hydroxypyrazoles. Bromination of these á,â-unsaturated-4-acetyl-5-hydroxypyrazoles with spontaneous cyclization, followed by dehydrobromination led to pyrano[2,3-c]pyrazol-4-one derivatives, respectively. Phototochemical excitation of 1-phenyl and 1-methylpyrano[2,3-c]pyrazol-4-ones in acetonitrile led to the formation of cis-head-to-tail [2+2] cycloaddition products. Irradiation in ethanol solvent led to photodimerization and to photofragmentation to yield pyrazole ethylesters.
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Desalegn, Nebiyou. "Kinetic Studies Of The Thermolysis Of 3-Halogenated-4,5-Dihydro-3h-Pyrazoles." Digital Archive @ GSU, 2005. http://digitalarchive.gsu.edu/chemistry_theses/1.
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3-Chloro-4,4,5-trimethyl-3,5-diphenyl-4,5-dihydro-3H-pyrazole (3b) and 3-bromo-4,4,5-trimethyl-3,5-diphenyl-4,5-dihydro-3H-pyrazole (3c) were prepared for the thermolysis project. The thermal decompositions of 3b and 3c were monitored using 1H NMR spectroscopy. Plots of ln (% starting material) vs. time (sec) were linear for at least two half lives and the first order rate constants were determined over at least a 30o temperature range. The relative reactivity was found to be 3c > 3b. The activation parameters determined for the thermal decomposition of the pyrazoline at 150oC were found to be: for 3b &#;H‡ = 33 &#;1.0 kcal/mol, &#;S‡ = -2.4 &#; 0.07eu , k150 0 = 7.34 &#; 0.44 x 10 -5 s-1 ; for 3c &#;H‡ = 30&#;0.2 kcal/mol, &#;S‡ = -6.9 &#;0.03 eu, k150o = 42.3&#;0.7 x 10-5 s-1. Thermal decomposition of 3b both neat and in dibromobenzene (DBB) resulted in the formation of an intermediate 2,3-diphenyl-4-methyl-1,3-pentadiene (8) as a major product and minor isomers of 8. These intermediates then thermally decomposed to 1,1,3-trimethyl-2-phenyl-1H-indene (9) via an acid catalyzed process. In order to gain a mechanistic understanding (ionic vs. radical pathways) of the thermal decomposition of 3b, a product study was conducted in protic solvents. In methanol and ethanol, 3b underwent an ionic reaction (SN1-type) with the solvent to produce 3-methoxy/ethoxy-4,4,5-trimethyl-3,5-diphenyl-4,5-dihydro-3H-pyrazole (3/3d) in good yield. The reaction of 3b with refluxing protic solvents led to the development of new method for the synthesis of alkoxy-4,5-dihydro-3H-pyrazoles which is both safe and efficient.
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Cooper, David Arthur. "The synthesis and characterization of some molybdenum, rhenium and rhodium complexes incorporating pyrazolylgallate ligands." Thesis, University of British Columbia, 1985. http://hdl.handle.net/2429/24597.
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Several uninegative ligands based on a gallium core and incorporating pyrazolyl groups have been synthesized and their metathesis reactions with molybdenum, rhenium and rhodium halides have been studied. The bidentate pyrazolylgallate ligand [formula omitted] has been incorporated in the complexes [formula omitted]. The unsymmetric tridentate pyrazolylgallate ligands [formula omitted] display a variable reactivity towards molybdenum, rhenium and rhodium precursors. Although no complexes incorporating L⁴ were isolated, L₂ and L₃ were shown to co-ordinate facially in the octahedral complexes [formula omitted] and [formula omitted]. In addition, a meridional co-ordination geometry of L₂ has been structurally characterized in the square planar rhodium(I) complex, L₂Rh(CO). This co-ordinatively unsaturated rhodium(I) species was shown to undergo an interesting oxidative addition reaction with methyl iodide followed by a methyl migration reaction to give a rhodium(III) acetyl derivative.
Less predictable products have also been obtained in this study; these include the dimeric species [formula omitted] formed from the reaction of NaL₃ with [formula omitted] and also an unexpected chlorine-containing complex, [formula omitted] from the reaction of [formula omitted]. [formula omitted] the product of the reaction between [formula omitted]. [Formula omitted] (the precursor of Ld) has been structurally shown to possess a novel eight-membered Ga-(N-C-S)₂-Ga ring.Science, Faculty of
Chemistry, Department of
Graduate
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Nakhai, Azadeh. "Synthetic studies of nitrogen containing heterocycles, particularly pyrazole and benzotriazine derivatives." Stockholm, 2009. http://diss.kib.ki.se/2009/978-91-7409-687-3/.
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Demirci, Deniz. "Synthesis Of 4-phenylselenyl-1h-pyrazoles By Electrophilic Cyclization." Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613910/index.pdf.
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In this study, the synthesis of 5-ferrocenyl/aryl-4-(phenylselenyl)-1H-pyrazole derivatives was investigated since the integration of ferrocenyl and selenium moieties into pyrazole derivatives may increase their current biological activities. Initially, the starting propargyl aldehydes were synthesized from corresponding acetylenes. Subsequently, propargyl aldehydes were reacted with hydrazines to yield corresponding hydrazones. Then the in situ synthesized hydrazones were subjected to electrophilic cyclization with phenylselenyl chloride, which afforded 5-ferrocenyl/aryl-4-(phenylselenyl)-1H-pyrazoles in one-pot manner. Subsequently, reaction conditions were optimized in terms of electrophile, base, temperature and solvent. Best results were obtained with phenylselenyl chloride and NaHCO3 at room temperature in DCM for ferrocenyl substituted pyrazoles and DCE for aryl substituted pyrazoles. In summary, by employing the electrophilic cyclizations of in situ synthesized acetylenic hydrazones, a variety of 5-ferrocenyl/aryl-4-(phenylselenyl)-1H-pyrazole derivatives were synthesized in one-pot way in moderate to good yields.
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Truong, Phong Minh. "Hexa-aryl/alkylsubstituted Cyclopropanes." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/chemistry_theses/2.
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A series of penta-aryl/alkyl-1-(toluene-4-sulfonyl)-4,5-dihydro-1H-pyrazole 5a-c was synthesized by addition of methyllithium or phenylllithium followed by trapping the nitrogen anion intermediate with tosyl-fluoride to cyclic azines 2a,b. Addition of methyllithium or phenyllithium to 5a-c generated a series of hexa-aryl/alkylsubstituted-4,5-dihydro-3H-pyrazoles 6a-c. Neat thermolysis of hexa-aryl/alkylsubstituted-4,5-dihydro-3H-pyrazoles 6a-c at 200◦C produced hexa-aryl/alkylsubstituted cyclopropanes 7a-c in high yield.
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Cottineau, Bertrand. "Contribution à l'étude du 3-hydroxy-1H-pyrazole-4-carboxylate d'éthyle : application à la synthèse de composés antidiabétiques." Orléans, 2002. http://www.theses.fr/2002ORLE2014.
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Le diabète est l'affection endocrinienne de loin la plus fréquente. Il touche environ deux millions de personnes en France et se caractérise par une élévation de la concentration plasmatique en glucose et triglycérides. Cette hyperglycémie chronique contribue à l'apparition de complications spécifiques. Dans le cadre d'une recherche de nouveaux agents antidiabétiques, nous avons préparé à partir d'un synthon commun, le 3-hydroxy-1H-pyrazole-4-carboxylate d'éthyle, des composés diversement fonctionnalisés notamment en position 1 et 3 via des réactions de O et N-alkylations régiospécifiques, et en position 5 via des réactions de couplage catalysées au palladium (0). Par la suite, la mise au point des réactions de type ± Eenie-Meenie α à partir du (3-méthoxy-1-méthyl-1H-pyrazol-4-yl)-méthanol a permis la synthèse de 4-benzylpyrazoles. Les tests pharmacologiques, effectués par la société Merck-Santé, ont montré que certains composés synthétisés présentent une bonne activité hypoglycémiante.
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DIB/, DIB-OUADAH LATIFA. "Analyse structurale de pyrazoles : rmn, etude conformationnelle et distribution electronique." Paris 7, 1993. http://www.theses.fr/1993PA077144.
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Le noyau pyrazolique fait l'objet d'un interet soutenu, tant sur un plan theorique en raison de ses possibilites de tautomerie, qu'a un niveau plus applique en raison de l'activite physiologique de nombre de ses derives. Dans une premiere partie, nous avons entrepris l'etude systematique des deplacements chimiques #1h pour une large serie de composes. Ceux-ci refletent en effet de facon tres fine les effets d'environnement electronique. Un interet particulier a ete porte aux structures presentant des contraintes steriques en vue d'apprehender leur geometrie. Les resultats sont analyses en termes d'increments additifs de substitution. En liaison avec les observations precedentes, dans la deuxieme partie du memoire, les methodes de la chimie quantique sont utilisees pour preciser les distributions electroniques et les geometries preferentielles dans le cas de phenyl pyrazoles diversement substitues. La determination des conformations privilegiees est d'abord envisagee en examinant les variations de l'energie moleculaire en fonction de l'angle de torsion des noyaux phenyle et pyrazole. Le calcul est effectue au niveau sto-3g par les methodes ab initio. Le raffinement de l'optimisation, avec possibilite de relaxation par allongement de liaison, ouverture d'angle ou rotation des groupes, modifie peu les resultats precedents. A partir des geometries preferentielles ainsi determinees, l'application du modele de bovey permet l'evaluation des effets d'anisotropie magnetique du noyau phenyle. La suite du memoire est consacree a l'etude des potentiels electrostatiques moleculaires d'une serie de 1-phenyl pyrazolo-pyrimidines, substituees sur le noyau phenyle, avec en vue la recherche d'indices susceptibles de guider l'interpretation de leur activite. Ces substances possedent en effet une activite antagoniste notable sur le recepteur adenosine a#1
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Foster, Robert Stephen. "Expanding the functionalisation of sydnones : developing flexible routes to pyrazoles." Thesis, University of Sheffield, 2013. http://etheses.whiterose.ac.uk/3681/.
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Tran, Gaël. "Synthèse de phosphonylpyrazoles et de fluoropyridazines." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066414/document.
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Dans le cadre de nos travaux, nous avons développés des voies de synthèses permettant d'accéder à deux familles d'hétérocycles aromatiques: les phosphonylpyrazoles, et les fluoropyridazines. La synthèse des pyrazoles phosphonylés a été réalisée en utilisant un couplage croisé pallado-catalysé de type Hirao, et nous avons démontré qu'un système catalytique unique à base de Pd(OAc)2/XantPhos pouvait catalyser le couplage entre une large gamme d'halogénopyrazoles et de H-phosphonyles. Bien que souffrant de certaines limites dans son champ d'application, notamment au niveau du motif de substitution de l'halogénopyrazole, cette méthode consiste probablement à l'heure actuelle la voie d'accès la plus modulable pour accéder aux pyrazoles phosphonylés.Les 5-fluoropyridazines ont été synthétisées par réactions de cycloadditions séquentielles [2+1]/[3+2] entres des alcynes, le difluorocarbène :CF2, et des diazoacétates d'alkyles. Nous avons démontré que cette séquence réactionnelle était compatible avec un grand nombre d'alcynes diversement substitués, et que les 5-fluoropyridazines ainsi obtenues pouvaient être aisément fonctionnaliséesThe work presented in this manuscript concerns the development of synthetic routes to two families of heterocycles, namely phosphonylpyrazoles and fluoropyridazines. Phosphonylpyrazoles were synthesized using a Hirao-type cross-coupling, and it was demonstrated during this study that a single catalytic system based on Pd(OAc)2/XantPhos could perform the cross-coupling between a wide range of halopyrazoles and H-phosphonyls. Significant limits have been met in the scope of this method, especially regarding the substitution pattern of the halopyrazole. Nevertheless, at this time, this method is arguably one of the most flexible ways to synthesize phosphonylpyrazoles. Fluoropyridazines were synthesized using a [2+1]/[3+2] cycloaddition sequence between alkynes, the difluorocarbene :CF2, and alkyl diazoacetates. It was demonstrated during this study that a wide range of alkynes could be involved in this sequence, and that the corresponding 5-fluoropyridazines could be easily diversified
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Hervé, Grégoire. "Progrès récents dans la chimie des molécules énergétiques : accès à de nouveaux hétérocycles azotés aromatiques très performants." Aix-Marseille 3, 2009. http://www.theses.fr/2009AIX30031.
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L'objectif de cette thèse consiste à mettre au point des molécules explosibles thermiquement stables, hautement énergétiques, à faible sensibilité selon des procédés de synthèse économiques et industriels. Certains composés énergétiques aromatiques bien ciblés, synthétisés dans le cadre de ces travaux, présentent des caractéristiques jamais égalées en terme de performance et de sensibilité (sûreté de fonctionnement). Ces avancées techniques offrent de nouvelles perspectives dans l’exploitation, la fabrication et l’utilisation de nouveaux matériaux énergétiques de défense performants à plus faible vulnérabilité. Ce travail fait également mention à un nouveau composé aromatique hautement nitré, lequel présente un niveau de stabilité sans équivalence en comparaison à tous les systèmes aromatiques analogues (nitroazoles, hexanitrobenzène, dinitrofurazane…)The purpose of this thesis work was to design and to prepare new stable, highly-energetic and insensitive (or low-sensitive at least) explosives by the means of economical and industrial synthetic pathways. The synthesis of certain aromatic energetic compounds prepared in this framework affords significant enhancement in terms of energetic and physical properties ensuring ease of utilization and handling of such new materials in respect with high energetic performance. Several explosives exhibit unprecedented properties and offer a remarkable performance/sensitivity balance. A novel fully C-nitrated aromatic explosive is presented here and has, by far, the most important thermal and chemical stability in these series versus all the known nitrocarbons (i. E. Hexanitrobenzene) and nitroazoles
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Chappuit, Lucrezia. "Design, synthèse et évaluation biochimique d’inhibiteurs des ADN Méthyltransférases." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS372.
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Ce manuscrit présente le développement de nouveaux inhibiteurs de la DNMT1 (DNA Methyl- transferase), enzyme impliquée dans les modifications épigénétiques de l’ADN et dont la dérégulation participe à l’évolution des cancers épigénétiques. La première partie de ces travaux a porté sur le design par modélisation moléculaire de nouveaux composés prolino-homo-tryptophanes capables d’interagir avec les deux sites de liaisons de la DNMT1. Dans une seconde partie, la modélisation moléculaire nous a permis de dessiner plusieurs composés pyrazoles comme nouveaux inhibiteurs potentiels de la DNMT1. A la suite de ces études, l’ensemble des composés dessinés ont été synthétisés puis évalués sur une DNMT1 humaine recombinante grâce à un test d’inhibition biochimique. L’évaluation biochimique a permis de mettre en évidence deux composés lead capables d’inhiber totalement la DNMT1 à forte concentration (500 μM)This manuscript presents the development of novel DNMT1 (DNA Methyltransferase) inhibi- tors. This enzyme is involved in epigenetic modification of DNA and its deregulation may lead to epigenetic cancers. The first part of this work focused on the design by molecular modeling of new prolino-homo-tryptophan compounds which can interact with both pockets of DNMT1. In a second time, molecular modeling allows us to design several pyrazole compounds as po- tential new DNMT1 inhibitors. Following these studies, all designed compounds were synthe- tized and tested on a recombinant human DNMT1enzyme thanks to a biochemical inhibition test. Biological evaluation bright to light two lead compounds which totally inhibit DNMT1 at high concentration (500 μM)
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Oleksik, Laurence. "Methodology for the synthesis of 4 or 5-substituted-3-perfluoroalkyl pyrazoles." Thesis, University of Leicester, 2004. http://hdl.handle.net/2381/30087.
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Initially the perfluoroacylation of a range of commercially available vinyl ethers and conversion of the resulting perfluoroacylated enol ethers to 1-H-pyrazoles via reaction with hydrazine is reported. The selective synthesis of a range of alpha-aryl vinyl ethers using Heck chemistry is then reported. Subsequent perfluoroacylations of the vinyl ethers followed by reaction of the resulting perfluoroacyl enol ethers with hydrazine affords a range of 5-aryl-3-perfluoroalkyl pyrazoles in good yields.;Alternative methodology for the synthesis of 5-aryl-3-perfluoroalkyl pyrazoles is then described in which resin bound esters are converted to vinyl ethers
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Duprez, Virginie. "Synthèse des hydroxyalkyl pyrazoles, leurs complexes de titane et application en polymérisation." Aix-Marseille 3, 2002. http://www.theses.fr/2002AIX30007.
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Dans ce travail visant à développer de nouveaux catalyseurs qualifiés de post métallocènes, nous nous sommes fixés trois objectifs. Le premier concerne la préparation de plusieurs familles de substrats hydroxyalkyl pyrazoliques simples d'accès à partir du noyau pyrazolique dont un atome d'azote est substitué par une chaîne hydroxyalkyle. Ces ligands hétéroatomiques ont été synthétisés via des réactions d'alkylation, d'ouverture d'époxydes et de condensation directe de composés b-dicarbonylés avec des dérivés de l'hydrazine. La seconde partie a porté sur l'étude des modes de coordination de ces différents ligands potentiellement bidentés au titane, la synthèse des complexes de Ti(IV) correspondant et leur caractérisation. Enfin, l'application de ces complexes de Ti(IV) en tant que catalyseur de polymérisation vis à vis d'alcènes a révélé une activité intéressante. Plusieurs de ces complexes catalysent notamment la formation d'un polyéthylène de masse moléculaire élevéeDuring this project consisting in the development of new post metallocene catalytic systems, we fixed us the following three objectives : the syntheses of new ligands, preparation of titanium complexes and polymerisation reactions. The first part describes the syntheses of several hydroxyalkyl pyrazoles families, easily access with the pyrazole nucleus in which one nitrogen is substituted with an hydroxy alkyl side chain. These heteroatomics ligands are synthesised via alkylation reaction, epoxide ring opening or direct condensation of b diketones with hydrazine derivatives. The second part deals with the study of coordination modes of the different ligands with Ti, the syntheses of Ti(IV) complexes and their characterisation. Finally, the application of these Ti complexes as polymerisation catalysts with alkenes revealed an interesting activity. Several of the single site catalysts are able to convert ethylene in high molecular weight polyethylene
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Paradis, Delphine. "Méthode d'analyse dans le miel de trois familles d'insecticides (nicotinoïdes, pyréthrinoïdes et pyrazoles) par chromatographies en phase gazeuse et en phase liquide couplées à la spectrométrie de masse en tandem. : application à l' étude de contamination de ruches." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4058.
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Les différentes techniques d'extraction et d'analyse existant pour étudier les insecticides contenus dans le miel ne permettent pas toujours d'atteindre de faibles limites de détection. Or, pour évaluer la toxicité des pesticides, des valeurs de limites de détection de l'ordre du ng/g doivent être obtenues. L'objectif de ce travail a été de développer des méthodes d'extraction et d'analyse compatibles avec différents types de miels (miels de nectars et de miellats, monofloraux et multifloraux) et permettant de rechercher 25 insecticides d'intérêt appartenant à 3 familles (nicotinoïdes, pyréthrinoïdes et pyrazoles,), avec des limites de détection les plus faibles possibles et en éliminant au maximum les interférences liées à la matrice. Après comparaison de différentes méthodes d'extraction, la technique retenue est basée sur la méthode QuEChERS EN 15662, qui consiste en une extraction et une purification à l'aide de sels adaptés à la matrice et aux composés à extraire. Les analyses ont ensuite été effectuées en chromatographie en phase gazeuse couplée à la spectrométrie de masse en tandem (GC-MS²), pour les pyrazoles et les pyréthrinoïdes, et en chromatographie liquide haute performance couplée à la spectrométrie de masse en tandem (LC-MS²) pour les nicotinoïdes et un pyrazole, les réglages des appareils devant être optimisés pour permettre d'obtenir une limite de détection très basse. Les rendements d'extraction obtenus sont majoritairement compris entre 60 et 140%. Les méthodes développées sont spécifiques pour les miels testésSeveral extraction and analytical techniques existing to study insecticides in honey do not always allow reaching low limits of detection. However, to evaluate the toxicity of pesticides, values of limits of detection have to be close to 1 ng/g. The aim of this work was to develop extraction and analytical methods compatible with various types of honey (nectars and honeydews, monofloral and multifloral) and allowing to look for 25 insecticides belonging to 3 families (nicotinoids, pyrethroids and pyrazoles), with the lowest possible limits of detection and eliminating the maximum interference due to the matrix. After comparison of different extraction methods, the reserved technique is based on the QuEChERS EN 15662 method, which consists of an extraction and a purification with mixtures of salts adapted to the matrix and to the compounds to be extracted. Analysis were then performed using gas chromatography coupled with tandem mass spectrometry (GC-MS²) for the pyrazoles and the pyrethroids, and using high performance liquid chromatography coupled with tandem mass spectrometry (LC-MS²) for the nicotinoids and one pyrazole. Device settings have to be optimized to obtain a very low limit of detection. The mean extraction yields were typically between 60 and 140%. The methods are specific for tested honeys. These methods are applicable to analyze commercial honeys and allow reaching limits of detection between 0.2 and 0.7 ng/g. In practice, the dosage of these 3 families in different types of honeys, at low concentrations can be made in routine in an analysis laboratory
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Poulsen, Sally-Ann, and n/a. "Pyrazolo(3,4-d)pyrimidines: Synthesis and Structure-Activity Relationships for Binding to Adenosine Receptors." Griffith University. School of Science, 1996. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20050901.161632.
Full textAbstract:
Chapter 1 of thesis is a literature review of adenosine research. The central importance of the contributions of both classical pharmacology and, more recently, molecular biology to adenosine research is demonstrated. These disciplines have enabled the classification and characterisation of adenosine receptors and as well an understanding of the physiological significance of endogenous adenosine. The significant benefits of developing therapeutics for regulation of the diverse physiological functions of adenosine, by regulation of adenosine receptors, is outlined. For this therapeutic potential to be realised both high affinity and subtype selective adenosine agonists and antagonists are required. The structure-activity relationships for agonists and xanthine antagonists are discussed. The assimilation of these structure-activity relationships have guided the development of ligand based models of the adenosine receptor pharmacophore. The 'flipped', 'N6-C8' and 'three binding domain' models were described. These models aim to direct the future design of high affinity and selective ligands for adenosine receptors. The development of receptor based models by modelling of the receptor-ligand complex is also presented. The main body of this thesis presents a study of the structure-activity relationships for pyrazolo(3,4-d) pyrimidines binding to adenosine Ai and A2a receptors. Prior to this study few non-xanthine adenosine antagonists had been well defined or optimised in terms of structure-activity relationships. However, the value of such ligands is immense, facilitating further definition of structural requirements for high affinity and selective adenosine receptor binding. These ligands should complement existing agonists and xanthine antagonists in developing an understanding of adenosine receptor binding. The experimental approach to development of the lead compound of this study, a-(6-(l'-carbamoylethylthio)- l-phenylpyrazolo(3,4-d)pyrimidin-4-ylthio)propanamide (5), is outlined in Chapter 2 of this thesis. 5 is substituted at C-4, C-6 and N-i of the pyrazolo(3,4-d)pyrimidine heterocycle. The experimental approach to optiniising 5 was approached in a rational manner, requiring an iterative approach i.e. design of generation I target compounds --synthesis -- biological evaluation -- structure-activity relationships -- design of generation II target compounds, etc. Chapters 3, 4 and 5 of this thesis describe this experimental approach as it relates to optimising the lead compound, 5, for adenosine receptor affinity and subtype selectivity. The importance of receptor interactions with multiple ligand domains, to achieve both potency and selectivity, was recognised so that optimisation of the C-4, C-6 and N-i substituents of the lead compound was targeted and achieved. Previous structure-activity studies with agonists and xanthine antagonists have concentrated on modifying a single ligand domain. Chapter 3 presents twelve generation I target compounds to examine C-4 and C-6 substituent structure-activity relationships. Chapter 4 presents twelve generation II target compounds to further examine C-4 and C-6 substituent structure-activity relationships. Chapter 5 presents sixteen generation ifi target compounds to examine N-I substituent structure-activity relationships. A major outcome from the research presented in these chapters was the development of highly potent and highly selective ligands for the adenosine A1 receptor subtype. a(4-Methylamino- I -phenylpyrazolo(3,4-d)pyrimidin-6-ylthio)hexanamide (29) was the most potent ligand at the Ai receptor identified in this study, and is one of the most potent Ai selective antagonists ever reported. 29 has an A1 K1 value of 0.745±0.045 nM and is 332-fold selective for the A1 receptor over the A2a receptor. a-(1-Phenyl-4-propylthiopyrazolo(3,4-d)pyrimidin-6-ylthio)butanainide (27) was the most selective ligand of this study. It is four orders of magnitude selective for the A1 receptor (up to 16900-fold), and one of the most selective antagonists ever reported. This high selectivity has been achieved with the maintenance of good A1 affinity (A1 K1 = 29.5±6.6 nM). These results prove the value of modifying multiple substituents of adenosine receptor ligands, generating ligands which bind with high potency and selectivity to adenosine Al receptors compared to adenosine A2a receptors.
21
Grimes-Marchan, Thomas V. Cundari Thomas R. "Quantum perspectives on physical and inorganic chemistry." [Denton, Tex.] : University of North Texas, 2007. http://digital.library.unt.edu/permalink/meta-dc-5172.
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Toto, Patrick. "Contribution à l'étude du 1H-pyrazole-4-carboxylate d'éthyle et de ses dérivés : application à la synthèse de nouveaux hétérocycles polycondensés." Orléans, 2004. http://www.theses.fr/2004ORLE2001.
Full textAbstract:
Le Diabète est une affection due à une déficience des mécanismes de régulation de la glycémie, dont la fréquence a augmentée de façon régulière et significative au sein des pays riches occidentaux durant les trente dernières années. Les hypoglycémiants de synthèse sont employés dans le cadre du traitement du Diabète non insulino-dépendant. Afin de synthétiser de nouvelles molécules hypoglycémiantes, des méthodologies de fonctionnalisation du 1H-pyrazole-4-carboxylate d'éthyle ont été développées à partir des 3 et 5 aminopyrazole-4-carboxylate d'éthyle. Dans un premier temps les positions 3 et 5 ont été halogénées par diazotation ou substitution électrophile. Les halogénopyrazoles obtenus ont permit d'accéder à divers pyrazoles tétrasubstitués par métallation, couplage ou SNar. Dans un deuxième temps des pontages N1-C5, C3-C4, C4-C5 ont conduit à de nouveaux hétérocycles polycondensés tel que les thiéno[2,3c]pyrazoles ou les 4-thia-1,8a-diaza-azulènes obtenus par métathèse.
23
Poulsen, Sally-Ann. "Pyrazolo(3,4-d)pyrimidines: Synthesis and Structure-Activity Relationships for Binding to Adenosine Receptors." Thesis, Griffith University, 1996. http://hdl.handle.net/10072/365893.
Full textAbstract:
Chapter 1 of thesis is a literature review of adenosine research. The central importance of the contributions of both classical pharmacology and, more recently, molecular biology to adenosine research is demonstrated. These disciplines have enabled the classification and characterisation of adenosine receptors and as well an understanding of the physiological significance of endogenous adenosine. The significant benefits of developing therapeutics for regulation of the diverse physiological functions of adenosine, by regulation of adenosine receptors, is outlined. For this therapeutic potential to be realised both high affinity and subtype selective adenosine agonists and antagonists are required. The structure-activity relationships for agonists and xanthine antagonists are discussed. The assimilation of these structure-activity relationships have guided the development of ligand based models of the adenosine receptor pharmacophore. The 'flipped', 'N6-C8' and 'three binding domain' models were described. These models aim to direct the future design of high affinity and selective ligands for adenosine receptors. The development of receptor based models by modelling of the receptor-ligand complex is also presented. The main body of this thesis presents a study of the structure-activity relationships for pyrazolo(3,4-d) pyrimidines binding to adenosine Ai and A2a receptors. Prior to this study few non-xanthine adenosine antagonists had been well defined or optimised in terms of structure-activity relationships. However, the value of such ligands is immense, facilitating further definition of structural requirements for high affinity and selective adenosine receptor binding. These ligands should complement existing agonists and xanthine antagonists in developing an understanding of adenosine receptor binding. The experimental approach to development of the lead compound of this study, a-(6-(l'-carbamoylethylthio)- l-phenylpyrazolo(3,4-d)pyrimidin-4-ylthio)propanamide (5), is outlined in Chapter 2 of this thesis. 5 is substituted at C-4, C-6 and N-i of the pyrazolo(3,4-d)pyrimidine heterocycle. The experimental approach to optiniising 5 was approached in a rational manner, requiring an iterative approach i.e. design of generation I target compounds --synthesis -- biological evaluation -- structure-activity relationships -- design of generation II target compounds, etc. Chapters 3, 4 and 5 of this thesis describe this experimental approach as it relates to optimising the lead compound, 5, for adenosine receptor affinity and subtype selectivity. The importance of receptor interactions with multiple ligand domains, to achieve both potency and selectivity, was recognised so that optimisation of the C-4, C-6 and N-i substituents of the lead compound was targeted and achieved. Previous structure-activity studies with agonists and xanthine antagonists have concentrated on modifying a single ligand domain. Chapter 3 presents twelve generation I target compounds to examine C-4 and C-6 substituent structure-activity relationships. Chapter 4 presents twelve generation II target compounds to further examine C-4 and C-6 substituent structure-activity relationships. Chapter 5 presents sixteen generation ifi target compounds to examine N-I substituent structure-activity relationships. A major outcome from the research presented in these chapters was the development of highly potent and highly selective ligands for the adenosine A1 receptor subtype. a(4-Methylamino- I -phenylpyrazolo(3,4-d)pyrimidin-6-ylthio)hexanamide (29) was the most potent ligand at the Ai receptor identified in this study, and is one of the most potent Ai selective antagonists ever reported. 29 has an A1 K1 value of 0.745±0.045 nM and is 332-fold selective for the A1 receptor over the A2a receptor. a-(1-Phenyl-4-propylthiopyrazolo(3,4-d)pyrimidin-6-ylthio)butanainide (27) was the most selective ligand of this study. It is four orders of magnitude selective for the A1 receptor (up to 16900-fold), and one of the most selective antagonists ever reported. This high selectivity has been achieved with the maintenance of good A1 affinity (A1 K1 = 29.5±6.6 nM). These results prove the value of modifying multiple substituents of adenosine receptor ligands, generating ligands which bind with high potency and selectivity to adenosine Al receptors compared to adenosine A2a receptors.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Science
Science, Environment, Engineering and Technology
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Karabiyikoglu, Sedef. "Synthesis Of Ferrocenyl Substituted Pyrazoles By Sonogashira And Suzuki-miyaura Cross-coupling Reactions." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/3/12612139/index.pdf.
Full textAbstract:
Pyrazoles constitute one of the most important classes of heterocyclic compounds due to their interesting chemical and biochemical features. Researchers have studied many pyrazole containing structures for almost over a century in order to investigate the various biological activities possessed by these molecules. A new and important trend in these studies is to produce ferrocenyl substituted pyrazoles since ferrocene attracts considerable interest in the research field of organometallic and bioorganometallic chemistry because of its valuable chemical characteristics like high stability, low toxicity and enhanced redox properties. Moreover, the results of the studies focusing on ferrocenyl compounds have been quite promising. Therefore, the scope of this project involves the combination of the essential structural features of pyrazoles with a ferrocene moiety, which could provide new derivatives with enhanced biological activities. In the course of the project the synthesis of new pyrazole derivatives was performed through Sonogashira and Suzuki-Miyaura cross-coupling reactions of 5-ferrocenyl-4-iodo-1-phenyl-1H-pyrazole with terminal alkynes and boronic acids respectively in the presence of a catalytic amount of PdCl2(PPh3)2. Although Sonogashira and Suzuki-Miyaura coupling reactions are well known in literature, they were not studied in much detail with multi-substituted pyrazoles. This also revealed the requirement of the reinvestigation of the reactions and improvement of the yields of pyrazoles by optimizing the reaction conditions.
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Karahan, Dag Fulya. "Synthesis Of 5-ferrocenyl-4-((4-nitrophenyl)sulfenyl)-1h-pyrazoles By Electrophilic Cyclization." Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613443/index.pdf.
Full textAbstract:
Pyrazoles have been intensely studied in the design and synthesis of biologically active agents because they display considerable medicinal activities. Recent studies have shown that integration of a ferrocenyl unit with structural features of pyrazoles can result in the formation of the new products with enhanced or/and unexpected biological activity since several ferrocene derivatives have already been illustrated to be active against a number of tumors. Therefore, we have investigated the electrophilic cyclizations of the hydrazones to afford 5-ferrocenyl-4-((4-nitrophenyl)sulfenyl)-substituted pyrazole derivatives. First, the requisite hydrazone derivatives were synthesized by the reactions of ferrocenyl propargyl aldehydes or ketones with a series of hydrazines. Then electrophilic cyclizations of these hydrazones were investigated by treating with 4-(nitrophenyl)sulfenyl chloride as electrophile. By employing these electrophilic cyclizations, a series of 5-ferrocenyl-4-((4-nitrophenyl)sulfenyl)-1H-pyrazoles, 5-ferrocenyl-4-((4-nitrophenyl) sulfenyl)-3-methyl-1H-pyrazoles and 5-ferrocenyl-4-((4-nitrophenyl)sulfenyl)-3-phenyl-1H-pyrazoles have been synthesized in moderate to good yields.
26
Moukhliss, Maâti. "Synthèse de pyrazoles chiraux à squelette pinanique et cycloisomérisation catalytique de diènes-1,6." Aix-Marseille 3, 2001. http://www.theses.fr/2001AIX30029.
Full textAbstract:
L'objectif de cette thèse est l'étude de la réaction de cycloisomérisation énantiosélective de diènes-1,6 par des complexes cationiques et neutres du palladium. Dans un premier temps, nous avons préparé une série de nouveaux ligands azotés chiraux : des pyrazoles annelés à partir du " pool chiral ". Ces composés sont obtenus par condensation de dicétones chirales avec l'hydrazine. Une nouvelle voie de synthèse, en une séquence " one pot " a été mise au point. Elle consiste à condenser, le myrténal et l'énone correspondante avec une hydrazine substituée par un groupement tosyle. L'alkylation de ces pyrazoles a permis d'obtenir de nouveaux ligands mixtes (amino-alcools, amides, esters d'acides β-aminés). Nous avons, ensuite, étudié la réaction de cyclisation de diènes-1,6. Au cours de cette étude, nous avons démontré que la sélectivité de la réaction de cyclisation du bis-allyle malonate, pris comme modèle, dépend de la nature du complexe de palladium et de sa charge. Si les complexes neutres et monocationiques favorisent la formation exclusive d'un cyclopentène, les complexes dicationiques, favorisent la formation d'un cyclopentaneThe aim of this thesis is the study of the enantioselective cycloisomerisation of 1,6-dienes by cationic and neutral palladium catalysts. A first, we prepared a series of new chiral nitrogen centred ligands, essentially, annelated pyrazoles from the " chiral pool ". These composed are obtained by condensation of chiral diketones with the hydrazine. A new synthetic way, in a " one-pot " sequence was finalised. It consists in condensing, under basic conditions, a conjugated enal or enone with the hydrazine substituted with a tosyle group. Subsequently, the alkylation of the chiral pyrazoles allowed to obtain some new mixed ligands (amino-alcohols, amides, and of β-amino-esters). A C2 symmetric bis-pyrazoles was obtained from 2,2-dimethoxypropane. At a second time, we studied the cycloisomerisation of 1,6-dienes. During this study, we could show that the selectivity of the cyclisation of the diallyle malonate, take as model, depends on the nature of the palladium complex and of its charge. Neutral and monocationic complexes, favour the exclusive formation of a cyclopentene (non-symmetric), whereas dicationic complexes favour the forming of an exomethylene cyclopentane
27
Grimes-Marchan, Thomas V. "Quantum Perspectives on Physical and Inorganic Chemistry." Thesis, University of North Texas, 2007. https://digital.library.unt.edu/ark:/67531/metadc5172/.
Full textAbstract:
Applications of computational quantum chemistry are presented, including an analysis of the photophysics of cyclic trinuclear coinage metal pyrazolates, an investigation into a potential catalytic cycle utilizing transition metal scorpionates to activate arene C-H bonds, and a presentation of the benchmarking of a new composite model chemistry (the correlation consistent composite approach, ccCA) for the prediction of classical barrier heights. Modeling the pyrazolate photophysics indicates a significant geometric distortion upon excitation and the impact of both metal identity and substituents on the pyrazolates, pointing to ways in which these systems may be used to produce rationally-tuned phosphors. Similarly, thermodynamic and structural investigations into the catalyst system points to promising candidates for clean catalytic activation of arenes. The ccCA was found to reproduce classical reaction barriers with chemical accuracy, outperforming all DFT, ab initio, and composite methods benchmarked.
28
Nguyen, Xuan Anh. "Synthèse de nouvelles familles de molécules à visée thérapeutique anti-herpétique : optimisation par des approches de "cheminformatique" et de chimie médicinale." Lyon 1, 2006. http://www.theses.fr/2006LYO10203.
Full textAbstract:
Le virus de l'herpès simplex (HSV-1 et HSV-2) est responsable de l'infection de près de 90 % de la population mondiale. Les infections de l'herpès sont habituellement bénignes, mais peuvent provoquer dans certains cas des complications graves (herpès néo-natal ou chez des immuno-déprimés). La maladie est d'autant plus contagieuse que les manifestations peuvent être asymptomatiques. Le traitement principal disponible depuis des années 70 est à base d'acyclovir ; traitement dont on dénombre de plus en plus de cas de résistance virale. Le point de départ de cette thèse est la validation par une équipe du CNRS de la voie des polyamines comme nouvelle voie thérapeutique contre les infections de l'herpès. Une enzyme de cette voie (la SAMDC) a ainsi été validée comme cible anti-herpétique. L'objectif de cette thèse était donc de synthétiser et d'optimiser de nouveaux composés actifs contre cette cible désignée. Pour ce faire, nous avons adopté deux voies d'accès complémentaires : la chimie classique et la chimie rationnelle. Par ces deux voies nous avons obtenu deux familles de molécules qui ont été ensuite optimisées. Finalement, nous avons sélectionné deux molécules qui ont passé avec succès le premier test sur animalThe virus of the herpes simplex (HSV-1 and HSV-2) is responsible for the infection of almost 90% to the world population. The infections of the herpes are usually benign, but can cause in certain cases of the serious complications (néo-native herpeses or at immuno-depressed). The disease is all the more contagious as the demonstrations can be asymptomatic. The principal treatment available since the Seventies is containing acyclovir; treatment which one counts case of viral resistance more and more. The starting point of this thesis is the validation by a team of the CNRS of the way of the polyamines like new therapeutic way against the infections of the herpes. An enzyme of this way (the SAMDC) was thus validated like antiherpetic target. The objective of this thesis was thus to synthesize and optimize new active compounds against this indicated target. With this intention, we adopted two complementary access roads: traditional chemistry and rational chemistry. By these two ways we obtained two families of molecules which were then optimized. Finally, we selected two molecules which passed successfully the first test on animal
29
Rochais, Christophe. "Synthèse et étude physico-chimique de nouvelles pyrrolo- et pyrazolopyrrolizines à visée anticancéreuse." Caen, 2005. http://www.theses.fr/2005CAEN4061.
Full textAbstract:
Le travail décrit dans ce mémoire porte sur la synthèse, l'étude physico-chimique et l'évaluation biologique de nouvelles 3-aryl-pyrrolo[2,3-b]pyrrolizin-8-ones et 3-aryl-pyrazolo[3,4-b]pyrrolizin-8-ones. Ce programme fait suite à de nombreux travaux de recherche effectués au Centre d'Etudes et de Recherche sur le Médicament de Normandie ces dernières années. Après une description des différentes cibles envisagées et de leurs inhibiteurs, les travaux antérieurs réalisés au laboratoire dans le domaine des " tripentones " sont évoqués. L'essentiel de ce travail est toutefois consacré au développement de nouveaux aminoesters du pyrrole et du pyrazole puis à la synthèse et à la pharmacomodulation de nouvelles tripentones pyrroliques et pyrazoliques. Les travaux de synthèse sont suivis de la description des résultats pharmacologiques obtenus par nos composés dans le domaine de la cancérologie. Enfin une étude de modélisation moléculaire nous permet d'établir de nouvelles perspectives de pharmacomodulation. La partie expérimentale de ce manuscrit comporte l'ensemble des structures chimiques, leurs caractéristiques physico-chimiques et les modes opératoires nécessaires à leur synthèse. Enfin, plus de deux cents références bibliographiques sont citéesThe work described in this document decides to the synthesis, the physico-chemical study and the biological evaluation of new 3-aryl-pyrrolo[2,3-b]pyrrolizin-8-ones and 3-aryl-pyrazolo[3,4-b]pyrrolizin-8-ones. The discovery of this new family of compounds derives from many research programs developed at the “Centre d'Etudes et de Recherche sur le Médicament de Normandie”. Following a description of different biological targets and their inhibitors, previous works carried in our laboratory about a new heterocyclic family the “tripentones” are reviewed. The development of new pyrrolic and pyrazolic aminoesters and their use for the synthesis and study of novel tripentones in these series constitute the main subject of this thesis. Their prospective anticancer properties are supported by pharmacological results. Lastly, a molecular modelling study that opens new prospects for pharmacomodulation is presented. The experimental part describes the procedures and the physicochemical properties of all the compounds presented. Incidentally, more than 200 bibliographical references are cited
30
Delaunay, Thierry. "Synthèses concises de pyrazoles et pyridones diversement fonctionnalisées dans le but d’effectuer des réactions de couplages croisés sélectifs." Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10274/document.
Full textAbstract:
Ce mémoire est subdivise en deux parties. La première partie concerne la synthèse de pyrazoles présentant un intérêt sur le plan agrochimique. En effet, le noyau pyrazole est présent dans de nombreux composes ayant des activités biologiques diverses et en particulier antifongique. Au cours de ce travail, nous avons développé diverses approches convergentes de pyrazoles diversement substitués au moyen de réactions de couplages croisés pallado-catalyses sélectifs et séquentiels à partir de pyrazoles possédant différents points d’encrages. Dans la deuxième partie, nous nous sommes intéressés à la synthèse de diverses furopyridones en tant qu’analogues de produits naturels possédant une activité antifongique, et notamment le Cladobotryal. Dans ce but, diverses alcynylpyridones ont été synthétisées et mises en jeu dans divers processus de cyclisation pour atteindre de manière divergente une série de furo[3,2-c]pyridin-4-ones, furo[3,2-c]pyridin-6-ones et furo[2,3-b]pyridin-4-onesThis thesis is subdivided into two principal parts. The first part is focussed on the synthesis of pyrazole derivatives of agrochemical relevance. Indeed, the pyrazole nucleus is found in numerous compounds possessing interesting biological properties, and notably antifungal activities. Various convergent approaches to diversely substituted pyrazoles have therefore been developed by means of site-selective palladium-catalyzed cross-coupling reactions conducted sequentially on pyrazole scaffolds. In the second part, we have been involved in the synthesis of furopyridones as simplified analogues of natural compounds possessing antifungal activities such as Cladobotryal. Toward this end, various alkynylpyridones have been synthesizes and involved in diverse cyclization processes to access a series of furo[3,2-c]pyridin-4-ones, furo[3,2-c]pyridin-6-ones, and furo[2,3-b]pyridin-4-ones
31
Pinar, Ayse Nur. "Reaction Of Propargyl Aldehydes With Hydrazinium Salts: Synthesis Of Ferrocenyl And Phenyl Substituted Pyrazoles." Master's thesis, METU, 2008. http://etd.lib.metu.edu.tr/upload/3/12609769/index.pdf.
Full textAbstract:
Pyrazoles have been focus of a large number of investigations in the design and
synthesis of novel biologically active agents that show remarkable medicinal
activities. Although pyrazoles have been studied for over a century as an important
class of heterocyclic compounds, they still continue to attract considerable attention
due to the wide range of medicinal activities they possess. Recent studies have
shown that combination of a ferrocenyl unit with structural features of pyrazoles can
lead to products with enhanced or/and unexpected biological activity since several
ferrocene derivatives have already been shown to be active against a number of
tumors. As a result, we have investigated the reaction of 3-ferrocenylpropynal with
hydrazinium salts. As anticipated, these reactions afforded two kinds of pyrazoles,
namely 1-alkyl/aryl-5-ferrocenylpyrazoles (1,5-isomer) and 1-alkyl/aryl-3-
ferrocenylpyrazoles (1,3-isomer). In most cases, 1,5-pyrazole isomers have resulted
from these reactions as the single or the major product of the reactions. The
structures of 1-benzyl-5-ferrocenylpyrazole, 1-phenyl-5-ferrocenyl-pyrazole and 1-
(2-hydroxy-ethyl)-3-ferrocenylpyrazole were identified by X-ray single crystal
analysis. The analogous reactions between 3-phenylpropynal and hydrazinium salts
were also studied, which afforded 1-alkyl/aryl-5-phenylpyrazoles (1,5-isomer) and/or
v
1-alkyl/aryl-3-phenylpyrazoles (1,3-isomer). The regioselectivity of the reactions is
mainly governed by the nature of the substituents in hydrazine derivative.
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Santos, Nádia Alexandra Esteves. "Synthesis and evaluation of new pyrazoles, glycosylpyrazoles and rutheniumpyrazoles for antioxidant and antitumoral activity." Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/22521.
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Mestrado em Biotecnologia - Biotecnologia MolecularO cancro é a segunda maior razão de morte em Portugal, a seguir às doenças cardiovasculares. A quimioterapia continua a ser o tratamento mais utilizado e eficaz, no entanto o intervalo onde a dose é eficiente e ao mesmo tempo segura ainda é muito pequeno, podendo ser tóxico para o organismo do paciente. Dessa forma, a procura de novos agentes antitumorais eficientes e seguros tem sido crucial, tendo os pirazóis e os complexos de ruténio (II) um papel muito importante. Vários compostos contendo o anel de pirazol nas suas estruturas já demonstraram grande poder antitumoral ao inibirem enzimas cinases, tais como as aurosa cinases e as cinases dependentes de ciclina, ao induzirem a apoptose e até agindo como agentes citotóxicos contra linhas celulares tumorais. Os complexos de ruténio, por sua vez, contribuem para uma ação antitumoral mais seletiva, por terem propriedades redox ou pela incorporação de ligandos lábeis que criam locais de ligação a biomoléculas. Neste trabalho pretende-se sintetizar novos derivados de pirazol, proceder à sua glicosilação e ligação com um complexo de ruténio. Serão feitos estudos de citotoxicidade dos compostos sintetizados, para estudar o seu efeito antitumoral, e ainda testes para avaliar a sua atividade antioxidante, uma vez que a formação de espécies reativas de oxigénio, inflamação crónica e o desenvolvimento de cancro, estão muitas vezes associados. Com base nestes estudos estabelecer-se-ão importantes relações estrutura-atividade biológica que ajudarão a perceber quais os requisitos estruturais mais importantes para a atividade destes compostos.
Cancer is the second main cause of death in Portugal, after cardiovascular diseases. Chemotherapy is still the most used and effective treatment, however the window in which the dose is still safe and efficient is small and consequently it can be toxic to patient’s body. For that reason, the design and discovery of non-traditional antitumoral agents that are both efficient and safe is a key research issue, where pyrazoles and ruthenium (II) complexes have an important role. Several pyrazole-derived compounds have already demonstrated great antitumoral activity by inhibiting kinase enzymes such as aurora kinases and cyclin-dependent kinases, by inducing apoptosis and also by being cytotoxic to several cancer cell lines. Ruthenium complexes contribute to the antitumoral action by having redox properties and by being able to incorporate labile ligands that create, in vivo, active bonding sites for biomolecules. The present work aims the synthesis of new pyrazole derivatives, following by their glycosylation and incorporation into ruthenium(II) complexes. Cytotoxicity studies will be carried out to evaluate their antitumoral effect. In addition, antioxidant activities will be studied since reactive oxygen species, chronic inflammation and cancer development are often connected. Finally, important structure-activity relationships will be established, based on the results of the biological tests, highlighting the key structural requirements needed for the activity of these compounds.
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RAPETTI, FEDERICA. "New different catecholic and heterocyclic compounds able to interfere with different pathways in inflammation and cancer." Doctoral thesis, Università degli studi di Genova, 2022. http://hdl.handle.net/11567/1083981.
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During my 3 years of PhD, I followed in parallel two projects:
1) synthesis of selective PDE4D3 inhibitors (PDE4Is), characterized by a substituted catechol scaffold, typical of Rolipram (pan-PDE4I), connected to an amino/amide tail through different linkers; 2) synthesis and biological evaluation of new compounds in which catechol moiety is connected to pyrazole and imidazo-pyrazole scaffolds through an acylhydrazonic linker to obtain potential anti-inflammatory and anticancer agents.
In the 1st part of my PhD, I performed the chiral resolution of our lead GEBR-32a racemate, a PDE4D3I with no side-effects, to verify the potency of single enantiomers; I was also involved in the identification of an enzyme useful for the enantioselective synthesis of GEBR-library compounds (Industrial Organic Chemistry and Biotechnology Department at Bielefeld). Finally, to obtain more selective PDE4D3Is and expand SAR information, three new classes of compounds were designed and synthesized, in detail: a) isosteric derivatives of GEBR-32a; b) molecules with more rigid catecholic core; c) molecules with bulkier linkers. All the new compounds will be tested on PDE4D catalytic domain and PDE4D3 enzyme to evaluate their inhibitory activity. Crystallographic studies will be also performed (Latvian Institute of Organic Synthesis, Riga, Latvia).
In the 2nd part of my PhD, based on previous compounds able to inhibit neutrophil chemotaxis towards inflamed tissues and having in mind the potential role of PDE4Is in inflammation, cancer and angiogenesis process, we designed new hybrid compounds to obtain molecules able to act on inflammation through different intracellular mechanisms. These new compounds, characterized by a pyrazole and imidazo-pyrazole scaffolds, were tested on platelet to evaluate their inhibition on ROS production and were also submitted to a large screening to evaluate their anticancer activity at National Cancer Institute (NCI) and Policlinico San Martino Hospital (IRCCS).
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Scammells, Peter J., and n/a. "Pyrazolo(3,4-d)Pyrimidines and adenosine receptors: a structure/activity study." Griffith University. Division of Science and Technology, 1990. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20050826.141630.
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Pyrazolopyrimidines are a general class of compounds which exhibit Aj adenosine receptor affmity. A number of pyrazolo(3,4-d)pyrimidine analogues of isoguanosine and i-methylisoguanosine has been synthesised. All compounds were tested forAi adenosine receptor affinity using a (311) R-PIA competitive binding assay. The N-i and N-5 positions were substituted with a number of different ailcyl and aryi groups. 3-Chiorophenyl substitution of the N-i position and butyl substitution of the N-5 position greatly enhanced the overall adenosine receptor affinity. Substitution by a methyl group at the N-7 position fixed the C-4 position in the imino tautomeric form. This resulted in a marked reduction in activity. The substitution of the N-2 position with a phenyl group produced an analogue with a similar structure to i,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX). A 2-phenyl substituent was favourable for interaction with the adenosine receptor. A number of pyrazolo(3,4-d)pyrirnidine analogues of 4,6-bis-a-carbamoylethylthio-i-phenylthiopyrazolo(3,4-d)pyrinhidine (DJB-KK) has also been synthesised and tested for Aj adenosine receptor affinity. 4,6-Bis-alkylthio-1-phenylpyrazolo(3,4-d)pyrimidines with a-carbamoylethyl and u-carbamoylpropyi groups were compared. The additional methyiene of the a-carbamoylpropyl group produced increased adenosine receptor affinity. 6-a-Carbamoylethylthio-4-mercapto-1-phenylpyrazolo(3,4-d)pyrimidine and 4-cc-carbamoylethylthio- i-phenylpyrazolo(3,4-dlpyrimidine were compared. Substitution of the C-6 position maintained activity, while substitution of the C-4 reduced activity.
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Dunham, Jason C. "Synthesis of 4-alkyl-3,5-diamino-1-phenylpyrazoles." Virtual Press, 2006. http://liblink.bsu.edu/uhtbin/catkey/1339144.
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The goal of this project is to synthesize and purify a library of novel 4-alkyl-3,5-diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazoles. These molecules are similar to other fiproles, which have been shown by Sammelson et al. to have pesticidal activities at the GABA receptor.' Fiproles are analogues of Fipronil, a very important pesticide. Replacing the cyano group normally located at the 3-position of the pyrazole ring with an amino group will change the binding potency of the phenylpyrazoles. Changes in binding produced by the changes introduced in molecular structure can create more information about the GABA receptor.Synthesis of our target compounds starts with production of monosubstituted malononitriles. Conventionally a two-step process, our research developed a new, efficient one-step process using borohydride as the only reagent. We utilized this method in the synthesis of desired monosubstituted malononitriles. These were converted to unsymmetrical disubstituted malononitriles, and to our target fiprole compounds, through a 4-alkyl-3,5-diaminopyrazole intermediate.Department of Chemistry
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Frideling, Aline. "Composés pyrazoliques et tétrahydroacriniques dérivant d'un squelette monoterpénique." Aix-Marseille 3, 2001. http://www.theses.fr/2001AIX30057.
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Les tétrahydroacridines représentent une classe de composés très intéressante pour leurs activités biologiques ; elles agissent notamment sur la maladie d'Alzheimer. Les pyrazoles sont, eux aussi, une classe de composés très répandue dans divers aspects de la chimies organique. Nous avons synthétisé de nouvelles molécules issues de ces deux familles en partant de cétones monoterpéniques optiquement actives. Les synthèses ont été conduites de deux façons, par les méthodes classiques et par les synthèses assistées par micro-ondes. Nous avons donc mis au point de nouvelles voies d'accès aux 1,2,3,4-tétrahydroacrinines, 9-chloro-1,2,3,4-tétrahydroacrinines et 9-amino-1,2,3,4-tétrahydroacrinines. La synthèse assistée par mico-ondes a également permis de greffer des pyrazoles sur des tétrahydroacrinines, et de trimériser des pyrazolesTetrahydroacridines are an important component category, because of their biological activity, for example their effect on Alzheimer disease. Pyrazoles are frequent compounds in many aspects of organic chemistry. We synthetized new molecules of those two families, with, as precursors, optically actives monoterpenic ketones. Synthesis were made by two ways, classical methods and microwaves assisted synthesis. We found new way to obtain 1,2,3,4-tetrahydroacridones, 9-chloro-1,2,3,4-tetrahydroacridines and 9-amino-1,2,3,4-tetrahydroacridines. With assisted synthesis we made an hybrid between pyrazoles and tetrahydroacridines, and made a trimerisation of pyrazoles
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Scammells, Peter. "Pyrazolo(3,4-d)Pyrimidines and adenosine receptors: a structure/activity study." Thesis, Griffith University, 1990. http://hdl.handle.net/10072/365214.
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Pyrazolopyrimidines are a general class of compounds which exhibit Aj adenosine receptor affmity. A number of pyrazolo(3,4-d)pyrimidine analogues of isoguanosine and i-methylisoguanosine has been synthesised. All compounds were tested forAi adenosine receptor affinity using a (311) R-PIA competitive binding assay. The N-i and N-5 positions were substituted with a number of different ailcyl and aryi groups. 3-Chiorophenyl substitution of the N-i position and butyl substitution of the N-5 position greatly enhanced the overall adenosine receptor affinity. Substitution by a methyl group at the N-7 position fixed the C-4 position in the imino tautomeric form. This resulted in a marked reduction in activity. The substitution of the N-2 position with a phenyl group produced an analogue with a similar structure to i,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX). A 2-phenyl substituent was favourable for interaction with the adenosine receptor. A number of pyrazolo(3,4-d)pyrirnidine analogues of 4,6-bis-a-carbamoylethylthio-i-phenylthiopyrazolo(3,4-d)pyrinhidine (DJB-KK) has also been synthesised and tested for Aj adenosine receptor affinity. 4,6-Bis-alkylthio-1-phenylpyrazolo(3,4-d)pyrimidines with a-carbamoylethyl and u-carbamoylpropyi groups were compared. The additional methyiene of the a-carbamoylpropyl group produced increased adenosine receptor affinity. 6-a-Carbamoylethylthio-4-mercapto-1-phenylpyrazolo(3,4-d)pyrimidine and 4-cc-carbamoylethylthio- i-phenylpyrazolo(3,4-dlpyrimidine were compared. Substitution of the C-6 position maintained activity, while substitution of the C-4 reduced activity.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Division of Science and Technology
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Kivrak, Arif. "Development Of New Methods For The Synthesis Of Pyrazoles, 4-iodopyrazoles, Isoxazoles And 1,2,4-oxadiazoles." Phd thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12612945/index.pdf.
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Synthesis of five-membered heteroaromatic compounds such as pyrazoles, isoxazoles and 1,2,4-oxadiazoles are important for pharmaceutical industry and material science due to their applications. Although there are many methods to prepare such compounds, new variants continue to appear since they exhibit a wide range of biological and medicinal activities.
In this thesis, new methods were developed for the synthesis of 4-iodopyrazoles, pyrazoles, isoxazoles, 1,2,4-oxadiazoles and/or 1,2,4-oxadiazepines. In the first part of the study, electrophilic cyclization of &alpha,&beta
-alkynic hydrazones by molecular iodine and copper iodide were investigated as new ways for the synthesis of 4-iodopyrazoles and pyrazoles, respectively. Initially, &alpha
,&beta
-alkynic hydrazones were prepared by the reactions of propargyl aldehydes and ketones with hydrazines. Then &alpha
,&beta
-alkynic hydrazones were treated with molecular iodine in the presence of NaHCO3, which afforded 4-iodopyrazoles in good to excellent yields. Subsequently, the same reactions were carried out with CuI in the presence of NEt3, which furnished corresponding pyrazoles in good yields. Moreover, ferrocenyl-substituted 4-iodopyrazoles and pyrazole derivatives were synthesized from corresponding
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Prado, Guilherme Cervi. "Study of reaction parameters in ball mill in the Synthesis of aryl(heteroaryl)-1h-pyrazoles." Universidade Federal de Santa Maria, 2012. http://repositorio.ufsm.br/handle/1/10505.
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Conselho Nacional de Desenvolvimento Científico e TecnológicoIn order to eliminate the problems related to deficient intake of vitamins folate class, many food products are being subjected to the enrichment process. Among them, all types of wheat flour must be enriched with folic acid. Therefore, it is evident the need of analytical methods for routine able to effectively determine the levels of folic acid in enriched matrix. The objective of this work was the development and validation of a rapid method for determination of folic acid added to wheat flour, using the technique of high performance liquid chromatography with UV detection. Folic acid was separated using a C8 column. Was used for elution gradient mobile phase with water acidified with glacial acetic acid (pH 2.8) and acetonitrile. Detection was performed with a diode array detector employing a wavelength of 290 nm. External standard was used for quantification. Vitamin matrix was extracted with aqueous potassium hydroxide, 0.1 mol L-1 and aqueous sodium tetraborate 0.04 mol L-1 pH 8.5, followed by cleaning step of the extract of the sample through SPE using SAX cartridges. The method was efficient, with recovery values between 96 and 99%, RSD from 1.3 to 3.8% and LOD and LOQ of 0.28 and 0.937 mg kg-1, respectively. In the analysis of real samples of five brands tested, only one brand presented concentration of folic acid above the minimum required by law.
Com o objetivo de suprimir os problemas relacionados à deficiência de ingesta de vitaminas da classe dos folatos, muitos produtos alimentícios estão sendo submetidos ao processo de enriquecimento. Entre eles, todos tipos de farinha de trigo devem ser enriquecidos com ácido fólico. Portanto, fica evidenciada a necessidade de métodos analíticos para a rotina capazes de determinar com eficácia os níveis de ácido fólico na matriz enriquecida. O objetivo deste trabalho foi o desenvolvimento e validação de um método rápido para determinação de ácido fólico adicionado a farinha de trigo, através da técnica de cromatografia líquida de alta eficiência com detector espectrofotométrico. O ácido fólico foi separado utilizando-se coluna de C8. Utilizou-se eluição por gradiente na fase móvel, com água acidificada com ácido acético glacial (pH 2,8) e acetonitrila. A detecção foi efetuada com detector por arranjo de diodos empregando o comprimento de onda de 290 nm. Foi utilizada padronização externa para quantificação. A vitamina foi extraída da matriz com solução aquosa de hidróxido de potássio 0,1 mol L-1 e solução aquosa de tetraborato de sódio 0,04 mol L-1 de pH 8,5; seguida por etapa de limpeza do extrato da amostra através de SPE, utilizando cartuchos de SAX. O método mostrou-se eficiente, com valores de recuperação entre 96 e 99%, RSD de 1,3 a 3,8% e LOD e LOQ de 0,28 e 0,937 mg kg-1, respectivamente. Nas análises das amostras reais, das cinco marcas analisadas, somente uma marca apresentou concentração de ácido fólico acima do mínimo exigido pela legislação.
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Grosse, Sandrine. "Imidazo[1, 2-b]pyrazoles, imidazo[1, 2-a]imidazoles : synthèse, fonctionnalisation et évaluation biologique." Thesis, Orléans, 2013. http://www.theses.fr/2013ORLE2056.
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Les imidazo[1,2-b]pyrazoles tout comme les imidazo[1,2-a]imidazoles sont des entités présentant diverses applications intéressantes notamment dans le domaine pharmacologique. Cependant, malgré ce potentiel, ces structures hétérobicycliques ont été, jusqu’à ce jour, relativement peu étudiées tant au niveau de leur préparation que de leur fonctionnalisation. De ce fait, ces travaux de thèse ont pour objet la mise au point de nouvelles voies d’accès à ces systèmes bicycliques et ce, au départ de substrats facilement accessibles. Des stratégies de fonctionnalisation de ces charpentes moléculaires ont ensuite été développées dans le but de concevoir des librairies diversifiées de ce type de composés, librairies destinées à être évaluées biologiquement. Les premiers résultats d’évaluation sur des lignées cancéreuses de dérivés imidazo[1,2-b]pyrazoliques sont également présentésImidazo[1,2-b]pyrazoles and imidazo[1,2-a]imidazoles are entities with some interesting applications in pharmacology. However, despite this potential, few methods of preparation and direct functionalisation of the heterocyclic moiety have been described. In this context, the overall goal of our research is to develop new routes to these bicyclic systems from readily available starting materials. Strategies of functionalisation of the heterocyclic moiety were then explored in order to design diversified libraries for the evaluation of potential biological activities. Herein, the results of the tests of imidazo[1,2-b]pyrazole series against various cancer lines are reported
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Paul, Tobias [Verfasser], and Nicolai [Akademischer Betreuer] Burzlaff. "Ligands and Coordination Chemistry Based on Vinyl and Alkynyl Substituted Pyrazoles / Tobias Paul. Gutachter: Nicolai Burzlaff." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2015. http://d-nb.info/1076120520/34.
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Aubert, Philippe. "Bis-silanes propargyliques et bis-propargyliques : applications en synthèse." Poitiers, 1996. http://www.theses.fr/1996POIT2286.
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Dans la premiere partie, nous decrivons a partir de bis-silanes -fonctionnels du type me#3sich#2-cc-ch(sime#3)-ch#2ch#2y (y = osime#3, nhr), la synthese et la protodesilylation de silanes -alleniques heterocycliques, afin de preparer des dienes conjugues heterocycliques. Dans la deuxieme partie, nous avons mis au point une methode d'acces a des bis-silanes bis-propargyliques du type me#3sich#2-cc-(ch#2)#n-cc-ch#2sime#3 (n = 1 (10), 2 (11), 0 (12)) et nous les avons fait reagir avec certains reactifs electrophiles, en presence d'un acide de lewis. C'est ainsi qu'avec les aldehydes, les bis-silanes 10 et 11 forment des bis(vinylidene)oxanes (n = 1) et oxepanes (n = 2), tandis que le bis-silane 12 conduit a des cetones ,'-bis-insaturees trimethylsilylees. Avec les acetals, les bis-silanes 10 et 11 conduisent a des bis(vinylidene)diethers qui, pour n = 2, se transforment thermiquement en derives 1,4-disubstitues du benzocyclobutene ; le bis-silane 12 donne lieu a la formation de diethers dienyniques. Dans la reaction d'aminomethylation-desilylation, seul le bis-silane 10 se comporte comme prevu, conduisant avec les amines primaires a des n-alkyl-3,5-bis(vinylidene)piperidines. Le bis-silane 12 reagit par chauffage, en presence de cucl, avec les amines primaires ou avec l'hydrazine pour conduire a des pyrroles ou des pyrazoles, monosilyles ou non. Enfin, la pyrolyse des bis-silanes 10, 11 et 12 fournit plusieurs types structuraux de bis-silanes, isomeres du bis-silane de depart. Cette etude a donc permis plusieurs avancees dans le domaine de la substitution electrophile des propargylsilanes ; elle montre en particulier que les bis-silanes insatures sont des precurseurs interessants pour la synthese d'heterocycles et de carbocycles
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Despotopoulou, Christina. "Br/Mg-Exchange on 1,2-Dibromocyclopentene Derivatives and Regio- and Chemoselective Functionalizations of Pyrazoles and Related Heterocycles." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-104233.
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Wiley, Jack Scott. "C-H bond activation in iridium complexes /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/8510.
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Delaunay, Thierry. "Synthèses concises de pyrazoles et pyridones diversement fonctionnalisées dans le but d'effectuer des réactions de couplages croisés sélectifs." Phd thesis, Université Claude Bernard - Lyon I, 2010. http://tel.archives-ouvertes.fr/tel-00878928.
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Ce mémoire est subdivise en deux parties. La première partie concerne la synthèse de pyrazoles présentant un intérêt sur le plan agrochimique. En effet, le noyau pyrazole est présent dans de nombreux composes ayant des activités biologiques diverses et en particulier antifongique. Au cours de ce travail, nous avons développé diverses approches convergentes de pyrazoles diversement substitués au moyen de réactions de couplages croisés pallado-catalyses sélectifs et séquentiels à partir de pyrazoles possédant différents points d'encrages. Dans la deuxième partie, nous nous sommes intéressés à la synthèse de diverses furopyridones en tant qu'analogues de produits naturels possédant une activité antifongique, et notamment le Cladobotryal. Dans ce but, diverses alcynylpyridones ont été synthétisées et mises en jeu dans divers processus de cyclisation pour atteindre de manière divergente une série de furo[3,2-c]pyridin-4-ones, furo[3,2-c]pyridin-6-ones et furo[2,3-b]pyridin-4-ones
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Kolodych, Sergii. "Recherche de nouvelles réactions de couplage par criblage immuno-enzymatique." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA112145.
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La recherche de nouvelles réactions est un des enjeux fondamentaux de la chimie organique. En dehors de l’approche classique basée sur la conception d’une réaction en s’appuyant sur les propriétés chimiques des substrats, une nouvelle approche utilisant le criblage systématique de combinaisons aléatoires de fonctions réactives a été récemment adoptée par plusieurs groupes. Cette stratégie nécessite un outil analytique permettant de cribler un très grand nombre de réactions par jour et d’identifier les meilleures combinaisons conduisant à la formation de produits intéressants. Les travaux de thèse présentés dans ce mémoire s’inscrivent dans le contexte de l’utilisation des techniques de dosages immuno-enzymatiques (ELISA) comme outil de criblage pour la recherche de nouvelles réactions de couplage. Dans un premier temps le criblage de 2688 combinaisons de fonctions réactives et de catalyseurs choisies au hasard a été effectué. Ce criblage a permit de mettre en évidence deux nouveaux couplages en présence de sels de cuivre : une réaction entre les thiourées et les phénols conduisant à la formation des isourées et une réaction entre les N-hydroxythiourées et les alcynes conduisant à la formation des thiazole-2-imines. Dans un second temps le criblage de 2816 combinaisons de fonctions sélectionnées, cette fois-ci, de façon rationnelle a été effectué. Ce criblage a visé la découverte de nouvelles cycloadditions [3+2] répondant aux critères de la chimie « click ». Ainsi l’utilisation de dosage immuno-enzymatique a été étendue à l’optimisation des nouvelles réactions découvertes ainsi qu’à l’évaluation de leurs cinétique, chimiosélectivité et biocompatibilité. Près de 3000 tests complémentaires effectuées sur les « hits » issus du criblage primaire ont ainsi permit de mettre en évidence 4 nouvelles réactions de couplage dont une nouvelle réaction « click » : la cycloaddition sydnone-alcyne catalysée au cuivre (CuSAC). Dans la dernière partie de ce manuscrit les études plus détaillées sur la réaction CuSAC ont été effectuées, notamment l’identification de la structure du produit de couplage et l’étendue du champ d’application de cette réaction. Enfin, l’aspect « click » de la réaction CuSAC a été illustré par l’application de cette réaction au marquage d’une protéineDiscovery of new reactions is one of the fundamental goals in organic chemistry. In addition to the traditional approach to reaction discovery, consisting in designing a reaction on the basis of known chemical properties of reagents, new approaches based on the screening of random combinations of reactive functions and catalysts have been recently developed. The main prerequisite of this strategy is an analytical tool allowing screening of a big number of reactions per day and identifying combinations leading to the formation of unanticipated products. In the work presented herein a high-throughput immunoassay screening has been used for the discovery of new coupling reactions. In the first part of this work a screening of 2688 combinations of randomly chosen reactive functions and catalysts was carried out. This screening led to the discovery of two copper-promoted coupling reactions: a reaction between thioureas and phenols leading to the formation of isoureas through desulfurization; and a reaction between N-hydroxythioureas and alkynes leading to the formation of thiazole-2-imines. In the second part of the work a screening of 2816 combinations of rationally designed chemical functions and catalysts was carried out. This screening was focused on the discovery of catalytic [3+2] cycloadditions that comply with the standards of “click” chemistry. In this study, the use of immunoassay screening was extended to optimize new reactions and to evaluate their kinetics, chemoselectivity and biocompatibility. Therefore, around 3000 complementary tests were carried out on the hits, identified in the primary screening. This allowed the discovery of 3 new coupling reactions and one new “click” reaction: a copper-catalyzed sydnone-alkyne cycloaddition (CuSAC). The last part of the work was focused on detailed studies of the CuSAC reaction. Identification of the structure of the coupling product and substrate scope of this reaction was carried out. Finally, the applicability of the CuSAC reaction for bioconjugation was demonstrated by an example of protein labeling
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Ainooson, Michael Kojo. "Binuclear late transition metal complexes with pyrazole based compartmental ligands: Scaffolds for cooperative organometallic transformations." Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://hdl.handle.net/11858/00-1735-0000-0023-98FC-E.
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Raboisson, Pierre. "Développement d'inhibiteurs de phosphodiestérase 4 et conception d'antagonistes purinergiques P2Y1 à partir de dérivés de l'adénine et de leurs analogues structuraux." Université Louis Pasteur (Strasbourg) (1971-2008), 2000. http://www.theses.fr/2000STR13243.
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Benderitter, Pascal Bourguignon Jean-Jacques. "Synthèse et intérêt pharmacologique d'analogues azahétérocycliques de la tétrahydroisoquinoline." Strasbourg : Université Louis Pasteur, 2008. http://eprints-scd-ulp.u-strasbg.fr:8080/939/01/BENDERITTER_Pascal_2006.pdf.
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Rosales, Pauline Fagundes. "Bi-heterociclos a partir do Ácido Levulínico: Síntese de 5-[(5-(trifluormetil)-5-hidroxi-(3-substituido)-4,5-diidro-1H-pirazol-1-il)-1-propan-1-ona-3-il]-2-metil-7-trifluormetil)pirazolo[1,5-a]pirimidinas." Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/10535.
Full textAbstract:
Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorAn efficient method to obtain 2-methyl-5-(methylpropanoate-3-yl)-7-trifluoromethylpyrazolo[1,5-a]pyrimidine 2 from the reaction of compound methyl 7,7,7-trifluoro-4-methoxy-6-oxo-heptenoate with 3-amino-5-methyl-1H-pyrazol. This compound 2 brought to reaction with hydrazine monohydrate to obtain 2-methyl-7-trifluoromethylpyrazolo[1,5-a]pyrimidine-5-propanehydrazine 3 and after were later brought to cyclocondensation reaction with a series of β-alkoxyvinyltrifluoromethyl ketones giving the series of news bi-heterocyclic 5-[(5-(trifluoromethyl)-5-hydroxy- (3-substituted)-4,5-dihydro-1H-pyrazol-1-yl)-1-propan-1-one-3-yl]-2-methyl-7-trifluoro methyl)pyrazolo[1,5-a]pyrimidines compounds 5a-l. Compound 2-methyl-5-(methylpropanoate-3-yl)-7-trifluoromethylpyrazolo[1,5-a]pyrimidine 2 brought to transesterification reaction and hydrolises reaction for obtaining the compounds 6 and 7. The structures of all synthesized compounds were confirmed by 1H, 13C, 19F NMR data, and two-dimensional NMR techniques like HETCOR and COLOC, mass spectrometry data.
Este trabalho descreve um método eficiente para a obtenção de 2-metil-5-(propanoato-3-il de metila)-7-trifluormetilpirazolo[1,5-a]pirimidina 2 a partir da reação de ciclocondensação do composto 7,7,7-trifluor-4-metoxi-6-oxo-4-heptenoato de metila com 3-amino-5-metil-1H-pirazol. Este composto 2 foi levado à reação com monohidrato de hidrazina obtendo-se a 2-metil-7-trifluormetilpirazolo[1,5-a]pirimidina-5-propanohidrazina 3. Posteriormente, o composto 3 foi levado à reação de ciclocondensação do tipo [3+2] com uma série de β-alcoxivniltrifluormetil cetonas alquil e aril substituídas utilizando etanol como solvente, resultando em uma série de compostos bi-heterocíclicos inéditos 5-[(5-trifluormetil)-5-hidróxi-(3-substituidos)-4,5-diidro-1H-pirazol-1-il)-1-propan-1-ona-3-il]-2-metil-7-trifluormetilpirazolo[1,5-a]pirimidina 5a-l. O composto 2-metil-5-(propanoato-3-il de metila)-7-trifluormetilpirazolo[1,5-a]pirimidina 2 foi levado à reação de transesterificação e à reação de hidrólise para a formação dos respectivos compostos 6 e 7. As estruturas de todos os compostos sintetizados foram confirmadas por dados de RMN 1H, 13C, 19F e técnicas de RMN bidimensionais como HETCOR e COLOC, além de dados de espectrometria de massas.