3,5-Dibromo-2-aminobenzamide was reacted with 1,3-cyclohexanedione derivatives in the presence of iodine as catalyst in toluene under reflux to afford novel 6,8-dibromo-2-[3-(2´-alkyl-1´,2´,3´,4´-tetrahydro-6´,8´-dibromo-4´-oxoquinazoline-2yl)propyl]quinazolin-4(3H)-ones in high yields. Suzuki-Miyaura cross-coupling of the latter with arylboronic acids in the presence of Pd(PPh3)2Cl2–Xphos catalyst complex and K2CO3 as a base in dioxane-water mixture (3:1, v/v) afforded the corresponding polyaryl-substituted bis-heterocycles in a single step operation. The resultant compounds were characterized using a combination of NMR (1H and 13C) and IR spectroscopic techniques, as well as mass spectrometry. The electronic absorption and emission properties of these polyaryl-substituted bis-heterocycles comprising 2,3-dihydroquinazolin-4(1H)-one and quinazolin-4(3H)-one moieties linked by a flexible carbon chain were measured in dimethylsulfoxide (DMSO) and acetic acid by means of UV-Vis and fluorescence spectroscopic techniques. The absorption spectra of the resultant polyaryl-substituted bis-heterocycles showed blue-shift in acetic acid and red-shift in DMSO, while their emission spectra are blue-shifted in DMSO and red-shifted in acetic acid. The 4-methoxy groups on aryl-substituents caused red shift on π‒π* transition of the aryl-substituents. Moreover, it was also observed that as the propyl linkage becomes more substituted, the absorption and emission intensities decrease. / Chemistry / M. Sc. (Chemistry)

The known 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones 122 were dehydrogenated using thallium(III) p-tolylsulfonate in dimethoxyethane under reflux to afford the 2-aryl-6,8-dibromoquinolin-4(1H)-ones 136. Palladium-catalyzed Sonogashira cross-coupling of the 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones with terminal alkynes in the presence of PdCl2(PPh3)2-CuI (as homogeneous catalyst source) and 10% Pd/C-PPh3-CuI (as heterogeneous catalyst source) catalyst mixture and NEt3 as a base and co-solvent in ethanol under reflux afforded the corresponding 6,8-dialkynyl-2-aryl-2,3-dihydroquinolin-4(1H)-ones 138 and 8-alkynyl-2-aryl-6-bromo-2,3-dihydroquinolin-4(1H)-ones 137, respectively. PdCl2-catalyzed electrophilic cyclization of the 8-alkynyl-2-aryl-6-bromo-2,3-dihydroquinolin-4(1H)-ones in acetonitrile under reflux afforded the 4-aryl-8-bromo-2-phenyl-6H-pyrrolo[3,2,1-ij]quinolin-6-ones 139 or the 2-aryl-6-bromo-8-(4-hydroxybutanoyl)-2,3-dihydroquinolin-4(1H)-ones 140 from the 4-phenylethynyl-substituted or 4-alkylethynyl-substituted precursors, respectively. The 2-aryl-6,8-dibromoquinolin-4(1H)-ones 136 wturn, subjected to similar homogeneous and heterogeneous palladium catalyst sources using NEt3 as a base in DMF-water mixture under reflux and K2CO3 as a base in dioxane under reflux afforded 2,8-disubstituted 4-aryl-6-oxopyrrolo[3,2,1-ij]quinolines 143 and 2-substituted 4-aryl-8-bromo-6-oxopyrrolo[3,2,1-ij]quinolines 142, respectively. The monoalkynylated 4-aryl-8-bromo-2-phenyl-6H-pyrrolo[3,2,1-ij]quinolin-6-ones 139 and 2-substituted 4-aryl-8-bromo-6-oxopyrrolo[3,2,1-ij]quinolines 142 were subsequently transformed using palladium-catalyzed Suzuki-Miyaura cross-coupling with arylboronic acids in the presence of PdCl2(PPh3)2-PCy3 catalyst mixture and K2CO3 as a base in dioxane-water mixture to afford the corresponding novel 8-substituted 2-phenyl-6H-pyrrolo[3,2,1-ij]quinolin-6-ones 141 and 2,8-disubstituted 4-aryl-6-oxopyrrolo[3,2,1-ij]quinolines 144, respectively. All the new compounds were characterized using a combination of 1H NMR, 13C NMR, IR, mass spectroscopic techniques and X-ray crystallography. / Chemistry / D. Phil. (Chemistry)

Dans ce travail, de nombreux hétérocycles porteurs d’un groupement CF3 ou C2F5 ont été décrits : des cétals, des benzo[1,3]dixoles, des pyran-2H-ones, des isocoumarines, des benzofuranes et des indolo[2,3-c]pyran-1-ones. Ces hétérocycles représentent une classe importante de produits biologiquement actifs. L’hydroalkoxylation intermoléculaire des dérivés du 4,4,4-perfluorobut-2-ynoate d’éthyle en présence d’une quantité catalytique de sodium métallique dans des conditions simples et douces a permis la synthèse de cétals fluorés d’une manière totalement régiosélective. La méthodologie a été étendue par la suite aux dérivés phénols pour préparer ,dans un premier temps, stériosélectivement des éthers d’énols. Des benzofuranes fluorées ont été synthétisées par la suite par cyclisation de quelques éthers vinyliques dans les conditions de Heck. Dans les mêmes conditions et en utilisant des dérivés du catéchol, nous avons réalisé des synthèses totalement régiosélective des hétérocycles de type : benzo[1,3]dioxoles, benzo[1,3]oxazoles et benzo[1,3]oxothiazoles. l’hydrocarboxylation du 4,4,4-perfluorobut-2-ynoate d’éthyle en utilisant des dérivés de l’acide 2-iodobenzoïque suivi d’une cyclisation intramoléculaire de manière ‟one-potˮ utilisant des sels de cuivres (II) nous a permis d’accéder régiosélectivement aux isocoumarines porteuses d’un groupement fluoroalkyle. Cette réaction a été étendue par la suite à la série hétéroaromatique faisant appel aux dérivés indoliques porteurs d’une fonction acide en positions 2 et d’un atome d’iode en position 3. Cette approche a permis de synthétiser de nouveaux hétérocycles fluorés à savoir des indolo[2,3-c]pyran-1ones. Nous avons exploité aussi une partie de potentiel offert par les structures énynoates synthétisées pour synthétiser des pyran-2H-ones originales porteuses d’un groupement fluoroalkyle par une stratégie d’iodolactonisation. Les réactions du couplage de type Sonogashira ont permis la synthèse d’une diversité d’alpha pyrones. / Fluorinated heterocyclic compounds can be found among potent pharmaceuticals,crop protection agents, and products of technical importance. This mergingarea of organic, heterocyclic, and fluoroorganic chemistry is still rapidly growing andin the past decades a large number of fluorinated heterocyclic materials have been discovered. In this work, an efficient and original method was developed for the synthesis of 3,3-dialkoxy propionate bearing a perfluoroalkyl group in b-position from fluorinated alkyne and alcohols using base-catalyzed double Michael addition reaction. This method provides easy access to a-perfluoro ketals with reasonable to good yields with total regioselectivity. This procedure was extended to the phenol derivatives, and a fluorinated enol ether derivatives were selectively synthesized. The use of catechol and derivative allowed the synthesis of fluorinated heterocycles such as benzo[1,3]dioxoles, benzo[1,3]oxazoles and benzo[1,3]oxothiazoles. Copper-catalyzed annulation of aromatic and heteroaromatic b-iodo-a,b-unsaturated carboxylic acids with fluorinated alkyne 1 was developed. This strategy offers a simple and efficient route for the synthesis of isocoumarins and indolo[2,3-c]pyrane-1-ones. This family of compounds are known to have various biological properties; indolo[2,3-c]pyrane-1-one derivatives exhibit anti-cancer potential towards human cervix adenocarcinoma and antinociceptive and anti-inflammatory activity. Fluorinated pyrane-2H-ones bearing an iodine atom in position 5 have been also described. The a-pyrones constitute an important class of biologically active compounds.

This is a qualitative study that explores the involvement of the relatives in the special housing based on the perspective of fourteen interviewees working in elderly care, at special housing. The purpose of this study is to analyze the nursing staff's view of the involvement of the relatives and the presence of care provision at special housing. The study is to find out what can constitute support or obstacles to the relatives. Three questions have been presented as the structural basis upon which the objective finds its conclusion. These questions try to explore and identify the forms of support that can help relatives in their involvement in elderly care. There are opportunities and obstacles for the involvement of the relatives in the care of the elderly as well as expectations of nursing staff on the role of the relatives in the care of the elderly which the following study focuses on. The research reflected in this study involves the care staff and their experiences and views on the relatives who have their older live permanently in residential care. In conclusion, the study identifies similar reasoning among respondents regarding to key aspects of the relatives at the special housing. They emphasizes that relatives are needed there and they are important resource for both the residents and the staff. The results indicate that there may be both opportunities and obstacles for the involvement of the relatives. On one side, factors that prevent relatives from their involvement are lack of communication, poor attitude, different views of relatives and staff about care and conflicts between them. On the other side, there are opportunities that can facilitate relatives' involvement, namely the fact that they need support from the staff. The interviewees pointed out that the relationship between relatives and the elderly is the basis of the relatives' involvement.

Doctor of Philosophy / Department of Chemistry / Duy H. Hua / Three research projects are described in this dissertation, and they are: (i) discovery of piperidine derivatives as T-type calcium channel inhibitors for the treatment of epilepsy and neuropathic pain and as protein disulfide isomerase inhibitors for the treatment of influenza viral infection; (ii) discovery of peptide-based calcitonin gene-related peptide receptor antagonists for the treatment of inflammatory pain; and (iii) synthesis of substituted 6-(dimethylamino)-2-phenylisoindolin-1-ones for the inhibition of luciferase. T-type calcium channels are important regulators of nervous system, and upregulated T-type calcium channel activities have been found to link to various types of neurological disorders, such as epilepsy and neuropathic pain. To discover novel T-type calcium channel blockers, a series of 1,4-disubstituted piperidine derivatives were designed and synthesized. Among them, compound 1-4 was found to be a good T-type calcium channel inhibitor with an IC₅₀ of 1 nM for Ca[subscript v]3.2 inhibition. It also showed 86% suppression of seizure induced death in mice and good in vivo analgesic effects on both thermal and mechanical pain thresholds in Spared Nerve Injury rat models. Therefore 1-4 can potentially be used as a T-type calcium channel blocker in the treatment of epilepsy and neuropathic pain. Influenza is a respiratory viral infection. Since viruses rely on host cell proteins for their entry, survival and replication, development of drugs targeting host cell proteins has identified as an effective strategy in controlling viral infections. We synthesized a series of 1,4-disubstituted piperidine derivatives for the inhibition of protein disulfide isomerase enzyme and influenza. Among them, 1-29 was found to possess strong anti-influenza activity (EC₅₀ = 2.5 µM). This suggests the potential use of piperidine scaffold in designing anti-influenza drugs in future. Calcitonin gene-related peptide (CGRP) receptor antagonism has been identified as a successful approach for the treatment of inflammatory pain. Therefore, a novel class of peptide antagonists of CGRP receptor was synthesized and screened for their binding affinities to the CGRP receptor and their analgesic effects on inflammatory-induced pain in rats. Among them, peptide 2-3 showed a higher binding affinity towards the CGRP receptor than previously reported peptide antagonists and exhibited analgesic effects up to 2 h in both Aδ and c-fiber pain tests. Therefore 2-3 indicates its potential use as a CGRP receptor antagonist in the treatment of inflammatory pain. Firefly luciferase is commonly used as a reporter in cells expressing a luciferase gene or its enzymatic activity under the control of a promoter of interest to assess its transcriptional activity. It has been found that some molecules such as molecules with carboxylic acid moiety can directly inhibit luciferase activity in cells. However, it is suggested that carboxylic acid moiety of the compounds may also be associated with side reactions in cells. Therefore, to study whether carboxylic acid moiety causes side effects, we designed two probe molecules, 3-1 and 3-2. Synthesis of probe molecule 3-2 is discussed. Synthesis of probe molecule 3-1 and further investigation of its luciferase inhibition will therefore be useful to understand the toxicity of carboxylic acid containing drugs in future.

O direito do trabalho nasceu no ambiente da Revolução Industrial. Contemporaneamente, a economia mundializada, aliada às transformações operadas nos modos de produção mantém a atividade produtiva em destaque. A aposentadoria, por sua vez, a cada momento fica mais assustadora. Não somente em razão dos dogmas sociais que cercam a fase da velhice. A crise no sistema previdenciário Estatal assusta aos mais otimistas. Tal fato faz com que aumente a opção pelo sistema de aposentadoria privada na modalidade fechada. Contudo, o contrato de aposentadoria nessa modalidade merece maior atenção por parte dos setores da sociedade em razão da inexistência de amparo ao trabalhador que está buscando meios de garantir renda capaz de lhe proporcionar uma velhice digna. Através de análise epistemológica da problemática do sistema de aposentadoria privada na modalidade fechada, tendo como pano de fundo a dignidade da pessoa humana do aposentado, partimos para reflexões acerca dos mecanismos necessários à implementação de uma situação de igualdade jurídica do trabalhador contratante frente à entidade previdenciária e patrocinadora do plano, no âmbito da iniciativa privada. Defendemos que sejam alinhadas ações individuais e coletivas, por meio da sociedade organizada, que acrescentem a esse sistema condições de auto-organização em favor da concretização da dignidade da pessoa humana do aposentado. / Submitted by Marcelo Teixeira (mvteixeira@ucs.br) on 2014-05-15T17:00:14Z No. of bitstreams: 1 Dissertacao Sandra Poletto.pdf: 1331934 bytes, checksum: ea7338ea42f6d925aa3047c5d2ade6a1 (MD5) / Made available in DSpace on 2014-05-15T17:00:14Z (GMT). No. of bitstreams: 1 Dissertacao Sandra Poletto.pdf: 1331934 bytes, checksum: ea7338ea42f6d925aa3047c5d2ade6a1 (MD5) / Labor laws were created during the Industrial Revolution. Nowadays the globalized economy, combined with the changes in the means of production, keep the production activities as the focus of attention. Retirement, however, is becoming dreadful. Not only because of the social dogmas involving old age. The crisis in the state social security scares the most optimistic ones. The consequence of this fact is an increase in the number of people who choose to contribute to closed private pension entities. Some sectors of our society should turn their attention to this type of retirement, though. There is no support for the workers trying to find ways which can provide them with a proper old age. Through an epistemological analysis of issues involving contributions to closed private pension entities and having in mind a retired person s dignity, we reflect on the mechanisms required to implement juridical equality between the worker and the private entity he hires the services of within the scope of private enterprise. We defend that individual and collective acts should work together in an organized society and add self-organization conditions to this system so as to make concrete a retired person s dignity.

O direito do trabalho nasceu no ambiente da Revolução Industrial. Contemporaneamente, a economia mundializada, aliada às transformações operadas nos modos de produção mantém a atividade produtiva em destaque. A aposentadoria, por sua vez, a cada momento fica mais assustadora. Não somente em razão dos dogmas sociais que cercam a fase da velhice. A crise no sistema previdenciário Estatal assusta aos mais otimistas. Tal fato faz com que aumente a opção pelo sistema de aposentadoria privada na modalidade fechada. Contudo, o contrato de aposentadoria nessa modalidade merece maior atenção por parte dos setores da sociedade em razão da inexistência de amparo ao trabalhador que está buscando meios de garantir renda capaz de lhe proporcionar uma velhice digna. Através de análise epistemológica da problemática do sistema de aposentadoria privada na modalidade fechada, tendo como pano de fundo a dignidade da pessoa humana do aposentado, partimos para reflexões acerca dos mecanismos necessários à implementação de uma situação de igualdade jurídica do trabalhador contratante frente à entidade previdenciária e patrocinadora do plano, no âmbito da iniciativa privada. Defendemos que sejam alinhadas ações individuais e coletivas, por meio da sociedade organizada, que acrescentem a esse sistema condições de auto-organização em favor da concretização da dignidade da pessoa humana do aposentado. / Labor laws were created during the Industrial Revolution. Nowadays the globalized economy, combined with the changes in the means of production, keep the production activities as the focus of attention. Retirement, however, is becoming dreadful. Not only because of the social dogmas involving old age. The crisis in the state social security scares the most optimistic ones. The consequence of this fact is an increase in the number of people who choose to contribute to closed private pension entities. Some sectors of our society should turn their attention to this type of retirement, though. There is no support for the workers trying to find ways which can provide them with a proper old age. Through an epistemological analysis of issues involving contributions to closed private pension entities and having in mind a retired person s dignity, we reflect on the mechanisms required to implement juridical equality between the worker and the private entity he hires the services of within the scope of private enterprise. We defend that individual and collective acts should work together in an organized society and add self-organization conditions to this system so as to make concrete a retired person s dignity.

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 présentés. / Imidazo[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.

This thesis is a compendium of three papers related to the magnetotelluric (MT) method and its application to the characterization of lithospheric-scale geoelectrical structures. The thesis begins with an Introduction where the motivation and the aims are presented as well as the geological context of the Pyrenees, the previous geophysical studies and the used data set. The Introduction also contains a description of the MT method with basic concepts useful to understand the MT analysis developed in the three papers. Then the three papers, which are the main part of the thesis, are exposed. After the papers, there is a Discussion where the results are commented and compared, extending some of the ideas proposed in the articles and including a new geoelectrical crustal model of the Western Pyrenees. Then there are the Conclusions and proposals of future works related to the MT sites acquired in the Pyrenees and the proposed method for processing MT data. At the end of the thesis there are the references of the cited works and an annex containing a copy of the two published papers and a copy of the submitted manuscript of the third paper. The first published paper determines the geoelectrical structures below the Central Pyrenees using new BBMT and LMT data acquired close to the ECORS-Pyrenees deep seismic profile. The aim of this study has been to improve the results obtained by Ledo (1996) and Pous et al. (1995a), taking advantage of the progress occurred in the last fifteen years associated with the MT method and the acquisition of MT data. The most important improvements that have been achieved are the better definition of the top of the electrical resistivity structure associated with the Iberian subducted lower crust (IBSLC) and the determination of the lithosphere-asthenosphere boundary (LAB) below the Iberian and the European plates close to the collision zone. Complementary, an analysis of the geological properties of the lower-crust and the dehydration point of the muscovite and biotite rocks provides more arguments in favour of the hypothesis of partial melting to explain the geophysical observations associated with the IBSLC. In the second paper the MT method has been applied to characterize the geoelectrical structures below the West-Central Pyrenees in a new MT profile across the Pyrenean mountain range. This new MT profile is 130 km long and is composed by twenty BBMT sites acquired in 2010, seven of them also with LMT data. Results have been compared with the ones obtained in the Central Pyrenees characterizing the main geoelectrical variations between the two MT profiles. An analysis of the thermal re-equilibration of the IBSLC has been developed completing the analysis of the previous paper about the presence or absence of partial melting in the IBSLC. This analysis corroborates partial melting as the best explanation for the low electrical resistivity values of the IBSLC. The LAB below the West-Central Pyrenees has been determined not only below the Iberian and the European plates, as in the Central Pyrenees, but also below the collision zone. Additionally, an unexpected geoelectrical structure completely buried below the Ebro basin has been associated with a Variscan boundary. In the third paper a new method is proposed for processing MT data. The proposed method uses the horizontal magnetic fields recorded at a neighbouring site to process the MT data of a local site from inter-station tensor relationships. Results obtained in the experiments validate the method. A parameter has been defined in order to determine, in each specific study for each used period, if the proposed method can be applied. / Aquesta tesi es composa de tres articles relacionats amb el mètode Magnetotelluric (MT) i la seva aplicació a la caracterització d’estructures geoelèctriques de la litosfera. La tesi comença amb una introducció on es presenten les motivacions d’aquesta i els objectius plantejats, així com el context geològic dels Pirineus, els estudis previs que s’han realitzat i les dades fetes servir pel desenvolupament de la tesis. La introducció conté també una descripció del mètode MT amb l’objectiu d’ajudar a entendre l’anàlisi que es desenvolupa en els articles. Tot seguit s’exposen els tres articles, es discuteixen els resultats obtinguts i s’exposen les conclusions a les que s’ha arribat. El primer article mostra les estructures geoelèctriques sota el Pirineu Central. L’objectiu d’aquest estudi ha estat millorar els resultats de Ledo (1996) i Pous et al. (1995a), aplicant els progressos que hi ha hagut en el camp de la MT en els darrers quinze anys. Els nous resultats han permès caracteritzar millor la zona de fusió parcial associada amb la subducció de l’escorça Ibèrica Inferior (IBSLC) i el límit litosfera astenosfera (LAB). De forma complementaria, s’ha dut a terme un anàlisi de les propietats de l’escorça inferior que ha permès aportar més arguments a favor de la hipòtesis de la fusió parcial. En el segon article el mètode MT s’ha fet servir per caracteritzar les estructures geoelèctriques sota el Pirineu Occidental-Central en un nou perfil de MT. En aquest estudi també s’han observat estructures geoelèctriques associades amb la fusió parcial de la IBSLC i amb el LAB. Sota la conca de l’Ebre s’ha observat per primer cop una anomalia geoelèctrica que s’ha associat amb la presència d’un límit Hercinià. Els resultats han estat comparats amb els del Pirineu Central per tal de caracteritzar l’evolució de les principals estructures geoelèctriques al llarg de la serralada. En el tercer article s’ha proposat un nou mètode per processar dades MT. Aquest mètode utilitza els camps magnètics horitzontals enregistrats en una estació veïna per processar les dades de la zona d’estudi únicament a partir de relacions tensorials entre estacions. Els experiments duts a terme corroboren la validesa del mètode.

En collaboration avec les Laboratoires Servier, nous présentons la synthèse d'une nouvelle famille d'inhibiteurs portant un groupe thiol ou carboxyle, développé comme antagoniste du TAFIa en vue d'une nouvelle thérapie antithrombotique et thrombolytique. L'étape clé de cette synthèse consiste en la formation de motifs β-lactames gem-difluorés. Dans ce but, la synthèse chimio- et stéréosélective de β-aminoesters et de β-lactames gem-difluorés à partir du bromodifluoroacétate d'éthyle et d'imines par réaction de Reformatsky a été étudiée. L'influence de paramètres réactionnels variés, la nature de l'amine et de l'aldéhyde, la nature de l'auxiliaire chiral ont été évaluées. De hauts degrés de stéréosélectivité (jusqu'à 98%) ont été obtenus pour les gem-difluoro-β-aminoesters et les gem-difluoroazétidin-2-ones en employant soit le (R)-phénylglycinol soit le (R)-méthoxyphénylglycinol. Nous avons également développé une procédure efficace pour effectuer la synthèse de gem-difluoro-β-lactames racémiques. Ces composés ont été obtenus par réaction de Reformatsky entre le bromodifluoroacétate d'éthyle et diverses imines de la p-méthoxybenzylamine. La synthèse de gem-difluoro-β-aminoesters racémiques est accomplie par réaction de Gilman-Speeter entre un sel d'iminium généré selon la procédure de Katritzky et le bromodifluoroacétate d'éthyle. Après une déprotection efficace de ces gem-difluoro-β-aminoesters et gem-difluoro-β-lactames, nous avons étudié la N-alkylation et la N-acylation pour l'introduction du groupe chélateur du zinc, e.g. un groupe portant un acide carboxylique ou un thiol, ainsi qu'un groupe espaceur. Après déprotection, ces composés ont été évalués pour l'inhibition de la carboxypeptidase U par la Division Angiologie de l'IdRS. Malheureusement tous ces dérivés n'ont présenté qu'une IC50 supérieure à 33 rM. Néanmoins, nous avons développé une méthode générale et efficace pour synthétiser des dérivés pseudopeptidiques gem-difluorés comme des building blocks originaux, avec une large gamme d'application.