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We gratefully acknowledge the National Cancer Institute NCI for biological evaluation of compounds on their cell panel. In this type of activity, the Hazard is omnipresent and the events, unexpected, often bring new perspectives. The synthetic methodologies we develop in our group since many years now have for heart the formation of N-acyliminiums cations, as stable species which generated generally in cara minum teh corp slim herbal medium.

This provide, after an ultimate functional arrangements, new structures based on new, simple, original and effective processes. In addition, the choice of the target molecules is closely linked to that of the collaborators or mutually depending on the case. In this presentation, the illustration of these processes comes through few major applications which we shall present.

Also the main factors pivotal during these reactions as well as the synthetic and mechanistic aspects will be presented and discussed. Tetrahedron56, Tetrahedron Lett.

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Synthesis Tetrahedron62 Heterocycles54, ; Sikoraiova, J. Pesquet, A. Arkivocviii, 27; Comesse, S. Martel, A. Lett,13, Tetrahedron60, ; Oukli, N. Tetrahedron67, ; Fleury, J.

Synlett In: Gary A. Molander and Paul Knochel eds. Two distinct families of L-glutamate receptors have been described: the ionotropic - ligand-gated ion channels - iGluRs, and the metabotropic - G-protein-coupled receptors - GPCRs.

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Reports early '90s indicated that molecules reducing the desensitization of AMPA receptors through a cara minum teh corp slim herbal allosteric modulation may be useful agents in the treatment of CNS disorders characterized by learning and memory impairments such as Alzheimer disease, Parkinson disease, schizophrenia or depressive disorders. Compounds belonging to two distinct chemical classes have been described: the benzamides early represented by aniracetam, and the benzothiadiazines early represented by cyclothiazide and IDRA A huge amount of work was done at Servier around benzothiadiazine structures: compound S entered the clinic late '90s but was finally discontinued.

The next generations of compounds provided several preclinical candidates. Among them, a large series of original pyrido- thieno- and benzothiadiazines has been developed in collaboration between the Servier Research Institute in France and Liège University in Belgium.

The present communication will be focused on the medicinal chemistry around the benzothiadiazine derivatives - design, synthesis, in vitro and in vivo evaluation, structure-activity relationships. Green access to heterocycles: aqueous media or solventless reactions?

The development of novel, simple and pierde greutatea paleo synthetic protocols through the valorization of biomass, the use of catalytic process as well as alternative media ranks among the most important green chemistry principles.

Among them, organic reactions in aqueous media and mechanochemistry have attracted much recent attention. Water is one of the most abundant, cheapest, and environmentally friendly solvents. The discovery of new reagents and catalysts for the production of novel transformations or make a classic reaction more efficient is a very promising area of research.

In the last two decades, native and modified cyclodextrins CD have been used as nano-reactors in various organic reactions as oxidation, addition, hydrolysis and even more recently in multicomponent cyclisation reactions in water. Furthermore, these supramolecules are inexpensive natural cyclic oligosaccharides.

CD can be recovered and reused in subsequent reactions without loss of activity. One of the main challenges in medicinal chemistry is the design and synthesis of biologically active molecule which calls for clean procedures avoiding the use of harmful organic solvent. In the second time we will report green alternative for access to heterocyclic pierderea în greutate după terminarea perioadei in solvent less condition by means of mechanochemistry.

Acknowledgements Ejercicios fat burn autors gratefully acknowledge two students Edita Vaiciunaite and Liudvikas Akelis for their contribution on the subject.

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References S. Menuel, J. Rousseau, C. Rousseau, E. Vaiciunaite, J. Dodonova, S. Tumkevicius, E. Rousseau, J. Rousseau, S. Menuel, E. Vaiciunaite, L. Akelis, J.

Monflier Green Chem. These tosylhydrazones, generating in situ metal carbenes are likely large synthetic applications, as we have already shown see scheme below.

Under this method, various poly-substituted alkenes are prepared in a convergent way. Pierdere în greutate camp new jersey chemical library of olefinic compounds has been established and tested for their tubulin polymerization inhibition and cytotoxic activities.

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These results will be presented here. F; Bernadat, G. Non-viral vectors for gene therapy Cristina M. Uritu1, Andrei I. Dascalu1, Dragos Peptanariu1, Stelian S.

Maier1'2, Bogdan C. In this respect, the nucleic acids chains to be inserted into the cells are generally incorporated into engineered viral or non-viral vectorsi. Non-viral vectorization of DNA has certain advantages against viral methods, including the ability of large scale production and the simplicity of use, besides the decrease of the occurrence of undesirable immune response. This is why non-viral carriers are of actual interest, and are developed preferentiallyii.

Polyethylene imine PEI is one of the most investigated polycation as transfectant entity, due to its abundantly positive charged amine groups. PEI molecule itself, although very effective in DNA packaging and release, shows a high cytotoxicity when tested in cell cultures.

Therefore it is aimed to conjugate PEI with various molecules in order to enhance the transfection efficiency in parallel with the cell viability. Biodegradability represents cara minum teh corp slim herbal severe issue, when the biological functionality of the cells must be preserved in vivo.

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To reduce the potential cytotoxicity of PEI and simultaneously to increase the biocompatibility of the transfectant carrier, PEG chains were also introduced. EYFP plasmid was used to evidentiate the gene transfer mediated by the synthesized carriers. References: i L. Novo, E. Mastrobattista, C. Bioconjugate Chem.

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Yu, J. Park, S. Theranostics2, Forrest, J. Koerber, D. A degradable polyethylenimine derivative with low toxicity for highly efficient gene delivery.

This acetylene is very densely functionalized, and by taking advantage of the chemical properties of the various functional groups, a variety of compounds have been synthesized [].

We are currently investigating the reactivity of derivatives of 1, e. These studies have resulted in a number of new products, and in the lecture the focus will be on syntheses of a variety of heterocyclic compounds which have been prepared in a regiospecific fashion and in very good yields. Leiv K. Sydnes, Bjarte Holmelid, Ole H. Bjarte Holmelid, Ole H. Kvernenes, Mari Hodne and Leiv K. Sydnes and Stig Valdersnes, Pure Appl.

Stig Valdersnes and Leiv K. Sydnes, Eur. Macrocycles, porous polymers and self-assembled aggregates with potential applications in Medicinal Chemistry Ion Grosu "Babe§-Bolyai" University, Faculty of Chemistry and Chemical Engineering, Department of Chemistry, Arany Janos 11,Cluj-Napoca The synthesis of various macrocycles I and cryptands II exhibiting phenothiazine, thiophene, triazine or tris 1,3-dioxanyl benzene units was carried out using classic procedures for macrocyclization reactions etherification, esterification, acetylenic coupling but also by an original method based on the Suzuki-Miyaura cross-coupling reaction Scheme 1.

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The formation of supramolecular aggregates by hydrogene bonding III, Scheme 1 starting from di- and tripodands exhibiting triazine, tris 1,3-dioxanyl or bicyclo[3. Porous polymers IV, Scheme 1 showing a tridimensional structure based on tetraphenyladamantane or spirobifluorene units were obtained by acetylene coupling or Sonogashira cross-coupling reactions.

References: covalenl organic frameworks IV 1. Medrut, I. Demeter, D. Pascanu, V. Circu, M. Pop, F. Grosu, I. Tetrahedron,68, Petran, A. Tetrahedron70, CrystEngComm14, Golban, M. Unfortunately, this process is unlikely to get any easier, as more and more stringent regulations are imposed on the perilous road to obtaining Product Licences. An answer to overcoming such difficulties may lie in the application of white biotechnology biotransformations and biocatalysis.

Difficult steps, or low-yielding reactions, may be simplified thus leading to major gains in overall selectivities and yields. We herein present a range of examples whereby different reactions of special interest have been made possible through the application of biotransformations and biocatalysis.

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In our group we use the "Microbial Model of Drug Metabolism" to access the synthesis of drug metabolites. Such metabolites are usually formed during the in vivo enzymatic transformations of their parents drugs and may often exhibit different toxicities or pharmacological activities. Their isolation and purification however remains time-consuming and therefore highly costly.

Microbial biotransformation offers a convenient way of obtaining such metabolites in a clean and cost-effective manner. Such reactions may also allow the metabolite to be isolated in large quantities, thus facilitating their characterisation and use in further studies. We shall therefore discuss some cases whereby the use of biotransformations has helped to generate new functionalised molecules as NCE or scaffolds for generating NCE allowing easy access to "chemical biodiversity".

As well as being applied, white biotechnology may also be exploited to obtain API's intermediates. As active pharmaceutical ingredients APIs become increasingly more sophisticated, the Pharmaceutical Chemist needs to come up with ever-more effective synthetic strategies to produce these substances.

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Here we will present a "case study" from a marketed drug. The CB2 cannabinoid receptor emerged as a promising therapeutic target in the treatment of these pathologies. Indeed, this GPCR has been identified within the gastrointestinal tract and plays a key role in the regulation of intestinal inflammation.

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Additionally, the CB2 receptor agonists have been shown to exert an anti-inflammatory effect both in intestinal epithelial cells and in experimental models of colitis in mice. In vitro experiments highlighted that CB2 receptor activation results in suppression of the release of pro-inflammatory cytokines.

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Data from in vivo studies emphasized the importance of this receptor in mediating protection against experimental colitis. Our groups previously described a series of 4-oxo-1,4-dihydroquinolinecarboxamide as selective ligands of the CB2 receptor. One of the commonly used strategies in drug design to increase affinity and selectivity of a given "flexible" lead for its pharmacological target is to conformationally constrain it to mimic the so-called bioactive conformation.

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Therefore, we designed constrained analogues of the 4-oxo-1,4-dihydroquinolinecarboxamide series based on a 2 -pyrazolo[4,3-c]quinolin-3 5 -one scaffold.