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Terme, Thierry.

ACL - Articles dans des revues à comité de lecture

48 références.
2018

  • Da Costa, L.; Scheers, E.; Coluccia, A.; Casulli, A.; Roche, M.; Di Giorgio, C.; Neyts, J.; Terme, T.; Cirilli, R.; La Regina, G.; Silyestri, R.; Mirabelli, C.; Vanelle, P. Journal of Medicinal Chemistry 2018, 61 (18), 8402-8416.
    Résumé : Rhinoviruses (RVs) have been linked to exacerbations of many pulmonary diseases, thus increasing morbidity and/or mortality in subjects at risk. Unfortunately, the wide variety of RV genotypes constitutes a major hindrance for the development of Rhinovirus replication inhibitors. In the current investigation, we have developed a novel series of pyrazole derivatives that potently inhibit the Rhinovirus replication. Compounds 10e and 10h behave as early stage inhibitors of Rhinovirus infection with a broad-spectrum activity against RV-A and RV-B species (EC50 < 0.1 mu M). We also evaluate the dynamics of the emerging resistance of these promising compounds and their in vitro genotoxicity. Molecular docking experiments shed light on the pharmacophoric elements interacting with residues of the drug-binding pocket.

  • Khoumeri, O.; Terme, T.; Vanelle, P. Synthesis-Stuttgart 2018, 50 (13), 2617-2623.
    Résumé : The first TDAE-initiated reaction between benzonitrile derivatives as substrates and substituted benzaldehydes to form substituted hydroxyethylbenzonitrile derivatives is reported. The 2-hydroxyethyl benzonitrile derivatives thus formed were good candidates for one-pot lactonization in a mixture of hydrochloric acid and methanol at 70 degrees C over five hours. These reactions furnished the corresponding 3-substituted isochroman-1-one derivatives in good yields.
2017

  • Biyogo, A. M.; Curti, C.; El-Kashef, H.; Khoumeri, O.; Terme, T.; Vanelle, P. Rsc Advances 2017, 7 (1), 106–111.
    Résumé : Manganese(III) acetate-mediated peroxycyclization between 2-hydroxy-3-methylnaphthoquinone and various alkenes was performed to obtain dihydronaphtho[2,3-c][1,2] dioxine-5,10(3H, 10aH)-diones. The reactivity of symmetrical or unsymmetrical 1,1-disubstituted alkenes and monosubstituted alkenes allowed the synthesis of more than 50 original molecules. Focusing on the excellent reactivity of 2-hydroxy-3-methylnaphthoquinone, we describe the first example of Mn(OAc)(3) reactivity with nitro-substituted alkenes. The scope, limitations and stereochemistry of the products synthesized are discussed. Starting from monosubstituted alkenes, the instability of a pair of diastereoisomers was observed, leading to ring opening.
    Mots-clés : 1, 1-disubstituted alkenes, 2+2+2 cycloaddition, antimalarial, cyclic peroxides, derivatives, endoperoxides, in-vitro activity, manganese(iii) acetate, molecular-oxygen, plasmodium-falciparum.

  • Da Costa, L.; Scheers, E.; Coluccia, A.; Rosetti, A.; Roche, M.; Neyts, J.; Terme, T.; Cirilli, R.; Mirabelli, C.; Silvestri, R.; Vanelle, P. European Journal of Medicinal Chemistry 2017, 140, 528–541.
    Résumé : Rhinovirus (RV), member of the Enterovirus genus, is known to be involved in more than half of the common colds. Through advances in molecular biology, rhinoviruses have also been associated with exacerbations of chronic pulmonary diseases (e.g. asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis). In the current investigation, we develop a novel series of 4,5-dimethoxybenzyl derivatives that potently inhibits rhinovirus replication. Compound (S)-7f blocks RV-B14 replication with an EC50 value of 0.25 mu M and shows a low toxicity in HeLa cells (CC50 \textgreater 271 mu M). Enantioseparation followed by an absolute configuration determination by a Mosher's method revealed the interest of enantiopure compounds. Molecular docking studies permitted the identification of key biological interactions within the drug-binding pocket and an in silico drug-like study revealed a good potential for the development of these derivatives. (C) 2017 Elsevier Masson SAS. All rights reserved.
    Mots-clés : 14 infection, absolute-configuration, Capsid-binder, common cold, compound, dynamics, Enantioseparation, entry, Heterocycles, inhibitors, Mosher's method, replication, rv-b14, virus, VP1 protein.

  • Spitz, C.; Giuglio-Tonolo, A. G.; Terme, T.; Vanelle, P. Molecules 2017, 22 (7), 1178.
    Résumé : A mild and metal-free regiodivergent addition of carbon nucleophiles to alpha,beta-unsaturated electrophiles was developed. Total 1,2-regioselectivity was observed in the addition of nitrobenzyl chloride derivative 1 to alpha,beta-unsaturated aldehydes 2 in the presence of TDAE. Moreover, the reaction between p-nitrobenzyl chloride 1a and alpha,beta -unsaturated iminium salts 4 led to the formation of the 1,4-adduct with total regioselectivity.
    Mots-clés : aldehydes, alpha, beta-unsaturated electrophiles, diastereoselective synthesis, imines, metal-free, mild, n-tert-butanesulfinylamines, original synthesis, p-nitrobenzyl chloride, regiodivergent, strategy, tdae approach, tetrakis(dimethylamino)ethylene.
2016

  • Broggi, J.; Rollet, M.; Clement, J. - L.; Canard, G.; Terme, T.; Gigmes, D.; Vanelle, P. Angewandte Chemie-International Edition 2016, 55 (20), 5994-5999.
    Résumé : Polymerization reactions with organic electron donors (OED) as initiators are presented herein. The metal-free polymerization of various activated alkene and cyclic ester monomers was performed in short reaction times, under mild conditions, with small amounts of organic reducing agents, and without the need for co-initiators or activation by photochemical, electrochemical, or other methods. Hence, OED initiators enabled the development of an efficient, rapid, room-temperature process that meets the technical standards expected for industrial processes, such as energy savings, cost-effectiveness and safety. Mechanistic investigations support an electron-transfer initiation pathway that leads to the reduction of the monomer.
    Mots-clés : 2-electron transfer, anionic-polymerization, carbanionic polymerization, chain-growth polymerization, electron transfer, free-radical polymerization, methyl-methacrylate, n-heterocyclic carbenes, organic electron donors, reaction mechanisms, reduction, ring-opening polymerization, single-electron, tetraazafulvalene.
  • Da Costa, L.; Roche, M.; Scheers, E.; Coluccia, A.; Neyts, J.; Terme, T.; Leyssen, P.; Silvestri, R.; Vanelle, P. European Journal of Medicinal Chemistry 2016, 115, 453-462.
    Résumé : Human rhinoviruses (HRV) are the predominant cause of common colds and flu-like illnesses, but are also responsible for virus-induced exacerbations of asthma and chronic obstructive pulmonary disease. However, to date, no drug has been approved yet for clinical use. In this study, we present the results of the structure-based lead optimization of a class of new small-molecule inhibitors that we previously reported to bind into the pocket beneath the canyon of the VP1 protein. A small series of analogues that we designed based on the available structure and interaction data were synthesized and evaluated for their potency to inhibit the replication of HRV serotype 14. 2-(4,5-Dimethoxy-2-nitrophenyI)-1-(4-(pyridin-4-yl)phenyl)ethanol (3v) was found to be a potent inhibitor exhibiting micromolar activity (EC50 = 3.4 +/- 1.0 mu M) with a toxicity for HeLa cells that was significantly lower than that of our previous hit (LPCRW_0005, CC50 = 104.0 +/- 22.2 mu M: 3v, CC50 > 263 mu M). (C) 2016 Elsevier Masson SAS. All rights reserved.
    Mots-clés : 3c protease, attachment, Capsid inhibitors, common cold, compound, derivatives, design, hrv14, In silico design, original synthesis, replication, strategy, tdae, tdae methodology, VP1 protein.

  • Hajri, M.; Esteve, M. - A.; Khoumeri, O.; Abderrahim, R.; Terme, T.; Montana, M.; Vanelle, P. European Journal of Medicinal Chemistry 2016, 124, 959-966.
    Résumé : We report a novel series of quinoxaline derivatives from which agents with antiproliferative activity have been identified. Two ethyl 3-(arylethynyl)quinoxaline-2-carboxylates demonstrated substantial anti proliferative activity against both human non-small cell lung carcinoma (A549) and glioblastoma (U87-MG) cell lines. Pyrido[4,3-b]quinoxalin-1(2H)-ones demonstrated poor activity against A549 and U87-MG cell lines. Three of the derivatives in ethyl 3-(arylethynyl)quinoxaline-2-carboxylate series demonstrated substantial antiproliferative activity. The arylethynyl derivative 2a and 2d proved to be the most cytotoxic with an IC50 value of 3.3 mu M for both A549 and U87-MG cell lines. (C) 2016 Elsevier Masson SAS. All rights reserved.
    Mots-clés : Antitumor activity, assay, cell-lines, Organic chemistry, Quinoxaline, reactivity, series, Structure-activity relationship, tdae strategy.

  • Khoumeri, O.; Vanelle, F. - X.; Crozet, M. D.; Terme, T.; Vanelle, P. Synlett 2016, 27 (10), 1547-1550.
    Résumé : We report herein the synthesis of 5-(substituted)quinolino[3,4-b]quinoxalin-6(5H)-one derivatives from ethyl 3-(2-bromophenyl)quinoxaline-2-carboxylate under one-pot Buchwald-Hartwig coupling-lactamization reaction.
    Mots-clés : agents, aromatic anilines, biological-activity, Buchwald-Hartwig reaction, catalyzed cyclization, derivatives, discovery, inhibitors, lactamization reaction, n-heterocycles, pot synthesis, Quinoxaline, quinoxaline antibiotics, series.

  • Rayala, R.; Giuglio-Tonolo, A.; Broggi, J.; Terme, T.; Vanelle, P.; Theard, P.; Medebielle, M.; Wnuk, S. F. Tetrahedron 2016, 72 (16), 1969-1977.
    Résumé : Studies directed toward the oxidative and reductive desulfurization of readily available 2'-S-ary1-2'thiouridine derivatives were investigated with the prospect to functionalize the C2'-position of nucleosides. The oxidative desulfurization-difluorination strategy was successful on 2-(arylthio)allcanoate surrogates, while extension of the combination of oxidants and fluoride sources was not an efficient fluorination protocol when applied to 2'-S-aryl-2'-thiouridine derivatives, resulting mainly in C5 halogenation of the pyrimidine ring and C2'-monofluorination without desulfurization. Cyclic voltammetry of 2'-arylsulfony1-2'-deoxyuridines and their 2'-fluorinated analogues showed that cleavage of the arylsulfone moiety could occur, although at relatively high cathodic potentials. While reductivedesulfonylation of 2'-arylsulfciny1-2'-deoxyuridines with organic electron donors (0EDs) gave predominantly base-induced furan type products, chemical (OED) and electrochemical reductivedesulfonylation of the cc-fluorosulfone derivatives yielded the 2'-deoxy-2'-fluorouridine and 2',3'-didehydro-2',3'-dideoxy-2'-fluorouridine derivatives. These results provided good evidence of the generation of a C2'-anion through carbon-sulfur bond cleavage, opening new horizons for the reductivefunctionalization approaches in nucleosides. (C) 2016 Elsevier Ltd. All rights reserved.
    Mots-clés : acid related-compounds, alkyl aryl thioethers, alpha-fluoro esters, Cyclic voltammetry, desulfurization-difluorination, Desulfurization-fluorination, electrochemical synthesis, Fluorination, medicinal chemistry, Nucleosides, organic electron donors, radical-mediated cleavage, Reductive desulfonylation, super-electron-donors.

  • Spitz, C.; Mathias, F.; Giuglio-Tonolo, A. G.; Terme, T.; Vanelle, P. Molecules 2016, 21 (11), 1472.
    Résumé : We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl) phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl-protected amine was easily deprotected under acidic conditions. Finally, the primary amine was coupled with different acid chlorides or acids to give the corresponding amides. The mild reaction conditions and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting 5-nitroimidazoles.
    Mots-clés : 5-nitroimidazoles, amides, derivatives, in-vitro, metal-free, metronidazole.

  • Spitz, C.; Terme, T.; Vanelle, P. Synlett 2016, 27 (2), 301-303.
    Résumé : A mild and metal-free regioselective 1,2-addition of carbon nucleophiles to alpha,beta-unsaturated imines has been developed. Good yields and total regioselectivities were achieved by addition of p-nitrobenzyl chloride or 2,3-bis(bromomethyl)quinoxaline to alpha,beta-unsaturated tosylimines.
    Mots-clés : addition, agents, aldehydes, alpha,beta-unsaturated tosylimines, derivatives, metal-free, p-nitrobenzyl chloride, regioselectivity, series, strategy, tdae.
2015

  • Biyogo, A. M.; Khoumeri, O.; Terme, T.; Curti, C.; Vanelle, P. Synthesis-Stuttgart 2015, 47 (17), 2647-2653.
    Résumé : An original and short synthesis of substituted 2,3-dihydrobenzo[g]indol-5-ones by S(RN)1-mediated synthesis of 2-nitroalkyl-substituted naphthalene-1,4-diones followed by a one-pot reduction-cyclization reaction is reported.

  • Bolibrukh, K.; Polovkovych, S.; Khoumeri, O.; Halenova, T.; Nikolaeva, I.; Savchuk, O.; Terme, T.; Vanelle, P.; Lubenets, V.; Novikov, V. Scientia Pharmaceutica 2015, 83 (2), 221-231.
    Résumé : Thiosulfonate derivatives based on quinones were synthesized for studying "structure-activity relationship" compounds with an acylated and a free amino-group. Anti-platelet activity of the synthesized compounds was determined and the influence of substituents on the activity of the derivatives was assessed.

  • Kabri, Y.; Crozet, M. D.; Terme, T.; Vanelle, P. European Journal of Organic Chemistry 2015, Nᵒ 17, 3806-3817.
    Résumé : An efficient, sequential, one-pot strategy for synthesizing polyfunctionalized quinazoline derivatives is presented. After selective amination of 6,8-dibromo-2,4-dichloroquinazoline at the C-4 position, 2,6,8-trisubstituted 4-aminoquinazoline derivatives were prepared through one-pot chemoselective sequential tris-Suzuki-Miyaura or SNAr/bis-Suzuki-Miyaura reactions under microwave irradiation in an aqueous medium. This approach, used with a variety of boronic acids, affords polysubstituted quinazoline derivatives in good to excellent yields in only a few steps and in the environmentally benign solvent water.

  • Nadji-Boukrouche, A. R.; Khoumeri, O.; Terme, T.; Liacha, M.; Vanelle, P. Molecules 2015, 20 (1), 1262-1276.
    Résumé : We describe an original pathway to produce new 5-substituted 3-methyl-6-nitro-benzoxazolones by the reaction of aromatic carbonyl and alpha-carbonyl ester derivatives with a benzoxazolinonic anion formed exclusively via the TDAE strategy.

  • Nadji-Boukrouche, A. R.; On, S.; Khoumeri, O.; Terme, T.; Vanelle, P. Tetrahedron Letters 2015, 56 (17), 2272-2275.
    Résumé : A new series of 1-methyl-1H-benzo[f]indole-4,9-dione derivatives was prepared via a one-pot 'Sonogashira-Cyclization' reaction with propagylic alcohol in the presence of a palladium catalyst leading to regio-isomers of 2- and 3-(chloromethyl)-1-methyl-1H-benzo[f]indole-4,9-dione after chlorination. The reaction of the 2- and 3-(chloromethyl)-1-methyl-1H-benzo[f]indole-4,9-dione derivatives with various aldehydes and N-sulfonimides in the presence of TDAE under mild conditions led to the corresponding alcohols and N-sulfonamide derivatives in good yield. (C) 2015 Elsevier Ltd. All rights reserved.
2014

  • Benmohammed, A.; Khoumeri, O.; Djafri, A.; Terme, T.; Vanelle, P. Molecules 2014, 19 (3), 3068-3083.
    Résumé : We present herein the synthesis in good yields of two series of highly functionalized thiazolidinone derivatives from the reactions of various 4-phenyl-3-thio-semicarbazones with ethyl 2-bromoacetate and diethyl acetylenedicarboxylate, respectively.

  • Bolibrukh, K.; Khoumeri, O.; Polovkovych, S.; Novikov, V.; Terme, T.; Vanelle, P. Synlett 2014, 25 (19), 2765-2768.
    Résumé : 2-Bromo-3-(2-bromophenyl)naphthalene-1,4-dione was synthesized as a key precursor to obtain a number of functionalized benzo[b]carbazole-6,11-diones by double Buchwald-Hartwig coupling reaction.

  • Broggi, J.; Terme, T.; Vanelle, P. Angewandte Chemie-International Edition 2014, 53 (2), 384-413.
    Résumé : One-electron reduction is commonly used in organic chemistry for the formation of radicals by the stepwise transfer of one or two electrons from a donor to an organic substrate. Besides metallic reagents, single-electron reducers based on neutral organic molecules have emerged as an attractive novel source of reducing electrons. The past 20 years have seen the blossoming of a particular class of organic reducing agents, the electron-rich olefins, and their application in organic synthesis. This Review gives an overview of the different types of organic donors and their specific characteristics in organic transformations.
  • Crozet, M. D.; Terme, T.; Vanelle, P. Letters in Drug Design & Discovery 2014, 11 (5), 531-559.
    Résumé : 5-Nitroimidazoles are drugs having both antiprotozoal and antibacterial activity, but show mutagenicity and development of resistance particularly with metronidazole. For the development of new potentially safer derivatives, we investigated new strategies of synthesis: such as Vicarious Nucleophilic Substitution of hydrogen (VNS), palladium-catalyzed cross-coupling reactions (Suzuki-Miyaura, Sonogashira...) and electron transfer reactions (Unimolecular Radical Nucleophilic Substitution (SRN1), TDAE methodology) applied in 5-nitroimidazole series.

  • Giuglio-Tonolo, A. G.; Spitz, C.; Terme, T.; Vanelle, P. Tetrahedron Letters 2014, 55 (16), 2700-2702.
    Résumé : We developed a rapid and green synthesis of various isocyanurates by cyclotrimerization of isocyanates using TDAE (tetrakis(dimethylamino)ethylene). TDAE displays excellent performance in catalytic quantities, affording the corresponding trimer of isocyanates very rapidly, under air and at room temperature in good to excellent yields. (C) 2014 Elsevier Ltd. All rights reserved.

  • Kavitha, S. R.; Umadevi, M.; Vanelle, P.; Terme, T.; Khoumeri, O. European Physical Journal D 2014, 68 (10), 308.
    Résumé : Silver nanoparticles (Ag NPs) of different sizes from 9 to 17 nm were synthesized by Creighton method and characterized using UV-vis spectroscopy and high resolution transmission electron microscopy (HRTEM). Fluorescence quenching of 1,4-dimethoxy-2,3-dibromomethylanthracene-9,10-dione (DMDBMAD) in methanol has been studied by fluorescence spectroscopy combined with UV-vis absorption spectroscopic techniques. It has been observed that the fluorescence intensity of DMDBMAD decrease with increase in the size of the Ag NPs. The quenching rate constant and association constant were determined using Stern-Volmer and Benesi-Hildebrand plots. The Stern-Volmer plot suggested that the quenching of DMDBMAD fluorescence by silver NPs was a dynamic process. The obtained value of the association constant infers that there is an association between DMDBMAD and the Ag NPs. Using Forster resonance energy transfer (FRET) theory, the distance between the donor (DMDBMAD) to acceptor (Ag NPs) and the critical energy transfer distance were obtained. Long range dipole-dipole interaction between the excited donor and ground state acceptor molecules is the dominant mechanism responsible for the energy transfer.

  • Lacroix, C.; Querol-Audi, J.; Roche, M.; Franco, D.; Froeyen, M.; Guerra, P.; Terme, T.; Vanelle, P.; Verdaguer, N.; Neyts, J.; Leyssen, P. Journal of Antimicrobial Chemotherapy 2014, 69 (10), 2723-2732.
    Résumé : Objectives: To study the characteristics and the mode of action of the anti-rhinovirus compound 4-[ 1-hydroxy-2( 4,5-dimethoxy-2-nitrophenyl) ethyl] benzonitrile (LPCRW_0005). Methods: The antiviral activity of LPCRW_0005 was evaluated in a cytopathic effect reduction assay against a panel of human rhinovirus (HRV) strains. To unravel its precise molecular mechanism of action, a time-of-drugaddition study, resistance selection and thermostability assays were performed. The crystal structure of the HRV14/LPCRW_0005 complex was elucidated as well. Results: LPCRW_0005 proved to be a selective inhibitor of the replication of HRV14 (EC50 of 2+ 1 mM). Time-ofdrug- addition studies revealed that LPCRW_0005 interferes with the earliest stages of virus replication. Phenotypic drug-resistant virus variantswere obtained (>= 30-fold decrease in susceptibility to the inhibitory effect of LPCRW_0005), which carried either an A150T or A150V amino acid substitution in the VP1 capsid protein. The link between the mutant genotype and drug-resistant phenotype was confirmed by reverse genetics. Crossresistance studies and thermostability assays revealed that LPCRW_0005 has a similar mechanism of action to the capsid binder pleconaril. Elucidation of the crystal structure of the HRV14/LPCRW_0005 complex revealed the existence of multiple hydrophobic and polar interactions between the VP1 pocket and LPCRW_0005. Conclusions: LPCRW_0005 is a novel inhibitor of HRV14 replication that acts as a capsid binder. The compound has a chemical structure that is markedly smaller than that of other capsid binders. Structural studies show that LPCRW_0005, in contrast to pleconaril, leaves the toe end of the pocket in VP1 empty. This suggests that extended analogues of LPCRW_0005 that fill the full cavity could be more potent inhibitors of rhinovirus replication.

  • Montana, M.; Correard, F.; Khoumeri, O.; Esteve, M. - A.; Terme, T.; Vanelle, P. Molecules 2014, 19 (9), 14987-14998.
    Résumé : Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. In order to obtain new compounds active on neuroblastoma cell lines, we investigated the reactivity of carbanion formed via TDAE in quinoxaline series. The new synthesized compounds were tested for their anti-proliferative activity on two neuroblastoma cell lines, and seven oxirane derivatives obtained interesting activities.

  • Neilde, K.; Crozet, M. D.; Terme, T.; Vanelle, P. Tetrahedron Letters 2014, 55 (27), 3652-3657.
    Résumé : We report here the first example of an S(RN)1 reaction on propargylic chloride in heterocyclic series. The reaction of 4-(3-chloroprop-1-ynyl)-1,2-dimethyl-5-nitro-1H-imidazole with nitronate anions led to both the formation of the C-alkylated product through an S(RN)1 mechanism and the predominant ethylenic compound resulting from nitrous acid elimination on the C-alkylated product. Interestingly, in contrast to our previous works on S(RN)1 reactivity, no O-alkylated product was observed. (C) 2014 Elsevier Ltd. All rights reserved.

  • Primas, N.; Neilde, K.; Kabri, Y.; Crozet, M. D.; Terme, T.; Vanelle, P. Synthesis-Stuttgart 2014, 46 (3), 348-356.
    Résumé : We describe herein the preparation of 4-[4-(chloromethyl) styryl]-1,2-dimethyl-5-nitro-1H-imidazole via a Stille cross-coupling reaction. After determining the best reaction conditions, we investigated the reactivity of this activated chloromethyl compound in a TDAE [tetrakis(dimethylamino) ethylene] strategy toward 10 various electrophiles, obtaining 4-(4-substituted)styryl-1,2-dimethyl-5-nitro-1H-imidazoles in moderate to good yields.

  • Roche, M.; Lacroix, C.; Khoumeri, O.; Franco, D.; Neyts, J.; Terme, T.; Leyssen, P.; Vanelle, P. European Journal of Medicinal Chemistry 2014, 76, 445-459.
    Résumé : Human rhinoviruses are a common cause of respiratory infections, and thus constitute an important target for medicinal chemistry. Still, no drug has been approved for clinical use. We report herein the discovery of dibenzenic derivatives with potent and specific in vitro anti-rhinoviral 14 activity. A total of 99 structural analogues were synthesized by an original synthesis method, i.e. through one organic agent Tetrakis(DimethylAmino)Ethylene (TDAE) and a structure-activity relationship was established. It was shown that 4,5-dimethoxy scaffold and the presence of a C-4 substituted aromatic moiety were necessary to the in vitro activity of these original agents. However, modifications on liker were not convincing. The benzonitrile derivative 23 was identified as the most potent and selective inhibitor of rhinovirus replication in these series (EC50 of 2 +/- 0.5 mu M, CC50 of 184 mu M, selectivity index of 92). (C) 2014 Elsevier Masson SAS. All rights reserved.

  • Spitz, C.; Lin, A.; Terme, T.; Vanelle, P. Synthesis-Stuttgart 2014, 46 (23), 3229-3232.
    Résumé : A mild and metal-free diastereoselective synthesis of N-tert-butanesulfinylamines was developed by using a strategy based on tetrakis(dimethylamino)ethylene. Good yields and diastereoselectivities were achieved by addition of o-nitrobenzyl chloride or 4-[4-(chloromethyl)phenyl]-1,2-dimethyl-5-nitro-1H-imidazole to readily available N-tert-butanesulfinimines.
2013
2012

  • Khoumeri, O.; Montana, M.; Terme, T.; Vanelle, P. Tetrahedron Letters 2012, 53 (19), 2410-2413.
    Résumé : We report herein an original and rapid synthesis of substituted 2-tosyl-1,2,3,4-tetrahydropyrido[3,4-b]quinoxaline derivatives by TDAE strategy from 2,3-bis(bromomethyl)quinoxaline and N-(toluenesulfonyl)benzylimines. (C) 2012 Elsevier Ltd. All rights reserved.

  • Roche, M.; Terme, T.; Vanelle, P. Tetrahedron Letters 2012, 53 (32), 4184-4187.
    Résumé : We report here the first example of a Long-Distance S(RN)1 (LD-S(RN)1) reaction on a propargylic chloride. The reaction of 1-(3-chloroprop-1-ynyl)-4-nitrobenzene (1) with nitronate anions led to both the formation of the C-alkylation product through an LD-S(RN)1 mechanism and the ethylenic compound resulting from nitrous acid elimination on the C-alkylation product 2. In contrast with previous work on LD-S(RN)1 reactivity, no O-alkylation product was observed. Only one original product 4 was isolated under phase transfer conditions, resulting from a nucleophilic attack by 2-nitropropane anion on the electrophilic allcyne. This LD-S(RN)1 reactivity did not extend to sulfinate anions: the reaction of 1 with sulfinate anions yielded original ethylenic disulfone compounds which were formed via an ionic process. (C) 2012 Elsevier Ltd. All rights reserved.
  • Tabele, C.; Montana, M.; Curti, C.; Terme, T.; Rathelot, P.; Gensollen, S.; Vanelle, P. Journal of Pharmacy and Pharmaceutical Sciences 2012, 15 (1), 124-140.
    Résumé : Since 1976, fibrin glues have been attracting medical interest, spreading from their initial use as a hemostatic agent in cardiovascular surgery to other fields of surgery. Studies have compared the efficacy of fibrin glues vs sutures in surgery. However, few comparisons have been made of the efficacy and safety of the different fibrin glues commercially available. Recently, fibrin glues have been tested as a scaffold delivery system for various substances inside the body (drugs, growth factors, stem cells). The infectious risk (viruses, new germs) of this blood-derived product was also studied in assays on viral inactivation methods. The development of autologous fibrin glues offers a solution to the problem of infectious risk. This review examines the current state of knowledge on the efficacy, safety and future potential of fibrin glues.
2011

  • Juspin, T.; Zink, L.; Crozet, M. D.; Terme, T.; Vanelle, P. Molecules 2011, 16 (8), 6883-6893.
    Résumé : We report herein the synthesis of substituted 2-[4-(1,2-dimethyl-5-nitro-1H-imidazol-4-yl) phenyl]-1-arylethanols, ethyl 3-[4-(1,2-dimethyl-5-nitro-1H-imidazol-4-yl)phenyl]-2-hydroxypropanoate and 2-[4-(1,2-dimethyl-5-nitro-1H-imidazol-4-yl)benzyl]-2-hydroxy-acenaphthy len-1(2H)-one from the reactions of 4-[4-(chloromethyl) phenyl]-1,2-dimethyl-5-nitro-1H-imidazole with various aromatic carbonyl and alpha-carbonyl ester derivatives using tetrakis(dimethylamino) ethylene (TDAE) methodology.

  • Khoumeri, O.; Giuglio-Tonolo, G.; Crozet, M. D.; Terme, T.; Vanelle, P. Tetrahedron 2011, 67 (34), 6173-6180.
    Résumé : We report herein an original and rapid synthesis of 2-substituted-4,11-dimethoxy-1-(phenylsulfonyl)-2,3-dihydro-1H-naphtho[2 ,3-f]indole-5,10-diones by TDAE mediated synthesis of N-benzylsulfonamides followed by an intramolecular N-arylation using Cu-catalyzed system. (C) 2011 Elsevier Ltd. All rights reserved.

  • Rognon, A.; Curti, C.; Montana, M.; Terme, T.; Rathelot, P.; Vanelle, P. Therapie 2011, 66 (6), 481-491.
    Résumé : Efficacy and Future of the Aerosoltherapy in the Treatment of Cystic Fibrosis Patients Infected by Pseudomonas aeruginosa. Pseudomonas aeruginosa is considered as the most redoubtable pathogenic agent at cystic fibrosis patients. Its eradication is a priority to avoid the passage to chronic infection, the real turning point of the disease. For this, a wide therapeutic panel of intravenous antibiotics exists, and for some years, the research teams concentrate more and more on the inhaled way. The synthesis of the literature data presented herein focuses on both already experienced molecules (colistin and tobramycin), and on new therapeutics. This review aims at loosening advantages and inconveniences of each of these therapeutic options, while bringing to light the necessity of follow-up studies in order to prove the therapeutic interests of molecules in development.

  • Since, M.; Khoumeri, O.; Verhaeghe, P.; Maillard-Boyer, M.; Terme, T.; Vanelle, P. Tetrahedron Letters 2011, 52 (29), 3810-3813.
    Résumé : We report herein the first example of a SNAr reaction using TDAE-initiated carbanions in quinazoline series. The o-nitrobenzyl carbanion, formed by the action of TDAE on o-nitrobenzyl chloride, reacts with 4-chloro-2-trihalomethylquinazolines 4 and 5 via a SNAr mechanism. This enabled a new series of 4-benzyl-2-trihaloquinazoline derivatives to be synthesized in good yields under mild reaction conditions offering promising prospects for pharmacomodulation. (C) 2011 Elsevier Ltd. All rights reserved.

  • Zink, L.; Crozet, M. D.; Terme, T.; Vanelle, P. Tetrahedron Letters 2011, 52 (51), 6991-6996.
    Résumé : New reductive alkylating agents in 4- and 5-nitroimidazole series produce exclusively O-alkylation with nitronate anions under classical S(RN)1 conditions at room temperature. Electron-transfer C-alkylation is observed under microwave irradiation or under conventional heating. Furthermore, X-ray spectroscopy shows that the dihedral angles between the phenyl and imidazole rings for the two series are different, which could greatly influence reactivity in 4- and 5-nitroimidazole series. (C) 2011 Elsevier Ltd. All rights reserved.
2010

  • El-Kashef, H.; Farghaly, A. - R.; Al-Hazmi, A.; Terme, T.; Vanelle, P. Molecules 2010, 15 (4), 2651-2666.
    Résumé : The synthesis of the title compounds was achieved using ethyl 2-amino-6-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate (1) as starting material. The reaction of the amino ester 1 with phenylisothiocyanate in boiling ethanol afforded the thiourea derivative 5. The cyclization reactions of 5 under different reaction conditions led to different pyridothienopyrimidine derivatives. Other reactions of the latter derivatives leading to pyrido[4 ',3 ': 4,5]thieno[2,3-d]triazolo[1,5-a]pyrimidines are also presented.

  • Juspin, T.; Giuglio-Tonolo, G.; Terme, T.; Vanelle, P. Synthesis-Stuttgart 2010, Nᵒ 5, 844-848.
    Résumé : We report herein the first tetrakis(dimethylamino) ethylene (TDAE)-mediated double addition of nitrobenzylic anions to aromatic dialdehydes such as terephthalaldehyde and isophthalaldehyde, and have developed a new methodology that allows us to observe the double addition. This TDAE-mediated approach is an original and mild method with which to generate tri-aromatic diols.

  • Juspin, T.; Laget, M.; Terme, T.; Azas, N.; Vanelle, P. European Journal of Medicinal Chemistry 2010, 45 (2), 840-845.
    Résumé : A series of new imidazo[2,1-b]thiazoles was prepared in moderate to good yields in a four step synthesis using the TDAE methodology from 6-chloromethyl-5-nitroimidazo[2,1-b]thiazole and keto esters, ketomalonates and ketolactams. All compounds were tested for their antibacterial and antifungal activities against four bacterial strains (two Gram positive and two Gram negative ones) and four yeasts. Among these synthesized 5-nitroimidazo[2,1-b]thiazoles, the compounds I and 6 showed potent antimicrobial activities against all candida. strains and compound 3e showed an interesting antifungal potential against Candida tropicalis. (C) 2009 Elsevier Masson SAS. All rights reserved.
  • Montana, M.; Terme, T.; Vanelle, P. Letters in Organic Chemistry 2010, 7 (6), 453-456.
    Résumé : A new series of quinoxalinic oxirane derivatives was synthesized from reaction between 2-(dibromomethyl) quinoxaline and alpha-dicarbonyl compounds using tetrakis(dimethylamino) ethylene (TDAE).

  • Montana, M.; Verhaeghe, P.; Ducros, C.; Terme, T.; Vanelle, P.; Rathelot, P. Therapie 2010, 65 (6), 533-541.
    Résumé : Few studies show the reluctance of the people to get vaccinated against A (H1N1) influenza for fear of side effects of squalene (MF59, AS03, AF03) and thimerosal. The aim of this paper is to assess the safety in using these adjuvants and preservative reviewing data of clinical trials relative to wich formulation includes these compounds. In the current state of knowledge, these vaccines have proved to be effective even though they more frequently give local adverse events than non-adjuvanted influenza vaccines. Systemic side effects are generally not serious. In the studies, adjuvanted vaccines do not increase neither the risk of Guillain Barre syndrome nor auto-immune diseases. There is no convincing evidence that exposure to thimerosal in vaccines had any deletorious effect on physiological outcome.
  • Nadji-Boukrouche, A. R.; Khoumeri, O.; Terme, T.; Liacha, M.; Vanelle, P. Arkivoc 2010, 358-370.
    Résumé : We present herein an extension of the TDAE strategy using original heterocyclic carbaldehyde as electrophiles. We also evaluate the influence of the presence of nitro group on the reactivity. The TDAE-initiated reactions of various halomethyl and gem-dihalomethyl derivatives with non-nitrated carbaldehyde 1 or 2 formed the expected products accompagnied by original rearranged products while the presence of a nitro group just like the carbaldehyde 21 furnished only the expected products in good yields.