Sfogliando per Digitare "conference object"
  • Pubblicazione
    1,2,4-Triazolo[1,5-a]-1,3,5-triazine nucleus: a possible template for adenosine receptor subtypes.
    (Comitato organizzatore del VNPCF, 2011)
    FEDERICO, STEPHANIE
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    Paoletta, Silvia
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    Cheong, Siew Lee
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    Pastorin, Giorgia
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    Cacciari, Barbara
    ;
    Stragliotto, Stefano
    ;
    Klotz, Karl Norbert
    ;
    Siegel, Jeffrey
    ;
    Gao, Zhan Guo
    ;
    Jacobson, Kenneth A.
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    MORO, STEFANO
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    SPALLUTO, GIAMPIERO
      22
  • Pubblicazione
    [1,2,4]Triazolo[1,5-a][1,3,5]Triazine Derivatives as Antagonists for the Adenosine Receptors: a Preliminary Study on Affinity at the A3 Subtype
    (Divisione di Chimica Farmaceutica della Società Chimica Italiana, 2013)
    FEDERICO, STEPHANIE
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    Ciancetta, Antonella
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    Cacciari, Barbara
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    Klotz, Karl Norbert
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    Moro, Stefano
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    SPALLUTO, GIAMPIERO
    In the last 20 years intense medicinal chemical efforts led to the synthesis of a variety of adenosine receptor (AR) agonists and antagonists for the pharmacological characterization of this family of G protein-coupled receptors.1 Several classes of heterocyclic derivatives have been reported as AR antagonists with high levels of both affinity and selectivity. Recently, the synthesis of more simplified heterocyclic derivatives has been strongly investigated in order to obtain derivatives with a better pharmacokinetic profile. In particular bicyclic systems such as adenine, triazolo-pyrazine, triazolo-pyrimidines and triazolo-triazine could be considered some of the most promising targets.2 One of the most appealing bicyclic core is the triazolo-triazine nucleus, which led in the past to the discovery of potent and selective A2A AR antagonists, such as ZM241385.3 In the past, our group performed a study on this nucleus trying to optimize substitution at the C5 and N7 positions with the aim of improving affinity and selectivity versus the hA2BAR and hA3AR subtypes. In particular, inclusion at the N7 position of arylcarbamoyl (for A3) or arylacetyl (for A2B) moieties, which gave good results in the pyrazolotriazolopyrimidine family, has been investigated.4 Unfortunately, none of these substitutions led to the desired selectivity. Regarding the A3 subtype, lack of affinity was probably observed because only lipophilic moieties were present at the 5 position (phenoxy, dimethylamino, thiomethyl) avoiding the formation of hydrogen bonds with residues inside the binding pocket of the A3 adenosine receptor. Our aim, in this work, was to synthesise new [1,2,4]triazolo[1,5-a][1,3,5]triazines introducing substituents at the 5 position able to form hydrogen bonds, such as monosubstituted amines, in order to verify if it is capable of enhance affinity and selectivity towards the A3 AR. The analogues were docked in a homology model of the hA3 AR, and the per residue electrostatic and hydrophobic contributions to the binding were assessed and stabilizing factors were proposed in order to support the experimental binding data.References (1) Moro, S, et al. Med. Res. Rev. 2006, 26, 131-159. (2) Muller, C, et al. Biochim. Biophys. Acta 2010, 1808, 1290-1308. (3) Poucher, SM, et al. Br. J. Pharmacol. 1995, 115, 1096–1102. (4) Pastorin, G, et al. Bioorg. Med. Chem. 2010, 18, 2524-2536.
      25
  • Pubblicazione
    [1,2,4]Triazolo[1,5-c]pyrimidine Nucleus as Adenosine Receptor Antagonists: Shift in Selectivity from A2A to A3 Adenosine Receptors.
    (Purine club, 2012)
    FEDERICO, STEPHANIE
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    Ciancetta, Antonella
    ;
    Paoletta, Silvia
    ;
    Cacciari, Barbara
    ;
    Klotz, Karl Norbert
    ;
    Moro, Stefano
    ;
    SPALLUTO, GIAMPIERO
    [1,2,4]Triazolo[1,5-c]pyrimidine derivatives are reported in literature as A2A adenosine receptor (AR) antagonists useful for the treatment of Parkinson’s disease (PD), senile dementia and depression (1).[1] Several classes of heterocyclic derivatives have been reported as AR antagonists.[2] Among them, the Schering compound, preladenant (2), a pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine (PTP) A2A antagonist (which is under phase III clinical trials for the treatment of PD), possesses the same lateral subtituent of compound 1.[2,3] In the [1,2,4]triazolo[1,5-c]pyrimidine compound (1) the pyrazole moiety of preladenant was substituted by a phenyl spacer, leading to a compound which displays the same affinity at the A2A AR. The [1,2,4]-triazolo[1,5-c]pyrimidine nucleus possesses a simpler structure and less nitrogen atoms than PTPs, thus it may be a scaffold with promising pharmacokinetics properties. So, starting from the similar behavior of [1,2,4]triazolo[1,5-c]pyrimidines and PTPs on ARs, and our experience on PTP as A3 AR antagonists, we decided to explore the [1,2,4]triazolo[1,5-c]pyrimidine scaffold as antagonists towards A3 AR. Initially, we introduced on the bicyclic scaffold the same substituents those give affinity and selectivity at the A3 AR in the PTP nucleus. On the basis of obtained results, the optimization of substitutions allow us, after 4 series (147compounds) of [1,2,4]triazolo[1,5-c]pyrimidine derivatives, to discover a potent and selective A3 AR antagonist, with a Ki of 0.47 nM. [1] Kyowa Hakko Kogyo Cp., Ltd., Tokyo (JP). Shimada, J.; Imma, H.; Osakada, N.; Shiozaki, S.; Kanda, T.; Kuwana, Y. [1,2,4]Triazolo[1,5-c]pyrimidine derivatives. 2003, US6545000. [2] Muller, C.E.; Jacobson, K.A. Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim. Biophys. Acta. 2011, 1808, 1290–1308. [3] Neustadt, B.R.; Hao, J., Lindo, N.; Greenlee, W.J.; Stamford, A.W.; Tulshian, D.; Ongini, E.; Hunter, J.; Monopoli, A.; Bertorelli, R.; Foster, C.; Arik, L.; Lachowicz, J.; Nga, K.; Feng, K.I. Potent, selective, and orally active adenosine A2A receptor antagonists: arylpiperazine derivatives of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines. Bioorg. Med. Chem. Lett. 2007, 17, 1376–1380.
      24
  • Pubblicazione
    1,2,4]Triazolo[1,5-c]pyrimidines as New Potent Human A3 Adenosine Receptor Antagonists.
    (Comitato organizzatore NPCF7, 2013)
    SPALLUTO, GIAMPIERO
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    FEDERICO, STEPHANIE
    ;
    Ciancetta, Antonella
    ;
    Cacciari, Barbara
    ;
    Klotz, Karl Norbert
    ;
    Moro, Stefano .
    [1,2,4]Triazolo[1,5-c]pyrimidine derivatives are reported in literature as A2A adenosine receptor (AR) antagonists useful for the treatment of Parkinson’s disease (PD), senile dementia and depression (1).1 We decided to explore the [1,2,4]triazolo[1,5-c]pyrimidine scaffold in order to obtain antagonists selective towards hA3 AR. Inactivation of the A3 AR is being studied in glaucoma but also in inflammatory diseases such as asthma.2 In a previous work, we have found that, in order to obtain good hA3 AR antagonists, the better substitutions at the 5 and 8 positions are a little alkylamino (methyl or ethylamino) and an ethylester moieties, respectively. Here we report a novel series of [1,2,4]triazolo[1,5-c]pyrimidines where we have introduced different alkyl, cycloalkyl, aryl and heteroaryl moieties at the 2 position (2). Surprisingly, the introduction of substituted-phenyl rings led to subnanomolar affinities at the hA3 AR. The best compound of this series is represented by the ethyl 2-(4-methoxyphenyl)-5-(methylamino)-[1,2,4]triazolo[1,5-c]pyrimidine-8-carboxylate (3) which shows a Ki of 0.47 nM towards hA3 AR and a 4200- and 8400-fold selectivity over hA1 and hA2A ARs, respectively.1. Shimada, J.; Imma, H.; Osakada, N.; Shiozaki, S.; Kanda, T.; Kuwana, Y. [1,2,4]Triazolo[1,5-c]pyrimidine derivatives. 2003, US6545000. 2. Cheong, S.L; Federico, S.; Venkatesan, G.; Mandel, A.L.; Shao, Y.M.; Moro, S.; Spalluto, G.; Pastorin, G. The A3 adenosine receptor as multifaceted therapeutic target: pharmacology, medicinal chemistry and in silico approaches. Med. Res. Rev. 2013, 33, 235-335.
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  • Pubblicazione
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  • Pubblicazione
    1-Substituted 3-(ω-aminoalkyl)-1H-indole derivatives as possibile s ligands.
    (--, 2005)
    MAMOLO, MARIA GRAZIA
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    D. ZAMPIERI
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    L. VIO
    ;
    S. COLLINA
    ;
    O. AZZOLINA
    ;
    C. FLORIO
      6
  • Pubblicazione
    1-substituted-3-(o-aminoalkyl)-1H-indole derivatives as possible sigma ligands.
    (Osterreichische Apotheker-Verlagsgesellschaft m.b.h., Wien, 2005)
    MAMOLO, MARIA GRAZIA
    ;
    ZAMPIERI, DANIELE
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    VIO, LUCIANO
    ;
    S. COLLINA
    ;
    O. AZZOLINA
    ;
    FLORIO, CHIARA
    Sigma (σ) receptors are involved in several functions such as modulation and biosynthesis of several neurotransmitters, motor control, cell growth and proliferation [1]. The lack of any endogenous ligand and the existence of at least two sigma receptors subtypes σ1 and σ2 make it difficult to characterize their biological role. The interest for σ ligands stems from the possibility to develop clinical agents for the treatment of several CNS diseases (affective and motor disorders, cocaine abuse, cognitive impairment), for neuroprotection, tumor treatment and diagnosis[2]. The σ2 receptor agonists results in morphological changes and apoptosis in various cell lines, including breast tumor cells. Thus, σ2 receptors may be involved in regulating cell growth and proliferation. Several classes of structurally unrelated compounds interact with σ receptors, but only few σ2 ligands are known. With the aim to obtain new σ selective ligands, we synthesized some benzooxazol-2-one and benzooxazol-2-thione (1 and 2) derivatives.
      7
  • Pubblicazione
    1. “Isolation, characterization and long-term 3D culture of periosteal Osteo-chondroblastic murine cells”,
    (society of pathology, 2005)
    FERRO F
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    F. CURCIO
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    M. MORETTI
    ;
    M. TOLLER
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    R. SPELAT
    ;
    AP BELTRAMI
    ;
    D. CESSELLI
    ;
    F. CURCIO
    Periosteum contains mesenchymal stem cells (Pe-MSCs) that contribute to normal bone growth, healing, and turnover; understanding Pe-MSC capabilities may shed light over the treatment of bone defects using tissue engineering. Bone tissue regeneration needs in vitro bone precursors or stem cell coculture onto specific scaffolds but, despite extensive research in the field, very little is known about the matrix structure of the tissue-engineered tissues and the scaffold's effects on cell differentiation. To this purpose we have selected a clonal population (murine Pe-MSCs) that was seeded and differentiated onto an acellular bone scaffold. Cell differentiation was assessed after 3 months and 1 year by molecular, histological, biochemical, and biophysical analyses and results were compared with the same osteoinduced clonal cells cultured as cellular aggregates. Our data show that Pe-MSCs cultured onto acellular bone scaffold develop a complex three-dimensional matrix and an osteoblastic phenotype but do not produce hydroxyapatite (HA); moreover, they seem able to reabsorb the colonized bone scaffold. On the contrary, cells cultured as three-dimensional aggregates differentiate and produce osteoblastic markers and HA nanocrystals.
  • Pubblicazione
    1.2 kW, 12 v Regulated Sigma Converter for 48 v Data Centers with 1 kW/in3Power Density
    (Institute of Electrical and Electronics Engineers Inc., 2023)
    Ursino M.
    ;
    Rizzolatti R.
    ;
    Deboy G.
    ;
    Saggini S.
    ;
    Zufferli K.
    The increasing interest in cloud-based services, the Internet-of-Things and the take-over of artificial intelligence computing require constant improvement of the power distribution network. As higher voltage distribution yields lower conduction losses on the rack power lines, vendors are moving from the classical 12 V rack to 48 V: this enables a 16-fold loss reduction for a given delivered power. In most cases, the server board is required to withstand input variations between 40 V and 60 V. As a consequence, the VRM (Voltage Regulator Module) must be designed to operate at these boundary conditions, which decrease this stage's efficiency also at nominal input voltage. This work addresses this issue by proposing a regulated Intermediate Bus Converter (IBC) which can maintain a fixed intermediate voltage for a wide input variation. As inductor-based, high-step-down IBCs would be inefficient, this solution exploits a non-isolated sigma connection (or ISOP, Input-Series Output-Parallel connection) between two sub-converters to maintain a high power density and efficiency. As a result, most of the power flows through a high-efficiency, soft-switched hybrid converter, while regulation is achieved with a fraction of the processed power through a boost converter. This paper shows results for a 1.2 kW solution performing a 40-60 V to 12 V semi-regulated conversion in a 25x 51 mm area, with a power density exceeding 1 kW/in3.
  • Pubblicazione
    10. New Technologies for the Great Baths of Aquileia: Results and Prospects
    (CEUR WORKSHOP PROCEEDINGS, 2011)
    RUBINICH, Marina
    The Great Baths were a large and sumptuous public building of late Roman Aquileia, with refined mosaics and inlay-work floors. Today they are completely concealed below cultivated fields, because vaults, walls and their architectural decorations were despoiled already in the Middle Age. Therefore, the university of Udine Archaeological Mission needs to employ both traditional and new technologies to reconstruct their original luxury, their complete layout and the subsequent landscape transformations suffered by the area: a meticulous stratigraphical excavation, the analysis of aerial photographs and historical maps, photogrammetric, laser-scanner and geophysical surveys. Other research projects are involved in the 3D-modelling of the buildings and photorealistic reconstructions of mosaic floors, to prepare multimedia aids for the foreseen opening to the public. All of these works are in progress: the main results and future prospects are presented here.
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  • Pubblicazione
    12. Cardiomiopatia dilatativa: storia naturale e fattori determinanti l'evoluzione e la prognosi.
    (Ed.Librex, 1989)
    A. DI LENARDA
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    G. LARDIERI
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    B. PINAMONTI
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    D. MIANI
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    L. MESTRONI
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    SINAGRA, GIANFRANCO
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    F. CAMERINI
      4
  • Pubblicazione
    “125 grammi, 872 giorni, 630.000 persone..." Memorie da un Assedio
    (EUT, 2020)
    Margherita De Michiel
    Tra omocausto e onoreficenze "per la difesa di Leningrado": cifre e simboli di un assedio, racconto e testimonianza di una delle difese più tragiche ed eroiche della Grande Guerra Patria. Un intervento attraversato da inevitabile emozione, con lettura da pagine di scrittori russi inedite in italiano offerte in traduzione autoriale per l'occasione, accompagnate dalla lettura di brani scelti delle edizioni più recenti sull'argomento. La testimonianza inoltre di come la Russia racconti oggi queste pagine tragiche attraverso iniziative di ristrutturazione museale all'avanguardia (cfr. Muzej GULAGa di Mosca) e la conquista di generi editoriali "altri" (e.g. il fumetto), per raggiungere la coscienza e la conoscenza di un pubblico sempre più vasto. Una polifonia di voci passate e presenti a rispecchiare la verità di un Paese che si è salvato con la cultura.
      1
  • Pubblicazione
    12th European Conference on Earthquake Engineering
    (Elsevier Science, 2002)
    Magonette Georges
    ;
    Molina Francisco Javier
    ;
    Viaccoz Bruno
    ;
    Sorace Stefano
    ;
    Terenzi Gloria
  • Pubblicazione
      1
  • Pubblicazione
      1
  • Pubblicazione
    14-Electron Metal Complexes Stabilized by M h3-H2C Agostic Interactions
    (Universita' di Firenze, 2005)
    BARATTA, Walter
    ;
    HERDTWECK E.
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    IENCO A.
    ;
    MASON S. A.
    ;
    MEALLI C.
    ;
    RIGO Pierluigi
    ;
    STOCCORO S.