Letteratura scientifica selezionata sul tema "Dihydroxypyrimidines"

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Articoli di riviste sul tema "Dihydroxypyrimidines":

1

Powdrill, Megan H., Jerome Deval, Frank Narjes, Raffaele De Francesco e Matthias Götte. "Mechanism of Hepatitis C Virus RNA Polymerase Inhibition with Dihydroxypyrimidines". Antimicrobial Agents and Chemotherapy 54, n. 3 (22 dicembre 2009): 977–83. http://dx.doi.org/10.1128/aac.01216-09.

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ABSTRACT We studied the biochemical mechanisms associated with inhibition and resistance to a 4,5-dihydroxypyrimidine carboxylate that inhibits the hepatitis C virus (HCV) RNA-dependent RNA polymerase NS5B. On the basis of the structure of the pharmacophore, it has been suggested that these compounds may act as pyrophosphate (PPi) mimics. We monitored nucleotide incorporation events during the elongation phase and showed that the polymerase activity of wild-type NS5B was inhibited by the dihydroxypyrimidine at a 50% inhibitory concentration (IC50) of 0.73 μM. Enzymes with the G152E or P156L mutation, either of which confers resistance to this compound, showed four- to fivefold increases in IC50s. The inhibitor was competitive with respect to nucleotide incorporation. It was likewise effective at preventing the PPi-mediated excision of an incorporated chain terminator in a competitive fashion. In the absence of the dihydroxypyrimidine, the reaction was not significantly affected by the G152E or P156L mutation. These data suggest that the resistance associated with these two mutations is unlikely due to an altered interaction with the pyrophosphate-mimicking domain of the compound but, rather, is due to altered interactions with its specificity domain at a region distant from the active site. Together, our findings provide strong experimental evidence that supports the notion that the members of this class of compounds can act as PPi mimics that have the potential to mechanistically complement established nucleoside and nonnucleoside analogue inhibitors.
2

Guo, Di-Liang, Xing-Jie Zhang, Rui-Rui Wang, Yu Zhou, Zeng Li, Jin-Yi Xu, Kai-Xian Chen, Yong-Tang Zheng e Hong Liu. "Structural modifications of 5,6-dihydroxypyrimidines with anti-HIV activity". Bioorganic & Medicinal Chemistry Letters 22, n. 23 (dicembre 2012): 7114–18. http://dx.doi.org/10.1016/j.bmcl.2012.09.070.

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3

Novais, H. M., e S. Steenken. "Reactions of oxidizing radicals with 4,6-dihydroxypyrimidines as model compounds for uracil, thymine, and cytosine". Journal of Physical Chemistry 91, n. 2 (gennaio 1987): 426–33. http://dx.doi.org/10.1021/j100286a034.

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4

Telvekar, Vikas N., e Kavitkumar N. Patel. "Pharmacophore Development and Docking Studies of the HIV-1 Integrase Inhibitors Derived from N-methylpyrimidones, Dihydroxypyrimidines, and Bicyclic Pyrimidinones". Chemical Biology & Drug Design 78, n. 1 (25 maggio 2011): 150–60. http://dx.doi.org/10.1111/j.1747-0285.2011.01130.x.

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5

Astrat'ev, A. A., D. V. Dashko, A. Yu Mershin, A. I. Stepanov e N. A. Urazgil'deev. "ChemInform Abstract: Some Specific Features of Acid Nitration of 2-Substituted 4,6-Dihydroxypyrimidines. Nucleophilic Cleavage of the Nitration Products." ChemInform 32, n. 51 (23 maggio 2010): no. http://dx.doi.org/10.1002/chin.200151070.

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Winterbourn, Christine C., e Rex Munday. "Concerted Action Of Reduced Glutathione And Superoxide Dismutase In Preventing Redox Cycling Of Dihydroxypyrimidines, And Their Role In Antioxidant Defence". Free Radical Research Communications 8, n. 4-6 (gennaio 1990): 287–93. http://dx.doi.org/10.3109/10715769009053361.

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Jansa, Petr, Antonín Holý, Martin Dračínský, Viktor Kolman, Zlatko Janeba, Petra Kostecká, Eva Kmoníčková e Zdeněk Zídek. "5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production". Medicinal Chemistry Research 23, n. 10 (9 maggio 2014): 4482–90. http://dx.doi.org/10.1007/s00044-014-1018-9.

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8

Shi, Daqing, Lihui Niu e Qiya Zhuang. "Clean synthesis of pyrido[2,3-d]pyrimidines in aqueous media". Journal of Chemical Research 2005, n. 10 (ottobre 2005): 648–50. http://dx.doi.org/10.3184/030823405774663048.

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Abstract (sommario):
The reaction of substituted cinnamonitriles and 4-amino-2,6-dihydroxypyrimidine or 2,4-diamino-6-hydroxypyrimidine in water in the presence of triethylbenzylammonium chloride (TEBA) as catalyst affords a clean synthesis of pyrido[2,3-d]pyrimidine derivatives.
9

Kufelnicki, Aleksander, Jan Jaszczak, Urszula Kalinowska-Lis, Cecylia Wardak e Justyn Ochocki. "Complexes of Uracil (2,4-Dihydroxypyrimidine) Derivatives". Journal of Solution Chemistry 35, n. 5 (maggio 2006): 739–51. http://dx.doi.org/10.1007/s10953-006-9017-1.

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10

Novais, H. M., e S. Steenken. "ESR studies of electron and hydrogen adducts of thymine and uracil and their derivatives and of 4,6-dihydroxypyrimidines in aqueous solution. Comparison with data from solid state. The protonation at carbon of the electron adducts". Journal of the American Chemical Society 108, n. 1 (gennaio 1986): 1–6. http://dx.doi.org/10.1021/ja00261a001.

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Tesi sul tema "Dihydroxypyrimidines":

1

Garlatti, Laura. "Development of Bunyavirales endonucleases inhibitors by in situ click chemistry". Electronic Thesis or Diss., Aix-Marseille, 2022. http://www.theses.fr/2022AIXM0586.

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Les virus de l'ordre des Bunyavirales constituent un problème de santé publique en raison du manque d’options thérapeutiques et de leur répartition mondiale. La protéine L gouvernant le système de réplication virale possède une activité endonucléase responsable du mécanisme du vol-de-coiffe permettant la transcription. Cette enzyme clé a été identifiée comme une cible thérapeutique de choix pour développer des antiviraux. Son mécanisme d’hydrolyse de l’ARN médié par les ions Mg2+ permet de développer des inhibiteurs chélateurs de métaux de type dicéto-acide (DCA). La synthèse guidée par la cible biologique est une méthode puissante qui met au centre la cible thérapeutique qui assemble ses propres inhibiteurs en son site-actif. Nous décrivons l’utilisation des endonucléases de Bunyavirales comme « moule de réaction » pour la génération de leurs propres inhibiteurs chélateurs de métaux. Une librairie de 25 composés N-triazolyl-DCA (NT-DCA), C-triazolyl-DCA (CT-DCA) et C-triazolyl-DHP (CT-DHP) a été générée par des voies de synthèses nouvelles par chimie click. Les composés ont été caractérisés biophysiquement par Thermophorèse à Micro-échelle (MST) et par Fluorimétrie Différentielle à Balayage (DSF) et leur pouvoir inhibiteur a été évalué in vitro et dans des cellules infectées. De plus, la synthèse d’un ligand fluorescéine-DCA a été conduite pour développer un test par compétition par Polarisation de Fluorescence (FP) pour tester l’activité des composés. Des ligands à haute affinité possédant une forte activité in vitro et en cellules infectées ont été identifiés. Dans le contexte de la pandémie de COVID-19, la librairie a été repositionnée sur l'exonucléase du SARS-CoV-2
With a worldwide repartition and limited therapeutic options Bunyavirales viruses represent a major public health issue. The replication machinery of these viruses is governed by the intricate L-protein that displays an endonuclease activity responsible for the cap-snatching mechanism that allows viral transcription. This key enzyme was identified as a promising target to develop antivirals. Its catalytic mechanism of RNA hydrolysis mediated by Mg2+ ions enables the development of diketo acid (DKA) metal-chelating inhibitors. Target-Guided-Synthesis (TGS) is a powerful method that directly involves the therapeutic target that assembles its own inhibitors in its active site like LEGOs®. Herein, we describe the use of Bunyavirales endonucleases as reaction vessels for the In Situ generation of metal-chelating inhibitors. A library of 25 N-triazolyl-DKA (NT-DKA), C-triazolyl-DKA (CT-DKA) and C-triazolyl-DHP (CT-DHP) compounds was generated with new and original synthesis pathways via click chemistry. The compounds were biophysically characterized by Microscale Thermophoresis (MST) and Differential Scanning Fluorimetry (DSF) and their inhibitory potency was evaluated in vitro and in infected cells culture. Moreover, a fluorescein-DKA ligand was synthesized for the development of a competition Fluorescence Polarization (FP) assay to determine the activity of the compounds. High-affinity ligands that demonstrated a potent efficiency in vitro and in cellula were identified. In the context of the COVID-19 pandemic, the compounds library was repositioned against SARS-CoV-2 exonuclease which opened new possibilities for the development of metal-chelating Coronavirus inhibitors
2

Chen, Hui-Fang, e 陳惠芳. "Self-Assembly of dihydroxypyrimidine-based Metal Complexes". Thesis, 2007. http://ndltd.ncl.edu.tw/handle/40715693163039617195.

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碩士
中國文化大學
應用化學研究所
95
Abstract This thesis focuses on the preparation of novel-based metal-organic frameworks based on nucleobases via self-assembly strategy and the study of the influence of pH-values and alkali hydroxide (NaOH, KOH, CsOH). We chosen two uracil-derivatives 4,6-dihydroxypyrimidine (dhp-H2) and 2,4-dihydroxypyrimidine-5-carboxylic acid (H3L1), and 2-methyl-1H-benzo[d]imidazole-5-carboxylic acid (H2L2), as potential organic ligands. At first, assembly of Ni2+, Co2+or Zn2+ ions with dhp-H2 in water or alcohol at ambient temperature led to the formation of discrete molecules, [Ni(Hdhp)2(H2O)4] (HF-1) and [Co(Hdhp)2(H2O)4] (HF-2), and three-dimensional metal-organic frameworks [Co(dhp)(H2O)]n (HF-3) and [Zn(dhp)(H2O)]n (HF-4). It is found that pH-values has a dramatically effect for the preparation of HF-1-HF-4. The aptitude range of pH-values for HF-1 and HF-2 is from 9 to 10, while for HF-3 and HF-4, the values range from 11 to12. When Tb3+and Eu3+ is reacted with H3L in water or alcohol at ambient temperature, compound {K2[Tb(H2L1)4(OH)].2H2O}n (HF-5), {K2[Eu(H2L1)4(OH)].2H2O}n (HF-6) and [Tb(H2L1)(HL1)(H2O)4].3H2O (HF-7) were obtained. In this system, the influence of pH-value to the formation of HF-5-HF-7 was also observed. The aptitude range of pH-values for HF-5-HF-7 is from 9 to 10. Finally, the self-assembly reaction of Cu2+ and 2-methyl-1H-benzo[d]imidazole-5-carboxylic acid in water or alcohol at ambient temperature gave compound {[Cu(HL2)2(H2O)].1/2 H2O }n (HF-8) , which adopts a one-dimensional chain-like architecture. The solid-state structures of the products were characterized by single-crystal X-ray diffraction analyses and their properties were examined by TGA and PXRD, etc.
3

Chen, Han-Yin, e 陳函听. "Self-assembly, Structures, and Properties of Coordination Compounds Based on Dihydroxypyrimidine". Thesis, 2013. http://ndltd.ncl.edu.tw/handle/psfr2d.

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Abstract (sommario):
碩士
國立臺北科技大學
化學工程研究所
101
This thesis focuses on the preparation of based metal–organic frameworks based on nucleobases via a self-assembly strategy. Two uracil-derivatives, 4,6-dihydroxypyrimidine (H2dhp) and 2,4-dihydroxypyrimidine-5-carboxylic acid (H3dhpca), were selected for use as potential organic ligands. The assembly of CaII, NiII ions with 4,6-dihydroxypyrimidine (H2dhp) in water or alcohol at ambient temperature led to the formation of the discrete molecule [Ni(Hdhp)2(H2O)4] (1) and a 2D metal–organic frameworks {[Ca(Hdhp)2(H2O2)]•THF}n (2). When MnII, MgII and ZnII were reacted with 2,4-dihydroxypyrimidine-5-carboxylic acid (H3dhpca) in water or alcohol at ambient temperature, the discrete compounds [Mn(H2dhpca)2(H2O)2] (3), {[Mg(H2-dhpca)2(H2O)2]•2H2O} (4) , and {[K2(H2O)6][Zn(H2dhpca)2(H2O)2]} (5) were produced. The solid-state structures of the products were characterized by single-crystal X-ray diffraction analyses and their thermal stabilities were examined by TGA method.

Capitoli di libri sul tema "Dihydroxypyrimidines":

1

Ishikawa, T. "From 5-Amino-2,6-dihydroxypyrimidine-4-carboxylic Acid". In Six-Membered Hetarenes with Two Identical Heteroatoms, 1. Georg Thieme Verlag KG, 2004. http://dx.doi.org/10.1055/sos-sd-016-01777.

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Atti di convegni sul tema "Dihydroxypyrimidines":

1

Vu, Tuan, Xuan Nguyen, Nikolai Yudin e Alexander Kushtaev. "KINETICS AND NITRATION MECHANISM OF 4,6-DIHYDROXYPYRIMIDINE AND ITS DERIVATIVES IN THE PRESENCE OF NITROUS ACID". In Chemistry of nitro compounds and related nitrogen-oxygen systems. LLC MAKS Press, 2019. http://dx.doi.org/10.29003/m752.aks-2019/199-205.

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