- Synthesis and reactions of some glycosylamine derivatives of 6-azauracil nucleosides
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Reaction of the silylated 6-azauracil (2) with 2-acetamido-1,3,4,6-tetra- O-acetyl-2-deoxy-D-glucose (3) gave 1-(2-acetamido-3,4,6-tri-O-acetyl-2- deoxy-β-D-glucopyranosyl)-6-azauracil (4), which gave the free nucleoside 5 on deblocking. Acetalation of 5 gave the monoacetal 6 which was oxidized into the ketone 7. Reduction of 7 gave the allo-nucleoside 9 which on hydrolysis afforded the free nucleoside 10. Alternatively, compound 10 was obtained from mesylation of 6 to give 8 followed by subsequent acetolysis and hydrolysis.
- Al-Masoudi,Al-Atoom
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Read Online
- Synthesis and DNA topoisomerase-II inhibitory activity of unnatural nucleosides
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The synthesis and biological activities of a number of unnatural nucleosides (23-43) is described. Nucleosides have been synthesized by SnCl 4-catalyzed condensation of amino sugar acetates and silylated modified pyrimidines. Few of the 2′-O-acetyl derivatives of the nucleosides were hydrolyzed to the respective hydroxy derivatives by treatment with methanol saturated with ammonia. The compounds were screened against Filarial DNA-topoisomerase-II but only one of the compounds (29) inhibited this enzyme at 40 μg/mL of reaction mixture.
- Mishra, Ram Chandra,Dwivedi, Namrata,Tripathi, Rama Pati,Bansal, Iti,Saxena, Jitendra Kumar
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Read Online
- Chitosan–silica sulfate nanohybrid: a highly efficient and green heterogeneous nanocatalyst for the regioselective synthesis of N-alkyl purine, pyrimidine and related N-heterocycles via presilylated method
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Abstract: The presilylation of purine and pyrimidine nucleobases as well as other related N-heterocycles with HMDS utilizing chitosan–silica sulfate nanohybrid (CSSNH) is described. CSSNH is proved to be a useful, highly efficient and eco-friendly heterogeneous nanohybrid catalyst for silylation of nucleobases. The presilylated nucleobases then underwent the reaction with different sources of carbon electrophiles to afford the desired N-alkyl-substituted derivatives in good-to-excellent yields. CSSNH exhibits several advantageous involving ease of handling and preparation, low cost, reusability and environmental benignity. These unique properties render the CSSNH to be an ideal candidate for use in green industrial processes. Graphic abstract: [Figure not available: see fulltext.].
- Behrouz, Somayeh,Soltani Rad, Mohammad Navid,Piltan, Mohammad Amin
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p. 113 - 124
(2019/07/30)
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- Efficient and selective catalytic N-Alkylation of pyrimidine by ammonium Sulfate?Hydro-thermal carbone under eco-friendly conditions
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Abstract: An efficient and inexpensive method for the N-alkylation of pyrimidines using ammonium sulfate coated Hydro-Thermal-Carbone (HTC) (AS?HTC) as reused heterogeneous catalyst was developed. The catalyst was characterized by several analytical techniques such as SEM, XRD, and FTIR. The effect of various parameters was studied including catalyst loading, mole ratio, to achieve excellent selectivity and yields in 80–90%. Significantly, the present protocol offers the use of an inexpensive and environmentally friendly catalyst and simple workup. The simplicity of the procedure, excellent yield of the products, and the recyclability of the catalyst are the main advantages of this method. Graphic Abstract: Ammonium sulfate coated Hydro-Thermal-Carbone (HTC) (AS?HTC); an efficient and reused heterogeneous catalyst of the N-alkylation of pyrimidines was developed. Excellent selectivity and yields (80–90%) toward N1-alkylpyrimidines were achieved. Significantly, the present protocol offers the use of an inexpensive and environmentally friendly catalyst and simple workup.[Figure not available: see fulltext.]
- Ait Ali, Mustapha,Belkharchach, Soumia,Ighachane, Hana,Lachgar, Abdessadek,Lazrek, Hassan B
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- HMDS/KI a simple, a cheap and efficient catalyst for the one-pot synthesis of N-functionalized pyrimidines
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The syntheses of N-Alkylpyrimidine derivatives by reacting pyrimidin-2,4-diones with appropriate alkyl halide under microwave irradiation at 400 W were compared to the conventional synthesis route. These methodologies are regioselective and compatible with numerous substrates and furnish the corresponding N-alkylpyrimidines in good yields using a cheap catalyst HMDS/KI in MeCN. A comparison study between these two different modes of heating was investigated.
- Mansouri, Az-Eddine El,Zahouily, Mohamed,Lazrek, Hassan B.
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supporting information
p. 1802 - 1812
(2019/05/15)
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- Synthesis and antibacterial evaluation of 6-azapyrimidines with α-methylene-γ-(4-substituted phenyl)-γ-butyrolactone pharmacophores
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A series of 6-substituted 2-[(4-methylene-5- oxo-2-(4-substituted phenyl) tetrahydrofuran-2-yl)methyl]-1, 2,4-triazine-3,5(2H,4H)-diones (5, 6) and 2,4-bis[(4-methylene- 5-oxo-2-(4-substituted phenyl) tetrahydrofuran-2-yl) methyl]-1,2,4-triazine-3,5(2H,4H)-diones (9, 10) were designed, synthesized, and evaluated for antibacterial activity against Gram-positive and Gram-negative microorganisms. The synthesis of these compounds involved the Reformatsky-type reaction between ethyl α-(bromomethyl) acrylate and the proper ketones. Among these compounds, 2-[(4-methylene-5-oxo-2-phenyl tetrahydrofuran-2-yl) methyl]- 1,2,4-triazine-3,5(2H,4H)-dione (5a) is the most active compound and shown the selective inhibition activity against Proteus vulgaris. Springer Science+Business Media, LLC 2010.
- Huang, Po-Jui,Lee, Kuan-Han
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experimental part
p. 1081 - 1090
(2012/05/05)
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- Synthesis of new oxabicyclo[3.3.0]octane nucleoside analogues with pyrimidine bases
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Synthesis of new nucleosides with an oxabiciclo[3.3.0]octane fragment in the sugar moiety was performed by Vorbruggen nucleoside synthesis with silylated pyrimidine bases: 5-FU, 5-ClU, 5-BrU, C and 6-aza-U. The compounds were characterized by IR, MS, 1H-NMR and 13C-NMR spectra and tested for their antitumor activity comparatively with U-34 and 5IU-34. Our study points out that Cl-U-34, Br-U-34 and I-U-34 might be more efficient than U-34 against the multiplication of cancer cells, like Jurkat T lymphoblasts.
- Tanase, Constantin,Cocu, Florea G.,Caproiu, Miron T.,Draghici, Constantin,Neagoe, Ionela Victoria,Manda, Gina
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body text
p. 341 - 346
(2012/01/12)
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- A procedure for facile synthesis of nucleosides using N, O-Bistrimethyl- silylacetamide in the presence of natural phosphate coated with potassium iodide
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Several α-D/L-arabino and β-D/L- xylonucleosides were synthesized in good yields under mild conditions by N-glycosylation of 1-O-acetyl D/L- arabino, and xylofuranose, with silylated nucleobases (uracil, thymine and 6- azauracil) in acetonitrile using natural phosphate (NP) coated with potassium iodide in BSA as catalyst.
- Baddi, Laila,Smietana, Michael,Sebti, Said,Vasseur, Jean-Jacques,Lazrek, Hassan B.
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experimental part
p. 196 - 199
(2011/07/08)
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- Silica sulfuric acid (SSA) as a highly efficient heterogeneous catalyst for persilylation of purine and pyrimidine nucleobases and other N-heterocycles using HMDS
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Purine and pyrimidine nucleobases and other N-heterocycles have been silylated with HMDS in excellent yields in the presence of a catalytic amount of silica sulfuric acid (SSA) as a heterogeneous catalyst. SSA utilizes a shorter reaction time and higher yields of silylated nucleobases. SSA is reusable for several times without a decrease in reactivity or yield of silylated adducts. Copyright
- Rad, Mohammad Navid Soltani,Khalafi-Nezhad, Ali,Divar, Masoumeh,Behrouz, Somayeh
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experimental part
p. 1943 - 1954
(2010/11/16)
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- 1,2,4,-TRIAZIN-3,5-DIONE COMPOUNDS FOR TREATING DISORDERS THAT RESPOND TO MODULATION OF THE DOPAMINE D3 RECEPTOR
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The invention relates to compounds of the formula (I), wherein A is a saturated or unsaturated hydrocarbon chain having a chain length of 4 to 6 carbon atoms, the hydrocarbon chain being unsubstituted or substituted by 1, 2 or 3 methyl groups; R1 is selected from the group consisting of hydrogen, C1-C3alkyl and fluorinated C1-C3alkyl; R2 is hydrogen, halogen, cyano, C1-C3alkyl, C1-C3alkoxy, fluorinated C1-C3alkyl or fluorinated C1-C3alkoxy; R3 is selected from the group consisting of branched C4-C6alkyl and C3-C6cycloalkyl, and R4 is C1-C6alkyl, C3-C6cycloalkyl, fluorinated C1-C3alkyl and fluorinated C3-C6cycloalkyl. and the physiologically tolerated salts of these compounds and the N-oxides thereof. The invention also relates to a pharmaceutical composition that comprises at least one compound of the formula (I) and/or at least one physiologically tolerated acid addition salt thereof, and furtherto amethod for treating disorders that respond beneficially to dopamine D3receptor antagonists or dopamine D3agonists, said method comprising administering an effective amount of at least one compound or physiologically tolerated acid addition salt of the formula (I) to a subject in need thereof.
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Page/Page column 18
(2009/06/27)
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- 6-Azauracil or 8-aza-7-deazaadenine nucleosides and oligonucleotides: The effect of 2′-fluoro substituents and nucleobase nitrogens on conformation and base pairing
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The stereoselective syntheses of 6-azauracil- and 8-aza-7-deazaadenine 2′-deoxy-2′-fluoro-β-d-arabinofuranosides 1c and 2c employing nucleobase anion glycosylation with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-α-d- arabinofuranosyl bromide 6 as the sugar component are described; the 6-azauracil 2′-deoxy-2′-fluoro-β-d-ribofuranoside 1d was prepared from 6-azauridine 8via the 2,2′-anhydro intermediate 9 and transformation of the sugar with DAST. Compounds show a preferred N-conformer population (100% N for 1c, 1d and 78% N for 2c) being rather different from nucleosides not containing the combination of a fluorine atom at the 2′-position and a nitrogen next to the glycosylation site. Oligonucleotides incorporating 1c and 2c were synthesized using the phosphoramidites 3b and 4. Although the N-conformation is favoured in the series of 6-azauracil- and 8-aza-7-deazaadenine 2′-deoxy-2′-fluoroarabinonucleosides only the pyrimidine compound 1c shows an unfavourable effect on duplex stability, while oligonucleotide duplexes containing the 8-aza-7-deazaadenine-2′-deoxy- 2′-fluoroarabinonucleoside 2c were as stable as those incorporating dA or 8-aza-7-deaza-2′-deoxyadenosine 2a. The Royal Society of Chemistry 2008.
- Seela, Frank,Chittepu, Padmaja
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experimental part
p. 596 - 607
(2008/10/09)
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- Inhibition of hepatitis B virus (HBV) replication by pyrimidines bearing an acyclic moiety: Effect on wild-type and mutant HBV
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Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. The main clinical limitation of a current antiviral drug for HBV, lamivudine, is the emergence of drug-resistant viral strains upon prolonged therapy. A group of 5-, 6-, or 5,6-substituted acyclic pyrimidine nucleosides with a 1-[(2-hydroxyethoxy)methyl] moiety were synthesized and evaluated for antiviral activities. The target compounds were prepared by the reaction of silylated uracils possessing a variety of substituents at the C-5 or C-6 positions or both with 1,3-dioxolane in the presence of potassium iodide and chlorotrimethylsilane by a convenient and single-step synthesis. Among the compounds tested, 5-chloro and 5-bromo analogues possessing an acyclic glycosyl moiety were the most effective and selective antiviral agents in the in vitro assays against wild-type duck HBV (EC50 = 0.4-2.2 and 3.7-18.5 μM, respectively) and human HBV-containing 2.2.15 cells (EC50 = 4.5-45.4 and 18.5-37.7 μM, respectively). These compounds were also found to retain sensitivity against lamivudine-resistant HBV containing a single mutation (M204I) and double mutations (L180M/M204V). The compounds investigated did not show cytotoxicity to host HepG2 and Vero cells, up to the highest concentration tested. The results presented here confirm and accentuate the potential of acyclic pyrimidine nucleosides as anti-HBV agents and extend our previous observations. We herein report the capability of acyclic pyrimidine nucleosides to inhibit the replication of both wild-type and drug-resistant mutant HBV.
- Semaine, Wassila,Johar, Monika,Tyrrell, D. Lorne J.,Kumar, Rakesh,Agrawal
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p. 2049 - 2054
(2007/10/03)
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- Monocyclic L-nucleosides, analogs and uses thereof
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Novel monocyclic L- nucleoside compounds have general formula (I). Embodiments of these compounds are contemplated to be useful in treating a wide variety of diseases including infections, infestations, neoplasms, and autoimmune diseases. Viewed in terms of mechanism, embodiments of the novel compounds show immunomodulatory activity, and are expected to be useful in modulating the cytokine pattern, including modulation of Th 1 and Th 2 response.
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- Synthesis and biological evaluation of 1,3-oxathiolane 5-azapyrimidine, 6-azapyrimidine, and fluorosubstituted 3-deazapyrimidine nucleosides
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(2R,5S)-5-Amino-2-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2,4- triazine-3(2H)-one (8) and (2R,5R)-5-amino-2-[2-(hydroxymethyl)-1,3- oxathiolan-5-yl]-1,2,4-triazine-3(2H)-one (9) have been synthesized via a multi-step procedure from 6-azauridine. (2R,5S)-4-Amino-1-[2-(hydroxymethyl)- 1, 3-oxathiolan-5-yl]-1,3,5-triazine-2(1H)-one (11) and (2R,5R)-4-amino-1-[2- (hydroxymethyl)-1,3-oxathiolan-5-yl]-1,3,5-triazine-2(1H)-one (12), and the fluorosubstituted 3-deazanucleosides (19-24) have been synthesized by the transglycosylation of (2R,5S)-1-{2-[[(tert-butyldiphenylsilyl) oxy]methyl]- 1,3-oxathiolan-5-yl}cytosine (2) with silylated 5-azacytosine and the corresponding silylated fluorosubstituted 3-deazacytosines, respectively, in the presence of trimethylsilyl trifluoromethanesulfonate as the catalyst in anhydrous dichloroethane, followed by deprotection of the blocking groups. These compounds were tested in vitro for cytotoxicity against L1210, B16F10, and CCRF-CEM tumor cell lines and for antiviral activity against HIV-1 and HBV.
- Liu, Mao-Chin,Luo, Mei-Zhen,Mozdziesz, Diane E.,Lin, Tai-Shun,Dutschman, Ginger E.,Gullen, Elizabeth A.,Cheng, Yung-Chi,Sartorelli, Alan C.
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p. 603 - 618
(2007/10/03)
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- Synthesis and structural studies of monocyclic 4'-aza-L-nucleosides
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Monocyclic 4'-Aza-L-Nucleosides in which the sugar ring oxygen is replaced with a nitrogen atom are synthesized from D-lyxose. The configurational assignments of the structures of newly derived compounds were established by 1D and 2D 1H NMR experiments.
- Varaprasad, Chamakura V.,Averett, Devron,Ramasamy, Kanda S.,Wu, Jiejun
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p. 13345 - 13368
(2007/10/03)
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- Acyclic nucleosides: Synthesis of 1-[(1-hydroxy-2-propoxy)methyl]thymine, 6-azathymine, uracil, and 6-azauracil as potential antiviral agents
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A series of acyclic nucleosides have been synthesized. Thymine, 6- azathymine, uracil, and 6-azauracil were silylated with hexamethyldisilazane in the presence of ammonium sulfate and then coupled with 1-benzyloxy-2- chloromethoxypropane to give the corresponding 1-(1-benzyloxy-2- propoxy)methyl derivatives. A minor quantity of benzyloxymethylated product was also obtained in each case. Hydrogenolysis of the protected acyclic nucleosides with palladium(II) hydroxide afforded the title compounds. None of the compounds exhibited significant antiviral activity against human immunodeficiency virus (HIV).
- Wang,Chen,Tzeng
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p. 1201 - 1213
(2007/10/02)
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- TRIMETHYLIODOSILANE IN THE GLYCOSYLATION OF 5-SUBSTITUTED 6-AZAURACILS
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Intermediate quaternary salts of heterocycles with trimethyliodosilane are formed in glycosylation of 2,4-bistrimethylsilylized 5-substituted 6-azauracils with the participation of trimethyliodosilane as condensing medium.
- Kobylinskaya, V. I.,Dashevskaya, T. A.,Shalamai, A. S.,Levitskaya, Z. V.
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p. 912 - 915
(2007/10/02)
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