23643-36-9Relevant articles and documents
Structure-activity relationship of uridine-based nucleoside phosphoramidate prodrugs for inhibition of dengue virus RNA-dependent RNA polymerase
Wang, Gang,Lim, Siew Pheng,Chen, Yen-Liang,Hunziker, Jürg,Rao, Ranga,Gu, Feng,Seh, Cheah Chen,Ghafar, Nahdiyah Abdul,Xu, Haoying,Chan, Katherine,Lin, Xiaodong,Saunders, Oliver L.,Fenaux, Martijn,Zhong, Weidong,Shi, Pei-Yong,Yokokawa, Fumiaki
, p. 2324 - 2327 (2018/05/28)
To identify a potent and selective nucleoside inhibitor of dengue virus RNA-dependent RNA polymerase, a series of 2′- and/or 4′-ribose sugar modified uridine nucleoside phosphoramidate prodrugs and their corresponding triphosphates were synthesized and evaluated. Replacement of 2′-OH with 2′-F led to be a poor substrate for both dengue virus and human mitochondrial RNA polymerases. Instead of 2′-fluorination, the introduction of fluorine at the ribose 4′-position was found not to affect the inhibition of the dengue virus polymerase with a reduction in uptake by mitochondrial RNA polymerase. 2′-C-ethynyl-4′-F-uridine phosphoramidate prodrug displayed potent anti-dengue virus activity in the primary human peripheral blood mononuclear cell-based assay with no significant cytotoxicity in human hepatocellular liver carcinoma cell lines and no mitochondrial toxicity in the cell-based assay using human prostate cancer cell lines.
Synthesis process of (2R')-2'-deoxyl-2'-fluoro-2'-methyluridine
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Paragraph 0022; 0025; 0054, (2018/09/13)
The invention discloses a synthesis process of (2R')-2'-deoxyl-2'-fluoro-2'-methyluridine, relates to the technical field of synthesis of medicines, and solves the technical problems of high cost andlow product yield of the existing process. According to the synthesis process, sodium borohydride or potassium borohydride is used for reducing ribose lactone, so that an expensive reductive reagent which is sodium dihydro-bis-(2-methoxyethoxy)aluminate or lithium tri-tert-butoxyaluminum hydride is not used, and the cost is greatly reduced; N,O-bis(trimethylsilyl)acetamide is used as a silicon etherification reagent, so that the yield of glycosylation reaction is increased; the product yield can reach 85-90% and is far higher than that in route III by 58%; the product yield is obviously increased; hydroxyl at the 5' site is protected, so that side reaction in ring-closing reaction can be avoided; meanwhile, a common polar solvent which is dimethylformamide is used; the product yield undercatalysis of sodium hydrogen carbonate can reach 87-92%. The synthesis process is easy to operate; the process condition is more easily controlled; the cost is reduced; the synthesis process is applicable to large-batch production.
A (2 'R) -2' - deoxy -2 '- fluoro -2' - methyl urea glucoside preparation method (by machine translation)
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Paragraph 0041, (2017/02/28)
The invention discloses a (2 'R) -2' - deoxy -2 '- fluoro -2' - methyl urea glucoside (type I) synthetic method. Cheap and easily available starting material, through the hydroxyl protection, cyclization, the links such as fluoride, obtains the type I compound. (by machine translation)
NMR-based conformational analysis of 2′,6-disubstituted uridines and antiviral evaluation of new phosphoramidate prodrugs
Da Paix?o Soares, Fábio,Groaz, Elisabetta,Lescrinier, Eveline,Neyts, Johan,Leyssen, Pieter,Herdewijn, Piet
, p. 5809 - 5815 (2015/11/11)
Six novel phosphoramidate prodrugs of uridine analogues, with structural modifications introduced at the 6- and 2′,6-positions, have been prepared and evaluated for selective antiviral activity against hepatitis C virus, as well as other positive-stranded RNA viruses. An analysis of the conformational properties of the parent nucleosides was carried out using two-dimensional NMR spectroscopy based experiments, highlighting a 3′-endo (North) sugar puckering preference and syn orientation.
Aspartic acid based nucleoside phosphoramidate prodrugs as potent inhibitors of hepatitis C virus replication
Maiti, Munmun,Maiti, Mohitosh,Rozenski, Jef,De Jonghe, Steven,Herdewijn, Piet
, p. 5158 - 5174 (2015/05/13)
In view of a persistent threat to mankind, the development of nucleotide-based prodrugs against hepatitis C virus (HCV) is considered as a constant effort in many medicinal chemistry groups. In an attempt to identify novel nucleoside phosphoramidate analogues for improving the anti-HCV activity, we have explored, for the first time, aspartic acid (Asp) and iminodiacetic acid (IDA) esters as amidate counterparts by considering three 2′-C-methyl containing nucleosides, 2′-C-Me-cytidine, 2′-C-Me-uridine and 2′-C-Me-2′-fluoro-uridine. Synthesis of these analogues required protection for the vicinal diol functionality of the sugar moiety and the amino group of the cytidine nucleoside to regioselectively perform phosphorylation reaction at the 5′-hydroxyl group. Anti-HCV data demonstrate that the Asp-based phosphoramidates are ～550 fold more potent than the parent nucleosides. The inhibitory activity of the Asp-ProTides was higher than the Ala-ProTides, suggesting that Asp would be a potential amino acid candidate to be considered for developing novel antiviral prodrugs.
COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF VIRAL INFECTIONS
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Page/Page column 70, (2012/10/08)
Provided herein are compounds, compositions and methods for the treatment of liver disorders, including HCV infections. In one embodiment, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.
Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists
Ko, Hyojin,Carter, Rhonda L.,Cosyn, Liesbet,Petrelli, Riccardo,de Castro, Sonia,Besada, Pedro,Zhou, Yixing,Cappellacci, Loredana,Franchetti, Palmarisa,Grifantini, Mario,Van Calenbergh, Serge,Harden, T. Kendall,Jacobson, Kenneth A.
, p. 6319 - 6332 (2008/12/21)
The phosphate, uracil, and ribose moieties of uracil nucleotides were varied structurally for evaluation of agonist activity at the human P2Y2, P2Y4, and P2Y6 receptors. The 2-thio modification, found previously to enhance P2Y2 receptor potency, could be combined with other favorable modifications to produce novel molecules that exhibit high potencies and receptor selectivities. Phosphonomethylene bridges introduced for stability in analogues of UDP, UTP, and uracil dinucleotides markedly reduced potency. Truncation of dinucleotide agonists of the P2Y2 receptor, in the form of Up4-sugars, indicated that a terminal uracil ring is not essential for moderate potency at this receptor and that specific SAR patterns are observed at this distal end of the molecule. Key compounds reported in this study include 9, α,β-methylene-UDP, a P2Y6 receptor agonist; 30, Up4-phenyl ester and 34, Up4-[1]glucose, selective P2Y2 receptor agonists; dihalomethylene phosphonate analogues 16 and 41, selective P2Y2 receptor agonists; 43, the 2-thio analogue of INS37217 (P1-(uridine-5′)-P4-(2′-deoxycytidine- 5′)tetraphosphate), a potent and selective P2Y2 receptor agonist.
BICYCLIC NUCLEOSIDES AND NUCLEOTIDES AS THERAPEUTIC AGENTS
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Page/Page column 56-57, (2008/06/13)
The invention relates to the use of bicyclic nucleosides and nucleotides based on formula (II) for the treatment of infectious diseases, and in particular, viral infections.
NM 283, an efficient prodrug of the potent anti-HCV agent 2′-C-methylcytidine
Pierra,Benzaria,Amador,Moussa,Mathieu,Storer,Gosselin
, p. 767 - 770 (2007/10/03)
In order to improve the oral bioavailability of 2′-C-methylcytidine, a potent anti-HCV agent, the corresponding 3′-O-L-valinyl ester derivative (NM 283) has been synthesized. Based on its ease of synthesis and its physicochemical properties, NM 283 has emerged as a promising antiviral drug for treatment of chronic HCV infection. Copyright Taylor & Francis, Inc.
Synthesis of the phosphoramidite derivative of 2′-deoxy-2′-C-β-methylcytidine
Li, Nan-Sheng,Piccirilli, Joseph A.
, p. 6799 - 6802 (2007/10/03)
2′-Deoxy-2′-C-β-methylnucleosides elicit interest as potential therapeutic agents and as analogues for the analysis of nucleic acid structure and function. An efficient route for the synthesis of 2′-deoxy-2′-C-methyluridine (11), 2′-deoxy-2′-C-methylcytidine (12), and the phosphoramidite derivative of 2′-deoxy-2′-C-β-methylcytidine (10, 46% overall yield) from 1,2,3,5-tetra-O-benzoyl-2-C-β-methylribofuranose (1) is described.
