- Synthesis, antiviral activity, and stability of nucleoside analogs containing tricyclic bases
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A series of 3,9-dihydro-9-oxo-5H-imidazo[1,2-A]purine nucleosides (tricylic nucleosides) were synthesized from 9-[4-α-(hydroxymethyl)cyclopent-2-ene-1-α-yl]guanine (CBV) 5, (-)-β-D-(2R,4R)-1,3-dioxolane-guanosine (DXG) 6, 3′-azido-3′-deoxy-guanosine (AZG)
- Amblard, Franck,Fromentin, Emilie,Detorio, Mervi,Obikhod, Alexander,Rapp, Kimberly L.,McBrayer, Tamara R.,Whitaker, Tony,Coats, Steven J.,Schinazi, Raymond F.
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body text
p. 3845 - 3851
(2009/12/04)
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- The phosphoramidate ProTide approach greatly enhances the activity of β-2′-C-methylguanosine against hepatitis C virus
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β-2′-C-Methyl purines (1, 2) are known inhibitors of hepatitis C virus (HCV). We herein report the synthesis, biological and enzymatic evaluation of their 5′-phosphoramidate ProTides. Described herein are seven l-alanine phosphoramidate derivatives with v
- McGuigan, Christopher,Perrone, Plinio,Madela, Karolina,Neyts, Johan
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scheme or table
p. 4316 - 4320
(2010/06/19)
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- CHEMICAL COMPOUNDS
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Phosphoramidate derivatives of nucleoside compounds derived from bases such as adenine and guanine have enhanced therapeutic potency, in particular, enhanced potency with respect to the prophylaxis or treatment of a viral infection such as hepatitis C vir
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Page/Page column 25-26
(2008/12/05)
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- Efficient synthesis of 2′-C-β-methylguanosine
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2′-β-Methyl nucleosides have potential value as therapeutic agents and as nucleoside analogues for exploring RNA biology. Here we develop a strategy for efficient synthesis for 2′-C-β-methylguanosine (3). Starting from 1,2,3,5-tetra-O-benzoyl-2-C-β-methyl
- Li, Nan-Sheng,Piccirilli, Joseoh A.
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p. 4018 - 4020
(2007/10/03)
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- Structure-Activity Relationship of Purine Ribonucleosides for Inhibition of Hepatitis C Virus RNA-Dependent RNA Polymerase
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As part of a continued effort to identify inhibitors of hepatitis C viral (HCV) replication, we report here the synthesis and evaluation of a series of nucleoside analogues and their corresponding triphosphates. Nucleosides were evaluated for their ability to inhibit HCV RNA replication in a cell-based, subgenomic replicon system, while nucleoside triphosphates were evaluated for their ability to inhibit in vitro RNA synthesis mediated by the HCV RNA-dependent RNA polymerase, NS5B. 2′-C-Methyladenosine and 2′-C-methylguanosine were identified as potent inhibitors of HCV RNA replication, and the corresponding triphosphates were found to be potent inhibitors of HCV NS5B-mediated RNA synthesis. The data generated in the cell-based assay demonstrated a fairly stringent structure- activity relationship around the active nucleosides. Increase in steric bulk beyond methyl on C2, change in the stereo- or regiochemistry of the methyl substituent, or change of identity of the heterobase beyond that of the endogenous adenine or guanine was found to lead to loss of inhibitory activity. The results highlight the importance of the ribo configuration 2′- and 3′-hydroxy pharmacophores for inhibition of HCV RNA replication in the cell-based assay and demonstrate that inclusion of the 2′ -C-methylribonucleoside pharmacophore leads to increased resistance to adenosine deaminase and purine nucleoside phosphorylase mediated metabolism.
- Eldrup, Anne B.,Allerson, Charles R.,Bennett, C. Frank,Bera, Sanjib,Bhat, Balkrishen,Bhat, Neelima,Bosserman, Michele R.,Brooks, Jennifer,Burlein, Christine,Carroll, Steven S.,Cook, P. Dan,Getty, Krista L.,MacCoss, Malcolm,McMasters, Daniel R.,Olsen, David B.,Prakash, Thazha P.,Prhavc, Marija,Song, Quanlai,Tomassini, Joanne E.,Xia, Jie
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p. 2283 - 2295
(2007/10/03)
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