- NOVEL 3′-DEOXY-3′-METHYLIDENE- -L-NUCLEOSIDES
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The present invention includes novel 3′-deoxy-3′-methylidene-β-L-nucleosides, pharmaceutical composition comprising such compounds, as well as the methods to treat or to prevent viral infections and in particular HBV and/or HIV infections. In accordance with the present invention, there are provided compounds represented by Formula (I), wherein B is selected from A1 and A2;
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Page/Page column 49-50
(2011/07/07)
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- IMPROVED PROCESS FOR THE PREPARATION OF CLEVUDINE AS ANTI-HBV AGENT
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Disclosed herein is an improved method for preparing l -(2'-deoxy-2'- fluoro-beta-L-arabinofuranosyl) thymine (clevudine) useful as an anti-HBV (hepatitis B vims) agent. The method comprises an improved purification process of 2-O-imidazolylsulfonyl-l,3,5
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Page/Page column 11
(2008/12/06)
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- Synthesis and Antiviral Activity of 2′-Deoxy-2′-fluoro-L-arabinofuranosyl 1,2,3-Triazole Derivatives
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The title compounds were prepared by building up the triazole ring at the anomeric position via the glycosyl azides 5 a,b. The anomeric configurations of these nucleosides were assigned by using 1H, 13C and NOESY NMR spectroscopy. Th
- Oelgen, Suereyya,Chu, Chung K.
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p. 804 - 811
(2007/10/03)
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- A practical synthesis of L-FMAU from L-arabinose
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A practical synthesis of 2'-deoxy-2'-fluoro-5-methyl-β-L- arabinofuranosyl uracil (14, L-FMAU) was developed from L-arabinose. L- Arabinose was convened to L-ribose 5, which was used for the synthesis of bromosugar 12 via 2,3,5-O-tribenzoyl-1-O-acetyl-β-L-ribofuranose 8, which was subjected to condensation with silylated thymine and the resulting protected L-FMAU 13 was deprotected to afford L-FMAU in 14 steps in 8% overall yield.
- Du, Jinfa,Choi, Yongseok,Lee, Kyeong,Chun, Byoung K.,Hong, Joon H.,Chu, Chung K.
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p. 187 - 195
(2007/10/03)
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- Structure-activity relationships of 1-(2-deoxy-2-fluoro-β-L-arabino- furanosyl)pyrimidine nucleosides as anti-hepatitis B virus agents
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Since 2'-fluoro-5-methyl-β-L-arabinofuranosyluracil (L-FMAU) has been shown to be a potent anti-HBV agent in vitro, it was of interest to study the structure-activity relationships of related nucleosides. Thus, a series of 1- (2-deoxy-2-fluoro-β-L-arabinofuranosyl)pyrimidine nucleosides have been synthesized and evaluated for antiviral activity against HBV in 2.2.15 cells. For this study, L-ribose was initially used as the starting material. Due to the commercial cost of L-ribose, we have developed an efficient procedure for the preparation of L-ribose derivative 6. Starting from L-xylose, 6 was obtained in an excellent total yield (70%) through the pyridinium dichromate oxidation of the 3-OH group followed by stereoselective reduction with NaBH4. It was further converted to the 1,3,5-tri-O-benzoyl-2-deoxy-2- fluoro-α-L-arabinofuranose (10), which was then condensed with various 5- substituted pyrimidine bases to give the nucleosides. Among the compounds synthesized, the lead compound, L-FMAU (13), exhibited the most potent anti- HBV activity (EC50 0.1 μM). None of the other uracil derivatives showed significant anti-HBV activity up to 10 μM. Among the cytosine analogues, the cytosine (27) and 5-iodocytosine (35) derivatives showed moderately potent anti-HBV activity (EC50 1.4 and 5 μM, respectively). The cytotoxicity of these nucleoside analogues has also been assessed in 2.2.15 cells as well as CEM cells. None of these compounds displayed any toxicity up to 200 μM in 2.2.15 cells. Thus, compound 13 (L-FMAU), 27, and 35 showed a selectivity of over 2000, 140, and 40, respectively.
- Ma, Tianwei,Pai, S. Balakrishna,Zhu, Yong Lian,Lin, Ju Sheng,Shanmuganathan, Kirupa,Du, Jinfa,Wang, Chunguang,Kim, Hongbum,Newton, M. Gary,Cheng, Yung Chi,Chu, Chung K.
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p. 2835 - 2843
(2007/10/03)
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