- Synthesis and hypnotic and anti-human immunodeficiency virus-1 activities of N3-substituted 2'-deoxy-2'-fluorouridines
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Reaction of 9-[3,5-di-O-(tetrahydropyran-2-yl)-β-D- arabinofuranosyl]uracil (2) with diethylaminosulfur trifluoride in the presence of pyridine afforded 2'-deoxy-2'-flouroriboside 3a, from which 2'- deoxy-2'-fluorocytidine (14b) has been synthesized in good yield. Compound 3a was deprotected and subsequently treated with various benzyl halides or 2- chloro-4-fluoroacetophenone to give corresponding N3-substituted 2'-deoxy- 2'-fluorouridines 5a-c and 6. Compounds 5a-c, as well as 6, showed weak hypnotic activity in mice. Compound 4b showed moderate antiviral activity against human immunodeficiency virus-1 but 3b, 5a-c, and 6 were virtually inactive.
- Sato,Utsumi,Maruyama,Kimura,Yamamoto,Richman
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- Antisense modulation of CD40 ligand expression
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Antisense compounds, compositions and methods are provided for modulating the expression of CD40 ligand. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CD40 ligand. Methods of using these compounds for modulation of CD40 ligand expression and for treatment of diseases associated with expression of CD40 ligand are provided.
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Page/Page column 18
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- Synthesis and in vitro anti-HCV activity of β-D- and L-2′-deoxy-2′-fluororibonucleosides
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Based on the discovery of β-D-2′-deoxy-2′-fluorocytidine as a potent anti-hepatitis C virus (HCV) agent, a series of β-D- and L-2′-deoxy-2′-fluororibonucleosides with modifications at 5 and/or 4 positions were synthesized and evaluated for their in vitro activity against HCV and bovine viral diarrhea virus (BVDV). The introduction of the 2′-fluoro group was achieved by either fluorination of 2,2′-anhydronucleosides with hydrogen fluoride-pyridine or potassium fluoride, or a fluorination of arabinonucleosides with DAST. Among the 27 analogues synthesized, only the 5-fluoro compounds, namely β-D-2′- deoxy-2′,5-difluorocytidine (5), had anti-HCV activity in the subgenomic HCV replicon cell line, and inhibitory activity against ribosomal RNA. As β-D-N4-hydroxycytidine (NHC) had previously shown potent anti-HCV activity, the two functionalities of the N4-hydroxyl and the 2′-fluoro were combined into one molecule, yielding β-D-2′- deoxy-2′-fluoro-N4-hydroxycytidine (12). However, this nucleoside showed neither anti-HCV activity nor toxicity. All the L-forms of the analogues were devoid of anti-HCV activity. None of the compounds showed anti-BVDV activity, suggesting that the BVDV system cannot reliably predict anti-HCV activity in vitro. Copyright Taylor & Francis, Inc.
- Shi, Junxing,Du, Jinfa,Ma, Tianwei,Pankiewicz, Krzysztof W.,Patterson, Steven E.,Hassan, Abdalla E. A.,Tharnish, Phillip M.,McBrayer, Tamara R.,Lostia, Stefania,Stuyver, Lieven J.,Watanabe, Kyoichi A.,Chu, Chung K.,Schinazi, Raymond F.,Otto, Michael J.
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p. 875 - 879
(2007/10/03)
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- Antisense modulation of polo-like kinase expression
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Antisense compounds, compositions and methods are provided for modulating the expression of polo-like kinase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding polo-like kinase. Methods of using these compounds for modulation of polo-like kinase expression and for treatment of diseases associated with expression of polo-like kinase are provided.
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- Modulation of CEACAM1 expression
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Compounds, compositions and methods are provided for modulating the expression of CEACAM1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding CEACAM1. Methods of using these compounds for modulation of CEACAM1 expression and for diagnosis and treatment of disease associated with expression of CEACAM1 are provided.
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Page/Page column 26
(2010/02/11)
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- Modulation of DC-SIGN expression
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Compounds, compositions and methods are provided for modulating the expression of DC-SIGN. The compositions comprise oligonucleotides, targeted to nucleic acid encoding DC-SIGN. Methods of using these compounds for modulation of DC-SIGN expression and for diagnosis and treatment of diseases and conditions associated with expression of DC-SIGN are provided.
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Page/Page column 12
(2008/06/13)
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- Antisense modulation of perilipin expression
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Antisense compounds, compositions and methods are provided for modulating the expression of perilipin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding perilipin. Methods of using these compounds for modulation of perilipin expression and for treatment of diseases associated with expression of perilipin are provided.
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Page/Page column 18
(2008/06/13)
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- Antisense modulation of EDG5 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of EDG5. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding EDG5. Methods of using these compounds for modulation of EDG5 expression and for treatment of diseases associated with expression of EDG5 are provided.
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Page/Page column 18
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- ANTISENSE MODULATION OF EDG1 EXPRESSION
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Antisense compounds, compositions and methods are provided for modulating the expression of EDG1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding EDG1. Methods of using these compounds for modulation of EDG1 expression and for treatment of diseases associated with expression of EDG1 are provided.
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Page/Page column 18
(2008/06/13)
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- Antisense modulation of resistin expression
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Antisense compounds, compositions and methods are provided for modulating the expression of resistin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding resistin. Methods of using these compounds for modulation of resistin expression and for treatment of diseases associated with expression of resistin are provided.
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Page/Page column 18
(2010/02/05)
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- ANTISENSE MODULATION OF ENDOTHELIAL LIPASE EXPRESSION
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Antisense compounds, compositions and methods are provided for modulating the expression of Endothelial Lipase (EL). The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding EL. Methods of using these compounds for modulation of EL expression and for treatment of diseases associated with expression of EL are provided.
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- Modulation of diacylglycerol acyltransferase 1 expression
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Compounds, compositions and methods are provided for modulating the expression of diacylglycerol acyltransferase 1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding diacylglycerol acyltransferase 1. Methods of using these compounds for modulation of diacylglycerol acyltransferase 1 expression and for diagnosis and treatment of disease associated with expression of diacylglycerol acyltransferase 1 are provided.
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Page/Page column 12
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- Antisense modulation of PPP3CB expression
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Antisense compounds, compositions and methods are provided for modulating the expression of PPP3CB. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PPP3CB. Methods of using these compounds for modulation of PPP3CB expression and for treatment of diseases associated with expression of PPP3CB are provided.
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(2008/06/13)
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- Antisense modulation of Notch (Drosophila) homolog 4 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of Notch (Drosophila) homolog 4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Notch (Drosophila) homolog 4. Methods of using these compounds for modulation of Notch (Drosophila) homolog 4 expression and for treatment of diseases associated with expression of Notch (Drosophila) homolog 4 are provided.
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Page/Page column 16
(2010/02/06)
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- Antisense modulation of G protein-coupled receptor 12 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of G protein-coupled receptor 12. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding G protein-coupled receptor 12. Methods of using these compounds for modulation of G protein-coupled receptor 12 expression and for treatment of diseases associated with expression of G protein-coupled receptor 12 are provided.
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Page/Page column 19
(2010/11/30)
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- Antisense modulation of phosphoinositide-3-kinase, regulatory subunit 4, p150 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of phosphoinositide-3-kinase, regulatory subunit 4, p150. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding phosphoinositide-3-kinase, regulatory subunit 4, p150. Methods of using these compounds for modulation of phosphoinositide-3-kinase, regulatory subunit 4, p150 expression and for treatment of diseases associated with expression of phosphoinositide-3-kinase, regulatory subunit 4, p150 are provided.
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- Antisense modulation of Rb2/p130 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of Rb2/p130. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Rb2/p130. Methods of using these compounds for modulation of Rb2/p130 expression and for treatment of diseases associated with expression of Rb2/p130 are provided.
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- Notch1 inhibitors for inducing apoptosis
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Compounds, compositions and methods are provided for modulating the expression of Notch1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding Notch1. Methods of using these compounds for modulation of Notch1 expression and for diagnosis and treatment of disease associated with expression Notch1 are provided.
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- Antisense modulation of PLML expression
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Antisense compounds, compositions and methods are provided for modulating the expression of PLML. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PLML. Methods of using these compounds for modulation of PLML expression and for treatment of diseases associated with expression of PLML are provided.
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- OLIGONUCLEOTIDES HAVING MODIFIED NUCLEOSIDE UNITS
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Disclosed are oligonucleotides and oligonucleosides that include one or more modified nucleoside units. The oligonucleotides and oligonucleosides are particularly useful as antisense agents, ribozymes, aptamer, siRNA agents, probes and primers or, when hybridized to an RNA, as a substrate for RNA cleaving enzymes including RNase H and dsRNase.
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- Antisense modulation of MARK3 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of MARK3. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding MARK3. Methods of using these compounds for modulation of MARK3 expression and for treatment of diseases associated with expression of MARK3 are provided.
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- Antisense modulation of histone deacetylase 2 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of histone deacetylase 2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding histone deacetylase 2. Methods of using these compounds for modulation of histone deacetylase 2 expression and for treatment of diseases associated with expression of histone deacetylase 2 are provided.
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- Antisense modulation of prox-1 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of prox-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding prox-1. Methods of using these compounds for modulation of prox-1 expression and for treatment of diseases associated with expression of prox-1 are provided.
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- Antisense modulation of PPP3R1 expression
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Antisense compounds, compositions and methods are provided for modulating the expression of PPP3R1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PPP3R1. Methods of using these compounds for modulation of PPP3R1 expression and for treatment of diseases associated with expression of PPP3R1 are provided.
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- 132. Structural Comparison of Oligoribonucleotides and Their 2′-Deoxy-2′-fluoro Analogs by Heteronuclear NMR Spectroscopy
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1-(2′-Deoxy-2′-fluororibofuranosyl)pyrimidines were synthesized and incorporated into an RNA oligonucleotide to give 5′-r[CfGCf(UfUfC fG)GCfG]-3′ (Cf: short form of Cd2′f2′ = 2′-deoxy-2′-fluorocytidine; Uf: short form of Ud2′f2′ = 2′-deoxy-2′-fluorouridine). The oligomer was investigated by means of UV, CD, and NMR spectroscopy to address the question of how F-labels can substitute 13C-labels in the ribose ring. Through-space (NOE) and through-bond (scalar couplings) experiments were performed that make use of the ameliorated chemical-shift dispersion induced by 19F as an alternative heteronucleus. A comparison of the structures of fluorinated vs. unmodified oligomer is given. It turns out that the fluorinated oligonucleotide exists in a 14:3 equilibrium between a hairpin and a duplex conformation, in contrast to the unmodified oligonucleotide which predominantly adopts the hairpin conformation. Furthermore, the fluorinated hairpin structure adopts two distinct conformations that differ in the sugar conformation of the Uf5 and Cf6 nucleoside units, as detected by the 19F-NMR chemical shifts. The role of the 2′-OH group as stabilizing element in RNA secondary structure is discussed.
- Reif, Bernd,Wittmann, Valentin,Schwalbe, Harald,Griesinger, Christian,Woerner, Karlheinz,Jahn-Hofmann, Kerstin,Engels, Joachim W.,Bermel, Wolfgang
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p. 1952 - 1971
(2007/10/03)
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- Transformation of Uridine Derivatives into Cytidines via Selective Amination
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The synthesis of some 5-fluorosubstituted cytidine 2 derivatives via amination of corresponding uridine derivatives 1 is described. 5-Substituted 4-tetrazolo pyrimidinone derivatives 5 are key intermediates in the procedure.The method used is extended to other fluorinated starting materials, e.g. fluorinated uridinedinucleotides 7 or 2'-deoxy-2'-fluorouridine 9.The fluoro containing products are easily available by fluorination with elemental fluorine or hydrogene fluoride.
- Krug, A.,Schmidt, S.,Lekschas, J.,Lemke, K.,Cech, D.
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p. 835 - 842
(2007/10/02)
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