- 4'-HALOGEN CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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Disclosed are halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections. Such viral infections can include tongaviridae, bunyaviridae, arenaviridae, coronaviridae, flaviviridae, picornaviridae, Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infections.
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Page/Page column 325
(2021/07/10)
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- 4'-HALOGEN CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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Disclosed are halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections. Such viral infections can include tongaviridae, bunyaviridae, arenaviridae, coronaviridae, flaviviridae, picornaviridae, Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infections.
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Page/Page column 305
(2019/10/01)
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- Copper(II)nitrate catalyzed regioselective protection of primary alcohols with 4,4′-dimethoxytrityl and 2,7-dimethyl-9-phenyl xanthen-9-yl groups in nucleosides and carbohydrates
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Regioselective protection of primary hydroxyl group in nucleoside and carbohydrate analogs was accomplished using dimethoxytrityl alcohol (DMTr-OH) or dimethylpixyl alcohol (DMPx-OH) in presence of copper(II)nitrate as a Lewis acid catalyst. Excellent selectivity was observed for the protection of primary hydroxyl group over secondary while glycosidic bond remain unaffected. Utility of this methodology was further exemplified via DMTr- and DMPx-protection of alipahtic acyclic and cyclic diols.
- Penjarla, Srishylam,Prasad, S. Rajendra,Reddy, Dhande Sudhakar,Banerjee, Shyamapada,Penta, Santhosh,Sanghvi, Yogesh S.
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p. 232 - 247
(2018/05/14)
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- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 161
(2017/09/27)
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- ALKYNE CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 325
(2017/12/09)
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- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 85
(2017/07/14)
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- Oligonucleotide with protected base
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The present invention provides a protected nucleotide for elongation, which can be purified efficiently and in a high yield by a liquid-liquid extraction operation, and can achieve an oligonucleotide production method by a phosphoramidite method. It has been found that the above-mentioned problem can be solved by a particular oligonucleotide comprising a protected base and/or particular oligonucleotide protected by a branched chain-containing aromatic group at 3′-position.
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Page/Page column 78
(2016/07/27)
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- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTICS COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 346
(2016/09/26)
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- Anti-flavivirus Activity of Different Tritylated Pyrimidine and Purine Nucleoside Analogues
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A series of tritylated and dimethoxytritylated analogues of selected pyrimidine and purine nucleosides were synthesized and evaluated for their in vitro inhibitory activity against two important members of the genus Flavivirus in the Flaviviridae family, the yellow fever (YFV) and dengue viruses (DENV). Among all compounds tested, the 5′-O-tritylated and the 5′-O-dimethoxytritylated 5-fluorouridine derivatives exerted potency against YFV. Interestingly in the series of purine analogues, the 5′O, N-bis-tritylated fludarabine derivative revealed strong inhibitory activity against DENV at μm concentrations, however significantly weaker potency against YFV.
- McGuigan, Christopher,Serpi, Michaela,Slusarczyk, Magdalena,Ferrari, Valentina,Pertusati, Fabrizio,Meneghesso, Silvia,Derudas, Marco,Farleigh, Laura,Zanetta, Paola,Bugert, Joachim
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p. 227 - 235
(2016/07/07)
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- Discovery of 4′-chloromethyl-2′-deoxy-3′,5′-di- O -isobutyryl-2′-fluorocytidine (ALS-8176), A first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection
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Respiratory syncytial virus (RSV) is a leading pathogen of childhood and is associated with significant morbidity and mortality. To date, ribavirin is the only approved small molecule drug, which has limited use. The only other RSV drug is palivizumab, a monoclonal antibody, which is used for RSV prophylaxis. Clearly, there is an urgent need for small molecule RSV drugs. This article reports the design, synthesis, anti-RSV activity, metabolism, and pharmacokinetics of a series of 4′-substituted cytidine nucleosides. Among tested compounds 4′-chloromethyl-2′-deoxy-2′-fluorocytidine (2c) exhibited the most promising activity in the RSV replicon assay with an EC50 of 0.15 μM. The 5′-triphosphate of 2c (2c-TP) inhibited RSV polymerase with an IC50 of 0.02 μM without appreciable inhibition of human DNA and RNA polymerases at 100 μM. ALS-8176 (71), the 3′,5′-di-O-isobutyryl prodrug of 2c, demonstrated good oral bioavailability and a high level of 2c-TP in vivo. Compound 71 is a first-in-class nucleoside RSV polymerase inhibitor that demonstrated excellent anti-RSV efficacy and safety in a phase 2 clinical RSV challenge study.
- Wang, Guangyi,Deval, Jerome,Hong, Jin,Dyatkina, Natalia,Prhavc, Marija,Taylor, Joshua,Fung, Amy,Jin, Zhinan,Stevens, Sarah K.,Serebryany, Vladimir,Liu, Jyanwei,Zhang, Qingling,Tam, Yuen,Chanda, Sushmita M.,Smith, David B.,Symons, Julian A.,Blatt, Lawrence M.,Beigelman, Leo
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p. 1862 - 1878
(2015/04/22)
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- BASE-PROTECTED OLIGONUCLEOTIDE
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The present invention provides a protected nucleotide for elongation, which can be purified efficiently and in a high yield by a liquid-liquid extraction operation, and can achieve an oligonucleotide production method by a phosphoramidite method. It has been found that the above-mentioned problem can be solved by a particular oligonucleotide comprising a protected base and/or particular oligonucleotide protected by a branched chain-containing aromatic group at 3'-position.
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Paragraph 0370
(2015/01/18)
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- SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
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Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a norovirus, with a nucleoside, a nucleotide and an analog thereof.
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Paragraph 0225; 0344
(2015/01/16)
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- SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
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Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.
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Paragraph 0520; 0521; 0634; 0635
(2013/07/05)
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- OLIGONUCLEOTIDE WITH PROTECTED BASE
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The present invention provides a protected nucleotide for elongation, which can be purified efficiently and in a high yield by a liquid-liquid extraction operation, and can achieve an oligonucleotide production method by a phosphoramidite method. It has been found that the above-mentioned problem can be solved by a particular oligonucleotide comprising a protected base and/or particular oligonucleotide protected by a branched chain-containing aromatic group at 3′-position.
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Page/Page column
(2013/10/22)
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- Synthesis and anti-HCV activity of 3′,4′-oxetane nucleosides
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Hepatitis C virus afflicts approximately 180 million people worldwide and currently there are no direct acting antiviral agents available to treat this disease. Our first generation nucleoside HCV inhibitor, RG7128 has already established proof-of-concept
- Chang, Wonsuk,Du, Jinfa,Rachakonda, Suguna,Ross, Bruce S.,Convers-Reignier, Serge,Yau, Wei T.,Pons, Jean-Francois,Murakami, Eisuke,Bao, Haiying,Steuer, Holly Micolochick,Furman, Phillip A.,Otto, Michael J.,Sofia, Michael J.
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scheme or table
p. 4539 - 4543
(2010/11/03)
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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
(2008/06/13)
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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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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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- 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
(2008/06/13)
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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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- 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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- 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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- 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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- Uniformly modified 2'-deoxy-2'-fluoro phosphorothioate oligonucleotides as nuclease-resistant antisense compounds with high affinity and specificity for RNA targets
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'Uniformly' modified phosphodiester or phosphorothioate oligonucleotides incorporating 2'-deoxy-2'-fluoroadenosine, -guanosine, -uridine, and - cytidine, reported herein for the first time, when hybridized with RNA afforded consistent additive enhancement of duplex stability without compromising base-pair specificity. CD spectra of the 2'-deoxy-2'-fluoro- modified oligonucleotides hybridized with RNA indicated that the duplex adopts a fully A-form conformation. The 2'-deoxy-2'-fluoro-modified oligonucleotides in phosphodiester form were not resistant to nucleases; however, the modified phosphorothioate oligonucleotides were highly nuclease resistant and retained exceptional binding affinity to the RNA targets. The stabilizing effects of the 2'-deoxy-2'-fluoro modifications on RNA-DNA duplexes were shown to be superior to those of the 2'-O-methylribo substitutions. RNA hybrid duplexes with uniformly 2'-deoxy-2'-fluoro-modified oligonucleotides did not support HeLa RNase H activity; however, incorporation of the modifications into 'chimeric' oligonucleotides has been shown to activate mammalian RNase H. 'Uniformly' modified 2'-deoxy-2'-fluoro phosphorothioate oligonucleotides afforded antisense molecules with (1) high binding affinity and selectivity for the RNA target and (2) stability toward nucleases.
- Kawasaki,Casper,Freier,Lesnik,Zounes,Cummins,Gonzalez,Cook
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p. 831 - 841
(2007/10/02)
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