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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 5751. Отображено 100.
15-03-2012 дата публикации

Modified nucleotide and real-time polymerase reaction using the same

Номер: US20120064531A1
Автор: Dae-Ro AHN
Принадлежит: Korea Advanced Institute of Science and Technology KAIST

The present invention relates to a modified nucleotide and real-time polymerase reaction using the nucleotide. Specifically, the present invention relates to a fluorescence material linked-nucleotide, a composition for real-time polymerase reaction comprising the nucleotide, an analysis kit and an analysis method. In the present invention, the fluorescence material linked-nucleotide serves the dual roles of producing fluorescence signal as well as being used as a substrate. Therefore, the present invention is economically advantageous because it is unnecessary to prepare probes, but can be applied to analyze various real-time polymerase reactions such as PCR, RCA and isothermal polymerization reaction, and shows higher quality of performance than the past methods.

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Номер записи: 1
03-05-2012 дата публикации

Labelling Strategies for the Sensitive Detection of Analytes

Номер: US20120107943A1
Автор: Anja Schwoegler, Glenn A. Burley, Johannes Gierlich, Mohammad Reza Mofid, Thomas Carell
Принадлежит: BASECLICK GMBH

The present invention relates to methods and reagents for detecting analytes, e.g. nucleic acids. The new methods and reagents allow a simple and sensitive detection even in complex biological samples.

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Номер записи: 2
03-05-2012 дата публикации

Phosphonate nucleosides useful as active ingredients in pharmaceutical compositions for the treatment of viral infections, and intermediates for their production

Номер: US20120108531A1
Автор: Christophe Pannecouque, Erik De Clercq, Piet Herdewijn, Tongfei Wu
Принадлежит: KU Leuven Research and Development

Disclosed herein are novel phosphonate nucleosides and thiophosphonate nucleosides comprising a phosphonalkoxy-substituted or phosphonothioalkyl-substituted five-membered, saturated or unsaturated, oxygen-containing or sulfur-containing ring coupled to a heterocyclic nucleobase such as a pyrimidine or purine base. The invention further relates to compounds having HIV (Human Immunodeficiency Virus) replication inhibiting properties and to compounds having antiviral activities with respect to other viruses. The invention also relates to methods for preparation of all such compounds and pharmaceutical compositions comprising them. The invention further relates to the use of said compounds as a medicine and in the manufacture of a medicament useful for the treatment of subjects suffering from HIV infection, as well as for treatment of other viral, retroviral or lentiviral infections and to the treatment of animals suffering from FIV, viral, retroviral or lentiviral infections.

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Номер записи: 3
19-07-2012 дата публикации

Modulators of cell cycle checkpoints and their use in combination with checkpoint kinase inhibitors

Номер: US20120184505A1
Автор: Janeta Popovici-Muller, Kristin E. Rosner, Timothy J. Guzi
Принадлежит: Individual

In its many embodiments, the present invention provides a novel class of pyrimidine analogs as targeted mechanism-based modulators of cell cycle checkpoints. Cancers and/or malignancies can be treated by administration of a cell cycle checkpoint modulator of the invention. Also discussed are suitable combinations of the cell cycle checkpoint modulator with a checkpoint kinase inhibitor to produce synergistic apoptosis in cancer cells. The invention also includes methods of treating cancers by administering the combination of the cell cycle checkpoint modulator and the checkpoint kinase inhibitor, pharmaceutical compositions comprising the cell cycle checkpoint modulator as well as combinations and pharmaceutical kits. An example cell cycle checkpoint modulator is shown below: formula (I).

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Номер записи: 4
04-10-2012 дата публикации

Compounds and pharmaceutical compositions for the treatment of viral infections

Номер: US20120251487A1
Автор: Dominique Surleraux
Принадлежит: IDENIX Pharmaceuticals LLC

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.

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Номер записи: 5
11-10-2012 дата публикации

Cross-linking atp analogs

Номер: US20120258481A1
Автор: Mary Kay Pflum
Принадлежит: WAYNE STATE UNIVERSITY

An adenosine 5′-triphosphate analogs modified at the gamma-phosphate with a reactive reagent. A method of forming the analog by activating a 4-amino benzoic acid, incubating the activated acid to obtain an amine, and coupling the amine with ATP in the presence of water soluble EDCI. A method of detecting the efficacy of a therapeutic by adding a gamma-phosphate modified ATP analog to a protein substrate, reacting the target proteins with the ATP analog, and analyzing the resulting cross-linked product, wherein the amount of product present correlates to the efficacy of the therapeutic is also provided.

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Номер записи: 6
13-12-2012 дата публикации

Synthesis of purine nucleosides

Номер: US20120316327A1
Автор: Bruce Ross, Byoung-Kwon Chun, Dhanapalan Nagarathnam, Ganapati REDDY PAMULAPATI, Hai-Ren Zhang, Jinfa Du, Michael Joseph Sofia, Suguna Rachakonda, Wonsuk Chang
Принадлежит: GILEAD PHARMASSET LLC

A process for preparing phosphoramidate prodrugs or cyclic phosphate prodrugs of nucleoside derivatives, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof.

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Номер записи: 7
17-01-2013 дата публикации

Methods and compositions for treating hepatitis c virus

Номер: US20130017171A1
Автор: Jean-Pierre Sommadossi, Paulo Lacolla
Принадлежит: IDENIX Pharmaceuticals LLC, Universita Degli Studi Di Cagliari

A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

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Номер записи: 8
31-01-2013 дата публикации

Nucleoside phosphoramidate prodrugs

Номер: US20130029929A1
Автор: Dhanapalan Nagarathnam, Jinfa Du, Michael Joseph Sofia, Peiyuan Wang
Принадлежит: GILEAD PHARMASSET LLC

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

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Номер записи: 9
21-03-2013 дата публикации

PHOTOCLEAVABLE LABELED NUCLEOTIDES AND NUCLEOSIDES AND METHODS FOR THEIR USE IN IN DNA SEQUENCING

Номер: US20130072388A1
Автор: Litosh Vladislav A., Metzker Michael L., Stupi Brian P., Wu Weidong
Принадлежит:

Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3′-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a photocleavable terminating group. The photocleavable-fluorescent group is designed to terminate DNA synthesis as well as be cleaved so that DNA oligomers can be sequenced efficiently in a parallel format. The design of such rapidly cleavable fluorescent groups on nucleotides and nucleosides can enhance the speed and accuracy of sequencing of large oligomers of DNA in parallel, to allow rapid whole genome sequencing, and the identification of polymorphisms and other valuable genetic information, as well as allowing further manipulation and analysis of nucleic acid molecules in their native state following cleavage of the fluorescent group. 2. A compound according to claim 1 , wherein the cleavable terminating moiety is attached to the base through a linkage selected from the group consisting of benzyl amine claim 1 , benzyl ether claim 1 , carbamate claim 1 , carbonate claim 1 , 2-(o-nitrophenyl)ethyl carbamate claim 1 , and 2-(o-nitrophenyl)ethyl carbonate.4. A compound according to claim 3 , wherein Rand Rare selected from the group consisting of —CH claim 3 , —CHCH claim 3 , —CHCHCH claim 3 , isopropyl claim 3 , tert-butyl claim 3 , phenyl claim 3 , 2-nitrophenyl claim 3 , and 2 claim 3 ,6-dinitrophenyl.5. A compound according to claim 3 , wherein Rand Rare selected from the group consisting of alkyl and aromatic groups optionally containing at least one heteroatom in the alkyl or aromatic groups claim 3 , and further wherein the aromatic group may optionally be an aryl or polycyclic group.6. A compound according to claim 3 , wherein R claim 3 , R claim 3 , R claim 3 , and Rare selected from an aromatic group consisting of aryl and ...

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Номер записи: 10
04-04-2013 дата публикации

MODIFIED NUCLEOSIDES, ANALOGS THEREOF AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM

Номер: US20130084576A1
Автор: Prakash Thazha P., Seth Punit P., Swayze Eric E.
Принадлежит: Isis Pharmaceuticals, Inc.

The present invention provides modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides and analogs thereof that are useful for incorporation at the terminus of an oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. 158.-. (canceled)60. The compound of wherein Mis O.61. The compound of wherein J claim 60 , J claim 60 , Jand Jare each H.62. The compound of wherein Jforms a bridge with one of Jor J.64. The compound of wherein Qand Qare each H.66. The compound of wherein G is halogen claim 65 , OCH claim 65 , OCHF claim 65 , OCHF claim 65 , OCF claim 65 , OCHCH claim 65 , O(CH)F claim 65 , OCHCHF claim 65 , OCHCF claim 65 , OCH—CH═CH claim 65 , O(CH)—OCH claim 65 , O(CH)—SCH claim 65 , O(CH)—OCF claim 65 , O(CH)—N(R)(R) claim 65 , O(CH)—ONO(R)(R) claim 65 , O(CH)—O(CH)—N(R)(R) claim 65 , OCHC(═O)—N(R)(R) claim 65 , OCHC(═O)—N(R)—(CH)—NR)(R) or O(CH)—N(R)—C(═NR)[N(R)(R)] wherein R claim 65 , R claim 65 , Rand Rare each claim 65 , independently claim 65 , H or C-Calkyl.67. The compound of wherein said heterocyclic base moiety is a pyrimidine claim 66 , substituted pyrimidine claim 66 , purine or substituted purine.68. The compound of wherein said heterocyclic base moiety is uracil claim 67 , thymine claim 67 , cytosine claim 67 , 5-methylcytosine claim 67 , adenine or guanine.70. The oligomeric compound of wherein Mis O.71. The oligomeric compound of wherein J claim 70 , J claim 70 , Jand Jare each H.72. The oligomeric compound of wherein Jforms a bridge with one of Jor J.74. The oligomeric compound of wherein Qand Qare each H.76. The oligomeric compound of wherein Ris O and Rand Rare each claim 75 , independently claim 75 , OCH claim 75 , OCHCHor OCH(CH). ...

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Номер записи: 11
11-04-2013 дата публикации

Phosphonate analogs of hiv inhibitor compounds

Номер: US20130090299A1
Автор: Adrian S. Ray, Constantine G. Boojamra, David Y. Markevitch, Kuei-Ying Lin, Lijun Zhang, Oleg V. Petrakovsky, Richard L. Mackman
Принадлежит: Gilead Sciences Inc

The invention is related to phosphorus substituted anti-viral inhibitory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

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Номер записи: 12
11-04-2013 дата публикации

ANTIVIRAL COMPOUNDS

Номер: US20130090302A1
Автор: Boojamra Constantine G., Lin Kuei-Ying, Mackman Richard L., Markevitch David Y., Petrakovsky Oleg V., Ray Adrian S., ZHANG Lijun
Принадлежит: Gilead Sciences, Inc.

The invention is related to phosphorus substituted anti-viral inhibitory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds. 1103-. (canceled) This application claims priority to U.S. Application No. 60/591,811, filed Jul. 27, 2004, the disclosures of which are incorporated by reference in their entirety. In particular, the figures described on pages 161 to 184 are incorporated as Figures herein.The invention relates generally to compounds with HIV inhibitory activity.Improving the delivery of drugs and other agents to target cells and tissues has been the focus of considerable research for many years. Though many attempts have been made to develop effective methods for importing biologically active molecules into cells, both in vivo and in vitro, none has proved to be entirely satisfactory. Optimizing the association of the inhibitory drug with its intracellular target, while minimizing intercellular redistribution of the drug, e.g., to neighboring cells, is often difficult or inefficient.Most agents currently administered to a patient parenterally are not targeted, resulting in systemic delivery of the agent to cells and tissues of the body where it is unnecessary, and often undesirable. This may result in adverse drug side effects, and often limits the dose of a drug (e.g., glucocorticoids and other anti-inflammatory drugs) that can be administered. By comparison, although oral administration of drugs is generally recognized as a convenient and economical method of administration, oral administration can result in either (a) uptake of the drug through the cellular and tissue barriers, e.g., blood/brain, epithelial, cell membrane, resulting in undesirable systemic distribution, or (b) temporary residence of the drug within the gastrointestinal tract. Accordingly, a major goal has been to develop methods for ...

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Номер записи: 13
18-04-2013 дата публикации

SUBSTITUTED 3',5'-CYCLIC PHOSPHATES OF PURINE NUCLEOTIDE COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF VIRAL INFECTIONS

Номер: US20130095064A1
Автор: Dousson Cyril B., Parsy Christophe Claude, Surleraux Dominique
Принадлежит: IDENIX PHARMACEUTICALS, INC.

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents 2. The compound of wherein Ris hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , isobutyl or t-butyl.3. The compound of wherein Ris methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , isobutyl claim 1 , 2-butyl claim 1 , cyclopentyl claim 1 , cyclobutyl claim 1 , cyclopropyl or t-butyl.7. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient claim 1 , carrier or diluent.8. The pharmaceutical composition of claim 7 , wherein the composition is an oral formulation.9. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient claim 5 , carrier or diluent.10. The pharmaceutical composition of claim 9 , wherein the composition is an oral formulation.11. A method for the treatment of a host infected with a hepatitis C virus claim 1 , comprising the administration of an effective treatment amount of a compound of .12. The method of claim 11 , wherein the host is a human.13. The method of claim 11 , wherein said administration directs a substantial amount of said compound or pharmaceutically acceptable salt or stereoisomer thereof to the liver of said host.14. The method of claim 11 , wherein said compound is administered in combination or alternation with a second anti-viral agent optionally selected from the group consisting of an interferon claim 11 , a ribavirin claim 11 , an interleukin claim 11 , a NS3 protease inhibitor claim 11 , a cysteine protease inhibitor claim 11 , a phenanthrenequinone claim 11 , a thiazolidine derivative claim 11 , a thiazolidine claim 11 , a benzanilide claim ...

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Номер записи: 14
18-04-2013 дата публикации

3'-OH UNBLOCKED NUCLEOTIDES AND NUCLEOSIDES BASE MDIFIED WITH NON-CLEAVABLE, TERMINATING GROUPS AND METHODS FOR THEIR USE IN DNA SEQUENCING

Номер: US20130095471A1
Автор: Litosh Vladislav A., Metzker Michael L., Stupi Brian P., Wu Weidong
Принадлежит:

Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3′-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a non-cleavable terminating group. The non-cleavable-fluorescent group is designed to terminate DNA synthesis so that DNA oligomers can be sequenced efficiently in a parallel format. These reagents and methods will lead to more accurate identification of polymorphisms and other valuable genetic information. 2. The compound of claim 1 , wherein the non-cleavable terminating moiety is attached to the base through a linkage selected from the group consisting of benzyl amine claim 1 , benzyl ether claim 1 , carbamate claim 1 , carbonate claim 1 , 2-(o-nitrophenyl)ethyl carbamate claim 1 , and 2-(o-nitrophenyl)ethyl carbonate.4. The compound of claim 3 , wherein Rand Rare each independently selected from the group consisting of H claim 3 , —CH claim 3 , —CHCH claim 3 , —CHCHCH claim 3 , isopropyl claim 3 , tert-butyl claim 3 , and phenyl.5. The compound of claim 3 , wherein Rand Rare each independently selected from the group consisting of H claim 3 , alkyl and aromatic groups optionally containing at least one heteroatom in the alkyl or aromatic groups claim 3 , and further wherein the aromatic group may optionally be an aryl or polycyclic group.6. The compound of claim 3 , wherein R claim 3 , R claim 3 , R claim 3 , and Rare each H.78-. (canceled)9. A method of determining the sequence of a target nucleic acid comprising(i) adding a target nucleic acid to a Sanger or Sanger-type sequencing apparatus,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(ii) adding one or more compounds according to to the sequencing apparatus, with the proviso that where more than one type of base is present, each base is attached to a different fluorophore;'}(iii) ...

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Номер записи: 15
25-04-2013 дата публикации

METHODS AND COMPOSITIONS RELATED TO MODIFIED ADENOSINES FOR CONTROLLING OFF-TARGET EFFECTS IN RNA INTERFERENCE

Номер: US20130102652A1
Автор: Burrows Cynthia J., Ghanty Uday
Принадлежит: UNIVERSITY OF UTAH RESEARCH FOUNDATION

Disclosed are compositions and methods related to modified nucleobases. Also disclosed are compositions and methods related to modified interfering RNAs. Also disclosed are compositions and methods related to modified adenonsine for controlling off-target effects in RNA interference. 2. The compound of claim 1 , wherein Rcomprises a protected phosphate.4. The compound of claim 1 , wherein Ris chloride.8. The nucleoside of claim 7 , wherein Ris chloride.14. A method of blocking the binding of an off-target molecule to an siRNA molecule claim 7 , comprising claim 7 ,modifying at least one adenosine base of the siRNA molecule, andadministering to a subject the siRNA molecule.15. The method of claim 14 , wherein the siRNA molecule comprises two or more modified adenosine bases.16. The method of claim 14 , wherein the siRNA molecule comprises three or more modified adenosine bases.17. The method of claim 14 , wherein the modified adenosine base comprises the compound of .18. The method of claim 14 , wherein the off-target molecule is a double stranded RNA-binding motif (dsRBM).19. The method of claim 18 , wherein the dsRBM is RNA dependent protein kinase (PKR).20. The method of claim 18 , wherein the dsRBM is adenosine deaminase (ADAR).21. The method of claim 14 , wherein the off-target molecule is Toll-Like Receptor-7 claim 14 , Toll-Like Receptor-8 claim 14 , or Toll-Like Receptor-9.22. The method of claim 14 , wherein the efficacy of the siRNA molecule is increased.23. An siRNA molecule comprising at least one modified adenosine.24. The siRNA molecule of claim 23 , wherein the base opposite the modified adensosine is not complementary.25. A kit comprising the compound of .26. A kit comprising the compound of .27. A kit comprising the nucleoside of .28. A kit comprising the oligonucleotide of .29. A kit comprising the polynucleotide of .30. A set of nucleotides comprising at least one compound of .31. A set of nucleotides comprising at least one oligonucleotide or ...

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Номер записи: 16
25-04-2013 дата публикации

ALKYNYL-DERIVATIZED CAP ANALOGS, PREPARATION AND USES THEREOF

Номер: US20130102655A1
Автор: Gee Kyle, Kore Anilkumar R., Muthian Shanmugasundaram
Принадлежит: LIFE TECHNOLOGIES CORPORATION

Alkynyl-derivatized cap analogs, alkynyl-modified capped RNA, 1,4-disubstituted triazole-derivatized capped RNA, methods of preparation, methods of isolation, and uses thereof are provided. The “click” modification facilitates detection and isolation of capped RNAs and the 1,4-disubstituted triazole derivatives formed by the “click” reaction are useful for producing RNA transcripts and encoded protein. 1. A composition comprising an alkynyl-derivatized cap analog having the structure:{'sub': '3', 'sup': '7,3′-O-alkynyl', 'RG[5′]p[p]np[5′]G,'}{'sub': '3', 'sup': '7,3′-O-alkynyl', 'RG[5′]p[p]np[5′]A,'}{'sub': '3', 'sup': '7,2′-O-alkynyl', 'b': '5', 'RG[′]p[p]np[5′]G,'}{'sub': '3', 'sup': '7,2′-O-alkynyl', 'b': '5', 'RG[′]p[p]np[5′]A,'} [{'sub': '3', 'Ris alkyl or arylalkyl,'}, 'the alkynyl moiety comprises 3-24 carbon atoms, a terminal alkyne, and is optionally substituted,', 'n is 1, 2, or 3,', 'A is adenosine, and', 'G is guanosine., 'wherein'}, 'or a salt thereof,'}2. A composition comprising RNA having a cap analog of covalently bonded thereto.4. The composition of claim 3 , wherein Rcomprises O(CH)C≡CH and m is 1 to 6 claim 3 , and Rcomprises OH.5. The composition of claim 3 , wherein Rcomprises O(CH)C≡CH and m is 1 to 6 claim 3 , and Rcomprises OH.6. The composition of claim 4 , wherein m is 1.7. The composition of wherein the alkyl is methyl claim 3 , ethyl claim 3 , propyl claim 3 , isopropyl claim 3 , butyl or isobutyl.8. The composition of attached to the 5′ end of an RNA molecule.9. The composition of wherein the RNA molecule is a mRNA molecule.10. A method of producing alkynyl-modified capped RNA comprising: contacting a nucleic acid substrate with a RNA polymerase and the alkynyl-derivatized cap analog of in the presence of nucleotide triphosphates under conditions and for a time to produce alkynyl-modified capped RNA.11. The method of further comprising contacting the alkynyl-modified capped RNA with an azide-derivatized moiety to form a 1 claim 10 ,4- ...

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Номер записи: 17
25-04-2013 дата публикации

NEURITE OUTGROWTH AGENT

Номер: US20130102771A1
Автор: Ikeda Tsuyoshi, Kaminishi Hidenori, Kinjo Junei, Sakamoto Akihiro, Tsuchihashi Ryota
Принадлежит:

An object of the present invention is to provide a non-peptidic nerve axon and/or neurite outgrowth agent for allowing a nerve axon and a neurite to elongate. 3-(Aminocarbonyl)-1-[5-O-[[1-(6-amino-9H-purin-9-yl)-1-deoxy-β-D-ribofuranos-5-O-yl]phosphonyloxy(oxylato)phosphinyl]-β-L-ribofuranosyl]pyridinium that is an analogue of nicotinamide adenine dinucleotide (NAD) comprising β-L-ribose as the sugar component is used as a nerve axon and/or neurite outgrowth agent or composition, a cancer cell growth suppressing and/or apoptosis inducing agent, or a cancer cell growth suppressing and/or apoptosis inducing composition. 1. A compound that is 3-(aminocarbonyl)-1-[5-O-[[1-(6-amino-9H-purin-9-yl)-1-deoxy-β-D-ribofuranose-5-O-yl]phosphonyloxy(oxylato)phosphinyl]-β-L-ribofuranosyl]pyridinium.210.-. (canceled) The present invention relates to a nerve axon and/or neurite outgrowth agent and an anticancer agent. More specifically, the present invention relates to: a nerve axon and/or neurite outgrowth agent and a cancer cell growth suppressing and/or apoptosis inducing agent, each of which comprises, as an active ingredient, a nicotinamide adenine dinucleotide (NAD) analogue in which the sugar component of the nicotinamide mononucleotide portion thereof is β-L-ribose; and food and a food material comprising the nicotinamide adenine dinucleotide (NAD) analogue, which are used for the functional recovery of cranial nerve or the prevention and/or treatment of cancer.Once a neural circuit network is damaged by brain injury or spinal cord injury and the network is thereby cut off or results in nerve cell death, the physiological and/or motor functions governed by nerves are lost, and it becomes extremely difficult to restore the neural circuit. However, in order to recover and/or restore various lost functions, the reconstruction of networks among surviving nerve cells is essential, and thus, nerve axons extending from the surviving nerve cells and neurites extending from the ...

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Номер записи: 18
02-05-2013 дата публикации

Method of ameliorating oxidative stress and supplementing the diet

Номер: US20130108605A1
Автор: Boyd E. Haley, Niladri Narayan Gupta
Принадлежит: University of Kentucky Research Foundation

A method of supplementing a diet and ameliorating oxidative stress in a mammal includes administering a pharmaceutically effective amount of lipid soluble, hydrophobic active compounds having a chemical structure: wherein R 1 is an aromatic backbone and R 2 is a sulfur containing ligand. Through formation of disulfide linkages other moieties can be attached to R 2 converting the hydrophobic base into a water soluble entity, for ease of delivery, which can be reconverted back to the original compound by biochemical reduction in the blood stream.

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Номер записи: 19
23-05-2013 дата публикации

AGENT FOR ENHANCING THE EFFECT OF SKIN-WHITENING INGREDIENTS AND USES THEREOF

Номер: US20130129651A1
Автор: Fukuda Shigeharu, Iwaki Kanso, Miyake Masaki, Okura Takanori, Sano Osamu
Принадлежит: HAYASHIBARA CO., LTD.

The present invention has objects to provide an agent for enhancing the effect of skin-whitening ingredients which enhances the skin-whitening action of skin-whitening ingredients and has an improved safeness, and to provide a skin-whitening agent, which contains the above agent and a skin-whitening ingredient(s) and has an improved and enhanced skin-whitening action. The present invention solves the above objects by providing an agent for enhancing the effect of skin-whitening ingredients, which contains one or more members selected from the group consisting of guanine and derivatives thereof as an effective ingredient(s); and a skin-whitening agent which contains the above agent along with a skin-whitening ingredient(s) particularly, members derivatives thereof and/or equol including derivatives thereof. 1. An agent for enhancing the effect of skin-whitening ingredients , which comprises one or more members selected from the group consisting of guanine including derivatives thereof as an effective ingredient(s).2. The agent of claim 1 , wherein said guanine including derivatives thereof is one or more members selected from the group consisting of guanine claim 1 , guanosine claim 1 , guanosine monophosphate claim 1 , guanosine diphosphate claim 1 , guanosine triphosphate claim 1 , and glucosylguanosine.3. The agent of claim 1 , which enhances the skin-whitening action of adenine including derivatives thereof and/or equol including derivatives thereof.4. The agent of claim 3 , wherein said adenine including derivatives thereof is one or more members selected from the group consisting of adenine claim 3 , adenosine claim 3 , adenosine monophosphate claim 3 , adenosine diphosphate claim 3 , adenosine triphosphate claim 3 , and glucosyladenosine.5. The agent of claim 3 , wherein said equol including derivatives thereof is equol and/or glycosylequol.6. A skin-whitening agent claim 1 , which comprises the agent of and adenine including derivatives thereof claim 1 , ...

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Номер записи: 20
23-05-2013 дата публикации

OLIGONUCLEOTIDES COMPRISING ACYCLIC AND ABASIC NUCLEOSIDES AND ANALOGS

Номер: US20130130378A1
Автор: Jayaprakash Narayanannair K., Lackey Jeremy, Manoharan Muthiah, Rajeev Kallanthottathil G.
Принадлежит: ALNYLAM PHARMACEUTICALS, INC.

This invention relates to acyclic and abasic nucleosides and oligonucleotides prepared therefrom. For instance, oligonucleotides can be prepared having one or more of the following formulas (I-III):, or isomers thereof. 54. The monomer of any of - claims 1 , wherein Ris a protecting group and Ris a reactive phosphorous group or solid support.64. The monomer of any of - claims 1 , wherein Ris a reactive phosphorous group or solid support and Ris a protecting group.76. The monomer of any of - claims 1 , wherein the reactive phosphorus group is selected from the group consisting of phosphoramidite claims 1 , H-phosphonate claims 1 , alkyl-phosphonate claims 1 , and phosphate triester.87. The monomer of any of - claims 1 , wherein the protecting group is a hydroxyl protecting group selected from the group consisting of acetyl claims 1 , benzyl claims 1 , t-butyldimethylsilyl claims 1 , t-butyldiphenylsilyl claims 1 , trityl claims 1 , monomethoxytrityl claims 1 , and dimethoxytrityl.98. An oligonucleotide comprising at least one monomer of any of -.16. The oligonucleotide of claim 15 , wherein n1 or n2 is 1-20.1716. The oligonucleotide of any of - claims 9 , wherein the monomer is at the 5′-end terminal position of the oligonucleotide.1816. The oligonucleotide of any of - claims 9 , wherein the monomer is at the 3′-end terminal position of the oligonucleotide.1916. The oligonucleotide of any of - claims 9 , wherein the monomer is at an internal position of the oligonucleotide.2016. The oligonucleotide of any of - claims 9 , wherein the monomer is at both the 5′- and 3′-end terminal position of the oligonucleotide.2116. The oligonucleotide of any of - claims 9 , wherein the monomer is present at the 5′-end terminal position and at least one internal position of the oligonucleotide.2216. The oligonucleotide of any of - claims 9 , wherein the monomer is present at the 3′-end terminal position and at least one internal position of the oligonucleotide.2316. The ...

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Номер записи: 21
06-06-2013 дата публикации

TANAPROGET DERIVATIVES, METABOLITES, AND USES THEREOF

Номер: US20130143827A1
Автор: Chandrasekaran Appavu, DeMaio William, Keating Kelly, McConnell Oliver J., Shen Li
Принадлежит: WYETH LLC

A method of generating synthetic metabolites of tanaproget derivatives thereof is provided. These compounds and methods of using these derivatives for detecting tanaproget metabolites in samples are provided. 1. A method for detecting metabolites of tanaproget in a sample , said method comprising:(a) isolating said metabolite of tanaproget in said sample;(b) characterizing said metabolite of tanaproget to determine the structure of said metabolite of tanaproget; and(c) comparing said structure to the structures of synthetic N- and S-glucuronide derivatives of tanaproget.2. The method according to claim 1 , wherein said synthetic glucuronide derivative of tanaproget is an S-glucuronide derivative.3. The method according to claim 1 , wherein said synthetic glucuronide derivative of tanaproget is an N-glucuronide derivative.4. An antibody generated using a synthetic glucuronide derivative of tanaproget claim 1 , said antibody being specific for tanaproget or a derivative thereof.5. The antibody according to claim 4 , wherein said synthetic glucuronide derivative of tanaproget is an S-glucuronide derivative.6. The antibody according to claim 4 , wherein said synthetic glucuronide derivative of tanaproget is an N-glucuronide derivative.7. A kit for monitoring therapy with tanaproget claim 6 , said kit comprising an antibody according to .8. A method for detecting metabolites of tanaproget claim 6 , said method comprising detecting binding to an antibody according to .9. A method for detecting metabolites of tanaproget claim 6 , said method comprising comparison of a sample to a tanaproget derivative selected from the group consisting of:(a) an enzymatically derived tanaproget glucuronide derivative;(b) tanaproget having a sulfate moiety located on the thiocarbonyl group;(c) tanaproget having a hydroxy group located on the pyrrole ring;(d) tanaproget having a hydroxy group located on the phenylpyrrole ring; and(e) tanaproget having a carbamate located on the thiocarbonyl ...

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Номер записи: 22
20-06-2013 дата публикации

Novel Synthesis of Nucleoside 5'-Triphosphates and Their Derivatives

Номер: US20130158249A1
Автор: Zhen Huang
Принадлежит: Sena Res Inc

Disclosed are compounds of nucleoside 5′-triphosphates of formula (I), or derivatives thereof, or pharmaceutically acceptable salts of said nucleoside 5′-triphosphates or said derivatives, wherein the Base of formula (I) is Adenine (A), Cytosine (C), Guanine (G), Thymine (T), Uracil (U), modified nucleobase or unnatural nucleobase; R 1 is H or OH, R 2 is H or OH, X is independently selected from the group consisting of O, S and Se; and Y is independently selected from the group consisting of O, B (borano, or BH 3 ), S, and Se. Also disclosed are processes of preparing the compounds of formula (I), said process comprising steps according to Scheme A:

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Номер записи: 23
27-06-2013 дата публикации

Substituted nucleotide analogs

Номер: US20130164261A1
Автор: Guangyi Wang, Leonid Beigelman
Принадлежит: Alios Biopharma Inc

Disclosed herein are phosphorothioate nucleotide analogs, methods of synthesizing phosphorothioate nucleotide analogs and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with the phosphorothioate nucleotide analogs.

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Номер записи: 24
27-06-2013 дата публикации

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Номер: US20130165400A1
Автор: Beigelman Leonid, Deval Jerome, Prhavc Marija, Smith David Bernard, Wang Guangyi
Принадлежит: ALIOS BIOPHARMA, INC.

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. 3. The compound of claim 1 , wherein Ris an optionally substituted acyl.4. The compound of claim 1 , wherein Ris H.5. The compound of claim 1 , wherein Ris an optionally substituted O-linked amino acid.7. The compound of claim 6 , wherein both Rand Rare independently selected from the group consisting of an optionally substituted Calkyl claim 6 , an optionally substituted Calkenyl claim 6 , an optionally substituted Calkynyl claim 6 , an optionally substituted Ccycloalkyl claim 6 , an optionally substituted Ccycloalkenyl claim 6 , an optionally substituted aryl claim 6 , an optionally substituted heteroaryl and an optionally substituted aryl(Calkyl).10. The compound of claim 6 , wherein Ris selected from the group consisting of absent claim 6 , hydrogen claim 6 , an optionally substituted Calkyl claim 6 , an optionally substituted Calkenyl claim 6 , an optionally substituted Calkynyl claim 6 , an optionally substituted Ccycloalkyl and an optionally substituted Ccycloalkenyl; and Ris independently selected from the group consisting of an optionally substituted Calkyl claim 6 , an optionally substituted Calkenyl claim 6 , an optionally substituted Calkynyl claim 6 , an optionally substituted Ccycloalkyl claim 6 , an optionally substituted Ccycloalkenyl and NRR.11. The compound of claim 6 , wherein Ris an optionally substituted aryl; and Ris an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.12. The compound of claim 6 , wherein Rand Rare both an optionally substituted N-linked amino acid ...

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Номер записи: 25
18-07-2013 дата публикации

METHOD FOR PREPARING RIBONUCLEOSIDE PHOSPHOROTHIOATE

Номер: US20130184450A1
Автор: Nukaga Yohei, Wada Takeshi
Принадлежит: THE UNIVERSITY OF TOKYO

A method for preparing a phosphorothioate RNA based on the oxazaphospholidine method, wherein cyanoethoxymethyl group is used instead of tert-butyldimethylsilyl group as a protective group of 2′-hydroxyl group of RNA. 2. The method according to claim 1 , wherein Ris a phenyl group.3. The method according to claim 1 , wherein Ris a 4 claim 1 ,4′-dimethoxytrityl group.4. The method according to claim 1 , wherein the condensation is performed in the presence of an activator.5. The method according to claim 4 , wherein N-(cyanomethyl)pyrrolidinium triflate or N-phenylimidazolium triflate is used as the activator.6. The method according to claim 1 , wherein dimethyl thiuram disulfide is used as a sulfurizing agent.7. The method according to claim 1 , which comprises the step of repeating the aforementioned step n+1 times using a compound represented by the general formula (III) in which n is 0 as a starting material.8. The method according to claim 1 , wherein the reaction is performed by the solid phase method.9. The method according to claim 8 , wherein a compound represented by the formula (III) claim 8 , in which n is 0 and which is bound to a solid phase carrier optionally via a linker claim 8 , is used.10. The method according to claim 1 , wherein all of n+1 of X are divalent groups represented by the formula (II-Sp) claim 1 , or all of them are divalent groups represented by the formula (II-Rp).11. A ribonucleoside phosphorothioate represented by the formula (I) mentioned in claim 1 , wherein claim 1 , R claim 1 , Bs claim 1 , n claim 1 , and X have the same meanings as those defined above claim 1 , and Rrepresents a cyanoethoxymethyl group claim 1 , or a salt thereof.12. An oxazaphospholidine ribonucleoside represented by the formula (IVa) or (IVb) mentioned in claim 1 , wherein claim 1 , Bs claim 1 , CEM claim 1 , R claim 1 , and Rhave the same meanings as those defined above. The present invention relates to a method for stereoselectively preparing a ...

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Номер записи: 26
08-08-2013 дата публикации

COMPOUNDS FOR TREATING BACTERIAL INFECTIONS

Номер: US20130203694A1
Автор: Ben Yehuda Sigal, Glaser Gad, Kaspy Ilana, Katzhendler Joshua, Mawasi Hafiz, Oppenheimer-Shaanan Yaara, Vidavski Roee, Wexselblatt Ezequiel
Принадлежит: YISSUM RESEARCH DEVELOPMENT CO. OF THE HEBREW UNIVERSITY OF JERUSALEM LTD.

Rel proteins as a novel therapeutic agent for treating bacterial threats. More specifically, a novel class of compounds of Formula (I) as disclosed herein which possess anti-bacterial activity and which inhibit RelA, RelSeq or RelSpo synthetic activity or bacterial spore formation. Also, pharmaceutical compositions of such compounds and a method of combating bacteria, or treating bacterial infections, by administering to a subject in need thereof such compounds or pharmaceutical compositions. 143.-. (canceled)47. The compound according to claim 44 , wherein Ris H or —CO—CH(CH).49. The compound according to claim 44 , wherein Rand Rare each independently H or methyl.50. The compound according to claim 44 , wherein Ris independently at each occurrence H claim 44 , methyl claim 44 , ethyl or benzyl.51. The compound according to claim 44 , wherein Ris H or phenyl.63. An anti-bacterial pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 44 , and a pharmaceutically acceptable carrier or excipient.64. A method of combating bacteria claim 44 , or treating bacterial infections claim 44 , comprising the step of administering to a subject in need thereof a compound according to claim 44 , or a pharmaceutical composition comprising such compound. The present invention generally relates to Rel proteins as a novel therapeutic target for treating bacterial threats and more specifically to a novel class of 2′-deoxyguanosine analogs, which possess anti-bacterial activity, to pharmaceutical compositions comprising such compounds, and to methods of use thereof for combating bacteria and treating bacterial infections.Bacteria cells present an outstanding ability to rapidly react to various changes in their growth environment. The number of useful antibiotic agents is decreasing fast. Thus, there is an urgency for finding alternative ways to deal with the crisis.The natural environment of bacteria is often characterized by changes in ...

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Номер записи: 27
08-08-2013 дата публикации

NUCLEOSIDES WITH ANTIVIRAL AND ANTICANCER ACTIVITY

Номер: US20130203978A1
Автор: Wagner Carston R.
Принадлежит: Regents of the University of Minnesota

The invention provides a compound of formula (I), wherein R1-R6 and X have any of the values described, as well as pharmaceutical compositions comprising such compounds and therapeutic methods comprising the administration of such compounds. 2. The compound of wherein Ris guanine.3. The compound of wherein Ris NRR claim 1 , wherein Ris phenylmethyl and Ris hydrogen.4. The compound of wherein Ris (C-C)alkyl optionally substituted with one or more halo claim 1 , hydroxy claim 1 , (C-C)alkoxy claim 1 , (C-C)cycloalkyloxy claim 1 , (C-C)alkanoyloxy claim 1 , trifluoromethyl claim 1 , azido claim 1 , cyano claim 1 , (C-C)alkyl claim 1 , (C-C)cycloalkyl claim 1 , (C-C)cycloalkyl(C-C)alkyl claim 1 , (C-C)alkyl-S—(C-C)alkyl- claim 1 , aryl claim 1 , Het claim 1 , aryl(C-C)alkyl claim 1 , or Het(C-C)alkyl claim 1 , or NRR; wherein each Rand Ris independently hydrogen claim 1 , (C-C)alkyl claim 1 , (C-C)cycloalkyl claim 1 , phenyl claim 1 , benzyl claim 1 , or phenethyl.5. The compound of wherein Ris (C-C)alkyl optionally substituted with one or more halo claim 1 , hydroxy claim 1 , (C-C)alkoxy claim 1 , (C-C)alkanoyloxy claim 1 , trifluoromethyl claim 1 , cyano claim 1 , aryl claim 1 , or Het.6. The compound of wherein Ris (C-C)alkyl optionally substituted with one or more aryl or Het.7. The compound of wherein Ris (C-C)alkyl substituted with a phenyl claim 6 , naphthyl claim 6 , pyridyl claim 6 , indolyl claim 6 , isoindolyl claim 6 , furyl claim 6 , thienyl claim 6 , pyrrolyl claim 6 , benzofuranyl claim 6 , benzothienyl claim 6 , imidazolyl claim 6 , thiazoyl claim 6 , pyrrolidinyl claim 6 , piperidinyl claim 6 , piperazinyl claim 6 , or morpholino ring claim 6 , which ring is optionally substituted with one or more substituents selected from the group consisting of halo claim 6 , hydroxy claim 6 , (C-C)alkyl claim 6 , (C-C)cycloalkyl claim 6 , (C-C)alkoxy claim 6 , (C-C)cycloalkyloxy claim 6 , (C-C)alkanoyl claim 6 , (C-C)alkanoyloxy claim 6 , trifluoromethyl claim 6 , ...

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Номер записи: 28
15-08-2013 дата публикации

DOUBLE-LIVER-TARGETING PHOSPHORAMIDATE AND PHOSPHONOAMIDATE PRODRUGS

Номер: US20130210757A1
Автор: Huang Qiang, Liu Runcong
Принадлежит: Nanjing Molecular Research, Inc.

This application discloses phosphoramidate and phosphonoamidate prodrugs of alcohol-based therapeutic agents, such as nucleosides, nucleotides, acyclonucleosides, C-nucleosides, and C-nucleotides, and use of these prodrugs for treatment of diseases or disorders, including infectious diseases and cancers. This application also discloses a general method for enhancing bioavailability and/or liver-targeting property of alcohol drugs through converting the alcohol drugs to phosphoramidate or phosphonoamidate prodrugs, and methods of preparation of these prodrugs. 6. The compound of claim 1 , wherein Y is a nucleoside moiety claim 1 , or a pharmaceutically acceptable salt or solvate thereof.7. The compound of claim 1 , wherein Ris M claim 1 , and Y is a nucleoside moiety claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein M is selected from the group consisting of NH claim 1 , K claim 1 , Na claim 1 , Ca claim 1 , and Mg.11. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein X is CH claim 1 , or a pharmaceutically acceptable salt or solvate thereof.12. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein X is O claim 1 , and Y is a moiety of an acyclic nucleoside selected from the group consisting of acyclovir claim 1 , ganciclovir and pencyclovir.13. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein X is O claim 1 , and Y is a moiety of a C-nucleoside comprising a nucleic base and a sugar moiety connected with each other through a carbon-carbon bond.16. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , and a pharmaceutically acceptable carrier or diluent.17. A method of treating a viral infection or cancer claim 1 , comprising administration of a compound of claim 1 , or a pharmaceutically acceptable salt or ...

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Номер записи: 29
29-08-2013 дата публикации

NUCLEOSIDE PHOSPHORAMIDATES

Номер: US20130225519A1
Автор: Du Jinfa, NAGARATHNAM Dhanapalan, Sofia Michael Joseph, Wang Peiyuan
Принадлежит: GILEAD PHARMASSET LLC

A nucleoside compound having activity against hepatitis C virus is disclosed. 2. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to .3. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus claim 1 , West Nile virus claim 1 , yellow fever virus claim 1 , dengue virus claim 1 , rhinovirus claim 1 , polio virus claim 1 , hepatitis A virus claim 1 , bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to .4. The method of treatment according to wherein the subject is infected with hepatitis C virus.5. A method of treatment in a subject in need thereof claim 1 , which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to .7. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to .8. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus claim 6 , West Nile virus claim 6 , yellow fever virus claim 6 , dengue virus claim 6 , rhinovirus claim 6 , polio virus claim 6 , hepatitis A virus claim 6 , bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to .9. The method of treatment according to wherein the subject is infected with hepatitis C virus.10. A method of treatment in a subject in need thereof claim 6 , which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to .11. The compound of wherein Ris OMe.12. The compound of wherein Ris OH.13. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to .14. A pharmaceutical composition comprising a pharmaceutically acceptable medium and ...

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Номер записи: 30
12-09-2013 дата публикации

Use of 2',5'-oligoadenylate derivative compounds

Номер: US20130237492A1
Автор: Christiaan Roelant, Kenny De Meirleir
Принадлежит: Protea Biopharma NV

The invention relates to the therapeutic uses of 2′,5′-oligoadenylate derivative compounds, more particularly for the treatment of chronic fatigue syndrome (CFS) and in the treatment of infection by a gamma-retrovirus.

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Номер записи: 31
12-09-2013 дата публикации

BUILDING BLOCKS AND METHODS FOR THE SYNTHESIS OF 5-HYDROXYMETHYLCYTOSINE-CONTAINING NUCLEIC ACIDS

Номер: US20130237697A1
Автор: CARELL Thomas, Munzel Martin
Принадлежит: LUDWIG-MAXIMILIANS-UNIVERSITÄT MÜNCHEN

The present invention relates to building blocks and methods for the efficient synthesis of 5-hydroxymethylcytosine-containing nucleic acids such as DNA or RNA. 2. The compound of claim 1 , wherein Z is a 5- or 6-membered cyclic radical claim 1 , particularly a ribose claim 1 , ribose analogue or deoxyribose radical claim 1 , wherein the 3′-OH group of the ribose claim 1 , ribose analogue or deoxyribose radical may be substituted by a phosphor-containing group claim 1 , e.g. a phosphate claim 1 , phosphoester or phosphoramidite group and wherein the 5′-OH group of the ribose claim 1 , ribose analogue or deoxyribose radical may be substituted by a protection group.4. The compound of claim 3 , wherein Ris an aliphatic linear or cyclic group comprising up to 6 C-atoms and optionally up to 2 heteroatoms such as N or O claim 3 , e.g. a C(halo) alkyl group claim 3 , or a C(hetero) alkyl group claim 3 , or a Caryl or heteroaryl group optionally substituted by OH claim 3 , halo claim 3 , CN claim 3 , (O)C(halo) alkyl or N(R) claim 3 , wherein Ris as defined for the compound of formula (II).5. A method of introducing a formyl substituent at position 5 of a cytosine cytidine claim 3 , or deoxycytidine compound comprising reacting a 5-halo substituted starting compound with CO under catalysis of Pd.6. A method for the synthesis of a nucleic acid claim 1 , comprising incorporating a compound of into said nucleic acid.7. A method of claim 6 , wherein the nucleic acid synthesis is carried out by a phosphoramidite procedure.8. A nucleic acid molecule having incorporated at least one compound of . The present invention relates to building blocks and methods for the efficient synthesis of 5-hydroxymethylcytosine-containing nucleic acids such as DNA or RNA.The genetic material is constructed from the four canonical bases dA, dC, dG, and dT. The dC base is furthermore subject to epigenetic modification. In eucaryotes the dC base is often methylated at position C5 to give the base 5- ...

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Номер записи: 32
26-09-2013 дата публикации

Uridine diphosphate derivatives, compositions and methods for treating neurodegenerative disorders

Номер: US20130252919A1
Автор: Jinbo Lee, Jinghui DONG, Philip Haydon, Raquel REVILLA-SANCHEZ, Stephen Moss
Принадлежит: TUFTS UNIVERSITY

This disclosure relates to uridine diphosphate (UDP) derivatives, compositions comprising therapeutically effective amounts of those UDP derivatives and methods of using those derivatives or compositions in treating disorders that are responsive to ligands, such as agonists, of P 2 Y 6 receptor, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease) and traumatic CNS injury, as well as pain.

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Номер записи: 33
03-10-2013 дата публикации

3,5-Disubstituted and 3,5,7-Trisubstituted-3H-Oxazolo and 3H-Thiazolo[4,5-d]pyrimidin-2-one Compounds and Prodrugs Thereof

Номер: US20130259831A1
Автор: Haley Gregory J., Lennox Joseph R., Rueden Erik J., Webber Stephen E., Xiang Alan Xin
Принадлежит: Anadys Pharmaceuticals, Inc.

The invention is directed to 3,5-disubstituted and 3,5,7-trisubstituted-3H-oxazolo and 3H-thiazolo[4,5-d]pyrimidin-2-one compounds and prodrugs thereof that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and pharmaceutical compositions containing them, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds and prodrugs. 140-. (canceled)42. The method according to claim 41 , wherein the tumor or cancer is selected from the group consisting of carcinomas claim 41 , sarcomas claim 41 , and leukemias.43. The method according to claim 42 , wherein the carcinoma is a liver claim 42 , mammary claim 42 , colon claim 42 , bladder claim 42 , lung claim 42 , prostate claim 42 , stomach claim 42 , or pancreas carcinoma.44. The method according to claim 41 , further comprising administering to said patient a therapeutically effective amount of a therapeutic agent selected from the group consisting of antibiotics claim 41 , antiemetic agents claim 41 , antidepressants claim 41 , antifungal agents claim 41 , anti-inflammatory agents claim 41 , antiviral agents claim 41 , anticancer agents claim 41 , immunomodulatory agents claim 41 , β-interferons claim 41 , alkylating agents claim 41 , hormones claim 41 , and cytokines.47. The method according to claim 46 , wherein the tumor or cancer is selected from the group consisting of carcinomas claim 46 , sarcomas claim 46 , and leukemias.48. The method according to claim 47 , wherein the carcinoma is a liver claim 47 , mammary claim 47 , colon claim 47 , bladder claim 47 , lung claim 47 , prostate claim 47 , stomach claim 47 , or pancreas carcinoma.49. The method according to claim 46 , further comprising administering to said patient a therapeutically effective amount of a therapeutic agent selected from the group consisting of antibiotics claim 46 , antiemetic agents claim 46 , antidepressants claim ...

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Номер записи: 34
03-10-2013 дата публикации

Conformationally restricted dinucleotide monomers and oligonucleotides

Номер: US20130260460A1
Автор: Eric E. Swayze, Ivan Zlatev, Jeremy Lackey, Kallanthottathil Rajeev, Muthiah Manoharan, Thazha P. Prakash
Принадлежит: ISIS PHARMACEUTICALS INC

This invention relates to conformationally locked dinucleotide motifs for exo- and phosphate stabilization. For instance, oligonucleotides can be prepared having one or more of the following formulas (IV-IX).

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Номер записи: 35
24-10-2013 дата публикации

SYNTHESIS OF PHOSPHITYLATED COMPOUNDS USING A QUATERNARY HETEROCYCLIC ACTIVATOR

Номер: US20130281682A1
Автор: Grössel Olaf, Hohlfeld Andreas, Kirchhoff Christina, Lange Meinholf, Link Fritz, Omelcenko Nadja, Schönberger Andreas
Принадлежит: Girindus AG

A method for preparing a phosphitylated compound comprising the step of:—reacting a hydroxyl containing compound with a phosphitylating agent in the presence of an activator having the formula (I) wherein R=alkyl, cycloalkyl, aryl, aralkyl, heteroalkyl, heteroaryl R, R=either H or form a 5 to 6-membered ring together. X, X=independently either N or CH Y=H or Si(R), with R=alkyl, cycloalkyl, aryl, aralkyl, heteroalkyl, heteroaryl B=deprotonated acid. The hydroxyl containing compound is preferably a sugar moiety or a nucleoside or an oligomer derived therefrom. 118-. (canceled)21. The method of claim 19 , wherein said hydroxyl containing compound comprises a sugar moiety.22. The method of claim 19 , wherein said hydroxyl containing compound is a nucleoside or an oligomer derived therefrom.23. The method of claim 19 , wherein said hydroxyl containing compound is a 5′-O-protected nucleoside having a 3′-hydroxyl group or a 3′-O-protected nucleoside having a 5′-hydroxyl group.24. The method of claim 19 , wherein said activator is prepared in-situ and used without purification.26. The method of claim 25 , wherein claim 25 , prior to said reaction step claim 25 , said corresponding base is brought into contact with said hydroxyl containing compound and said phosphitylating agent and an acid HB is added.28. The method of claim 19 , wherein said phosphitylating agent is 2-cyanoethyl-N claim 19 ,N claim 19 ,N′ claim 19 ,N′-tetraisopropylphosphorodiamidite.29. The method of claim 19 , wherein B is selected from the group consisting of trifluoroacetate claim 19 , dichloroacetate claim 19 , mesylate claim 19 , triflate claim 19 , o-chlorophenolate claim 19 , and mixtures thereof.30. A phosphoramidite prepared according to the method of claim 19 , wherein said phosphoramidite is selected from the group consisting of adenosine phosphoramidite; cytosine phosphoramidite; guanosine phosphoramidite; uracil phosphoramidite; desoxyadenosine phosphoramidite; desoxyguanosine ...

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Номер записи: 36
21-11-2013 дата публикации

METHODS AND COMPOSITIONS FOR TREATING FLAVIVIRUSES AND PESTIVIRUSES

Номер: US20130310336A1
Автор: LACOLLA Paolo, SOMMADOSSI Jean-Pierre
Принадлежит:

A method and composition for treating a host infected with flavivirus or pestivirus comprising administering an effective flavivirus or pestivirus treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided. 2. The method of claim 1 , wherein Rand Rare independently H; phosphate; monophosphate; diphosphate; triphosphate; or a stabilized phosphate prodrug.3. The method of claim 1 , wherein Rand Rare each hydrogen.4. The method of claim 1 , wherein X is O.5. The method of claim 1 , wherein Ris methyl.6. The method of claim 1 , wherein Base is a purine or pyrimidine base selected from the group consisting of adenine claim 1 , N-alkylpurine claim 1 , N-acylpurine claim 1 , N-benzylpurine claim 1 , N-halopurine claim 1 , N-vinylpurine claim 1 , N-acetylenic purine claim 1 , N-acyl purine claim 1 , N-hydroxyalkyl purine claim 1 , N-thioalkyl purine claim 1 , N-alkylpurine claim 1 , N-alkyl-6-thiopurine claim 1 , thymine claim 1 , cytosine claim 1 , 5-fluorocytosine claim 1 , 5-methylcytosine claim 1 , 6-azapyrimidine claim 1 , 6-azacytosine claim 1 , 2- and/or 4-mercaptopyrimidine claim 1 , uracil claim 1 , 5-halouracil claim 1 , 5-fluorouracil claim 1 , C-alkylpyrimidine claim 1 , C-benzylpyrimidine claim 1 , C-halopyrimidine claim 1 , C-vinylpyrimidine claim 1 , C-acetylenic pyrimidine claim 1 , C-acyl pyrimidine claim 1 , C-hydroxyalkyl purine claim 1 , C-amidopyrimidine claim 1 , C-cyanopyrimidine claim 1 , C-nitropyrimidine claim 1 , C-aminopyrimidine claim 1 , N-alkylpurine claim 1 , N-alkyl-6-thiopurine claim 1 , 5-azacytidinyl claim 1 , 5-azauracilyl claim 1 , triazolopyridinyl claim 1 , imidazolopyridinyl claim 1 , pyrrolopyrimidinyl claim 1 , pyrazolopyrimidinyl claim 1 , guanine claim 1 , hypoxanthine claim 1 , 2 claim 1 ,6-diaminopurine claim 1 , and 6-chloropurine.7. The method of claim 1 , wherein Base is a purine or pyrimidine base selected from the group consisting of adenine claim ...

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Номер записи: 37
28-11-2013 дата публикации

Methods and compositions for treating flaviviridae infections

Номер: US20130315863A1
Автор: Jean-Pierre Sommadossi, Paolo Lacolla
Принадлежит: IDENIX Pharmaceuticals LLC, Universita Degli Studi Di Cagliari

A method and composition for treating a host infected with flavivirus or pestivirus comprising administering an effective flavivirus or pestivirus treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

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Номер записи: 38
28-11-2013 дата публикации

MACROCYCLIC NUCLEOSIDE PHOSPHORAMIDATE DERIVATIVES

Номер: US20130315864A1
Автор: Ma Jun, Or Yat Sun, Wang Guoqiang
Принадлежит: Enanta Pharmaceuticals, Inc.

The present invention provides nucleoside phosphoramidate compounds of Formula I, 2. The compound of claim 1 , wherein:{'sup': '1', 'Ris hydrogen;'}{'sup': '2a', 'sub': '2', 'Ris methyl or —CHF;'}{'sup': '2b', 'Ris —OH or halogen;'}{'sup': 3', '4', '5a', '5b, 'R, R, Rand Rare each hydrogen;'}{'sup': '6', 'Ris aryl;'}{'sup': '7', 'Ris hydrogen;'}{'sup': 8a', '8b, 'sub': 1', '8, 'one of Rand Ris hydrogen and the other is normal or branched C-C-alkyl;'}X is O;{'sub': 4', '10', '4', '10', '2', 'n', '2', 'm, 'W is optionally substituted C-C-alkylene, optionally substituted C-C-alkenylene, or —(CH)—Y—(CH)—, where Y is O, S, NH or NMe and n and m are each independently 2 to 6; and'}M is O, NH, —OC(O)NH—, or C(O)NH.9. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable carrier or excipient.10. A method of treating a viral infection in a subject claim 9 , comprising administering to the subject an inhibitory amount of a pharmaceutical composition according to .11. The method according to claim 10 , wherein the viral infection is hepatitis C virus.12. A method of inhibiting the replication of hepatitis C virus claim 8 , the method comprising supplying a hepatitis C viral NS3 protease inhibitory amount of the pharmaceutical composition of .13. The method of claim 11 , further comprising administering concurrently an additional anti-hepatitis C virus agent.14. The method of claim 13 , wherein said additional anti-hepatitis C virus agent is selected from the group consisting of a-interferon claim 13 , β-interferon claim 13 , ribavarin claim 13 , and adamantine.15. The method of claim 13 , wherein said additional anti-hepatitis C virus agent is an inhibitor of hepatitis C virus helicase claim 13 , polymerase claim 13 , metalloprotease claim 13 , or IRES.16. The pharmaceutical composition of claim 9 , further comprising another anti-HCV agent.17. The pharmaceutical composition of claim 9 , further comprising an agent selected from ...

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Номер записи: 39
28-11-2013 дата публикации

3',5'-CYCLIC PHOSPHORAMIDATE PRODRUGS FOR HCV INFECTION

Номер: US20130315866A1
Автор: Alexandre Francois-Rene, Dousson Cyril B., Dukhan David, MAYES Benjamin Alexander, MOUSSA Adel M., Parsy Christophe Claude, Pierra Claire, STEWART Alistair James, Surleraux Dominique
Принадлежит:

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. 2. The compound of wherein each Z is independently a carboxylene-substituted alkyl claim 1 , a cycloalkyl-substituted alkyl claim 1 , or both.3. (canceled)4. The compound of wherein:{'sub': p', '3', 'p', '3', 'p, 'each Z is -LC(O)O(L)CR, -LOC(O)(L)CR, or -LC(O)O(L)Cy;'}each L is independently alkylene, or substituted alkylene;each Cy is independently cycloalkyl or substituted cycloalkyl; andeach p is independently 0 or 1.5. The compound of claim 4 , wherein each L is independently C-Calkylene claim 4 , C-Cor C-Csubstituted alkylene.6. The compound of claim 4 , wherein each Cy is independently C-Ccycloalkyl or C-Csubstituted cycloalkyl.7. (canceled)8. (canceled)9. (canceled)10. The compound of wherein X is C-Calkoxyl.11. The compound of wherein X is hydroxyl.12. The compound of wherein X is hydrogen.13. The compound of wherein Y is fluoro.14. The compound of wherein Y is acetoxyl.15. The compound of wherein Y is hydroxyl.18. The compound of wherein:{'sub': p', '3', 'p', '3, 'each Z is independently -L-S—S-(L)CRor -LSC(O)(L)CR;'}each L is independently alkylene, or substituted alkylene; andeach p is independently 0 or 1.19. (canceled)20. (canceled)21. (canceled)22. (canceled)23. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient claim 1 , carrier or diluent.24. The pharmaceutical composition of claim 23 , wherein the composition is an oral formulation.25. A method for the treatment of a host infected with a hepatitis C virus claim 1 , comprising the administration of an effective treatment amount of a compound of .26. The method of claim 25 , wherein the host is a human.27. The method of claim 25 , wherein the ...

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Номер записи: 40
28-11-2013 дата публикации

3',5'-CYCLIC PHOSPHATE PRODRUGS FOR HCV INFECTION

Номер: US20130315867A1
Автор: Alexandre Francois-Rene, Dousson Cyril B., Dukhan David, Gosselin Gilles, Parsy Christophe Claude, Rahali Houcine, Surleraux Dominique
Принадлежит:

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. 2. (canceled)3. (canceled)4. The compound of claim 1 , wherein each L is independently C-Calkylene or C-Csubstituted alkylene.520-. (canceled)21. The compound of any of claim 1 , wherein:{'sub': 3', '2', 'n', '2', 'n', '3, 'each B is independently CR(CR)OC(O)CR(B—)NRC(O)O(CR)CR;'}{'sub': 2', 'n, 'where B— denotes the attachment position to the toluenyl group, Ar, L, or —(CR)—; and'}each n is independently an integer selected over the range of 0 to 10.22. The compound of claim 1 , wherein each E is independently C-Calkyl claim 1 , C-Csubstituted alkyl claim 1 , C-Caryl claim 1 , or C-Cheteroaryl.23. The compound of claim 1 , wherein each Ar is independently C-Carylene or C-Cheteroarylene.24. The compound of claim 1 , wherein each R is independently hydrogen claim 1 , C-Calkyl claim 1 , C-Csubstituted alkyl claim 1 , C-Caryl claim 1 , or C-Cheteroaryl.25. The compound of claim 1 , wherein each Ris independently a 3-20 membered carbocyclic or heterocyclic ring.2628-. (canceled)29. The compound of wherein Y is fluoro.30. The compound of wherein Y is acetoxyl.31. The compound of wherein Y is hydroxyl.32. (canceled)33. (canceled)35. The compound of claim 34 , wherein each Z is independently -LOC(O)LC(O)O(L)CRor -LOC(O)LNRC(O)O(L)CR.36. (canceled)37. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient claim 1 , carrier or diluent.38. The pharmaceutical composition of claim 37 , wherein the composition is an oral formulation.39. A method for the treatment of a host infected with a hepatitis C virus claim 1 , comprising the administration of an effective treatment amount of a compound or composition of .40. The method of claim ...

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Номер записи: 41
28-11-2013 дата публикации

D-AMINO ACID COMPOUNDS FOR LIVER DISEASE

Номер: US20130315868A1
Автор: MAYES Benjamin Alexander, MOUSSA Adel M., STEWART Alistair James
Принадлежит:

Provided herein are compounds, compositions and methods for the treatment of liver disease and conditions, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. 2. The compound of wherein each Ris independently alkyl claim 1 , cycloalkyl claim 1 , heterocyclylalkyl claim 1 , aryl claim 1 , heteroaryl claim 1 , arylalkyl claim 1 , heteroarylalkyl claim 1 , alkylcarbonylthioalkyl claim 1 , alkoxycarbonylalkyl claim 1 , arylalkoxycarbonylalkyl claim 1 , alkylcarbonylalkoxy(arylalkyl) claim 1 , (alkoxycarbonyl)(alkoxycarbonylamino)alkyl claim 1 , cycloalkylcarbonylalkoxyl claim 1 , alkoxycarbonylaminoalkylcarbonylthioalkyl claim 1 , hydroxylalkylcarbonylthioalkyl claim 1 , aminoalkylcarbonylalkoxycarbonylthioalkyl claim 1 , or hydantoinylalkyl.4. The compound of wherein Rand Rare H.510-. (canceled)11. The compound of wherein W is O claim 1 , and Ris Cl claim 1 , F or OH.12. (canceled)15. The compound of wherein Ris alkylamino.18. The Rcompound of .19. The Scompound of .20. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient claim 1 , carrier or diluent.21. The pharmaceutical composition of claim 20 , wherein the composition is an oral formulation.22. A method for the treatment of a host infected with a hepatitis C virus claim 1 , comprising the administration of an effective treatment amount of a compound of .23. The method of claim 22 , wherein the host is a human.24. The method of claim 22 , wherein the administration directs a substantial amount of the compound claim 22 , or pharmaceutically acceptable salt or stereoisomer thereof claim 22 , to a liver of the host.25. The method of claim 22 , wherein the compound or composition is administered in combination or alternation with a second anti-viral agent selected from the group consisting of an interferon claim 22 , a ...

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Номер записи: 42
28-11-2013 дата публикации

ANTIVIRAL PHOSPHONATE ANALOGS

Номер: US20130316969A1
Автор: "OSHEA Rosemarie", Boojamra Constantine G., Cannizzaro Carina E., CHEN James M., CHEN XIAOWU, Cho Aesop, Chong Lee S., FARDIS Maria, HIRSCHMANN Ralph, HUANG Alan X., Jin Haolun, Kim Choung U., Kirschberg Thorsten A., Lee Christopher P., LEE William A., Mackman Richard L., Markevitch David Y., OARE David A., PRASAD Vidya K., Pyun Hyung-jung, Ray Adrian S., Swaninathan Sundaramoorthi, Watkins William J., Zhang Jennifer
Принадлежит: Gilead Sciences, Inc.

The invention is related to phosphorus substituted compounds with antiviral activity, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds. 2. The conjugate of wherein C-Csubstituted alkyl claim 1 , C-Csubstituted alkenyl claim 1 , C-Csubstituted alkynyl claim 1 , C-Csubstituted aryl claim 1 , and C-Csubstituted heterocycle are independently substituted with one or more substituents selected from F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , OH claim 1 , —NH claim 1 , —NH claim 1 , —NHR claim 1 , —NR claim 1 , —NR claim 1 , C-Calkylhalide claim 1 , carboxylate claim 1 , sulfate claim 1 , sulfamate claim 1 , sulfonate claim 1 , 5-7 membered ring sultam claim 1 , C-Calkylsulfonate claim 1 , C-Calkylamino claim 1 , 4-dialkylaminopyridinium claim 1 , C-Calkylhydroxyl claim 1 , C-Calkylthiol claim 1 , —SOR claim 1 , —SOAr claim 1 , —SOAr claim 1 , —SAr claim 1 , —SONR claim 1 , —SOR claim 1 , —COR claim 1 , —C(═O)NR claim 1 , 5-7 membered ring lactam claim 1 , 5-7 membered ring lactone claim 1 , —CN claim 1 , —N claim 1 , —NO claim 1 , C-Calkoxy claim 1 , C-Ctrifluoroalkyl claim 1 , C-Calkyl claim 1 , C-Ccarbocycle claim 1 , C-Caryl claim 1 , C-Cheterocycle claim 1 , polyethyleneoxy claim 1 , phosphonate claim 1 , phosphate claim 1 , and a prodrug moiety.3. The conjugate of wherein protecting group is selected from a carboxyl ester claim 1 , a carboxamide claim 1 , an aryl ether claim 1 , an alkyl ether claim 1 , a trialkylsilyl ether claim 1 , a sulfonic acid ester claim 1 , a carbonate claim 1 , and a carbamate.5. The conjugate of wherein X is O and each Ris H.14. The conjugate of wherein Z is H.15. The conjugate of wherein B is adenine.18. The conjugate of wherein Yis O.19. The conjugate of wherein Yis N(CH).21. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a conjugate as described in ...

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Номер записи: 43
28-11-2013 дата публикации

Nucleotide analogue, method of synthesis of nucleotide analogue, use of nucleotide analogue, antiviral pro-nucleotide, pharmaceutical composition

Номер: US20130316970A1
Автор: Adam Kraszewski, Agnieszka Szymanska-Michalak, Andrzej Lipniacki, Andrzej Piasek, Jacek Stawinski, Jerzy Boryski, Joanna Romanowska, Michal Sobkowski
Принадлежит: INSTYTUT CHEMII BIOORGANICZNEJ PAN, NARODOWY INSTYTUT LEKOW

The object of the invention are nucleotide analogues, antiviral pro-nucleotides, a use of nucleotide analogues and pharmaceutical composition, a phosphorylating agent for synthesis of nucleotide analogue, and a method of synthesis of nucleotide analogue. More precisely, the invention applies to the new group of nucleotide analogues and their use in partial or complete inhibition of human immunodeficiency virus (HIV).

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Номер записи: 44
12-12-2013 дата публикации

Method of Preparation of Antiviral Compounds and Useful Intermediates Thereof

Номер: US20130331561A1
Автор: Cheng Qingzhong, He Xungui, Li Jie, Liu Chuanjun, Wang Yanling, Wang Yuan, Yuan Mingyong, Zhu Jirang
Принадлежит: SYNERGY PHARMACEUTICALS INC.

The invention is directed to processes for synthesizing bicyclic nucleoside antiviral compounds and for synthesizing the intermediates used in the process. The invention is also directed to novel intermediate compounds useful in the process. The anti-viral compounds are useful in the treatment of herpes zoster (i.e., varicella zoster virus, VZV, shingles) and for the prevention of post herpetic neuralgia (PHN) resulting from this viral infection. 2. (canceled)3. The process of claim 1 , for the synthesis of the compound of Formula (V) from the compound of Formula (IIIa) claim 1 , wherein:{'sub': 1', '6, 'X is halo, optionally substituted arylsulfonyl or C-Calkylsulfonyl.'}4. The process of claim 3 , wherein X is selected from the group consisting of halo and tosyl.5. The process of claim 4 , wherein X is selected from the group consisting of Cl claim 4 , Br claim 4 , and I.6. (canceled)7. (canceled)8. The process of claim 1 , for the synthesis of the compound of Formula (VII) from the compound of Formula (VI) claim 1 , wherein the acid is selected from the group consisting of acetic acid claim 1 , hydrochloric acid claim 1 , trichloroacetic acid and trifluoroacetic acid.9. (canceled)10. (canceled)11. The process of claim 1 , wherein{'sup': '1', 'Ris n-pentyl;'}{'sup': 4', '5, 'Rand Rare each methyl;'}or a pharmaceutically acceptable salt or hydrate thereof.12. (canceled)14. (canceled)15. (canceled)16. (canceled)17. (canceled)19. A process for the purification of (S)-((2R claim 1 ,3S claim 1 ,5R)-(3-hydroxy-5-(2-oxo-6-(4-pentylphenyl)furo[2 claim 1 ,3-d]pyrimidin-3(2H)-yl)-tetrahydrofuran-2-yl)methyl 2-amino-3-methylbutanoate hydrochloride comprising the steps of1) dissolving the crude (S)-((2R,3S,5R)-(3-hydroxy-5-(2-oxo-6-(4-pentylphenyl)furo[2,3-d]pyrimidin-3(2H)-yl)-tetrahydrofuran-2-yl)methyl 2-amino-3-methylbutanoate hydrochloride in a suitable solvent to form a solution;2) adding sufficient anti-solvent to the solution to effect formation of a solid precipitate ...

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Номер записи: 45
19-12-2013 дата публикации

Chemosensory Receptor Ligand-Based Therapies

Номер: US20130338095A1
Автор: Baron Alain D., Beeley Nigel R.A., Brown Martin R., Jones Christopher R.G.
Принадлежит: Elcelyx Therapeutics, Inc.

Provided herein are methods for treating conditions associated with a chemosensory receptor, including diabetes, obesity, and other metabolic diseases, disorders or conditions by administering a composition comprising a chemosensory receptor ligand. Also provided herein are chemosensory receptor ligand compositions and methods for the preparation thereof for use in the methods of the present invention. 193-. (canceled)120. A composition according to claim 94 , wherein the composition further releases at least some of the chemosensory receptor ligand in the stomach.121. A composition according to claim 94 , wherein one or more regions of the intestine are the duodenum claim 94 , jejunum claim 94 , ileum claim 94 , caecum claim 94 , colon and/or rectum.122. A composition according to claim 94 , wherein the composition releases at an onset of about 5 to about 45 minutes claim 94 , about 105 to about 135 minutes claim 94 , about 165 to about 195 minutes claim 94 , about 225 to about 255 minutes or a combination of times thereof following administration to a subject.123. A composition according to claim 94 , wherein the composition releases at an onset of about pH 5.0 claim 94 , about pH 5.5 claim 94 , about pH 6.0 claim 94 , about pH 6.5 claim 94 , about pH 7.0 claim 94 , or combination thereof following administration to a subject.124. A composition according to claim 94 , the composition further comprising a second chemosensory receptor ligand selected from the group consisting of a sweet receptor ligand claim 94 , a bitter receptor ligand claim 94 , an umami receptor ligand claim 94 , a fat receptor ligand claim 94 , a sour receptor ligand and a bile acid receptor ligand.125. A composition according to claim 124 , wherein the sweet receptor ligand is selected from the group consisting of sucralose claim 124 , aspartame claim 124 , Stevioside claim 124 , Rebaudioside A claim 124 , Rebaudioside B claim 124 , Rebaudioside C claim 124 , Rebaudioside D claim 124 , ...

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Номер записи: 46
19-12-2013 дата публикации

Compositions for the Treatment or Prophylaxis of Viral Infections

Номер: US20130338096A1
Автор: Balzarini Jan, Camarasa Maria Jose, Velazquez Sonsoles
Принадлежит:

A compound of the general formula (III): wherein X is O, S, NH or CH; Y is O, S or NH; Z is O, S or CH; Ris Calkyl, especially Calkyl, preferably n-alkyl, e.g., n-pentyl or n-hexyl; at least one of Rand Ris H—[R—R]—R—, in which: H—[R—R]— comprises an oligopeptide, Rbeing an amino acid and Rbeing an amino acid selected from proline, alanine, hydroxyproline, dihydroxyproline, thiazolidinecarboxylic acid (thioproline), dehydroproline, pipecolic acid (L-homoproline), azetidinecarboxylic acid, aziridinecarboxylic acid, glycine, serine, valine, leucine, isoleucine and threonine, Ris a neutral, non-polar amino acid moiety that is bonded to Rby a peptide bond, and n is 1, 2, 3, 4 or 5; and the other of Rand Ris H—[R—R]n-R— or H; or a pharmaceutically acceptable salt thereof. 2. The method of claim 1 , wherein 100-500 mg of said compound is administered once daily (s.i.d.).3. The method of claim 1 , wherein said compound is administered with a pharmaceutically acceptable excipient.4. The method of claim 1 , wherein one of Rand Ris H—[R—R]—R— and the other is H.5. The method of claim 1 , wherein both of Rand Ris H—[R—R]—R—.6. The method of claim 5 , wherein Rand Rare the same.7. The method of claim 1 , wherein n=1.8. The method of claim 1 , wherein Ris selected from alanine claim 1 , arginine claim 1 , asparagine claim 1 , aspartic acid claim 1 , cysteine claim 1 , glutamine claim 1 , glutamic acid claim 1 , glycine claim 1 , histidine claim 1 , isoleucine claim 1 , leucine claim 1 , lysine claim 1 , methionine claim 1 , phenylalanine claim 1 , proline claim 1 , serine claim 1 , threonine claim 1 , tryptophan claim 1 , tyrosine and valine claim 1 , preferably valine.9. The method of claim 1 , wherein Ris selected from proline claim 1 , alanine claim 1 , glycine claim 1 , serine claim 1 , valine and leucine claim 1 , preferably proline or alanine.10. The method of claim 1 , wherein the oligopeptide —[R—R]— is selected from Val-Pro claim 1 , Asp-Pro claim 1 , Ser-Pro claim 1 , ...

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Номер записи: 47
26-12-2013 дата публикации

NOVEL ANTI-VIRAL THERAPEUTIC

Номер: US20130345162A1
Автор: Gershon Paul D., Rozovics Janet M., Semler Bert L., Virgen-Slane Richard
Принадлежит: The Regents of the University of California

Anti-viral therapeutics for use in viral targets having VPg unlinkase activity, including the broad class of picornaviruses, and therapeutic methods directed at suppression of such activity are provided. Such anti-viral therapies for use against human rhinovirus, for example, are particularly desirable as they would lessen both the severity and duration of upper respiratory distress in both normal and asthmatic individuals. Assays and purification protocols for detecting and purifying VPg unlinkase are also provided. 1. An anti-viral therapeutic for viruses having VPg unlinkase activity , comprising:a therapeutically effective amount of a VPg unlinkase enzyme suppressor.2. The anti-viral therapeutic of claim 1 , wherein the VPg unlinkase enzyme is TDP2.3. The anti-viral therapeutic of claim 1 , wherein the suppressor is 5′FSBA.4. The anti-viral therapeutic of claim 1 , wherein the virus is selected from the group consisting of picornaviruses claim 1 , plant viruses and caliciviruses.5. The anti-viral therapeutic of claim 4 , wherein the picornavirus is selected from the group consisting of CVB3 claim 4 , EMCV claim 4 , HRV16 VPg and PVI VPg.6. The anti-viral therapeutic of claim 4 , wherein the plant virus is selected from the group consisting of cowpea mosaic virus claim 4 , sobemovirus claim 4 , and rye grass mottle virus.7. The anti-viral therapeutic of claim 4 , wherein the calicivirus is selected from the group consisting of Norwalk virus claim 4 , feline calicivirus claim 4 , and murine norovirus.8. A method of treating a viral infection for a virus having VPg unlinkase activity comprising:administering a therapeutically effective amount of a VPg unlinkase enzyme suppressor.9. The method of claim 8 , wherein the VPg unlinkase enzyme is TDP2.10. The method of claim 8 , wherein the suppressor is 5′FSBA.11. The method of claim 8 , wherein the virus is selected form the group consisting of picornaviruses claim 8 , plant viruses and caliciviruses.12. The method of ...

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Номер записи: 48
09-01-2014 дата публикации

Anti-Viral Pyrimidine Nucleoside Analogues

Номер: US20140011764A1
Автор: Balzarini Jan, McGuigan Christopher
Принадлежит:

A compound of formula (I) wherein Ar can be one six-membered or two fused six-membered aromatic rings; Rand Rcan be hydrogen, alkyl, cycloalkyl, halogen, amino, alkylamino, dialkylamino, nitro, cyano, alkyoxy, aryloxy, thiol, alkylthiol, arythiol, or aryl; Q can be O, S or CY, where Y may be H, alkyl or halogen; X can be O, NH, S, N-alkyl, (CHR)where m is 1 to 10, and CY; Z can be O, S, NH, or N-alkyl; U″ is H and U′ can be H or CHwherein: T can be OH, H, halogen, O-alkyl, O-acyl, O-aryl, CN, NHor N; T′ and T″ can be H or halogen; and W can be H or a phosphate group. Compounds show anti-viral activity, for example with respect to varicella zoster virus. 2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.3. A method of prophylaxis or treatment of a viral infection comprising administering to a patient in need of such treatment an effective dose of a compound of . The present application is a continuation application of U.S. application Ser. No. 12/889,980, filed Sep. 24, 2010, allowed, which is a divisional application of U.S. application Ser. No. 10/257,855, filed Oct. 17, 2002 (now U.S. Pat. No. 7,820,631), which is a National Stage application of International Application No. PCT/GB01/01694, filed Apr. 12, 2001, which claims the benefit of United Kingdom Patent Application GB 0009486.2, filed Apr. 17, 2000, all of said applications incorporated herein by reference.The present invention relates to a class of nucleoside analogues and to their therapeutic use in the prophylaxis and treatment of viral infection for example by varicella zoster virus (VZV). Varicella zoster virus is the aetiological agent in chickenpox and shingles which can cause considerable human illness and suffering.The following references and other information are pertinent to the background of the invention:WO 98/49177 describes a class of nucleoside analogues demonstrating anti-viral properties. A representative of the compounds disclosed in WO ...

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Номер записи: 49
23-01-2014 дата публикации

ANTI-MICROBIAL AGENTS AND USES THEREOF

Номер: US20140024611A1
Автор: Cisar Justin Scott, Ferreras Julian Alberto, Lu Xuequan, Quadri Luis E. N., Ryu Jae-Sang, Tan Derek Shieh
Принадлежит:

Many pathogens, including and , rely on an iron acquisition system based on siderophores, secreted iron-chelating compounds with extremely high Fe(III) affinity. The compounds of the invention are inhibitors of domain salicylation enzymes, which catalyze the salicylation of an aroyl carrier protein (ArCP) domain to form a salicyl-ArCP domain thioester intermediate via a two-step reaction. The compounds include the intermediate mimic 5′-O—[N-(salicyl)sulfamoyl]-adenosine (salicyl-AMS) and analogs thereof. These compounds are inhibitors of the salicylate activity of MbtA, YbtE, PchD, and other domain salicylation enzymes involved in the biosynthesis of siderophores. Therefore, these compounds may be used in the treatment of infection caused by microorganisms which rely on siderphore-based iron acquisition systems. Pharmaceutical composition and methods of using these compounds to treat or prevent infection are also provided as well as methods of preparing the inventive compounds. 17. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable excipient.18. The pharmaceutical composition of comprising approximately 1 mg to approximately 500 mg of the compound.19. The pharmaceutical composition of suitable for treating an infection.20. A method of treating a subject infected with a microorganism comprising administering to the subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof. This application is a divisional of and claims priority under 35 U.S.C. §120 to U.S. patent application, U.S. Ser. No. 11/911,525, filed Nov. 17, 2008, which claims priority to and is a national stage filing under 35 U.S.C. §371 of international PCT application, PCT/US2006/014394, filed Apr. 14, 2006, which claims priority under 35 U.S.C. §119(e) to U.S. provisional patent application, U.S. Ser. No. 60/671,994, filed Apr. 15, 2005, each of ...

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Номер записи: 50
06-02-2014 дата публикации

ADENOSINE ANALOGS AND THEIR USE

Номер: US20140038912A1
Автор: Becker Oren, Ben-Zeev Efrat, Jacques Vincent, Marantz Yael, McCauley Dilara, Orbach Pini, Reddy A. Sekar, Saha Ashis K., Shacham Sharon, Xie Michael, Zhang Zhaoda
Принадлежит: MICRODOSE THERAPEUTX, INC.

Provided are adenosine analog compounds of the general formula that act as P2Y receptors, e.g., the P2Yreceptor, including pharmaceutical compositions; and uses thereof to treat or prevent diseases associated with that receptor, e.g., disorders relating to mucus secretion, such as cystic fibrosis, chronic obstructive pulmonary disorder (COPD), asthma, constipation, chronic idiopathic constipation, dry mouth (xerostomia), gum disease, and gastrointestinal problems caused by radiation and chemotherapy for cancer. 131-. (canceled)50. A method of treating cystic fibrosis claim 32 , sinusitis claim 32 , otitis media claim 32 , ventilator associated pneumonia claim 32 , chronic bronchitis claim 32 , chronic obstructive pulmonary disorder claim 32 , primary ciliary dyskinesia claim 32 , asthma claim 32 , bronchiectasis claim 32 , post-operative atelectasis claim 32 , Kartagener's syndrome claim 32 , constipation claim 32 , chronic idiopathic constipation claim 32 , dry mouth claim 32 , mouth ulcer claim 32 , gum disease claim 32 , mycositis claim 32 , gastro-esophageal reflux disease claim 32 , peptic ulcer claim 32 , heartburn claim 32 , esophagitis claim 32 , Sjogren's syndrome claim 32 , inflammatory bowel disease claim 32 , constipation claim 32 , gastrointestinal problems caused by radiation or chemotherapy for cancer claim 32 , or a disease associated with expression or activity of a P2Y receptor in a subject claim 32 , comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .51. The method of claim 50 , wherein the subject is a human.52. A method of treating cystic fibrosis claim 33 , sinusitis claim 33 , otitis media claim 33 , ventilator associated pneumonia claim 33 , chronic bronchitis claim 33 , chronic obstructive pulmonary disorder claim 33 , primary ciliary dyskinesia claim 33 , asthma claim 33 , bronchiectasis claim 33 , post-operative atelectasis claim 33 , Kartagener's syndrome claim 33 , constipation ...

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Номер записи: 51
06-02-2014 дата публикации

O-(substituted benzyl) phosphoramidate compounds and therapeutic use

Номер: US20140038916A1
Автор: Suping Zhou, Zheng Wang
Принадлежит: NANJING MOLECULAR RESEARCH Inc

This application discloses novel phosphoramidate and phosphonoamidate prodrugs of nucleosides, nucleotides, C-nucleosides, C-nucleotides, phosphonates, and other alcohol-containing drugs; use of these prodrugs for treatment of infectious diseases and cancers, in particular, liver infections and cancers; and methods of preparing these novel phosphoramidate and phosphonoamidate prodrugs.

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Номер записи: 52
13-02-2014 дата публикации

Nucleoside phosphoramidate prodrugs

Номер: US20140045783A1
Автор: Dhanapalan Nagarathnam, Jinfa Du, Michael Joseph Sofia, Peiyuan Wang
Принадлежит: GILEAD PHARMASSET LLC

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment uses, and processes for preparing each of which utilize the compound represented by formula I.

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Номер записи: 53
20-02-2014 дата публикации

DIARYLSULFIDE BACKBONE CONTAINING PHOTOLABILE PROTECTING GROUPS

Номер: US20140051605A1
Автор: Stengele Klaus-Peter
Принадлежит: NimbleGen Systems GmbH

The present disclosure relates to photoactivable protecting groups containing a diarylsulfide chromophore, a method for the synthesis thereof and their use as photoactivable protecting groups using maskless photolithography based array synthesis. 2. The compound according to wherein R1 is a phenyl-group claim 1 , a tert-butyl-phenyl group claim 1 , a 1- or 2-naphthyl-group claim 1 , a 2-pyridyl-group an aminophenyl-group claim 1 , an N-alkylaminophenyl-group claim 1 , an N-Acylaminophenyl-group claim 1 , a carboxyphenyl-group claim 1 , a phenylcarboxylic ester or an amide.3. The compound according to wherein A is —CH(CH)—CH—.4. The compound according to wherein R2 is a phosphoramidite or —P(OCHCHCN)(N-iPr).5. The compound according to wherein R3 is H or an ethyl group.6. The compound according to wherein R4 is H and R5 is H.7. The compound according to wherein B is selected from the group consisting of adenine claim 1 , cytosine claim 1 , guanine claim 1 , thymine or uracil.8. The compound according to wherein when B is adenine claim 1 , cytosine or guanine the protecting group is phenoxyacetyl- claim 1 , 4-tert-butyl-phenoxyacetyl- claim 1 , 4-isopropyl-phenoxyacetyl- or dimethylformamidino-residues claim 1 , when B is adenine the protecting group is benzoyl- or p-nitro-phenyl-ethoxy-carbonyl-(p-NPPOC)-residues claim 1 , when B is guanine the protecting group is isobutyroyl- claim 1 , p-nitrophenylethyl (p-NPE) or p-NPEOC-residues and when B is cytosine the protecting group is benzoyl- claim 1 , isobutyryl- or p-NPEOC-residues.9. The compound according to wherein R7 is a natural amino acid.10. A method for preparing a diarylsulfide backbone containing one or more photolabile protecting group(s) according to comprising the steps ofa) Provision of p-diethylbenzene as a starting material;b) Bromination of the phenylring;c) Nitration of the obtained compound in Nitric- and Sulfuric Acid in the position para- to the Bromine;d) Purification and crystallization;e) ...

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Номер записи: 54
06-03-2014 дата публикации

PURINE NUCLEOSIDE MONOPHOSPHATE PRODRUGS FOR TREATMENT OF CANCER AND VIRAL INFECTIONS

Номер: US20140066395A1
Автор: Cho Jong Hyun, Coats Steven J., SCHINAZI RAYMOND F., Zhang Hongwang, ZHOU Longhu
Принадлежит:

The present invention is directed to compounds, compositions and methods for treating or preventing cancer and viral infections, in particular, HIV, HCV, Norovirus, Saporovirus, HSV-1, HSV-2, Dengue virus, Yellow fever, and HBV in human patients or other animal hosts. The compounds are certain 6-substituted purine monophosphates, and pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof. In particular, the compounds show potent antiviral activity against HIV-1, HIV-2, HCV, Norovirus, Saporovirus, HSV-1, HSV-2, Dengue virus, Yellow fever, and HBV. 2. The compound of claim 1 , wherein Rselected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , OH claim 1 , SH claim 1 , NH claim 1 , NHOH claim 1 , NHNH claim 1 , C(O)OH claim 1 , CN claim 1 , C(O)NH claim 1 , C(S)NH claim 1 , C(O)OR claim 1 , R claim 1 , OR claim 1 , SR claim 1 , SSR claim 1 , NHR claim 1 , and NR.3. The compounds of claim 1 , wherein Ris selected from the group consisting of NH claim 1 , dimethylamine claim 1 , methyl-allyl-amine claim 1 , methoxy claim 1 , chloro claim 1 , cyclopropylamine claim 1 , 5-hydroxy-pentylamine claim 1 , 1 claim 1 ,1-dimethyl-ethanolamine claim 1 , and 2-methoxy-ethylamine.4. The compounds of claim 1 , wherein the compounds are in the β-L- or β-D configuration claim 1 , or a racemic mixture thereof.5. A method for treating a host infected with HIV-1 or HIV-2 claim 1 , preventing an HIV-1 or HIV-2 infection claim 1 , or reducing the biological activity of an HIV-1 or HIV-2 infection in a host claim 1 , comprising administering an effective amount of a compound of to a patient in need of treatment thereof.6. The method of claim 5 , wherein the HIV-1 or HIV-2 infection is caused by a virus comprising a mutation selected from the group consisting of TAM mutations and the M184V mutation.7. The method of claim 5 , wherein the compound is administered in another anti-HIV agent.8. The method of claim 7 , wherein the HIV- ...

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Номер записи: 55
20-03-2014 дата публикации

SUBSTRATE REDUCTION THERAPY

Номер: US20140080769A1
Автор: Lloyd-Evans Emyr, Platt Frances Mary, Porter Forbes Dennison
Принадлежит:

The present invention provides a compound which is an inhibitor of sphingolipid biosynthesis for use in the treatment of a disease which has a secondary Niemann-Pick type C disease like cellular phenotype. 1. A method of treating a subject having a disease which has a secondary Niemann-Pick type C disease like cellular phenotype , provided that the disease is other than mucopolysaccharidosis and other than mucolipidosis IV , wherein the method comprises selecting the subject having the disease , and administering to the subject an effective amount of an inhibitor of sphingolipid biosynthesis.26-. (canceled)10. The method of wherein the inhibitor of sphingolipid biosynthesis is selected from N-butyldeoxynojirimycin; N-nonyldeoxynojirimycin; N-butyldeoxygalactonojirimycin; N-5-adamantane-1-yl-methoxypentyl-deoxynojirimycin; alpha-homogalactonojirimycin; nojirimycin; deoxynojirimycin; N7-oxadecyl-deoxynojirimycin; deoxygalactonojirimycin; N-butyl-deoxygalactonojirimycin; N-nonyl-deoxygalactonojirimycin; N-nonyl-6deoxygalactonojirimycin; N7-oxanonyl-6deoxy-DGJ; alpha-homoallonojirimycin; beta-1-C-butyl-deoxygalactonojirimycin; 1 claim 1 ,5-dideoxy-1 claim 1 ,5-imino-D-glucitol claim 1 , 1 claim 1 ,5-(Butylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Methylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Hexylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Nonylylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(2-Ethylbutylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(2-Methylpentylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Benzyloxycarbonylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Phenylacetylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Benzoylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Butylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Ethyl malonylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , ...

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Номер записи: 56
27-03-2014 дата публикации

SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF

Номер: US20140088028A1
Автор: Kaul Ramesh, LIU Kun, McEachern Ernest J., Mu Changwei, Selnick Harold G., Vocadlo David J., Wang Xiaona, Wang Yaode, Wei Zhongyong, Zhou Yuanxi
Принадлежит:

The invention provides compounds of formula (I) with substituents as specified in Claim for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceuticals compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to over-expression of O-GlcNAcase or accumulation of O-GlcNac. 2. The compound of wherein:{'sup': 2', '7, 'sub': '3', 'Ris N, NHR, azetidin-1-yl, or 3-hydroxyazetidin-1-yl.'}3. The compound of wherein:{'sup': 2', '5', '6, 'sub': 3', '2', '2', '2', '2', '3', '2, 'Ris OCH, OCHF, OC(O)NR, OCHR, or O(SO)N(CH).'}4. The compound of wherein:{'sup': '1', 'sub': '3', 'each Ris independently H or C(O)CH; and'}{'sup': '2', 'sub': 3', '2', '3', '2', '3', '3', '2', '2', '3', '2', '2', '3', '2', '3', '2', '3', '2', '3', '2', '3', '3', '3', '2', '2', '2', '2', '2', '3', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '3', '3, 'Ris selected from the group consisting of: OCH, OCHF, OC(O)NHCH, OC(O)NHCHCH, OC(O)N(CH), OC(O)N(CHCH), O(SO)N(CH), O(benzyl), O(4-F-benzyl), O(4-methoxy-benzyl), O(3-methoxy-benzyl), N, NH, NHCH, NHCHCH, NH(CH)CH, NHCH(CH), NHCHCH═CH, NH(CH)OCH, NH(benzyl), NH(cyclopropyl), NH(cyclobutyl), NH(cyclopentyl), NH(cyclohexyl), NH(tetrahydro-2H-pyran-4-yl), NH(CH)OH, azetidin-1-yl, 3-hydroxyazetidin-1-yl, NH(CH)OH, NH(CH)OH, NH(CH)CH(OH)(CHOH), NH(CHCN), NH(CH)COH, NH(CH)COCH, NH(1H-pyrazol-3-yl), NHC(O)CH, and pyrrolidin-2-one-1-yl.'}5. The compound of wherein the compound is a compound described in Table 1.6. The compound of wherein the compound is selected from the following group:(3aR,5R,6S,7R,7aR)-2-(ethylamino)-5-(methoxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol;((3aR,5R,6S,7R,7aR)-6,7-dihydroxy-2-(methylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-5-yl)methyl ethylcarbamate;((3aR,5R,6S,7R,7aR)-6,7-dihydroxy-2-(methylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-5-yl)methyl methylcarbamate ...

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Номер записи: 57
03-04-2014 дата публикации

DESIGN AND SYNTHESIS OF CLEAVABLE FLUORESCENT NUCLEOTIDES AS REVERSIBLE TERMINATORS FOR DNA SEQUENCING BY SYNTHESIS

Номер: US20140093869A1
Автор: Cao Huanyan, Guo Jia, Ju Jingyue, Li Zengmin, Meng Qinglin, Zhang Shenglong
Принадлежит: The Trustees of Columbia University in the City of New York

This invention provides novel azido linkers for deoxynucleotide analogues having a detectable marker attached thereto. 2. The compound of claim 1 , wherein the first portion comprises a deoxynucleotide or a dideoxynucleotide and the third portion comprises a detectable marker.3. The compound of claim 2 , wherein the detectable marker is a fluorescent dye.4. The compound of claim 2 , wherein the first portion is a deoxynucleotide comprising a methylazido group attached to a 3′ O atom thereof.720-. (canceled)2253-. (canceled)56. The method of claim 54 , wherein a linker is cleaved by contacting the linker with tris(2-carboxyethyl)phosphine.57. The method of claim 54 , wherein one or more linkers are photocleavable or chemically cleavable.58. The method of claim 54 , wherein one or more chemical groups are photocleavable or chemically cleavable.59. The method of claim 54 , wherein R in the structures set forth in steps a) and or j) is independently chosen from a —Ngroup or an allyl group.60. The method of claim 54 , wherein the cleavable chemical group in step g) is independently chosen from a —Ngroup or an allyl group.6176-. (canceled) This application is a continuation of U.S. Ser. No. 12/734,227, filed Apr. 19, 2010, §371 national stage of PCT International Application No. PCT/US2008/011891, filed Oct. 17, 2008, and claims the benefit of U.S. Provisional Application No. 60/999,576, filed Oct. 19, 2007, the contents of each of which are hereby incorporated by reference in their entirety into this application.This invention was made with government support under grant number P50-HG00358205 awarded by the National Institutes of Health. The government has certain rights in the invention.This application incorporates-by-reference nucleotide and/or amino acid sequences which are present in the file named “131210057578341-AA-PCT-US_SegListing_JAK.txt”, which is 5 kilobytes in size, and which was created Nov. 6, 2013 in the IBM-PCT machine format, having an operating system ...

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Номер записи: 58
10-04-2014 дата публикации

2'-CHLORO NUCLEOSIDE ANALOGS FOR HCV INFECTION

Номер: US20140099283A1
Автор: Alexandre Francois-Rene, Dousson Cyril B., Gosselin Gilles, GRIFFON Jean-Francois, MAYES Benjamin Alexander, Milhau Julien, MOUSSA Adel M., Parsy Christophe Claude, Pierra Claire, Rahali Houcine, Surleraux Dominique
Принадлежит:

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2′-chloro nucleosides according to Formula 2001: 4. The compound of wherein each X is independently an N-linked amino acid claim 1 , or a derivative thereof.5. The compound of wherein each X is independently an N-linked L-amino acid claim 1 , or a derivative thereof.6. The compound of wherein each X is independently an N-linked D-amino acid claim 1 , or a derivative thereof.7. The compound of wherein each X is independently an N-linked D-alanine claim 1 , or a derivative thereof.8. (canceled)9. (canceled)10. The compound of wherein:W is O;{'sup': 1', '1', '2, 'each X is independently —ORor —NRR;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '1', 'sub': p', '3', 'p', 'p', '3', 'p', '3', 'p', '3', 'p', '3', '2, 'each Ris independently -(L)CR, -(L)Ar, -LC(O)O(L)CR, -LSC(O)(L)CR, -LOC(O)(L)CR, -LOC(O)(L)Cy, -LSC(O)LNHC(O)OCR, -LSC(O)LOC(O)LNH, -LC(O)LOAr, -LC(O)OLAr, or -LSC(O)LOH;'}each L is independently alkylene;each R is independently hydrogen, alkyl, aryl, or heteroaryl;each Ar is independently aryl, or heteroaryl;each Cy is independently cycloalkyl; andeach p is independently 0 or 1.1119-. (canceled)21. (canceled)22. (canceled)24. The compound of wherein Ris alkylamino.26. (canceled)2933-. (canceled)34. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient claim 1 , carrier or diluent.35. (canceled)36. A method for the treatment of a host infected with a hepatitis C virus claim 1 , comprising the administration of an effective treatment amount of a compound of .37. (canceled)38. The method of claim 36 , wherein the administration directs a substantial amount of the compound claim 36 , ...

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Номер записи: 59
10-04-2014 дата публикации

METHOD TO IMPROVE ANTIVIRAL ACTIVITY OF NUCLEOTIDE ANALOGUE DRUGS

Номер: US20140100186A1
Автор: KASHEMIROV Boris A., Krylov Ivan S., McKENNA Charles E., Zakharova Valeria M.
Принадлежит:

A method of modifying a nucleotide or a nucleotide analogue to increase its overall effectiveness in treating an antiviral disease is provided. In some cases, a compound comprising a base, sugar, phosphonate moiety, and amino acid residue is provided, where the base-sugar may be a nucleoside, and the amino acid residue may be a tyrosine residue. In certain cases, the tyrosine residue contains a long chain alkyl group on the carboxamide group of the residue. Methods of inhibiting viral replication and methods of treating a viral infection are also provided. 1. A compound of the formula: base-sugar-A-X , or a salt thereof ,{'sub': '6', 'wherein the base-sugar is a nucleoside or an analogue thereof, A is a phosphonate moiety, and X is an amino acid residue, a dipeptide, or a derivative of an amino acid residue or dipeptide, wherein X comprises a side-chain oxygen which is connected to the phosphonate moiety by an ester linkage and comprises an alkylamido group comprising a Cor greater alkyl group, and wherein the compound has antiviral activity.'}2. The compound of claim 1 , wherein the Cor greater alkyl group is a Calkyl claim 1 , Calkyl claim 1 , Calkyl claim 1 , or Calkyl group3. The compound of claim 1 , wherein X is a tyrosine claim 1 , serine or threonine residue claim 1 , or a derivative thereof.4. The compound of claim 3 , wherein the amino acid residue or derivative thereof comprises a carboxamide group NRR′ claim 3 , wherein R═H and R′=a Calkyl group5. The compound of claim 1 , wherein the amino acid residue is a tyrosine residue or a derivative thereof.6. The compound of claim 5 , wherein the tyrosine residue or derivative thereof comprises a carboxamide group NRR′ claim 5 , wherein R═H and R′=a Calkyl group.7. The compound of claim 1 , wherein the base-sugar is the nucleoside portion of a nucleotide or nucleotide analogue that has antiviral activity.8. The compound of claim 7 , wherein the base-sugar is the nucleoside portion of HPMPA claim 7 , cyclic HPMPA ...

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Номер записи: 60
07-01-2016 дата публикации

D-AMINO ACID COMPOUNDS FOR LIVER DISEASE

Номер: US20160002281A1
Автор: Alexandre Francois-Rene, Dousson Cyril B., Gosselin Gilles, GRIFFON Jean-Francois, MAYES Benjamin Alexander, MOUSSA Adel M., Parsy Christophe Claude, Pierra Claire, Rahali Houcine, STEWART Alistair James, Surleraux Dominique
Принадлежит:

Provided herein are compounds, compositions and methods for the treatment of liver disease and conditions, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. 12-. (canceled)428-. (canceled)46. The pharmaceutical composition of claim 45 , wherein said composition provides a therapeutically effective amount of said compound for treating a human infected with HCV.53. The pharmaceutical composition of claim 51 , wherein said compound is a designated enantiomer claim 51 , and said composition is substantially free of other stereoisomers of said compound.54. The pharmaceutical composition of claim 52 , wherein said compound is a designated enantiomer claim 52 , and said composition is substantially free of other stereoisomers of said compound. Provided herein are compounds, methods and pharmaceutical compositions for use in treatment of liver diseases and conditions, including viral infections such as hepatitis C virus infections in hosts in need thereof. In certain embodiments, D-amino acids linked to therapeutic nucleoside analogs are provided which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human.The hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide. (Boyer, N. et al., 32:98-112, 2000). HCV causes a slow growing viral infection and is the major cause of cirrhosis and hepatocellular carcinoma (Di Besceglie, A. M. and Bacon, B. R., , October: 80-85, 1999; Boyer, N. et al., 32:98-112, 2000). It is estimated there are about 130-170 million people with chronic hepatitis C virus infection, and there are about 350,000 deaths from hepatitis C-related liver diseases each year (Hepatitis C Fact Sheet, 164, June 2011). Cirrhosis caused by chronic hepatitis C infection accounts for 8,000-12,000 deaths per year in the United States, and HCV ...

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Номер записи: 61
05-01-2017 дата публикации

Cyclic nucleotide analogs

Номер: US20170002037A1
Автор: David Bernard Smith, Jerome Deval, Leonid Beigelman, Vivek Kumar Rajwanshi
Принадлежит: Alios Biopharma Inc

Disclosed herein are cyclic nucleotide analogs, methods of synthesizing cyclic nucleotide analogs and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with cyclic nucleotide analogs.

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Номер записи: 62
05-01-2017 дата публикации

LABELLED NUCLEOTIDES

Номер: US20170002407A1
Автор: Balasubramanian Shankar, BARNES Colin, Liu Xiaohai, Milton John
Принадлежит:

Nucleosides and nucleotides are disclosed that are linked to detectable labels via a cleavable linker group. 125-. (canceled)26. A nucleotide or nucleoside molecule having a ribose or deoxyribose sugar moiety and a base linked to a detectable label via a cleavable linker , wherein the sugar moiety comprises a protecting group attached via the 3′ oxygen atom , and wherein said protecting group comprises an azido group and can be modified or removed to expose a 3′ OH group.27. The molecule of claim 26 , wherein the base is a purine claim 26 , or a pyrimidine.28. The molecule of claim 26 , wherein the base is a deazapurine.29. The molecule of claim 26 , which is a deoxyribonucleotide triphosphate.30. The molecule of claim 26 , wherein the detectable label is a fluorophore.31. The molecule of claim 26 , wherein the linker is acid labile claim 26 , photolabile or contains a disulphide linkage.32. The molecule of claim 26 , wherein the cleavable linker and the protecting group are cleavable under identical conditions.33. The molecule of claim 26 , wherein the protecting group comprises azidomethyl (CHN).34. A nucleotide or nucleoside molecule having a ribose or deoxyribose sugar moiety and a base linked to a detectable label via a cleavable linker claim 26 , wherein the sugar moiety comprises a protecting group attached via the 3′ oxygen atom claim 26 , and wherein said protecting group comprises cyanoethyl ((CH)CN) and can be modified or removed to expose a 3′ OH group.35. The molecule of claim 34 , wherein the base is a purine claim 34 , or a pyrimidine.36. The molecule of claim 34 , wherein the base is a deazapurine.37. The molecule of claim 34 , which is a deoxyribonucleotide triphosphate.38. The molecule of claim 34 , wherein the detectable label is a fluorophore.39. The molecule of claim 34 , wherein the linker is acid labile claim 34 , photolabile or contains a disulphide linkage.40. The molecule of claim 34 , wherein the cleavable linker and the protecting group ...

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Номер записи: 63
05-01-2017 дата публикации

LABELLED NUCLEOTIDES

Номер: US20170002408A1
Автор: Liu Xiaohai, Milton John, Ruediger Silke
Принадлежит:

The invention provides a nucleotide or nucleoside having a base attached to a detectable label via a cleavable linker, characterised in that the cleavable linker contains a moiety selected from the group comprising: Formula (I) (wherein X is selected from the group comprising O, S, NH and NQ wherein Q is a Csubstituted or unsubstituted alkyl group, Y is selected from the group comprising O, S, NH and N(allyl), T is hydrogen or a Csubstituted or unsubstituted alkyl group and * indicates where the moiety is connected to the remainder of the nucleotide or nucleoside). 160-. (canceled)61. A nucleoside or nucleotide comprising a base attached to a detectable label via a phosphine cleavable linker comprising a disulfide.62. The nucleoside or nucleotide of claim 61 , wherein the nucleoside or nucleotide further comprises a dideoxyribose moiety.63. The nucleoside or nucleotide of claim 61 , wherein the nucleoside or nucleotide further comprises a ribose or deoxyribose moiety with a hydroxyl protecting group attached to the 2′ or 3′ oxygen atom.64. The nucleoside or nucleotide of claim 63 , wherein the linker and protecting group are cleavable under the same conditions.65. The nucleoside or nucleotide of claim 63 , wherein the protecting group is azidomethyl.66. The nucleoside or nucleotide of claim 61 , wherein the base is a purine claim 61 , pyrimidine or deazapurine.67. The nucleoside or nucleotide of claim 61 , wherein the detectable label is a fluorophore.68. An oligonucleotide comprising the nucleoside or nucleotide of .69. The oligonucleotide of claim 68 , wherein the oligonucleotide is attached to a solid support.70. A solid support comprising the oligonucleotide of .71. A composition comprising four nucleosides or nucleotides claim 68 , wherein each nucleoside or nucleotide comprises a base attached to a detectable label via a phosphine cleavable linker comprising a disulfide claim 68 , wherein each nucleoside or nucleotide carries a different detectable label.72. ...

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Номер записи: 64
04-01-2018 дата публикации

Phosphorodiamidate Backbone Linkage for Oligonucleotides

Номер: US20180002367A1
Автор: Pongracz Krisztina, RAMASESHAN Mahesh
Принадлежит:

This invention relates to antisense oligonucleotides comprising at least one N3′→P5′ phosphorodiamidate linkage (NPN) in the backbone as well as methods for using the same. The antisense oligonucleotides can effectively prevent or decrease protein expression. 114.-. (canceled)16. The compound of claim 15 , or a salt thereof claim 15 , wherein W is O.17. The compound of claim 15 , or a salt thereof claim 15 , wherein Bis independently selected from purinyl and pyrimidinyl.18. The compound of claim 15 , or a salt thereof claim 15 , wherein Bis independently selected from 4-benzoyl-1-cytosinyl claim 15 , 6-benzoyl-9-adeninyl claim 15 , 6-dimethylformamidino-9-adeninyl claim 15 , 2-isobutyryl-9-guaninyl claim 15 , 2-dimethylformamidino-9-guaninyl claim 15 , 9-adeninyl claim 15 , 9-guaninyl claim 15 , 1-cytosinyl claim 15 , 1-thyminyl and 1-uracilyl.19. The compound of claim 15 , or a salt thereof claim 15 , wherein Bis selected from adenine claim 15 , guanine claim 15 , cytosine claim 15 , thymine claim 15 , and uracil.20. The compound of claim 15 , or a salt thereof claim 15 , wherein Ris hydrogen.21. The compound of claim 15 , or a salt thereof claim 15 , wherein Rand Rare methyl.22. The compound of claim 15 , or a salt thereof claim 15 , wherein Ris selected from trityl claim 15 , dimethoxytrityl and methoxytrityl.23. The compound of claim 15 , or a salt thereof claim 15 , wherein Ris selected from chloro claim 15 , iodo claim 15 , bromo claim 15 , fluoro claim 15 , methanesulfonyloxy claim 15 , tosyloxy claim 15 , triflyloxy claim 15 , nitro-phenylsulfonyloxy and bromo-phenylsulfonyloxy.24. The compound of claim 15 , or a salt thereof claim 15 , wherein Ris halogen.25. The compound of claim 15 , or a salt thereof claim 15 , wherein Ris selected from trityl claim 15 , dimethoxytrityl and methoxytrityl and Ris halogen.2640.-. (canceled)4260.-. (canceled)62. The method of claim 61 , wherein the phosphorylating reagent is dimethylaminophosphoryl compound.63. The method ...

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Номер записи: 65
07-01-2021 дата публикации

SUBSTITUTED PYRIDOPYRROLOPYRIMIDINE RIBONUCLEOSIDES FOR THERAPEUTIC USES

Номер: US20210002321A1
Автор: DZUBAK Petr, HAJDUCH Marian, HOCEK Michal, VESELOVSKA Lucia
Принадлежит:

Substituted pyridopyrrolopyrimidine ribonucleosides of general formula I, wherein R is as described in the independent claim, preferably R is selected from the group comprising thiophen-3-yl, furan-2-yl, furan-3-yl, benzofuran-2-yl, methylsulfanyl, methoxy, amino, dimethylamino, methyl; and pharmaceutically acceptable salt thereof, their optical isomers and mixtures of such optical isomers. Compounds according to the invention show strong cytostatic and cytotoxic effects on cell lines of tumor origin in a wide variety of diseases including tumors of different histogenetic origin. 2. Substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1 , where R is selected from the group comprising amino claim 1 , C1-C5 alkyl claim 1 , phenyl claim 1 , naphthyl claim 1 , furan-2-yl claim 1 , furan-3-yl claim 1 , thiophen-2-yl claim 1 , thiophen-3-yl claim 1 , benzofuryl claim 1 , C1-C5 alkylsulfanyl claim 1 , C1-C5 alkylamino claim 1 , di(C1-C5 alkyl)amino claim 1 , C1-C5 alkoxy group.3. Substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1 , where R is selected from the group comprising amino claim 1 , thiophen-3-yl claim 1 , furan-2-yl claim 1 , furan-3-yl claim 1 , benzofuran-2-yl claim 1 , methylsulfanyl claim 1 , methoxy claim 1 , dimethylamino claim 1 , methyl or chloro.4. Substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1 , being selected from the following compounds:4-methyl-9-(β-D-ribofuranosyl)-9H-pyrido[2′,3′:4,5]pyrrolo[2,3-d]pyrimidine4-amino-9-(β- D-ribofuranosyl)-9H-pyrido[2′,3′:4,5]pyrrolo[2,3-d]pyrimidine4-(benzofuran-2-yl)-9-(β-D-ribofuranosyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidine4-methyl-9-(β-D-ribofuranosyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidine4-amino-9-(β-D-ribofuranosyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidine4-methoxy-9-(β-D-ribofuranosyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidine4-(methylsulfanyl)-9-(β-D- ...

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Номер записи: 66
07-01-2021 дата публикации

MODULATORS OF 5'-NUCLEOTIDASE, ECTO AND THE USE THEREOF

Номер: US20210002322A1
Автор: DEBIEN Laurent Pierre Paul, JAEN Juan Carlos, KALISIAK Jaroslaw, LAWSON Kenneth V., LELETI Manmohan Reddy, LINDSEY Erick Allen, MILES Dillon Harding, NEWCOMB Eric, POWERS Jay Patrick, ROSEN Brandon Reid, SHARIF Ehesan Ul
Принадлежит:

Compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided. 1. A compound having the formulaor a pharmaceutically acceptable salt thereof. This application is a continuation application of U.S. application Ser. No. 16/273,843, filed Feb. 2, 2019, which is a continuation application of U.S. application Ser. No. 15/400,748, filed Jan. 6, 2017, now U.S. Pat. No. 10,239,912, which claims priority benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 62/276,564, filed Jan. 8, 2016 and U.S. Provisional Application No. 62/324,077, filed Apr. 18, 2016, each of which is herein incorporated by reference in its entirety for all purposes.Not ApplicableNot ApplicableProvided herein are, for example, compounds and compositions for inhibition of adenosine by 5′-nucleotidase, ecto, also known as CD73, and pharmaceutical compositions comprising same. Also provided herein are, for example, methods of treating or preventing a disease, disorder or condition, or a symptom thereof, mediated by inhibition of adenosine by 5′-nucleotidase, ecto.Purinergic signaling, a type of extracellular signaling mediated by purine nucleotides and nucleosides such as ATP and adenosine, involves the activation of purinergic receptors in the cell and/or in nearby cells, resulting in the regulation of cellular functions. Most cells have the ability to release nucleotides, which generally occurs via regulated exocytosis (see Praetorius, H. A.; Leipziger, J. (1 Mar. 2010) 72(1): 377-393). The released nucleotides can then be hydrolyzed extracellularly by a variety of cellular membrane-bound enzymes referred to as ...

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Номер записи: 67
03-01-2019 дата публикации

POLYPEPTIDE TAGGED NUCLEOTIDES AND USE THEREOF IN NUCLEIC ACID SEQUENCING BY NANOPORE DETECTION

Номер: US20190002968A1
Автор: Bergmann Frank, Gremyachinskiy Dmitriy, HILLRINGHAUS Lars, KUCHELMEISTER Hannes, SEIDEL Christoph, TRANS Andrew
Принадлежит:

The present disclosure relates to compositions and methods based on polypeptide-tagged nucleotide, and the use of such polypeptide-tagged nucleotides in nanopore devices and methods. 1. A compound of structural formula (I){'br': None, 'N-P-L-T\u2003\u2003 (I)'} N is a nucleoside;', 'P is an oligophosphate covalently attached to a 5′-O group of the nucleoside,', 'wherein the oligophosphate consists of 3 to 12 phosphate groups;', 'L is a linker covalently attached to a terminal phosphate group of the oligophosphate; and', 'T is a polypeptide tag covalently attached to the linker, wherein the polypeptide has an overall charge and comprises at least one helical structure., 'wherein,'}3. The compound of claim 1 , wherein the length of the polypeptide tag is at least 16 amino acid residues claim 1 , optionally wherein the length of the polypeptide tag is at least 20 amino acid residues claim 1 , at least 25 amino acid residues claim 1 , at least 30 amino acid residues claim 1 , at least 40 amino acid residues claim 1 , at least 50 amino acid residues claim 1 , at least 60 amino acid residues claim 1 , at least 70 amino acid residues claim 1 , at least 80 amino acid residues claim 1 , or at least 90 amino acid residues.4. The compound of claim 1 , wherein the helical structure comprises is at least 8 amino acid residues claim 1 , optionally wherein the polypeptide helical structure comprises at least 16 amino acid residues claim 1 , at least 20 amino acid residues claim 1 , at least 25 amino acid residues claim 1 , at least 30 amino acid residues claim 1 , at least 40 amino acid residues claim 1 , at least 50 amino acid residues claim 1 , or at least 60 amino acid residues.5. The compound of claim 1 , wherein the helical structure is an α-helix claim 1 , optionally wherein the length of the α-helix is at least 10 amino acid residues claim 1 , at least 16 amino acid residues claim 1 , at least 20 amino acid residues claim 1 , at least 25 amino acid residues claim 1 , at ...

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Номер записи: 68
01-01-2015 дата публикации

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Номер: US20150005251A1
Автор: Beigelman Leonid, Dyatkina Natalia, Rajwanshi Vivek Kumar, Wang Guangyi
Принадлежит:

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 paramyxovirus viral infection, with a nucleoside, a nucleotide and an analog thereof. 2. The compound of claim 1 , wherein Ris azidomethyl.3. The compound of claim 1 , wherein Ris aminomethyl.5. The compound of claim 4 , wherein Rand Rare both hydrogen or absent.6. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. (canceled)17. (canceled)18. (canceled)19. (canceled)20. (canceled)21. (canceled)22. (canceled)23. (canceled)24. The compound of claim 4 , wherein Ris an optionally substituted aryl; and Ris an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.25. (canceled)26. (canceled)27. (canceled)28. (canceled)29. The compound of claim 4 , wherein Rand Rare both an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.30. (canceled)31. (canceled)32. (canceled)34. The compound of claim 33 , wherein m is 0 claim 33 , and Rand Rare independently absent or hydrogen.35. The compound of claim 33 , wherein m is 1 claim 33 , and R claim 33 , Rand Rare independently absent or hydrogen.36. The compound of claim 1 , wherein Ris H.37. The compound of claim 1 , wherein Ris an optionally substituted acyl.38. The compound of claim 1 , wherein Ris an optionally substituted O-linked amino acid.39. (canceled)42. (canceled)45. (canceled)46. (canceled)47. The compound of claim 1 , wherein Ris OH.48. The compound of claim 1 , wherein Ris —OC(═O)R.49. The compound of claim 1 , wherein Ris O-linked amino acid.50. (canceled)51. The compound of claim 1 , wherein Ris hydrogen.52. (canceled)53. (canceled)54. The compound of claim 1 , wherein ...

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Номер записи: 69
27-01-2022 дата публикации

Cyclic Di-Nucleotide Compounds as STING Agonists

Номер: US20220024964A1
Автор: Benjamin Wesley TROTTER, HONG Liu, Jared N. Cumming, Michael D. Altman, Wonsuk Chang
Принадлежит: Merck Sharp and Dohme LLC

A class of polycyclic compounds of general formula (I), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2a, R3, R3a, R4, R5, R5a, R6, R6a, R7, R7a, R8, R8a, and R9 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds (I).

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Номер записи: 70
08-01-2015 дата публикации

Substituted nucleosides, nucleotides and analogs thereof

Номер: US20150011497A1
Автор: Jerome Deval, Leonid Beigelman, Zhinan JIN
Принадлежит: Alios Biopharma Inc

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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Номер записи: 71
11-01-2018 дата публикации

BETA-D-2'-DEOXY-2'-SUBSTITUTED-4'-SUBSTITUTED-2-SUBSTITUTED-N6-SUBSTITUTED-6-AMINOPURINENUCLEOTIDES FOR THE TREATMENT OF PARAMYXOVIRUS AND ORTHOMYXOVIRUS INFECTIONS

Номер: US20180009836A1
Автор: Moussa Adel, SOMMADOSSI Jean-Pierre
Принадлежит: Atea Pharmaceuticals, Inc.

A compound or a pharmaceutically acceptable salt or composition thereof for the treatment of a host infected with or exposed to a virus of the Paramyxoviridae or Orthomyxoviridae family, or other disorders, in particular respiratory syncytial virus, more fully described herein. 2. The compound of claim 1 ,wherein{'sup': '1', 'Ris selected from methyl and cyclopropyl; and'}{'sup': '2', 'Ris hydrogen.'}3. The compound of claim 1 , wherein Ris methyl and Ris methyl.4. The compound of claim 1 , wherein Ris hydrogen.5. The compound of claim 1 , wherein Ris selected from Calkyl claim 1 , methyl claim 1 , Chaloalkyl claim 1 , and —CHCl.6. The compound of claim 1 , wherein Ris selected from Cl claim 1 , F claim 1 , and NRRwherein{'sup': '5', 'Ris hydrogen;'}{'sup': 6', '3C, 'Ris —C(O)R; and'}{'sup': '3C', 'Ris alkyl.'}7. The compound of claim 1 , wherein the stabilized phosphate prodrug is a phosphoramidate.8. The compound of claim 1 , wherein the stabilized phosphate prodrug is a thiophosphoramidate.10. The compound of claim 9 ,wherein{'sup': '1', 'Ris selected from methyl and cyclopropyl; and'}{'sup': '2', 'Ris hydrogen.'}11. The compound of claim 9 , wherein Ris methyl and Ris methyl.12. The compound of claim 9 , wherein Ris hydrogen.13. The compound of claim 9 , wherein Ris selected from Calkyl claim 9 , methyl claim 9 , Chaloalkyl claim 9 , and —CHCl.14. The compound of claim 9 , wherein Ris selected from Cl claim 9 , F claim 9 , and NRRwherein{'sup': '5', 'Ris hydrogen;'}{'sup': 6', '3C, 'Ris —C(O)R; and'}{'sup': '3C', 'Ris alkyl.'}15. The compound of claim 9 , wherein the stabilized phosphate prodrug is a phosphoramidate.16. The compound of claim 9 , wherein the stabilized phosphate prodrug is a thiophosphoramidate.18. The compound of claim 17 ,wherein{'sup': '1', 'Ris selected from methyl and cyclopropyl; and'}{'sup': '2', 'Ris hydrogen.'}19. The compound of claim 17 , wherein Ris methyl and Ris methyl.20. The compound of claim 17 , wherein Ris hydrogen.21. The ...

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Номер записи: 72
14-01-2021 дата публикации

LABELLED NUCLEOTIDES

Номер: US20210009622A1
Автор: Liu Xiaohai, Milton John, Ruediger Silke, Wu Xiaolin
Принадлежит:

The invention provides a nucleotide or nucleoside having a base attached to a detectable label via a cleavable linker, characterised in that the cleavable linker contains a moiety selected from the group comprising: Formula (I) (wherein X is selected from the group comprising O, S, NH and NQ wherein Q is a Csubstituted or unsubstituted alkyl group, Y is selected from the group comprising O, S, NH and N(allyl), T is hydrogen or a Csubstituted or unsubstituted alkyl group and * indicates where the moiety is connected to the remainder of the nucleotide or nucleoside). 1. (canceled)2. (canceled)4. The oligonucleotide of claim 3 , wherein R is not present.6. The oligonucleotide of claim 5 , wherein the dotted line connecting the Fluor and the benzene ring comprises one or more spacer units such that the Fluor is held a sufficient distance from the nucleobase so as not to interfere with any interaction between the nucleotide and an enzyme.7. The oligonucleotide of claim 6 , wherein the spacer unit comprises —O— claim 6 , —NH— claim 6 , or —N(alkyl)-.9. The oligonucleotide of claim 8 , wherein the Fluor comprises a cyanine claim 8 , a rhodamine claim 8 , or a coumarin dye.10. The oligonucleotide of claim 9 , wherein the Fluor is a rhodamine dye.11. The oligonucleotide of claim 9 , wherein the Fluor is a Cy5 dye.12. The oligonucleotide of claim 9 , wherein the Fluor is attached to the Linker by reacting an N-hydroxysuccinimide ester of the Fluor with an amino moiety of the Linker.17. The oligonucleotide of claim 8 , wherein the oligonucleotide is in contact with an aqueous solution comprising ethylenediaminetetraacetic acid (EDTA).18. The oligonucleotide of claim 8 , wherein the oligonucleotide is in contact with a mutant polymerase.19. The oligonucleotide of claim 8 , wherein the oligonucleotide is in contact with a water soluble phosphine.20. The oligonucleotide of claim 8 , wherein the oligonucleotide is hybridized to a target polynucleotide claim 8 , and wherein the ...

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Номер записи: 73
14-01-2021 дата публикации

Labelled nucleotides

Номер: US20210009623A1
Автор: John Milton, Silke Ruediger, Xiaohai Liu, Xiaolin Wu
Принадлежит: Illumina Cambridge Ltd

The invention provides a nucleotide or nucleoside having a base attached to a detectable label via a cleavable linker, characterised in that the cleavable linker contains a moiety selected from the group comprising: Formula (I) (wherein X is selected from the group comprising O, S, NH and NQ wherein Q is a C 1-10 substituted or unsubstituted alkyl group, Y is selected from the group comprising O, S, NH and N(allyl), T is hydrogen or a C 1-10 substituted or unsubstituted alkyl group and * indicates where the moiety is connected to the remainder of the nucleotide or nucleoside).

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Номер записи: 74
14-01-2021 дата публикации

CYCLIC DINUCLEOTIDE COMPOUNDS CONTAINING 2-AZA-HYPOXANTHINE OR 6H-PYTAZOLO[1,5-D][1,2,4]TRIZAIN-7-ONE AS STRING AGONISTS

Номер: US20210009627A1
Автор: FLECK Martin, HEIMANN Annekatrin Charlotte, KUTTRUFF Christian Andreas, OOST Thorsten
Принадлежит:

Compounds of formula I, wherein Base, Rand Rare defined as in claim , are modulators of STING. 2. A compound according to wherein Ris purine.3. A compound according to wherein Ris adenine.4. A compound according to wherein Ris guanine.5. A compound according to wherein Ris hypoxanthine.6. A compound according claim 1 , wherein Rdenotes F and Rdenotes H.7. A substantially pure (Sp claim 1 ,Sp) claim 1 , (Rp claim 1 ,Rp) claim 1 , (Sp claim 1 ,Rp) claim 1 , or (Rp claim 1 ,Sp) stereoisomer of a compound according to claim 1 , or a salt thereof.8. A pharmaceutically acceptable salt of a compound according to .9. A pharmaceutical composition comprising one or more compounds according to claim 1 , or pharmaceutically acceptable salts thereof claim 1 , optionally together with one or more inert carriers and/or diluents.10. A vaccine comprising a compound .11. A pharmaceutical composition comprising one or more compounds according to claim 1 , or pharmaceutically acceptable salts thereof claim 1 , and one or more additional therapeutic agents claim 1 , optionally together with one or more inert carriers and/or diluents.12. A pharmaceutical composition according to and one or more additional therapeutic agents.13. (canceled)14. A vaccine adjuvant comprising a compound according to .15. A method for the treatment of diseases or conditions associated with or modulated by STING claim 1 , comprising inflammation claim 1 , allergic or autoimmune diseases claim 1 , infectious diseases or cancer claim 1 , in a patient in need thereof claim 1 , the method being characterized in that one or more compounds according to are administered to the patient.16. A compound according to for the treatment of diseases or conditions associated with or modulated by STING claim 1 , comprising inflammation claim 1 , allergic or autoimmune diseases claim 1 , infectious diseases or cancer in a patient. This invention relates to novel cyclic dinucleotide compounds (“CDNs”) of formula I, and ...

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Номер записи: 75
14-01-2021 дата публикации

Beta-D-2'-DEOXY-2'-Alpha-FLUORO-2'-Beta-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

Номер: US20210009628A1
Автор: Adel Moussa, Jean-Pierre Sommadossi
Принадлежит: Atea Pharmaceuticals Inc

A compound of the structure: or a pharmaceutically acceptable salt or composition thereof for the treatment of a host infected with or exposed to an HCV virus or other disorders more fully described herein.

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Номер записи: 76
09-01-2020 дата публикации

SYNTHESIS OF POLYPHOSPHORYLATED MOLECULES FROM POLYPHOSPHATES

Номер: US20200010500A1
Автор: Cummins Christopher C., SHEPARD Scott
Принадлежит: Massachusetts Institute of Technology

Metaphosphate compounds can directly phosphorylate other compounds to provide easy synthetic access to phosphorylated compounds, including cyclic phosphate compounds. 1. A method of polyphosphorylating a compound comprising contacting the compound with an activated polyphosphate , wherein the compound includes a nucleophilic group.2. The method of claim 1 , wherein the activated polyphosphate is a triphosphate or a tetraphosphate claim 1 , optionally claim 1 , a cyclic phosphate.3. The method of claim 1 , wherein the activated polyphosphate is an N-oxy-amino polyphosphate ester.4. The method of claim 1 , wherein the activated polyphosphate is a trimetaphosphate 7-azabenzotriazole phosphoester or a trimetaphosphate benzotriazol-1-yl-oxy phosphoester or tetraphosphorylating agent anhydride [PO].5. The method of claim 1 , wherein the compound is HNuc claim 1 , wherein −Nuc includes an oxo claim 1 , amino claim 1 , or thio group.6. The method of claim 1 , wherein the compound is monohydrogen tetrametaphosphate.7. The method of claim 1 , wherein the activated polyphosphate is a phosphorus ylide.8. A compound comprising a triphosphorylated or tetraphosphorylated compound claim 1 , wherein the triphosphorylated or tetraphosphorlyated compound includes a cyclic phosphate.9. A compound comprising a trimetaphosphate 7-azabenzotriazole phosphoester claim 1 , a trimetaphosphate benzotriazol-1-yl-oxy phosphoester or tetraphosphorylating agent anhydride [PO].10. A method of polyphosphorylating a compound comprising contacting monohydrogen tetrametaphosphate with a protein coupling agent to form an activated polyphosphate and contacting the activated polyphosphate with the compound.11. The method of claim 10 , wherein the protein coupling agent is PyAOP claim 10 , PyBOP claim 10 , PyBrOP claim 10 , PyOxim claim 10 , or HATU.12. The method of claim 1 , wherein the compound is a biochemical substrate claim 1 , including a nucleoside claim 1 , an amino acid claim 1 , a sugar claim 1 ...

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Номер записи: 77
03-02-2022 дата публикации

Cyclic Di-Nucleotide Compounds as STING Agonists

Номер: US20220033431A1
Автор: Altman Michael D., Chang Wonsuk, Cumming Jared N., Liu Hong, Trotter Benjamin Wesley
Принадлежит: Merck Sharp & Dohme Corp.

A class of polycyclic compounds of general formula (I), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R, R1a, R2a, R3, R3a, R4, R4a, R5, R6, R6a, R7, R7a, R8, R8a, and R9 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds. (I) 13. A pharmaceutical composition , said pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) a compound according to or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof; and'}(b) a pharmaceutically acceptable carrier.14. A method of inducing an immune response in a subject claim 1 , said method comprising administering a therapeutically effective amount of a compound according to to the subject.15. A method of inducing an immune response in a subject claim 13 , said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to to the subject.16. A method of inducing a STING-dependent type I interferon production in a subject claim 1 , said method comprising administering a therapeutically effective amount of a compound according to to the subject.17. A method of inducing a STING-dependent type I interferon production in a subject claim 13 , said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to to the subject.18. A method of treating a cell proliferation disorder in a subject claim 1 , said method comprising administering a therapeutically effective amount of a compound according to to the subject.19. The method of claim 18 , wherein the cell proliferation disorder is cancer.20. A method of treating a cell proliferation disorder in a subject claim 13 , said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to to the subject.21. The method of ...

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Номер записи: 78
03-02-2022 дата публикации

PROCESS FOR PREPARING NUCLEOSIDE PRODRUGS

Номер: US20220033433A1
Автор: McGuigan (Deceased) Christopher, Pertusati Fabrizio
Принадлежит:

A process for preparing phosphoramidates of nucleosides where a desired enantiomer, having regard to the asymmetric chiral center of the phosphorus atom P, is provided in an enriched amount. The process comprises admixing a nucleoside with a phosphorochloridate in the presence of a catalyst comprising a metal salt selected from the group consisting of salts of Cu, Fe, La and Yb. 137-. (canceled)39. The method of treatment of claim 38 , wherein the composition further comprises a pharmaceutically acceptable carrier claim 38 , diluent or excipient.40. The method of treatment of claim 38 , wherein the cancer is breast cancer.41. The method of treatment of claim 38 , wherein the cancer is colon cancer.42. The method of treatment of claim 38 , wherein the cancer is prostate cancer.43. The method of treatment of claim 38 , wherein the cancer is leukemia.44. The method of treatment of claim 38 , wherein the composition is administered orally.45. The method of treatment of claim 38 , wherein the composition is administered parenterally.46. The method of treatment of claim 45 , wherein the composition is administered intravenously.47. The method of treatment of claim 38 , wherein the composition is administered topically. The present invention relates to a process for preparing chemical compounds and to the chemical compounds prepared by the present process.The chemical synthesis of a chiral compound usually results in a racemic mixture of the compound in which R and S enantiomers are present in equal amounts.Many biologically active systems, however, involve specific enantiomers or diastereoisomers of chiral compounds. Such chiral biological systems may react differently to the different enantiomers or diasteroisomers of a pharmaceutical chiral compound.Administering to a patient a racemic mixture of a chiral pharmaceutical compound may mean that only one enantiomer of the compound can partake in the desired therapeutic reaction. The synthesis of a chiral pharmaceutical ...

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Номер записи: 79
21-01-2016 дата публикации

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Номер: US20160016987A1
Автор: Beigelman Leonid, Smith David Bernard, Wang Guangyi
Принадлежит:

Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs.

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Номер записи: 80
15-01-2015 дата публикации

Compounds

Номер: US20150018300A1
Автор: Jinfa Du, Michael Joseph Sofia
Принадлежит: GILEAD PHARMASSET LLC

Disclosed herein are 2′-spiro-nucleosides and derivatives thereof useful for treating a subject infected by hepatitis C virus or dengue virus.

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Номер записи: 81
18-01-2018 дата публикации

A Process for the Preparation of Nucleic Acid by Means of 3'-O-Azidomethyl Nucleotide Triphosphate

Номер: US20180016609A1
Автор: Gordon R. MCINROY, Jiahao HUANG, Michael C. Chen, Radu A. LAZAR
Принадлежит: Nuclera Nucleics Ltd

The invention relates to a method of nucleic acid synthesis comprising the use of 3′-O-azidomethyl blocked nucleotide triphosphates which comprises the step of adding a capping group to any uncleaved 3′-O-azidomethyl groups and to the use of kits comprising said capping groups in a method of nucleic acid synthesis. The invention also relates to capped nucleotide triphosphates and 3′-O-azidomethyl capping groups.

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Номер записи: 82
17-01-2019 дата публикации

COMPOSITIONS AND METHODS FOR MODULATING ANGIOPOIETIN-LIKE 3 EXPRESSION

Номер: US20190016748A1
Автор: Crooke Rosanne M., Freier Susan M., Graham Mark J., Prakash Thazha P., Seth Punit P., Swayze Eric E.
Принадлежит: Ionis Pharmaceuticals, Inc.

Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof. 126.-. (canceled)28. The compound of claim 27 , wherein the nucleobase sequence of the modified oligonucleotide is at least 85% claim 27 , at least 90% claim 27 , at least 95% claim 27 , or 100% complementary to SEQ ID NOs: 1.29. The compound of claim 27 , wherein the modified oligonucleotide comprises at least one modified internucleoside linkage.30. The compound of claim 29 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.31. The compound of claim 27 , wherein the modified oligonucleotide comprises at least one modified sugar.32. The compound of claim 31 , wherein at least one modified sugar is selected from a bicyclic sugar claim 31 , a 2′-O-methoxyethyl modified sugar claim 31 , a constrained ethyl modified sugar claim 31 , a 3′-fluoro-HNA or a 4′-(CH)—O-2′ bridge claim 31 , wherein n is 1 or 2.33. The compound of claim 27 , wherein at least one nucleoside comprises a modified nucleobase.34. The compound of claim 33 , wherein the modified nucleobase is a 5-methylcytosine.35. The compound of claim 27 , wherein the modified oligonucleotide comprises:a gap segment consisting of linked deoxynucleosides;a 5′ wing segment consisting of linked nucleosides;a 3′ wing segment consisting of linked nucleosides;wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.36. The compound claim 27 , wherein the modified oligonucleotide comprises:a gap segment consisting of ten linked ...

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Номер записи: 83
17-01-2019 дата публикации

2'-substituted carba-nucleoside analogs for antiviral treatment

Номер: US20190016749A1
Автор: Michael O' Neil Hanrahan Clarke
Принадлежит: Gilead Sciences Inc

Provided are compounds of Formula I, as well as pharmaceutical compositions containing compounds of Formula I and methods for treating Orthomyxoviridae virus infections by administering these compounds. The compounds, compositions, and methods provided are particularly useful for the treatment of Human Influenza virus infections.

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Номер записи: 84
16-01-2020 дата публикации

MODIFIED NUCLEOTIDES

Номер: US20200017908A1
Автор: Barnes Colin Lloyd, Brennan Joseph, Liu Xiaohai, Milton John, Ruediger Silke, Smith Mark Edward Brennan, Wu Xiaolin
Принадлежит:

The invention provides modified nucleotide or nucleoside molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety having a removable 3′-OH blocking group covalently attached thereto, such that the 3′ carbon atom has attached a group of the structure —O—Z wherein Z is any of —C(R′)2-O—R″, —C(R′)2-N(R″)2, —C(R′)2-N(H)R″, —C(R′)2-S—R″ and —C(R′)2-F, wherein each R″ is or is part of a removable protecting group; each R′ is independently a hydrogen atom, an alkyl, substituted alkyl, arylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclic, acyl, cyano, alkoxy, aryloxy, heteroaryloxy or amido group, or a detectable label attached through a linking group; or (R′)2 represents an alkylidene group of formula=C(R′″)2 wherein each R′″ may be the same or different and is selected from the group comprising hydrogen and halogen atoms and alkyl groups; and wherein said molecule may be reacted to yield an intermediate in which each R″ is exchanged for H or, where Z is —C(R′)2-F, the F is exchanged for OH, SH or NH2, preferably OH, which intermediate dissociates under aqueous conditions to afford a molecule with a free 3′OH; with the proviso that where Z is —C(R′)2-S—R″, both R′ groups are not H. 1. (canceled)2. (canceled)3. A modified nucleoside triphosphate molecule comprising a base and a deoxyribose sugar moiety , wherein the 3′ carbon atom of the sugar moiety has covalently attached thereto a group of the structure:{'br': None, '—O—Z'}wherein Z is a removable protecting group comprising an azido group.4. The molecule of claim 3 , wherein the removable protecting group is azidomethyl.5. The molecule of claim 4 , wherein the base is a purine claim 4 , a pyrimidine or a deazapurine.6. The molecule of claim 4 , wherein the base is adenine claim 4 , 7-deazaadenine claim 4 , guanine claim 4 , or 7-deazaguanine.7. The molecule of claim 4 , wherein the base is cytosine claim 4 , thymine or uracil.8. The molecule of claim 4 , wherein the base is linked ...

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Номер записи: 85
17-04-2014 дата публикации

SUBSTITUTED 2'-THIO-BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM

Номер: US20140106451A1
Автор: Prakash Thazha P., Swayze Eric E.
Принадлежит:

Provided herein are novel bicyclic nucleosides, oligomeric compounds that include such bicyclic nucleosides and methods of using the oligomeric compounds. More particularly, the novel bicyclic nucleosides comprise a furanose ring system having a bridge comprising a 4′-methylene group attached to a 2′-sulfoxide or sulfone group and optionally including one or more substituent groups attached to the 4′-methylene and or the 5′-position. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. 2. The bicyclic nucleoside of wherein Bx is an optionally protected pyrimidine claim 1 , substituted pyrimidine claim 1 , purine or substituted purine.3. The bicyclic nucleoside of wherein Bx is uracil claim 2 , thymine claim 2 , cytosine claim 2 , 4-N-benzoylcytosine claim 2 , 5-methylcytosine claim 2 , 4-N-benzoyl-5-methylcytosine claim 2 , adenine claim 2 , 6-N-benzoyladenine claim 2 , guanine or 2-N-isobutyrylguanine.4. The bicyclic nucleoside of wherein at least one of Q claim 1 , Q claim 1 , Gand Gis CHand the remaining of Q claim 1 , Q claim 1 , Gand Gare each H.5. The bicyclic nucleoside of wherein Q claim 1 , Q claim 1 , Gand Gare each H.6. The bicyclic nucleoside of wherein Tis 4 claim 1 ,4′-dimethoxytrityl and Tis diisopropylcyanoethoxy phosphoramidite.7. The bicyclic nucleoside of wherein n is 1 and the configuration at the sulfur atom is R.8. The bicyclic nucleoside of wherein n is 1 and the configuration at the sulfur atom is S.9. The bicyclic nucleoside of wherein n is 2.10. The bicyclic nucleoside of wherein Q claim 1 , Q claim 1 , Gand Gare each H claim 1 , Tis 4 claim 1 ,4′-dimethoxytrityl and Tis diisopropylcyanoethoxy phosphoramidite.12. The oligomeric compound of wherein each Bx is claim 11 , independently claim 11 , uracil claim 11 , thymine claim 11 , cytosine claim 11 , 4-N-benzoylcytosine claim 11 , 5-methylcytosine claim 11 , 4-N-benzoyl- ...

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Номер записи: 86
10-02-2022 дата публикации

CYCLIC PHOSPHATE SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES

Номер: US20220040214A1
Автор: Alexandre Francois-Rene, Bogen Stephane, Dousson Cyril B., Dukhan David, Milhau Julien, Parsy Christophe Claude, Rahali Rachid, Rouviere Claire Pierra
Принадлежит:

The present invention relates to Cyclic Phosphate Substituted Nucleoside Derivatives of Formula (I): 2. The compound of claim 1 , wherein A is O claim 1 , or a pharmaceutically acceptable salt thereof.3. The compound of claim 2 , wherein Ris methyl claim 2 , or a pharmaceutically acceptable salt thereof.4. The compound of claim 2 , wherein Ris selected from Cl claim 2 , —N claim 2 , —CN claim 2 , and —C≡CH claim 2 , or a pharmaceutically acceptable salt thereof.5. The compound of claim 4 , wherein B is 9-guaninyl claim 4 , 1-cytosinyl claim 4 , 9-adeninyl claim 4 , or 1-urcilyl claim 4 , or a pharmaceutically acceptable salt thereof.7. The compound of claim 1 , wherein X is a bond claim 1 , or a pharmaceutically acceptable salt thereof.8. The compound of claim 7 , wherein Y is a bond claim 7 , or a pharmaceutically acceptable salt thereof.9. The compound of claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , t-butyl claim 1 , n-pentyl claim 1 , cyclopentyl or cyclohexyl claim 1 , or a pharmaceutically acceptable salt thereof.11. The compound of claim 1 , wherein X is a bond and Z is —CHR— claim 1 , and wherein Ris selected from H claim 1 , C-Calkyl claim 1 , —O—(C-Calkyl) claim 1 , —C(O)O—(C-Calkyl) and —O—C(O)—(C-Calkyl) claim 1 , or a pharmaceutically acceptable salt thereof.12. The compound of claim 10 , wherein Ris H and Y is —CH— or —CH(CH)— claim 10 , or a pharmaceutically acceptable salt thereof.14. A pharmaceutical composition comprising an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.15. The pharmaceutical composition of claim 14 , further comprising a second therapeutic agent selected from the group consisting of HCV protease inhibitors claim 14 , HCV NS5A inhibitors claim 14 , and HCV NS5B polymerase inhibitors.16. The pharmaceutical composition of claim 15 , further comprising a third therapeutic agent selected from the group ...

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Номер записи: 87
28-01-2016 дата публикации

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Номер: US20160024136A1
Автор: Beigelman Leonid, Smith David Bernard, Wang Guangyi
Принадлежит:

Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs. 2. The compound of claim 1 , wherein Ris halo.3. The compound of claim 1 , wherein Ris —OR.4. The compound of claim 3 , wherein Ris hydrogen.5. The compound of claim 1 , wherein Ris Nor NH.6. The compound of claim 1 , wherein Ris an optionally substituted Calkyl.7. The compound of claim 1 , wherein both - - - - - - are each absent.8. The compound of claim 7 , wherein Ris —OH.9. The compound of claim 7 , wherein Ris hydrogen.11. The compound of claim 10 , wherein Ris an optionally substituted N-linked amino acid or is an optionally substituted N-linked amino acid ester derivative; and Ris an optionally substituted N-linked amino acid or is an optionally substituted N-linked amino acid ester derivative.15. The compound of claim 10 , wherein Ris an optionally substituted N-linked amino acid or is an optionally substituted N-linked amino acid ester derivative; and Ris an —O-optionally substituted aryl claim 10 , an —O-optionally substituted heteroaryl or an —O-optionally substituted heterocyclyl.17. The compound of claim 10 , wherein Zis O.18. The compound of claim 1 , wherein both - - - - - - are each a single bond.19. The compound of claim 18 , wherein Ris an —O-optionally substituted Calkyl.20. (canceled)22. (canceled)24. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent claim 1 , excipient or combination thereof.25. A method of ameliorating or treating a HCV infection comprising administering to a subject suffering from the HCV infection an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.26. A method for inhibiting replication of a hepatitis C virus comprising contacting a cell ...

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Номер записи: 88
17-04-2014 дата публикации

Fused Pentacyclic Polyethers

Номер: US20140107060A1
Автор: Abraham William M., Baden Daniel G., Bourdelais Andrea J., Michelliza Sophie
Принадлежит: UNIVERSITY OF NORTH CAROLINA AT WILMINGTON

Disclosed are polycyclic polyether compounds of formula I and pharmaceutical compositions comprising such compounds. 23-. (canceled)4. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound claim 1 , pharmaceutically acceptable salt claim 1 , solvate claim 1 , hydrate claim 1 , ester claim 1 , amide claim 1 , or isomer of claim 1 , and at least one pharmaceutically acceptable carrier claim 1 , excipient claim 1 , solvent claim 1 , adjuvant claim 1 , diluent claim 1 , or mixtures thereof.56-. (canceled)7. A method of treating mucociliary dysfunction in a subject comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of claim 1 , or pharmaceutically acceptable salts claim 1 , solvates claim 1 , hydrates claim 1 , esters claim 1 , amides claim 1 , or isomers thereof.8. A method of treating mucociliary dysfunction in a subject comprising administering to a subject in need of such treatment a therapeutically effective amount of a pharmaceutical composition of .9. A method of treating claim 1 , preventing claim 1 , or treating and preventing diseases associated with decreased mucus clearance in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of or pharmaceutically acceptable salts claim 1 , solvates claim 1 , hydrates claim 1 , esters claim 1 , amides claim 1 , or isomers thereof.10. A method of treating claim 4 , preventing claim 4 , or treating and preventing diseases associated with decreased mucus clearance in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a pharmaceutical composition of .11. A method of treating diseases associated with decreased mucus clearance in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of or pharmaceutically acceptable salts claim 1 , ...

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Номер записи: 89
22-01-2015 дата публикации

NUCLEOSIDES WITH ANTIVIRAL AND ANTICANCER ACTIVITY

Номер: US20150025220A1
Автор: Wagner Carston R.
Принадлежит:

The invention provides a compound of formula I: 1. (canceled)3. The compound or salt thereof of wherein the peptide contains 2 to 25 peptidyl residues.4. The compound or salt thereof of wherein the peptide contains 5 to 20 peptidyl residues.5. The compound or salt thereof of wherein the peptide is linked to the phosphorous through the N-terminal nitrogen. This application is a continuation of U.S. application Ser. No. 14/229,292, filed on Mar. 28, 2014, which is a continuation of U.S. application Ser. No. 13/753,252, filed on Jan. 29, 2013, which issued as U.S. Pat. No. 8,765,935 on Jul. 1, 2014, which is a continuation of U.S. Ser. No. 11/721,325, filed on Aug. 18, 2009, which issued as U.S. Pat. No. 8,399,428 on Mar. 19, 2013, which is a National Stage Application of PCT/US2005/044442 filed on Dec. 8, 2005, and published as WO 2006/063149 on Jun. 15, 2006, which claims priority to U.S. Provisional Application Ser. No. 60/634,677, filed on Dec. 9, 2004, which applications and publications are incorporated by reference herein in their entirety.This invention was made with government support under CA089615 awarded by the National Institutes of Health. The government has certain rights in the invention.Histidine triad enzymes are a superfamily of relatively small (MW 28-34 Kda), homodimeric nucleoside monophosphate hydrolases and transferases containing an active site motif related to His-X-His-X-His-X—X, where X is a hydrophobic amino acid (Bieganowski, P., et al., 2002, 277, 10852-10860). The HINT branch is the most ancient branch, having representatives in all forms of life (Bieganowski, P., et al., 2002, 277, 10852-10860; and Brenner, C., et al., 1997, 4, 231-238).The signature histidine triad residues were shown to be largely responsible for stabilizing binding to the phosphates, while the base appeared to be sandwiched between two phenylalanines and an isoleucine (Brenner, C., et al., 1997, 4, 231-238; and Lima, C. D., et al., 1997, 278, 286-290). Further ...

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Номер записи: 90
23-01-2020 дата публикации

Substituted nucleosides, nucleotides and analogs thereof

Номер: US20200024297A1
Автор: David Bernard Smith, Guangyi Wang, Jerome Deval, Leonid Beigelman, Marija Prhavc
Принадлежит: Janssen Biopharma Inc

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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Номер записи: 91
28-01-2021 дата публикации

MODIFIED 2' AND 3'-NUCLEOSIDE PRODRUGS FOR TREATING FLAVIVIRIDAE INFECTIONS

Номер: US20210024565A1
Автор: Gosselin Gilles, La Colla Paolo, SOMMADOSSI Jean-Pierre, STORER RICHARD
Принадлежит:

2′ and/or 3′ prodrugs of 1′, 2′, 3′ or 4′-branched nucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions. 2. A compound of claim 1 , wherein B is a 3-7 membered carbocyclic ring.3. A compound of claim 1 , wherein B is a 3-7 membered heterocyclic ring having one or more O claim 1 , S and/or N atoms.4. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.5. A method for the treatment of a host infected with a hepatitis C virus claim 1 , comprising administering an effective treatment amount of a compound as claimed in claim 1 , or a pharmaceutically acceptable salt thereof.6. The method of claim 5 , wherein the compound or pharmaceutically acceptable salt thereof is administered in combination or alternation with a second anti-viral agent.7. The method of claim 6 , wherein the second anti-viral agent is selected from the group consisting of an interferon claim 6 , a ribavirin claim 6 , an interleukin claim 6 , a NS3 protease inhibitor claim 6 , a cysteine protease inhibitor claim 6 , a phenan-threnequinone claim 6 , a thiazolidine derivative claim 6 , a thiazolidine claim 6 , a benzanilide claim 6 , a phenan-threnequinone claim 6 , a helicase inhibitor claim 6 , a polymerase inhibitor claim 6 , a nucleotide analogue claim 6 , a gliotoxin claim 6 , a cerulenin claim 6 , an antisense phosphorothioate ...

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Номер записи: 92
28-01-2021 дата публикации

Nucleoside analogues for the treatment of parasitic infections

Номер: US20210024566A1
Автор: Fabian HULPIA, Guy CALJON, Louis Maes, Serge Van Calenbergh
Принадлежит: UNIVERSITEIT ANTWERPEN, Universiteit Gent

The present invention relates to novel nucleoside analogues and compositions containing said nucleoside analogues. Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the diagnosis, prevention and/or treatment of parasitic infections, more specifically for use in the diagnosis, prevention and/or treatment of a Trypanosoma infection.

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Номер записи: 93
24-04-2014 дата публикации

DINUCLEOTIDE COMPOUNDS FOR HCV INFECTION

Номер: US20140112886A1
Автор: ARUMUGASAMY Jeevanandam, MAYES Benjamin Alexander, MOUSSA Adel M., WANG Jingyang
Принадлежит:

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds comprise two 2′-methyl nucleotides linked according to Formula I: 4. The compound of wherein Baseis guanine claim 2 , 6-O-methyl-guanine claim 2 , 6-O-ethyl-guanine claim 2 , uracil claim 2 , 5′-fluorouracil claim 2 , adenine claim 2 , 2′ claim 2 ,6′-diaminopurine claim 2 , thymine or cytosine.5. The compound of wherein Baseis guanine claim 3 , 6-O-methyl-guanine claim 3 , 6-O-ethyl-guanine claim 3 , uracil claim 3 , 5′-fluorouracil claim 3 , adenine claim 3 , 2′ claim 3 ,6′-diaminopurine claim 3 , thymine or cytosine.6. The compound of wherein Baseis guanine claim 2 , 6-O-methyl-guanine claim 2 , 6-O-ethyl-guanine claim 2 , uracil claim 2 , 5′-fluorouracil claim 2 , adenine claim 2 , 2′ claim 2 ,6′-diaminopurine claim 2 , thymine or cytosine.7. The compound of wherein Ris —OH.8. The compound of wherein Ris —F.9. The compound of wherein Ris —OH.10. The compound of wherein Ris —F.11. (canceled)12. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient claim 1 , carrier or diluent.13. The pharmaceutical composition of claim 12 , wherein the composition is an oral formulation.14. A method for the treatment of a host infected with a hepatitis C virus claim 1 , comprising the administration of an effective treatment amount of a compound of .15. The method of claim 14 , wherein the host is a human.16. The method of claim 14 , wherein the administration directs a substantial amount of the compound claim 14 , or a pharmaceutically acceptable salt or stereoisomer thereof claim 14 , to the liver of the host.17. The method of claim 14 , wherein the compound or composition is administered in ...

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Номер записи: 94
24-04-2014 дата публикации

2',4'-BRIDGED NUCLEOSIDES FOR HCV INFECTION

Номер: US20140112887A1
Автор: MAYES Benjamin Alexander, MOUSSA Adel M., STEWART Alistair James
Принадлежит:

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2′,4′-bridged nucleosides which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human. In certain embodiments, the 2′,4′-bridged nucleosides are of Formula 3001: 3. The compound of claim 2 , wherein each B is independently guanine claim 2 , 2′-ethoxylguanine claim 2 , cytosine claim 2 , adenine claim 2 , 2′ claim 2 ,6′-diaminopurine claim 2 , thymine claim 2 , uracil claim 2 , or 5′-fluorouracil.5. The compound of claim 4 , wherein each Ris independently branched hydroxyalkyl.6. The compound of claim 4 , wherein each Ris —C(CH)CHOH.8. (canceled)10. (canceled)12. (canceled)14. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient claim 1 , carrier or diluent.15. The pharmaceutical composition of claim 14 , wherein the composition is an oral formulation.16. A method for the treatment of a host infected with a hepatitis C virus claim 1 , comprising the administration of an effective treatment amount of the compound of .17. The method of claim 16 , wherein the host is a human.18. The method of claim 16 , wherein the administration directs a substantial amount of the compound claim 16 , or pharmaceutically acceptable salt or stereoisomer thereof claim 16 , to a liver of the host.19. The method of claim 16 , wherein the compound is administered in combination or alternation with a second anti-viral agent selected from the group consisting of an interferon claim 16 , a nucleotide analogue claim 16 , a polymerase inhibitor claim 16 , an NS3 protease inhibitor claim 16 , an NS5A inhibitor claim 16 , an entry inhibitor claim 16 , a non ...

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Номер записи: 95
02-02-2017 дата публикации

ASYMMETRIC AUXILIARY GROUP

Номер: US20170029445A1
Автор: Shimizu Mamoru, Wada Takeshi
Принадлежит:

To provide a chiral reagent or a salt thereof. 3. The chiral reagent or a salt thereof in accordance with claim 2 , wherein each of Gand Gis a group of formula (II) claim 2 , wherein Gto Gare independently a hydrogen atom claim 2 , a nitro group claim 2 , a halogen atom claim 2 , a cyano group or Calkyl group.4. The chiral reagent or a salt thereof in accordance with claim 2 , wherein each of Gand Gis a group of formula (II) claim 2 , wherein each of Gto Gis a hydrogen atom.5. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom claim 2 , and Gis a group of formula (II) claim 2 , wherein Gto Gare independently a hydrogen atom claim 2 , a nitro group claim 2 , a halogen atom claim 2 , a cyano group or Calkyl group.6. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom and Gis a group of formula (II) claim 2 , wherein each of Gand Gis a hydrogen atom and Gis a nitro group.7. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom claim 2 , and Gis a group of formula (III) claim 2 , wherein Gto Gare independently Calkyl group claim 2 , Caryl group claim 2 , Caralkyl group claim 2 , Calkyl Caryl group claim 2 , Calkoxy Caryl group claim 2 , or Caryl Calkyl group.8. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom claim 2 , and Gis a group of formula (III) claim 2 , wherein Gto Gare independently Calkyl group claim 2 , Caryl group claim 2 , Caralkyl group claim 2 , Calkyl Caryl group claim 2 , Calkoxy Caryl group claim 2 , or Caryl Calkyl group.9. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom and Gis a group of formula (III) claim 2 , wherein Gto Gare independently Calkyl group claim 2 , or Caryl group.10. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom and Gis a group of formula (III) claim 2 , wherein Gto Gare ...

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Номер записи: 96
02-02-2017 дата публикации

Uracyl spirooxetane nucleosides

Номер: US20170029455A1
Автор: Abdellah Tahri, Ioannis Nicolaos Houpis, Pierre Jean-Marie Bernard Raboisson, Tim Hugo Maria Jonckers
Принадлежит: Janssen Sciences Ireland ULC

The present invention relates to compounds of the formula I: including any possible stereoisomers thereof, wherein R 9 has the meaning as defined herein,or a pharmaceutically acceptable salt or solvate thereof. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors, in HCV therapy.

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Номер записи: 97
02-02-2017 дата публикации

NUCLEOTIDES FOR THE TREATMENT OF LIVER CANCER

Номер: US20170029456A1
Автор: Dousson Cyril B., Dukhan David, Parsy Christophe Claude
Принадлежит: IDENIX Pharmaceuticals LLC

Provided herein are compounds, compositions and methods for the treatment of liver cancer such as hepatocellular carcinoma, cholangiocarcinoma, or biliary tract cancer. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-cancer agents. In certain embodiments, the compounds are nucleoside analogs of Formula I: (I); or a pharmaceutically acceptable salt thereof, wherein Base, Z, Z, Z, Z, V, W, X, Ar, Rand Rare as described herein. 13. The compound of claim 12 , or a pharmaceutically acceptable salt thereof claim 12 , wherein:Ar is aryl or heteroaryl;{'sup': '1', 'sub': 1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10, 'Ris hydrogen, Cto Cunsubstituted alkyl, Cto Csubstituted alkyl, —(Cto Cunsubstituted alkyl)-aryl, —(Cto Csubstituted alkyl)-aryl, —(Cto Cunsubstituted alkyl)-heteroaryl, or —(Cto Csubstituted alkyl)-heteroaryl;'}{'sup': 2', '1′', '2′', '1′', '2′', '1′', '1′', '2′', '1′', '1′', '2', '1′', '2′', '1′', '2′', '1′', '2′', '1′', '2′, 'sub': 1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10, 'Ris Cto Cunsubstituted alkyl, Cto Csubstituted alkyl, —(Cto Cunsubstituted alkyl)-aryl, —(Cto Csubstituted alkyl)-aryl, —(Cto Cunsubstituted alkyl)-heterocyclo, —(Cto Csubstituted alkyl)-heterocyclo, —(Cto Cunsubstituted alkyl)-C(O)OH, —(Cto Csubstituted alkyl)-C(O)OH, —(Cto Cunsubstituted alkyl)-heteroaryl, —(Cto Csubstituted alkyl)-heteroaryl, —(Cto Cunsubstituted alkyl)-NRR, —(Cto Csubstituted alkyl)-NRR, —(Cto Cunsubstituted alkyl)-OH, —(Cto Csubstituted alkyl)-OH, —(Cto Cunsubstituted alkyl)-NR—C(NH)—NRR, —(Cto Csubstituted alkyl)-NR—C(NH)—NRR, —( ...

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Номер записи: 98
04-02-2016 дата публикации

Modified nucleotides

Номер: US20160032378A1
Автор: Colin Barnes, John Milton, Joseph Brennan, Mark Smith, Silke Ruediger, Xiaohai Liu, Xiaolin Wu
Принадлежит: Illumina Cambridge Ltd

The invention provides modified nucleotide or nucleoside molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety having a removable 3′-OH blocking group covalently attached thereto, such that the 3′ carbon atom has attached a group of the structure —O—Z wherein Z is any of —C(R′)2-O—R″, —C(R′)2-N(R″)2, —C(R′)2-N(H)R″, —C(R′)2-S—R″ and —C(R′)2-F, wherein each R″ is or is part of a removable protecting group; each R′ is independently a hydrogen atom, an alkyl, substituted alkyl, arylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclic, acyl, cyano, alkoxy, aryloxy, heteroaryloxy or amido group, or a detectable label attached through a linking group; or (R′)2 represents an alkylidene group of formula ═C(R′″)2 wherein each R′″ may be the same or different and is selected from the group comprising hydrogen and halogen atoms and alkyl groups; and wherein said molecule may be reacted to yield an intermediate in which each R″ is exchanged for H or, where Z is —C(R′)2-F, the F is exchanged for OH, SH or NH2, preferably OH, which intermediate dissociates under aqueous conditions to afford a molecule with a free 3′OH; with the proviso that where Z is —C(R′)2-S—R″, both R′ groups are not H.

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Номер записи: 99
01-02-2018 дата публикации

BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'-BETA-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

Номер: US20180030081A1
Автор: Moussa Adel, SOMMADOSSI Jean-Pierre
Принадлежит:

A compound of the structure: 4. The pharmaceutical composition of claim 1 , in a dosage form.5. The pharmaceutical composition of claim 4 , in an oral dosage form.6. The pharmaceutical composition of claim 5 , in a tablet.7. The pharmaceutical composition of claim 5 , in a capsule.8. The pharmaceutical composition of claim 2 , in a dosage form.9. The pharmaceutical composition of claim 8 , in an oral dosage form.10. The pharmaceutical composition of claim 9 , in a tablet.11. The pharmaceutical composition of claim 9 , in a capsule.12. The pharmaceutical composition of claim 3 , in a dosage form.13. The pharmaceutical composition of claim 12 , in an oral dosage form.14. The pharmaceutical composition of claim 13 , in a tablet.15. The pharmaceutical composition of claim 13 , in a capsule.19. The pharmaceutical composition of claim 16 , in a dosage form.20. The pharmaceutical composition of claim 20 , in an oral dosage form.21. The pharmaceutical composition of claim 21 , in a tablet.22. The pharmaceutical composition of claim 21 , in a capsule.23. The pharmaceutical composition of claim 17 , in a dosage form.24. The pharmaceutical composition of claim 23 , in an oral dosage form.25. The pharmaceutical composition of claim 24 , in a tablet.26. The pharmaceutical composition of claim 24 , in a capsule.27. The pharmaceutical composition of claim 18 , in a dosage form.28. The pharmaceutical composition of claim 27 , in an oral dosage form.29. The pharmaceutical composition of claim 28 , in a tablet.30. The pharmaceutical composition of claim 28 , in a capsule. This application is a continuation of U.S. Ser. No. 15/063,461 filed on Mar. 7, 2016 and claims priority to U.S. Ser. No. 62/129,319 filed on Mar. 6, 2015; U.S. Ser. No. 62/253,958 filed on Nov. 11, 2015; and, U.S. Ser. No. 62/276,597 filed on Jan. 8, 2016. Each of these references is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses thereof ...

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Номер записи: 100