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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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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 20332. Отображено 100.
12-01-2012 дата публикации

5'-modified bicyclic nucleic acid analogs

Номер: US20120010393A1
Автор: Balkrishen Bhat, Eric E. Swayze, Punit P. Seth
Принадлежит: ISIS PHARMACEUTICALS INC

The present invention provides 5′-modified bicyclic nucleoside analogs and oligomeric compounds comprising at least one of these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 5′-carbon. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including for example enhanced nuclease resistance.

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Номер записи: 1
12-01-2012 дата публикации

Preparation of 2-chloro-9-(2'-deoxy-2'-fluoro-Beta-D-arabinofuranosyl)-adenine

Номер: US20120010397A1
Автор: Julian Paul Henschke, Lijun Mei, Xiaoheng Zhang, Yung-Fa Chen
Принадлежит: Scinopharm Taiwan Ltd

A process for making clofarabine comprising: fluorinating a compound of formula VII wherein each R 4 is independently a hydroxy protecting group, OR 6 is a leaving group, with a fluorinating agent in the presence of guanidine carbonate to give a compound of formula VIII: wherein R 4 is as defined above; and deprotecting the compound of formula VIII to give the clofarabine.

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Номер записи: 2
02-02-2012 дата публикации

Engineered fluorescent dye labeled nucleotide analogs for dna sequencing

Номер: US20120028248A1
Автор: Arkadusz Bibillo, Gene Shen, Paul Peluso
Принадлежит: Pacific Biosciences of California Inc

Engineered nucleotide compositions, having polymerase interacting components that improve the interactivity of the polymerase and the nucleotide, particularly for nucleic acid sequencing applications. Compositions include the interactive polymerases along with the nucleotide analogs. Kits, methods and systems are provided for analysis of nucleoc acid synthesis reactions.

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Номер записи: 3
09-02-2012 дата публикации

4'-substituted nucleoside derivatives as inhibitors of hcv rna replication

Номер: US20120034184A1
Автор: Christopher John Hobbs, Isabel Najera, John Herbert Merrett, Joseph Armstrong Martin, Nobuo Shimma, Rene Robert Devos, Takuo Tsukuda, Wen Rong Jiang
Принадлежит: Individual

The present invention relates to the use of nucleoside derivatives of formula I wherein B signifies a 9-purinyl residue B1 of formula or a 1-pyrimidyl residue B2 of formula wherein the symbols are as defined in the specification, and of pharmaceutically acceptable salts thereof; for the treatment of diseases mediated by the Hepatitis C Virus (HCV), for the preparation of a medicament for such treatment and to pharmaceutical compositions containing such compounds.

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Номер записи: 4
01-03-2012 дата публикации

Cyanine dyes

Номер: US20120052506A1
Автор: David Sun, Gene Shen, Stephen Yue
Принадлежит: Pacific Biosciences of California Inc

The invention provides a novel class of cyanine dyes that are functionalized with sulfonic acid groups and a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates.

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Номер записи: 5
01-03-2012 дата публикации

Phospholinked dye analogs with an amino acid linker

Номер: US20120052507A1
Автор: Gene Shen
Принадлежит: Pacific Biosciences of California Inc

In various embodiments, the present invention provides fluorescent dyes that are linked to another species through an amino acid or peptide linker. In an exemplary embodiment, the dye is linked to a polyphosphate nucleic acid through an amino acid or peptide linker. These conjugates find use in single molecule DNA sequencing and other applications. In various embodiments, the dye moiety is a cyanine dye. Cyanine dyes that are highly charged, such as those including muliple sulfonate, alkylsulfonate, carboxylate and/or alkylcarboxylate moieties are examples of cyanine dyes of use in the compounds of the invention.

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Номер записи: 6
08-03-2012 дата публикации

Phosphonate Compounds

Номер: US20120058975A1
Автор: Ganesh D. Kini, James R. Beadle, Karl Y. Hostetler
Принадлежит: UNIVERSITY OF CALIFORNIA

The present invention relates to phosphonate compounds, compositions containing them, processes for obtaining them, and their use for treating a variety of medical disorders, e.g., osteoporosis and other disorders of bone metabolism, cancer, viral infections, and the like.

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Номер записи: 7
08-03-2012 дата публикации

Methods of using oligomeric compounds comprising 2'-substituted nucleosides

Номер: US20120059045A1
Автор: Andrew M. Siwkowski, Balkrishen Bhat, Eric E. Swayze, Thazha P. Prakash
Принадлежит: ISIS PHARMACEUTICALS INC

The present disclosure provides oligomeric compounds comprising at least one 2′-fluoroethoxy modified nucleoside of formula I and methods of using these oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds. In certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

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Номер записи: 8
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: 9
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: 10
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: 11
10-05-2012 дата публикации

Method for the solid phase-based production of phosphate-bridged nucleoside conjugates

Номер: US20120116067A1
Автор: Chris Meier, Viktoria Caroline Tonn
Принадлежит: UNIVERSITAET HAMBURG

The invention relates to a method for producing phosphate-bridged nucleoside conjugates. In the method, a cyclosaligenyl nucleotide is produced first, to which a linker is added, which is used to perform the immobilization on a solid phase. A subsequent reaction with corresponding nucleophiles results in the desired phosphate-bridged nucleoside conjugates, which can then again be cleaved from the solid phase-bound linker.

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Номер записи: 12
17-05-2012 дата публикации

Lung-targeted drugs

Номер: US20120122818A1
Автор: James R. Beadle, Karl Y. Hostetler
Принадлежит: UNIVERSITY OF CALIFORNIA

Methods and compositions are provided for treating lung diseases, including but not limited to infections and small cell and non-small cell lung cancer, by conjugating a drug of interest to glycerol ethers or glycerol phosphate ethers.

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Номер записи: 13
14-06-2012 дата публикации

2'-fluoro arabino nucleosides and use thereof

Номер: US20120149657A1
Автор: Anita T. Fowler, John A. Secrist, III, Kamal N. Tiwari
Принадлежит: Southern Research Institute

A method of treating cancer using certain 2′-fluoro arabino nucleosides is provided. Also provided are compounds represented by the formula: (I & A) wherein R is alkyl; and pharmaceutically acceptable salts thereof; and pharmaceutical compositions containing these compounds.

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Номер записи: 14
05-07-2012 дата публикации

Nicotyl riboside compositions and methods of use

Номер: US20120172584A1
Автор: Anthony Andrew Sauve, TIANLE Yang
Принадлежит: CORNELL UNIVERSITY

The invention relates to compositions of nicotinoyl ribosides and nicotinamide riboside derivatives and their methods of use. In some embodiments, the invention relates to methods of making nicotinoyl ribosides. In some embodiments, the invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinoyl riboside. In further embodiments, the invention relates to methods of using nicotinoyl ribosides and nicotinamide riboside derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival.

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Номер записи: 15
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: 16
02-08-2012 дата публикации

Methods for transdifferentiation of body tissues

Номер: US20120196826A1
Автор: Steven Baranowitz
Принадлежит: Individual

The invention relates to methods for transdifferentiation of body tissues which can be used to generate specific cell types needed for regenerating organs or body parts, following cellular degeneration, injury or amputation. The present invention also describes the use of tissue transdifferentiation for treating cancer and autoimmune disease.

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Номер записи: 17
16-08-2012 дата публикации

Bridged artificial nucleoside and nucleotide

Номер: US20120208991A1
Автор: Aiko Yahara, Masaru Nishida, Satoshi Obika, Tetsuya Kodama, Yoshiyuki Hari
Принадлежит: Osaka University NUC

It is an object of the present invention to provide a novel molecule for antisense therapies which is not susceptible to nuclease degradation in vivo and has a high binding affinity and specificity for the target mRNAs and which can efficiently regulate expression of specific genes. The novel artificial nucleoside of the present invention has an amide bond introduced into a bridge structure of 2′,4′-BNA/LNA. The oligonucleotide containing the 2′,4′-bridged artificial nucleotide has a binding affinity for a single-stranded RNA comparable to known 2′,4′-BNA/LNA and has an increased nuclease resistance over LNA. Particularly, it is expected to be applied to nucleic acid drugs because of its much stronger binding affinity for single-stranded RNAs than S-oligo's affinity

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Номер записи: 18
30-08-2012 дата публикации

Method for the manufacture of 2-fluoro-ara-adenine

Номер: US20120220762A1
Автор: Clemens Bothe, Joachim Rehse, Mathias Berwe
Принадлежит: Alcafleu Management GmbH and Co KG

A method is described for the manufacture of pure 2-fluoro-ara-adenine of Formula (I) from 2-fluoro-ara-adenine triacetate using potassium carbonate (K 2 CO 3 ), wherein the 2-fluoro-ara-adenine has a reduced dimer contents, as well as the compound 2-fluoro-ara-adenine having a dimer contents of ≦0.3%.

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Номер записи: 19
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: 20
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: 21
11-10-2012 дата публикации

Inhibitors of e1 activating enzymes

Номер: US20120258927A1
Автор: Edward J. Olhava, Stepan Vyskocil, Steven P. Langston
Принадлежит: Millennium Pharmaceuticals Inc

This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

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Номер записи: 22
25-10-2012 дата публикации

Sialochimeric compounds

Номер: US20120269771A1
Автор: Anna Maria Veronesi, Emanuela Peschechera, Pablo E.A. Rodriguez, Paolo Alberto Veronesi
Принадлежит: Therapicon Srl

The present invention discloses a new class of compounds that exhibit an inhibitory effect on influenza virus type A and B, which may or may not be resistant to other drugs, as well as on other types of viruses, such as flavivirus but also on protozoa and other micro-organisms, their preparation methods, pharmaceutical formulations containing them and their use as medicinal products for the treatment of various conditions caused by particular microorganisms, including viruses, bacteria and protozoa, which affect animal and human health.

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Номер записи: 23
15-11-2012 дата публикации

Certain Compounds, Compositions and Methods

Номер: US20120289475A1
Автор: Bridget Duvall, Dana V. Ferraris, Gregory S. Hamilton, Rena Lapidus, Takashi Tsukamoto
Принадлежит: Eisai Inc

The present invention provides certain tetrahydrouridine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of making and using such compounds.

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Номер записи: 24
06-12-2012 дата публикации

Compounds and methods for treating bacterial infections

Номер: US20120309701A1
Автор: Corinne Cusumano, James W. Janetka, Jerome S. Pinkner, Scott Hultgren, Zhenfu Han
Принадлежит: Washington University in St Louis WUSTL

The present invention encompasses compounds and methods for treating urinary tract infections.

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Номер записи: 25
13-12-2012 дата публикации

Novel nucleic acid prodrugs and methods of use thereof

Номер: US20120316224A1
Автор: Gregory L. Verdine, Meena Meena, Naoki Iwamoto
Принадлежит: Ontorii Inc

Described herein are nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties. Also described herein are methods of making and using nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties.

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Номер записи: 26
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: 27
20-12-2012 дата публикации

Cytosine analogue, a method of preparation of a cytosine analogue, a dna methyltransferase 1 inhibitor, a method for dna methylation inhibition, the use of the analogue in the treatment of diseases associated with deviations from normal dna methylation

Номер: US20120322755A1
Автор: Agnieszka Fedoruk-Wyszomirska, Beata Plitta, Eliza Wyszko, Ewelina Adamska, Jan Barciszewski, Malgorzata Giel-Pietraszuk, Marcin Chmielewski, Maria Markiewicz, Tadeusz Kulinski, Wojciech T. Markiewicz
Принадлежит: INSTYTUT CHEMII BIOORGANICZNEJ PAN

This invention provides a cytosine analogue, a method of preparation of a cytosine analogue, a DNA rhethyltransferase 1 inhibitor, a method for DNA methylation inhibition, the use of the analogue in the treatment of diseases associated with deviations from normal DNA methylation. More precisely, the invention relates to various derivatives of cytosine, as well as methods of preparation of mono- and multi-1,4,5 and 6-substituted cytosines. In general, the solution relates to providing effective modulators of DNA methylation which could be used in prevention and treatment of diseases associated with DNA methylation level disorders.

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Номер записи: 28
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: 29
24-01-2013 дата публикации

Modular nucleotide compositions and uses therefor

Номер: US20130022968A1
Автор: Jeffrey Wegener, Jonas Korlach
Принадлежит: Pacific Biosciences of California Inc

Nucleic acid compositions, methods of making and using such compositions that comprise modular functional groups that can be configured to provide desired functionality to different nucleotide types, through a swappable and preferably non-covalent linkage component. Such compositions are useful in a variety of applications including nucleic acid analyses.

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Номер записи: 30
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: 31
14-02-2013 дата публикации

Compounds, Compositions and Methods of Using Same for Modulating Uric Acid Levels

Номер: US20130040907A1
Автор: David A. PAISNER, Esmir Gunic, Jean-Luc Girardet, Jean-Michel Vernier, Martina E. Tedder
Принадлежит: Ardea Biociences Inc

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

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Номер записи: 32
21-02-2013 дата публикации

N6-substituted adenosine derivatives and n6-substituted adenine derivatives and uses thereof

Номер: US20130045942A1
Автор: Chenggen Zhu, Jiachen Zi, Jiangong Shi, Jianjun Zhang, Li Sheng, Min Li, Ruiming Xu, Sheng Lin, Xiaona Fan, Yafang Wang, Yan Li, Ying Zhang, Yongchun Yang, Zhenggang Yue
Принадлежит: Institute of Materia Medica of CAMS

The present invention provides N 6 -substituted adenosine derivatives and N 6 -substituted adenine derivatives, manufacturing methods thereof, a pharmaceutical composition comprising the said compounds above, and uses of these compounds in manufacturing medicaments and health-care products for treating insomnia, convulsion, epilepsy, and Parkinson's diseases, and preventing and treating dementia.

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Номер записи: 33
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: 34
28-03-2013 дата публикации

2'-CHLOROACETYLENYL SUBSTITUTED NUCLEOSIDE DERIVATIVES

Номер: US20130078217A1
Автор: Kim In Jong, Or Yat Sun, Wang Guoqiang
Принадлежит:

The present invention relates to 2′-chloroacetylenyl-substituted nucleoside derivatives of the general formula (I): 9. A pharmaceutical composition comprising an inhibitory amount of a compound according to claim 1 , in combination with 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 9 , the method comprising supplying a hepatitis C viral NS3 protease inhibitory amount of the pharmaceutical composition of .13. The method of further comprising administering concurrently an additional anti-hepatitis C virus agent.14. The method of claim 11 , wherein said additional anti-hepatitis C virus agent is selected from the group consisting of α-interferon claim 11 , β-interferon claim 11 , ribavarin claim 11 , and adamantine.15. The method of claim 12 , wherein said additional anti-hepatitis C virus agent is an inhibitor of hepatitis C virus helicase claim 12 , polymerase claim 12 , metalloprotease claim 12 , 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 interferon claim 9 , ribavirin claim 9 , amantadine claim 9 , another HCV protease inhibitor claim 9 , an HCV polymerase inhibitor claim 9 , an HCV helicase inhibitor claim 9 , or an internal ribosome entry site inhibitor.18. The pharmaceutical composition of claim 9 , further comprising pegylated interferon.19. The pharmaceutical composition of claim 9 , further comprising another anti-viral claim 9 , anti-bacterial claim 9 , anti-fungal or anti-cancer agent claim 9 , or an immune modulator.20. The composition of claim 9 , further comprising a cytochrome P450 ...

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Номер записи: 35
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: 36
04-04-2013 дата публикации

ANTI-VIRAL TREATMENT AND ASSAY TO SCREENFOR ANTI-VIRAL AGENT

Номер: US20130085133A1
Автор: Ananthan Subramaniam, Chung Dong Hong, Jonsson Colleen B., Maddox Clinton Boykin, Maddry Joseph A., Pathak Ashish K., Rasmussen Lynn, Severson Bill, White Ellie Lucile
Принадлежит: Sourthern Research Institute Office of Commercialization and Intellectual Prop.

The present disclosure relates to novel compounds of formulas (1) through (19) and to a method for treating humans infected with a virus including various respiratory viruses such as members of the Paramyxoviridae family (respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), measles virus, and mumps virus) with a compound of formulas (1) through (19). The present disclosure also relates to a cytopathic effect (CPE)-based assay that will assess virus-induced CPE for screening of compounds for treating viral diseases or inhibiting a virus. 2. The method of wherein the virus is a respiratory virus.3. The method of wherein the virus is selected from the group consisting of the families Paramyxoviridae claim 1 , human metapneumovirus claim 1 , human parainfluenza virus claim 1 , measles virus claim 1 , and mumps virus.4. The method of wherein the virus is respiratory syncytial virus.6. The method of wherein the virus is a respiratory virus.7. The method of wherein the virus is selected from the group consisting of the families Paramyxoviridae claim 5 , human metapneumovirus claim 5 , human parainfluenza virus claim 5 , measles virus claim 5 , and mumps virus.8. The method of wherein the virus is respiratory syncytial virus.9. A method for screening for compounds for use as an anti-viral agent against a virus which comprises obtaining frozen cells infected with said virus claim 5 , thawing said infected cells and mixing said infected cells with uninfected cells of the same type as the infected cells claim 5 , contacting the mixture of said infected cells and uninfected cells with a compound to be screened and determining the viability of said cells.10. The method of wherein the virus is a respiratory virus.11. The method of wherein the virus is selected from the group consisting of the families Paramyxoviridae claim 9 , human metapneumovirus claim 9 , human parainfluenza virus claim 9 , measles virus claim 9 , and mumps virus. ...

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Номер записи: 37
04-04-2013 дата публикации

NEW WAY OF USING THERMOLABILE GROUPS TO PROTECT HYDROXYL FUNCTIONS, AND NEW COMPOUNDS FOR IMPLEMENTING THE PROCEDURE

Номер: US20130085272A1
Автор: Chmielewski Marcin Krzysztof
Принадлежит: INSTYTUT CHEMII BIOORGANICZNEJ POLSKIEJ AKADEMII NAUK

A procedure for using thermolabile groups to protect a hydroxyl function, above all in nucleosides, nucleotides, oligomers, nucleic acids during the reactions of organic synthesis. Various new compounds that can be used to implement the procedure. The way of using thermolabile groups to protect hydroxyl functions consists in a primary, secondary and tertiary hydroxyl group converting into a groups during the reaction between a compound and a compound whose hydroxyl group is to be blocked. The blocking reaction is carried out by means of widely known methods appropriate for that purpose in the presence of a chemically basic catalyst. The obtained product has its hydroxyl group blocked. Then the compound with the group blocked can be used for the purposes of various chemical processes. After their completion, the hydroxyl group is unblocked by dissolving it in a solvent at a temperature of 50-95° C. 123-. (canceled)27. The way of using thermolabile groups to protect a hydroxyl function according to claim 26 , wherein a compound of general formula 1 is used claim 26 , where Rstands for H; Rstands for H; R claim 26 , R claim 26 , R claim 26 , R claim 26 , Rare equal and stand for H; Rstands for CH.28. The way of using thermolabile groups to protect a hydroxyl function according to claim 26 , wherein the unblocking is carried out at a temperature of 70 -90° C.29. The way of using thermolabile groups to protect a hydroxyl function according to claim 26 , wherein a solvent can be made up of acetonitrile; or a homogenous mixture of alcohol and water; or a water buffer of a pH of 6-8; or a mixture of acetonitrile and a water buffer of a pH of 6-8 claim 26 , the volume fraction of the former being 5% to 50% claim 26 , and the concentration of the blocked form in the mixture being 0.5 mole to 0.01 millimole; or a mixture of alcohol with a water buffer of a pH of 6-8 claim 26 , the volume fraction of the former being 5% to 50% claim 26 , and the concentration of the blocked ...

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Номер записи: 38
11-04-2013 дата публикации

Fluorescent dyes

Номер: US20130089853A1
Автор: Praveen Pande, Zaiguo Li
Принадлежит: Enzo Life Sciences Inc

Provided are various compounds comprising the formula Also provided are fluorescent dyes comprising the above compound. Additionally, a fluorescence energy transfer system is provided that comprises the above-described fluorescent dye and a second dye, wherein the second dye is capable of energy transfer with the fluorescent dye. Further provided is a kit for labeling a target molecule, where the kit comprises the above-described fluorescent dye with additional reagents useful for labeling the target molecule. Additionally provided is a target molecule labeled with the above-described fluorescent dye. A method of labeling a target molecule is also provided. The method comprises contacting reactive group Z of the above-described fluorescent dye with the target molecule such that reactive group Z reacts with the target molecule to form a covalent bond between reactive group Z and the target molecule. Also, another method of labeling a target molecule is provided. The method comprises contacting the above-described fluorescent dye, which further comprises a member of a binding pair, with the target molecule, where the target molecule comprises a second member of the binding pair.

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Номер записи: 39
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: 40
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: 41
11-04-2013 дата публикации

CRYSTALLIZATION PROCESS OF CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE

Номер: US20130090466A1
Автор: Bai Jianxin, Chen Xiaochun, Chen Yong, Lin Xiaoqing, Qian Wenbin, Wu Jinglan, Xie Jingjing, Xiong Jian, Ying Hanjie
Принадлежит:

Provided is a crystallization process of cyclic adenosine 3′,5′-monophosphate, which comprises the following steps: 1) reacting an aqueous solution of cyclic adenosine 3′,5′-monophosphate with a base to obtain a salt of cyclic adenosine 3′,5′-monophosphate; 2) reacting the cyclic adenosine 3′,5′-monophosphate salt solution obtained in step 1) with an acid to obtain cyclic adenosine 3′,5′-monophosphate; 3) keeping cyclic adenosine 3′,5′-monophosphate obtained in step 2) at 0-15° C. 110-. (canceled)11. A crystallization method of 3′ ,5′-cyclic adenosine monophosphate , wherein said method comprises the following steps:1) reacting 3′,5′-cyclic adenosine monophosphate aqueous solution with a base to produce 3′,5′-cyclic adenosine monophosphate salt solution;2) reacting the 3′,5′-cyclic adenosine monophosphate salt solution produced in step 1) with an acid to produce 3′,5′-cyclic adenosine monophosphate; and3) preserving the 3′,5′-cyclic adenosine monophosphate produced in step 2) at 0-15° C.12. The method according to claim 11 , wherein in said step 1) claim 11 , 3′ claim 11 ,5′-cyclic adenosine monophosphate aqueous solution is reacted with a base until the pH value of the solution reaches pH 6.0-10.0.13. The method according to claim 12 , wherein said base is one or more selected from ammonia water and sodium hydroxide claim 12 , the concentration of which is 2-10 M.14. The method according to claim 12 , wherein the concentration of said 3′ claim 12 ,5′-cyclic adenosine monophosphate aqueous solution is 15-350 g/L.15. The method according to claim 11 , wherein in said step 2) claim 11 , 3′ claim 11 ,5′-cyclic adenosine monophosphate salt solution is reacted with an acid until the pH value of the solution reaches pH 1.0-5.0.16. The method according to claim 15 , wherein said acid is one or more selected from sulfuric acid claim 15 , hydrochloric acid and phosphoric acid claim 15 , the concentration of which is 0.01-10 M.17. The method according to claim 11 , wherein ...

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Номер записи: 42
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: 43
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: 44
18-04-2013 дата публикации

New Method of Using N-Thio Compounds for Oligonucleotide Synthesis

Номер: US20130096291A1
Автор: He Yigang, Mazur Wieslaw Adam, Sorokin Victor
Принадлежит: GIRINDUS AMERICA, INC.

A method for synthesizing an oligonucleotide which comprises using a sulfurizing agent of general formula (I) for sulfurizing at least one phosphorus internucleotide linkage of a precursor of the oligonucleotide, wherein R is an aryl group or a heteroaryl group, which is bonded to the S-atom through an annular carbon atom; and Rand Rare independently organic residues, preferably a C1-C20 hydrocarbon residue. The method may further comprise purifying the oligonucleotide. Also included is a process for the synthesis of the sulfurizing agent. 2. The method according to claim 1 , wherein R is a halophenyl or alkylphenyl claim 1 , Preferably 4-halophenyl claim 1 , especially preferably 4-chlorophenyl.3. The method according to any one of and wherein Rand Rare selected from lower alkyl or cycloalkyl (C1-C7) claim 1 , phenyl including substituted phenyl and naphthyl groups claim 1 , more preferably a methyl group.4. The method according to any one of to claim 1 , wherein the sulfurizing agent is dissolved in an organic solvent preferably a halogenated hydrocarbon solvent.5. The method according to any one of to claim 1 , wherein the molar ratio of sulfurizing agent to phosphorus internucleotide linkages to be sulfurized is from 1.0 to 2.0.6. The method according to any one of to claim 1 , wherein the precursor of said oligonucleotide contains nucleosides selected from ribonucleosides claim 1 , 2′-deoxyribonucleosides claim 1 , 2′-substituted ribonucleosides claim 1 , 2′-4′-locked-ribonucleosides claim 1 , 3′-amino-ribonucleosides claim 1 , 3′-amino-2′-deoxyribonucleosides.7. The method according to any one of to claim 1 , wherein the phosphorus internucleotide linkage is an H-phosphonate diester bond.8. The method according to claim 7 , wherein the coupling is carried out in solution phase.9. The method according to anyone of to which further comprises a step of purifying the oligonucleotide obtained according to anyone of to .10. The method according to which comprises at ...

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Номер записи: 45
25-04-2013 дата публикации

MODIFIED NUCLEOSIDES, NUCLEOTIDES, AND NUCLEIC ACIDS, AND USES THEREOF

Номер: US20130102034A1
Автор: Schrum Jason P.
Принадлежит:

The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using thereof. 1. A compound comprising a nucleotide that disrupts binding of a major groove binding partner with a nucleic acid comprising the nucleotide , wherein the nucleotide has decreased binding affinity to the major groove binding partner.2. The compound of claim 1 , wherein the nucleotide comprises a chemical modification located on the major groove face of a nucleobase portion of the nucleotide.3. The compound of claim 2 , wherein the nucleobase portion comprises a pyrimidine nucleobase claim 2 , and wherein the chemical modification comprises replacing or substituting an atom of the major groove face of the pyrimidine nucleobase with an amine claim 2 , an SH claim 2 , a methyl claim 2 , an ethyl claim 2 , a chloro or a fluoro group.4. The compound of claim 2 , wherein the chemical modification is located on a sugar portion of the nucleotide.5. The compound of claim 2 , wherein the chemical modification is located on a phosphate backbone of the nucleotide.9. The compound of claim 6 , wherein B is a nucleobase selected from the group consisting of cytosine claim 6 , guanine claim 6 , adenine claim 6 , and uracil.15. A nucleic acid sequence comprising at least two nucleotides claim 6 , the nucleic acid sequence comprising a nucleotide that disrupts binding of a major groove binding partner with the nucleic acid sequence claim 6 , wherein the nucleotide has decreased binding affinity to the major groove binding partner.19. The nucleic acid sequence of claim 16 , wherein B is a nucleobase selected from the group consisting of cytosine claim 16 , guanine claim 16 , adenine claim 16 , and uracil.20. The nucleic acid sequence of claim 16 , wherein the nucleic acid sequence contains a plurality of structurally unique compounds of Formula I-d.21. The nucleic acid sequence of claim 16 , wherein at least 25% of the cytosines are replaced by a compound of Formula I-d ...

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Номер записи: 46
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: 47
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: 48
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: 49
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: 50
02-05-2013 дата публикации

Detection or quantification of desirable target molecules, novel dyes, composite dyes, and oligonucleotides or polynucleotides comprising such dyes

Номер: US20130109847A1
Автор: Cheng Wei, Khazanchi Rajesh, Liu Dakai, Pande Praveen, Rabbani Elazar, Xiang Yuejun
Принадлежит: ENZO LIFE SCIENCES, INC. C/O ENZO BIOCHEM, INC.

The present invention provides dyes, reactive dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins and nucleic acids. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes are also provided that comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been modified by the addition of charged and polar groups to provide beneficial properties. 2. The dye of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , or Rfurther comprises a reactive group.3. The dye of claim 2 , wherein said reactive group comprises a nucleophilic reactive group claim 2 , an electrophilic reactive group claim 2 , a terminal alkene claim 2 , a terminal alkyne claim 2 , a coordinate group or an alkylating agent.4. The dye of claim 3 , wherein said nucleophilic reactive group comprises a thiol claim 3 , amine or hydroxyl group.5. The dye of claim 3 , wherein said electrophilic reactive group comprises an isocyanate claim 3 , isothiocyanate claim 3 , monochlorotriazine claim 3 , dichlorotriazine claim 3 , 4 claim 3 ,6 claim 3 ,-dichloro-1 claim 3 ,3 claim 3 ,5-triazines claim 3 , mono- or di-halogen substituted pyridine claim 3 , mono- or di-halogen substituted diazine claim 3 , maleimide claim 3 , haloacetamide claim 3 , aziridine claim 3 , sulfonyl halide claim 3 , acid halide claim 3 , hydroxysuccinimide ester claim 3 , hydroxysulfosuccinimide ester claim 3 , imido ester claim 3 , hydrazine claim 3 , azidonitrophenol claim 3 , azide claim 3 , 3-(2-pyridyl dithio)-proprionamide claim 3 , glyoxal or aldehyde group.6. The dye of claim 1 , wherein said dye further comprises one or more charged groups or polar groups.7. ...

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Номер записи: 51
02-05-2013 дата публикации

MODIFIED 5' DIPHOSPHATE NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM

Номер: US20130109850A1
Автор: Manoharan Muthiah, Prakash Thazha P., Rajeev Kallanthottathil G., Seth Punit P., Swayze Eric E., Zlatev Ivan
Принадлежит: Isis Pharmaceuticals, Inc

Provided herein are modified 5′ diphosphate nucleosides and oligomeric compounds prepared therefrom. More particularly, modified 5′ diphosphate nucleosides are provided that can be further modified at the 2′ and 5′ positions. 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. The oligomeric compounds are also expected to be useful as primers and probes in diagnostic applications. 150-. (canceled)52. The compound of wherein Bx is uracil claim 51 , thymine claim 51 , cytosine claim 51 , 5-methylcytosine claim 51 , adenine or guanine.53. The compound of any one of wherein r is 1 claims 52 , Mis H and Mis OH.54. The compound of any one of wherein r is 0 claims 53 , Mis O(CH)CN and Mis N[CH(CH)].55. The compound of wherein G is halogen claim 54 , OCH claim 54 , OCHF claim 54 , OCHF claim 54 , OCF claim 54 , OCHCH claim 54 , O(CH)F claim 54 , OCHCHF claim 54 , OCHCF claim 54 , OCH—CH═CH claim 54 , O(CH)—OCH claim 54 , O(CH)—SCH claim 54 , O(CH)—OCF claim 54 , O(CH)—N(R)(R) claim 54 , O(CH)—ON(R)(R) claim 54 , O(CH)—O(CH)—N(R)(R) claim 54 , OCHC(═O)—N(R)(R) claim 54 , OCHC(═O)—N(R)—(CH)—N(R)(R) or O(CH)—N(R)—C(═NR)[N(R)(R)] wherein R claim 54 , R claim 54 , Rand Rare each claim 54 , independently claim 54 , H or C-Calkyl.56. The compound of wherein G is halogen claim 55 , OCH claim 55 , OCF claim 55 , OCHCH claim 55 , OCHCF claim 55 , OCH—CH═CH claim 55 , O(CH)—OCH claim 55 , O(CH)—O(CH)—N(CH) claim 55 , OCHC(═O)—N(H)CH claim 55 , OCHC(═O)—N(H)—(CH)—N(CH)or OCH—N(H)—C(═NH)NH.57. The compound of wherein G is F claim 56 , OCH claim 56 , O(CH)—OCH claim 56 , OCHC(═O)—N(H)CHor OCHC(═O)—N(H)—(CH)—N(CH).58. The compound of wherein G is O(CH)—OCH.59. The compound of wherein each Pg is claim 58 , independently claim 58 , methyl claim 58 , ethyl claim 58 , isopropyl claim 58 , tert-butyl claim 58 , 2-cyanoethyl claim 58 , benzyl claim 58 , phenyl claim 58 , 4- ...

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Номер записи: 52
09-05-2013 дата публикации

QUINOLINE DERIVATIVES USED AS PET IMAGING AGENTS

Номер: US20130116206A1
Автор: Aboagye Eric, Pisaneschi Federica, Smith Graham, Spivey Alan
Принадлежит: IMPERIAL INNOVATIONS LIMITED

There is provided compounds of formula (I), wherein R, R, X, X, and Xhave meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful as positron emission tomography (PET) imaging agents, useful in the treatment of diseases in which inhibition of epidermal growth factor receptor tyrosine kinase activity or the inhibition of HER2 activity is desired and/or required, and useful in the treatment of cancer. 2. A compound as claimed in claim 1 , wherein Rrepresents Hetor a Calkyl group optionally substituted by one or more A groups.3. A compound as claimed in claim 1 , wherein A represents —N(R)R.5. A compound as claimed in claim 1 , wherein Rrepresents a C-alkoxy group optionally substituted by one or more halogen atoms claim 1 , or Het.7. A compound as claimed in claim 1 , wherein Xrepresents a halogen claim 1 , ORor SR.9. A compound as claimed in claim 1 , which is selected from the group:{(E)-3-[4-(3-Chloro-4-fluoro-phenylamino)-3-cyano-7-ethoxy-quinolin-6-ylcarbamoyl]-allyl}-prop-2-ynyl-carbamic acid tert-butyl ester;(E)-Pent-2-en-4-ynoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide;(E)-4-[(2-Fluoroethyl)methyl amino]-but-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxyquinoline-6-yl]amide;(E)-4-[(4-Fluorobenzyl)methylamino]-but-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxyquinoline-6-yl]amide;(E)-4-{[1-(2-Fluoro-ethyl)-1H-[1,2,3]triazol-4-ylmethyl]-amino}-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide hydrochloride;(E)-N-[4-(3-Chloro-4-fluorophenylamino)-3-cyano-7-ethoxyquinolin-6-yl]-3-[1-(2-fluoro-ethyl)-1H-[1,2,3]triazol-4-yl]-acrylamide;(E)-4-Methylamino-but-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-(2-fluoroethoxy)-quinolin-6-yl]-amide hydrochloride;(E)-4-Prop-2-ynylaminobut-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide hydrochloride;(E)-4-Methylamino- ...

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Номер записи: 53
09-05-2013 дата публикации

Compositions and Methods for Treating Cancer

Номер: US20130116207A1
Автор: Belyakov Sergei, Duvall Bridget, Ferraris Dana, Hamilton Gregory, Vaal Mark
Принадлежит: Eisai Inc.

Provided herein are compounds used to inhibit the deamination enzyme responsible for the inactivation of therapeutic compounds, and methods of using them. 5. The method of claim 3 , wherein the CDA substrate is decitabine.6. The method of claim 3 , wherein the CDA substrate is a non-decitabine CDA substrate.7. The method of claim 6 , wherein the CDA substrate is a is selected from the group consisting of gemcitabine claim 6 , 5-azacytidine claim 6 , ara-C claim 6 , tezacitabine claim 6 , 5-fluoro-2′-deoxycytidine claim 6 , and cytochlor.10. A method of treating a cancer in a subject claim 6 , comprising:administering to the subject a CDA substrate;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'sub': 1-6', '2-6, 'administering to the subject a compound of formula I as defined in or a pharmaceutically acceptable salt, a Calkyl ester, or a Calkenyl ester thereof; and'}administering to the subject a pharmaceutical agent selected from an anti-emetic agent, an agent that increases appetite, a cytotoxic or chemotherapeutic agent, or an agent that relieves pain.12. The method of claim 10 , wherein the CDA substrate is decitabine.13. The method of claim 10 , wherein the CDA substrate is a non-decitabine CDA substrate.14. The method of claim 13 , wherein the CDA substrate is a is selected from the group consisting of gemcitabine claim 13 , 5-azacytidine claim 13 , ara-C claim 13 , tezacitabine claim 13 , 5-fluoro-2′-deoxycytidine claim 13 , and cytochlor.15. A packaged cancer treatment comprising a compound of formula I as defined in or a pharmaceutically acceptable salt claim 1 , a Calkyl ester claim 1 , or a Calkenyl ester thereof; andinstructions for using an effective amount of the compound for treating cancer.17. The packaged cancer treatment of claim 15 , further comprising a CDA substrate.18. The packaged cancer treatment of claim 17 , wherein the CDA substrate is decitabine.19. The packaged cancer treatment of claim 17 , wherein the CDA substrate is a non- ...

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Номер записи: 54
09-05-2013 дата публикации

5' MODIFIED NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM

Номер: US20130116420A1
Автор: Prakash Thazha P., Seth Punit P., Swayze Eric E.
Принадлежит: Isis Pharmaceuticals, Inc.

The present invention provides 5′ modified nucleosides and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides having at least one 5′-substituent and an optional 2′ substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. 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. 146-. (canceled)48. The 5′ modified nucleoside of wherein Bx is uracil claim 47 , thymine claim 47 , cytosine claim 47 , 5-methylcytosine claim 47 , adenine or guanine.49. The 5′ modified nucleoside of wherein qand qare each claim 48 , independently claim 48 , OCH claim 48 , OCHCHor OC(H)(CH)and qis O.50. The 5′ modified nucleoside of wherein r is 1 claim 49 , Mis H and Mis hydroxyl or r is 0 claim 49 , Mis O(CH)CN and Mis N[CH(CH)].51. The 5′ modified nucleoside of wherein G is halogen claim 50 , OCH claim 50 , OCHF claim 50 , OCHF claim 50 , OCF claim 50 , OCHCH claim 50 , O(CH)F claim 50 , OCHCHF claim 50 , OCHCF claim 50 , OCH—CH═CH claim 50 , O(CH)—OCH claim 50 , O(CH)—SCH claim 50 , O(CH)—OCF claim 50 , O(CH)—N(R)(R) claim 50 , O(CH)—ON(R)(R) claim 50 , O(CH)—O(CH)—N(R)(R) claim 50 , OCHC(═O)—N(R)(R) claim 50 , OCHC(═O)—N(R)—(CH)—N(R)(R) or O(CH)—N(R)—C(═NR)[N(R)(R)] wherein R claim 50 , R claim 50 , Rand Rare each claim 50 , independently claim 50 , H or C-Calkyl.52. The 5′ modified nucleoside of wherein G is F claim 51 , OCH claim 51 , O(CH)—OCH claim 51 , OCHC(═O)—N(H)CHor OCHC(═O)—N(H)—(CH)—N(CH).53. The 5′ modified nucleoside of wherein g is 1.54. The 5′ modified nucleoside of wherein three of q claim 53 , q claim 53 , qand qare each H.55. The 5′ modified nucleoside of wherein one of qand qis H claim 53 , one of qand qis H and the other two of q claim 53 , q claim 53 , qand qare other than H.56. The 5′ modified nucleoside of wherein ...

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Номер записи: 55
16-05-2013 дата публикации

3'-OH UNBLOCKED, FAST PHOTOCLEAVABLE TERMINATING NUCLEOTIDES AND METHODS FOR NUCLEIC ACID SEQUENCING

Номер: US20130122489A1
Автор: Hersh Megan N., HERTZOG David, LI HONG, Metzker Michael L., MORRIS Sidney E., STUPI Brian, Wu Weidong
Принадлежит:

The present invention relates generally to 3′-OH unblocked nucleotides and nucleosides labeled and unlabeled with 5-methoxy-substituted nitrobenzyl-based photocleavable terminating groups for use in methods and systems related to DNA and RNA sequencing and analysis. These compounds may be used as reversible terminators as they exhibit fast nucleotide incorporation kinetics, single-base termination, high nucleotide selectivity, and rapid terminating group cleavage that results in a naturally occurring nucleotide. 2. The compound of claim 1 , further defined as a compound of formula I.3. The compound of claim 1 , further defined as a compound of formula II.4. The compound of claim 1 , further defined as a compound of formula III.5. The compound of claim 1 , further defined as a compound of formula IV.6. The compound of claim 1 , further defined as a compound of formula V.7. The compound of claim 1 , further defined as a compound of formula VI.8. The compound of claim 1 , further defined as a compound of formula VII.9. The compound of claim 1 , wherein Ris hydroxy.1011-. (canceled)12. The compound of claim 1 , wherein Ris a triphosphate.13. The compound of claim 1 , wherein Ris an α-thiotriphosphate.14. (canceled)15. The compound of claim 1 , wherein Ris hydrogen.16. The compound of claim 1 , wherein Ris hydroxy.17. The compound claim 1 , wherein Ris alkyl.18. (canceled)19. The compound of claim 1 , wherein Ris isopropyl.20. The compound of claim 1 , wherein Ris tert-butyl.21. The compound of claim 1 , wherein Ris hydrogen.22. The compound of claim 1 , wherein Ris nitro.23. The compound of claim 1 , wherein Ris hydrogen.24. The compound of claim 1 , wherein Ris iodo.25. The compound of claim 1 , wherein Ris alkoxy.26. The compound of claim 25 , wherein Ris methoxy.2736-. (canceled)37. The compound of claim 1 , wherein Ris a -linker-reporter.39. The compound of claim 38 , wherein X is alkynediyl.40. The compound of claim 39 , wherein X is —C≡C—.41. The compound of claim ...

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Номер записи: 56
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: 57
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: 58
23-05-2013 дата публикации

Epirubicin Derivatives

Номер: US20130131001A1
Автор: ZHANG Hesheng
Принадлежит:

Disclosed are compounds represented by formula (I), pharmaceutically acceptable salts thereof, solvates thereof, and solvates of the pharmaceutically acceptable salts thereof, 2. A compound of formula (I) claim 1 , a pharmaceutically acceptable salt thereof claim 1 , a solvate thereof claim 1 , or a solvate of the pharmaceutically acceptable salt thereof of claim 1 , wherein Rrepresents H claim 1 , CHor OCH.3. A compound of formula (I) claim 1 , a pharmaceutically acceptable salt thereof claim 1 , a solvate thereof claim 1 , or a solvate of the pharmaceutically acceptable salt thereof of claim 1 , wherein Rrepresents H claim 1 , F claim 1 , CH claim 1 , CHCH claim 1 , OH claim 1 , OCHor OCHCH.4. A compound of formula (I) claim 1 , a pharmaceutically acceptable salt thereof claim 1 , a solvate thereof claim 1 , or a solvate of the pharmaceutically acceptable salt thereof of claim 1 , wherein the optionally substituted saturated heterocyclic hydrocarbyl claim 1 , the optionally substituted unsaturated heterocyclic hydrocarbyl claim 1 , the optionally substituted aromatic heterocyclyl or the optionally substituted fused cyclic group further comprises one or two identical or different other heteroatoms.8. A compound of formula (I) claim 1 , a pharmaceutically acceptable salt thereof claim 1 , a solvate thereof claim 1 , or a solvate of the pharmaceutically acceptable salt thereof of claim 1 , wherein the compound of formula (I) is selected from the group consisting of:3′-pyrrolyl epirubicin,3′-succinimidyl epirubicin,3′-glutarimido epirubicin,3′-maleimidyl epirubicin,3′-(pyridino-(2,3)succinimidyl)epirubicin,3′-(benzo-(2,3)succinimidyl)epirubicin, and3′-butyrolactamyl epirubicin.9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of formula (I) claim 1 , a pharmaceutically acceptable salt thereof claim 1 , a solvate thereof claim 1 , or a solvate of the pharmaceutically acceptable salt ...

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Номер записи: 59
23-05-2013 дата публикации

Lipophilic monophosphorylated derivatives and nanoparticles

Номер: US20130131008A1
Автор: Dharmika S. P. Lansakara-P., Michael A. Sandoval, Zhengrong Cui
Принадлежит: University of Texas System

There are provided, inter alia, lipophilic monophosphorylated derivatives of gemcitabine. There are further provided nanoparticles compositions incorporating lipophilic monophosphorylated derivatives of gemcitabine, pharmaceutical compositions thereof, and a method of treating cancer or a viral infection in a subject in need thereof, which method includes administration of a pharmaceutical composition disclosed herein.

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Номер записи: 60
23-05-2013 дата публикации

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

Номер: US20130131147A1
Автор: Prakash Thazha P., Seth Punit P., Swayze Eric E.
Принадлежит: Isis Pharmaceuticals, Inc.

Provided herein are 2′-amino and 2′-thio bicyclic nucleosides and oligomenc compounds prepared therefrom. The novel bicyclic nucleosides provided herein are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as nuclease resistance. 192-. (canceled)94. The bicyclic nucleoside of wherein Bx is an optionally protected uracil claim 93 , thymine claim 93 , cytosine claim 93 , 5-methylcytosine claim 93 , adenine or guanine.95. The bicyclic nucleoside of wherein Tis 4 claim 93 ,4′-dimethoxytrityl and Tis diisopropylcyanoethoxy phosphoramidite.96. The bicyclic nucleoside of wherein Qand Qare each H.97. The bicyclic nucleoside of wherein one of Qand Qis H and the other of Qand Qis C-Calkyl or substituted C-Calkyl.98. The bicyclic nucleoside of wherein one of Qand Qis CH.99. The bicyclic nucleoside of wherein Gand Gare each H.100. The bicyclic nucleoside of wherein one of Gand Gis H and the other of Gand Gis C-Calkyl or substituted C-Calky.101. The bicyclic nucleoside of wherein at least one of Gand Gis CH.102. The bicycle nucleoside of wherein Z is NR wherein R is H claim 93 , C-Csubstituted C-Calkyl claim 93 , C-Calkoxy or substituted C-Calkoxy.103. The bicyclic nucleoside of wherein R is CHor methoxy.104. The bicyclic nucleoside of wherein Z is S.106. The bicyclic nucleoside of wherein three of Q claim 105 , Q claim 105 , Gand Gare H and the other one of Q claim 105 , Q claim 105 , Gand Gis CH.107. The bicyclic nucleoside of wherein two of Q claim 105 , Q claim 105 , Gand Gare H and the remaining two of Q claim 105 , Q claim 105 , Gand Gare CHwherein the two that are CHare selected from Qand G claim 105 , Qand G claim 105 , Qand G claim 105 , and Qand G.109. The oligomeric compound of wherein Bx is an optionally protected uracil claim 108 , thymine claim 108 , cytosine claim 108 , 5-methylcytosine claim 108 , adenine or guanine for each bicyclic nucleoside of Formula II.110. The oligomeric compound of ...

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Номер записи: 61
30-05-2013 дата публикации

Crystal Forms of 2--Adenosine

Номер: US20130136693A1
Автор: "ONeal Michael H.", Moorman Allan R.
Принадлежит: King Pharmaceuticals Research and Development, Inc

The present invention provides novel crystalline polymorphic forms of 2-cyclohexylmethylidenehydrazino adenosine, also known as binodenoson, methods of making the same, and methods for the manufacture of a pharmaceutical composition by employing such crystal forms, in particular, for the use of binodenoson in a subject, in need thereof, as a pharmacological stress agent to produce coronary vasodilation. 1. A crystal form of 2-{2-[(cyclohexyl)methylene]hydrazino}adenosine (binodenoson) which crystal form is substantially free of other polymorphic forms of binodenoson and has at least one of the following properties:(a) an endotherm by differential scanning calorimetry with an extrapolated onset melting temperature in the range of about 139° C. to about 146° C. when heated at 10° C./min;(b) a X-ray diffraction pattern with characteristic X-ray diffraction peaks at diffraction angles (2θ) of about 5.7±0.2, 10.2±0.2, 14.6±0.2, 19.9±0.2, 21.1±0.2 and 24.6±0.2;(c) an infrared reflectance spectrum with reflectance bands at about 1668±2 and 1592±2; and{'sup': '−1', '(d) a Raman spectrum with Raman shifts at about 1618±2 and 1593±2 cm.'}3. A crystal form according to claim 1 , which crystal form has all four of the properties (a) claim 1 , (b) claim 1 , (c) and (d).4. A crystal form of binodenoson which crystal form is substantially free of other polymorphic forms of binodenoson and has at least one of the following properties:(a) an endotherm by differential scanning calorimetry with an extrapolated onset melting temperature in the range of about 149° C. to about 154° C. when heated at 10° C./min;(b) a X-ray diffraction pattern with characteristic X-ray diffraction peaks at diffraction angles (2θ) of about 5.5±0.2, 10.4±0.2, 16.8±0.2, 20.2±0.2 and 26.0±0.2;{'sup': '−1', '(c) an infrared reflectance spectrum with reflectance bands at about 1646±2 and 1598±2 cm; and'}{'sup': '−1', '(d) a Raman spectrum with Raman shifts at about 1622±2 and 1588±2 cm.'}6. A crystal form ...

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Номер записи: 62
30-05-2013 дата публикации

NUCLEOSIDE PHOSPHORAMIDATES

Номер: US20130137654A1
Автор: Chun Byoung-Kwon, Pamulapati Ganapati Reddy, Rachakonda Suguna, Ross Bruce, Sofia Michael Joseph, Wang Peiyuan, Zhang Hai-Ren
Принадлежит: GILEAD PHARMASSET LLC

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. 181.-. (canceled)83. The compound according to claim 82 , wherein the compound is at least 98% of the Sstereoisomer represented by the formula (S-4) and not more than 2% of the Rstereoisomer represented by the formula (R-4).84. The compound according to claim 82 , wherein the compound is at least 99% of the Sstereoisomer represented by the formula (S-4) and not more than 1% of the Rstereoisomer represented by the formula (R-4).85. A pharmaceutical composition comprising the compound according to and a pharmaceutically acceptable medium.86. A pharmaceutical composition comprising the compound according to and a pharmaceutically acceptable medium.87. A pharmaceutical composition comprising the compound according to and a pharmaceutically acceptable medium.88. A method of treating a hepatitis C virus infection in a human comprising administering to the human an effective amount of the compound according to .89. The method according to further comprising administering to the human another antiviral agent.90. A method of treating a hepatitis C virus infection in a human comprising administering to the human an effective amount of the compound according to .91. The method according to further comprising administering to the human another antiviral agent.92. A method of treating a hepatitis C virus infection in a human comprising administering to the human an effective amount of the compound according to .93. The method according to further comprising administering to the human another antiviral agent. The right of priority is claimed to U.S. Provisional Patent Application Nos. 61/179,923, filed May 20, 2009, and 61/319,513, filed Mar. 31, 2010, the subject matter ...

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Номер записи: 63
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: 64
06-06-2013 дата публикации

HCV Polymerase Inhibitors

Номер: US20130143835A1
Автор: ENEROTH Anders, Klasson Björn, NILSSON MAGNUS, Pinho Pedro, Samuelsson Bertil, Sund Christian
Принадлежит: Medivir AB

The invention provides compounds of the formula: 2. The compound according to claim 1 , wherein Ris H.3. The compound according to claim 1 , wherein Ris C-Calkyl claim 1 , C-Ccycloalkyl or benzyl.4. The compound according to claim 1 , wherein Ris C-Calkyl.5. The compound according to claim 1 , wherein Ris H claim 1 , and R′ is H or C-Calkyl.6. The compound according to claim 1 , wherein one of Rand R′ is H and the other is methyl.7. The compound according to claim 1 , wherein Ris H claim 1 , R′ is C-Calkyl and Ris C-Calkyl or C-Ccycloalkyl.8. The compound according to claim 5 , wherein the configuration at the asymmetric carbon atom to which Rand R′ are attached is that of an L-amino acid.9. A compound according to claim 1 , for use as a medicament.10. The compound according to claim 1 , for use in the treatment or prophylaxis of hepatitis C virus infection.11. A pharmaceutical composition comprising a compound according to in association with a pharmaceutically acceptable adjuvant claim 1 , diluent or carrier.12. A pharmaceutical composition comprising a compound according to claim 1 , further comprising one or more additional other antiviral agent(s).13. A method for the treatment or prophylaxis of hepatitis C virus infection comprising the administration of a compound according to .14. The use of a compound according to in the manufacture of a medicament for the treatment or prophylaxis of hepatitis C virus infection. The present invention relates to inhibitors of the polymerase of hepatitis C virus (HCV), prodrugs thereof and their use in the treatment or prophylaxis of HCV infection.HCV is a single stranded, positive-sense RNA virus belonging to the Flaviviridae family of viruses in the hepacivirus genus. The NS5B region of the RNA polygene encodes an RNA dependent RNA polymerase (RdRp), which is essential to viral replication. Following the initial acute infection, a majority of infected individuals develop chronic hepatitis because HCV replicates ...

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Номер записи: 65
06-06-2013 дата публикации

PROCESS FOR THE SYNTHESIS OF CARBONUCLEOSIDE AND INTERMEDIATES FOR USE THEREIN

Номер: US20130144058A1
Автор: ALBERICO Dino, CLAYTON Joshua, Dixon Craig, Gorin Boris
Принадлежит: Alphora Research Inc.

Disclosed is a process for preparing a carbonucleoside of formula (1) and intermediates for use therein. The process involves the step of reacting a compound of formula (2) with a compound of formula (3) under Mitsunobu-type reaction conditions to obtain a compound of formula (4), wherein PG, PG, PGand PGare protecting groups. The compound of formula (4) is deprotected to form the compound of formula (1), as shown below. 2. The process according to claim 1 , wherein the Mitsunobu type reaction condition comprises an alkyl phosphine or an aryl phosphine claim 1 , and an azo-based compound.3. The process according to claim 2 , wherein the alkyl phosphine is PMe.4. The process according to claim 2 , wherein the aryl phosphine is PPh.5. The process according to claim 2 , wherein the azo based compound is selected from the group consisting of diethylazodicarboxylate (DEAD) claim 2 , diisopropylazodicarboxylate (DIAD) claim 2 , di-t-butylazodicarboxylate claim 2 , 2-(phenylazo)pyridine (azpy) claim 2 , di-p-chlorobenzylazodicarboxylate (DCAD) or 1 claim 2 ,1′-(azodicarboxyl)dipiperidine (ADDP).6. The process according to claim 2 , wherein the azo based compound is diisopropylazodicarboxylate (DIAD).7. The process according to claim 1 , wherein the Mitsunobu type reaction condition comprises a phosphorane ylide.8. The process according to claim 7 , wherein the phosphorane ylide is selected from the group consisting of (cyanomethylene)trimethyl phosphorane or tributylphosphorane.9. The process according to claim 1 , wherein solvent for the Mitsunobu type reaction is selected from the group consisting of tetrahydrofuran claim 1 , acetonitrile claim 1 , dichloromethane claim 1 , toluene claim 1 , or a mixture thereof.10. The process according to claim 1 , wherein solvent for the Mitsunobu type reaction is tetrahydrofuran.11. The process according to claim 1 , wherein the Mitsunobu type reaction is carried out at room temperature.12. The process according to claim 1 , wherein ...

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Номер записи: 66
13-06-2013 дата публикации

METHODS AND COMPOSITIONS FOR TREATING HEPATITIS C VIRUS

Номер: US20130149283A1
Автор: LACOLLA Paolo, SOMMADOSSI Jean-Pierre
Принадлежит:

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. 2. The method of claim 1 , wherein Rand Rare each independently H; phosphate; a stabilized phosphate prodrug; acyl; or a pharmaceutically acceptable leaving group which claim 1 , when administered in vivo claim 1 , provides a compound wherein Rand Rare each independently H or phosphate.3. The method of claim 1 , wherein Ris hydrogen claim 1 , acyl claim 1 , or phosphate.4. The method of claim 1 , wherein Ris hydrogen or phosphate.5. The method of claim 1 , wherein Ris phosphate.6. The method of claim 1 , wherein Ris hydrogen or acyl.7. The method of claim 1 , wherein Ris hydrogen.8. The method of claim 1 , wherein Ris alkyl.9. The method of claim 1 , wherein Ris methyl.10. The method of claim 1 , wherein Rand Rare each independently hydrogen claim 1 , OR claim 1 , hydroxy claim 1 , alkyl claim 1 , azido claim 1 , cyano claim 1 , alkenyl claim 1 , alkynyl claim 1 , Br-vinyl claim 1 , —C(O)O(alkyl) claim 1 , —C(O)O(lower alkyl) claim 1 , —O(acyl) claim 1 , —O(lower acyl) claim 1 , —O(alkyl) claim 1 , —O(lower alkyl) claim 1 , —O(alkenyl) claim 1 , chloro claim 1 , bromo claim 1 , iodo claim 1 , NO claim 1 , NH claim 1 , —NH(lower alkyl) claim 1 , —NH(acyl) claim 1 , —N(lower alkyl) claim 1 , or —N(acyl).11. The method of claim 1 , wherein Rand Rare each independently hydrogen claim 1 , OR claim 1 , alkyl claim 1 , azido claim 1 , cyano claim 1 , alkenyl claim 1 , alkynyl claim 1 , Br-vinyl claim 1 , —O(alkenyl) claim 1 , chloro claim 1 , bromo claim 1 , iodo claim 1 , NO claim 1 , NH claim 1 , —NH(lower alkyl) claim 1 , —NH(acyl) claim 1 , —N(lower alkyl) claim 1 , or —N(acyl).12. The method of claim 1 , wherein Rand Rare each independently hydrogen claim 1 , OR claim 1 , hydroxy claim 1 , azido claim 1 , cyano ...

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Номер записи: 67
13-06-2013 дата публикации

Bicyclic nucleosides and oligomeric compounds prepared therefrom

Номер: US20130150569A1
Автор: Benjamin R. Schroeder, Eric E. Swayze, Punit P. Seth, Stephen Hanessian
Принадлежит: ISIS PHARMACEUTICALS INC

The present invention provides novel 3′,5′-linked bicyclic nucleosides and oligomeric compounds prepared therefrom. The bicyclic nucleosides provided herein are useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as nuclease resistance.

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Номер записи: 68
20-06-2013 дата публикации

NOVEL GLYCOSIDE COMPOUNDS

Номер: US20130157970A1
Автор: Chao Yu-Sheng, Lee Jinq-Chyi
Принадлежит: National Health Research Institutes

Compounds of formula (I): 2. The compound of claim 1 , wherein Y is halo and Z is aryl substituted with C-Calkoxyl or C-Ccycloalkyl.6. The compound of claim 4 , wherein X is RC(O)NHCH— or RC(O)NHNHCH— claim 4 , Y is H or halo claim 4 , and Z is aryl substituted with C-Ccycloalkyl.9. The compound of claim 7 , wherein Y is H or halo claim 7 , and Z is unsubstituted aryl or aryl substituted with C-Ccycloalkyl.11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of .12. A method of treating a disorder related to sodium-dependent glucose co-transporter 2 claim 1 , comprising administering to a subject in need thereof an effective amount of a compound of .13. The method of claim 12 , wherein the disorder is type 1 diabetes mellitus claim 12 , type 2 diabetes mellitus claim 12 , or hyperglycemia.14. The method of claim 12 , further comprising administering to the subject an antidiabetic agent claim 12 , an anti-obesity agent claim 12 , an anti-diabetic complications agent claim 12 , an antihypertensive agent claim 12 , an antiplatelet agent claim 12 , an anti-atherosclerotic agent claim 12 , or a hypolipidemic agent.15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of .16. A method of treating a disorder related to sodium-dependent glucose co-transporter 2 claim 5 , comprising administering to a subject in need thereof an effective amount of a compound of .17. The method of claim 16 , wherein the disorder is type 1 diabetes mellitus claim 16 , type 2 diabetes mellitus claim 16 , or hyperglycemia.18. The method of claim 16 , further comprising administering to the subject an antidiabetic agent claim 16 , an anti-obesity agent claim 16 , an anti-diabetic complications agent claim 16 , an antihypertensive agent claim 16 , an antiplatelet agent claim 16 , an anti-atherosclerotic agent claim 16 , or a hypolipidemic agent.19. A pharmaceutical composition comprising a pharmaceutically ...

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Номер записи: 69
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: 70
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: 71
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: 72
27-06-2013 дата публикации

Nucleoside phosphoramidates

Номер: US20130165401A1
Автор: Bruce Ross, Byoung-Kwon Chun, Ganapati REDDY PAMULAPATI, Hai-Ren Zhang, Michael Joseph Sofia, Peiyuan Wang, Suguna Rachakonda
Принадлежит: GILEAD PHARMASSET LLC

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

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Номер записи: 73
27-06-2013 дата публикации

NUCLEOSIDE PHOSPHORAMIDATES

Номер: US20130165644A1
Автор: Chun Byoung-Kwon, Pamulapati Ganapati Reddy, Rachakonda Suguna, Ross Bruce, Sofia Michael Joseph, Wang Peiyuan, Zhang Hai-Ren
Принадлежит: GILEAD PHARMASSET LLC

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. 181.-. (canceled)83. The compound according to claim 82 , wherein LG′ is p-nitrophenoxide claim 82 , p-chlorophenoxide claim 82 , o-chlorophenoxide claim 82 , 2 claim 82 ,4-dinitrophenoxide claim 82 , or pentafluorophenoxide.84. The compound according to claim 82 , wherein LG′ is p-nitrophenoxide.85. The compound according to claim 82 , wherein LG′ is p-chlorophenoxide.86. The compound according to claim 82 , wherein LG′ is o-chlorophenoxide.87. The compound according to claim 82 , wherein LG′ is pentafluorophenoxide.88. A process for preparing the compound according to claim 82 , which comprises:{'sub': '2', 'sup': i', 'i, 'reacting (LG′)P(O)(LG), wherein LG and LG′ are independently leaving groups, with isopropyl-alanate and a first base to obtain (LG′)P(O)(LG)(NHAla-Pr), followed by reacting (LG′)P(O)(LG)(NHAla-Pr) with phenol and a second base.'}89. A process for preparing the compound according to claim 82 , which comprises:{'sub': '2', 'reacting (LG′)P(O)(LG), wherein LG and LG′ are independently leaving groups, with phenol and a first base to obtain (LG′)P(O)(LG)(OPh), followed by reacting (LG′)P(O)(LG)(OPh) with isopropyl-alanate and a second base.'}90. A process for preparing the compound according to claim 82 , which comprises:{'sub': '2', 'reacting (LG′)P(O)(LG), wherein LG and LG′ are independently leaving groups, with a combination of isopropyl-alanate, phenol, and at least one base.'}91. A process for preparing the compound according to claim 82 , which comprises:{'sub': '2', 'sup': i', 'i, 'reacting (PhO)P(O)(LG), wherein LG and LG′ are independently leaving groups, with isopropyl-alanate and a first base to obtain (PhO)P(O)(LG)(NHAla-Pr), ...

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Номер записи: 74
04-07-2013 дата публикации

LINKED PURINE PTERIN HPPK INHIBITORS USEFUL AS ANTIBACTERIAL AGENTS

Номер: US20130172285A1
Автор: Ji Xinhua, Shaw Gary X., Shi Genbin
Принадлежит:

The disclosure provides linked purine pterin compounds and analogues thereof that are novel HPPK inhibitors. The HPPK inhibitors described herein are compounds and the pharmaceutically acceptable salts thereof of general Formula I 5. A compound or salt thereof of claim 2 , wherein{'sub': 1', '3', '2, 'Ais oxo and each Ais independently chosen from hydrogen and methyl; and Ris —NH—.'}6. A compound or salt thereof of any one of claim 5 , wherein{'sub': '1', 'Ris methylene optionally substituted with —(C═O)—.'}7. (canceled)8. A compound or salt thereof of claim 2 , wherein{'sub': 1', '1', '1', '4', '1', '4', '1', '2', '1', '2, 'Lis an alkylene linker having from 2 to 4 carbon atoms, wherein Lis unsubstituted or substituted with 1 or more substituents independently chosen from hydroxyl, halogen, amino, C-Calkyl, C-Calkoxy, C-Chaloalkyl, and C-Chaloalkoxy; and'}{'sub': 2', '2', '1', '4', '1', '4', '1', '2', '1', '2', '1', '2, 'Lis an alkylene linker having from 1 to 2 carbon atoms, containing 1 heteroatom selected from oxygen, nitrogen, and sulfur, wherein Lis unsubstituted or substituted with 1 or more substituents independently chosen from hydroxyl, halogen, amino, C-Calkyl, C-Calkoxy, C-Chaloalkyl, and C-Chaloalkoxy; wherein the total number of carbon atoms in the Land Lalkylene linkers is from 3 to 5'}9. (canceled)10. A compound or salt thereof of claim 8 , wherein{'sub': 1', '1, 'Lis an alkylene linker having from 2 to 3 carbon atoms, wherein Lis unsubstituted or substituted with 1 or more substituents independently chosen from halogen and methyl;'}{'sub': 2', '2', '2, 'Lis an alkylene linker of the formula —SCH—, wherein Lis unsubstituted or substituted with 1 or more substituents independently chosen from halogen and methyl; and'}{'sub': 3', '3', '1', '2', '1', '2, 'Ris a piperidinyl, piperazinyl, or pyrrolidinyl ring; each of which Ris unsubstituted or substituted with 1 or more substituents independently chosen from hydroxyl, halogen, C-Calkyl, and C-Calkoxy.'} ...

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Номер записи: 75
04-07-2013 дата публикации

HYDROUS CRYSTALLINE 2-O-alpha-D-GLUCOSYL-L-ASCORBIC ACID, PARTICULATE COMPOSITION COMPRISING THE SAME, THEIR PREPARATION AND USES

Номер: US20130172542A1
Автор: Fukuda Shigeharu, Izawa Seisuke, Shibuya Takashi
Принадлежит: HAYASHIBARA CO., LTD.

The present invention has objects to provide a novel crystalline 2-O-α-glucosyl-L-ascorbic acid and its production process and uses, and solves the above objects by providing hydrous crystalline 2-O-α-glucosyl-L-ascorbic acid, a particulate composition containing hydrous crystalline 2-O-α-glucosyl-L-ascorbic acid, and their production processes and uses. 1. A hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid.2. The hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid of claim 1 , which exhibits diffraction peaks at least at diffraction angles (2θ) of 6.1° claim 1 , 9.2° claim 1 , 10.6° claim 1 , 11.4° and 12.1° in a powder X-ray diffraction pattern obtained by using a CuKα-ray as an X-ray source.3. The hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid of claim 1 , which contains about 2.7% by weight of crystallization water.4. The hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid of claim 1 , which exhibits an endothermic peak at around 156° C. when determined on differential scanning calorimetric analysis.5. A particulate composition comprising hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid claim 1 , which comprises said hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid of claim 1 , wherein the purity of said hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid is at least 85% by weight claim 1 , on a dry solid basis.6. A process for producing a hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid claim 1 , which comprises a step of evaporating water from an aqueous solution comprising a supersaturated amount of 2-O-α-D-glucosyl-L-ascorbic acid and a coexisting anhydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid to crystallize said hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid of .7. A process for producing a hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid claim 1 , which comprises the steps of adding said hydrous crystalline 2-O-α-D-glucosyl-L-ascorbic acid of as a seed crystal to an aqueous solution comprising 2-O-α-D-glucosyl-L- ...

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Номер записи: 76
04-07-2013 дата публикации

METHOD FOR OXIDIZING ALCOHOLS

Номер: US20130172543A1
Автор: HAYASHI Masaki, IWABUCHI Yoshiharu
Принадлежит: TOHOKU UNIVERSITY

A method for oxidizing an alcohol, wherein oxidation is performed in the presence of a compound represented by the following formula (I) and a bulk oxidant, which enables efficient oxidation of secondary alcohols as well as primary alcohols, and can attain high reaction efficiency even when air is used as a bulk oxidant. 2. The method according to claim 1 , wherein the alcohol is a secondary alcohol.3. The method according to claim 1 , wherein the bulk oxidant is a peracid claim 1 , hydrogen peroxide claim 1 , a hypohalogen acid or a salt thereof claim 1 , a perhalogen acid or a salt thereof claim 1 , a persulfuric acid salt claim 1 , a halogenating agent such as a halide and N-bromosuccinimide claim 1 , a trihalogenated isocyanuric acid claim 1 , a diacetoxyiodoallene claim 1 , a dialkyl azodicarboxylate claim 1 , oxygen claim 1 , air claim 1 , or a mixture thereof.4. The method according to claim 1 , wherein the bulk oxidant is air.5. The method according to claim 2 , wherein the bulk oxidant is a peracid claim 2 , hydrogen peroxide claim 2 , a hypohalogen acid or a salt thereof claim 2 , a perhalogen acid or a salt thereof claim 2 , a persulfuric acid salt claim 2 , a halogenating agent such as a halide and N-bromosuccinimide claim 2 , a trihalogenated isocyanuric acid claim 2 , a diacetoxyiodoallene claim 2 , a dialkyl azodicarboxylate claim 2 , oxygen claim 2 , air claim 2 , or a mixture thereof.6. The method according to claim 2 , wherein the bulk oxidant is air. The present invention relates to a method for oxidizing an alcohol utilizing an organic catalyst.Oxidation reactions of alcohols constitute one class of important reactions as methods for chemical conversion of compounds, and are frequently used in syntheses of organic compounds with high added values such as medicaments and agricultural chemicals and the like. Therefore variety of methods have been developed so far. However, many of those methods use explosive reagents, highly toxic metals and the ...

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Номер записи: 77
18-07-2013 дата публикации

METHOD AND COMPOSITIONS FOR THE DETECTION OF PROTEIN GLYCOSYLATION

Номер: US20130183712A1
Автор: Arndt Sabine, Hsieh-Wilson Linda, Khidekel Nelly, Tai Hwan-Ching
Принадлежит: California Institute of Technology

The invention provides methods and compositions for the rapid and sensitive detection of post-translationally modified proteins, and particularly of those with posttranslational glycosylations. The methods can be used to detect O-GlcNAc posttranslational modifications on proteins on which such modifications were undetectable using other techniques. In one embodiment, the method exploits the ability of an engine˜red mutant of β-1,4-galactosyltransferase to selectively transfer an unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once transferred, the ketone moiety serves as a versatile handle for the attachment of biotin, thereby enabling detection of the modified protein. The approach permits the rapid visualization of proteins that are at the limits of detection using traditional methods. Further, the preferred embodiments can be used for detection of certain disease states, such as cancer, Alzheimer's disease, neurodegeneration, cardiovascular disease, and diabetes. 2. The compound of claim 1 , wherein R is selected from the group consisting of straight chain or branched C-Ccarbon chain bearing a carbonyl group claim 1 , azide group claim 1 , straight chain or branched C-Ccarbon chain bearing an azide group claim 1 , straight chain or branched C-Ccarbon chain bearing an alkyne claim 1 , and straight chain or branched C-Ccarbon chain bearing an alkene.4. A labeled protein obtained from contacting a post-translationally modified protein comprising a pendant moiety with a labeling agent capable of reacting with the pendant moiety in the presence of an enzyme claim 1 , wherein the labeling agent comprises a chemical handle; and reacting the chemical handle with a detection agent.5. The labeled protein of claim 4 , wherein the pendant moiety is a glycosyl group.6. The method of claim 5 , wherein the glycosyl group is selected from the group consisting of glucose claim 5 , galactose claim 5 , mannose claim 5 , fucose claim 5 , GalNAc claim 5 , GlcNAc ...

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Номер записи: 78
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: 79
01-08-2013 дата публикации

Anhydrous polymorphs of [(2r,3s,4r,5r)-5-(6-(cyclopentylamino)-9h-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)} methyl nitrate and processes of preparation thereof

Номер: US20130196940A1
Автор: William K. Mcvicar
Принадлежит: Inotek Pharmaceuticals Corp

The present invention provides novel anhydrous polymorph forms of 2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl nitrate (Compound A). The present invention also provides processes for preparation of the anhydrous polymorphic forms of compound A.

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Номер записи: 80
01-08-2013 дата публикации

PARENTERAL FORMULATIONS OF ELACYTARABINE DERIVATIVES

Номер: US20130196941A1
Автор: Ahrabi Sayeh, Eriksen Ole Henrik, Myhren Finn
Принадлежит: CLAVIS PHARMA ASA

The present invention relates to parenteral formulations for certain long chain saturated and monounsaturated fatty acid derivatives of 1-β-D-arabinofuranosylcytosine (cytarabine). In particular, the present invention relates to a parenteral pharmaceutical composition and a method of the preparation thereof, in order to accommodate therapeutically effective doses of the said derivatives ameliorating compliance in treatment of cancer. 2. The pharmaceutical composition of claim 1 , wherein the active ingredient is Ara-C-5′-elaidic acid ester.3. The pharmaceutical composition according to claim 1 , wherein the solubilizer comprises one or more phospholipids selected from the group consisting of phosphatidylcholine claim 1 , lyso-phosphatidylcholine 1 claim 1 , lyso-phosphatidylcholine 2 phosphatidylglycerol claim 1 , phosphatidylethanolamine claim 1 , lyso-phosphatidylethanolamine claim 1 , phosphatidylinositol claim 1 , phosphatidylserine claim 1 , phosphatidic acid claim 1 , sphingomyelin and cardiolipin claim 1 , and the salts claim 1 , desalts claim 1 , hydrogenates and partial hydrogenates of any thereof.4. The pharmaceutical composition according to claim 1 , wherein the phospholipids are natural unsaturated phospholipids derived from hen egg.5. The pharmaceutical composition of claim 1 , wherein the co-solubilizer is sodium oleate.6. The pharmaceutical composition according to claim 1 , wherein the isotonocity agent is glycerol.7. The pharmaceutical composition according to claim 1 , wherein the pH of the formulation is between 6.0 and 8.0.8. The pharmaceutical composition according to claim 1 , wherein the formulation has a particle size of between 5-45 nm.9. The pharmaceutical composition according to claim 8 , wherein the particle size is between 9-25 nm.10. The pharmaceutical composition according to claim 1 , wherein the formulation has a drug:lipid molar ratio of between 1:20 and 1:7.11. The pharmaceutical composition according to claim 1 , wherein the ...

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Номер записи: 81
01-08-2013 дата публикации

OLIGOMERIC COMPOUNDS COMPRISING TRICYCLIC NUCELOSIDES AND METHODS FOR THEIR USE

Номер: US20130197062A1
Автор: Prakash Thazha P., Seth Punit P., Siwkowski Andrew M., Swayze Eric E.
Принадлежит: Isis Pharmaceuticals, Inc.

The present disclosure provides tricyclic nucleosides, oligomeric compounds comprising at least one of the tricyclic nucleosides and methods of using the oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds. In certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. 2. The oligomeric compound of wherein qand qare H for each of said tricyclic nucleosides having formula II.3. The oligomeric compound of wherein at least one of q claim 1 , q claim 1 , qand qis other than H for each of said tricyclic nucleosides having formula II.4. The oligomeric compound of wherein at least one of q claim 1 , q claim 1 , qand qis fluoro for each of said tricyclic nucleosides having formula II.5. The oligomeric compound of wherein at least one of qand qis fluoro for each of said tricyclic nucleosides having formula II.6. The oligomeric compound of wherein at least one of qand qis fluoro for each of said tricyclic nucleosides having formula II.7. The oligomeric compound of wherein qand qare each fluoro for each of said tricyclic nucleosides having formula II.8. The oligomeric compound of wherein at least one of q claim 2 , q claim 2 , qand qis C-Calkyl for each of said tricyclic nucleosides having formula II.9. The oligomeric compound of wherein at least one of q claim 8 , q claim 8 , qand qis methyl for each of said tricyclic nucleosides having formula II.10. The oligomeric compound of wherein each q claim 1 , q claim 1 , qand qis H.11. The oligomeric compound of wherein zis fluoro for each of said tricyclic nucleosides having formula II.12. The oligomeric compound of wherein zis fluoro for each of said tricyclic nucleosides having formula II.13. The oligomeric compound of wherein zand zare each fluoro for each of said tricyclic nucleosides having formula II.14. The oligomeric compound of claim 1 , wherein at ...

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Номер записи: 82
01-08-2013 дата публикации

Novel process for the preparation of 9-deoxo-9a-aza-9a-homoerythromycin a, modified in the c-44" of the cladinose ring by an epoxide group

Номер: US20130197204A1
Автор: Albert Codony, Oriol Martorell, Rafael Garcia
Принадлежит: Individual

The present invention concerns a process for the preparation of the compound of formula The compound of formula (1) is the key intermediate in the synthesis of some antibacterial agents of the triamilide class, such as Tulathromycin, useful to treat bacterial and protozoa infections.

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Номер записи: 83
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: 84
08-08-2013 дата публикации

2' AND 5' MODIFIED MONOMERS AND OLIGONUCLEOTIDES

Номер: US20130203836A1
Автор: Manoharan Muthiah, Prakash Thazha P., Rajeev Kallanthottathil G., Swayze Eric E.
Принадлежит:

The present invention provides nucleosides of formula (1) and oligonucleotides comprising at least on nucleoside of formula (2):Formula (1) and Formula (2). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. 10. The oligonucleotide of claim 5 , wherein at least one of Tand Tis methyl.11. The oligonucleotide of claim 5 , wherein one of Tand Tis methyl and the other of T claim 5 , and Tis H.12. The oligonucleotide of wherein Xis O.13. The oligonucleotide of wherein Xis S.14. The oligonucleotide of wherein Xis CHor CF.15. The oligonucleotide of wherein the oligonucleotide comprises:1-20 first-type regions, each first-type region independently comprising 1-20 contiguous nucleosides wherein each nucleoside of each first-type region comprises a first-type modification;0-20 second-type regions, each second-type region independently comprising 1-20 contiguous nucleosides wherein each nucleoside of each second-type region comprises a second-type modification; and0-20 third-type regions, each third-type region independently comprising 1-20 contiguous nucleosides wherein each nucleoside of each third-type region comprises a third-type modification;{'sub': 3', '2', '3, 'wherein the first-type modification, the second-type modification, and the third-type modification are each independently selected from the group consisting of 2′-F, 2′-OCH, 2′-O(CH)2OCH, BNA, F-HNA, 2′-H and 2′-OH.'}16. The oligonucleotide of claim 5 , wherein the oligonucleotide comprises at least one non-phosphodiester internucleoside linkage.17. The oligonucleotide of claim 16 , wherein at least one of the non-phosphodiester internucleoside linkage is selected from the group consisting of phosphorothioate claim 16 , phosphorodithioate claim 16 , alkyl- ...

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Номер записи: 85
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: 86
15-08-2013 дата публикации

Methods for the Identification of Methyltransferase Interacting Molecules and for the Purification of Methyltransferase Proteins

Номер: US20130210664A1
Автор: Addison Glynn, Drewes Gerard, Harrison John, Ramsden Nigel
Принадлежит: Cellzome AG

The present invention relates to immobilization compounds, immobilization products and preparations thereof as well as methods and uses for the identification of methyltransferase interacting compounds or for the purification or identification of methyltransferase proteins. 3. A method for the preparation of an immobilization product claim 1 , wherein the immobilization compound of is immobilized on a solid support claim 1 , in particular wherein the solid support is selected from the group consisting of agarose claim 1 , modified agarose claim 1 , sepharose beads (e.g. NHS-activated sepharose) claim 1 , latex claim 1 , cellulose claim 1 , and ferro- or ferrimagnetic particles.4. The method of claim 3 , wherein the immobilization product results from a covalent direct or linker mediated attachment of the immobilization compound to the solid support claim 3 , in particular wherein the linker is a Calkylene group claim 3 , which is optionally interrupted or terminated by one or more atoms or functional groups selected from the group consisting of S claim 3 , O claim 3 , NH claim 3 , C(O)O claim 3 , OC(O) claim 3 , C(O) claim 3 , NHC(O) claim 3 , and C(O)NH and wherein the linker is optionally substituted with one or more substituents independently selected from the group consisting of halogen claim 3 , OH claim 3 , NH claim 3 , C(O)H claim 3 , C(O)NH claim 3 , SOH claim 3 , NO claim 3 , and CN.5. (canceled)6. An immobilization product claim 1 , comprising the immobilization compound of immobilized on a solid support claim 1 , in particular wherein the solid support is selected from the group consisting of agarose claim 1 , modified agarose claim 1 , sepharose beads (e.g. NHS-activated sepharose) claim 1 , latex claim 1 , cellulose claim 1 , and ferro- or ferrimagnetic particles.7. A method for the identification of a methyltransferase interacting compound claim 1 , comprising the steps ofa) providing a protein preparation containing a variety of methyltransferases,{' ...

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Номер записи: 87
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: 88
15-08-2013 дата публикации

PURIFICATION OF SYNTHETIC OLIGONUCLEOTIDES

Номер: US20130211065A1
Автор: Fang Shiyue
Принадлежит: MICHIGAN TECHNOLOGICAL UNIVERSITY

This invention provides a method for purifying synthetic oligonucleotides comprising capping, polymerizing and separating any failure sequences produced during oligonucleotide synthesis. The invention also provides a method for purifying synthetic oligonucleotides comprising reacting a full length oligonucleotide with a compound to attach a polymerizable functional group to an end of the full length oligonucleotide, polymerizing the full length oligonucleotides and removing the failure sequences, and recovering the full length oligonucleotides. The invention also provides novel capping agents having a polymerizable functional group, and kits comprising at least one composition of the present invention. 2. The method of claim 1 , wherein Ris hydrogen.5. The method of claim 4 , wherein Ar is 1 claim 4 ,4-phenylenyl.6. The method of claim 4 , wherein Y is —O—.7. The method of claim 1 , wherein the failure sequences are polymerized via radical acrylamide polymerization.8. The method of claim 1 , wherein linker is (CH).9. The method of claim 1 , wherein Ris —N(CH(CH)).10. The method of claim 1 , wherein Ris —CH—-CH—CN.11. The method of claim 1 , wherein Ris methyl.12. The method of claim 1 , wherein Rand Rare each hydrogen.14. The method of claim 13 , wherein Rand Rare each hydrogen.17. The method of claim 16 , wherein Ris hydrogen.18. The method of claim 16 , wherein Ar is 1 claim 16 ,4-phenylenyl.19. The method of claim 16 , wherein Y is —O—.20. The method of claim 13 , wherein linker is (CH).22. The method of claim 21 , wherein Ris hydrogen.25. The method of claim 24 , wherein Ar is 1 claim 24 ,4-phenylenyl.26. The method of wherein Y is —O—.28. The method of claim 27 , wherein Ris hydrogen.29. The method of claim 27 , wherein Y is —O—.32. The method of claim 31 , wherein Ar is 1 claim 31 ,4-phenylenyl.33. The method of claim 31 , wherein Y is —O—.34. The method of claim 31 , wherein Z is —O—.36. The method of claim 13 , wherein Ris —N(CH(CH)).37. The method of claim ...

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Номер записи: 89
15-08-2013 дата публикации

Compounds useful in imaging and therapy

Номер: US20130211066A1
Автор: Alexander McEwan, Leonard Wiebe, Piyush Kumar
Принадлежит: ALBERTA HEALTH SERVICES, University of Alberta

Provided in the following specification are precursors or synthons that are useful for the synthesis of various arabinose based chemical and radiochemical derivatives of nitroimidazole-containing azomycin arabinosides, such as radioiodinated 1-#-D-(5-deoxy-5-[I*]-iodoarabinofuranosyl)-2-nitroimidazole (*IAZA), and radiofluorinated 1-#-D-(5-deoxy-5-[18F]-iodoarabinofuranosyl)-2-nitroimidazole (18FAZA). Such compounds are useful in imaging, therapy, or radiotherapy. Further, various syntheses of said precursors/synthons and the incorporation of said precursors/synthons into kits is provided. The precursors/synthons provided herein allow for an improved and facile manufacturing process for nitroimidazole-containing azomycin arabinosides.

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Номер записи: 90
15-08-2013 дата публикации

NOVEL SELENY-METHYLURACIL COMPOUNDS, RADIOSENSITIZER AND PHARMACEUTICAL COMPOSITION USING THEM

Номер: US20130211067A1
Автор: Greenberg Marc M., Hong In Seok, HONG Sung Hee
Принадлежит:

Provided are novel selenyl-methyluracil compounds and a pharmaceutical composition for enhancing the effect of radiation treatment. The composition contains at least one compound selected from the group consisting of the selenyl-methyluracil compounds or pharmaceutically acceptable salts thereof, as an active ingredient. 8. The pharmaceutical composition for treating cancer according to claim 7 , wherein the cancer is prostate cancer claim 7 , breast cancer claim 7 , brain tumor claim 7 , thyroid cancer claim 7 , pancreatic cancer claim 7 , pituitary cancer claim 7 , cervical cancer claim 7 , uterine cancer claim 7 , ovarian cancer claim 7 , esophageal cancer claim 7 , gastric cancer claim 7 , colon cancer claim 7 , rectal cancer claim 7 , liver cancer claim 7 , gallbladder cancer claim 7 , lung cancer claim 7 , oral cavity cancer claim 7 , skin cancer claim 7 , renal cancer claim 7 , leukemia claim 7 , lymphoma and myeloma. The present invention relates to novel selenyl-methyluracil compounds and a pharmaceutical composition for enhancing the effect of radiotherapy comprising the same.Methods for treating malignant tumors may be generally classified into surgical methods, chemotherapy and radiotherapy (radiation therapy). About 35% of all cancer patients in South-Korea and about 50% thereof in US receive some type of radiotherapy, at present, and the number of domestic patients who need to receive radiotherapy is increasing every year. Under this circumstance, the importance of radiotherapy in cancer treatment is presently increasing. Radiotherapy has been known as an essential treatment method for various types of cancer, however, it also has some problems such as resistance to radiation built in cancer cells, low efficiency against solid cancers, damages in normal tissue when high-dose of radiation is applied, or the like, resulting in lowering the efficiency in cancer treatment. For obtaining high anti-tumor effect, chemoradiotherapy, i.e., the combined therapy ...

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Номер записи: 91
22-08-2013 дата публикации

METHOD OF REDUCING INTRAOCULAR PRESSURE IN HUMANS

Номер: US20130217643A1
Автор: BARMAN Shikha, BAUMGARTNER Rudolf A.
Принадлежит: INOTEK PHARMACEUTICALS CORPORATION

Provided herein are compounds of Formula I, compositions comprising an effective amount of a compound of Formula I, and methods for reducing intraocular pressure comprising administering an effective amount of compounds of Formula I to a subject in need thereof. 118-. (canceled)19. A method of treating diseases and conditions caused by elevated intraocular pressure (IOP) in a human subject in need thereof by administering an effective amount of a selective adenosine Aagonist to an affected eye of the subject.20. The method of claim 19 , wherein the diseases and conditions caused by elevated IOP in a human are selected from the group consisting of normal-tension glaucoma claim 19 , ocular hypertension (OHT) claim 19 , and primary open-angle glaucoma (POAG).24. The method as claimed in wherein the selective adenosine Aagonist is selected from the group consisting of:((2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl nitrate;((2R,3S,4R,5R)-5-(2-chloro-6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl nitrate;sodium ((2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl sulfate; and((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-(tetrahydrofuran-3-ylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methyl nitrate.25. The method as claimed in wherein the IOP of the affected eye is reduced by at least 10%.26. The method as claimed in wherein the IOP of the affected eye is reduced by about 10-20%.27. The method as claimed in wherein the IOP of the affected eye is reduced by 20% or more.28. The method as claimed in wherein the IOP of the affected eye is reduced by at least 10% for more than 3 hours.29. The method as claimed in wherein the IOP of the affected eye is reduced by about 10-20% for more than 3 hours.30. The method as claimed in wherein the IOP of the affected eye is reduced by 20% or more for more than 3 hours.31. The method as claimed in wherein the IOP of the affected eye ...

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Номер записи: 92
22-08-2013 дата публикации

Uracyl Spirooxetane Nucleosides

Номер: US20130217648A1
Автор: Hu Lili, Jonckers Tim Hugo Maria, Raboisson Pierre Jean-Marie Bernard, Tahri Abdellah, Van Hoof Steven Maurice Paula, Vandyck Koen
Принадлежит:

Compounds of the formula I: 212-. (canceled)13. The compound of claim 1 , wherein Ris a monophosphate ester.14. A pharmaceutical composition comprising an anti-virally effective amount of a compound of and a pharmaceutically acceptable carrier.15. A method for inhibiting HCV claim 13 , comprising administering to a patient in need thereof an effective amount of a compound of .16. The compound of claim 1 , wherein Ris a diphosphate ester.17. A pharmaceutical composition comprising an anti-virally effective amount of a compound of and a pharmaceutically acceptable carrier.18. A method for inhibiting HCV claim 16 , comprising administering to a patient in need thereof an effective amount of a compound of .19. The compound of claim 1 , wherein Ris a triphosphate ester.20. A pharmaceutical composition comprising an anti-virally effective amount of a compound of and a pharmaceutically acceptable carrier.21. A method for inhibiting HCV claim 19 , comprising administering to a patient in need thereof an effective amount of a compound of . This invention relates to uracyl spirooxetane nucleosides that are inhibitors of the hepatitis C virus (HCV).HCV is a single stranded, positive-sense RNA virus belonging to the family of viruses in the hepacivirus genus. The NS5B region of the RNA polygene encodes a RNA dependent RNA polymerase (RdRp), which is essential to viral replication. Following the initial acute infection, a majority of infected individuals develop chronic hepatitis because HCV replicates preferentially in hepatocytes but is not directly cytopathic. In particular, the lack of a vigorous T-lymphocyte response and the high propensity of the virus to mutate appear to promote a high rate of chronic infection. Chronic hepatitis can progress to liver fibrosis, leading to cirrhosis, end-stage liver disease, and HCC (hepatocellular carcinoma), making it the leading cause of liver transplantations. There are six major HCV genotypes and more than 50 subtypes, which are ...

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Номер записи: 93
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: 94
29-08-2013 дата публикации

Uracyl Spirooxetane Nucleoside Phosphoramidates

Номер: US20130225520A1
Автор: Hu Lili, Jonckers Tim Hugo Maria, Raboisson Pierre Jean-Marie Bernard, Tahri Abdellah, Van Hoof Steven Maurice Paula, Vandyck Koen
Принадлежит:

This invention relates to a stereochemically pure uracyl spirooxetane nucleoside phosphoramidate which inhibits the hepatitis C virus (HCV). 2. The compound wherein said compound is a salt form.3. The compound of wherein the salt is a pharmaceutically acceptable salt.4. The compound of wherein said compound is a solvated form.5. The compound of having a stereoisomeric excess of at least 80%.6. The compound of having a stereoisomeric excess of at least 90%.7. The compound of having a stereoisomeric excess of at least 94%.8. A pharmaceutical composition comprising an anti-virally effective amount of a compound of claim 4 , and a pharmaceutically acceptable carrier.910-. (canceled)11. A method for treating a hepatitis C virus infection comprising contacting a cell with the compound of . This invention relates to an uracyl spirooxetane nucleoside phosphoramidate useful in the treatment of patients infected with the hepatitis C virus (HCV).HCV is a single stranded, positive-sense RNA virus belonging to the Flaviviridae family of viruses in the hepacivirus genus. The NS5B region of the RNA polygene encodes a RNA dependent RNA polymerase (RdRp), which is essential to viral replication. Following the initial acute infection, a majority of infected individuals develop chronic hepatitis because HCV replicates preferentially in hepatocytes but is not directly cytopathic. In particular, the lack of a vigorous T-lymphocyte response and the high propensity of the virus to mutate appear to promote a high rate of chronic infection. Chronic hepatitis can progress to liver fibrosis, leading to cirrhosis, end-stage liver disease, and HCC (hepatocellular carcinoma), making it the leading cause of liver transplantations. There are six major HCV genotypes and more than 50 subtypes, which are differently distributed geographically. HCV genotype 1 is the predominant genotype in Europe and in the US. The extensive genetic heterogeneity of HCV has important diagnostic and clinical ...

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Номер записи: 95
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: 96
12-09-2013 дата публикации

Cdk-inhibiting pyrrolopyrimidinone carboxamide derivative or pharmaceutically acceptable salt thereof, and pharmaceutical composition containing the same as active ingredient for preventing or treating hepatocellular carcinoma

Номер: US20130237495A1
Автор: Byeong Moon Kim, Seun Ju Cho, Seung Ki Lee, Young Jong Kim
Принадлежит: SNU R&DB FOUNDATION

The present invention relates to a CDK-inhibiting pyrrolopyrimidinone carboxamide derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing same as an active ingredient for preventing or treating liver cell cancer, and the composition containing the pyrrolopyrimidinone carboxamide derivative of the present invention suppresses the cell growth of SNU-354 cell, which is a liver cancer stem cell in humans, by inhibiting CDK1 and CDK2, and induces cell apoptosis of the cell by inhibiting CDK7 and CDK 7, and thus can be effective in use for preventing or treating liver cell cancer.

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Номер записи: 97
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: 98
19-09-2013 дата публикации

2'-SUBSTITUTED CARBA-NUCLEOSIDE ANALOGS FOR ANTIVIRAL TREATMENT

Номер: US20130243725A1
Автор: Clarke Michael ONeil Hanrahan
Принадлежит: Gilead Sciences, Inc.

Provided are compounds of Formula I, 3. The compound of claim 2 , wherein Ris H.5. The compound of claim 1 , wherein Ris H claim 1 , CHOH claim 1 , CHF claim 1 , CHF claim 1 , CH═CH claim 1 , C≡CH claim 1 , CN claim 1 , CHCH═CH claim 1 , N claim 1 , CH claim 1 , or CHCH.6. The compound of claim 5 , wherein Ris H.7. The compound of claim 1 , wherein Ris OH or O-benzyl.8. The compound of claim 7 , wherein Ris OH.9. The compound of claim 1 , wherein Ris F or N.10. The compound of claim 9 , wherein Ris F.11. The compound of claim 1 , wherein Ris NHand Ris H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , N claim 1 , CN claim 1 , CF claim 1 , NH claim 1 , SMe claim 1 , or SOMe.12. The compound of claim 1 , wherein Ris NHand Ris ═O claim 1 , OH claim 1 , OMe claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , NH claim 1 , NHMe claim 1 , NHcPr or SMe.13. The compound of claim 1 , wherein each of Rand Ris independently selected from the group consisting of H claim 1 , NH claim 1 , ═O claim 1 , NHMe claim 1 , NHcPr claim 1 , OH claim 1 , OMe claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , SMe claim 1 , F claim 1 , N claim 1 , CN claim 1 , CF claim 1 , and SOMe.14. The compound of claim 13 , wherein Ris H or NH.15. The compound of claim 13 , wherein Ris ═O or NH.17. The compound of claim 16 , wherein Ris H.18. The compound of claim 1 , wherein Ris H or OH.19. The compound of claim 18 , wherein Ris H.20. The compound of claim 1 , wherein Ris H claim 1 , Ris OH and Ris F.21. The compound of claim 20 , wherein Rand Rare NH claim 20 , H or ═O claim 20 , and Rand Rare hydrogen.25. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a therapeutically effective amount of a compound of , and a pharmaceutically acceptable carrier or excipient.'}26. The pharmaceutical composition of further comprising at least one additional therapeutic agent.27. The pharmaceutical composition of claim 26 , wherein the at least one additional therapeutic agent is ...

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Номер записи: 99
19-09-2013 дата публикации

Uracyl Spirooxetane Nucleoside Phosphoramidates

Номер: US20130244968A1
Автор: Hu Lili, Jonckers Tim Hugo Maria, Raboisson Pierre Jean-Marie Bernard, Tahri Abdellah, Van Hoof Steven Maurice Paula, Vandyck Koen
Принадлежит:

This invention relates to a stereochemically pure uracyl spirooxetane nucleoside phosphoramidate useful in the treatment of patients infected with the hepatitis C virus (HCV). 2. The compound of claim 1 , wherein said compound is a salt.3. The compound of wherein the salt is a pharmaceutically acceptable salt.4. The compound of claim 1 , wherein said compound is a solvate.5. The compound of claim having a stereoisomeric excess of at least 80%.6. The compound of having a stereoisomeric excess of at least 90%.7. The compound of having a stereoisomeric excess of at least 94%.8. A pharmaceutical composition comprising an anti-virally effective amount of the compound of claim claim 6 , and a pharmaceutically acceptable carrier.910-. (canceled)11. A method for treating a hepatitis C virus infection comprising contacting a cell with the compound of . This invention relates to an uracyl spirooxetane nucleoside phosphoramidate useful in the treatment of patients infected with the hepatitis C virus (HCV).HCV is a single stranded, positive-sense RNA virus belonging to the Flaviviridae family of viruses in the hepacivirus genus. The NS5B region of the RNA polygene encodes a RNA dependent RNA polymerase (RdRp), which is essential to viral replication. Following the initial acute infection, a majority of infected individuals develop chronic hepatitis because HCV replicates preferentially in hepatocytes but is not directly cytopathic. In particular, the lack of a vigorous T-lymphocyte response and the high propensity of the virus to mutate appear to promote a high rate of chronic infection. Chronic hepatitis can progress to liver fibrosis, leading to cirrhosis, end-stage liver disease, and HCC (hepatocellular carcinoma), making it the leading cause of liver transplantations. There are six major HCV genotypes and more than 50 subtypes, which are differently distributed geographically. HCV genotype 1 is the predominant genotype in Europe and in the US. The extensive genetic ...

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Номер записи: 100