Abstract: The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.

Abstract: Modified Tryptamine, Tryptamine-2?-deoxy-uridine (TrpdU) and TrpdU-phosphoramidites for oligonucleotide synthesis are provided, as well as improved methods of their synthesis and oligonucleotides comprising at least one modified TrpdU nucleotide.

Abstract: The present disclosure relates to the field of nucleic acid chemistry, specifically to 5-position modified uridines as well as phosphoramidite and triphosphate derivatives thereof. The present disclosure also relates to methods of making and using the same.

Abstract: Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Picornavirus and/or Flaviviridae infection with one or more nucleosides, nucleotides and nucleotide analogs.

Abstract: A novel method of simultaneously protecting two functions which are same or different, namely hydroxyl, amine, or thiol ones, particularly in sugars, polyalcohols, nucleosides, nucleotides, peptides, and nucleic acids during an organic synthesis, and to novel compounds for implementing this method, as well as to the method of obtaining these compounds. Method of simultaneously protecting two hydroxyl, amine, or thiol functions according to the invention by carrying out a protecting reaction between a compound having at least two free hydroxyl, amine, or thiol groups, and the disilane of formula 1, where R stands for Cl or Br, or I, or a substituent of formula 2, where X1, X2, X3, X4 are the same or different.

Abstract: The present invention provides novel heteroaryl compounds having a pyrimidine-containing core that is linked to a 4-trifluoromethoxyphenyl group via an amine linker. Such compounds are useful for the treatment of cancers.

Abstract: Methods and compositions disclosed herein relate to detecting, analyzing, isolating and inhibiting methyltransferases, methyltransferase substrates, S-adenosyl-methionine-binding proteins and RNA, including for the treatment of disease.

Abstract: A method for the prevention or treatment in a mammal of a disease preventable or treatable by the pharmacologically useful antisense or antigene activity of an oligonucleotide analogue or a pharmacologically acceptable salt thereof in the body of said mammal, which method comprises administering to said mammal in need of such prevention or treatment a pharmaceutically effective amount of an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of said nucleoside units is a structure of the formula (2): wherein A is methylene; and B is an unsubstituted purin-9-yl, an unsubstituted 2-oxo-pyrimidin-1-yl or a substituted purin-9-yl; or a pharmacologically acceptable salt thereof.

Abstract: This invention provides a nucleotide analogue comprising (i) a base selected from the group consisting of adenine, guanine, cytosine, thymine and uracil, (ii) a deoxyribose, (iii) an allyl moiety bound to the 3?-oxygen of the deoxyribose and (iv) a fluorophore bound to the base via an allyl linker, and methods of nucleic acid sequencing employing the nucleotide analogue.

Abstract: Compositions and methods to improve the pharmacokinetic profile of S-Adenosylmethionine (SAMe) are provided, as are methods of treating various disorders using SAMe formulations with improved pharmacokinetic profiles. More specifically, the invention is directed to methods of treating a disease or disorder in a subject and/or improving the nutritional status of a subject by administering formulations exhibiting improved pharmacokinetic profiles of exogenous SAMe. The method also includes the step of orally administering compositions of the invention to the subject once per day after overnight fast; that is prior to food intake in the morning.

Abstract: This invention relates to heteroaryl compounds, containing a purinyl moiety, that inhibit DNA methyltransferase (DNMT) activity—including DNMT1, DNMT3a, or DNMT3b—useful in the treatment of cancer and hyperproliferative diseases.

Abstract: 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. Examples of viral infections include a respiratory syncytial viral (RSV) and influenza infection.

Abstract: 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.

Abstract: The disclosure provides nucleotide analogues that comprise tetrahydrofuranyl or tetrahydrothienyl moieties with quaternary centers at the 3? position, the pharmaceutical formulations comprising the analogues, and methods of using the analogues and formulations for treating, preventing, and/or inhibiting diseases or conditions associated with cancers and viruses.

Abstract: Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 3?-deoxy nucleoside compounds according to Formula 3001a or 3001b: or a pharmaceutically acceptable salts, solvates, stereoisomeric forms, tautomeric forms, or polymorphic forms thereof, wherein PD, Base1 and Base2 are as provided herein.

Abstract: The invention is directed to processes of preparing phosphonate nucleosides comprising a phosphonalkoxy-substituted five-membered, saturated or unsaturated, oxygen-containing ring coupled to a heterocyclic nucleobase such as a pyrimidine or purine base.

Abstract: A novel class of pharmaceuticals which comprises a Locked Nucleic Acid (LNA) which can be used in antisense therapy. These novel oligonucleotides have improved antisense properties. The novel oligonucleotides are composed of at least one LNA selected from beta-D-thio/amino-LNA or alpha-L-oxy/thio/amino-LNA. The oligonucleotides comprising LNA may also include DNA and/or RNA nucleotides.

Abstract: The present invention relates to compositions and methods for improving outcomes in vascular interventional procedures. In particular, the present invention relates to compositions and methods for improving outcomes in vascular interventional procedures using an anti-no-reflow guide wire that attenuates the “no-reflow” phenomenon that is associated with negative outcomes.

Abstract: Compounds having the general formula (I): are provided which have enhanced inhibitory potency and are thus useful in methods of prophylaxis or treatment of a viral infection such as hepatitis C virus. The compounds are phosphoramidate derivatives of nucleoside compounds derived from bases such as adenine and guanine. The glycoside moiety of the nucleoside compound can be substituted at the ss-2? position with methyl and the phosphoramidate group can be 1-naphthyl linked by —O— to the P atom. These compounds can be administered as pharmaceutical compositions, and methods for their preparation are also provided.

Abstract: The present invention relates generally to labeled and unlabeled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.

Abstract: Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of 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.

Abstract: Embodiments are disclosed herein that involve C5-functionalized nucleic acids, which can be used for detecting a target in a nucleic acid. Particular embodiments disclose methods for making these compounds, wherein the compounds can be formed by coupling of an intermediate with a linker. Certain embodiments disclose the use of these compounds for detecting single nucleotide polymorphisms, and for increasing the thermal affinity of nucleic acid complements as compared to unmodified nucleic acid complements. In addition, the disclosed compounds can decrease enzymatic degradation of nucleic acids.

Abstract: The present invention has an object to provide an external dermal agent with a sustainable anti-wrinkle action, which has both the action of enhancing the proliferation and differentiation of keratinocytes in the skin and the action of enhancing the collagen production in the skin, and which assists the maintenance and the improvement of tissue structures and physiological functions of the epidermis and the dermis, whereby providing a remarkable skin improvement effect. The present invention solves the above abject by providing an external dermal agent containing ?-D-glucopyranosyl-(1?3?)-adenosine and/or ?-D-glucopyranosyl-(1?5?)-adenosine as an effective ingredient(s).

Abstract: The disclosure concerns the enzymatic synthesis of stable analogues of nicotinamide adenine dinucleotide NAD/NADH and nicotinamide adenine dinucleotide phosphate NADP/NADPH, the so-called “carba-NADs”, i.e. analogues of NAD/NADH or NADP/NADPH, respectively, comprising a carbacyclic sugar instead of ribose.

Abstract: The present invention relates to substituted purine and 7-deazapurine compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Abstract: An improved method of preparing a sugar modified nucleoside analog includes a protocol in which a hydroxy group of a sugar is selectively deprotected and oxidized prior to nucleophilic modification of the corresponding carbonyl group. The modified sugar is then coupled to a heterocyclic base that is modified with a dual nucleophilic reagent in a further step that provides N6-modified adenosine analogs with high stereoselectivity.

Abstract: The present invention provides a novel compound capable of inhibiting cardiac adenylyl cyclase. The present invention relates to a compound represented by the following formula (I) or a pharmaceutically acceptable salt, ester or solvate thereof: where R1, R2 and R3 each independently represent a hydrogen atom or an acyl group having an acidic or basic substituent, provided that all of R1, R2 and R3 are not simultaneously a hydrogen atom. The present invention also provides a modulator of adenylyl cyclase activity, a pharmaceutical composition and a food composition, all of which comprise the above-described compound or a pharmaceutically acceptable salt, ester or solvate thereof.

Abstract: The present invention relates to the use of nucleoside derivatives of formula Ia wherein the symbols are as defined in the specification, and of pharmaceutically acceptable salts thereof and to pharmaceutical compositions containing such compounds.

Abstract: The invention provides for novel 2-Deoxyadenosine compounds, which can treat HIV infection at low cytotoxicity values. Substitution at the 4?-position provided compounds which demonstrated low cytotoxicity values in an ATP-based cytotoxicity assay.

Abstract: 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.

Abstract: The present invention has an object to provide an effective and safe therapeutic agent for inflammatory diseases such as sepsis, hepatitis, and inflammatory bowel disease, and solves the above object by providing a therapeutic agent for inflammatory diseases containing adenosine N1-oxide or a derivative thereof as an effective ingredient.

Abstract: Many pathogens, including Mycobacterium tuberculosis and Yersinia pestis, rely on an iron acquisition system based on siderophores, secreted iron-chelating compounds with extremely high Fe(III) affinity. The compounds of the invention are inhibitors of domain salicylation enzymes, which catalyze the salicylation of an aroyl carrier protein (ArCP) domain to form a salicyl-ArCP domain thioester intermediate via a two-step reaction. The compounds include the intermediate mimic 5?-O—[N-(salicyl)sulfamoyl]-adenosine (salicyl-AMS) and analogs thereof. These compounds are inhibitors of the salicylate activity of MbtA, YbtE, PchD, and other domain salicylation enzymes involved in the biosynthesis of siderophores. Therefore, these compounds may be used in the treatment of infection caused by microorganisms which rely on siderphore-based iron acquisition systems.

Abstract: Conformationally locked 2?,4?-carbocylic nucleosides with improved thermal and nuclease stability are disclosed. Oligonucleotides incorporating the locked nucleosides, and methods of treating disease states, are also disclosed.

Abstract: The present invention relates to a method for inhibiting the induction of cell death by inhibiting the synthesis or secretion of AGE-albumin in cells of the mononuclear phagocyte system, to an AGE-albumin synthesis inhibitor, and to a pharmaceutical composition comprising the AGE-albumin synthesis inhibitor for preventing or treating degenerative disease and autoimmune disease. The AGE-albumin of the present invention is synthesized and secreted in human microglia or human macrophages in an Alzheimer's model, stroke model, Parkinson's disease model and rheumatoid arthritis model. The AGE-albumin synthesis and secretion are caused by oxidative stress. The expression of RAGE increases in first-order human neurons or cartilage cells to which AGE-albumin is administered, whereupon a MAPK signaling pathway is activated and the expression of Bax increases to induce an increase in calcium in mitochondria, thus finally inducing cell death.

Abstract: Compositions and methods are disclosed which are effective for modulating glucose homeostasis, calcium ion flux and cell death in target cells.

Abstract: The present invention relates to 2?-chloroacetylenyl-substituted nucleoside derivatives of the general formula (I): As well as pharmaceutical compositions comprising such compounds and methods to treat or prevent an HIV infection, HBV infection, HCV infection or abnormal cellular proliferation, comprising administering said compounds or compositions. In addition, the present invention includes processes for the preparation of such compounds, and the related ?-D and ?-L-nucleoside derivatives.

Abstract: An RNA of the present invention is an RNA containing a 5? cap structure and a coding region having a 5? initiation codon and a 3? stop codon on both ends of the coding region, the RNA having a nucleoside compound introduced at a site selected from among the 5? cap structure and 10 bases from a 5? end of the RNA, wherein the nucleoside compound is such that a group is attached to (i) a carbon atom at position 8 of a purine nucleus or (ii) a carbon atom at position 5 or 6 of a pyrimidine nucleus, the group being represented by formula (I): A-X?X-#??(I) where A represents an aryl group or a heteroaryl group, # represents a site where the group represented by the formula (I) is attached to the carbon atom at the position 8 of the purine nucleus or the carbon atom at the position 5 or 6 of the pyrimidine nucleus, and two Xs, which are identical to or different from each other, each represents a nitrogen atom or CH whose H may be substituted by alkyl.

Abstract: This disclosure provides novel reversibly terminated ribonucleotides which can be used as a reagent for DNA sequencing reactions. Methods of sequencing nucleic acids using the disclosed nucleotides are also provided.

Abstract: The present invention provides N6-substituted adenosine derivatives and N6-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.

Abstract: 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.

Abstract: [Problems] A derivative of a nucleic acid antimetabolite is demanded which can show a high therapeutic effect at a low dose. [Means For Solving Problems] Disclosed is a high molecular weight derivative of a nucleic acid antimetabolite, which is characterized by comprising a high molecular weight compound comprising a polyethylene glycol moiety and a polymer moiety having a carboxyl group in a side chain and a nucleoside derivative which can act as a nucleic acid antimetabolite, wherein the carboxyl group in the side chain is bound to a hydroxyl group in the nucleoside derivative via an ester bond. Also disclosed is a method for producing the high molecular weight derivative.

Abstract: The present invention includes novel 3?-deoxy-3?-methylidene-?-L-nucleosides, pharmaceutical composition comprising such compounds, as well as the methods to treat or to prevent viral infections and in particular HBV and/or HIV infections.

Abstract: The present invention provides therapeutic agents for preventing and treating neurodegenerative diseases. These agents synergistically target both the adenosine A2A receptor (A2AR) and the equilibrative nucleoside transporter 1 (ENT1).

Abstract: The present invention provides substituted 4-{3-[6-amino-9-(3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid esters and pharmaceutical compositions containing the same that are selective agonists of A2A adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.

Abstract: The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2?R)-2?-deoxy-2?-fluoro-2?-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.

Abstract: The present invention relates to 2?-allene-substituted nucleoside derivatives of the general formula (I): As well as pharmaceutical compositions comprising such compounds and methods to treat or prevent an HIV infection, HBV infection, HCV infection or abnormal cellular proliferation, comprising administering said compounds or compositions. In addition, the present invention includes processes for the preparation of such compounds, and the related ?-D and ?-L-nucleoside derivatives.

Abstract: Embodiments of the invention are to compounds, methods, and compositions for use in the treatment of viral infections. More specifically embodiments of the invention are 2?,4?-substituted nucleoside compounds useful for the treatment of viral infections, such as HIV, HCV, and HBV infections.

Abstract: Provided herein are alkoxy-carbonyl-amino-alkynyl-adenosine compounds and derivatives thereof and pharmaceutical compositions containing the same that are selective agonists of A2A adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.

Abstract: 5?-methylthioadenosine (MTA) is described as a compound that is susceptible to inhibiting and/or blocking the epithelial-mesenchymal transition (EMT), a process whereby epithelial cells become mesenchymal cells. The periodical intake of MTA [every 24 h for 21 days] significantly improves fibrosis and the markers for hepatic cellular damage in KO-Mdr2 mice with MTA (28 mg/kg). Following the daily oral administration of MTA, both the expression of EMT markers in the total liver and appreciable signs of fibrosis are significantly reduced, indicating the beneficial effect of MTA on the liver affected by the lack of Mdr2. MTA is proposed to be a safe drug, suitable for oral formulation and without secondary effects, to be used in the prevention and/or treatment of diseases associated with EMT, including chronic cholestatic diseases, fibrosis and cholangiocarcinoma.

Abstract: An oligo- or polynucleotide analogue having one or more structures of the general formula where B is a pyrimidine or purine nucleic acid base, or an analogue thereof, is disclosed. The use of this analogue provides an oligonucleotide analogue antisense molecule, which is minimally hydrolyzable with an enzyme in vivo, has a high sense strand binding ability, and is easily synthesized.