Abstract: The present invention provides 2,6-dinitrogen-containing substituted purine compounds of formula (A) or salts or solvates thereof or the solvates of salts thereof, as well as pharmaceutical compositions containing such compounds. The compounds of the present invention have the characteristics of lower toxicity, broad anticancer spectrum, higher anticancer activity, good stability and the like. The compounds are useful for the manufacture of an antitumor medicament. The present invention also provides a process for preparing these compounds.

Abstract: The present invention provides luminescent metal ion complexes for use in a wide range of biological and chemical studies. The luminescent metal ion complexes of the invention comprise a metal ion chelating component covalently bound to a carrier molecule. Also provided are methods of making and using the luminescent metal ion complexes.

Abstract: One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3?-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide.

Abstract: 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.

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: Crystals of a purine nucleoside compound, particularly crystals of 2?,3?-dideoxyinosine, which have excellent storage stability and have a concentration of phosphate attached to the crystal of 25 ppm or more, may be produce by: (1) preparing an aqueous solution containing phosphate ion (PO43?) and a purine nucleoside compound; and (2) crystallizing the purine nucleoside compound from the aqueous solution.

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: Disclosed herein are biomarkers for determining gamma radiation exposure by an animal or human. The biomarkers include 3-hydroxy-2-methylbenzoic acid 3-O-sulfate, N-hexanoylglycine, ?-thymidine, taurine, xanthine, xanthosine, 2?-deoxyuridine, 2?-deoxycytidine, 2?-deoxyxanthosine, or any salt, ion, or combination thereof. Also disclosed are methods for determining gamma radiation exposure by an animal or human, which include the step of measuring the amount of one or more biomarkers specific to gamma radiation in the biological fluid and correlating the amount of said biomarkers to the amount of gamma radiation exposure by the animal or human. Systems for determining gamma radiation exposure by an animal or human and methods of treating an animal or human for gamma radiation exposure are also disclosed.

Abstract: The present invention relates to novel methods and novel solid support materials for the tandem synthesis of two or more different oligonucleotides on the same solid support in one synthetic run. The methods involve novel support preparations comprised of two or more types of orthogonally protected anchor groups. Subsequent to the selective removal of the first of the respective protective groups, the first oligonucleotide is assembled on the deblocked anchor groups according to standard methods, preferably via phosphoramidite chemistry. Following the capping of said first oligonucleotide, the anchor groups blocked by a second type of protective group are selectively liberated and serve as the starting point for the assembly of a second oligonucleotide, and so forth. After completion of all the syntheses on the solid support, the oligonucleotides are released from the solid support and deprotected at the nucleobases, using standard methods.

Abstract: The invention relates to analogous compounds of 6-thioguanosine triphosphate of general formula (I). A compound of the general formula (I); wherein the dashed bond in the sugar moiety can be either single or double and wherein R1, R2, R3, R4 or R5, equal or different between each other, have general formula -(Int)m-Ter, wherein m is between 0 and 12 and Int and Ter are Internal and Terminal building blocks, wherein Int is selected from the group consisting of formula (II); and Ter is selected from the group consisting of formula (III).

Abstract: The present invention relates to novel chimeric oligomeric compounds having a plurality of alternating regions having either RNA like having northern or 3?-endo conformational geometry (3?-endo regions) or DNA like having southern or C2?-endo/O4?-endo conformational geometry. The oligomeric compounds of the present invention have shown reduction in mRNA levels in multiple in vitro and in vivo assay systems and are useful, for example, for investigative and therapeutic purposes.

Abstract: The invention provides compounds of formula I: wherein R1 and R2 have any of the values defined in the specification and salts thereof, as well as compositions comprising such compounds and therapeutic methods that utilize such compounds.

Abstract: The invention concerns the production of salts or chelates of methyl donors, in particular S-adenosyl-L-methionine or SAMe and betaine or N,N,N-trimethylglycine, with phytic acid or with phosphorylate inositol, possibly partially salified with metal cations, with the formation of stable, totally natural, compounds having a biological activity typical of the starting methyl donors and also combined with, and enhanced by, the biological activity typical of phytic acid or of inositol. The invention also concerns nutraceutical, pharmaceutical, dietary, phytopharmaceutical or veterinary compositions comrising one or more salts or complexes of methyl donors with phytic acid or its derivatives and the method for the synthesis thereof.

Abstract: This invention relates to cytidine deaminase inhibitors (Cytidine deaminase inhibitors) of cytidine deaminases and uses thereof.

Abstract: The present invention provides materials and methods for enhancing aptamers. More specifically, the materials and methods of the present invention are directed toward the modification of aptamers by the identification of one or more cleavage sites, and introduction of a chemical substitution at a position proximal to the cleavage site(s). Such aptamers are useful for the treatment of disease, in diagnostic and detection applications, and/or research, e.g., target validation.

Abstract: The present invention provides a thionucleoside-S-nitrosyl derivative of the following Formula I or a salt thereof: [wherein R1 represents ribose, 2-deoxyribose or a derivative of either, and R2 represents a hydrogen atom, an amino group, a hydroxyl group, a halogen atom, a R3-oxy group or a R3-amino group (wherein R3 represents an optionally substituted C1-15 alkyl group or an optionally substituted C1-15 acyl group)].

Abstract: An agent for inhibiting translesion DNA replication comprises a non-natural adenine ribose analog represented by those as set forth in FIG. 1.

Abstract: Disclosed are conjugates comprising a dendrimer and a ligand, which is a functionalized congener of an agonist or antagonist of a receptor of the G-protein coupled receptor (GPCR) superfamily, for example, wherein the functionalized congener is an A1 adenosine receptor agonist having a purine nucleoside moiety and a functional group at the N6 position of the purine nucleoside moiety, wherein the functional group has the formula (I): N6H—Ar1—CH2—C(?O)NH—R1 (I), wherein Ar1 and R1 as defined herein. Also disclosed are pharmaceutical compositions, methods of treating various diseases, and a diagnostic method employing such conjugates.

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: 2-Chloro-9-(2-deoxy-2-fluoro-?-D-arabinofuranosyl)-9H-purin-6-amine is synthesized by reacting a 2-chloro-6-substituted purine with a protected and activated 2-deoxy-2-fluoro-D-arabinofiranose; and reacting with a base such as ammonia to provide 2-chloro-9-(2-deoxy-2-fluoro-?-D-arabinofuranosyl)-9H-purin-6-amine. When the purine reactant is substituted in the 6 position with a halogen, a reaction step with an alkoxide is carried out prior to the reaction with ammonia.

Abstract: The invention provides oxogenous markers, designed and synthesized for the measurement and characterization of oxidative/nitrosative stress levels, thus enable the identification of the type of reactive ROS/NRS involved, characterization of the damaged products and their formation kinetics, and thereby the identification of pathological conditions associated with oxidative/nitrosative stress, before appearing or at the stage of development.

Abstract: The disclosure provides nucleotide analogs and methods of their use. Analogs of the invention comprise a reporter molecule (label) attached via the N4, N6, O4, or O6 position of the nitrogenous base portion of the analog. In a preferred embodiment, nucleotide analogs of the invention comprise a label attached to the nitrogenous base portion of the analog via a cleavable linker at the N4, O4, N6 or O6 position.

Abstract: Nucleotide analogs characterized by the presence of an amidate linked amino acid or an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise a phosphoamidate or ester bond that is hydrolyzed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for their synthesis and use are described.

Abstract: Disclosed are compounds, compositions and methods for treating hepatitis C virus infections.

Abstract: The present invention provides a 4?-C-substituted-2-haloadenosine derivative represented by the following formula [I], [II], or [III]: (wherein X represents a halogen atom, R1 represents an ethynyl group or a cyano group, and R2 represents hydrogen, a phosphate residue, or a phosphate derivative residue). The present invention also provides a pharmaceutical composition containing the derivative and a pharmaceutically acceptable carrier therefor.

Abstract: Analogs or derivatives of nitrobenzylthioinosine compounds. The use of these new analogs of nitrobenzylthioinosine and methods for the treatment of pain and various other indications using these analogs of nitrobenzylthioinosine as well as pharmaceutical compositions including analogs of nitrobenzylthioinosine.

Abstract: A production method for conveniently producing a 5?-acyloxynucleoside compound shown by the formula [A] in a good yield while suppressing formation of by-products, including subjecting a 2?,3?,5?-triacyloxynucleoside compound represented by the formula [I] to selective deacylation in an alcohol represented by the formula [II] using a base selected from the group consisting of alkali metal hydroxide, alkali metal alkoxide and alkali metal carbonate: wherein each symbol in the formula is as defined in the specification.

Abstract: A compound of the formula (1): wherein R1 and R2 are the same or different and represent a hydrogen atom, a hydroxyl protecting group, a phosphate group, or —P(R3)R4, wherein R3 and R4 are the same or different and represent a hydroxyl group, an amino group, an alkoxy group having from 1 to 4 carbon atoms, a cyanoalkoxy group having from 1 to 5 carbon atoms or an amino group substituted by an alkyl group having from 1 to 4 carbon atoms; A represents an alkylene group having from 1 to 4 carbon atoms and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group or a substituted 2-oxo-pyrimidin-1-yl group having a substituent ? selected from the group consisting of a hydroxyl group which may be protected, an alkoxy group having from 1 to 4 carbon atoms, a mercapto group which may be protected, an alkylthio group having from 1 to 4 carbon atoms, an alkoxy group having from 1 to 4 carbon atoms, an amino group which may be protected, a mono- or di-alkylamino group which may b

Abstract: A probe for a gene or a primer for starting amplification comprising an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of the nucleoside units is a structure of the formula (2): wherein A represents a C1-C4 alkylene group, and B is an unsubstituted purin-9-yl group, an unsubstituted 2-oxo-pyrimidin-1-yl-group, a substituted purin-9-yl-group or a substituted 2-oxo-pyrimidin-1-yl group. Also a method for preventing or treating a disease preventable or treatable by the antisense or antigene activity of an oligonucleotide by administering the oligonucleotide analogue.

Abstract: The invention relates to compositions and methods for isolating nucleic acids from biological samples, including whole tissue. The invention also provides kits for isolating nucleic acids from biological samples.

Abstract: Surfaces containing high purity silica (silicon dioxide) exhibit high loading potential for nucleic acids. Formulations containing nucleic acids and materials which mask the electrostatic interactions between the nucleic acids and surfaces are disclosed. By masking the phosphate charges of the nucleic acids, undesired interactions may be minimized or eliminated, thereby allowing the covalent bonding of the nucleic acids to the surface to proceed. The use of such formulations additionally minimizes nonspecific binding of the nucleic acids to the surface. Examples of materials to be included in such formulations include cations, xanthines, hexoses, purines, arginine, lysine, polyarginine, polylysine, and quaternary ammonium salts.

Abstract: Various 2?-beta-methyl-6-substituted adenosine analogs (including 2,6-disubstituted adenosine, 8-aza-6-substituted adenosine, and 2-aza-6-substituted adenosine) are prepared by conventional and combinatorial library approaches. Contemplated compounds are particularly useful as therapeutic agents, and especially as antiviral agents.

Abstract: Bicyclonucleoside analogues which exhibit anti-AIDS activity and intermediates to produce oligonucleotide analogues which have anti-sense or anti-gene activity as well as in vivo stability. Compounds of the following formula (1) or their pharmaceutically acceptable salts. wherein R1 represents a hydrogen atom or a protecting group for a hydroxy group, R2 represents an azido group or an optionally protected amino group or the like, B represents a purin-9-yl or a 2-oxo-1,2-dihydropyrimidin-1-yl group, which are optionally substituted with substituents selected from the group consisting of a halogen atom, an alkyl group having 1–6 carbon atoms, a hydroxy group, a mercapto group and an amino group.

Abstract: Disclosed are novel compounds that are partial and full A1 adenosine receptor agonists, useful for treating various disease states, in particular tachycardia and atrial flutter, angina, and myocardial infarction.

Abstract: Disclosed are novel compounds that are partial and full A1 adenosine receptor agonists, useful for treating various disease states, in particular tachycardia and atrial flutter, angina, and myocardial infarction.

Abstract: The present invention relates to compounds of the formula: and pharmaceutically acceptable salts and solvates thereof, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such compounds.

Abstract: Disclosed are A1 adenosine receptor agonists of the formula: wherein: R1 is optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; R2 is hydrogen, halo, trifluoromethyl, or cyano; R3 is hydrogen, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl, R4 and R5 are independently hydrogen or optionally substituted acyl; X is a covalent bond or lower alkylene optionally substituted by cycloalkyl; X1 is a covalent bond or alkylene; Y is a covalent bond or lower alkylene optionally substituted by hedroxy or cycloalkyl; and Z is —C?C—, —R6C?CR7—, or —CHR6CHR7—, in which R6 and R7 at each occurrence are hydrogen or lower alkyl.

Abstract: The present invention relates to a combination comprising (a) an adenosine A2a receptor agonist as defined herein and (b) an adrenergic ?2 receptor agonist, for simultaneous, sequential or separate administration by the inhaled route in the treatment of an obstructive airways or other inflammatory disease.

Abstract: 2-Chloro-9-(2-deoxy-2-fluoro-?-D-arabinofuranosyl)-9H-purin-9-amine is synthesized by reacting a 2-chloro-6-substituted purine with a protected and activated 2-deoxy-2-fluoro-D-arabinofuranose; and reacting with a base such as ammonia to provide 2-chloro-9-(2-deoxy-2-fluoro-?-D-arabinofuranosyl)-9H-purin-6-amine. When the purine reactant is substituted in the 6 position with a halogen, a reaction step with an alkoxide is carried out prior to the reaction with ammonia.

Abstract: The invention is directed to 3-?-D-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.

Abstract: The invention relates to compositions comprising 2?-deoxyribonucleosides. The invention also relates to methods of accelerating the healing of wounds, abrasions, cuts, incisions, and superficial burns induced by heat, sunlight, chemical agents, or infections, and methods for ameliorating the effects of aging of the epidermal tissues comprising administering the compositions of the present invention to an animal.

Abstract: Surfaces containing high purity silica (silicon dioxide) exhibit high loading potential for nucleic acids. Formulations containing nucleic acids and materials which mask the electrostatic interactions between the nucleic acids and surfaces are disclosed. By masking the phosphate charges of the nucleic acids, undesired interactions may be minimized or eliminated, thereby allowing the covalent bonding of the nucleic acids to the surface to proceed. The use of such formulations additionally minimizes nonspecific binding of the nucleic acids to the surface. Examples of materials to be included in such formulations include cations, xanthines, hexoses, purines, arginine, lysine, polyarginine, polylysine, and quaternary ammonium salts.

Abstract: The invention relates to certain oxypurine nucleosides, congeners of such oxypurine nucleosides, and acyl derivatives thereof, and compositions which contain at least one of these compounds. The invention also relates to methods of treating or preventing hematopoietic disorders and modifying hematopoiesis, and treating or preventing inflammatory diseases and bacterial infections by administering a compound or composition of the present invention to an animal.

Abstract: A3 agonists, methods of using such A3 agonists and pharmaceutical compositions containing such A3 agonists. The A3 agonists are useful for the reduction of tissue damage resulting from tissue ischemia or hypoxia.

Abstract: There are provided according to the invention, novel compounds of formula (I) wherein R1, R2 and R3 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory disease.

Abstract: The present invention relates to compounds of the formula: and pharmaceutically acceptable salts and solvates thereof, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such compounds.

Abstract: Disclosed are compounds, compositions and methods for treating hepatitis C virus infections.

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

Abstract: This invention relates to certain novel 2′-halomethylidene, 2′-ethenylidene and 2′-ethynyl cytidine, uridine and guanosine derivatives, and compositions thereof, which are useful in the treatment of patients afflicted with neoplastic or viral disease states.

Abstract: Disclosed are novel bicyclic tris(anhydride)s useful as intermediates in the synthesis of biologically active compounds, and the compounds which may be synthesized from such intermediates.