Abstract: The present disclosure provides novel anhydrate crystalline Forms 1 and 4 of 4?-Ethynyl-2-fluoro-2?-deoxyadenosine and pharmaceutical compositions thereof, each of which may be useful for the inhibition of HIV reverse transcriptase, the treatment or prophylaxis of HIV infection and/or the treatment, prophylaxis and/or delay in the onset or progression of AIDS or ARC.

Abstract: Compounds and methods for purifying oligonucleotides such as RNA and DNA. A target oligonucleotide is reacted with an orthoester linker comprising an affinity tag to form an orthoester oligonucleotide-orthoester linker conjugate which is subjected to a purification technique to separate the target oligonucleotide from impurities such as truncated oligonucleotides. The orthoester linker can be then removed under mild conditions to generate the target oligonucleotide in high purity.

Abstract: The invention relates to substituted 6-anilino-9-heterocyclylpurine derivatives of formula I wherein R denotes one to five substituents independently selected from the group hydrogen, halogen, hydroxy, amino, alkyloxy and alkyl group, R2 is selected from the group comprising amino, halogen, hydroxy, thio, and alkylthio group, Cyc is five- or six-membered heterocyclic ring containing one oxygen atom. The derivatives are useful for inhibition of plant stress.

Abstract: This invention claims aqueous compositions that comprise triphosphates of 2?-deoxynucleoside derivatives that have, instead of a 3?-OH moiety, a 3?-ONH2 moiety; wherein said compositions contain less than 0.5 mole percent contaminating triphosphate having a 3?-OH moiety, as well as processes for providing such compositions. The compositions further must contain insubstantial amounts of hydroxylamine.

Abstract: This disclosure relates to an improved process for the preparation of regadenoson, pharmaceutically acceptable salts thereof, and hydrates thereof, and for the preparation of intermediates useful in the synthesis of regadenoson. The disclosure also relates to a new crystalline form of regadenoson. Processes for the preparation of the crystalline form, compositions containing the crystalline form, and methods of use thereof are also described.

Abstract: This invention is directed to compounds of Formula (I) having the structure that are useful in the treatment of viral infections in mammals, particularly in humans, mediated, at least in part, by a virus in the Flaviviridae family of viruses.

Abstract: Disclosed is a synthesis suitable for large scale manufacture of an A2A-adenosine receptor agonist, and also relates to polymorphs of that compound, and to methods of isolating a specific polymorph.

Abstract: A method for the preparation of 2-(4-methoxycarbonylpyrazol-1-yl)adenosine of formula 1a and 2-(4-ethoxycarbonylpyrazol-1-yl)adenosine of formula 1b by reaction of 2-hydrazinoadenosine of formula III and the sodium salt of 3,3-dimethoxy-2-methoxycarbonylpropen-1-ol of formula Va or the sodium salt of 3,3-diethoxy-2-ethoxycarbonylpropen-1-ol of formula Vb in combination with a solvent and an acidic agent.

Abstract: A method for the preparation of 2-[4-[(methylamino)carbonyl]-1-H-pyrazol-1-yl]adenosine monohydrate of formula I by reaction of 2-(4-methoxycarbonylpyrazol-1-yl) adenosine of formula III with a solution of methylamine in a non-aqueous solvent, optionally in combination with another inert solvent, to produce anhydrous 2-[4-[(methylamino)carbonyl]-1-H-pyrazol-1-yl]adenosine, which is converted to 2-[4-[(methylamino)carbonyl]-1-H-pyrazol-1-yljadenosine monohydrate of formula I by addition of water.

Abstract: 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.

Abstract: This disclosure relates to an improved process for the preparation of regadenoson, pharmaceutically acceptable salts thereof, and hydrates thereof, and for the preparation of intermediates useful in the synthesis of regadenoson. The disclosure also relates to a new crystalline form of regadenoson. Processes for the preparation of the crystalline form, compositions containing the crystalline form, and methods of use thereof are also described.

Abstract: The present invention relates to novel 1,2,3-triazolyl purine derivatives. The invention also relates to using the derivatives to treat cancer and various viral infections.

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: Disclosed is a synthesis suitable for large scale manufacture of an A2A-adenosine receptor agonist, namely, (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide. Also, disclosed are polymorphs of this compound and methods for isolating a specific polymorph. Also, disclosed are pharmaceutical compositions and methods for preparing pharmaceutical compositions.

Abstract: 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.

Abstract: 2-adenosine N-pyrazole compounds having the following formula: and methods for using the compounds as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.

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 disclosure provides a process for the preparation of 2-adenosine N-pyrazole compounds exemplified by the structure shown below that are potent and selective agonists for A2A adenosine receptor, compositions comprising these compounds, and methods for using these compounds to stimulate mammalian coronary vasodilation for imaging the heart.

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: 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 2?-spiro-nucleosides and derivatives thereof useful for treating a subject infected by hepatitis C virus or dengue virus.

Abstract: This invention relates to a process of stereoselectively synthesizing a ?-nucleoside compound of formula (I): wherein R1, R2, and B are as defined in the specification; each of R3 and R4, independently, is H or fluoro. The process includes reacting, in the presence of a transition metal salt, a tetrahydrofuran compound of formula (II): wherein R1, R2, and L are as defined in the specification, with a nucleobase derivative; and each of R3 and R4, independently, is H or fluoro.

Abstract: A compound of formula (I), or stereoisomers or pharmaceutically acceptable salts thereof, wherein, R1a, R1b, R2a, R2b, U1, U2, X1, X2 and L are as defined herein.

Abstract: A compound of formula (I), or stereoisomers or pharmaceutically acceptable salts thereof, formula (1), or stereoisomers or pharmaceutically acceptable salts thereof, wherein A, U1, U2, R1a, R1b, R2 and R3 have the meanings as indicated in the specification, are useful for treating conditions mediated by activation of the adenosine A2A receptor, especially inflammatory or obstructive airways diseases. Pharmaceutical compositions that contain the compounds and a process for preparing the compounds are also described.

Abstract: Phosphoramidate compounds derived from guanine bases having enhanced therapeutic potency are provided, and these compounds in particular have enhanced potency with respect to treatment of viral infections, such as hepatitis C virus. Pharmaceutical compositions, methods of preparing the compounds, and methods of using the compounds and compositions to treat viral infections are also provided.

Abstract: Disclosed is a synthesis suitable for large scale manufacture of an A2A-adenosine receptor agonist, and also relates to polymorphs of that compound, and to methods of isolating a specific polymorph.

Abstract: Myocardial imaging methods are provided that are accomplished by administering doses of a pharmaceutical composition comprising one or more adenosine A2A receptor agonists, in particular regadenoson, useful for, among other indications, myocardial imaging and coronary vasodilation, in an amount sufficient to achieve at least a minimal increase in average coronary peak flow velocity.

Abstract: Compounds of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof, wherein W, R1, R2 and R3 have the meanings as indicated in the specification, are useful for treating conditions mediated by activation of the adenosine A2A receptor, especially inflammatory or obstructive airways diseases. Pharmaceutical compositions that contain the compounds and a process for preparing the compounds are also described.

Abstract: 2-adenosine N-pyrazole compounds having the following formula: and methods for using the compounds as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.

Abstract: This application provides a process for preparing enantiomerically pure ?-D-dioxolane nucleosides. In particular, a new synthesis of (?)-DAPD, suitable for large scale development, is described. In one embodiment the invention provides a process for preparing a substantially pure ?-D- or ?-L-1,3-dioxolane nucleosides comprising a) preparing or obtaining an esterified 2,2-dialkoxy ethanol; b) cyclizing the esterified 2,2-dialkoxy ethanol with glycolic acid to obtain a 1,3-dioxolane lactone; c) resolving the 1,3-dioxolane lactone to obtain a substantially pure D- or L-lactone; d) selectively reducing and activating the D- or L-chiral lactone to obtain a substantially pure D- or L-1,3-dioxolane; e) coupling the D- or L-1,3-dioxolane to an activated and/or protected purine or pyrimidine base; and f) optionally purifying the nucleoside to obtain a substantially pure protected ?-D- or ?-L-1,3-dioxolane nucleoside.

Abstract: The present invention comprises compounds useful as antiviral or antitumor agents. The compounds comprise nucleotide analogues that comprise tetrahydrofuranyl or tetrahydrothienyl moeities with quaternary centers at the 3? position. The nucleotide analogues can be used to inhibit cancer or viruses. Accordingly, the compounds of the present invention are useful for treating, preventing, and/or inhibiting diseases or conditions associated with cancers and viruses. Thus, the present invention also comprising pharmaceutical formulations comprising the compounds and methods of using the compounds and formulations to inhibit viruses or tumors and treat, prevent, or inhibit the foregoing diseases.

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 which inhibit HCV polymerase and are useful for treating a patient suffering from a HCV infection and to pharmaceutical compositions containing such compounds.

Abstract: The present invention relates to a method of increasing blood brain barrier permeability in a subject. This method involves selecting a subject who would benefit from increased blood brain barrier permeability and subjecting the selected subject to a treatment. That treatment increases adenosine level and/or bioavailability, modulates adenosine receptors, and/or increases CD73 level and/or activity under conditions effective to increase blood brain barrier permeability in the subject. Methods of decreasing blood brain barrier permeability in a subject, treatment of a subject for a disorder or condition of the central nervous system, and screening compounds effective in increasing blood brain barrier permeability, as well as pharmaceutical agents are also disclosed.

Abstract: 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.

Abstract: The crystal structure of the complex of S-adenosylmethionine methyl ester with h?doMetDC F223A, a mutant where the stacking of the aromatic rings of F7, adenine and F223 would be eliminated. The structure of this mutant with the ester shows that the ligand still maintains a syn conformation aided by pi-pi interactions to F7, hydrogen bonds to the backbone of Glu67, and electrostatic interactions. Several series of AdoMet substrate analogues with a variety of substituents at the 8 position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. To understand these results, virtual modeling of the enzyme inhibitor complexes and the crystal structures of human AdoMetDC with 5?-deoxy-5?-[N-methyl-N-[2-(aminooxy)ethyl]amino-8-methyl]adenosine (MAOEMA) and 5?-deoxy-5?-[N-methyl-N-[4-(aminooxy)butyl]amino-8-ethyl]adenosine (MAOBEA) at the active site have been determined experimentally.

Abstract: The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

Abstract: Disclosed is a synthesis suitable for large scale manufacture of an A2A-adenosine receptor agonist, and also relates to polymorphs of that compound, and to methods of isolating a specific polymorph.

Abstract: 2-adenosine N-pyrazole compounds having the following formula: and methods for using the compounds as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.

Abstract: A compound of formula (I) and salts and solvates thereof are disclosed. Compounds of formula (I) are agonists of the adenosine A2A receptor and are believed to be of potential use in the treatment of inflammatory diseases such as asthma and chronic obstructive pulmonary disease.

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, myocardial infarction and hyperlipidemia. The structure of the compounds is given by Formula (I): wherein R1, R2, R3, R4, R5, X, Y, Z, and T are as described herein.

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. The derivative is useful as a medicine for the treatment of Acquired Immune Deficiency Syndrome (AIDS).

Abstract: The present invention for the stereoselective preparation of 2-deoxy-?-D-adenine nucleosides wherein a blocked 2-deoxy-?-D-arabinofuranosyl halide is coupled with the salt of an adenine derivative.

Abstract: 2-adenosine C-pyrazole compounds having formula (a) and methods for using the compounds as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.

Abstract: This invention relates to the field of nucleic acid chemistry, more specifically to the field of compositions and processes that are nucleic acid analogs. More specifically, this invention relates to compositions that allow the sequencing of oligonucleotides by synthesis, and processes for sequencing by synthesis that exploit these compositions. Most specifically, the instant invention discloses compositions of matter that are 5?-triphosphates of ribo- and 2?-deoxyribonucleosides wherein the 3?-OH group is replaced by a 3?-ONHR group in the alpha configuration, wherein R is either a H or CH3 group. Also disclosed are these triphosphates where the nucleobase carries, via a linker, a reporter groups, such as a fluorescent species that can be used in single- or multi-copy DNA sequencing, or a tag that can be visualized by ultramicroscopy. Also disclosed are processes that use these compositions to do sequencing by synthesis.

Abstract: Synthesis of 2-substituted adenosines of formula (I) using 2-nitro pentabenzoyl adenosine, or 2-nitro pentaacetyl adenosine, as intermediate is described: Formula (I) wherein R=C1-6 alkoxy (straight or branched), a phenoxy group (unsubstituted, or mono-, or di-substituted by halo, amino, CF3—, cyano, nitro, C1-4 alkyl, or C1-4 alkoxy), a benzyloxy group (unsubstituted, or mono-, or di-substituted by halo, amino, CF3—, cyano, nitro, C1-6 alkyl, or C1-6 alkoxy), or a benzoyl group (unsubstituted, or mono-, or di-substituted by halo, amino, CF3—, cyano, nitro, C1-6 alkyl, or C1-6 alkoxy). The methods provide improved yield and purity of product.

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

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: Disclosed are novel compounds that are partial and full A1 adenosine receptor agonists having the structure of Formula I: which are useful for treating various disease states, in particular tachycardia and atrial flutter, angina, and myocardial infarction.

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. Such derivative is useful as medicine for the treatment of Acquired Immune Deficiency Syndrome (AIDS).

Abstract: Disclosed are novel compounds that are A3 adenosine receptor agonists, useful for treating various disease states, including cancer, cardiac ischemia, leukopenia, and neutropennia.