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: 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 is a method for preparing 2-halo-6-aminopurines, and more specifically for preparing the clinical agent cladribine (2-chloro-2?-deoxyadenosine, CldAdo, 4), a drug of choice against hairy-cell leukemia and other neoplasms, from 2-amino-6-oxopurines, which are readily obtained from the naturally occurring compound 2?-deoxyguanosine. According to the methods of the present invention, the 6-oxo group of a protected 2?-deoxyguanosine (1) is converted to a 6-(substituted oxy) leaving group, or alternatively to a 6-chloro leaving group, the 2-amino group is replaced with a 2-chloro group, the 6-(substituted oxy) leaving group, or alternatively the 6-chloro leaving group, is replaced with a 6-amino group or, alternatively, a 2,6-dichloro substituted compound is selectively replaced with a 6-amino group, and the protecting groups are removed.

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: 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 process for making clofarabine comprising: fluorinating a compound of formula VII wherein each R4 is independently a hydroxy protecting group, OR6 is a leaving group, with a fluorinating agent in the presence of guanidine carbonate to give a compound of formula VIII: wherein R4 is as defined above; and deprotecting the compound of formula VIII to give the clofarabine.

Abstract: Use of compounds of formula: (I) wherein R is C1-4 alkoxy and X is H or OH; for the prevention, treatment, or amelioration of cancer, inflammation, auto-immune disease, ischemia-reperfusion injury, epilepsy, sepsis, septic shock, neurodegeneration (including Alzheimer's Disease), muscle fatigue or muscle cramp is described. The compounds are effective at very low doses, and so can be administered at doses at which serious side effects are not observed.

Abstract: The present invention relates to pharmaceutical compositions and methods for promoting wound healing. The invention also relates to methods of making pharmaceutical compositions disclosed herein. Pharmaceutical compositions are disclosed comprising an effective amount of a 2-alkoxyadenosine or 2-aralkoxyadenosine, about 10% to about 70% w/w propylene glycol and a thickening agent.

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: Disclosed are structurally modified, metabolically stable nucleosides having antitumor activity wherein the formation of toxic metabolites is blocked and antimicrobial activity. The disclosure further relates to pharmaceutical compositions comprising one or more disclosed modified nucleosides and to methods of use thereof.

Abstract: A process for the preparation of cladribine of API grade is provided by direct coupling of O-protected 2-deoxy-ribofuranose with silylated 2-chloroadenine followed by deprotection of the resultant protected nucleoside in a separate step and then a purification step. Following the coupling, the desired N-9-glycosylated ?-anomer of the nucleoside is directly isolated as a solid from the coupling reaction mixture by filtration in relatively high purity and yield, and it does not require purification.

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: Compounds represented by the formula 1: A is selected from the group consisting of wherein each R individually is H or acyl, Y is X, N3, NH2, monoalkylamino, or dialkylamino; Z is O or S; and X is selected from the group consisting of hydrogen, halo, hydroxy, alkoxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, monoalkylamino, dialkylamino, thioaryl, thioalkyl, allylamino, cyano and nitro; tautomers thereof; and pharmaceutically acceptable salts thereof are provided along with methods for their fabrication. Various of these compounds can be used as anticancer agents, or antiviral agents or to inhibit DNA replication.

Abstract: The present invention relates to a method for preparing a 2-fluoropurine marked with the radioisotope 18F comprising a fluorination step for a 2-nitropurine derivative. The present invention comprises a 2-fluoropurine derivative marked with the radioisotope 18F which can be obtained by or during a method according to the invention and its various uses.

Abstract: The present invention relates to methods of treating viral disease using mutagenic nucleoside analogs.

Abstract: The invention relates to a method of improving oral drug absorption of adenosine analogues by the use of 2?-methoxy adenosine pro-drugs and to the use of these pro-drugs as medicaments. The invention further relates to compounds that are pro-drugs of adenosine receptor agonists, and to their use as therapeutic compounds, in particular as analgesic or anti-inflammatory compounds, or as disease modifying antirheumatic drugs (DMARDs), and to methods of preventing, treating or ameliorating pain or inflammation using these compounds.

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: This invention provides a method for inhibiting the release of interleukin-1? in a mammal. This invention also provides a method for preventing or treating pulmonary diseases, ophthalmic diseases, and autoimmune diseases that are associated with inflammation or inflammatory conditions. The invention also provides a method for preventing or treating neurodegenerative diseases, or pain in a mammal. The method comprises administering to a mammal in need thereof a therapeutically effective amount of a mononucleoside compound, which is an antagonist of P2X7 receptor.

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. The A2A-adenosine receptor agonist has the following formula: This compound is prepared by reacting the ethyl ester with methylamine in a sealed pressure reactor.

Abstract: Synthesis methods suitable for large scale manufacture of the A2A-adenosine receptor agonist (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide and precursors thereof.

Abstract: The present invention relates to methods of treating viral disease using mutagenic nucleoside analogs. In particular, the invention provides isoguanosine nucleosides and derivatives thereof as well a method of increasing the mutation rate of a virus such as bovine viral diarrhea virus (BVDV) and hepatitis C virus (HCV).

Abstract: The present invention is a method for preparing 2-halo-6-aminopurines, and more specifically for preparing the clinical agent cladribine (2-chloro-2?-deoxyadenosine, CldAdo, 4), a drug of choice against hairy-cell leukemia and other neoplasms, from 2-amino-6-oxopurines, which are readily obtained from the naturally occurring compound 2?-deoxyguanosine. According to the methods of the present invention, the 6-oxo group of a protected 2?-deoxyguanosine (1) is converted to a 6-(substituted oxy) leaving group, or alternatively to a 6-chloro leaving group, the 2-amino group is replaced with a 2-chloro group, the 6-(substituted oxy) leaving group, or alternatively the 6-chloro leaving group, is replaced with a 6-amino group or, alternatively, a 2,6-dichloro substituted compound is selectively replaced with a 6-amino group, and the protecting groups are removed.

Abstract: Phosphoramidate derivatives of nucleoside compounds such as cladribine, isocladribine, fludaribine and clofarabine have enhanced therapeutic potency in homo sapiens, in particular, enhanced potency with respect to a cancer such as leukaemia. Suitably the phosphoramidate is substituted at the P atom by Ar—O, where Ar is aryl or heteroaryl, either of which may be optionally substituted. Formula (I).

Abstract: The present invention is a method for preparing 2-halo-6-aminopurines, and more specifically for preparing the clinical agent cladribine (2-chloro-2?-deoxyadenosine, CldAdo, 4), a drug of choice against hairy-cell leukemia and other neoplasms, from 2-amino-6-oxopurines, which are readily obtained from the naturally occurring compound 2?-deoxyguanosine. According to the methods of the present invention, the 6-oxo group of a protected 2?-deoxyguanosine (1) is converted to a 6-(substituted oxy) leaving group, or alternatively to a 6-chloro leaving group, the 2-amino group is replaced with a 2-chloro group, the 6-(substituted oxy) leaving group, or alternatively the 6-chloro leaving group, is replaced with a 6-amino group or, alternatively, a 2,6-dichloro substituted compound is selectively replaced with a 6-amino group, and the protecting groups are removed.

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 methods of treating or preventing an autoimmune disorder comprising the administration of clofarabine or a pharmaceutically acceptable salt, hydrate, solvate, clathrate, prodrug or metabolite thereof to a patient in need of such treatment. The invention further relates to methods of treating or preventing an autoimmune disorder comprising the administration of clofarabine or a pharmaceutically acceptable salt, hydrate, solvate, clathrate, prodrug or metabolite thereof and an additional therapeutic agent to a patient in need of such treatment.

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: This invention relates to compounds of Formula I: and their use in the treatment of bacterial infections.

Abstract: Provided is a method for the synthesis of an aralkyloxyadenosine or an alkoxyadenosine. The method includes protecting the hydroxyl sugar groups with a protecting group to produce a protected halogenated adenosine. The protected halogenated adenosine is alkoxylated, and the hydroxyl sugar groups of the protected halogenated adenosine are deprotected to provide the aralkyloxyadenosine or alkoxyadenosine.

Abstract: Disclosed are purine nucleoside compounds that are selective to A3 adenosine receptors and are useful for the treatment of cancer and inflammatory diseases. The compounds are shown by the following general formula (I), including isomers thereof: wherein X is sulfur or oxygen; R1 is hydrogen, alkyl, benzyl, halobenzyl, or phenylalkyl; R2 is hydrogen, halogen, alkoxy, alkenyl, alkynyl, alkylthio, or thio; R3 and R3? are hydrogen, hydroxyalkyl, alkoxycarbonyl, or alkylaminocarbonyl, whereas R3 and R3? do not have identical substituents simultaneously; and R4 is hydrogen or alkyl. Also disclosed are a pharmaceutical composition comprising a compound of formula (I), an isomer, or its pharmacologically acceptable salt as an active ingredient and a method for preventing or treating various diseases, state, or condition, including asthma, inflammation, cerebral ischemia, heart diseases, and cancer.

Abstract: Compounds represented by the formula 1: A is selected from the group consisting of wherein each R individually is H or acyl, Y is X, N3, NH2, monoalkylamino, or dialkylamino; Z is O or S; and X is selected from the group consisting of hydrogen, halo, hydroxy, alkoxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, monoalkylamino, dialkylamino, thioaryl, thioalkyl, allylamino, cyano and nitro; tautomers thereof; and pharmaceutically acceptable salts thereof are provided along with methods for their fabrication. Various of these compounds can be used as anticancer agents, or antiviral agents or to inhibit DNA replication.

Abstract: Novel C2,8-disubstituted adenosine derivatives disclosed herein have been found to be potent adenosine receptor agonists, in particular for the A2A receptor. The said compounds have biological activity against conditions such as hypertension, ischemic heart disease, ischemic brain disease, psychosis and wound healing. Further, the invention also discloses a process for the preparation of such compounds and pharmaceutical compositions comprising them.

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: The present invention relates to novel compounds that are novel adenosine receptor analogues. Specifically, the compounds of the present invention preferably function as both adenosine receptor agonists and ganglionic blocking agents. To achieve this functionality, the compounds of the present invention, preferably contain a ganglionic blocking motif, is inserted into the adenosine molecule. The ganglionic blocking motif preferably includes an elongated carbon chain that, in a particularly preferred embodiment, contains two terminal amino groups. The ganglionic blocking motif preferably includes a carbon along the elongated carbon chain that is integral to a cyclic ketal that is part of the adenosine molecule. In presently-preferred embodiments, the elongated carbon chain ranges from two to sixteen carbons in length. The compounds of the present invention will be useful for treatment of a variety of conditions including, but not limited to, hypertension, vasodilation, and ischemia.

Abstract: The present invention relates to compounds of the formula and pharmaceutically acceptable salts and solvates thereof, to processes for the preparation of, intermediates used in the preparation of, and compositions containing such compounds and the uses of such compounds as adenosine A2a receptor agonists.

Abstract: Compounds represented by the formula 1: A is selected from the group consisting of wherein each R individually is H or acyl, Y is X, N3, NH2, monoalkylamino, or dialkylamino; Z is O or S; and X is selected from the group consisting of hydrogen, halo, hydroxy, alkoxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, monoalkylamino, dialkylamino, thioaryl, thioalkyl, allylamino, cyano and nitro; tautomers thereof; and pharmaceutically acceptable salts thereof are provided along with methods for their fabrication. Various of these compounds can be used as anticancer agents, or antiviral agents or to inhibit DNA replication.

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 as adenosine A2a receptor agonists.

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

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: 2′-Deoxyisoguanosine, isosteric analogues and isoguanosine derivatives of formulae I-V, processes for their production via compounds of the general formulae a or b and reaction with aroyl isocyanates or from compounds of the general formulae VI-IX by photochemical irradiation. A further production process is the conversion of deoxyguanosines or guanosines by means of persilylation, reaction with ammonia and deamination in the 2 position. The compounds are suitable as pharmaceutical agents with antiviral efficacy.

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

Abstract: The present invention provides compounds of formula (I): and pharmaceutically acceptable salts and solvates thereof, together with processes for the preparation of, compositions containing, uses of and intermediates used in the preparation of such compounds that have A2a receptor agonist activity.

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

Abstract: The invention provides tumor imaging agents comprising a radionuclide in association with a nucleotide polyphosphate targeting molecule. Methods for using the tumor imaging agents and kits containing the tumor imaging agents or components suitable for production of the tumor imaging agents are also provided.