Abstract: The invention provides new methods for synthesis of 2-aralkyloxyadenosines and 2-alkoxyadenosines. The invention is particularly useful for synthesis of 2-[2-(4-chlorophenyl)ethoxy]adenosine. Preferred methods of the invention include activating a guanosine compound followed by hydrolysis; alkylating the hydrolyzed compound with subsequent animation to provide a 2-aralkyloxyadenosine or a 2-alkoxyadenosine compound.

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 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: A polymerase inhibitor has first moiety coupled to a second moiety via an optional linker in which the first moiety binds to an initiation nucleotide binding site of a polymerase and forms at least two hydrogen bonds with an RNA template strand that is associated with the polymerase, and in which the second moiety comprised a compound that binds to a site proximal to the nucleotide binding site of the polymerase and thereby increases the affinity of the polymerase inhibitor to the polymerase.

Abstract: The invention provides a novel class of substituted nucleoside derivatives having the formula: A-Z1-L-Z2-G wherein: A and G are connected via Z1 and Z2 respectively, to a linker, L; and A is: wherein: X1 and X2 are N; X3 is —N?CH; R1 and R2 are independently H, alkyl, NH2, OH, SH, Cl, NHR9, or N?NR9, where R9 is alkyl, aryl, or arylalkyl; R5 and R6 are independently alkyl, or R5 and R6 taken together form a —C(CH3)2— group; Z1 is —CH2O—, —CH2NR10—, —CH2NR10C(O)—, —CONR10—, —CO2—, —CH2NHCONH—, —CH2—, —CH2NHCSNH—, —CO—, —CH2CO2—, —NHCO2—, —S—, —SO2—, —CH2S—, or —SO—; Z2 is —NR10CO—, —C(O)NR10—, —NHCONH—, —OC(O)—, —C(O)O—, NHCS, —CSNH—, —NHCSNH—, —O—, —CO—, —OCO—, —OCONH—, —NH—, —CH2—, —CH—alkyl—, —NHCO2—, —S—, —SO2—, CS—, or —SO—; L is H, O, S, C1-15 alkylene chain optionally substituted in one or more positions, a 5, 6 or 7 membered carbocycle, piperidine, piperazine, pyrole, imidazole, benzimidazole, tetrazoles, indole, isoquinoline, quinoline, or pyrrolidine, any of the 5, 6 or 7 membered carbocycl

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: A process for substantially enhancing the regio and stereoselective synthesis of 9-?-anomeric nucleoside analogs is described. The introduction of the sugar moiety onto a 6-substituted purine base was preformed so that only the 9-?-D- or L-purine nucleoside analogs were obtained. This regio and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs and in particular 2?-deoxy, 3?-deoxy, 2?-deoxy-2?-?-fluoro and 2?,3?-dideoxy-2?-?-fluoro purine nucleoside analogs in high yield without virtually any formation of the 7-positional isomers. The compounds are drugs or intermediates to drugs.

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 present invention is directed to a method to produce 8-amino-2′deoxyadenosine by treating 8-azido-2′deoxyadenosine with an aqueous solution of methylamine or dimethylamine.

Abstract: The present invention relates to novel compounds according to the to the general formulas I, II, III, IV or V: 1

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: 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.

Abstract: The present invention relates to a linker nucleoside, its preparation and use for the covalent bonding of biomolecules to oligonucleotides, in particular p-RNA oligonucleotides.

Abstract: Methods of treating and/or imaging tumors utilize A1 adenosine-receptor activated cells (such as monocytes and macrophages) are described. Activated cells may be administered systemically or locally, and may be radiolabelled to provide imaging and diagnostic functions. Macrophages resident in tissues may be primed and activated for use in treating and imaging tumors.

Abstract: The present invention relates to a support system for solid phase synthesis of oligomers, such as oligonucleotides, wherein the starting compound is bound to the support via a disiloxyl linkage. Furthermore, the invention relates to a method for synthesis of oligonucleotides on a solid support. The support system comprises a stable disiloxyl linkage providing high nucleoside loadings to the support and the method allows convenient non-laborious oligomer synthesis.

Abstract: The present invention relates to improved methods for the preparation of nucleoside phosphoramidites and oligonucleotides. In one aspect, the methods of the invention are used to prepare phosphitylating reagents using pyridinium salts as activators. In a further aspect, the methods of the invention are used to prepare internucleoside linkages using activators which include at least one pyridinium salt and at least one substituted imidazole. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having 2′-substituents using imidazolium or benzimidazolium salts as an activator. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having bioreversible protecting group that confers enhanced chemical and biophysical properties, without exocyclic amine protection, using imidazolium or benzimidazolium salts as an activator.

Abstract: A novel process for preparing 2-halo-6-aminopurine derivatives and their analogs is disclosed. The method comprises halogenation of 2,6-diaminopurine derivatives at the C-2 position in a specific combination of aprotic polar and nonpolar organic solvents to give the corresponding halogenated derivatives.

Abstract: The present invention provides oligomers which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the nucleoside moieties of the oligomer is modified to include a guanidinium group. These oligomers are useful for diagnostic, therapeutic and investigative purposes.

Abstract: There can be provided an excellent industrial process for producing compounds having sugar-moiety hydroxyl groups or halogen atoms reduced in nucleic acids or in derivatives thereof by allowing O-thiocarbonyl derivatives of sugar-moiety hydroxyl groups or allowing halogenated derivatives in the sugar-moiety, in the nucleic acids or in derivatives thereof to react with any one of hypophosphorous acids (including salts thereof) and phosphites (esters) which are inexpensive, non-toxic and safely usable as radical reducing agents in industrial scale, in the presence of a radical reaction initiator. The process of the present invention is an industrially useful and highly safe process for reducing sugar-moiety hydroxyl groups and halogen atoms in nucleic acids or derivatives thereof (including nucleic acid-related compounds) at low costs.

Abstract: Esters of N6-oxa, thia, thioxa and azacycloalkyl substituted adenosine derivatives having the following formula; wherein the compounds are selective adenosine type 1 receptor agonists that are useful for the treatment cardiovascular diseases and central nervous system disorders.

Abstract: New compounds of the general formula (I): Nu-O-Fa, wherein O represents an oxygen, Nu is a nucleoside or nucleoside analogue, and Fa is an acyl group of a mono-unsaturated C18 or 20 fatty acid. The invention also concerns anti viral pharmaceutical and veterinary compositions comprising a compound of formula (I) alone in a combination with a pharmaceutically acceptable carrier.

Abstract: Processes for the preparation of 3′,4′-cyclic acetals of pentopyranosylnucleosides, in which the pentopyranosyl nucleoside is reacted with an aldehyde, ketone, acetal, or ketal under reduced pressure of less than about 500 mbar.

Abstract: The invention provides new methods for synthesizing oligonucleotides that allow for deprotection of the oligonucleotides under more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups.

Abstract: Non-naturally-occurring compositions for use in amelioration of disruption of energy metabolism secondary to stress are described. These compositions comprise a flavonoid or derivative thereof and a synergist. Synergists include, but are not limited to, amino acids, carbohydrates, carnitines, flavonoids, nucleosides, and tocopherols and/or derivatives thereof. Methods of making these compositions and methods of ameliorating disruption of energy metabolism secondary to stress, comprising administering such synergistic compositions, are also disclosed.

Abstract: The present invention relates to compounds of the class of purin-2-ylcarboxamides, useful as anti-inflammatory agents, having the formula: and pharmaceutically acceptable salts and solvates thereof; wherein R1 is H, C1-C 6 alkyl or C3-C7 cycloalkyl, each optionally substituted by 1 or 2 of hydroxyl, fluorenyl, or optionally substituted phenyl or naphthyl ; A is a bond or C1-C6 alkylene; R2 is (i) H, C1-C6 alkyl, or optionally substituted C3-C7 cycloalkyl, phenyl, or naphthyl; or (ii) when A is C2-C6 alkylene, —NR3R3, —OR3, —COOR3, —OCOR4, —SO2R4, —CN, —SO2NR3R4, —NR3SO2R4, —NR3COR4 or —CONR3R3; or (iii) a C-linked, 4 to 11 membered, mono or bicyclic heterocycle having either from 1 to 4 ring nitrogen atom(s) or 1 or 2 nitrogen and 1 oxygen or 1 sulphur ring atoms, said heterocycle being optionally C-substituted or N-substituted; or (iv) when A is C2-C6 alkylene, optionally substituted N-linked azetidinyl, pyrrolidinyl, morpholinyl,

Abstract: Novel nucleoside or nucleotide analogs comprising 2′-O-amino residues, processes for their synthesis and incorporation into polynucleotides.

Abstract: Propargylethoxyamino nucleosides are disclosed having the structure wherein R1 and R2 are —H, lower alkyl, or label; B is a 7-deazapurine, purine, or pyrimidine nucleoside base; W1 is —H or —OH; W2 is —OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3′-position; and W3 is —PO4, —P2O7, —P3O10, phosphate analog, or —OH. Additionally, a primer extension method is provided employing the above propargylethoxyamino nucleosides.

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: Novel purine L-nucleoside compounds are disclosed, in which both the purine rings and the sugar are either modified, functionalized or both. The novel compounds or pharmaceutically acceptable esters or salts thereof may be used in pharmaceutical compositions, and such compositions may be used to treat an infection, an infestation, a neoplasm, or an autoimmune disease. The novel compounds may also be used to modulate aspects of the immune system, including modulation of Th1 and Th2.

Abstract: The present invention relates to a support system for the solid phase synthesis of oligomers, such as oligonucleotide, wherein the starting compound is bound to the support via a disiloxyl linkage. Furthermore, the invention relates to a method for synthesis of oligonucleotides on a solid support. The support system comprises a stable disiloxyl linkage providing high nucleoside loadings to the support and the method allows convenient non-laborious oligomer synthesis.

Abstract: A substituted N6-oxa, thia, thioxa and azacycloalkyl substituted adenosine derivative and a method for using the composition as an A1 adenosine receptor agonist.

Abstract: A process for the purification of nucleosides, and more particularly to a selective solvent extraction method for purifying protected nucleosides. In the purification process, solid particles of protected nucleosides are selectively washed to remove undesirable polar and/or non-polar impurities, while leaving the solid particles substantially undissolved.

Abstract: 2-adenosine N-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: This invention discloses a method for the preparation of 2′-modified nucleosides, using a palladium catalyst and an alkene functionalized with a heteroatom. Included in the invention are the novel pyrimidines and purines that can be prepared according to the method of the invention and oligonucleotides containing said modified pyrimidines and purines.

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: The invention provides 4′-C-ethynyl purine nucleosides represented by formula [I]: wherein B represents a base selected from the group consisting of purine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

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: A method is provided employing A2A adenosine receptor agonists as vasodilators to detect the presence and assess the severity of coronary artery stenosis.

Abstract: Tetrahydrofuranyl compounds are provided that are functionalized to include pendant conjugate groups, and which are useful in diagnosis assays and as research reagents. Novel intermediates for the synthesis of the compounds are also provided.

Abstract: N6 heterocyclic 8 modified adenosine derivatives that are selective, partial or full adenosine A1 receptor partial or full agonists, and as such, are useful for modifying cardiac activity, modifying adipocyte function, treating central nervous system disorders, and treating diabetic disorders and obesity in mammals, and especially in humans.

Abstract: The present invention relates to improved methods for the preparation of nucleoside phosphoramidites and oligonucleotides. In one aspect, the methods of the invention are used to prepare phosphitylating reagents using pyridinium salts as activators. In a further aspect, the methods of the invention are used to prepare internucleoside linkages using activators which include at least one pyridinium salt and at least one substituted imidazole. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having 2′-substituents using imidazolium or benzimidazolium salts as an activator. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having bioreversible protecting group that confers enhanced chemical and biophysical properties, without exocyclic amine protection, using imidazolium or benzimidazolium salts as an activator.

Abstract: Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2′-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.

Abstract: 2′-O-modified ribosyl nucleosides and modified oligonucleotides containing such nucleotides are disclosed. Oligonucleotides are disclosed that have increased binding affinity as shown by molecular modeling experiments. The 2′-O-modified nucleosides of the invention include ring structures that position the sugar moiety of the nucleosides preferentially in 3′ endo geometries.

Abstract: Nucleosides and linked nucleosides functionalized to include alkylthiol chemical functionality at ribofuranosyl positions, nucleosidic base positions, or on internucleoside linkages. In certain embodiments, the compounds of the invention further include steroids, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleosides through the alkylthio group.

Abstract: An efficient, regiocontrolled approach to the synthesis of 8-fluoropurines by direct fluorination of purines with dilute elemental fluorine, or acetyl hypofluorite, is provided. In a preferred embodiment, a purine compound is dissolved in a polar solvent and reacted with a dilute mixture of F2 in He or other inert gas.

Abstract: The invention relates to a 3′-substituted nucleoside derivative represented by the following general formula (1): wherein B means a nucleic acid base which may have a substituent, Z represents a lower alkynyl or lower alkenyl group which may be substituted by a group represented by the formula: in which Ra, Rb and Rc are individually a lower alkyl group or a phenyl group, or an oxiranyl group which may have at least one lower alkyl group, R1 and R2 individually represent H or an ester-forming residue capable of easily leaving in a living body, and R3 is H, a mono- or polyphosphoric acid residue, or an ester-forming residue capable of easily leaving in a living body, with the proviso that the sugar moiety is ribose, or a pharmaceutically acceptable salt thereof. The 3′-substituted nucleoside derivative according to the invention has an excellent antitumor activity and is hence useful for treatment for and prevention of cancers.

Abstract: This invention is directed to novel substituted nucleotide bases with a crosslinking arm which accomplish crosslinking between specific sites on adjoining strands of oligonucleotides a oligodeoxynucleotides. The invention is also directed to oligonucleotides comprising at least one of these crosslinking agents and to the use of the resulting novel oligonucleotides for diagnostic and therapeutic purposes.