Abstract: The method of preparing compounds of Formula I is described: 1

Abstract: The present application is directed to pyrazolopyrirnidine and furopyrimidine analogs of the formula (I) 1

Abstract: The present invention provides novel compounds of the Formula (I) its prodrug forms, or pharmaceutically acceptable salts thereof. Preferred (I) compounds of the present invention comprise a pyrrolo pyridinyl, pyrrolo pyrimidinyl or indole nucleus. The compounds of this invention are inhibitors of Factor Xa (FXa), Factor VIIa (FVIIa) and/or serine proteases, Urokinase (uPA), and have utility as anti-coagulants for the treatment or prevention of thromboembolic disorders in mammals and as anticancer agents.

Abstract: Modified LNA units are provided that comprises unique base groups. Desirable nucleobase and nucleosidic base substitutions can mediate universal hybridization when incorporated into nucleic acid strands. The novel LNA compounds may be used in a wide variety of applications, such as PCR primers, sequencing, synthesis of antisense oligonucleotides, diagnostics and the like.

Abstract: The invention is based on the discovery that compounds of Formula I are unexpectedly highly potent and selective inhibitors of the adenosine A1 receptor. Adenosine A1 antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable.

Abstract: Resolved enantiomers of the formula (IA) and (IB) wherein B is a purine or pyrimidine base or aza and/or deaza analogs thereof are useful in antiviral pharmaceutical compositions to treat retroviral infections.

Abstract: The invention is based on the discovery that compounds of Formula I are unexpectedly highly potent and selective inhibitors of the adenosine A1 receptor. Adenosine A1 antagonists can be usefull in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula I: wherein: R3 is an optionally substituted bicyclic, tricylic, or pentacyclic group selected from:  and wherein R1, R2, R6, X1, X2, and Z are as described in the specification.

Abstract: Compounds of the formula 1

Abstract: Compounds of the formula wherein Ar is aryl, R1 and R2 are hydrogen alkyl, alkyl substituted with phenyl, and aryl, O, NH, NR4 and S, R5 is hydrogen, alkyl or aryl or alkylene when taken with R1, and R3 is hydrogen, alkyl, alkyl substituted with phenyl, aryl, a heterocyclic group or a polycyclic group, are antiviral agents. A typical embodiment is (1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol O-[phenyl-(methoxy-L-alaninyl)]phosphate.

Abstract: The present invention is in the field of nucleic acid binding compounds comprising 7-substituted 7-deaza-8aza-2,6-diamino-purine bases, compounds useful for the preparation of such compounds, various uses thereof and methods for the determination of nucleic acids using said compounds in the field of diagnostics.

Abstract: The present invention relates to certain novel pyrimidine intermediates and their salts, processes for their preparation and processes for their conversion to 9-substituted-2-aminopurines which are useful in medical therapy.

Abstract: The invention provides new methods for synthesis of nucleotide-based compounds and new libraries of such compounds. Compounds of the invention are useful for a variety of therapeutic applications, including treatment of viral or bacterial infections and associated diseases and disorders.

Abstract: The present invention concerns methods and reagents useful in modulating EGFR (HER1, HER2, HER3, and/or HER4) gene expression in a variety of applications, including use in therapeutic, diagnostic, agricultural, target validation, and genomic discovery applications. Specifically, the invention relates to short interfering nucleic acid (siNA) or short interfering RNA (siRNA) molecules capable of mediating RNA interference (RNAi) against epidermal growth factor receptor targets.

Abstract: The invention pertains to novel cyclin dependent kinase inhibitors (cdks) and specifically, but not exclusively, as inhibitors of cdk/cyclin complexes. As described herein, the inhibitors of this invention are capable of inhibiting the cell-cycle machinery and consequently may be useful in modulating cell-cycle progression, ultimately controlling cell growth and differentiation. Such compounds would be useful for treating subjects having disorders associated with excessive cell proliferation.

Abstract: Novel tricyclic compounds are found to be useful for the treatment or prevention of symptoms or manifestations associated with diseases or disorders affected by cytokine intracellular signaling.

Abstract: The 2-amino-6-arylthiopurinephosphonate of the present invention has no toxicity such as bone marrow cell growth inhibition and mutagenicity, and has a high anti-viral activity, oral absorbency and safety. Furthermore, the compound of the present invention can be produced in a short process. Therefore, the present invention can provide an excellent anti-viral agent which can efficiently be produced.

Abstract: Compounds of Formula I and II are disclosed as antagonists of subtype A1 adenosine receptors. These compounds are useful for treatment of various diseases and disorders, including systemic hypertension, renal failure, diabetes, asthma, an edematous condition, congestive heart failure, and renal dysfunction.

Abstract: A novel compound, 2′/3′-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2′ and 3′ regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2′-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2′/3′-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2′/3′-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2′/3′-O-acetyl-ADP-ribose are also provided.

Abstract: The present invention provides substituted 2-aminopyridines useful in treating cell proliferative disorders. The novel compounds of the present invention are potent inhibitors of cyclin-dependent kinases 4 (cdk4).

Abstract: Novel oligomers, and synthesis thereof, comprising one or more bi-, tri, or polycyclic nucleoside analogues are disclosed herein. The nucleoside analogues have a “locked” structure, termed Locked Nucleoside Analogues (LNA). LNA's exhibit highly desirable and useful properties. LNA's are capable of forming nucleobase specific duplexes and triplexes with single and double stranded nucleic acids. These complexes exhibit higher thermostability than the corresponding complexes formed with normal nucleic acids. The properties of LNA's allow for a wide range of uses such as diagnostic agents and therapeutic agents in a mammal suffering from or susceptible to, various diseases.

Abstract: L-nucleosides are conformationally constrained by at least one additional ring formed by a bridge connecting at least two atoms within a sugar moiety of the nucleoside. While a single additional ring is formed by bridging C1-C4 atoms, two additional rings are formed by bridging both C1-C2, and C3-C4 atoms, or C1-C3 and C2-C4 atoms by bridges having the general structure A—B—Z. The conformationally constrained nucleosides may be incorporated into oligonucleotides and dinucleotides, and it is contemplated that compositions including the conformationally constrained nucleosides may have superior viral inhibitory or antineoplastic properties.

Abstract: Novel oligomers, and synthesis thereof, comprising one or more bi-, tri, or polycyclic nucleoside analogues are disclosed herein. The nucleoside analogues have a “locked” structure, termed Locked Nucleoside Analogues (LNA). LNA's exhibit highly desirable and useful properties. LNA's are capable of forming nucleobase specific duplexes and triplexes with single and double stranded nucleic acids. These complexes exhibit higher thermostability than the corresponding complexes formed with normal nucleic acids. The properties of LNA's allow for a wide range of uses such as diagnostic agents and therapeutic agents in a mammal suffering from or susceptible to, various diseases.

Abstract: A method and composition for the treatment of HIV infection, HBV infection, or abnormal cellular proliferation in humans and other host animals is disclosed that includes the administration of an effective amount of a 1,3-oxaselenolane nucleoside or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.

Abstract: Aryl substituted phosphoryl derivatives of the formula 1

Abstract: The invention relates to a labeling reactant of formula (I) useful for labeling an oligonucleotide 1

Abstract: Polyamines containing at least two nitrogen atoms monosubstituted with pendant arms capable of coordinating metal cations, or with precursors of such pendant arms, all nitrogen atoms of the polyamines except two being fully substituted and the remaining two bearing one H atom each, are cyclized by reaction with a bridging agent that contains two sites that each bear a reactive group capable of undergoing a nucleophilic attack by one of the two N-H groups on the polyamine. Unlike the prior art, cyclization occurs in preference over polymerization of the polyamine, even in reaction mixtures in which the polyamine is at high concentration. A process is also disclosed whereby linear polyamines in which the terminal amine groups are primary amines are substituted with methylenephosphonate ester groups, with one such substituent on each nitrogen atom of the polyamine.

Abstract: The invention features linker molecules that have at one terminus a amino-protecting group and at the other terminus a phosphorous activating group, typically phosphoramidite. The linker molecules can be used, for example, to produce amino-modified linkers that space an oligonucleotide from a solid support. The invention also features an amino-protected nucleotide that includes an activated phosphorous group such as a phosphoramidite for the production of a 5′ amino-modified oligonucleotide. The invention further provides a phthalimido-modified support that can be used to synthesize a polynucleotide that includes an amino group at the 3′ terminus.

Abstract: An oligo- or polynucleotide analogue having one or more structures of the general formula 1

Abstract: This invention features conjugates, compositions, methods of synthesis, and applications thereof, including folate derived conjugates of nucleosides, nucleotides, non-nucleosides, and nucleic acids including enzymatic nucleic acids and antisense nucleic acid molecules.

Abstract: This invention relates to compounds of the general formula: 1

Abstract: This invention relates to compounds of the general formula: 1

Abstract: Photoreactive phosphoramidites useful for attaching photoreactive sites to nucleic acids and oligonucleotides are synthesized. The resultant nucleic acid or oligonucleotide probes incorporating the photoreactive sites are then attached to a polymer-coated support by a [2+2] cycloaddition to form a microarray.

Abstract: Modified oligonucleotides containing both A-form conformation geometry and B-from conformation geometry nucleotides are disclosed. The B-form geometry allows the oligonucleotide to serve as substrates for RNase H when bound to a target nucleic acid strand. The A-form geometry imparts properties to the oligonucleotide that modulate binding affinity and nuclease resistance. By utilizing C2′ endo sugars or O4′ endo sugars, the B-form characteristics are imparted to a portion of the oligonucleotide. The A-form characteristics are imparted via use of either 2′-O-modified nucleotides that have 3′ endo geometries or use of end caps having particular nuclease stability or by use of both of these in conjunction with each other.

Abstract: The present invention provides compounds that are irreversible inhibitors of tyrosine kinases. Also provided is a method of treating cancer, restenosis, atherosclerosis, endometriosis, and psoriasis and a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases.

Abstract: A process for preparing purine derivatives, such as famiciclovir and penciclovir, by reacting, in the presence of a palladium (0) catalyst and a ligand, a compound of the formula with a compound of the formula wherein X is H, OH or halo; Y is a leaving group; and R1 and R2 are selected independently from C1-12alkyl, aryl, C1-12alkylaryl, C1-12alkylsilyl, arylsilyl and C1-12alkyldiarylsilyl or are joined together to form a moiety of the formula wherein R3 and R4 are selected independently from H, C1-12alkyl and aryl.

Abstract: Various substituted nitrogen heterocyclic derivatives and their pharmaceutically acceptable salt derivatives are provided for use as medicaments, and particularly, as antimitotic, anti-viral, anti-cancer, anti-degenerative, immunosuppressive, and anti-microbial drugs or vaccines. These heterocyclic derivatives can be used as an active agent in a pharmaceutical, as well as a diagnostic utility. To this end, several families of heterocyclic derivatives are provided including pyrrolopyrimidines, pyrazolopyrimidines, purines, and imidazopyridines. In particular, certain tri-substituted and tetra-substituted purines and pyrazolopyrimidines and their deaza analogues are provided for inhibiting cyclin-dependent kinase (“cdk”) proteins, viruses, and immunostimulation.

Abstract: Disclosed are compounds of the formula (I) wherein: R2, R7, RI3, R14 and R15 are independently hydrogen, or (un)substituted lower alkyl, (un)substitued lower alkenyl, (un)substituted lower alkynyl, or (un)substituted —(CH2)nR12; R5 is halogen, cyano, nitro, —R9, —NR9R10, or —OR9; R6 is halogen, cyano, nitro, —R9, —NR9R10, —OR9, —Co2R9, —COR9, —CONR9R10, —NR9COR10, (un)substiuted lower alkenyl, or (un)substituted lower alkynyl; R8 is —CO2R13, —COR13, —CONR13R14, —CSNR13R14, —C(NR13)NR14R15, —SO3R13, —SO2R13, —SO2NR13R14, —PO3R13R14, —POR13R14, —PO(NR13R14)2; R9 and R10 are independently hydrogen or (un)substituted lower alkyl; R11 is a heteroaryl or a heterocyclic group; R12 is a cycloalkyl, a heterocyclic, an aryl, or a heteroaryl group; and n is 0,1,2, or 3.

Abstract: Synthetic processes are provided for the solution phase synthesis of oligonucleotides, especially phosphorothioate oligonucleotides, and intermediate compounds useful in the processes.

Abstract: Novel 2,4,5-triaryl imidazole compounds and compositions for use in therapy.

Abstract: Novel ethylene glycol compounds bearing various functional groups are used to prepare oligomeric structures. The ethylene glycol monomers can be joined via standard phosphate linkages including phosphodiester and phosphorothioate linkages. Useful functional groups include nucleobases as well as polar groups, hydrophobic groups, ionic groups, aromatic groups and/or groups that participate in hydrogen-bonding.

Abstract: Disclosed is a specific regulator of Ii protein expression or immunoregulatory function. Specifically disclosed are several forms of the specific regulator of Ii, including those which function through the formation of a duplex molecule with an RNA molecule encoding mammalian Ii protein to inhibit Ii protein synthesis at the translation level. This class includes copolymers comprised of nucleotide bases which hybridize specifically to the RNA molecule encoding mammalian Ii protein, and also expressible reverse gene constructs. In other aspects, the disclosure relates to MHC class II-positive antigen presenting cells containing a specific regulator of Ii expression. Such cells are useful, for example, in the display of autodeterminant peptides in association with MHC class II proteins. Compositions of the invention find application in methods for treating diseases, for example malignancies and autoimmune disorders, in a patient by enhancing immunological attack on undesired cells.

Abstract: The present invention provides selenium derivatives of nucleosides, nucleoside phosphoramidites, nucleotides, nucleotide triphosphates, oligonucleotides, polynucleotides, and larger nucleic acids and methods for their synthesis. Selenium derivatives of both ribonucleic acids and deoxyribonulcleic acids, as well as methods for their synthesis, crystallization and uses in structural determinations, particularly by X-ray crystallographic techniques are disclosed. The selenium derivatives of the present invention are also useful as food supplements.

Abstract: Compounds are described comprising purines substituted at the C-8 position and pyrimidines substituted at the C-4 position with a linker and quencher. These compounds, when incorporated into hairpin oligonucleotides quench the fluorescence of fluorophores linked to the 5′-terminus of the oligonucleotide. These nucleotide-quencher compounds are also easily incorporated into oligonucleotides using conventional or automated oligonucleotide synthetic techniques.

Abstract: Synthetic processes are provided wherein mixed backbone oligomeric compounds are prepared having at least one phosphodiester internucleoside linkage in addition to one or more phosphorothioate, phosphoramidate and boranophosphate internucleoside linkages. Novel H-phosphonate intermediates are also disclosed that are useful in the synthetic processes. The synthetic processes use a novel oxidation step to oxidize H-phosphonate internucleoside linkages to phosphodiester internucleoside linkages without degradation of adjacent phosphorothioate, phosphoramidate and boranophosphate internucleoside linkages. Also provided are synthetic intermediates useful in such processes.

Abstract: The present invention relates to (1R, cis)-4-(4-Amino-7H-pyrrolo[2,3-(d)]pyrimidine-7-yl)-2-cyclopentene-1-methanol derivatives for the treatment of viral infections.

Abstract: This patent describes the invention of a series of novel therapeutic oligonucleotides targeted at inhibiting expression of genes coding for Phosphodiesterase 4. They are useful as analytical tools in the study of individual PDE isoforms and in the therapeutic treatment of depression, thrombosis, cystic fibrosis, gastric lesions, pulmonary hypertension, glaucoma, multiple sclerosis, atopic dermatitis, asthma and other allergic disorders as well as other illnesses in which an increase of cyclic AMP or a decrease in phosphodiesterase levels is useful.

Abstract: Inosine compounds, compositions comprising an inosine compound and methods for treating or preventing an inflammation disease or a reperfusion disease comprising administering an effective amount of an inosine compound to a patient in need thereof are disclosed.

Abstract: The present invention relates to analogs of (1S, cis)-4-(2-amino-9H-purin-9-yl)-2-cyclopentene-1-methanol for use in treating viral infections.

Abstract: Conformationally restricted 2′, 4′-bridged nucleoside analogues are described herein. The compounds can be prepared by cyclization at C2′ and C4′ of nucleosides through a linker or linking molecule. These novel nucleosides have a desired, locked sugar pucker and are potentially useful as pharmaceutical ingredients, and especially for use in treatment of HCV.

Abstract: Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure —OC(R2)2OC(O)X(R)a, wherein R2 independently is H, C1-C12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR3 in which R3 is C1-C12 alkyl; X is N or O; R is independently H, C1-C12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, —O—, —N═, —NR4—, —N(R4)2— or OR3, R4 independently is —H or C1-C8 alkyl, provided that at least one R is not H; and a is 1 or 2, with the proviso that when a is 2 and X is N, (a) two R groups can be taken together to form a carbocycle or oxygen-containing heterocycle, or (b) one R additionally can be OR3.