Abstract: The present invention relates to compositions for lowering the total amount of cholesterol in the blood and methods of using the compositions. The compositions are a mixture of pravastatin and one or more vitamins selected from riboflavins, d-&agr;-tocopherols, ascorbic acids and inositol hexanicotinate.

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: A compound of the formula (1): 1

Abstract: Nucleosides and other compounds to selectively modulate Th1 and Th2 responses relative to each other in the treatment of disease. In one aspect of the invention, administration of a nucleoside or other compound reduces the dosage at which a primary drug is administered. In another aspect of the invention, an abnormality reflected in increased response in one group of cytokines is treated by administering a nucleoside or other compound that increases response in another group of cytokines. In yet another aspect of the invention, a patient is prophylactically treated by administering a nucleoside or other compound that selectively reduces Th1 activity without significantly reducing Th2 activity. In yet another, aspect of the invention, a nucleoside or other compound is administered to a patient at a dose that reduces the patient's GTP pool to a degree that selectively reduces one of the Th1 or Th2 responses without significantly reducing the other response.

Abstract: The present invention relates to pharmaceutical compositions for use in inducing proliferation of the hematopoietic system, in particular, of bone marrow cells, comprising a pharmaceutically acceptable carrier, excipient or diluent and, as an active ingredient, an effective amount of an adenosine A1 receptor agonist. The pharmaceutical composition of the present invention may be used to induce proliferation of bone marrow cells, in a variety of clinical situations where such proliferation is therapeutically beneficial. The active ingredient within the pharmaceutical composition of the invention may be a compound of general formula (I) as described herein or any other compound or substance which specifically binds to and/or activates the A1 adenosine receptor and acts as an agonist to the receptor's natural ligand.

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: A compound which comprises a backbone having a plurality of chiral carbon atoms, the backbone bearing a plurality of ligands each being individually bound to a chiral carbon atom of the plurality of chiral carbon atoms, the ligands including one or more pair(s) of adjacent ligands each containing a moiety selected from the group consisting of a naturally occurring nucleobase and a nucleobase binding group, wherein moieties of the one or more pair(s) are directly linked to one another via a linker chain; building blocks for synthesizing the compound; and rises of the compound, particularly in antisense therapy.

Abstract: The invention relates to the use of riboflavin and of flavin derivatives with chitinase-inhibitory action for controlling arthropods, nematodes and chitin-containing fungi.

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: Methods are provided for treating heart failure, increasing cardiac muscle contractility, increasing cardiac diastolic relaxation, and increasing vasodilation employing AMP, ADP, and ATP analogues.

Abstract: The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a purinerginic receptor ligand, which is a mononucleoside polyphosphate or dinucleoside polyphosphate defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with other therapeutic agents or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of helicase-moi. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding helicase-moi. Methods of using these compounds for modulation of helicase-moi expression and for treatment of diseases associated with expression of helicase-moi are provided.

Abstract: Compositions and methods for the treatment and diagnosis of diseases or conditions amenable to treatment through modulation of expression of a gene encoding a p38 mitogen-activated protein kinase (p38 MAPK) are provided. Methods for the treatment and diagnosis of diseases or conditions associated with aberrant expression of one or more p38 MAPKs are also provided.

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 invention provides antisense antiviral compounds and methods of their use in inhibition of growth of viruses of the picornavirus, calicivirus, togavirus and flavivirus families, as in treatment of a viral infection. The antisense antiviral compounds are substantially uncharged oligomers having a targeting base sequence that is substantially complementary to a viral target sequence which spans the AUG start site of the first open reading frame of the viral genome.

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: Antisense compositions targeted against an mRNA sequence coding for a selected protein, at a region having its 5′ end from 1 to about 25 base pairs downstream of a normal splice acceptor junction in the preprocessed mRNA, are disclosed. The antisense compound is RNase-inactive, and is preferably a phosphorodiamidate-linked morpholino oligonucleotide. Such targeting is effective to inhibit natural mRNA splice processing, produce splice variant mRNAs, and inhibit normal expression of the protein.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of liver glycogen phosphorylase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding liver glycogen phosphorylase. Methods of using these compounds for modulation of liver glycogen phosphorylase expression and for treatment of diseases associated with expression of liver glycogen phosphorylase are provided.

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: In recognition of the need to facilitate the use of riboflavin as a pharmaceutical and additionally to increase the efficacy and stability of water soluble forms of riboflavin (that may contain precipitated riboflavin or that are subject to photodegradation), the present invention provides solubilized riboflavin, methods for solubilizing riboflavin, kits comprising solubilized riboflavin and provides photostable compositions comprising riboflavin and derivatives thereof.

Abstract: The present invention is directed to a method of treating pain. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a P2X receptor antagonist. The methods of the present invention are useful in reducing pain, such as traumatic pain, neuropathic pain, organ pain and pain associated with diseases. The P2X receptor antagonists particularly useful for this invention are mononucleoside polyphosphate derivatives or dinucleoside polyphosphate derivatives of general Formula I. The compounds of the present method can be used alone to treat pain. The compounds of the present method can also be used in conjunction with other therapeutic agents or adjunctive therapies commonly used to treat pain, thus enhancing the overall pain-reducing effect in a subject in need of such treatment.

Abstract: The present invention is directed to a method for treating hepatitis B virus infection in humans comprising administering a synergistically effective amount of agents having known anti-hepatitis B virus activity in combination or alternation. Specifically, the invention is directed to a method for treating hepatitis B virus infection comprising administering FTC in combination or alternation with penciclovir, famciclovir or Bis-POM-PMEA. Additionally, the invention is directed to a method for treating hepatitis B virus infection comprising administering L-FMAU in combination or alternation with DAPD, penciclovir or Bis-POM-PMEA. The invention is further directed to a method for treating hepatitis B virus infection comprising administering DAPD in combination or alternation with Bis-POM-PMEA.

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: 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. In one embodiment, the invention features a compound of formula I: R3 is an optionally substituted group selected from: and wherein X1, X2, Z, R1, R2, and R6 are as described in the specification.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of BCL2-associated X protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding BCL2-associated X protein. Methods of using these compounds for modulation of BCL2-associated X protein expression and for treatment of diseases associated with expression of BCL2-associated X protein are provided.

Abstract: It has unexpectedly been found that the administration of high doses of riboflavin or derivatives thereof (including, but not limited to salts and prodrugs), results in an effective treatment for sepsis. Thus, the present invention provides methods for treating sepsis by administering to a subject in need thereof a high dose of a composition comprising riboflavin or derivatives thereof.

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: 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: Disclosed is a pharmaceutical composition comprising a ribonucleoside analogue in accordance with general formula I or II as herein defined, in admixture with a physiologically acceptable excipient diluent or carrier.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of apolipoprotein(a). The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding apolipoprotein(a). Methods of using these compounds for modulation of apolipoprotein(a) expression and for treatment of diseases associated with expression of apolipoprotein(a) are provided.

Abstract: Aryl substituted phosphoryl derivatives of the formula 1

Abstract: The invention features a method for treating a patient having an immunoinflammatory disorder, by administering to the patient (i) a tetra-substituted pyrimidopyrimidine, and (ii) a corticosteroid simultaneously or within 14 days of each other in amounts sufficient to reduce or inhibit immunoinflammation.

Abstract: 2-amino-6-arylthiopurinephosphonate used in the antiviral agent of the present invention has no toxicity such as bone marrow cell growth inhibition or mutagenicity, and has a high antiviral activity, oral absorbency and safety. Furthermore, the compound of the present invention is effective for a mutant virus which is known to exhibit resistance to the conventional antiviral agents. Therefore, the present invention can provide a useful antiviral agent which leads to the establishment of a method for treating hepatitis B, which is a medically important object.

Abstract: The present invention provides compositions and methods for the prevention and treatment of a neurodegenerative disease, specifically Huntington's disease. In particular, the invention provides single-stranded, modified oligonucleotides for the targeted alteration of the genetic sequence of the Huntington's disease gene, and mehods of treating or preventing Huntington's disease using the same.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of vascular endothelial growth factor receptor-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding vascular endothelial growth factor receptor-1. Methods of using these compounds for modulation of vascular endothelial growth factor receptor-1 expression and for treatment of diseases associated with expression of vascular endothelial growth factor receptor-1 are provided.

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: Antisense compounds, compositions and methods are provided for modulating the expression of Interleukin-15. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Interleukin-15. Methods of using these compounds for modulation of Interleukin-15 expression and for treatment of diseases associated with expression of Interleukin-15 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of acyl coenzyme A cholesterol acyltransferase-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding acyl coenzyme A cholesterol acyltransferase-1. Methods of using these compounds for modulation of acyl coenzyme A cholesterol acyltransferase-1 expression and for treatment of diseases associated with expression of acyl coenzyme A cholesterol acyltransferase-1 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of hormone-sensitive lipase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding hormone-sensitive lipase. Methods of using these compounds for modulation of hormone-sensitive lipase expression and for treatment of diseases associated with expression of hormone-sensitive lipase are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of acyl CoA cholesterol acyltransferase-2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding acyl CoA cholesterol acyltransferase-2. Methods of using these compounds for modulation of acyl CoA cholesterol acyltransferase-2 expression and for treatment of diseases associated with expression of acyl CoA cholesterol acyltransferase-2 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of sphingosine-1-phosphate lyase. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding sphingosine-1-phosphate lyase. Methods of using these compounds for modulation of sphingosine-1-phosphate lyase expression and for treatment of diseases associated with expression of sphingosine-1-phosphate lyase are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of vascular endothelial growth factor receptor-2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding vascular endothelial growth factor receptor-2. Methods of using these compounds for modulation of vascular endothelial growth factor receptor-2 expression and for treatment of diseases associated with expression of vascular endothelial growth factor receptor-2 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of IL-1 receptor-associated kinase-4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding IL-1 receptor-associated kinase-4. Methods of using these compounds for modulation of IL-1 receptor-associated kinase-4 expression and for treatment of diseases associated with expression of IL-1 receptor-associated kinase-4 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of fibroblast growth factor receptor 3. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding fibroblast growth factor receptor 3. Methods of using these compounds for modulation of fibroblast growth factor receptor 3 expression and for treatment of diseases associated with expression of fibroblast growth factor receptor 3 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Protein Kinase R. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Protein Kinase R. Methods of using these compounds for modulation of Protein Kinase R expression and for treatment of diseases associated with expression of Protein Kinase R are provided.

Abstract: The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of microsomal triglyceride transfer protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding microsomal triglyceride transfer protein. Methods of using these compounds for modulation of microsomal triglyceride transfer protein expression and for treatment of diseases associated with expression of microsomal triglyceride transfer protein are provided.

Abstract: The present application describes novel spiro-cyclic &bgr;-amino acid derivatives of formula I: 1