Abstract: Provided is a composition comprising, as an active ingredient, at least one material selected from the group consisting of uridine and derivatives thereof which promote synthesis of hyaluronic acid in animal and human cell and body, and a pharmaceutical preparation containing the same. The composition and pharmaceutical preparation of the present invention is effective in the treatment and prevention of dry eye syndrome.

Abstract: The present invention provides a P2Y12 receptor antagonist compound-eluting stent, wherein the stent is coated with one or more P2Y12 receptor antagonist compounds or a pharmaceutically acceptable salt, solvate, or hydrate thereof. When the stent is placed in a narrowed or damaged arterial vessel, a therapeutically effective amount of the P2Y12 receptor antagonist compound is eluted continuously from the stent to the local environment of the stent. The P2Y12 receptor antagonist compound-eluting stents are useful in preventing thrombosis and restenosis, and are effective in inhibiting the contraction of vascular smooth muscle cells, inhibiting cell proliferation, and reducing inflammation.

Abstract: 2-Substituted-5?-O-(1-boranotriphosphate)adenosine derivatives having at position 2 a radical R1 selected from the group consisting of H; halogen; O-hydrocarbyl; S-hydrocarbyl; NR3R4; and hydrocarbyl optionally substituted by halogen, CN, SCN, NO2, OR3, SR3 or NR3R4; wherein R3 and R4 are each independently H or hydrocarbyl or R3 and R4 together with the nitrogen atom to which they are attached form a saturated or unsaturated heterocyclic ring optionally containing 1-2 further heteroatoms selected from oxygen, nitrogen and sulfur, and pharmaceutically acceptable salts or diastereoisomers thereof or a mixture of diastereoisomers, are useful for treatment of type 2 diabetes.

Abstract: Novel compositions and methods are provided for identifying agents which affect chromosomal stability and aging.

Abstract: The present invention provides compounds having the formula: wherein A is chosen from a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group; both B and C are hydrogen, or either B or C is a halogen, amino, or thiol group and the other of B or C is hydrogen; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.

Abstract: The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds, which comprise a phosphocholine moiety covalently conjugated with one or more therapeutic agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt or a prodrug thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus.

Abstract: The present invention provides compounds having the formula: wherein A is a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group, the group being further substituted with an electron contributing moiety; B is hydrogen, or a halogen, amino, or thiol group; C is hydrogen, or a halogen, amino, or thiol group; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.

Abstract: Uridine analogs and techniques for making and using uridine analogs are disclosed in this invention. These uridine analogs include nucleoside phosphates having a 5-aminouracil group. These nucleotides can be incorporated into a nucleic acid as an unnatural base, as a substitute for uridine or thymine. The nucleic acid can then be treated with an oxidizing agent and an alkaline solution, which causes cleavage of the nucleic acid at the position of the unnatural base. The nucleoside phosphate analogs can be used in many ways, including measuring chemical interactions between nucleic acids and other compounds, or sequencing nucleic acids. Additional compounds can also be derivitized onto the amino group, allowing other functionalities to be added to the nucleoside phosphate, or to the nucleic acid incorporating the nucleoside phosphate.

Abstract: The present invention is directed to the field of organic chemistry in general and specifically to the preparation of hydrophobic derivatives of cyclic ADP ribose. One form of the present invention is the composition of one or more hydrophobic derivatives of cyclic ADP ribose. In another form of the present invention, a method for preparing a hydrophobic composition is described. Compositions of the present invention are useful for the study of in vivo calcium metabolism.

Abstract: The invention describes a process for producing P1,P4-di(uridine-5′-)tetraphosphate (U2P4) or a salt thereof from uridine 5′-monophosphate (UMP); wherein the process comprises at least one of the steps (a) and (b): (a) adding UMP diphenylphosphate (UMP-DPP) in divided portions during a step of reacting UMP-DPP with an organic alkali salt of pyrophosphate (PP1) to produce a reaction mixture; wherein at least one equivalent of a first base is present during one portion of the reaction; (b) reacting UMP-DPP with a PPi-organic alkali salt in the presence of at least one equivalent of a second base to produce a reaction mixture, wherein the first base and the second base may be the same or different; (c) subsequently adding water to the reaction mixture to produce an aqueous reaction mixture; and optionally (d) adding an alkali to the aqueous reaction mixture.

Abstract: The present invention is directed to a method of stimulating ciliary beat frequency to promote mucociliary or cough clearance of retained mucus secretions from the lungs, sinuses, upper airways, ears, eyes, genito-urinary tract, spermatozoa, ovaries, fallopian tubes, neutrophils, and macrophages of a patient. The method comprises administering uridine triphosphates, adenosine triphosphates, cytidine triphosphates, or dinucleoside tetraphosphates and the derivatives thereof to an affected body of a patient, to treat dysfunction of the mucociliary clearance system as a result of impaired ciliary movement in the patient.

Abstract: The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds which comprise a phosphocholine moiety covalently conjugated with one or more antiviral agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions and kits for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and for facilitating delivery of a therapeutic agent to a mammalian cell.

Abstract: The present invention relates to certain novel dinucleoside polyphosphates of general Formulae I, II and III, and formulations thereof which are selective ligands of the P2Y purinergic receptors. Applicants have discovered that dinucleoside polyphosphates of general Formulae I, II and III are effective in clearing retained mucous secretions, balancing tissue hydration and fluid secretion, and/or inhibiting or preventing early stages of platelet activation, platelet degranulation, and platelet aggregation.

Abstract: The invention provides crystals of P1,P4-di(uridine 5′-)tetraphosphate or a salt thereof; a process for producing the crystals; and a process for producing P1,P4-di(uridine 5′-)tetraphosphate (U2P4) or a salt thereof from UMP serving as a starting material and by use of DPC and PPi, which process comprises at least one of the following treatment steps: (a) adding UMP diphenylphosphate (UMP-DPP) in divided portions during a step of reaction of UMP-DPP with a PPi-organic alkali salt; (b) carrying out reaction of UMP-DPP with a PPi-organic alkali salt in the presence of a base; and (c) further treating the synthesized U2P4 with an alkali. The crystals of U2P4 or a salt thereof obtained through the process according to the invention have high purity and stability and a less hygroscopicity as compared with a lyophilized product, to thereby serve as a useful raw material for preparing a pharmaceutical.

Abstract: The invention provides crystals of p1,P4-di(uridine 5′-) tetraphosphate or a salt thereof; a process for producing the crystals; and a process for producing P1,P4-di(uridine 5′-) tetraphosphate (U2P4) or a salt thereof from UMP serving as a starting material and by use of DPC and PPi, which process comprises at least one of the following treatment steps: (a) adding UMP diphenylphosphate (UMP-DPP) in divided portions during a step of reaction of UMP-DPP with a PPi-organic alkali salt; (b) carrying out reaction of UMP-DPP with a PPi-organic alkali salt in the presence of a base; and (c) further treating the synthesized U2P4 with an alkali. The crystals of U2P4 or a salt thereof obtained through the process according to the invention have high purity and stability and a less hygroscopicity as compared with a lyophilized product, to thereby serve as a useful raw material for preparing a pharmaceutical.

Abstract: Compounds are disclosed for treating AIDS, herpes, and other viral infections by means of lipid derivatives of antiviral agents. The compounds consist of nucleoside analogues having antiviral activity which are linked, commonly through a phosphate group at the 5′ position of the pentose residue, to one of a selected group of lipids. The lipophilic nature of these compounds provide advantages over the use of the nucleoside analogue alone. It also makes it possible to incorporate them into the lamellar structure of liposomes, either alone or combined with similar molecules. In the form of liposomes, these antiviral agents are preferentially taken up by macrophages and monocytes, cells which have been found to harbor the target HIV virus. Additional site specificity may be incorporated into the liposomes with the addition of ligands, such as monoclonal antibodies or other peptides or proteins which bind to viral proteins.

Abstract: The present invention relates to certain novel dinucleotide polyphosphates of general Formulae I, II and III, and formulations thereof which are selective agonists of the P2Y purinergic receptors. They are useful in the prevention, management or treatment of diseases and disorders associated with abnormalities of tissue fluid secretion, hydration and clearance, including chronic obstructive pulmonary diseases (chronic bronchitis, PCD, cystic fibrosis, immobility-associated pneumonia), sinusitis, otitis media, nasolacrimal duct obstruction, dry eye disease, glaucoma, retinal degeneration, and edematous retinal disorders, including retinal detachment, vaginal dryness, and gastrointestinal tract disease. Finally, these novel dinucleotides may be useful for diagnostic purposes, such as the facilitation of sputum induction and expectoration for the analysis of respiratory tract secretions.

Abstract: The present invention provides methods for the synthesis of a pharmaceutically useful dinucleotide, P1, P4-di(uridine 5′)-tetraphosphate, and demonstrates the applicability to the production of large quantities. The methods of the present invention substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less. The tetrasodium, ammonium, lithium and potassium salts of P1, P4-di(uridine 5′)-tetraphosphate prepared by these methods are stable, soluble, nontoxic, of high purity and easy to handle during manufacture.

Abstract: The present invention relates to certain novel dinucleotides and formulations thereof which are highly selective agonists of the P2Y2 and/or P2Y4 purinergic receptor. They are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, PCD, cystic fibrosis, as well as prevention of pneumonia due to immobility. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis, otitis media and nasolacrimal duct obstruction. They are also useful for treatment of dry eye disease and retinal detachment as well as facilitating sputum induction and expectoration.

Abstract: The invention discloses a two-step process for recovery of thuringiensin, comprising adsorbing the thuringiensin from fermentation broth by calcium silicate, and dissociating the thuringiensin by dibasic sodium phosphate. The resulting thuringiensin can be further purified by using semi-preparative HPLC and electrodialysis to remove the excess salts from the recovered thuringiensin solution.

Abstract: The specification discloses purine nucleotide analogues which modulate cardiac muscle contractility and possess vasodilator activity. In addition, related methods of administration and the identity of receptors that bind these compounds are disclosed.