Abstract: The present invention is directed to methods of treating movement disorders by administering an effective amount of one or more adenosine A2A receptor antagonists to a patient in need thereof. The present invention also provides methods of decreasing the adverse effects of L-DOPA in patients receiving L-DOPA therapy in the treatment of Parkinson's disease. The present invention further provides methods and compositions for treating Parkinson's disease patients with sub-clinically effective doses of L-DOPA by combining L-DOPA treatment with an effective amount of one or more adenosine A2A receptor antagonists (i.e., L-DOPA sparing effect). The present invention further provides methods of effective treatment of Parkinson's disease by co-administering at least one adenosine A2A receptor antagonist, L-DOPA and a dopamine agonist and/or a COMT inhibitor and/or a MAO inhibitor.

Abstract: Method of preventing or reducing diarrhea and correcting fat malabsorption (steatorrhea) and loss of body mass in HIV-positive patients being treated with High Activity Antiretroviral drugs (HAART) containing protease inhibitors, nucleoside reverse transcriptase inhibitors or non-nucleoside reverse transcriptase inhibitors and by co-administering with the HAART a buffered pancrelipase composition. The method includes the steps of: administering to the HIV-positive patient a High Activity Antiretroviral drug containing a protease inhibitor, a nucleoside reverse transcriptase inhibitor or a non-nucleoside reverse transcriptase inhibitor; and co-administering with the HAART drug a gastric acid-resistant polymer-coated and buffered pancrelipase enzyme composition containing pancreatic proteases, lipases, co-lipases, nucleases, amylases and other bio-active substances produced by the pancreatic gland.

Abstract: Compounds which are active against viruses have the following Formulas: wherein B is a purine or pyrimidine heterocyclic ring and is preferably selected from the group consisting of 6-aminopurine (adenine), 2,6-diaminopurine, 2-amino-6-azidopurine, 2-amino-6-cyclopropylaminopurine, 6-hydroxypurine (hypoxanthine), 2-amino-6-halo substituted purines, 2-amino-6-alkoxy substituted purines, 2-amino-6-hydroxypurine (guanine), 3-deazapurines, 7-deaza-purines, 8-azapurines, cytosine, 5-halo substituted cytosines, 5-alkyl substituted cytosines, thymine, uracil and 6-azapyrimidines; X is O; and, R1 and R2 are alkyl or aryl groups. The compounds of the present invention also include the R- and S-enantiomers of the above compounds. The R1X and/or R2X can also be amino acid residues with X as NH.

Abstract: Disclosed are processes for the synthesis of novel compounds that are A2B adenosine receptor antagonists, useful for treating various disease states, including asthma and diarrhea.

Abstract: A method of inhibiting HIV infection in a mammal by administering to said mammal in need thereof a small molecule compound having a molecular weight of less than about 1,000 dalton, wherein said compound interacts with HIV-gp120 in such a manner as to cause conformational change in said gp120 thereby preventing interaction between said gp120 and leukocyte CD4.

Abstract: Compound of general formula I: wherein R1, R2, R3, R4, X, Y and R5 have the meanings given herein which are useful in the curative and prophylactic treatment of a medical condition for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.

Abstract: The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.

Abstract: The present invention relates to compounds of formula (I), in which B, D, E, G, X, Y, Z, R1, R2 and s have the meanings indicated in the claims, their physiologically tolerable salts and their prodrugs. The compounds of formula (I) are valuable pharmacologically active compounds. They are vitronectin receptor antagonist and inhibitors of cell adhesion and are suitable for the therapy and prophylaxis of illnesses which are based on the interaction between vitronectin receptors and their ligands in cell-cell or cell-matrix interaction processes or which can be prevented, alleviated or cured by influencing such interactions. For example, they can be applied for inhibiting bone resorption by osteoclasts and thus for treating and preventing osteoporosis, or for inhibiting undesired angiogenesis or prolifertion of cells of the vascular smooth musculature.

Abstract: The present invention concerns the use of an active ingredient selected from the group consisting of agonists of the adenosine receptor system, for inhibiting viral replication in cells. In particular, the invention provides a composition and method for inhibiting viral replication in cells, the method comprising presenting to the cells an effective amount of the active ingredient. According to one embodiment, the adenosine agonist is an A3 receptor agonist (A3RAg). The invention is particularly useful, for although not limited to, inhibiting the replication of HIV virus in human cells.

Abstract: The present invention provides a method of optimizing therapeutic efficacy and reducing toxicity associated with 6-mercaptopurine drug treatment of an immune-mediated gastrointestinal disorder such as inflammatory bowel disease. The method of the invention includes the step of determining the level of one or more 6-mercaptopurine metabolites in the patient having an immune-mediated gastrointestinal disorder.

Abstract: Purine derivatives represented by the following formula and salts thereof: wherein R1 represents a C1-C4 alkyl group or difluoromethyl group; R2 represents tetrahydrofuranyl group, a C1-C7 alkyl group and the like; X represents hydrogen atom, a halogen atom or nitro group; and A represents a group represented by the following formula: wherein R3 represents hydrogen atom, a halogen atom and the like; R4 and R5 represent hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxyl group and the like, which are useful as active ingredients of medicaments such as antiasthmatic agents.

Abstract: Methods of treating thrombotic and hemostatic conditions related to platelet activity are described herein. The methods of treating thrombotic and hemostatic conditions use active agents that modulate production of guanosine 3′, 5′ cyclic monophosphate (cGMP) or the function of cGMP-dependent protein kinase (PKG), and its downstream effectors, the ERK and p38 pathways.

Abstract: Pyrazolopyrimidine compounds which are selective inhibitors of cGMP PDE are useful in the treatment of erectile dysfunction (impotence) in male animals, including man.

Abstract: Dihydrate of 4-[[9-[(3-cyclopentyloxy-4-methoxy)benzyl]-6,8-dimethylpurin]-2-yl-3-oxypropyl]pyridine N-oxide, drugs containing the same and a compound useful as an intermediate in the production of this dihydrate.

Abstract: The present invention relates to fused bicyclic metalloproteinase inhibitors of the formula 1

Abstract: Disclosed are therapeutic compounds having the formula: (R)j—(CORE MOIETY), including resolved enantiomers, diastereomers, hydrates, salts, solvates or mixtures thereof where j is an integer from one to three. The core moiety is a bicyclic ring structure having at least one heterocyclic ring that contains five to six ring atoms and up to two nitrogen heteroatoms. R is selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C1-6 alkyl or C1-6 alkenyl, and at least one R has the formula I: n is an integer from 1 to 20, at least one of X or Y is —OH. Another of X or Y, which is not —OH, is hydrogen, CH3—, CH3—CH2—, CH3—(CH2)2—or (CH3)2—CH2—, and each W1, W2, and W3 is independently hydrogen, CH3—, CH3—CH2—, CH3—(CH2)2— or (CH3)2—CH2—.

Abstract: The present invention relates to a method for treating a tumor in a tissue of a human or non-human animal, the tumor having an elevated level of glutathione relative to the tissue, the method comprising the steps of administering to the animal a prodrug comprising a thiopurine having a sulfur heteroatom conjugated to an alpha-, beta-unsaturated carbonyl moiety, in combination with a pharmaceutically acceptable carrier, the moiety comprising a double bond having an alpha end and a beta end, the beta end being accessible to glutathione in an addition-elimination reaction, the prodrug lacking an ionizable carboxylic acid group; and observing a reduction in growth of the tumor.

Abstract: The present invention is directed to methods for readily generating hepatocyte precursor cell lines that retain hepatocyte-specific functions after extensive in vitro culturing. The methods comprise isolating and culturing hepatocyte precursor cell lines under permissive culture conditions that suppress asymmetric cell kinetics and allow exponential growth of the precursor cells, followed by transferring the hepatocyte precursor cell lines to non-permissive culture conditions that allow expression of asymmetric cell kinetics and induce expression of hepatocyte-specific characteristics.

Abstract: The invention provides an isolated nucleic acid molecule having substantially the same nucleotide sequence as SEQ ID NO:1. Also provided is an isolated oligonucleotide having at least 15 contiguous nucleotides of a nucleotide sequence referenced as SEQ ID NO:11. An isolated polypeptide having substantially the same amino acid sequence as SEQ ID NO:2 is further provided as well as an antibody, or antigen binding fragment thereof, which specifically binds to an ATX polypeptide and has an amino acid sequence as referenced in SEQ ID NO:2. A method for identifying an ATX-modulatory compound is additionally provided. The method consists of measuring the level of an ATX polypeptide in the presence of a test compound, wherein a difference in the level of said ATX polypeptide in the presence of said test compound compared to in the absence of said test compound indicating that said test compound is an ATX-modulatory compound, and wherein said ATX-modulatory compound is not caffeine or wortmannin.

Abstract: Compositions and methods for delivering active agents to the skin of a subject, including a polymer, an active ingredient and a solvent are disclosed, the compositions being capable of delivery by rolling, spreading, aerosol or in droplets and of forming a film in contact with the skin.

Abstract: Antigen specific immune tolerance is induced in a mammalian host by administration of a toleragen in combination with a regimen of immunosuppression. The methods optionally include a preceding conditioning period, where immunosuppressive agents are administered in the absence of the toleragen. After the tolerizing regimen, the host is withdrawn from the suppressive agents, but is able to maintain specific immune tolerance to the immunogenic epitopes present on the toleragen. Optimally, the toleragen will have high uptake properties that allow uptake in vivo at low concentrations in a wide variety of tolerizing cell types.

Abstract: The present invention relates to methods for modulating calcium sensitivity of cardiac muscle. In preferred aspects, the invention provides methods for enhancing myocardial contractility and cardiac performance, and methods for treatment of heart failure and other disorders associated with cardiac contractility by administration of one or more xanthine oxidase inhibitor compounds.

Abstract: This invention discloses pyrimidine compounds, and pharmaceutically acceptable salts, solvates and prodrugs thereof, useful in therapeutically and/or prophylactically treating patients with cancer by inhibiting receptor tyrosine kinases and/or dihydrofolate reductase and/or thymidylate synthase. The compounds, and methods of using these compounds, are disclosed.

Abstract: The present invention provides a medicament having a gentle but strong defecation-promoting action without causing diarrhea. That is, it provides a defecation-promoting agent comprising a compound having an adenosine A2 receptor antagonism, preferably an adenosine A2b receptor antagonism, or a salt thereof.

Abstract: This invention relates to the use of cyclic guanosine 3′,5′-monophosphate phosphodiesterase type five (cGMP PDE5) inhibitors, including in particular the compound sildenafil, for the treatment of neuropathy, including in particular the treatment of diabetic neuropathy.

Abstract: The invention provides methods for treating female sexual dysfunctions by administering to a female individual a therapeutically effective amount of at least one compound that donates, transfers or release nitrogen monoxide, that induces the production of endogenous endothelium-derived relaxing factor, that stimulates endogenous synthesis of nitrogen monoxide, or that is a substrate for nitric oxide synthase. The methods may further comprise administering a therapeutically effective amount of a phosphodiesterase inhibitor and/or a nitrosated and/or nitrosylated phosphodiesterase inhibitor.

Abstract: The present invention relates to inhibitors of JNK, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Abstract: Compounds provided herein are novel substituted tetrahydropurinones of Formula (I): 1

Abstract: A method of treating cystic fibrosis in a patient comprising: administering to said patient an effective amount of a type V cyclic nucleotide phosphodisterase inhibitor, wherein said inhibitor is a compound of formula (I):  wherein A is a five- or six-membered ring containing one or more N atoms, X is a substituent of formula (II):  wherein R1 represents C1-4 alkyl, and X is positioned at either or both of the 2-position and/or the 8-position in (I).

Abstract: The present invention relates to the delivery of caffeine through an inhalation route. Specifically, it relates to aerosols containing caffeine that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of caffeine. In a method aspect of the present invention, caffeine is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of caffeine, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. In a kit aspect of the present invention, a kit for delivering caffeine through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of caffeine; and, b) a device that forms a caffeine containing aerosol from the composition, for inhalation by the mammal.

Abstract: The present invention provides a procaryotic host cell stably transformed or transfected by a vector including a DNA sequence encoding for purine nucleoside phosphorylase or hydrolase. The transformed or transfected procaryotic host cell can be used in combination with a purine substrate to treat tumor cells and/or virally infected cells.

Abstract: A pharmaceutical formulation is provided for treating erectile dysfunction in a mammalian male individual. The pharmaceutical formulation includes a phosphodiesterase inhibitor or a pharmaceutically acceptable salt, ester, amide or derivative thereof, that is administered transmucosally within the context of an effective dosing regimen. Preferred modes of administration include transbuccal, sublingual and transrectal routes. A kit for the administration of the pharmaceutical formulation is also provided.

Abstract: There is provided compounds of formula IA and of formula IB, wherein R1, R2, R3, Het1 and X have meanings given in the description, which are useful in the curative and prophylactic treatment of medical conditions for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.

Abstract: There is provided compounds of formula IA and of formula IB, wherein R1, R2, R3, Het1 and X have meanings given in the description, which are useful in the curative and prophylactic treatment of medical conditions for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.

Abstract: The present invention provides a preventive or therapeutic agent of a new type for diabetes mellitus and diabetic complications on the basis of an adenosine A2 receptor antagonistic action. A purine compound represented by the formula (I), its pharmacologically acceptable salt or hydrates thereof has an adenosine A2 receptor antagonistic action and is useful for prevention or therapy of diabetes mellitus and diabetic complications. In addition, adenosine A2 receptor antagonists having different structures from those of the compounds described above, for example KW6002, are also effective for prevention or therapy of diabetes mellitus and diabetic complications. In the formula, W is —CH2CH2—, —CH═CH— or —C≡C—; R1 is: (in the formula, X is hydrogen atom, hydroxyl group, a lower alkyl group, a lower alkoxy group, etc.

Abstract: Compound of general formula I: 1

Abstract: Nucleoside analogues or base analogues having structure (1), where X=O or NH or S, Y=N or CHR6 or CR6, W=N or NR6 or CHR6 or CR6 or S, n=1 or 2; each R6 is independently H or O or alkyl or alkenyl or alkoxy or aryl or a reporter moiety; where necessary (i.e. when Y and/or W is N or CR6 where R6 is not O) a double bond is present between Y and W or W and W, and Q is H or a sugar or a sugar analogue or a nucleic acid backbone or backbone analogue.

Abstract: Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K&dgr;) activity, and methods of treating diseases, such as disorders of immunity and inflammation, in which PI3K&dgr; plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3K&dgr;, while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3K&dgr; activity, including compounds that selectively inhibit PI3K&dgr; activity. Methods of using PI3K&dgr; inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3K&dgr; inhibitory compounds to inhibit PI3K&dgr;-mediated processes in vitro and in vivo.

Abstract: A pharmaceutical product comprising a nucleoside analogue active against herpes simplex virus, such as acyclovir/valaciclovir or penciclorivir/famciclovir, and an immunosuppressant, as a combined preparation for simultaneous, separate or sequential use in the treatment and/or prevention of herpes simplex virus infections.

Abstract: Several lines of evidence have shown a role for the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway in the development of spinal hyperalgesia. However, the roles of effectors for cGMP are not fully understood in the processing of pain in the spinal cord. cGMP-dependent protein kinase (PKG) I&agr; but not PKGI&bgr; was localized in the neuronal bodies and processes, and was distributed primarily in the superficial laminae of the spinal cord. Intrathecal administration of an inhibitor of PKGI&agr;, Rp-8-[(4-Chlorophenyl)thio]-cGMPS triethylamine, produces significant antinociception. Moreover, PKGI&agr; protein expression was dramatically increased in the lumbar spinal cord after noxious stimulation. This upregulation of PKGI&agr; expression was completely blocked not only by a neuronal NO synthase inhibitor, and a soluble guanylate cyclase inhibitor, but also by an N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801.

Abstract: There is provided compounds of formula IA and of formula IB, 1

Abstract: There is provided compounds of formula IA and of formula IB, 1

Abstract: Trauma, surgery, inflammation, subfertility, pregnancy, lactation problems, gut disorders, infant nutrition, cancer, arthritis and other joint problems, vascular problems and cardio-or cerebro-vascular problems, ischaemia, aging, impaired immune function, burns, sepsis, malnutrition, problems with liver, pancreas or kidneys, malaria, cystic fibrosis, migraine, neurological problems, respiratory infections, improvement of sports results, muscle soreness, drug intoxication and pain can be treated with a nutritional composition containing effective amounts of ribose and folic acid, optionally combined with other components such as niacin, histidine, glutamine, orotate, vitamin B6 and other components.

Abstract: Methods for reducing or preventing transplant rejection in the eye of an individual are described, comprising: a) performing an ocular transplant procedure; and b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.

Abstract: Novel, heterocyclic compounds having at least one ring nitrogen, disclosed side chains and, in some embodiments, an oxygen ortho to the ring nitrogen inhibit inflammatory responses associated with TNF-&agr; and fibroblast proliferation in vivo and in vitro. The compounds of the invention neither appreciably inhibit the activity of cAMP phosphodiesterase nor the hydrolysis of phosphatidic acid, and are neither cytotoxic nor cytostatic. Preferred compounds of the invention are esters. Methods for the use of the novel compounds to inhibit ceramide-mediated intracellular responses in stimuli in vivo (particularly TN-&agr;) are also described. The methods are expected to be of use in reducing inflammatory responses (for example, after angioplasty), in limiting fibrosis (for example, of the liver in cirrhosis), in inhibiting cell senescence, cell apoptosis and UV induced cutaneous immune suppression. Compounds having enhanced water solubility are also described.

Abstract: The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions containing at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one phosphodiesterase inhibitor, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents.

Abstract: The present invention provides a method of transplanting hematopoietic cells between genetically unrelated individuals, comprising administering to the recipient, in combination with the administration of the hematopoietic cells, an amount of mononuclear cells which are treated so as to substantially reduce their ability to cause graft versus host disease while they retain their ability to proliferate in the recipient. The treated mononuclear cells can facilitate engraftment of hematopoietic cells when transplanted in combination with hematopoietic cells, treat or prevent infections, and treat cancer.

Abstract: One aspect of the present invention is a method of treating a condition or disease associated with the activity of a multidrug transporter protein comprising administering to a mammal with a condition or disease associated with the activity of a multidrug transporter protein an effective quantity of a purine derivative or analogue, a tetrahydroindolone derivative or analogue, or a pyrimidine derivative or analogue. If the compound is a purine derivative, the purine moiety can be guanine or hypoxanthine. A particularly preferred bifunctional purine derivative is N-4-carboxyphenyl-3-(6-oxohydropurin-9-yl) propanamide. Methods according to the present invention can be used to treat cancer, a microbial or parasitic infection, HIV, infection, or a condition associated with inflammation such as asthma or rheumatic disease.

Abstract: There is provided compounds of formula IA and of formula IB, wherein R1, R2, R3, Het1 and X have meanings given in the description, which are useful in the curative and prophylactic treatment of medical conditions for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.

Abstract: The small particle liposome or lipid complex aerosol compounds and methods of treatment of the present invention involve lipid- or water soluble anti-cancer drugs incorporated into liposomes or other lipid complexes. The liposomes and complexes are administered in aqueous dispersions from a jet nebulizer to the respiratory tract of an individual. Various anti-cancer drugs may be used, including 20-S-Camptothecin, 9-Nitro-camptothecin, 9-Amino-camptothecin, 10,11 -methylenedioxy-camptothecin and taxol or its derivatives. Administration of these drugs by inhalation provides faster and more efficient absorption of the anticancer drug than does intramuscular administration or oral administration.