Abstract: The present invention is predicated on the discovery of certain interactions between cellular growth factors and opposing actions that control differentiation and migration or invasion of cytotrophoblasts into the uterine endometrium during pregnancy. IGF-II and latent transforming growth factor beta (TGF?), the inactive precursor of TGF?, compete for binding to the CIM6P receptor. IGF-II prevents latent TGF? binding to the CIM6P receptor. The invention therefore offers a method of regulating and directing cytotrophoblast differentiation and function based on the interaction between IGF-II, latent TGF? and the CIM6P receptor. There is disclosed a method of regulating cytotrophoblast and stem cell differentiation and migration characterized by adjusting levels of insulin-like growth factor II (IGF-II) available for binding to the cation-independent mannose-6-phosphate (CIM6P) receptor. The discovery may be applied to embryonic or adult stem cells to control their differentiation and migratory behaviour.

Abstract: Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined and were used to design substrate analogs of the natural -2 substrate that can inhibit the function of memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. The inhibition constant of OM99-2 is 1.6×10?9 M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bound to this inhibitor was used to determine the three dimensional structure of the protein, and the importance of the various residues in binding. This information is useful for designing new inhibitors to memapsin 2, for diagnosing and treating and/or preventing Alzheimer's disease.

Abstract: Pharmaceutical compositions and methods are described comprising at least a parathyroid hormone peptide (PTH) preferably PTH1-34 and one or more mucosal delivery-enhancing agents for enhanced nasal mucosal delivery of PTH, for treating or preventing osteoporosis or osteopenia in a mammalian subject, preferably a human.

Abstract: The present invention discloses a method of treating an ophthalmic infection by administering to a vertebrate inflicted with the ophthalmic infection an ophthalmologically effective amount of an antimicrobial peptide which is derived from alpha-melanocyte-stimulating hormone (?-MSH) and biologically functional equivalents thereof. Specifically, the antimicrobial peptides derived from alpha-melanocyte-stimulating hormone (?-MSH) include ?-MSH (1–13) which is SYSMEHFRWGKPV, ?-MSH (4–10) which is MEHFRWG, ?-MSH (6–13) which is HFRWGKPV, ?-MSH (11–13) which is KPV, and a KPV dimer. The ophthalmic infection can be caused by a microorganism which include a bacteria, a fungi or a virus. The vertebrate includes a bird and a mammal. The antimicrobial peptide has anti-bacterial, antifungal, and antiviral property and therefore can be administered at the onset of the ophthalmic infection before the microorganism causing the infection is determined as well as thereafter.

Abstract: The invention concerns a pharmaceutical composition comprising, as active principle, at least a calpain inhibiting substance and at least a substance trapping reactive oxygen species (ROS), and optionally an acceptable pharmaceutical carrier. The invention also concerns a product comprising at least a calpain inhibiting substance and at least a substance trapping reactive oxygen species (ROS), selectively or not, as combination product, the active principle being separate.

Abstract: The present invention relates to aminoglycoside compounds having antibiotic activity. Moreover, the present invention relates to L-aminoglycoside compounds and diastereomers thereof which posses antibiotic activity and are not susceptible to development of resistant bacterial strains. The present invention also relates to methods of treatment and pharmaceutical compositions that utilize or comprise one or more of aminoglycoside compounds provided by the invention.

Abstract: Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus. Such compounds are represented by Formula I as follows: wherein, T, Y, W, W1 and W2 are as defined herein.

Abstract: Methods and devices for delivering aerosolized formulations containing polynucleotides to specified regions within a subject's respiratory tract are disclosed. The methods find use in the delivery of ribozymes, antisense polynucleotides, and DNA and RNA expression vectors into airway epithelial cells, alveoli, pulmonary macrophages and other cells in the respiratory tract (including the oropharynx, nose, nasopharynx). These methods may be used for optimization of transfection efficiency and expression in vivo, and for in vivo expression, for example for generating an immune response, or inducing immunological tolerance.

Abstract: Compositions and methods for enhancing the effect of vaccines in animals, such as domestic, sport, or pet species, and humans are disclosed. More particularly, vaccine compositions comprising ribavirin and an antigen, preferably an antigen that has an epitope present in Hepatitis C virus (HCV), are disclosed for use in treating and preventing disease, preferably HCV infection.

Abstract: In accordance with the present invention there is provided a pharmaceutical composition useful for the treatment or prophylaxis of viral infections comprising tipranavir and at least one antiviral active compound of formula (I) wherein Base is selected from the group consisting of thymine, cytosine, adenine, guanine, inosine, uracil, 5-ethyluracil and 2,6-diaminopurine, or a pharmaceutically acceptable salt or prodrug thereof.

Abstract: The present invention relates to methods of treating viral disease using mutagenic nucleoside analogs. In particular, the invention provides 5-aldehydo-uracil nucleosides and derivatives thereof, and methods of administration thereof to increase the virus mutation rate in a virally infected cell.

Abstract: The present invention is directed to novel water-soluble prodrugs of aliphatic or aromatic hindered hydroxyl group containing pharmaceuticals.

Abstract: This invention discloses 2-methylene-19,26,27-trinor-(20S)-vitamin D analogs, and specifically 2-methylene-19,26,27-trinor-(20S)-1?-hydroxyvitamin D3 and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also has little, if any, calcemic activity and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. This compound may also be used for the treatment or prevention of obesity.

Abstract: A solid mixture or aqueous solution of amoxicillin antibacterial agent with a material that aids in its dissolution in water to render it ingestive and palatable.

Abstract: The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

Abstract: Compounds of the general formula (I): wherein m, n, R1, R2, R3 and R4 are as described in the specification. Further included are pharmaceutical compositions comprising the compounds, processes for their preparation, as well as the use of the compounds for the preparation of a medicament for the treatment of 5-HT2A receptor-related disorders or medical conditions.

Abstract: The present invention relates to furanopyrimidinone compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

Abstract: A compound of formula I: or solvate thereof, wherein n is 1 to 10, and M and M? are independently selected from monovalent pharmaceutically acceptable cations, or together represent a divalent pharmaceutically acceptable cation.

Abstract: Disclosed are compounds of the formula: where variables Z, X, R15, R2, R3, and RC are defined herein. Compounds disclosed herein are inhibitors of the beta-secretase enzyme and are therefore useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal.

Abstract: Compounds of formula (I) and pharmaceutically acceptable salts thereof are disclosed: wherein A is optionally substituted phenyl, naphthyl, indolyl, quinolinyl, quinazolinyl, indazolyl, isoquinolinyl or benzofuranyl; b is 1, 2 or 3 and c is 1, 2 or 3, wherein b+c is 2, 3, 4 or 5; X is carbon, Y is CH, is a double bond and e is 0; or X is carbon, Y is CH2 or oxygen, is a single bond and e is 1; or X is nitrogen, Y is CH2, is a single bond and e is 0; R1 is hydrogen, cyano, halogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, NHCOCH3 or OCONR5R6, wherein R5 and R6 are independently hydrogen or C1-6alkyl; R2 is halogen, cyano or C1-6alkoxy; d is 0, 1, 2 or 3; R3 is hydrogen, C1-6alkyl, C1-6alkanoyl, fluoroC1-6alkanoyl, C1-6alkylsulfonyl, fluoroC1-6alkylsulfonyl, carbamoyl, C1-6alkylcarbamoyl or arylC1-6alkyl; and R4, together with the nitrogen atom to which it is attached, forms an optionally substituted 5 to 7 membered heterocyclic group fused to the benzene ring, provided that when a compoun

Abstract: Compounds, pharmaceutical compositions and methods that are useful in the treatment or prevention of metabolic and cell proliferative diseases or conditions are provided herein. In particular, the invention provides compounds which modulate the activity of proteins involved in lipid metabolism and cell proliferation.

Abstract: The present invention relates to the compounds of general formula 1 wherein the groups R, R1, R2, R3 and A may have the meanings given in the claims and specification, processes for preparing them and their use as medicaments, particularly for the treatment of inflammatory and obstructive respiratory complaints.

Abstract: The invention relates to 7H-pyrrolo[2,3-d]pyrimidine derivatives of formula I wherein the symbols and substituents are as defined in the description, to processes for the preparation thereof, to pharmaceutical compositions comprising such derivatives and to the use of such derivatives-alone or in combination with one or more other pharmaceutically active compounds-for the preparation of pharmaceutical compositions for the treatment especially of a proliferative disease, such as a tumour

Abstract: A 2-iminopyrrolidine derivative represented by the formula: {wherein ring B represents a benzene ring, pyridine ring, etc.; R101–R103 represent hydrogen, halogen, C1-6 alkyl, etc.; R5 represents hydrogen, C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, etc.; R6 represents hydrogen, C1-6 alkyl, C1-6 alkyloxycarbonyl, etc.; Y1 represents a single bond, —CH2—, etc.; Y2 represents a single bond, —CO—, etc.; and Ar represents hydrogen, a group represented by the formula: [wherein R10—R14 represent hydrogen, C1-6 alkyl, hydroxyl, C1-6 alkoxy, etc.; and R11 and R12 or R12 and R13 may bond together to form a 5- to 8-membered heterocyclic ring], etc.}, or a salt thereof.

Abstract: The present invention relates to 6-methylpyridine derivatives useful as an antiviral agent. More particularly, the present invention relates to novel 6-methylpyridine derivatives having an excellent inhibitory effect on replication of Hepatitis C virus (HCV), or pharmaceutically acceptable salts thereof, to a method for preparing thereof, and to an antiviral pharmaceutical composition comprising the compound as an active ingredient.

Abstract: The present invention provides hydrophobic prodrugs of bases, nucleosides, and nucleotides as well as methods of using the prodrugs as antiviral and anti-cancer chemotherapeutic agents.

Abstract: The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2, FGFR-1, PDGFR, HER-1, HER-2, thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.

Abstract: The invention relates to hexahydro-pyrido[1,2-a]pyrazine derivatives having interesting neurokinin-NK1 receptor antagonistic activity. The invention also relates to methods for the preparation of these compounds, to pharmaceutical compositions containing a pharmacologically active amount of at least one of these compounds as an active ingredient, as well as to the use of these compositions for the treatment of disorders in which neurokinin receptors are involved. The invention relates to compounds represented by the general formula (1) wherein the symbols have the meanings as given in the description.

Abstract: Described herein are compounds that are useful as protein kinase inhibitors of formula I: or a pharmaceutically acceptable salt thereof, wherein Ring B, Z1, Z2, U, p, Q, R1, R2, R3, and R3 are as defined herein. These compounds, and pharmaceutically acceptable compositions thereof, are useful for treating or lessening the severity of a variety of disorders, including stroke, inflammatory disorders, autoimmune diseases such as SLE lupus and psoriasis, proliferative disorders such as cancer, and conditions associated with organ transplantation.

Abstract: The invention provides 6-chloro-5-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-2-pyrazin-2-yl-N-[(1S)-2,2,2-trifluoro-1-methylethyl]pyrimidin-4-amine hemifumarate which is a tubulin inhibitor useful in the treatment of cancer and processes of making hemifumarate compounds and compositioning of the present invention.

Abstract: The present invention relates to a compound of the general formula: wherein R1 is a 4-pyrimidinyl ring substituted at the 6-position by halo, hydroxy, 2-cyanophenoxy, 2,6-difluorophenoxy, 2-nitrophenoxy or 2-thiocarboxamidophenoxy and wherein R2 is any group which can be transesterified to form a methyl ester. The present invention is also directed to a process of preparing said compound.

Abstract: Compounds represented by Formula I: which are useful as are alpha-1A/B adrenoceptor antagonists, to methods of treating conditions associated with the activity of alpha-1A/B adrenoceptors, and to methods of making said compounds, wherein Ar, Z, R, R?, R5 and R10 are as defined herein.

Abstract: Novel compounds, compositions, and kits are provided. Methods of modulating A? levels, and methods of treating a disease associated with aberrant A? levels are also provided.

Abstract: The present invention provides compounds of formula (I): wherein all variables are as defined herein, pharmaceutical compositions containing the same, processes for preparing the same and their use as pharmaceutical agents.

Abstract: The invention relates to novel fredericamycin derivatives of general formula (Ia) or (Ib), to medicaments containing the fredericamycin derivatives or salts thereof, and to the use of the fredericamycin derivatives for treating diseases, especially tumor diseases.

Abstract: A pharmaceutical composition comprising: (a) an anticholinergic of formula 1 wherein X? is an anion with a single negative charge; (b) a corticosteroid; and (c) a betamimetic, wherein each component (a), (b), and (c) are optionally in the form of the solvates or hydrates thereof, processes for preparing them, and their use in the treatment of respiratory diseases.

Abstract: Selectively BRS-3-agonistic compounds of formula I wherein A1, A2, A3, R1, R2, R3, Ar1, Ar2, Ar3, m and n have the meanings given in the description, and also pharmaceutical compositions containing these compounds and a process for the preparation of compounds of Formula I are described.

Abstract: Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-dependent sodium channels. More particularly, the invention provides substituted piperidines, and compositions containing these compounds. Also provided are methods using the compounds of the invention for the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrance of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a channel that includes a PN3 subunit.

Abstract: The compounds of the present invention are of formula I: wherein A, R3, R4 is as defined herein, are useful as ligands for nicotinic receptors.

Abstract: The present invention relates to novel heterocyclic antagonists of Formula (I) and pharmaceutical compositions comprising said antagonists of the corticotropin releasing factor receptor (“CRF receptor”) useful for the treatment of depression, anxiety, affective disorders, feeding disorders, post-traumatic stress disorder, headache, drug addiction, inflammatory disorders, drug or alcohol withdrawal symptoms and other conditions the treatment of which can be effected by the antagonism of the CRF-1 receptor.

Abstract: The present invention relates to imidazole derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals.

Abstract: The invention provides novel pyridines, pharmaceutical compositions comprising such pyridines, and the use of such compositions in treating injured mammalian nerve tissue, including but not limited to an injured spinal cord. In one embodiment, the compounds, compositions, and methods of the instant invention treat a mammalian nerve tissue injury by restoring action potential or nerve impulse conduction through a nerve tissue lesion. Significantly, in vivo application of compounds of the instant invention established, on the basis of SSEP testing, that the compounds provide longer lasting effects at lower concentrations than comparable treatment with the known agent 4-aminopyridine (4 AP).

Abstract: The present invention provides compositions and methods for lowering plasma Lp(a) levels in humans. The present invention provides compositions and methods for lowering the risk factors for cardiovascular diseases. Moreover, this invention provides therapeutic alternatives to current pharmaceutical interventions for the lowering of cholesterol, LDL-cholesterol, triglycerides and other metabolic risk factors.

Abstract: The invention relates to novel active compound combinations of certain cyclic ketoenols and certain active compounds that together have unexpectedly good insecticidal and acaricidal properties.

Abstract: The present invention is related to the preparation and pharmaceutical use of novel benzamide derivatives as defined in the specification of formula (I) as histone deacetylase inhibitors (HDACI), their preparations and the methods of using these compounds or their pharmaceutically acceptable salt in the treatment of cell proliferative diseases, e.g.

Abstract: The present invention concerns the compounds having the formula N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het1, Het2; R1 may also be a radical of formula (R11aR11b)NC(R10aR10b)CR9—; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is —C(?O)—, —O—C(?O)—, —NR8—C(?O)—, —O—C1-6alkanediyl-C(?O)—, —NR8—C1-6alkanediyl-C(?O)—, —S(?O)2—, —O—S(?O)2—, —NR8—S(?O)2; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(?O), carboxyl, aminoC(?O), mono- or di(C1-4alkyl)aminoC(?O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; A is C1-6alkanediyl, —C(?O)—, —C(?S)—, —S(?O)2—, C1-6alkanediyl-C(?O)—, C1-6alkanediyl-C(?S)— or C1-6alkanediyl-S(?O)2—; R5 is H, OH, C1-6alkyl, Het1C1-6alkyl, Het2C1-6alkyl, optionally substituted aminoC1-6alkyl; R6 is C1-6alkylO, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6

Abstract: The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated.

Abstract: The invention relates to the compounds (2R,4R), (2S,4R)-2-methylthiazolidine-2,4-dicarboxylic acid and (2RS,4R)-2-methylthiazolidine-2,4-dicarboxylic acid and salts of said compounds, the use thereof for the prophylaxis and/or treatment of neurodegenerative diseases, methods for the prophylaxis and/or treatment of neurodegenerative diseases, and pharmaceutical compositions containing said compounds together with physiologically compatible carriers, auxiliary agents, and/or solvents.

Abstract: Disclosed are compounds of formula I: and the pharmaceutically acceptable salts thereof wherein the variables RN, R1, R2, R3, RP and RC are defined herein. These compounds are useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Abstract: Certain 1,5-disubstituted benzimidazol-2-one compounds useful as therapeutic agents. The compounds may be of the Formula I wherein: R? represents hydrogen or alkyl; R? represents halogen or trihalogenmethyl; and Hlg represents halogen; provided, however, that if Hlg is F, then R? is not Cl. Also, use of the 1,5-disubstituted benzimidazol-2-one compounds, or pharmaceutically-acceptable addition salts thereof, in applications that benefit from increasing the blood-brain barrier permeability.