Abstract: A composition for delivery of superoxide dismutase to neuronal cells comprise a superoxide dismutase linked by a linker to a neuronal cell targeting component, which component comprises a first domain that binds to a neuronal cell and a second domain that translocates the superoxide dimutase into the neuronal cell. After translocation, the linker is cleaved to release superoxide dimutase from the neuronal cell targeting domain. Also described is use of the composition for treatment of oxidative damage to neuronal cells and further targeting of the composition using human mitochondrial leader sequences. A hybrid polypeptide is described that contains a bacterial superoxide dismutase plus a sequence that targets a human mitochondira.

Abstract: Compositions, kits and methods for the prevention of, for example, spontaneous abortion, preeclampsia, preterm labor or implantation failure during assisted reproduction are provided. The compositions, kits and methods provide an effective amount of granulocyte colony stimulating factor to prevent, for example, spontaneous abortion, preeclampsia, preterm labor or implantation failure of an embryo.

Abstract: A mixture of conjugates in which each conjugate in the mixture comprises an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may also be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may also result in less inter-subject variability than polydispersed mixtures of similar conjugates.

Abstract: The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

Abstract: Fibroblast growth factor-18 (FGF-18) binds with FGF receptors-2 and -3. Compositions comprising an FGF-18 component can be used to target cells that express these receptors. Suitable targets include tumor cells that express constitutively activated forms of FGF receptors-2 and -3. For example, conjugates of FGF-18 and saporin can be used to target tumor cells that express FGF receptors-2 or -3, and to inhibit the proliferation of these cells.

Abstract: The present invention relates to use of Ulinastatin and its pharmaceutical composition for treating and/or preventing Severe Acute Respiratory Syndrome (SARS). Ulinastatin is effective for treating and/or preventing SARS, particularly Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS). Ulinastatin is generally used as the pharmaceutical composition, preferably in the form of freeze-dried powder or aqueous solution for injection.

Abstract: The present invention provides methods of treating an angiogenesis-related disease of a subject using a therapeutically effective amount of a modified endostatin protein. In particular, the methods encompass treating an angiogenesis-related disease of a subject using a combination of the modified endostatin, and a known cancer therapy agent such as a chemotherapy agent, or a radiotherapy agent.

Abstract: A method of using an osteocrin (Ostn) or a NPR-C specific Ostn peptide derivative for increasing osteogenesis in a mammal comprising administering a therapeutically effective amount of said Ostn or NPR-C specific Ostn peptide derivative to the mammal.

Abstract: The present invention is drawn to methods of screening for new compounds for the treatment of obesity and obesity-related diseases and disorders, as well as methods of treating obesity-related diseases and disorders, based on the discovery of the role of the leptin-LSR interaction in obesity.

Abstract: Novel polypeptides or derivatives comprising cdk2 binding site are disclosed. The novel polypeptides or derivatives have growth suppressive activity. Nucleic acids encoding those polypeptides are also disclosed. The polypeptides identified herein are also useful in methods for treating or preventing cancer. The treatment methods comprise administration of the polypeptide to the patient. The methods also comprise contacting the sample with the above-described polypeptide or derivative, wherein the polypeptide or derivative also comprises a covalently attached detectable moiety, then determining whether the polypeptide or derivative is binding cdk2 from the sample.

Abstract: The invention relates to novel 5-thioxylose compounds, preferably derivatives of the 5-thioxylopyranose type, to the method for their preparation and to their use as active principles of drugs intended especially for the treatment or prevention of thromboses or cardiac insufficiency.

Abstract: This invention is in the field of chemical restructuring of pharmaceutical agents known to cause tissue toxicity as a side effect, by producing their orotate derivatives. More particularly, it concerns orotate derivatives of the anthracyclines, doxorubicin and daunorubicin, that are found to reduce levels of the pharmaceutical agent in noncancerous tissues. There orotate derivatives are equally efficacious in inhibiting the SCCAKI-1 kidney tumor in animals and the reduction in the heart tissue of doxorubicin compared with doxorubicin HCl suggests a reduction in toxicity induced by free radical generation by the anthrracyclines.

Abstract: Compositions and methods are disclosed for the therapeutic use of an atonal-associated nucleic acid or amino acid sequence. Also, an animal heterozygous for an atonal-associated gene inactivation is also disclosed having at least one atonal-associated nucleic acid sequence replaced by insertion of a heterologous nucleic acid sequence used to detect expression driven by an atonal-associated promoter sequence, wherein the inactivation of the atonal-associated nucleic acid sequence prevents expression of the atonal-associated gene.

Abstract: The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides an immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunostimulatory oligonucleotides of the invention preferably comprise novel purines. The immunostimulatory oligonucleotides according to the invention further comprise at least two oligonucleotides linked at their 3? ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunostimulatory oligonucleotide and having an accessible 5? end.

Abstract: The present invention provides a pharmaceutical composition, comprising a non-infectious, non-integrating polynucleotide construct comprising a polynucleotide encoding an interferon ? and one or more cationic compounds. The present invention also provides methods of treating cancer in a mammal, comprising administering into a tissue of the mammal a non-infectious, non-integrating polynucleotide construct comprising a polynucleotide encoding a cytokine. In addition, the present invention also relates to the methodology for selective transfection of malignant cells with polynucleotides expressing therapeutic or prophylactic molecules in intra-cavity tumor bearing mammals. More specifically, the present invention provides a methodology for the suppression of an intra-cavity dissemination of malignant cells, such as intraperitoneal dissemination.

Abstract: The present invention relates, in general, to a method of modulating physiological and pathological processes and, in particular, to a method of modulating intra- and extracellular levels of oxidants and thereby processes in which such oxidants are a participant. The invention also relates to compounds and compositions suitable for use in such methods.

Abstract: Compounds of formula (I): (wherein variable groups are as defined within) pharmaceutically acceptable salts, solvates, solvates of such salts and prodrugs thereof and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia are described.

Abstract: The invention encompasses constrained bicyclic and tricyclic CGRP-receptor antagonists, methods for identifying them, pharmaceutical compositions comprising them, and methods for their use in therapy for treatment of migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.

Abstract: The invention encompasses constrained bicyclic and tricyclic CGRP-receptor antagonists, methods for identifying them, pharmaceutical compositions comprising them, and methods for their use in therapy for treatment of migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.

Abstract: This invention features pyrimidine compounds of formula (I): R1 is each of R2 and R4 is H; R3 is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl; R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is NRc; Y is covalent bond, CH2, C(O), C?N—Rc, C?N—ORc, C?N—SRc, O, S, S(O), S(O2), or NRc; Z is N or CH; one of U and V is N, and the other is CRc; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and Rc is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl.

Abstract: Compounds of the following structure, wherein R1, R2, R4, R4?, R6, R7, and R15 are defined above, are provided: These compounds are useful in treating neurological disorders or complications due to stroke or head injury. The compounds are therefore useful as neuroprotective and neuroregenerative agents.

Abstract: Compounds of formula I, of trans relative configuration: wherein: X represents an oxygen atom or an NR2 group, Y represents a group selected from —CH2—, —(CH2)2— and —CH?CH—, R1 and R2, which may be the same or different, each represents a hydrogen atom or a group selected from alkyl, cycloalkyl and cycloalkylalkyl, in racemic form or in the form of optical isomers, and also addition salts thereof with a pharmaceutically acceptable acid, and hydrates thereof. Medicinal products containing the same which are useful in the treatment of disorders of the central nervous system that involve the dopaminergic system.

Abstract: The present invention relates to a compound of formula I wherein R1, R2, R3, R4, R7, m and n are as defined herein. These compounds are high potential NK-3 receptor antagonists useful for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

Abstract: This invention features pyrimidine compounds of formula (I): R1 is in which one of Ra and Rb is H or alkyl, and the other is aryl or heteroaryl optionally substituted with Rd and Rem; each of R2 and R4 is H; R3 is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl; R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is NRc; Y is covalent bond, CH2, C(O), C?N—Rc, C?N—ORc, C?N—SRc, O, S, S(O), S(O2), or NRc; Z is N or CH; one of U and V is N, and the other is CRc; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which Rc is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl; Rd is halogen, CN, alkyl, alkyloxy, alkylcarbonyl, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, hydroxyalkyl, alkylamino, or alkylaminocarbonyl; Re is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl; and m is 0, 1, 2, 3, or 4. The pyrimidine compounds can be used to treat an IL-12 overproduction-related disorder (e.g.

Abstract: The present invention is related to benzazole derivatives notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such benzazole derivatives. Said benzazole derivatives are efficient modulators of the JNK pathway, they are in particular efficient and selective inhibitors of JNK2 and/or 3. The present invention is furthermore related to novel benzazole derivatives as well as to methods of their preparation. X is O, S or NR0, with R0 being H or an unsubstantiated or substituted C1-C6 alkyl; G is an unsubstantiated or substituted pyrimidinyl group.

Abstract: Aryl oxime derivatives of the formula (I), in which R1, R2, R3, X and B are as defined in Claim 1, act as phosphodiesterase IV inhibitors and can be employed for the treatment of osteoporosis, tumours, cachexia, atherosclerosis, rheumatoid arthritis, multiple sclerosis, diabetes mellitus, inflammatory processes, allergies, asthma, autoimmune diseases, myocardial diseases and AIDS.

Abstract: A compound of the formula (I): wherein: A and B together represent an optionally substituted, fused aromatic ring; D is selected from: (i) where Y1 is selected from CH and N, Y2 is selected from CH and N, Y3 is selected from CH, CF and N; and (ii) where Q is O or S; RD is: wherein RN1 is selected from H and optionally substituted C1-10 alkyl; X is selected from a single bond, NRN2, CRC3RC4 and C?O; RN2 is selected from H and optionally substituted C1-10 alkyl; RC3 and RC4 are independently selected from H, R, C(?O)OR, where R is optionally substituted C1-10 alkyl, optionally substituted C5-20 aryl or optionally substituted C3-20 heterocyclyl; Y is selected from NRN3 and CRC1RC2; RC1 and RC2 are independently selected from H, R, C(?O)OR, where R is optionally substituted C1-10 alkyl, optionally substituted C5-20 aryl or optionally substituted C3-20 heterocyclyl; RC1 and RC2 together with the carbon atom to which they are attached may form an optionally substituted spiro-

Abstract: Disclosed are compounds of the general formula (I), where the definition of the substituents A, B, D, E, R1 and R2 are detailed in the description, and the physiologically tolerated salts thereof, a process for the preparation of these compounds and their use as pharmaceuticals. These compounds are kinase inhibitors, in particular inhibitors of the kinase CDK2 (cyclin-dependent kinase 2).

Abstract: Use of 4-(2-Fluorophenyl)-6-Methyl-2-(1-Piperazinyl)Thieno[2,3-D]Pyrimidine or a salt thereof for the manufacture of a medicament for the treatment of functional bowel disorder.

Abstract: The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction, wherein A, L, D and B1 are as described in the specification.

Abstract: Disclosed are compounds of formula (I) which inhibit production of cytokines involved in inflammatory processes and are thus useful for treating diseases and pathological conditions involving inflammation such as chronic inflammatory disease. Also disclosed are processes for preparing these compounds and pharmaceutical compositions comprising these compounds.

Abstract: The invention is directed to compounds having the following Formula I: and methods of using them for the treatment of proliferative diseases.

Abstract: Pyrimidone compounds of formula (I): are inhibitors of the enzyme Lp-PLA2 and are of use in treating atheroscelerosis.

Abstract: In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

Abstract: The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase enzymes thereby making them useful as anti-cancer agents.

Abstract: The present invention provides compounds of the following formula and pharmaceutical compositions that are selective antagonists of A2B adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.

Abstract: The compounds of the following formula: wherein R, R2, R3 and A have the meanings given in the specification, are endowed with selective A3 adenosine receptor antagonist activity. These compounds can be used in a pharmaceutical composition to treat disorders caused by excessive activation of the A3 receptor, or can be used in a diagnostic application to determine the relative binding of other compounds to the A3 receptor. The compounds can be labeled, for example with fluorescent or radiolabels, and the labels used in vivo or in vitro to determine the presence of tumor cells which possess a high concentration of adenosine A3 receptors.

Abstract: The present invention relates to certain trisubstituted aryl and heteroaryl derivatives of Formula (I) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

Abstract: Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV inhibitors comprising Formula I: wherein the substituents are as described herein.

Abstract: The present invention relates to new substituted five-membered compounds and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds.

Abstract: Novel compounds of the formula I in which R1, R1?, L, E, G, M, Q, U, R2, m, p and q have the meanings indicated. Further, the compounds of formula I can be used as, for example, inhibitors of tyrosine kinases, for example TIE-2 , and can be employed, for example, for the treatment of tumours or other diseases.

Abstract: Yohimbine derivatives are disclosed having modification of the C-16 carboxyl group to include a sidechain and where the resulting derivative does not possess a second yohimbine pharmacophore (i.e., the compound is not a yohimbine dimer). The yohimbine derivatives of the present invention are preferably characterized by selective activity as ?2c-AR antagonists. Use of the compounds, or pharmaceutical composition containing them, for treating or preventing an ?2c adrenergic receptor mediated condition or disorder, and for antagonizing activity of an ?2c adrenergic receptor are also disclosed.

Abstract: The compounds of formula I in which R1, R2, R3, R4, R5, R6 and n have the meanings as indicated in the description, are novel effective PDE3/4 inhibitors.

Abstract: The present invention discloses compounds of formula (I) wherein A, n, q, K, W, X, Y; Z, R1, R2, R3, R4, R5, and R6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and its sequelae.

Abstract: The invention relates to cycloalkyl-substituted 7-amino-4-quinolone-3-carboxylic acid derivatives and to the physiologically tolerated salts and physiologically functional derivatives thereof. The invention relates to compounds of the formula I in which the radicals have the stated meanings, and to the physiologically tolerated salts thereof. The compounds are suitable for example as medicaments for the prevention and treatment of type 2 diabetes.

Abstract: A crystalline clopidogrel naphthalenesulfonate or a hydrate thereof, a method for preparing same, and a pharmaceutical composition containing same are provided.

Abstract: The invention relates to compounds of the general formula (I): in which R1, R2, X, and A are as defined in claim 1. These compounds can be used in the treatment of hyperglycaemia-related pathologies.

Abstract: Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.

Abstract: This invention relates to N-aroyl cyclic amine derivatives of formula (I), wherein X represents a bond, oxygen, NR3 or a group (CH2), wherein n represents 1, 2 or 3; Y represents CH2, CO, CH(OH), or CH2CH(OH); Het is an optionally substituted bicyclic heteroaryl group containing up to 4 heteroatoms selected from N, O and S; Ar2 represents an optionally substituted phenyl or a 5- or 6-membered heterocyclyl group containing up to 3 heteroatoms selected from N, O and S and their use as pharmaceuticals, specifically as orexin receptor antagonists.

Abstract: The present invention relates to piperidine substituted cyclohexane-1,4-diamine compounds of Formula (I) and pharmaceutically acceptable forms thereof, as ?1a/?1d adrenoreceptor modulators for the treatment of benign prostatic hypertrophy and lower urinary tract symptoms. The present invention also relates to pharmaceutical compositions comprising said new compounds, new processes to prepare these new compounds and new uses as a medicine as well as method of treatments.