Abstract: The invention provides compounds represented by the general formula I wherein the substituents are defined in the application. The compounds are useful in the treatment of an affective disorder, including depression, anxiety disorders including general anxiety disorder and panic disorder and obsessive compulsive disorder.

Abstract: The invention provides methods of treating cancer with a combination of compounds which inhibit kinases, more specifically MEK and PI3K.

Abstract: The present invention relates to novel aryl indolyl sulfonamide compounds of the formula (I), their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates described herein and pharmaceutically acceptable compositions containing them.

Abstract: The present invention provides for a method for treating a disease condition associated with PI3-kinase ? and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase ? and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth.

Abstract: The present invention is concerned with novel substituted triazole derivatives of Formula (I) wherein Het1, R1, R2, A1, A2, A3, A4, L1, and L2 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Abstract: A hydrazone derivative of formula [I]: wherein Ring A is aryl or heteroaryl, Ring T is heteroaryl or heterocycle, R1 and R2 are independently hydrogen atom, halogen atom, cycloalkylsulfonyl, etc., R3 and R4 combine each other together with the adjacent nitrogen atom to form substituted or unsubstituted heterocycle, R5 is hydrogen atom, halogen atom, cyano, nitro, tetrazolyl, etc., and R6 is hydrogen atom, etc.; or a pharmaceutically acceptable salt thereof is useful as a glucokinase activation agent.

Abstract: The present invention relates to N-benzyl,N?-arylcarbonylpiperazine derivatives having the general formula I to pharmaceutical compositions comprising the same, and to the use of a these N-benzyl,N?-arylcarbonylpiperazine derivatives for the manufacture of a medicament for treating or preventing atherosclerosis and related disorders associated with cholesterol and bile acids transport and metabolism.

Abstract: Disclosed are compounds having the formula: wherein X1, X2, X3, R1, R2, Y, Q, X, B and L are as defined herein, and methods of making and using the same.

Abstract: Fused pyridine derivatives shown as the general formula (I), and their pharmaceutically acceptable salts, stereoisomers or solvates thereof are disclosed, which belong to the technical field of medicines. The R1, R2, R3, Q, X and Y substituents in formula (I) are defined as in the description. Also disclosed are the preparation methods, pharmaceutical compositions comprising the compounds and uses of the compounds in the manufacture of the medicine for the treatment and/or prevention of noninsulin-dependent diabetes, hyperglycemia, hyperlipidemia and insulin resistance.

Abstract: The present invention provides a novel compound having an excellent antitumor effect. The compound of the present invention is represented by the following general formula (1) wherein R1 and R2 are aryl or the like; A is lower alkylene; Ring X is optionally substituted arylene; E is bond or lower alkenylene; Ring Y is optionally substituted heterocycloalkylene containing one or more nitrogen atoms, one of which is attached to the adjacent carbonyl group; G is —NH-G2-, —N(lower alkyl)-G2-, —NH—CH2-G2-, —N(lower alkyl)-CH2-G2- or —CH2-G2-, [wherein G2 binds to R2, G2-R2 is bond-R2, phenylene-G3-R2, phenylene-G4-O—R2, phenylene-G5-NH—R2, phenylene-G6-N(lower alkyl)-R2 or quinolinediyl-O—R2, the phenylene of said phenylene-containing groups being optionally substituted with one or more substituents; G3-R2 is —O-lower alkylene-R2 or the like; G4-O— is lower alkylene-O— or the like; G5 is lower alkylene; G6 is lower alkylene].

Abstract: The present invention relates to diazepane-acetamide derivatives of formula I as selective inhibitors of the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11?-HSD-1) and the use of such compounds for the treatment and prevention of metabolic syndrome, diabetes, insulin resistance, obesity, lipid disorders, glaucoma, osteoporosis, cognitive disorders, anxiety, depression, immune disorders, hypertension and other diseases and conditions.

Abstract: Compounds useful as antibacterial agents are provided. The compounds are analogs of indole-3-carbinol and have a backbone selected from dihydroindolo[2,3-b]carbazole, 2,2?-diindolylmethane, 2?,3-diindolylmethane, and 3,3?-diindolylmethane. The compounds are useful therapeutic and prophylactic treatment of bacterial infections in mammals. Methods of synthesis of the compounds are provided, as are pharmaceutical compositions containing the compounds.

Abstract: The invention relates to 1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile derived Cathepsin S inhibitors of Formula (I), wherein R1 is H or (C1-3)alkyl; R2 is halogen or (C1-4)alkyl, optionally substituted with one or more halogens; n is 1-3; X is O or CH2; U, V and W are CH; or one of U, V and W is N; Y is a group capable of interacting with the Sn . . . S2 substites of the active site of Cathepsin S; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same as well as to the use of these derivatives for the preparation of a medicament for the treatment of cathepsin S related diseases such as atherosclerosis, obesity, inflammation and immune disorders, such as rheumatoid arthritis, psoriasis, cancer, and chronic pain, such as neuropathic pain.

Abstract: The compounds and pharmaceutical compositions of the present invention are believed to significantly inhibit Dyrk 1a activity which suggests that the agents could provide therapeutic benefit for Down syndrome, since Dyrk 1a overproduction in Down syndrome appears to account for the developmental cognitive impairment and reduction in neurogenesis. The compounds and pharmaceutical compositions, administered during early post-natal development, may increase neurogenesis and thereby reduce cognitive impairment which may ultimately allow individuals with Down syndrome to live a more independent life.

Abstract: The present invention relates to compounds corresponding to formula (I): in which: A represents a divalent aromatic radical; X represents a —CH— group or a nitrogen atom; R1 represents a (C1-C4)alkyl or a (C1-C4)alkoxy; R2 represents a group Alk; R3 represents a hydroxyl or a group —NR7R8; R4 represents a hydrogen atom, a halogen atom, a cyano, a phenyl, a group Alk, a group OAlk or a group —NR9R10; R5 represents a hydrogen atom, a halogen atom or a group Alk; R6 represents a hydrogen atom, a halogen atom, a cyano, a group —COOAlk or a —CONH2 group.

Abstract: The invention relates to pyrido[2,3-b]pyrazine compounds of general formulae (Ia) and (Ib), to their preparation and use, for example, for the treatment of malignant disorders and other disorders based on pathological cell proliferations.

Abstract: The present invention relates to 5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine derivatives, to their preparation and to their therapeutic use.

Abstract: The present invention provides novel pyrimidine amines of formula (I) which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD and rheumatoid arthritis.

Abstract: Compounds which are tricyclopyrazole derivatives or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed; these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, viral infection, prevention of AIDS development in HIV-infected individuals, cell proliferative disorders, autoimmune and neurodegenerative disorders; also disclosed is a process under Solid Phase Synthesis conditions for preparing the compounds of the invention and chemical libraries comprising a plurality of them.

Abstract: The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. This invention further provides new oxime derivatives of the general formula (I) consisting of modulators of nervous system receptors sensitive to glutamate, which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. In particular embodiments, the new oxime derivatives of the invention are modulators of metabotropic glutamate receptors (mGluRs). The invention further provides positive allosteric modulators of mGluRs and more specifically positive alSosteric modulators of mGluR4.

Abstract: Substituted indazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a deregulated protein kinase activity, like cancer.

Abstract: The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain amido-thiophene compounds that, inter alia, inhibit 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11?-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11?-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.

Abstract: Thieno- and furo-pyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the modulation of histamine H4 receptor activity and for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as inflammation.

Abstract: The present invention encompasses compounds of general formula (1) wherein R1 to R4 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a pharmaceutical composition having the above-mentioned properties.

Abstract: Methods and compositions that down regulate the activity of orexins to treat panic disorder and panic-like responses associated with hypercapnic conditions are disclosed.

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L1, M and R11 are as defined herein. The compounds of Formula (I) are selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: Compounds and methods for preventing and treating viral infections are provided. In some embodiments, novel compounds broad-spectrum antiviral activity are provided. In more specific embodiments, the compounds and methods are effective against viruses such as Venezuelan Equine Encephalitis, West Nile Virus, and Hepatitis C.

Abstract: New compounds are disclosed which have utility in the treatment of a variety of metabolic related conditions in a patient. The compounds of this invention have the structure (I): wherein R1, R2, R3, n, p, q, and Ar are as defined herein, including stereoisomers, and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions comprising a compound of this invention, as well as methods relating to the use thereof in a patient in need thereof.

Abstract: The present invention relates to aryl- or heteroaryl-substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

Abstract: Polycyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl activity are also disclosed.

Abstract: The present invention relates to substituted aminoquinoxaline compounds of general formula (I) in which (II), R2, R3, R4, R6, R7, n and m are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

Abstract: Compounds having formula I, or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.

Abstract: The invention relates to compounds of the general formula (1) or the acid addition salts thereof with organic and/or inorganic acids; as well as to the use of the compounds of the general formula (1) in medicine.

Abstract: The present invention relates to inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

Abstract: Compounds of Formula (I): and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4 and R5 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases and pain.

Abstract: This invention provides a therapeutic target for pancreatic cancer. The invention further provides methods of screening of new therapeutic agents using the target. The invention also provides a pharmaceutical composition comprising fasudil or derivatives thereof for pancreatic cancer treatment, and a kit comprising such a pharmaceutical composition.

Abstract: The invention relates to substituted (heteroarylmethyl) thiohydantoin compounds of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, and their use for the preparation of medicaments for the treatment and/or prophylaxis of disorders, in particular of prostate cancer.

Abstract: The present invention relates to the use of novel pyrrolopyrazine derivatives of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.

Abstract: The invention provides methods, compositions, and kits for the inhibition of members of the Rho GTPase family. Specifically, the invention provides methods, compositions and kits for the inhibition of RhoA and/or RhoC transcriptional signalling. The invention finds use in treatment of Rho-mediated disease states (e.g., tumor metastasis, inflammation, inflammatory disease), Rho-mediated biological conditions, and in cell signaling research.

Abstract: The present invention relates to compounds of the formula (I), in which R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, M1, M2, M3, M4, Y1, Y2, V, W, n, m and o have the meanings given in Claim 1, and physiologically acceptable salts, derivatives, prodrugs, solvates, tautomers and stereoisomers thereof, including mixtures thereof in all ratios, for use in the treatment of diseases which are influenced by inhibition of Sph kinase 1.

Abstract: The present invention relates to tetrahydroquinoxaline urea derivatives, to their preparation and to their therapeutic application.

Abstract: Disclosed are pyruvate kinase M2 activators, which are, bis sulfonamide piperazinyl compounds of Formula (I) and 2,4-disubstituted 4H-thieno[3,2-b]pyrrole-2-(substituted benzyl)pyridazin-3(2H)ones of Formula (II), wherein L and R1 to R16 are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer and anemia,

Abstract: The present invention includes therapeutic methods that include the administration of a compound of Formula I or II: or a pharmaceutically acceptable salt, solvate, and/or ester thereof, to a subject in need of such, and therapeutic methods that include the administration of such compounds with at least one additional active agent.

Abstract: The disclosure relates to (heterocycle-tetrahydropyridine)(piperazinyl)-1-alkanone and (heterocycle-dihydropyrrolidine)(piperazinyl)-1-alkanone derivatives of formula (I): wherein A, B, m, n, W, and R2 are as defined in the disclosure; to the methods of preparing said derivatives, and to the therapeutic uses thereof.

Abstract: The disclosure relates to (heterocycle-fused piperidine)-(piperazinyl)-1-alkanone derivatives and (heterocycle-fused pyrrolidine)-(piperazinyI)-1-alkanone derivatives of formula (I): wherein A, W, R2 and n are as defined in the disclosure, to the method of preparation thereof and the therapeutic use thereof.

Abstract: Compounds having the formula are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

Abstract: The present invention is directed to compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

Abstract: Disclosed is a method of treating cancer in a patient comprising administering to the patient an effective amount of a diazeniumdiolated (N2O2-containing) compound or a pharmaceutically acceptable salt thereof, wherein the cancer cell has an elevated level of reactive oxygen species (ROS) and/or a decreased level of one or more of PRX1, PRX6, and OGG1, compared to a normal cell of the same tissue or tissue type. An example of a diazeniumdiolated compound is Formula (I), wherein X and Q are defined herein. Also disclosed are diazeniumdiolated compounds, pharmaceutical compositions, and methods of use including enhancing the chemotherapeutic treatment of chemotherapeutic agents and high energy radiation.

Abstract: The invention relates to certain amino-pyrimidine compounds that inhibit IKK epsilon and/or TBK1, methods of making such compounds, pharmaceutical compositions comprising such compounds, and the use of these compounds in treating a variety of diseases and disorders.

Abstract: Thieno- and furo-pyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the modulation of histamine H4 receptor activity and for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as inflammation.