Abstract: Aryl- and heteroaryl-substituted urea compounds useful in the treatment of diseases and conditions related to DNA damage or lesions in DNA replication are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division also are disclosed.

Abstract: This invention relates to compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion, and to pharmaceutical compositions containing such compounds. Even more specifically, the invention relates to compounds that inhibit, regulate and/or modulate kinases, particularly Checkpoint Kinases, even more particularly Checkpoint Kinase 1, or Chk1. Methods of therapeutically or prophylactically using the compounds and compositions to treat kinase-dependent diseases and conditions are also an aspect of the invention, and include methods of treating cancer, as well as other disease states associated with unwanted angiogenesis and/or cellular proliferation, by administering effective amounts of such compounds.

Abstract: A compound, or a pharmaceutically acceptable salt thereof, represented by the formula (1), (wherein, the carbon atom marked with an * is in the R-configuration, R1 represents a hydrogen atom, a halogen atom, an amino group, a hydroxyl group, a hydroxyamino group, a nitro group, a cyano group, a sulfamoyl group, a C1-C6 alkyl group, or a C1-C6 alkoxy group, R2 represents a C3-C6 cycloalkylsulfanyl group, a C3-C6 cycloalkylsulfinyl group, or a C3-C6 cycloalkylsulfonyl group, and A represents a substituted or unsubstituted heteroaryl group).

Abstract: The present invention provides a pharmaceutical composition comprising a combination of an Hsp 90 family protein inhibitor and at least one compound, the said pharmaceutical composition wherein the Hsp 90 family protein inhibitor is a benozoyl compound represented by formula (I): [wherein n represents an integer of 1 to 5; R1 represents substituted or unsubstituted lower alkyl, CONR7R8 (wherein R7 and R8, which may be the same or different, each represent a hydrogen atom, substituted or unsubstituted lower alkyl, or the like), or the like; R2 represents substituted or unsubstituted aryl, or the like; R3 and R5, which may be the same or different, each represent a hydrogen atom, substituted or unsubstituted lower alkyl, or the like; R4 represents a hydrogen atom, hydroxy or halogen; and R6 represents a hydrogen atom, halogen, substituted or unsubstituted lower alkyl, or the like], or a prodrug thereof; or a pharmaceutically acceptable salt thereof, and the like.

Abstract: Disclosed is a pharmaceutical composition comprising a pyrazine derivative represented by the general formula: [wherein R1 and R2 independently represent a hydrogen atom or a halogen atom; and R3 represents a hydrogen atom or an amino-protecting group] or a salt thereof and at least one neuraminidase inhibitor. The pharmaceutical composition is useful for a treatment including the treatment or prevention of influenza. Also disclosed is a method of using these components in combination. The method is useful for a treatment including the treatment or prevention of influenza.

Abstract: The present invention relates to compositions and methods for treating neoplasms, including refractory or relapsed neoplasms, using VEGF antagonists. Furthermore, the present invention provides therapy regimens for treating those diseases.

Abstract: The invention provides N-pyrazinyl-phenyl-sulphonamides of formula (I) for use in the treatment of chemokine mediated diseases. Particularly inflammatory diseases, such as asthma.

Abstract: A device for administering two or more therapeutic agents simultaneously, comprising two or more nebulizers and a single connector linking the nebulizers to a nebulizer mouthpiece. Also provided is a method of administering two or more therapeutic agents simultaneously, comprising administering the therapeutic agents simultaneously with the device of the present invention to a subject in need thereof.

Abstract: A compound having the following formula (I): wherein —R1 is hydrogen, optionally substituted lower alkyl, cyclo(lower)alkyl, cyclo(higher)alkyl, optionally substituted aryl, optionally substituted heterocyclyl, or aryl-fused cyclo(lower)alkyl, R2 is hydrogen or halogen, Z is CH or N, X is formula (II) R3 is lower alkyl which may be substituted with —OH or optionally substituted aryl, or lower alkanoyl, R4 is hydrogen or lower alkyl, Y is optionally substituted lower alkylene, or a salt thereof. The compound is useful as a histone deacetylase inhibitor.

Abstract: This invention provides a compound of the formula (I): a pharmaceutically acceptable salt or solvate thereof, wherein R1 is optionally substituted lower alkyl, Y is —S(O)n— wherein n is 1 or 2, or —CO—, R2 is hydrogen or lower alkyl, R7 is hydrogen or lower alkyl, X is lower alkylene, lower alkenylene, arylene, cycloalkylene or the like, and Z is lower alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl or the like.

Abstract: The present invention relates to new sulfonylurea inhibitors of ATP-sensitive potassium channels, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention relates to a method of treating and/or preventing myocardial infarction comprising administering an iron chelator to a warm-blooded animal. The iron chelator is preferably 4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic.

Abstract: The present disclosure provides compounds having the general structure A or pharmaceutically acceptable salts thereof: R—X??(A) wherein R is an alkyl or aryl moiety comprising heterocyclic structures; and X is a metal-chelatin group selected from: This disclosure further provides a focused library of compounds for use in the discovery and design of metallo-enzyme inhibitors. This fragment-based approach provides an assembly of a library of low molecular weight compounds (MW<300 Da) containing a variety of potential metal-chelating groups. The identification of the inhibitory scaffolds among these compounds provides the initial hit fragments that may be optimized for affinity against a particular target using common medicinal chemistry, structure-based or NMR-based approaches.

Abstract: The invention provides N-pyrazinyl-phenyl-sulphonamides of formula (I) for use in the treatment of chemokine mediated diseases. Particularly inflammatory diseases, such as asthma.

Abstract: A dry powder suitable for inhalation in a dry powder inhaler, the powder comprising a carrier, an active agent and at least 0.5% by weight of magnesium stearate, the powder being further characterized in that the less than 10% of the surface of the carrier material is covered with particles of magnesium stearate. The invention is also directed to a method of making dry powders by blending together the ingredients mentioned in a diffusion blender for a period time that is less than 60 minutes.

Abstract: This invention relates to: (a) compounds of formula I and salts thereof that, inter alia, are useful as hepatitis C virus (HCV) inhibitors; (b) intermediates useful for the preparation of such compounds and salts; (c) pharmaceutical compositions comprising such compounds and salts; and (d) methods of use of such compounds, salts, and compositions.

Abstract: The invention provides a method of treating hepatitis C, by providing compound of Formula I (shown below) in combination with a second active agent to a patient infected with the hepatitis C virus. Also provided herein are pharmaceutical combinations comprising a compound of Formula I and a second active agent. The pharmaceutical combination may be a unit dosage form or a packaged pharmaceutical composition. Packaged pharmaceutical combinations include a compound of Formula I and a second active agent in a package with instructions for using the formulation to treat a hepatitis C infection.

Abstract: The invention relates to a method of treatment or prophylaxis of demyelinating disease, in particular the neurodegenerative phase of demyelinating disease, which comprises administration of an acid sensing ion channel (ASIC) antagonist. The invention also relates to a pharmaceutical composition comprising an ASIC antagonist in combination with an additional therapeutic agent, in particular an anti-inflammatory or immunmodulatory agent.

Abstract: The present invention relates to modulators of metalloproteinase activity.

Abstract: The present invention relates to sodium channel blockers. The present invention also includes a variety of methods of treatment using these inventive sodium channel blockers.

Abstract: The present invention relates to derivatives of 5,6-bisaryl-2-pyridine-carboxamide, their preparation and their application in therapeutics as antagonists of urotensin II receptors.

Abstract: The present invention relates to a blocker of sodium channels in cell membranes, particularly in membranes of epithelial cells of organs belonging to the respiratory tract to be used as the pharmaceutically active ingredient in a medicament for treating an obstructive lung disease in a patient.

Abstract: The present invention relates to compounds of the formula I: wherein R1 to R8 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of CB1 receptors, such as obesity.

Abstract: DGAT-1 inhibitor compounds of formula (I), pharmaceutically-acceptable salts and pro-drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, Ring A is optionally substituted 2,6-pyrazindiyl; X is ?O; Ring B is optionally substituted 1,4-phenylene; Y1 is a direct bond or —O—; Y2 is —(CH2)r— wherein r is 2 or 3; n is 0 or n is 1 when Y1 is a direct bond between Ring B and Ring C and when Ring B is 1,4-phenylene and Ring C is (4-6C)cycloalkane; Ring C is optionally substituted (4-6C)cycloalkane, (7-10C)bicycloalkane, (8-12C)tricycloalkane, phenylene or pryidindiyl; L is a direct bond or —O—; p is 0, 1 or 2 and when p is 1 or 2 RA1 and RA2 are each independently hydrogen or (1-4C)alkyl; Z is carboxy or a mimic or bioisostere thereof.

Abstract: The present invention relates to preventives or remedies for Alzheimer's disease, or to amyloid protein fibril-formation inhibitors, which include as an active ingredient a compound of general formula (I) below or a pharmacologically permitted salt thereof; and also to nitrogen-containing heteroaryl derivatives having specific substituents, or pharmacologically permitted salts thereof, which are valuable as preventives or remedies for Alzheimer's disease, or as amyloid protein fibril-formation inhibitors: (where, R1 and R2 are H or alkyl; Z1 and Z2 are H, alkyl, alkoxy, haloalkyl or halogeno; Z3 is alkoxy, SH, alkylthio, NH2, mono- or di-alkylamino, OH or halogeno; Z4 and Z5 are H or halogeno; and A is 4,6-pyrimidine-1,3-diyl, 1,3,5-triazine-2,6-diyl, etc).

Abstract: The present invention relates to preventives or remedies for Alzheimer's disease, or to amyloid protein fibril-formation inhibitors, which include as an active ingredient a compound of general formula (I) below or a pharmacologically permitted salt thereof; and also to nitrogen-containing heteroaryl derivatives having specific substituents, or pharmacologically permitted salts thereof, which are valuable as preventives or remedies for Alzheimer's disease, or as amyloid protein fibril-formation inhibitors: (where, R1 and R2 are H or alkyl; Z1 and Z2 are H, alkyl, alkoxy, haloalkyl or halogeno; Z3 is alkoxy, SH, alkylthio, NH2, mono- or di-alkylamino, OH or halogeno; Z4 and Z5 are H or halogeno; and A is 4,6-pyrimidine-1,3-diyl, 1,3,5-triazine-2,6-diyl, etc).

Abstract: The present invention provides antituberculous therapeutic drugs with a higher potency. The present invention provides also antituberculous therapeutic drugs containing oxazole compounds represented by (I) general formula (1): [wherein R1 represents a hydrogen atom or C1-6 alkyl group, n represents an integer of 0-6, and R2 represents general formula (A) or the like, wherein R3 represents a phenoxy group (at least one group selected from the group consisting of a halogen atom, an optionally halogen-substituted C1-6 alkyl group and an optionally halogen-substituted C1-6 alkoxy group may be substituted on the phenyl ring) or the like], optically active forms thereof or salts thereof, and drugs (II) such as primary antituberculous drugs.

Abstract: The invention provides a Chk-1 kinase inhibiting compound of the formula (I) or a salt, solvate or tautomer thereof, wherein: G is CH2, O, NH, NHCO or CONH; A is a group (CH2)n where n is 1 to 4 provided that when G is O or NH, n is at least 2; X1 is nitrogen or CH; X2 is nitrogen or a group CR5; X3 is nitrogen or a group CR5; X4 is nitrogen or CH; provided that no more than two of X2, X3 and X4 are nitrogen; and R1; R2; R3; R4; R5 and R6 are as defined in the claims.

Abstract: A method of potentiating the efficacy of an antineoplastic agent such as temozolomide, comprises the administration of an antifolate agent as defined herein. Also disclosed are compositions, including pharmaceutical compositions, comprising the antineoplastic agent and an antifolate agent, and the use of such compounds and compositions thereof to treat a variety of cancers, such as melanoma. Unit dosage forms and kits are also contemplated and disclosed.

Abstract: The invention relates to methods of inhibiting cardiac PAI-1 by administering a PAI-1 antagonist.

Abstract: Potent inhibitors of fatty acid amide hydrolase (FAAH) are constructed having Ki's below 200 pM and activities 102-103 times more potent than the corresponding trifluoromethyl ketones. The potent inhibitors combine several features, viz.: 1.) an ?-keto heterocylic head group; 2.) a hydrocarbon linkage unit employing an optimal C12-C8 chain length; and 3.) a phenyl or other ?-unsaturation corresponding to the arachidonyl ?8,9/?11,12 and/or oleyl ?9,10 positions. A preferred ?-keto heterocylic head group is ?-keto N4 oxazolopyridine, with incorporation of a second weakly basic nitrogen. Fatty acid amide hydrolase is an enzyme responsible for the degradation of oleamide (an endogenous sleep-inducing lipid) and anandamide (an endogenous ligand for cannabinoid receptors).

Abstract: Compounds of the formula wherein: Y? is O or S, W? is optionally substituted, Z? is selected from the group consisting of wherein Q? is OR7 and R7 is C1-3alkyleneC3-8heterocycloalkyl useful in the treatment of diseases and conditions related to DNA damage or lesions in DNA replication are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division also are disclosed.

Abstract: Prophylactic treatment methods are provided for protection of individuals and/or populations against infection from airborne pathogens. In particular, prophylactic treatment methods are provided comprising administering amiloride, benzamil, phenamil or pharmaceutically acceptable salts thereof to one or more members of a population at risk of exposure to or already exposed to one or more airborne pathogens, either from natural sources or from intentional release of pathogens into the environment.

Abstract: Novel compounds of the formula (I) in which R1, D, X, W, Y and T have the meaning indicated in Patent Claim (1), e.g. (II), are inhibitors of coagulation factor Xa and can be employed for the prophylaxis and/or therapy of thromboembolic diseases and for the treatment of tumors.

Abstract: The present invention relates to pyrazine derivatives of the formula and pharmaceutically acceptable salts thereof, wherein R1 to R8 are as defined in the description and claims for use as HDL-cholesterol raising agents in the treatment and/or prophylaxis of diseases or disorders that can be treated with such agents such as dyslipidemia.

Abstract: Selective phenyl substituted aminopyrazine inhibitors of GSK3 useful for the prevention and/or treatment of cognitive disorders.

Abstract: The present invention relates to new compounds of formula (I) wherein Z is N; Y is CONR5, NR5CO, SO2NR5, NR5SO2, CH2NR5, NR5, NR5CONR5, CH2CO, CO, O or CH2O; X is CH or N; P is phenyl or a 5 or 6 membered heteroaromatic ring containing one or more heteroatoms selected from N, O or S and said phenyl ring or 5 or 6 membered heteroaromatic ring may optionally be fused with a 5 or 6 membered saturated, partially saturated or unsaturated ring containing one or more atoms selected from C, N, O or S; Q is C1-6alkyl, C2-6alkenyl or C2-6alkynyl, a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy, such as provide compounds having a selective inhibiting effect at GSK3.

Abstract: The present invention provides pharmaceutical compositions comprising: (a) a modulator of hepatic parasympathetic tone, (b) at least one diabetes drug, and (c) a pharmaceutically acceptable carrier. The present invention includes methods for the treatment and/or prevention of insulin resistance, type 2 diabetes, impaired glucose intolerance, and other associated disorders with pharmaceutical compositions described herein. The invention also provides for a kit comprising a pharmaceutical composition and instructions for its use.

Abstract: The present invention is concerned with novel pyrazine 2-carboxyamide derivatives of formula (I) wherein R1, R2 and R3 are as defined in the specification. These compounds are useful for the treatment of CNS disorders.

Abstract: Pharmaceutical fixed dose combination products are formed by merging a fixed dose of a first pharmaceutical formulation from primary module, with a fixed dose of a second pharmaceutical formulation from a secondary module In a preferred embodiment the first and second pharmaceutical formulations are separated from one another in a three piece capsule, a capsule-in-a-capsule or a tablet-in-a-capsule, and the primary and secondary modules are interchangeable.

Abstract: The present invention relates to sodium channel blockers. The present invention also includes a variety of methods of treatment using these inventive sodium channel blockers.

Abstract: The present invention relates to sodium channel blockers. The present invention also includes a variety of methods of treatment using these inventive sodium channel blockers.

Abstract: The present invention relates to new compounds of formula (I) wherein: Z is N and X is CH or N; Y is CONR5; P is phenyl or a 5 or 6 membered heteroaromatic ring containing one or more heteroatoms selected from N, O or S; Q is phenyl or a 5 or 6 membered aromatic heterocyclic ring containing one or more nitrogen atoms; R is C1-6alkylNR10R11 or C1-6alkylazetidine; R10 is hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C0-6alkylC3-6cycloalkyl, C0-6alkylaryl, C0-61alkylheteroaryl or C1-6alkylNR8R9; R11 is C1-6alkylNR8R9, C0-6alkylC3-6cycloalkyl or C0-6alkylheterocycloalkyl; as a free base or a pharmaceutically acceptable salt, solvate or solvate of salt thereof, a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy.

Abstract: The present invention relates to immunosuppressants, processes for their production, their uses and pharmaceutical compositions containing them. The invention provides a novel class of compounds useful in the treatment or prevention of diseases or disorders mediated by lymphocyte interactions, particularly diseases associated with EDG receptor mediated signal transduction. This application relates to compounds selected from Formula (Ia), (Ib), (Ic) and (Id).

Abstract: Polyaromatic sodium channel blockers represented by the formula: are provided where the structural variables are defined herein. The invention also includes a variety of compositions, combinations and methods of treatment using these inventive sodium channel blockers.

Abstract: The present invention relates to compounds of the formula and pharmaceutically acceptable salts and solvates thereof, to processes for the preparation of, intermediates used in the preparation of, and compositions containing such compounds and the uses of such compounds for the treatment of pain.

Abstract: Novel 2-alkylcycloalk(en)ylcarboxamides of the formula (I) in which X, s, R1, L, R2 and A are as defined in the description, a plurality of processes for preparing these compounds and their use for controlling unwanted microorganisms, and also novel intermediates and their preparation.

Abstract: Methods and compositions for treating disease caused by infectious agents, particularly tuberculosis. In particular, methods and compositions comprising substituted ethylene diamines for the treatment of infectious diseases are provided. In one embodiment, these methods and compositions are used for the treatment of mycobacterial infections, including, but not limited to, tuberculosis. In certain embodiments, the present invention comprises compositions comprising novel substituted ethylene diamine compounds further comprising antitubercular agents such as rifampicin, isoniazid, pyrazinamide and ethambutol.

Abstract: The invention relates to topical formulations of flucytosine which demonstrate a clear advantage over currently available therapeutic regimens for the treatment and maintenance of fungal infections, particularly vulvovaginal candidiasis. The invention provides compositions which solve the long-standing need for antimicrobial agents which treat effectively resistant strains of Candida spp., especially C. albicans, C. glabrata, and C. tropicalis, and which pose limited risk of side effects, adverse reactions, or the development of resistant pathogens. The invention provides novel topical formulations of flucytosine designed to allow the active drug to act at the local application area, but which inhibit or moderate transdermal or transmucosal absorption of the drug, thus limiting systemic exposure.

Abstract: Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.