Abstract: The present invention provides compounds of Formula (I) or Formula (III): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

Abstract: Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula Ia or Ib, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

Abstract: The present invention relates to 1-aza-bicy-cloalkyl derivatives of Formula (I); wherein the substituents are as defined in the specification, to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them. Formula (I), wherein A represents O or N(R?); Y represents a group of formula, or wherein the left bond is attached to the A group and the right bond is attached to the R group; R represents a substituted or unsubstituted C5-C10aryl, substituted or unsubstituted hetero-C5-C10aryl, a group N(R1)(R4), or a group N(R2)(CHP3R4); R represent a hydrogen, C1-C4alkyl, or CF3; R2 represents hydrogen, C1-C4alkyl, or CF3; R3 represents hydrogen, C1-C4alkyl, or CF3; R4 represents a substituted or unsubstituted C5-C10 aryl or a substituted or unsubstituted C5-C10heteroaryl; in free base or acid addition salt form.

Abstract: There is described a novel group of cyclic amine derivative compounds, having an EP4 receptor antagonistic activity and specifically pharmaceutical compounds which are useful for the treatment or alleviation of Prostaglandin E mediated diseases. The present invention therefore relates to novel compounds which are selective antagonists of the EP4 subtype of PGE2 receptors with analgesic and antinflammatory activity, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments, inter alia for the treatment or alleviation of Prostaglandin E mediated diseases such as acute and chronic pain, osteoarthritis, inflammation-associated disorder as arthritis, rheumatoid arthritis, cancer, migraine and endometriosis.

Abstract: The invention relates to N-substituted hetero-bicyclic furanone compounds of formula (I), to the enantiomers, diastereomers and salts thereof and to compositions comprising such compounds. The invention also relates to methods and uses of these N-substituted hetero-bicyclic furanone compounds, and of compositions comprising thereof, for combating and controlling animal pests. Furthermore the invention relates also to pesticidal methods of applying such N-substituted hetero-bicyclic furanone compounds. The N-substituted hetero-bicyclic furanone compounds of the present invention are defined by the following formula I: wherein A, X, Het, W1, W2, W3, R1, R2 and R4 are defined as in the description.

Abstract: The present invention provides compounds of formula (I) including stereoisomers or a racemate or a mixture or a pharmaceutically acceptable salt thereof: wherein X is NH, or O; Q is 5-6 membered heteroaryl group, which may be substituted by one or more substituents independently selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; A is phenyl or a 5-6 heteroaryl group, which may be substituted by one or more substituents independently selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; B may assume different meanings from A and is phenyl or a 5-6 membered heteroaryl group, which may be substituted by one or more substituents independently selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; and processes for their preparation, pharmaceutical compositions containing them and their use as dual antagonists of the Orexin 1 and Orexin 2 receptors.

Abstract: The invention provides 8-azabicyclo[3.2.1]octyl-2-hydroxybenzamide compounds of formula (I): wherein R2, R7, and m are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

Abstract: The present invention relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein W1, W2, W3, R1, Q, X1, X2 and X3 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

Abstract: The present invention provides compounds of Formula (I) or Formula (III): [INSERT CHEMICAL STRUCTURE HERE] (I) [INSERT CHEMICAL STRUCTURE HERE] (III) as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

Abstract: The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

Abstract: The present invention is directed to methods of treating pain by administering a therapeutically effective amount of an ?7 nAChR ligand or a pharmaceutically acceptable salt thereof, to a mammal in need of treatment thereof and to pharmaceutical compositions comprising such a compound or salt.

Abstract: Disclosed herein are indolizine compounds of general formula I, wherein R1-R7, X and Y are as disclosed in the application, useful as inhibitors of lipoprotein associated phospholipase A2 (Lp-PLA2) and/or 15-lipoxygenase (15-LOX), as well as methods of preparation and use thereof, and compositions thereof Advantageously, certain compounds disclosed herein are capable of inhibiting both Lp-PLA2 and 15-LOX. Accordingly, provided herein are methods of inhibiting one or both of Lp-PLA2 and 15-LOX, and methods of treating diseases or conditions associated with Lp-PLA2 and/or 15-LOX.

Abstract: The invention generally relates to nuclear transport modulators, e.g CRM1 inhibitors, and more particularly to a compound represented by formula (I): or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of structural formula (I), or a pharmaceutically acceptable salt or composition thereof, e.g, in the treatment, modulation and/or prevention of physiological conditions associated with CRM1 activity.

Abstract: Disclosed is a compound represented by formula (1) or a pharmacologically acceptable salt thereof (In the formula, A represents a group that is represented by formula (A-1); R1a and R1b may be the same or different and each independently represents a C1-6 alkyl group which may be substituted by one to three halogen atoms; m and n each independently represents an integer of 0-5; X1 represents a hydroxyl group or an aminocarbonyl group; Z1 represents a single bond or the like; and R2 represents an optionally substituted C1-6 alkyl group, an optionally substituted C6-10 aryl group or the like).

Abstract: There is described a method for increasing the maximal tolerated close and thus the efficacy of an acetyl choline esterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia by decreasing concomitant adverse effects by administration of said AChEI in combination with a non-anticholinergic antiemetic agent, whereby an enhanced acetyl choline esterase inhibition in the CNS of said patient is achieved and alleviation of the symptoms of Alzheimer type dementia in said patient is thereby improved to a greater extent. The use of a non-anticholinergic antiemetic agent for the preparation of a pharmaceutical composition for the treatment of Alzheimer type dementia in combination with an acetyl choline esterase inhibitor (AChEI) and pharmaceutical compositions comprising (a) a 5HT3 receptor antagonist, a dopamine antagonist, a H1-receptor antagonist, a cannabinoid agonist, aprepitant or casopitant as an antiemetic agent and (b) an acetylcholine esterase inhibitor are also described.

Abstract: A Medicaments for inhibiting thrombus formation contains active ingredients which are triflusal and clopidogrel bisulfate, wherein a mass ratio of triflusal to clopidogrel bisulfate is (100-650):(30-150), preferably (1-20):1, more preferably (3-6):1, and even more preferably 3:1 or 6:1.

Abstract: Provided herein are compounds, pharmaceutical compositions and combination therapies for inhibition of hepatitis C.

Abstract: This invention relates to 2-Aza-bicyclo[2.2.2]octane-3-carboxylic acid (benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.

Abstract: The present invention provides transdermal therapeutic systems for dispensing a pharmaceutical product, in particular a pharmaceutical product with a low tendency to spontaneously crystallize. The matrix layer or at least one of the matrix layers in said systems contains a silicone hot-melt adhesive, a pharmaceutical product, and particles made of crosslinked polyvinylpyrrolidone. The invention also relates to a method for producing said transdermal therapeutic systems.

Abstract: The present invention relates to novel Substituted Biphenylene Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein Y1, Y2, R1, R2, R4, Ra and Rb are as defined herein. The present invention also relates to compositions comprising at least one Substituted Biphenylene Compound, and methods of using the Substituted Biphenylene Compounds for treating or preventing HCV infection in a patient.

Abstract: The invention provides sprayable aqueous compositions containing zolpidem or single stereoisomer, mixtures of stereoisomers, pharmaceutically acceptable salts or prodrugs thereof, a solubilizing agent, a water soluble polymer with bioadhesive property. When administered intranasally using a spray device, zolpidem is rapidly absorbed with prolonged intranasal residence time and improved bioavailability. The compositions can be applied for the treatment of insomnia-related disorders such as difficulties with sleep initiation or middle of the night awakenings.

Abstract: This invention relates to compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.

Abstract: The present invention relates to Bicyclic Heterocycle Derivatives, compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of GPR119 in a patient.

Abstract: The present invention provides compounds of formula (I): wherein A, R1, R2, R3 IX, and Z are defined herein, which are potassium channel inhibitors. The invention further provides pharmaceutical compositions comprising the compounds of formula (I) and their use in therapy, in particular in treatment of diseases or conditions that are mediated by Kir3.1 and/or Kir3.4 or any heteromultimers thereof, or that require inhibition of Kir3.1 and/or Kir3.4 or any heteromultimers thereof.

Abstract: The invention provides modulators for the orphan nuclear receptor ROR? and methods for treating ROR? mediated diseases by administrating these novel ROR? modulators to a human or a mammal in need thereof. Specifically, the present invention provides pyrrolo carboxamide compounds of Formula (1) and the enantiomers, diastereomers, N-oxides, tautomers, solvates and pharmaceutically acceptable salts thereof.

Abstract: The invention relates to the design and synthesis of novel anabaseine-based compounds, which are useful in treating or preventing a wide variety of conditions, including nervous system diseases or disorders, such as, schizophrenia, Alzheimer's disease, Parkinson's disease, drug dependence, and substance addiction, and compositions, kits, and methods thereof. The invention also provides novel anabaseine-based compounds, compositions, kits, and methods thereof for treating or preventing non-nerve system diseases or disorders (such as, inflammation and cancer) in a subject identified in need thereof. Certain enantiomeric compounds of the invention exhibited enhanced selectivity toward ?7 nAChRs relative to alpha4beta2 nAChRs. Other enantiomeric compounds of the invention exhibited enhanced selectivity for alpha4beta2 nAChRs relative to ?7 nAChRs.

Abstract: This invention relates to bicyclic 1-carboxylic-acid (benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.

Abstract: Provided are methods for increasing fat locally in a body of a subject in need thereof comprising percutaneously administering to the subcutaneous fat of the subject a thiazolidinedione or an orexigenic compound, or a pharmaceutically acceptable salt or prodrug thereof, optionally delivered as a composition comprising a pharmaceutically acceptable carrier, as described herein. In certain embodiments, the pharmaceutically acceptable carrier comprises a percutaneous carrier, as described herein. Further provided are compositions comprising a thiazolidinedione or an orexigenic compound, or a pharmaceutically acceptable salt or prodrug thereof, for use according to the invention.

Abstract: Described is a method for treating an individual having a neurological disorder with an associated mutation or mutations in a gene encoding a lysosomal enzyme. Specifically, the individual is administered a specific pharmacological chaperone for the lysosomal enzyme which increases trafficking of the protein from the ER to the lysosome in neural cells, with or without concomitantly increasing enzyme activity in neural cells. Restoration of trafficking relieves cell stress and other toxicities associated with accumulation of mutant proteins. Restoration of enzyme activity relieves substrate accumulation and pathologies associated with lipid accumulation. In a specific embodiment, the neurological disorder is Parkinson's disease or parkinsonism which is associated with mutations in glucocerebrosidase.

Abstract: There is described a method for increasing the maximal tolerated close and thus the efficacy of an acetyl choline esterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia by decreasing concomitant adverse effects by administration of said AChEI in combination with a non-anticholinergic antiemetic agent, whereby an enhanced acetyl choline esterase inhibition in the CNS of said patient is achieved and alleviation of the symptoms of Alzheimer type dementia in said patient is thereby improved to a greater extent. The use of a non-anticholinergic antiemetic agent for the preparation of a pharmaceutical composition for the treatment of Alzheimer type dementia in combination with an acetyl choline esterase inhibitor (AChEI) and pharmaceutical compositions comprising (a) a 5HT3 receptor antagonist, a dopamine antagonist, a H1-receptor antagonist, a cannabinoid agonist, aprepitant or casopitant as an antiemetic agent and (b) an acetylcholine esterase inhibitor are also described.

Abstract: A PEGylated cyclopamine analog, preparation method, uses thereof and methods for treating proliferative diseases using the same are disclosed. The PEGylated cyclopamine analog is a compound represented by the following formula I, a compound comprising at least one group represented by the following formula I (in formula I, R is straight or branched polyethylene glycol having a molecular weight between 200 and 200,000 Dalton, L and X are linking groups), or their single enantiomers, mixture of enantiomers, mixture of diastereomers, pharmaceutically acceptable salts, solvates, or hydrates.

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 disclosure provides substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes, of Formula I D-M-D??(Formula I) useful as antiviral agents. In certain embodiments disclosed herein M is a group —P-A-P— where A is Certain substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes disclosed herein are potent and/or selective inhibitors of viral replication, particularly Hepatitis C virus replication. Pharmaceutical compositions/and combinations containing one or more substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes and a pharmaceutically acceptable carrier are also provided by this disclosure. Methods for treating viral infections, including Hepatitis C viral infections are provided by the disclosure.

Abstract: A method for administering a polymeric-based delivery system to a subject is described. The method comprises contacting a housing comprising a polymer-based delivery system with a heat-generating component for a period of time; and injecting the delivery system into the subject.

Abstract: An oral pharmaceutical composition comprises multiple populations of at least one of beads, pellets, tablets and granules provided in a capsule, the composition comprising: a first population of a pharmaceutical active comprising a pharmaceutical active substance releasable at a first rate; a population of a basic substance; and a second population of a pharmaceutical active comprising a pharmaceutical active substance releasable at a second rate. In another embodiment, the oral pharmaceutical composition comprises multiple populations of at least one of beads, pellets, tablets and granules provided in a capsule, the composition comprising: a population of a pharmaceutical active; a population of a basic substance; a population of enteric coated pharmaceutical active; and a population of enteric coated basic substance. The composition can provide multiple site specific delivery of a pharmaceutical active in a rapid, delayed and/or sustained release manner into the plasma.

Abstract: This invention relates to 2-Aza-bicyclo[2.2.1]heptane-3-carboxylic acid (cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.

Abstract: The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and methods of using the same in the treatment or prevention of diseases mediated by the activation of ?3-adrenoceptor. (I).

Abstract: The present invention relates to novel dihydroazole of formula (I) and salts thereof: Wherein R1, A1, A2, G, X and Y are as defined in the description, compositions thereof, processes for their preparation and their uses to prevent or treat parasitic infections or infestations in animals and as pesticides.

Abstract: Novel substituted benzamide based inhibitors, their use in therapy, pharmaceutical compositions comprising the compounds, the use of said compounds in the manufacture of medicaments, and therapeutic methods comprising the administration of said compounds are described. The present compounds modulate the activity of 11?-hydroxysteroid dehydrogenase type 1 (11?HSD1) and are accordingly useful in the treatment of diseases in which such a modulation is beneficial, such as the metabolic syndrome.

Abstract: The present invention relates to processes for the preparation of quinoline-3-carboxamide derivatives, such as sodium 5-chloro-3-(ethylphenylcarbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-olate (Laquinimod sodium). The present invention further relates to intermediates formed in such processes.

Abstract: The present invention relates to the use of an agent that inhibits the activity of an enzyme that mediates repair of a DNA strand break in the manufacture of a medicament for the treatment of diseases caused by a defect in a gene that mediates homologous recombination.

Abstract: The present invention provides compositions containing clopidogrel, present as a free base or a pharmaceutically acceptable salt thereof, and sulfoalkyl ether cyclodextrin (SAE-CD). The compositions can be liquid, suspension or solid compositions. They can be adapted for oral, peroral or parenteral administration. The SAE-CD serves to aid in dissolution and stabilization of the clopidogrel in aqueous media. The stability of clopidogrel against hydrolytic degradation, thermal degradation, and photolytic degradation are improved. SAE-CD provides improved results over other cyclodextrin derivatives. The SAE-CD-containing composition of clopidogrel can be provided in liquid form, solid form or as a reconstitutable powder. Both ready-to-use and concentrated liquid compositions can be prepared. The liquid composition is optionally available as a clear solution.

Abstract: The present invention provides compounds of formula (I), their use as an inhibitor of a p53-MDM2 interaction as well as pharmaceutical compositions comprising said compounds of formula (I).

Abstract: Disclosed are muscarinic agonist compounds including oxadiazole derivatives, compositions and preparations thereof. Also disclosed are methods of synthesizing such oxadiazole compounds. Further disclosed are methods for treating a subject with said muscarinic agonists or a pharmaceutically suitable form thereof to enhance cognitive function.

Abstract: Delivery systems and compositions comprised of a biodegradable polyorthoester polymer, an aprotic solvent, and a drug are described. The solvent is selected to modulate release of drug from the composition, where, in some embodiments, the solvent is rapidly released after administration and provides a corresponding rapid rate of drug release. Alternatively, in other embodiments, the solvent is slowly released from the composition after its administration, and provides a correspondingly slow rate of drug release.

Abstract: The present invention provides agents for treating or preventing diseases such as mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastrointestinal disease, drug addiction, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, head injury, inflammation, immune-related disease, alopecia, and so forth.

Abstract: Delivery systems and compositions comprised of a biodegradable polyorthoester polymer, an aprotic solvent, and a drug are described. The solvent is selected to modulate release of drug from the composition, where, in some embodiments, the solvent is rapidly released after administration and provides a corresponding rapid rate of drug release. Alternatively, in other embodiments, the solvent is slowly released from the composition after its administration, and provides a correspondingly slow rate of drug release.

Abstract: This invention relates to bicyclic 1-carboxylic-acid (benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.

Abstract: This invention relates to 2-Aza-bicyclo[2.2.2]octane-3-carboxylic acid (benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.

Abstract: A chemical compound represented by the formula [I]: (wherein R1 represents a hydroxyl group or the like, m represents 0 or an integer of 1 to 5, R2 represents a halogen atom or the like, k represents 0 or an integer of 1 to 4, R3, R31, R4, R41, R5, R51, R6, R61, and R7 each independently represents a hydrogen atom or the like, X represents an oxygen atom or the like, and n represents 1), a salt, an N-oxide of the chemical compound represented by formula [I], and a pest control agent containing the formula [I] as its active constituent.