Abstract: The present application relates to novel, substituted 4-arylimidazol-2-ones and 5-aryl-1,2,4-triazolones, processes for the production thereof, the use thereof alone or in combinations for the treatment and/or prevention of diseases and the use thereof for the production of medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular diseases.

Abstract: The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

Abstract: The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of BRAF. In particular embodiments, the invention concerns mutations in a BRAF sequence that confer resistance to a BRAF inhibitor. Identification of such mutations in a BRAF sequence allows the identification and design of second-generation BRAF inhibitors. Methods and kits for detecting the presence of a mutant BRAF sequence in a sample are also provided.

Abstract: A compound having Formula (I) or Formula (II) is disclosed as an P2X7 antagonist, wherein A, B, C, Y, Y, Z, m, v, R1, R2, R3, R4, and R5, are as defined in the description. Methods and compositions for treating disease or condition modulated by P2X7 are also disclosed.

Abstract: In one aspect, the invention relates to compounds having the formula: wherein: Ar, r, Z, X, R3, and R5-7 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

Abstract: The present invention encompasses compounds of general formula (I) wherein the groups R2 to R4, A, X and m are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, pharmaceutical preparations which contain compounds of this kind and their use as medicaments.

Abstract: Compounds and methods are provided for the treatment of, inter alia, Type II diabetes and other diseases associated with poor glycemic control.

Abstract: This invention relates to the use of triazolone derivatives of Formula (I) for the modulation, notably the inhibition of the activity or function of fatty acid synthase (FAS). Suitably, the present invention relates to the use of triazolones in the treatment of cancer.

Abstract: Methods and compositions for the treatment and/or management of cancer are disclosed, which comprise the use of tryptophan hydroxylase inhibitors.

Abstract: A bicontinuous microemulsion of water, a monomer, and a surfactant copolymerizable with the monomer is polymerized to form a polymeric material, the polymeric material comprising a polymer matrix defining interconnected pores. The polymeric material may additional comprise at least one photochromic agent. The photochromic agent may be dispersed in one or both of the polymer matrix or the interconnected pores. The polymeric material may be used to form photochromic articles including ophthalmic articles such as contact lenses.

Abstract: Provided is a 1,3,4-oxadiazole-2-carboxamide compound which has STAT3 inhibitory activity and is useful as an anticancer agent. Provided is a 1,3,4-oxadiazole-2-carboxamide compound represented by formula (I) or a pharmacologically acceptable salt thereof (in the formula, Ar represents a furyl group or the like; R1 represents a hydrogen atom or the like; and —X—Y represents a diaryl group such as a biphenyl group).

Abstract: A method for assessing if a subject has or is at risk of developing cardiac arrhythmia is described. The method includes determining the activity of Rap1A protein in a bodily sample of the subject and comparing the activity of Rap1A protein from the bodily sample of the subject to at least one Rap1A control. A decreased level of Rap1A activity in the bodily sample of the subject as compared to the at least one Rap1A control indicates that the subject is at risk of developing or has cardiac arrhythmia. Methods for evaluating the efficacy of treatment of a subject having decreased Rap1A activity with an antiarrhythmic agent are also described.

Abstract: The present invention relates to compounds of formula (I) and (IA): and pharmaceutically acceptable salts thereof, wherein R1-R5 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

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: Novel 1,2,4-oxadiazole benzoic acid compounds, methods of using and pharmaceutical compositions comprising an 1,2,4-oxadiazole benzoic acid derivative are disclosed. The methods include methods of treating or preventing a disease ameliorated by modulation of premature translation termination or nonsense-mediated mRNA decay, or ameliorating one or more symptoms associated therewith.

Abstract: [Problem]A compound which is useful as a GK activator is provided. [Means for Solution] The present inventors have conducted studies on compounds having a GK activating action, which are promising as active ingredients of pharmaceutical compositions for the treatment of diabetes, type 2 diabetes mellitus, obesity, metabolic syndrome and related diseases caused by the aforementioned diseases, and as a result, they have confirmed that a benzamide compound of the present invention has an excellent GK activating action, thereby completing the present invention. That is, the benzamide compound of the present invention has a GK activating action and can be used as an agent for preventing and/or treating diabetes, type 2 diabetes mellitus, obesity, metabolic syndrome, and related diseases caused by the aforementioned diseases.

Abstract: The invention provides pyridyl-triazine derivatives to inhibit the hedgehog signaling pathway and the use of such compounds in the treatment of hyperproliferative diseases and angiogenisis mediated diseases.

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: Methods are provided for treating a subject for a condition caused by an abnormality in the subject's autonomic nervous system. In accordance with the subject methods, at least a portion of a subject's autonomic nervous system is pharmacologically modulated with at least one beta-blocker in a manner that is effective to treat the subject for the condition. The subject methods find use in the treatment of a variety of different conditions, where such conditions include various disease conditions. Also provided are systems and kits for use in practicing the subject methods.

Abstract: A drug delivery system (DDS) comprised of segmented biodegradable implants sized and suitable for implantation in an ocular region or site and methods for treating ocular conditions. The segmented implants provide an extended release of an active agent at a therapeutically effective amount for a period of time between 50 days and one year, or longer, and permit the DDS to have segments that possess individual and different drug release characteristics.

Abstract: The present invention provides novel methods and formulations for treating anxiety disorders, including Post Traumatic Stress Disorder, in human subjects employing coordinate treatment using ? and ? blockers alone or in combination with additional psychotherapeutic medications to treat the anxiety disorder and reduce symptomology in treated subjects.

Abstract: Disclosed is a novel 1-(biphenyl-4-yl-methyl)-1H-imidazole derivative represented by general formula (I), which has both angiotensin II receptor antagonist activity and PPAR-? activating activity and is useful as a prophylactic and/or therapeutic agent for cardiovascular diseases and metabolic diseases. Also disclosed is a pharmaceutical composition which contains the novel 1-(biphenyl-4-yl-methyl)-1H-imidazole derivative. In general formula (I), ring A represents a group represented by formula (II) or (III); R1 represents a C1-6 alkyl group; R2 represents a C1-6 alkyl group which may be substituted by a hydroxy group, or a group represented by formula —CO—R4 (wherein R4 represents a hydroxy group, a C1-6 alkoxy group, an amino group, a mono(C1-6 alkyl)amino group, a di(C1-6 alkyl)amino group, a morpholino group, a piperidino group or a pyrrolidino group); R3 represents a halogen atom or a C1-6 alkoxy group; and X and Y may be the same or different and each represents a nitrogen atom or CH.

Abstract: A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof: which is used for preventive and/or therapeutic treatment of a disease caused by abnormal activity of tau protein kinase 1 such as a neurodegenerative diseases (e.g. Alzheimer disease).

Abstract: The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1-R5 are as defined herein.

Abstract: Disclosed are compounds for inhibiting prostaglandin transporter (PGT) activity, pharmaceuticals compositions including the compounds, and methods of treating subjects using the compounds.

Abstract: The present invention comprises inter alia compounds as shown in formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to morpholinothiazole derivatives and pharmaceutically acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to positive allosteric modulators of nicotinic acetylcholine receptors, such positive allosteric modulators having the capability to increase the efficacy of nicotinic receptor agonists.

Abstract: There is provided a compound of formula I wherein Z is selected from N and CR22, wherein R22 is H or a bond with D; wherein D is selected from a bond, C?O, and linear or branched hydrocarbon groups having a carbon chain of from 1 to 6 carbon atoms, wherein the carbon chain optionally contains an oxy group (?O), an ether (—O—) or thioether (—S—) link, wherein R1 is selected from: triazolyl, imidazolyl, pyrimidinyl radical wherein each of R2 to R6 is independently selected from —H, NO2, halo, —CN, —N[(C?O)0-1R12][(C?O)0-1R13] and —(CH2)0-1R14, or two adjacent groups of R2 to R6, together with the carbon atoms to which they are attached, form a ring, wherein at least one of R2 to R6 is —CN, wherein (i) at least one of R2 to R6 is —(CH2)0-1R14, or (ii) at least one of R2 to R6 is —N[(C?O)0-1R12][(C?O)0-1R13], or (iii) at least two adjacent groups of R2 to R6 together with the carbon atoms to which they are attached, form a ring, or (iv) at least one of R2 to R6 is —(CH2)0-1—O—R?14, wherein R12 and R13

Abstract: The present invention is based on the use of a broad family of 5-imino-1,2,4-thiadiazoles as potential new drugs for the treatment of diseases in which PDE7 inhibition is important, specially inflammatory diseases, autoimmune and neurodegenerative disorders. On the other hand, compounds of the 5-imino-1,2,4-thiadiazole family are here described, as well as their synthetic procedures, and they may have great application as drug or drug candidates.

Abstract: The present invention relates to substituted triazole compounds of the formula (I): and salts thereof, to pharmaceutical compositions containing them and their use in medicine. In particular, the invention relates to compounds for inhibiting SCD activity.

Abstract: A pyrimidone derivative represented by general formula (I) or a pharmaceutically acceptable salt thereof: wherein X represents hydrogen atom and Y represents hydroxyl group, or X represents fluorine atom and Y represents hydrogen atom; R1 represents a C1-6 alkyl group; R2 represents a morpholin-4-yl group which may be substituted, or the like, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).

Abstract: The invention relates to novel substituted piperidines, to processes for preparation thereof, to the use thereof for treatment and/or prophylaxis of diseases and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of cardiovascular disorders and tumour disorders.

Abstract: The disclosure provides compounds of formula I, including pharmaceutically acceptable salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

Abstract: The invention relates to novel heteroaryl-substituted piperidines, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular diseases and tumour diseases.

Abstract: The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of liver X receptors (LXRs).

Abstract: In one aspect, the invention relates to compounds having the formula: where R1-R6, a, b, Z, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

Abstract: Compounds of the formula I: or a pharmaceutically acceptable salt thereof, wherein, R1 is optionally substituted tetrazolyl, R2 is optionally substituted phenyl, optionally substituted pyridinyl or optionally substituted thienyl, and R3, R4, R5 and R6 are as defined herein. Also provided are methods of using the compounds for treating diseases associated with the P2X3 and/or a P2X2/3 receptor antagonist and methods of making the compounds.

Abstract: Disclosed are compounds of Formula 1, including all stereoisomers, N-oxides, and salts thereof, wherein Y is a 5-membered, fully or partially unsaturated heterocyclic ring containing 2-4 carbon atoms and 2-3 nitrogen atoms as ring members, the ring substituted with Z on a ring member atom connected through an adjacent single ring member atom to the ring member atom attaching the heterocyclic ring to the phenyl ring of Formula 1, and optionally further substituted with up to 2 substituents independently selected from R5 on carbon atom ring members and from R6 on nitrogen atom ring members; Z is an 8-, 9-, 10- or 11-membered fused heterobicyclic ring system containing ring members selected from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2O, up to 2S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(?O) and C(?S), and the sulfur atom ring members are independently selected from S(?O)u(?NR7)z, the ring system optionally substituted wi

Abstract: This invention provides compounds of formula I: wherein R1, R2, CY, Y1, Y2, X1, X2, and X3 are as described in the specification. The compounds are inhibitors of PI3K and are thus useful for treating proliferative, inflammatory, or cardiovascular disorders.

Abstract: The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound.

Abstract: The present invention relates to the medical use of the compound of formula 1, 2, 3 or 4:

Abstract: The invention provides Triazine derivatives and further provides methods of using these compounds to modulate protein kinases and for treating diseases and conditions mediated by protein kinases.

Abstract: The invention relates to compounds of formula wherein R1, R2, R3, R4, and Ar are as defined in the specification and claims, or to pharmaceutically active acid addition salts of such compounds. Compounds of formula I are modulators for amyloid beta and may be useful for the treatment or prevention of a disease associated with the deposition of ?-amyloid in the brain, in particular Alzheimer's disease, and other diseases such as cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica and Down syndrome.

Abstract: [Problems] The object is to improve the absorbability of a heterocyclic compound including s-triazine and a pyrimidine derivative in vitro. [Means for Solving Problems] Disclosed is, for example, an amorphous body of a heterocyclic compound as represented by the general formula (I) [wherein each of R's and others is as defined in the description] including s-triazine and a pyrimidine derivative, or a hydrate, a solvate or a pharmaceutically acceptable salt of the heterocyclic compound. Also disclosed is a process for producing the amorphous body. Further disclosed are: a solid dispersion comprising the amorphous body; and a medicinal preparation comprising the solid dispersion.

Abstract: Compounds, compositions and methods are provided for the prophylaxis and treatment of infections caused by viruses of the Pneumovirinae subfamily of Paramyxoviridae and diseases associated with such infection.

Abstract: The present invention relates to substituted benzamide derivatives of the general Formula I and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, prodrugs, metabolites, and polymorphs and can be useful for treating disease states mediated by glucokinase. Compounds disclosed herein can be used for reducing blood glucose levels and for increasing insulin secretion for treating type II diabetes. The invention also relates to processes for the preparation of the compounds of invention, pharmaceutical compositions containing the compounds, and their use.

Abstract: Disclosed are pharmaceutical compositions comprising brimondine and timolol for topical ophthalmic delivery and a method of treatment comprising administering said composition when indicated for glaucoma and associated conditions such as elevated intraocular pressure in the eyes of humans.

Abstract: The invention provides an aqueous eye drop containing latanoprost, a surfactant, and an aliphatic mono- or di-carboxylic acid having a carbon number of 3-10 or a salt thereof. In addition, the invention provides a method of suppressing adsorption of latanoprost to a resin in an aqueous solution, by adding a surfactant and an aliphatic mono- or di-carboxylic acid having a carbon number of 3-10 or a salt thereof.

Abstract: A method is provided for the prevention of cancer metastasis in a patient comprising administering an adrenergic receptor antagonist to a patient in need thereof. The invention also includes an adrenergic receptor antagonist for use in the prevention of tumour recurrence in a patient. Also provided is a kit of parts for use in such methods comprising an adrenergic receptor antagonist, and an administration vehicle. A method is further included for identifying a patient at risk of developing cancer comprising the step of assaying for levels of expression of adrenergic receptor genes and proteins in said patient.

Abstract: The Wnt signaling pathways are involved in embryo development as well as in tumorigenesis. Dishevelled (Dvl) tranduces Wnt signals from the receptor Frizzled (Fz) to downstream components in canonical and non-canonical Wnt signaling pathways, and the Dvl PDZ domain plays an essential role in both pathways, and the Dvl PDZ domain binds directly to Fz receptors. In the present invention using NMR-assisted virtual ligand screening, several compounds were identified and were found to bind to the Dvl PDZ domain. Molecular dynamics simulation was used to analyze the binding between the PDZ domain and these compounds in detail. These compounds provide a basis for rational design of high-affinity inhibitors of the PDZ domain, which can block Wnt signaling by interrupting the Fz-Dvl interaction.