Abstract: The present invention refers to compounds with inhibitory activity against 14-3-3 proteins and their use in the treatment of tumors, in particular chronic myeloid leukemia. The invention also provides methods for the identification of 14-3-3 protein inhibitors.

Abstract: A combination comprising as components (a) the compound 3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol, and (b) one or more non-steroidal anti-inflammatory drugs (NSAIDs); a pharmaceutical salt comprising said components; a compound derived from said components; a pharmaceutical formulation and a dosage form comprising said combination, salt, or compound; as well as a method of treating pain, e.g. chronic or acute pain, in a mammal characterized in that components (a) and (b) are administered simultaneously or sequentially to a mammal, wherein component (a) may be administered before or after component (b) and wherein components (a) or (b) are administered to the mammal either via the same or a different pathway of administration.

Abstract: The present invention provides methods and compounds for treating viral infections using modulators of host cell enzymes relating to long chain fatty acid and lipid droplet metabolism. It includes a method of treating viral infections using triacsin C and its relatives, analogues and derivatives as well as other inhibitors of long chain fatty acid metabolism and lipid droplet metabolism.

Abstract: Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1 comprising administering to a subject in need thereof a compound described here.

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: The invention relates to a combination which comprises: (a) a HDAC inhibitor; and (b) an anti-thrombocytopenia drug, for simultaneous, concurrent, separate or sequential use, especially for use in the treatment of a proliferative diseases.

Abstract: Invented is a method of treating thrombocytopenia in a human, in need thereof which comprises the in vivo administration of a therapeutically effective amount of a peptide or a non-peptide TPO receptor agonist and an anti-clotting agent or agents, and optional further active ingredients, to such human.

Abstract: The present invention relates to compounds of the formula I, as well as pharmaceutically-acceptable salts thereof, pharmaceutical compositions containing said compounds and methods of using said compounds in the treatment or prophylaxis of diseases and disorders. The compounds and compositions disclosed herein are glucokinase activators useful for the treatment or prophylaxis of metabolic diseases and disorders, for example diabetes mellitus, including type II diabetes mellitus.

Abstract: The present invention provides methods for treating cancer comprising inhibiting the activity of p300/CBP histone acetyltransferase (HAT). Also provided are p300/CBP HAT inhibitors for treating a subject having cancer. In addition, the present invention includes biomarkers for p300/CBP HAT inhibition, which are used to i) monitor the effectiveness of cancer therapy, and ii) identify anti-cancer agents for use in combination therapy.

Abstract: Invented is a method of treating degenerative diseases/injuries, in a mammal, including a human, in need thereof which comprises the administration of a therapeutically effective amount of a non-peptide TPO receptor agonist to such mammal.

Abstract: In one aspect, the invention relates to compounds having the formula: where R1, R2a, R2b, R3-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: A composition comprising a carboxamide compound represented by following formula (I), wherein R1 represents a hydrogen atom or a methyl group, and R2 represents a methyl group, a difluoromethyl group or a trifluoromethyl group, and one or more phenylpyrazole compounds selected from group (A) consisting of fipronil and ethiprole is provided by the present invention, and this composition has an excellent pesticidal effect.

Abstract: The present invention relates to a compound of formula (I) as well as pharmaceutically acceptable salt thereof, wherein R1 to R4 have the significance given in claim 1. The compound may be used, for example, for the treatment or prophylaxis of obesity, hyperglycemia, dyslipidemia, and type 1 or type 2 diabetes.

Abstract: The invention provides a method of manufacturing a patch preparation comprising (a) pouring a composition for forming an adhesive layer into a container having a concave part with a shape corresponding to a patch preparation to be manufactured, wherein the composition contains a drug, an adhesive polymer, and an organic solvent; (b) removing the organic solvent from the composition through drying to form a drug-containing adhesive layer in the concave part; and (c) laminating a support on the drug-containing adhesive layer to provide the patch preparation comprising a support and the drug-containing adhesive layer formed on one surface of the support.

Abstract: Invented are non-peptide TPO mimetics. Also invented are novel processes and intermediates used in the preparation of the presently invented compounds. Also invented is a method of treating thrombocytopenia, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a selected hydroxy-1-azobenzene derivative.

Abstract: 3-Heteroaroylamino-propionic acid derivatives and their use as pharmaceuticals The present invention relates to compounds of the formula I, wherein Ht, G, R10, R30, R40, R50 and R60 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. They are inhibitors of the protease cathepsin A, and are useful for the treatment of diseases such as atherosclerosis, heart failure, renal diseases, liver diseases or inflammatory diseases, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use and pharmaceutical compositions comprising them.

Abstract: The present invention relates to compounds of the formula I, wherein A, D, E, G, R10, R30, R40, R50 and R60 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. They are inhibitors of the protease cathepsin A, and are useful for the treatment of diseases such as atherosclerosis, heart failure, renal diseases, liver diseases or inflammatory diseases, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use and pharmaceutical compositions comprising them.

Abstract: The present invention discloses a novel thyroid like compounds of formula (I), wherein R1 R2, R3, R4 and Z are as defined in the specification, method for its preparation, composition containing such compounds and use of such compounds and composition as medicament. Further, compounds of formula (I) has significantly low binding affinity to thyroid receptors and thus considerably devoid of thyrotoxic effects. The invention also relates to the use of the compound of formula (I) for the preparation of a medicament for treating various disease conditions such as obesity, dyslipidemia, metabolic syndrome and co-morbidities associated with metabolic syndrome.

Abstract: New polymorphs of Eltrombopag and Eltrombopag ethanolamine salt have been obtained and characterized. These polymorphs and pharmaceutical compositions comprising them are useful, for example, in treating conditions leading to thrombocytopenia.

Abstract: The bicyclo-substituted pyrazolon-azo derivatives of formula (I) or pharmaceutical acceptable salts, hydrates or solvates thereof, methods for their preparation, pharmaceutical compositions containing the same and their use as a therapeutic agent, especially as thrombopoietin (TPO) mimetics and their use as agonists of thrombopoietin receptor are disclosed. The definition of substituents in formula (I) are the same as defined in the description.

Abstract: The present invention provides for, inter alia, novel topical formulations comprising at least one 1-N-arypyrazole derivative and amitraz and to methods for treating, controlling, or preventing parasite infestations on mammals or birds The inventive formulations include spot-on, pour-on or spray formulations and may include a further ectoparasiticide, such as an IGR compound, an avermectin or milbemycin derivative, or a pyrethroid insecticides, and anthelmintics, such as benzimidazoles and imidazothiazoles. The inventive formulation provides a larger duration of parasite control at a faster rate of control. The inventive formula remains effective up to three months from the first application. Moreover, the inventive formulations prevent tick attachment to the animal, thereby providing protection against tick borne diseases. The ectoparasites which may be controlled, treated or prevented by the present invention includes ticks, fleas, mites, mange, lice, mosquitoes, flies and cattle grubs.

Abstract: Suggested are biocide compositions, comprising (a) Glycerol(ether)phosphates; (b) Biocides and optionally (c) Oil components or co-solvents and/or (d) Emulsifiers. The compositions show excellent adjuvant and complexing properties.

Abstract: In one aspect, the invention relates to compounds having the formula: where R1, R2, R3, a, R4, R5, and R6 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 process and intermediates for preparing such compounds.

Abstract: The present invention relates to a process for the of a pyrazole derivative, characterized in that 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile (II) is reacted with a sulfinylating agent selected from trifluoromethylsulfinic acid, trifluoromethylsulfinic acid anhydride, and a trifluoromethylsulfinate alkaline or alkaline earth metal salt and mixtures of the acid and/or the salt(s), in the presence of at least one amine acid complex wherein the amine(s) are selected from tertiary amines and the acid(s) are selected from hydrofluoric, hydrochloric, hydrobromic and hydroiodic acid and sulfonic acid derivatives, and with the addition of a halogenating agent.

Abstract: Invented is a method of treating cancer and pre-cancerous syndromes in a mammal, including a human, in need thereof which comprises the administration of a therapeutically effective amount of a non-peptide TPO receptor agonist to such mammal.

Abstract: Invented is a method of treating cancer or a pre-cancerous syndrome in a mammal, including a human, in need thereof which comprises the administration of an effective amount of a non-peptide thrombopoietin (TPO) receptor agonist to such mammal, suitably a human.

Abstract: The present invention features pyrazolidinyl compounds, pharmaceutical compositions of substituted pyrazolidinyl compounds and methods of treating a patient suffering from cancer or viral infection, the method comprising administering to a patient one or more pyrazolidinyl compounds of the invention.

Abstract: Compounds of the formula I wherein R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a branched C5-C10 alkyl chain, C2-C4haloalkyl or —CH2C3-C7 cycloalkyl; R4 is C1-C6alkyl, C1-C6haloalkyl, C1-C6alkylamino or C1-C6dialkylamino; for use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

Abstract: The present invention relates to compounds of the formula I, as well as pharmaceutically-acceptable salts thereof, pharmaceutical compositions containing said compounds and methods of using said compounds in the treatment or prophylaxis of diseases and disorders. The compounds and compositions disclosed herein are glucokinase activators useful for the treatment or prophylaxis of metabolic diseases and disorders, for example diabetes mellitus, including type II diabetes mellitus.

Abstract: An improved phenylbutazone carrier composition provides increased palatability to horses. Additionally, the composition improves the bioavailability of the phenylbutazone and thus increases the horse's blood plasma levels of the medicine for the same effective dosage of the medicine.

Abstract: Disclosed herein are cannabinoid receptor ligands of formula (I) wherein Ring A and R1 are as defined in the specification. Compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions are also described.

Abstract: Invented is a method of treating cardiovascular disease/injury, in a mammal, including a human, in need thereof which comprises the administration of a therapeutically effective amount of a non-peptide TPO receptor agonist to such mammal.

Abstract: A method for recognizing and evaluating the presence and function of GnRH receptors on tumor cells including those originating in the brain and/or nervous system and/or the meninges and/or reactive neuroglia cells and/or primitive neuroectodermal tumor cells and/or on Kaposi sarcoma is provided. Furthermore, a method for reducing degenerate GnRH-positive tumor cells and/or for decreasing cellular replication of the above GnRH-positive tumor cells comprising administering to a cell or to a subject a replication decreasing amount of a GnRH agonist and/or GnRH antagonist and/or an erythropoietin agonist, and/or a thrombopoietin agonist, and/or a endothelin antagonist and/or a gonadotropin inhibiting hormone agonist is also provided. Furthermore, a diagnostic kit for detecting GnRH receptors on tumor cells according to the present methods is disclosed.

Abstract: New polymorphs of Eltrombopag and Eltrombopag ethanolamine salt have been obtained and characterized. These polymorphs and pharmaceutical compositions comprising them are useful, for example, in treating conditions leading to thrombocytopenia.

Abstract: The present invention relates to a novel crystalline modification of fipronil, to a process for the preparation of the same, to pesticidal and parasiticidal mixtures and compositions comprising said crystalline modification and to their use for combating pests and parasites.

Abstract: The invention relates to new compounds of the formula I to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

Abstract: The present invention features pyrazolidinyl compounds, pharmaceutical compositions of substituted pyrazolidinyl compounds and methods of treating a patient suffering from cancer or viral infection, the method comprising administering to a patient one or more pyrazolidinyl compounds of the invention.

Abstract: The present invention relates to pre-formulations comprising low viscosity, non-liquid crystalline, mixtures of: a) at least one neutral diacyl lipid and/or at least one tocopherol; b) at least one phospholipid; c) at least one biocompatible, oxygen containing, low viscosity organic solvent; wherein at least one opioid bioactive agent is dissolved or dispersed in the low viscosity mixture and wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with an aqueous fluid. The preformulations are suitable for generating parenteral, non-parenteral and topical depot compositions for sustained release of active agents. The invention additionally relates to a method of delivery of an active agent comprising administration of a preformulation of the invention, a method of treatment comprising administration of a preformulation of the invention and the use of a preformulation of the invention in a method for the manufacture of a medicament.

Abstract: The present invention relates to pre-formulations comprising low viscosity, non-liquid crystalline, mixtures of: a) at least one neutral diacyl lipid and/or at least one tocopherol; b) at least one phospholipid; c) at least one biocompatible, oxygen containing, low viscosity organic solvent; wherein at least one bioactive agent is dissolved or dispersed in the low viscosity mixture and wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with an aqueous fluid. The preformulations are suitable for generating parenteral, non-parenteral and topical depot compositions for sustained release of active agents. The invention additionally relates to a method of delivery of an active agent comprising administration of a preformulation of the invention, a method of treatment comprising administration of a preformulation of the invention and the use of a preformulation of the invention in a method for the manufacture of a medicament.

Abstract: Cannabinoid receptor ligands of formula (I) wherein Ring A and R1 are as defined in the specification. Compositions including such compounds, and methods of treating conditions and disorders using such compounds and compositions are also described.

Abstract: An improved thrombopoietin mimetic, the bis-(monoethanolamine) salt of 3?-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2?-hydroxy-[1,1?-biphenyl]-3-carboxylic acid.

Abstract: The present invention discloses and claims a series of substituted N-phenyl-pyrrolidinylmethylpyrrolidine amides of formula (I). Wherein R, R1, R2, R3 and R4 are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted pyrrolidinylmethylpyrrolidine amides and intermediates therefor.

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.

Abstract: New polymorphs of Eltrombopag and Eltrombopag ethanolamine salt have been obtained and characterized. These polymorphs and pharmaceutical compositions comprising them are useful, for example, in treating conditions leading to thrombocytopenia.

Abstract: This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.

Abstract: The pharmaceutically acceptable salts of bicycle-substituted pyrazolon azo derivatives represented by the general formula (I), their preparation methods, pharmaceutical compositions containing the same and their use as a therapeutic agent, especially as thrombopoietin (TPO) mimetics and their use as agonists of thrombopoietin receptor. The definitions of substituents in the general formula (I) are the same as the description.

Abstract: In one aspect, the invention relates to compounds having the formula: where R1-R6, a, b, 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: A powder-particle dosage form obtained by granulating an excipient and/or a disintegrating agent with a liquid in which a bitter taste masking base is dissolved and/or suspended, and a drug having solubility in water (20° C.) of not higher than 1 g/mL is dissolved or suspended, or a tablet obtained by compressing the powder-particle dosage form could mask bitter taste of a drug.

Abstract: Invented is a method of treating thrombocytopenia in a human in need thereof which comprises the administration of a therapeutically effective amount of a 3?-{N?-[1-(3,4-Dimethylphenyl)-3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene]hydrazino}-2?-hydroxybiphenyl-3-carboxylic acid to such human.

Abstract: Bacterial infections, including Methicillin resistant Staphylococcus aureus (MRSA) infections are a major health problem that has created a pressing need for new antibiotics. Pyridazinone, rhodanine, and pyrazolethione compounds effective inhibit the enzymatic activity of sortase A (srtA) found in gram positive bacteria are disclosed. A structure activity relationship (SAR) analysis led to the identification of several pyridazinone and pyrazolethione analogs that inhibit SrtA with IC50 values in the sub-micromolar range. Compounds that inhibit the S. aureus SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Many of these molecules also inhibit the sortase enzyme from B. anthracis suggesting that they may be generalized sortase inhibitors. The novel compounds, compositions, uses, formulations, medicaments, articles of manufacture provide improved materials, uses, and treatments useful in combating infectious disorders.