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AMINOTRIAZOLOPYRIDINE FOR USE IN THE TREATMENT OF INFLAMMATION, AND PHARMACEUTICAL COMPOSITIONS THEREOF

The present invention relates to the novel medical use of the compound according to Formula I, in particular in the treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons. In particular, the compound inhibits JAK a family of tyrosine kinases, and more particularly JAK1. The present invention also provides pharmaceutical compositions comprising the compound, methods for the prophylaxis and/or treatment of diseases involving inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons by administering the compound.

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PROCESS FOR PREPARATION OF PYRIDINE DERIVATIVES

The present invention relates to a process for the manufacture of compounds of formula wherein the substituents are as described herein which comprises the steps of a) reacting a compound of formula with a compound of formula to form a compound of formula b) converting the OH/=O function of compounds of formula XIV/XIVa into a leaving group P with a reagent containing a leaving group, selected from POCl3, PBr3, MeI and (F 3CSO2)2O to form a compound of formula wherein P is halogen or trifluoromethanesulfonate; c) substituting R2 for the leaving group P by reacting compound XV with HR2 to form a compound of formula and d) hydrolyzing the nitrile function in an acidic medium selected from H2SO4, HCl and acetic acid, to form a compound of formula I The compounds of formula I are valuable intermediates for the manufacture of therapeutically active compounds which have NK-1 antagonist activity.

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SUBSTITUTED PYRAZOLO[3,4-b]PYRIDIN-6-CARBOXYLIC ACIDS AND METHOD OF USE

The present invention provides for compounds of formula (I) wherein R1, R2, R3, and R4 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by CFTR, including cystic fibrosis, Sjoegren’s syndrome, pancreatic insufficiency, chronic obstructive lung disease, and chronic obstructive airway disease. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

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GLYCINE COMPOUND

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that a compound of the present invention or a salt thereof exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. The present invention further relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound of the present invention or a salt thereof, and an excipient.

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Extended knowledge of 39093-93-1

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PIPERIDINE DERIVATIVES AS NK3 RECEPTOR ANTAGONISTS

The present application relates to compounds of formula (I) wherein the definitions are as described in claim 1. It has been found that the present compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson’s disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

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1,3,4-OXADIAZOLE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

The present invention relates to novel compounds having a histone deacetylase 6 (HDAC6) inhibitory activity, optical isomers thereof or pharmaceutically acceptable salts thereof, a pharmaceutical use thereof, and a method for preparing the same. According to the present invention, the novel compounds, optical isomers thereof or pharmaceutically acceptable salts thereof have the histone deacetylase 6 (HDAC6) inhibitory activity, and are effective in preventing or treating HDAC6-related diseases, comprising infectious diseases; neoplasm; internal secretion; nutritional and metabolic diseases; mental and behavioral disorders; neurological diseases; eye and ocular adnexal diseases; circulatory diseases; respiratory diseases; digestive diseases; skin and subcutaneous tissue diseases; musculoskeletal system and connective tissue diseases; and teratosis or deformities, and chromosomal aberration.

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TETRAHYDROQUINOXALINE UREA DERIVATIVES, PREPARATION THEREOF, AND THERAPEUTIC USE THEREOF

The invention relates to compounds of formula (I), where: A is a bond, an oxygen, or an ?CH2? group; Ar1 is a phenyl or heteroaryl group; Ar2 is a phenyl, heteroaryl, or heterocycloalkyl group; R1a,b,c and R2a,b,c are hydrogen or halogen, or an alkyl, cycloalkyl, or lkyl-cycloalkyl group optionally, substituted by one or more halogen atoms, or a ?OR5 (hydroxy or alkoxy), hydroxy-alkyl, alkoxy-alkyl, alkoxy-alkoxy, halogenoalkyl, ?O-halogenoalkyl, oxo, ?CO-alkyl, ?CO-alkyl-NR6R7, ?CO-halogenoalkyl, ?COOR5, alkyl-COOR5, ?O-alkyl-COOR5, ?SO2-alkyl, ?SO2-cycloalkyl, ?SO2-alkyl-cycloalkyl, ?SO2-alkyl-OR5, ?SO2-alkyl-COOR5, ?SO2-alkyl-NR6R7, ?SO2-halogenoalkyl, alkyl-SO2-alkyl, ?SO2?NR6R7, ?SO2-alkyl-O-alkyl-OR5, ?CONR6R7, -alkyl-CONR6R7, or -alkyl-NR6R7 group, or further R1a, R1b, and R1c are bonded to R2a, R2b, R2c, respectively, and to the carbon atom having same, and are -alkyl-O?; R3 is a hydrogen atom or an alkyl group; R4 is a hydrogen or halogen atom or a cyano, ?OR5, hydroxyalkyl, ?COOR5, ?NR6R7, ONR6R7, ?SO2-alkyl, SO2?NR6R7, ?NR6?COOR5, ?NR6?COR5, or ?CO?NR6-alkyl-OR5 group; R5, R6, and R7 are a hydrogen, or an alkyl or alkyl-phenyl group; and R8 is an alkyl, alkyl-Si(alkyl)3, ?SO2-alkyl-Si(alkyl)3, phenyl, alkoxy-imino group, or alkyl-cycloalkyl group optionally substituted by one or more halogen atoms or one or more hydroxyl or hydroxyl-alkyl groups; or R8 and R9, together with the carbon atoms to which they are bonded, form a cycloalkyl group optionally substituted by one or more halogen atoms or one or more carboxy groups; and R9 is a hydrogen atom or an alkyl group; with the proviso that, when R8 is an alkyl group, it is bonded onto the Ar2 silicon atom. The invention also relates to a method for preparing same and to the therapeutic use thereof.

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PYRROLOPYRIDAZINE DERIVATIVES

The invention relates to compound of the formula (I) or its salt, in which R1, R2, R3 and R4 are as defined in the description, their use of as medicament, the process for their preparation and use for the treatment of PDE-IV or TNF-alpha mediated diseases.

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COMPOUNDS AND COMPOSITIONS AS SYK KINASE INHIBITORS

Provided here in area novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated Syk kinase activity

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Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP

Among epigenetic “writers”, “readers”, and “erasers”, the lysine methyltransferases G9a and GLP, which catalyze mono- and dimethylation of histone H3 lysine 9 (H3K9me2) and nonhistone proteins, have been implicated in a variety of human diseases. A “toolkit” of well-characterized chemical probes will allow biological and disease hypotheses concerning these proteins to be tested in cell-based and animal models with high confidence. We previously discovered potent and selective G9a/GLP inhibitors including the cellular chemical probe UNC0638, which displays an excellent separation of functional potency and cell toxicity. However, this inhibitor is not suitable for animal studies due to its poor pharmacokinetic (PK) properties. Here, we report the discovery of the first G9a and GLP in vivo chemical probe UNC0642, which not only maintains high in vitro and cellular potency, low cell toxicity, and excellent selectivity, but also displays improved in vivo PK properties, making it suitable for animal studies.

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