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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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Reference£º
Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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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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Reference£º
Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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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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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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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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Thiomorpholine – Wikipedia,
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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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Morpholylureas are a new class of potent and selective inhibitors of the type 5 17-beta-hydroxysteroid dehydrogenase (AKR1C3)

Inhibitors of the aldo-keto reductase enzyme AKR1C3 are of interest as potential drugs for leukemia and hormone-related cancers A series of non-carboxylate morpholino(phenylpiperazin-1-yl)methanones were prepared by palladium-catalysed coupling of substituted phenyl or pyridyl bromides with the known morpholino(piperazin-1-yl)methanone, and shown to be potent (IC 50 ? 100 nM) and very isoform-selective inhibitors of AKR1C3 Lipophilic electron-withdrawing substituents on the phenyl ring were positive for activity, as was an H-bond acceptor on the other terminal ring, and the ketone moiety (as a urea) was essential These structure-activity relationships are consistent with an X-ray structure of a representative compound bound in the AKR1C3 active site, which showed H-bonding between the carbonyl oxygen of the drug and Tyr55 and His117 in the ‘oxyanion hole’ of the enzyme, with the piperazine bridging unit providing the correct twist to allow the terminal benzene ring to occupy the lipophilic pocket and align with Phe311

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OXADIAZOLE DERIVATIVES WITH CRTH2 RECEPTOR ACTIVITY

Compounds of formula (I) are CRTH2 ligands, useful for treatment of inflammatory, autoimmune, respiratory or allergy disease: wherein R1 is hydrogen or methyl and R2 is optionally substituted cycloalkyl, or optionally substituted non-aromatic heterocyclyl having 4 to 6 ring atoms; or R1 and R2, taken together with the carbon atom to which they are attached form an optionally substituted cycloalkyl, or optionally substituted non-aromatic heterocyclyl ring having 4 to 6 ring atoms; R is hydrogen or an optional substituent; the phenyl ring containing the substituent R is optionally substituted by 1 , 2 or 3 optional substituents; A is hydrogen or C1-C3 alkyl; and ring Ar is an optionally substituted phenyl or 5- or 6- membered monocyclic heteroaryl ring.

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Thiomorpholine – Wikipedia,
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FLUORINE-SUBSTITUTED INDAZOLE COMPOUNDS AND USES THEREOF

Fluorine-substituted indazole compounds, pharmaceutical compositions containing these compounds and uses thereof. The compounds and pharmaceutical compositions can be used as soluble guanylate cyclase simulators.

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Thiomorpholine – Wikipedia,
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