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A BRD4 inhibitors (by machine translation)

The invention of the formula I indicated by the BRD4 inhibitors, which belongs to the technical field of pharmaceutical compounds. The present invention provides the compounds of prostate cancer cell proliferation has very good inhibition action, the compounds of the invention can be used for the preparation of anti-tumor, autoimmune or inflammatory disease, virus infection, especially anti-prostate cancer drug. (by machine translation)

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Indazole derivatives for use in the treatment of influenza virus infection

The present invention is directed to compounds for use in the treatment or prevention of influenza virus infection.

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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 39093-93-1, name is Thiomorpholine 1,1-dioxide, introducing its new discovery. HPLC of Formula: C4H9NO2S

TETRAHYDROPYRAN DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS

The present invention relates compounds of the formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R15 and R16 represent a variety of substituents; and pharmaceutically acceptable salts thereof. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migaine, emesis or postherpetic neuralgia.

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Triazolopyridines as selective JAK1 inhibitors: From hit identification to GLPG0634

Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified JAK1 as a possible new target for arthritis at Galapagos, the compound library was screened against JAK1, resulting in the identification of a triazolopyridine-based series of inhibitors represented by 3. Optimization within this chemical series led to identification of GLPG0634 (65, filgotinib), a selective JAK1 inhibitor currently in phase 2B development for RA and phase 2A development for Crohn’s disease (CD).

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Parallel synthesis and structure-activity relationships of a series of highly potent, selective, and neutral factor Xa inhibitors

Parallel synthesis and iterative optimization led to the discovery of a series of potent and specific factor Xa inhibitors demonstrating excellent in vitro activity with promising pharmacokinetics.

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I hope this article can help some friends in scientific research. I am very proud of our efforts over the past few months and hope to 39093-93-1, help many people in the next few years.Computed Properties of C4H9NO2S

In heterogeneous catalysis, the catalyst is in a different phase from the reactants. Computed Properties of C4H9NO2S, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 39093-93-1, name is Thiomorpholine 1,1-dioxide. In an article£¬Which mentioned a new discovery about 39093-93-1

Concerning the Reactivity of Unsubstituted and Alkyl Substituted Thiomorpholines, 5. On the Joint Action of Elementary Sulfur and Gaseous Ammonia on Ketones, 95

The syntheses of 4-amino-thiomorpholine-1,1-dioxide (12) and 4-hydroxy-thiomorpholine-1,1-dioxide (11) from 1,4-thioxane-1,1-dioxide (1) by pressureless reaction of 1 with hydrazine hydrate and hydroxylamine, resp. is described.In analogy various other N-substituted thiomorpholine-1,1-dioxides are obtained with prim. amines (2-8) and diamines (9,10). 12 condensates with aldehydes (14-24) and ketones (25-29); reaction of 12 with 1 gives N,N’-dithiomorpholine-1,1-dioxide (13).Acylation of 12 with monochlorides (30-35), dichlorides of dicarboxylic acids (36-40) and carbo xylic acid anhydrides (41-43) proceeds smoothly.Compounds 38-43 are cyclic imides.Isocyanates give with 12 the expected compounds 45-48. 12 reacts with chlorinated 1,3,5-triazines to compounds which can be purified only with difficulty (49-51).Quaternization of the N-substituted thiomorpholine-1,1-dioxides with benzylbromide (52,53) and methyliodide (54,55) is possible.Ethylenbromide reacts with 9 to give the bis quaternization product 56.Further reactions of thiomorpholine-1,1-dioxide (57) with sulfuryl chloride (58), bromo cyanide (59), allylic chloride (60), chloro acetonitrile (61) and trityl chloride (62) are described. 11 reacts with carboxylic acid chlorides (63-65) and iso-cyanates (66-70) to yield the expected compounds.Propylene oxide gives with 12 the addition product 71; sulfur dioxide is added to 11 to thiomorpholine-1,1-dioxide sulfonic acid (72). – Keywords: 4-Aminothiomorpholine-1,1-dioxide; 4-Hydroxy-thiomorpholine-1,1-dioxide; Reactivity; Synthesis.

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Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD)

Discovery of a new class of DFG-out p38alpha kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the alphaC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38alpha IC50 = 22 nM) and highly selective (?150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.

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FUSED RING PYRIDINE COMPOUND

[Problem] To provide a compound useful as a novel agent which is excellent in preventing and/or treating cannabinoid receptor type 2-related diseases, based on agonist action on a cannabinoid receptor type 2 [Means for Solution] The present inventors conducted thorough investigation regarding compounds having agonist action on a cannabinoid receptor type 2. They confirmed that the fused ring pyridine compound of the present invention has excellent agonist action on the cannabinoid receptor type 2, thereby completing the present invention. The fused ring pyridine compound of the present invention has agonist action on the cannabinoid receptor type 2, and can be used as an agent for preventing and/or treating cannabinoid receptor type 2-related diseases, for example, inflammatory diseases and pain.

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3-((R)-4-(((R)-6-(2-Bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholin-2-yl)propanoic Acid (HEC72702), a Novel Hepatitis B Virus Capsid Inhibitor Based on Clinical Candidate GLS4

The inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. On the basis of the preclinical properties and clinical results of GLS4, we carried out further investigation to seek a better candidate compound with appropriate anti-HBV potency, reduced hERG activity, decreased CYP enzyme induction, and improved pharmacokinetic (PK) properties. To this end, we have successfully found that morpholine carboxyl analogues with comparable anti-HBV activities to that of GLS4 showed decreased hERG activities, but they displayed strong CYP3A4 induction in a concentration-dependent manner, except for morpholine propionic acid analogues. After several rounds of modification, compound 58 (HEC72702), which had an (R)-morpholine-2-propionic acid at the C6 position of its dihydropyrimidine core ring, was found to display no induction of the CYP1A2, CYP3A4, or CYP2B6 enzyme at the high concentration of 10 muM. In particular, it demonstrated a good systemic exposure and high oral bioavailability and achieved a viral-load reduction greater than 2 log in a hydrodynamic-injected (HDI) HBV mouse model and has now been selected for further development.

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Design, synthesis and biological evaluation of novel 6-alkenylamides substituted of 4-anilinothieno[2,3-d]pyrimidines as irreversible epidermal growth factor receptor inhibitors

A novel series of 6-alkenylamides of 4-anilinothieno[2,3-d]pyrimidine derivatives was designed, synthesized and evaluated as irreversible inhibitors of the epidermal growth factor receptor (EGFR). Most of the compounds exhibited good potency against EGFR wild type (EGFR wt) and EGFR T790M/L858R. Among these, the half-maximal inhibitory concentration (IC50) values of 17 compounds against EGFR wt were less than 0.020 muM, and those of 12 compounds were less than 0.010 muM. The IC50 values of 10 compounds against EGFR T790M/L858R were less than 0.005 muM. Compounds 8l, 9n, 9o, 9q and 9v almost completely blocked the phosphorylation of EGFR in the A431 cell line at 1 muM. Compounds 8l, 9n, 9o, 9q and 9v blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (1 muM), and compound 8l was confirmed to be an irreversible inhibitor through the dilution method.

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