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INDAZOLE-CARBOXAMIDE COMPOUNDS

The invention provides novel indazole-carboxamide 5-HT4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds.

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JAK kinase inhibitors and uses thereof (by machine translation)

The invention discloses a having the following general formula (I) compound. The invention also disclosed comprising this compound JAK kinase inhibitor and the compounds in the preparation of the treatment in the JAK related diseases of the application. JAK kinase inhibitors of the present invention, can inhibit the signal transduction of the involved in various JAK1, JAK2, JAK3 and TYK2 kinase biological activity, can effectively clinical treatment of various inflammatory diseases and JAK-mediated signal transduction by the driving of various diseases, very broad application prospects. . (by machine translation)

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Indole and indazole compounds as an inhibitor of cellular necrosis

The present invention refers to a formula (1) compounds of, pharmaceutically acceptable salts or isomers thereof thereof, and characterized by by containing as active ingredients-associated diseases, cell death and method for the prevention or treatment of relates and compositions. [Formula 1] In formula said R 1, R 2, R 3, R 4, R 5, R 6, A, X, n and m to equal the specification. (by machine translation)

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Synthesis and characterization of 8-ethynyl-1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives: New potent non-competitive metabotropic glutamate receptor 2/3 antagonists. Part 1

A series of 1,3-dihydrobenzo[b][1,4]diazepin-2-one derivatives was evaluated as non-competitive mGluR2/3 antagonists. Attachment of an 8-(2-aryl)-ethynyl-moiety produced compounds inhibiting the binding of [3H]-LY354740 to rat mGluR2 with low nanomolar affinity and consistent functional effect at both mGluR2 and mGluR3.

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BROAD SPECTRUM ANTIVIRAL COMPOSITIONS AND METHODS

Novel thiazole- and isoquinoline- containing compounds are presented that are useful for treating and/or preventing broad-spectrum viral infections. Methods of treating and/or preventing broad-specturm viral infections are also presented. These compounds have shown inhibitio of HCMV, influenza viruses, Zika virus, BK Virus and RSV replication in cell-based assays.

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QUINOLINONE-CARBOXAMIDE COMPOUNDS

The invention provides novel quinolinone-carboxamide 5-HT4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds.

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3-(4-amidopyrrol-2-ylmethylidene)-2-indolinone derivatives as portein kinase inhibitors

The present invention relates to pyrrole substituted 2-indolinone compounds and their pharmaceutically acceptable salts which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.

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6,7-Dimethoxy-2-(4-thiomorpholinyl)-4-quinazolinamine and related sulfoxide and sulfone

Disclosed are a series of quinazoline derivatives which have activity as hypotensive agents.

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Novel sulfamoyl benzamides as selective CB2 agonists with improved in vitro metabolic stability

A lead optimization campaign in our previously reported sulfamoyl benzamide class of CB2 agonists was conducted to improve the in vitro metabolic stability profile in this series while retaining high potency and selectivity for the CB2 receptor. From this study, compound 14, N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide, was identified as a potent and selective CB2 agonist exhibiting moderate in vitro metabolic stability and oral bioavailability. Compound 14 demonstrated in vivo efficacy in a rat model of post-surgical pain.

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The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy

RPR132331, a 2-(2-dioxanyl)imidazole, was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNFalpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb/c mice (ED50 = 6 mg/kg). At oral doses between 10 and 30 mg/kg/day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens. The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability. The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies.

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