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IMIDAZOPYRIDINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY

A series of imidazo[l,2-a]pyridine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

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Thiomorpholine – Wikipedia,
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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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Thiomorpholine – Wikipedia,
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Triazolo[1,5-c]pyrimidines and bronchodilation use thereof

1,2,4-Triazolo[1,5-c]pyrimidines substituted at the 7 position through a nitrogen atom which is part of a 1-oxo- or 1,1-dioxothiomorpholine ring have been found to have potent bronchodilator activity. Pharmacological methods of using these compounds and pharmaceutical compositions containing these compounds are also disclosed.

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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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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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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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Anilinoquinazoline inhibitors of the RET kinase domain – Elaboration of the 7-position

We have previously reported a series of anilinoquinazoline derivatives as potent and selective biochemical inhibitors of the RET kinase domain. However, these derivatives displayed diminished cellular potency. Herein we describe further optimisation of the series through modification of their physicochemical properties, delivering improvements in cell potency. However, whilst cellular selectivity against key targets could be maintained, combining cell potency and acceptable pharmacokinetics proved challenging.

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SOLID FORMS OF 1,L-DIOXO-4-THIOMORPHOLINYL)-[6-[[3(4-FLUOROPHENYL)-5-METHYL-4-ISOXAZOLYL]METHOXY]-3-PYRIDINYL]-METHANONE

The instant invention relates to novel solid forms of the compound of formula (I), as well as solvates, inclusion complexes with other suitable compounds, processes for their manufacture, pharmaceutical compositions containing these solid forms, and their use as medicaments.

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Design, synthesis, and biological activity of pyridopyrimidine scaffolds as novel PI3K/mTOR dual inhibitors

The design, synthesis, and screening of dual PI3K/mTOR inhibitors that gave nanomolar enzymatic and cellular activities on both targets with an acceptable kinase selectivity profile are described. A docking study was performed to understand the binding mode of the compounds and to explain the differences in biological activity. In addition, cellular effects of the best dual inhibitors were determined on six cancer cell lines and compared to those on a healthy diploid cell line for cellular cytotoxicity. Two compounds are highly potent on cancer cells in the submicromolar range without any toxicity on healthy cells. A more detailed analysis of the cellular effect of these PI3K/mTOR dual inhibitors demonstrated that they induce G1-phase cell cycle arrest in breast cancer cells and trigger apoptosis. These compounds show an interesting kinase profile as dual PI3K/mTOR tool compounds or as a chemical series for further optimization to progress into in vivo experiments.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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PROCESS FOR THE PREPARATION OF ISOXAZOLYL- METHOXY NICOTINIC ACIDS

The present invention relates to a process for the preparation of a compound of formula (I) wherein R1 and R2 are as defined herein, which is useful as an intermediate in the preparation of active pharmaceutical compounds.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem