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COMPOUNDS, DEVICES, AND USES THEREOF

The present invention provides compounds, e.g., compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are implantable elements (e.g., devices and materials) comprising the same, as well as methods of use thereof, e.g., for treating or preventing a disease, disorder, or condition.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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CINNAMIC ACID AMIDE DERIVATIVE

The present invention provides a cinnamic acid amide derivative having an excellent analgesic action. The cinnamic acid amide derivative of the present invention is a compound showing excellent analgesic actions to not only a nociceptive pain model animal but also a neuropathic pain model animal, which is very useful as an agent for treating various pain diseases showing acute or chronic pains or neuropathic pains.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Fenretinide derivatives act as disrupters of interactions of serum retinol binding protein (sRBP) with transthyretin and the sRBP receptor

Serum retinol binding protein (sRBP) is released from the liver as a complex with transthyretin (TTR), a process under the control of dietary retinol. Elevated levels of sRBP may be involved in inhibiting cellular responses to insulin and in generating first insulin resistance and then type 2 diabetes, offering a new target for therapeutic attack for these conditions. A series of retinoid analogues were synthesized and examined for their binding to sRBP and their ability to disrupt the sRBP-TTR and sRBP-sRBP receptor interactions. A number inhibit the sRBP-TTR and sRBP-sRBP receptor interactions as well as or better than Fenretinide (FEN), presenting a potential novel dual mechanism of action and perhaps offering a new therapeutic intervention against type 2 diabetes and its development. Shortening the chain length of the FEN derivative substantially abolished binding to sRBP, indicating that the strength of the interaction lies in the polyene chain region. Differences in potency against the sRBP-TTR and sRBP-sRBP receptor interactions suggest variant effects of the compounds on the two loops of sRBP guarding the entrance of the binding pocket that are responsible for these two protein-protein interactions.

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

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Discovery of novel urea-based hepatitis C protease inhibitors with high potency against protease-inhibitor-resistant mutants

The macrocyclic urea 2, a byproduct in the synthesis of benzoxaborole 1, was identified to be a novel and potent HCV protease inhibitor. We further explored this motif by synthesizing additional urea-based inhibitors and by characterizing them in replicase HCV protease-resistant mutants assay. Several compounds, exemplified by 12, were found to be more potent in HCV replicon assays than leading second generation inhibitors such as danoprevir and TMC-435350. Additionally, following oral administration, inhibitor 12 was found in rat liver in significantly higher concentrations than those reported for both danoprevir and TMC-435350, suggesting that inhibitor 12 has the combination of anti-HCV and pharmacokinetic properties that warrants further development of this series.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists-Increasing selectivity over hERG

A direct correlation between hERG binding and QTc prolongation was established for a series of aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists. Compounds within this class with greater selectivity over hERG were developed. Compound 4h proved to have the best profile, with MCH-R1 Ki = 16 nm and hERG IC50 = 25 muM.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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INDAZOLE-CARBOXAMIDE COMPOUNDS AS 5-HT4 RECEPTOR AGONISTS

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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Reference£º
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

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

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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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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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