Category: 39093-93-1

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Potent inhibitors of subgenomic hepatitis C virus RNA replication through optimization of indole-N-acetamide allosteric inhibitors of the viral NS5B polymerase

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. Compounds that block replication of subgenomic HCV RNA in liver cells are of interest because of their demonstrated antiviral effect in the clinic. In followup to our recent report that indole-N-acetamides (e.g., 1) are potent allosteric inhibitors of the HCV NS5B polymerase enzyme, we describe here their optimization as cell-based inhibitors. The crystal structure of 1 bound to NS5B was a guide in the design of a two-dimensional compound array that highlighted that formally zwitterionic inhibitors have strong intracellular potency and that pregnane X receptor (PXR) activation (an undesired off-target activity) is linked to a structural feature of the inhibitor. Optimized analogues devoid of PXR activation (e.g., 55, EC50 = 127 nM) retain strong cell-based efficacy under high serum conditions and show acceptable pharmacokinetics parameters in rat and dog.

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Thiomorpholine | C4H9NS – PubChem

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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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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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CHEMICAL COMPOUNDS-821

The invention relates to chemical compounds of the formula (I), or pharmaceutically acceptable salts thereof, which possess ALK5 (TGFbetaR1) inhibitory activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an anti-cancer effect in a warm-blooded animal such as man

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Process for preparing 10alpha-[4′-(S,S-dioxothiomorpholin-1′-yl)]-10-deoxo-10-dihydroartemisinin

A novel one-stage process for preparing 10alpha-[4?-(S,S-dioxothiomorpholin-1?-yl)]-10-deoxo-10-dihydroartemisinin (1a) by reacting a compound of the formula (1b) in which X is a halogen atom with thiomorpholine dioxide at a temperature in the range of ?30 C. to +20 C. is provided.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

Application of 39093-93-1, A catalyst don’t appear in the overall stoichiometry of the reaction it catalyzes, but it must appear in at least one of the elementary reactions in the mechanism for the catalyzed reaction. 39093-93-1, Name is Thiomorpholine 1,1-dioxide, molecular formula is C4H9NO2S. In a Patent£¬once mentioned of 39093-93-1

5-HT4 RECEPTOR AGONIST 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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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

In heterogeneous catalysis, the catalyst is in a different phase from the reactants. Recommanded Product: Thiomorpholine 1,1-dioxide, 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

4-Anilino-7-pyridyl-3-quinolinecarbonitriles as Src kinase inhibitors

A series of 4-anilino-7-pyridyl-3-quinolinecarbonitriles was prepared as Src kinase inhibitors. A systematic SAR study of substitutions on both the pyridine ring and the 3-quinolinecarbonitrile core established the requirements for optimal activity. The lead compound, 17, showed potent activity in both the Src enzyme assay and cell assays, and demonstrated in vivo anti-tumor activity in a xenograft model.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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SGC STIMULATORS

The present patent application discloses at least the compounds according to Formula 1 shown below, or pharmaceutically acceptable salts thereof, wherein ringjB,n, JD, J,0, X, X1, J, RC, and W are as defined herein. These compounds are useful as simulators of soluble sGC.

We¡¯ll also look at important developments in the pharmaceutical industry because understanding organic chemistry is important in understanding health, medicine, the role of 39093-93-1, and how the biochemistry of the body works.Application of 39093-93-1

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Discovery and Development of N-[4-(1-Cyclobutylpiperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide Dihydrochloride (SUVN-G3031): A Novel, Potent, Selective, and Orally Active Histamine H3 Receptor Inverse Agonist with Robust Wake-Promoting Activity

A series of chemical optimizations guided by in vitro affinity at a histamine H3 receptor (H3R), physicochemical properties, and pharmacokinetics in rats resulted in identification of N-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide dihydrochloride (17v, SUVN-G3031) as a clinical candidate. Compound 17v is a potent (hH3R Ki = 8.73 nM) inverse agonist at H3R with selectivity over other 70 targets, Compound 17v has adequate oral exposures and favorable elimination half-lives both in rats and dogs. It demonstrated high receptor occupancy and marked wake-promoting effects with decreased rapid-eye-movement sleep in orexin-B saporin lesioned rats supporting its potential therapeutic utility in treating human sleep disorders. It had no effect on the locomotor activity at doses several fold higher than its efficacious dose. It is devoid of hERG and phospholipidosis issues. Phase-1 evaluation for safety, tolerability, and pharmacokinetics, and long-term safety studies in animals have been successfully completed without any concern for further development.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Arylsulfonamide CB2 receptor agonists: SAR and optimization of CB2 selectivity

A high-throughput screening campaign resulted in the discovery of a highly potent dual cannabinoid receptor 1 (CB1) and 2 (CB2) agonist. Following a thorough SAR exploration, a series of selective CB2 full agonists were identified.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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[1, 2, 4] Triazolo [1, 5 – a] pyridine compound and its preparation method and medical use (by machine translation)

The present invention relates to [1, 2, 4] triazolo [1, 5 – a] pyridine compound and its preparation method and medical use. In particular, the invention relates to compounds of the general formula I shown, its preparation method and containing pharmaceutical compositions of the compounds, and their use as JAK kinase inhibitors, the compound and its containing pharmaceutical compositions of the compounds can be used for treating diseases associated with JAK kinase activity, such as inflammation, autoimmune disorders, such as cancer. Wherein the general formula I in the definition of each substituent as defined in the specification. (by machine translation)

A reaction mechanism is the microscopic path by which reactants are transformed into products. Each step is an elementary reaction. In my other articles, you can also check out more blogs about 39093-93-1

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem