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IMIDAZOPYRIDAZINE DERIVATIVES AS RhoIota3Kappabeta INHIBITORS

The present invention relates to substituted imidazopyridazine derivatives of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as pIota3Kappabeta inhibitors. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Mitigation of cardiovascular toxicity in a series of CSF-1R inhibitors, and the identification of AZD7507

The potent and selective 3-amido-4-anilinoquinoline CSF-1R inhibitor AZ683 suffered from cardiovascular liabilities, which were linked to the off-target activities of the compound and ion channel activity in particular. Less basic and less lipophilic examples from both the quinoline and cinnoline series demonstrated cleaner secondary pharmacology profiles. Cinnoline 31 retained the required potency and oral PK profile, and was progressed through the safety screening cascade to be nominated into development as AZD7507.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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Structure-kinetic relationship studies of cannabinoid CB2 receptor agonists reveal substituent-specific lipophilic effects on residence time

A decade ago, the drug-target residence time model has been (re-)introduced, which describes the importance of binding kinetics of ligands on their protein targets. Since then, it has been applied successfully for multiple protein targets, including GPCRs, for the development of lead compounds with slow dissociation kinetics (i.e. long target residence time) to increase in vivo efficacy or with short residence time to prevent on-target associated side effects. To date, this model has not been applied in the design and pharmacological evaluation of novel selective ligands for the cannabinoid CB2 receptor (CB2R), a GPCR with therapeutic potential in the treatment of tissue injury and inflammatory diseases. Here, we have investigated the relationships between physicochemical properties, binding kinetics and functional activity in two different signal transduction pathways, G protein activation and beta-arrestin recruitment. We synthesized 24 analogues of 3-cyclopropyl-1-(4-(6-((1,1-dioxidothiomorpholino)methyl)-5-fluoropyridin-2-yl)benzyl)imidazoleidine-2,4-dione (LEI101), our previously reported in vivo active and CB2R-selective agonist, with varying basicity and lipophilicity. We identified a positive correlation between target residence time and functional potency due to an increase in lipophilicity on the alkyl substituents, which was not the case for the amine substituents. Basicity of the agonists did not show a relationship with affinity, residence time or functional activity. Our findings provide important insights about the effects of physicochemical properties of the specific substituents of this scaffold on the binding kinetics of agonists and their CB2R pharmacology. This work therefore shows how CB2R agonists can be designed to have optimal kinetic profiles, which could aid the lead optimization process in drug discovery for the study or treatment of inflammatory diseases.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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In heterogeneous catalysis, the catalyst is in a different phase from the reactants. category: Thiomorpholine, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 114525-81-4, name is (R)-4-(tert-Butoxycarbonyl)thiomorpholine-3-carboxylic acid. In an article£¬Which mentioned a new discovery about 114525-81-4

Heterocyclic core analogs of a direct thrombin inhibitor

Thrombin is a serine protease that plays a key role in blood clotting. Pyrrolidine 1 is a potent thrombin inhibitor discovered at Merck several years ago. Seven analogs (2-8) of 1 in which the pyrrolidine core was replaced with various heterocycles were prepared and evaluated for activity against thrombin, clotting factors VIIa, IXa, Xa, and XIIa, and trypsin. The thiomorpholine analog 6 was the most active, essentially matching the thrombin inhibitory activity of 1 with slightly improved selectivity over trypsin.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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NITROGEN-CONTAINING FIVE-MEMBERED HETEROCYCLIC COMPOUND

The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof. The compound of the present invention has a glucokinase activity, and is useful as a medicament such as an agent for the prophylaxis or treatment of diabetes, obesity and the like, and the like.

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Investigation of flexibility of neuraminidase 150-loop using tamiflu derivatives in influenza A viruses H1N1 and H5N1

This study focuses on design, synthesis and in vitro evaluation of inhibitory potency of two series of sialylmimetic that target an exosite (?150-cavity?) adjacent to the active site of influenza neuraminidases from A/California/07/2009 (H1N1) pandemic strain and A/chicken/Nakorn-Patom/Thailand/CU-K2-2004 (H5N1). The structure-activity analysis as well as 3-D structure of the complex of parental compound with the pandemic neuraminidase p09N1 revealed high flexibility of the 150-cavity towards various modification of the neuraminidase inhibitors. Furthermore, our comparison of two methods for inhibition constant determination performed at slightly different pH values suggest that the experimental conditions of the measurement could dramatically influence the outcome of the analysis in the compound-dependent manner. Therefore, previously reported Ki values determined at non-physiological pH should be carefully scrutinized.

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One of the major reasons for studying chemical kinetics is to use measurements of the macroscopic properties of a system, Quality Control of Thiomorpholine 1,1-dioxide, such as the rate of change in the concentration of reactants or products with time.In a article, mentioned the application of 39093-93-1, Name is Thiomorpholine 1,1-dioxide, molecular formula is C4H9NO2S

Special ergolines efficiently inhibit the chemokine receptor CXCR3 in blood

The structure-activity relationship of highly potent special ergolines which selectively block the chemokine receptor CXCR3 is reported. The most potent compounds showed IC50 values below 10 nM in both ligand binding and Ca2+-mobilization assays. However, these compounds were poorly active in an assay that measures receptor occupancy in blood. Introduction of polar substituents led to derivatives with IC50 values below 10 nM in this assay. Among them was compound 11a which showed both a favorable PK profile and cross reactivity with rodent CXCR3 making it a promising tool compound to further explore the role of CXCR3 in animal models.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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RORGAMMA MODULATORS AND USES THEREOF

The present invention provides novel compounds of formula (la) that are modulators of RORgamma. These compounds, and pharmaceutical compositions comprising the same, are suitable means for treating any disease wherein the modulation of RORgamma has therapeutic effects, for instance in autoimmune diseases, autoimmune-related diseases, inflammatory diseases, metabolic diseases, fibrotic diseases, or cholestatic diseases.

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Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem

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PIPERAZINYL PYRIMIDINE DERIVATIVES, PREPARATION METHOD AND USE THEREOF

Provided are piperazinyl pyrimidine derivatives of formula I having CCR4 antagonism, and the preparation method, pharmaceutical composition and use thereof in the preparation of a medicament. The medicament is useful for the treatment and prevention of CCR4-related diseases.

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Thiomorpholine – Wikipedia,
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HETEROCYCLIC COMPOUNDS WHICH MODULATE THE CB2 RECEPTOR

Compounds which modulate the CB2 receptor are disclosed. Compounds according to the invention bind to and are agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.

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Thiomorpholine – Wikipedia,
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