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Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5)

Bile acid signaling and metabolism in the gastrointestinal tract have wide-ranging influences on systemic disease. G protein-coupled bile acid receptor 1 (GPBAR1, TGR5) is one of the major effectors in bile acid sensing, with demonstrated influence on metabolic, inflammatory, and proliferative processes. The pharmacologic utility of TGR5 agonists has been limited by systemic target-related effects such as excessive gallbladder filling and blockade of gallbladder emptying. Gut-restricted TGR5 agonists, however, have the potential to avoid these side effects and consequently be developed into drugs with acceptable safety profiles. We describe the discovery and optimization of a series of gut-restricted TGR5 agonists that elicit a potent response in mice, with minimal gallbladder-related effects. The series includes 12 (TGR5 EC50: human, 143 nM; mouse, 1.2 nM), a compound with minimal systemic availability that may have therapeutic value to patients with type 2 diabetes mellitus, nonalcoholic steatohepatitis, or inflammatory bowel disease.

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Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem

 

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An efficient synthesis of benzene fused six-, seven- and eight-membered rings containing nitrogen and sulfur by benzyne ring closure reaction

3,4-Dihydro-2-H-benzo[1,4]thiazines (3a-c), 2,3,4,5-tetrahydro[b]-[1,4] thiazapines (3d-f) and 2,3,4,5-tetrahydro-2H-benzo[b][1,4]thiazocines (3g-i) were prepared by the cyclization of the respective 2-bromophenylsulfanyl derivatives of ethylamine (1a-c), propylamine (2d-f) and butylamine (2g-i).

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Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem

 

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Scandium-Catalyzed para-Selective Alkylation of Aromatic Amines with Alkenes

An efficient para-alkylation of primary and secondary anilines with a variety of sterically encumbered alkenes using a simple beta-diketiminato scandium catalyst is reported. This protocol features 100% atom economy, excellent chemo- and regioselectivity, broad substrate scope, and good functional group tolerance. Mechanistic studies disclosed that the reaction probably proceeded via a tandem hydroamination/Hofmann-Martius rearrangement.

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Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem

 

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Production Method of Nitrogen-Containing Fused Ring Compounds

[Problems] The present invention provides a superior production method and a superior purification method of compounds effective for the treatment or prophylaxis of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like. [Means] A compound represented by the following formula [2] or a pharmaceutically acceptable salt thereof can be produced by reacting a compound represented by the following formula [3] or a salt thereof with a compound represented by the following formula [4], a salt thereof or a reactive derivative thereof. Moreover, crystallization of a compound represented by the formula [2] can be performed with industrially superior workability, and high quality crystals of a compound represented by the formula [2] can be obtained. wherein each symbol is as defined in the description.

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Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem

 

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INHIBITORS OF CYCLIN DEPENDNT KINASE 7 (CDK7)

The present invention provides novel compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

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Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem

 

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Barbituric acid derivatives as inhibitors of TNF-alpha converting enzyme (TACE) and/or matrix metalloproteinases

The present application describes novel barbituric acid derivatives of formula I: 1or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, B, L, R1, R2, R3, R4, R5, n, W, U, X, Y, Z, Ua, Xa, Ya, and Za are defined in the present specification, which are useful as TNF-alpha converting enzyme (TACE) and matrix metalloproteinases (MMP) inhibitors.

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Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem

 

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Sodium Triethylborohydride-Catalyzed Controlled Reduction of Unactivated Amides to Secondary or Tertiary Amines

The first transition-metal-free catalytic protocol for controlled reduction of amide functions using cheap and bench-stable hydrosilanes as reducing agents has been established. By altering the hydrosilane and solvent, the new method enables the selective cleavage of unactivated C-O bonds in amides and allows the C-N bonds to selectively break via the deacylated cleavage. Overall, this novel process may offer a versatile alternative to current methodologies employing stoichiometric metal systems for the controlled reduction of carboxamides.

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Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem

 

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The invention relates to a bromo two fluorine ethyl acetate as a acylation reagent prepared N – aryl formamide (by machine translation)

The invention discloses a bromo two fluorine ethyl acetate as a acylation reagent prepared N – aryl formamide, to N – alkyl amine as the raw material, bromo two fluorine ethyl acetate as a acylating agent, copper as a catalyst, by adding different ligand, alkali and the like, in a solvent in the reaction, for 100 – 120 C lower, stirring for 10 – 14 hours; the end of the reaction, the reaction solution is filtered, the filtrate obtained; to the filtrate to concentrate and the Rotavapor for removing the solvent the residue obtained, through the silica gel column chromatography of the residue, and by the eluant for executing leaching, according to the actual gradient of collecting the effluent; combining contains product effluent, towards the combined effluent concentrate to solvent, finally through drying under vacuum to obtain the target product. Raw materials of the invention is simple and easy, simple preparation process, less pollution, low energy consumption, advantage of high productive rate. (by machine translation)

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Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem

 

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Quinolonecarboxylic Acids. 2. Synthesis and Antibacterial Evaluation of 7-Oxo-2,3-dihydro-7H-pyrido<1,2,3-de><1,4>benzothiazine-6-carboxylic Acids

A series of pyridobenzothiazine acid derivatives was synthesized and their in vitro antibacterial activity was evaluated.The 1,4-benzothiazine intermediates, which by Gould-Jacobs quinoline synthesis produced pyridobenzothiazine acids, were prepared by hydrolytic basic cleavage of substituted 2-aminobenzothiazoles and successive cyclocondensation with 1-bromo-2-chloroethane or alternatively with monochloroacetic acid, hence reduction by LiAlH4.The pyridobenzothiazine acids 10c, 30, and 31 show potent antibacterial activities against Gram-positive and Gram-negative pathogens.Structure-activity relationships are discussed.The compound 9-fluoro-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido<1,2,3-de><1,4>benzothiazine-6-carboxylic acid (31) (MF-934) has been found to possess, together with the antibacterial activity, a weak acute toxicity and interesting pharmacokinetic characteristics in several animal species (rat, dog, monkey, man).

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Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem

 

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Half-Chair Conformations of Unsaturated Heterocyclic Compounds

The vicinal proton coupling constants were obtained for some 6-membered ring unsaturated heterocyclic compounds.The R values and ring dihedral angles were determined and found to be consistent with half-chair conformations.Relative to saturated heterocyclic compounds, the effect of the sulfur atom on ring puckering was attenuated.However, an increase in ring puckering resulted from the sulfone group and was attributed to torsional energy.

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Reference£º
Thiazine – an overview | ScienceDirect Topics,
Thiazine | C4H5NS – PubChem