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Design, synthesis, and antidiabetic activity of 4-phenoxynicotinamide and 4-phenoxypyrimidine-5-carboxamide derivatives as potent and orally efficacious TGR5 agonists

4-Phenoxynicotinamide and 4-phenoxypyrimidine-5-carboxamide derivatives as potent and orally efficacious TGR5 agonists are reported. Several 4-phenoxynicotinamide derivatives were found to activate human and mouse TGR5 (hTGR5 and mTGR5) with EC50 values in the low nanomolar range. Compound 23g, with an EC50 value of 0.72 nM on hTGR5 and an EC 50 value of 6.2 nM on mTGR5, was selected for further in vivo efficacy studies. This compound exhibited a significant dose-dependent glucagon-like peptide-1 (GLP-1) secretion effect. A single oral dose of 23g (50 mg/kg) significantly reduced blood glucose levels in db/db mice and caused a 49% reduction in the area under the blood glucose curve (AUC)0-120min following an oral glucose tolerance test (OGTT) in imprinting control region (ICR) mice. However, 23g stimulated gallbladder filling, which might result in side effects to the gallbladder.

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

 

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Indoline and piperazine containing derivatives as a novel class of mixed D2/D4 receptor antagonists. Part 1: Identification and structure-activity relationships

Optimization of the lead compound 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,3-dihydro-indol-1-yl)-ethanone 1 by systematic structure-activity relation (SAR) studies lead to two potent compounds 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)- ethanone 2n and 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)- ethanone 7b. Their related synthesis was also reported.

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

 

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An odorless, one-pot synthesis of nitroaryl thioethers via SNAr reactions through the in situ generation of S-alkylisothiouronium salts

A newly developed C-S bond formation nucleophilic aromatic substitution (SNAr) reaction in aqueous Triton X-100 (TX100) micelles has been disclosed. This chemistry, in which odorless, cheap and stable thiourea in place of thiols is used as the sulfur reagent, provides an efficient approach for the generation of nitroaryl thioethers, which are useful structural units of many bioactive molecules, rendering this methodology attractive to both synthetic and medicinal chemistry.

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

 

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A non-metal catalytic three-stage aromatic amide-way selective reduction of the new method (by machine translation)

The invention relates to a high efficiency, two-way selective tertiary aromatic amide and organic silicon reagent silicon hydrogenation reduction reaction green new method. Selecting non-metal catalytic system, under mild conditions can be successfully catalytic three-stage aromatic amide with low-cost of the peripheric (PHMS) or triethoxy silane to selective production of secondary or tertiary organic amine compound. The first time the use of organosilicon reagent breakthrough of electronic effect of steric differences and realize three-stage aromatic amide-way selective reduction reaction, is the reduction of amides and derivatives thereof provides a completely new strategy, also the method overcomes the prevailing poor substrate functional group compatibility, high costs of production and the like, industrial production or laboratory preparation amine compounds have provided broad prospects. (by machine translation)

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

 

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1-PROPANOL AND 1-PROPYLAMINE DERIVATIVES AND THEIR USE AS GLUCOCORTICOID LIGANDS

Compounds of Formula (I) wherein R1, R2 R3, R4, R5, R6, and X are as defiend herein for Formula (IA) and Formula (IB), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocoricoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

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

 

Discovery of 3,4-Dihydro-2H-benzo[b][1,4]thiazine

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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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The design and synthesis of related molecules that are more effective, more selective, and less toxic than aspirin are important objectives of biomedical research.Keep reading other articles of 3,4-Dihydro-2H-benzo[b][1,4]thiazine!Formula: C8H9NS

Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? , Formula: C8H9NS, The answer is in thermodynamics and kinetics.In a document type is Patent, and a compound is mentioned, 3080-99-7, Name is 3,4-Dihydro-2H-benzo[b][1,4]thiazine, molecular formula is C8H9NS. In a article£¬once mentioned of 3080-99-7

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

 

Discovery of 3,4-Dihydro-2H-benzo[b][1,4]thiazine

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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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Regiospecific synthesis of unsubstituted basic skeletons of heterocycles containing nitrogen neighboring an aromatic ring by the reductive ring expansion reaction using diisobutylaluminum hydride

A systematic investigation of reductive ring expansion reaction of oximes with diisobutylaluminum hydride (DIBAH) was performed. The reaction regiospecifically provided a variety of unsubstituted bicyclic heterocycles 3a-3g or tricyclic heterocycles 3h, 3j-3l that contained nitrogen attached to an aromatic ring.

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

 

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Construction of nitrogen-fused tetrahydroquinolines via a domino reaction

An efficient domino approach for the diastereoselective synthesis of polyfunctionalized nitrogen-fused tetrahydroquinoline frameworks under mild conditions has been developed. The scope and limitation of this transformation were investigated by using a range of readily accessible enamides and benzyl azides. This method is also applicable to the formation of 2,3-functionalized enamides.

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