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An Approach to Polysubstituted Triazipines, Thiadiazoles and Thiazoles Based on Benzopyran Moiety Through The Utility of Versatile Hydrazonoyl Halides as In Vitro Monoamine Oxidase Inhibitors

The chromene compound 1 is used as a key intermediate for synthesis of new heterocyclic compounds, and it reacted with hydrazonoyl chlorides in presence of TEA to give the amidrazone derivatives 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, which were cyclized to the corresponding triazepines 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h on boiling with sodium ethoxide. Conversion of compound 1 to the methylthiocarbamate derivative 6 was performed through its reaction with carbon disulfide and KOH followed by treatment with methyl iodide. Compound 6 reacted with hydrazonoyl chlorides in presence of TEA to give thiadiazoles 8a, 8b, 8c, 8d, 8e, 8f, 8g. In addition, chromene 1 combined with aminodithiocarbamic acid in DMF under reflux to furnish the thiosemicarbazide derivative 9, which in turn interacted with several hydrazonoyl chlorides to give the thiazole derivatives 11a, 11b, 11c, 11d, 11e. The structures of the prepared compounds were confirmed from their spectroscopic data and elemental analysis. The synthesized compounds were tested against both monoamine oxidase (MAO)-A and MAO-B and corrected to analyses showed good inhibitory activities especially against MAO-A.

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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem

 

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Thiazine Red(+) platelet inclusions in Cerebral Blood Vessels are first signs in an Alzheimer’s Disease mouse model

Strong evidence shows an association between cerebral vascular diseases and Alzheimer’s disease (AD). In order to study the interaction of beta-amyloid (A beta) plaques with brain vessels, we crossbred an AD mouse model (overexpressing amyloid precursor protein with the Swedish-Dutch-Iowa mutations, APP_SweDI) with mice expressing green fluorescent protein (GFP) under the flt-1/VEGFR1 promoter in vessels (GFP_FLT1). Our data show, that only very few A beta plaques were seen in 4-months old mice, focused in the mammillary body and in the lateral septal nucleus. The number of plaques markedly increased with age being most prominent in 12-months old mice. Thiazine Red was used to verify the plaques. Several Thiazine Red(+) inclusions were found in GFP(+) vessels, but only in non-perfused 4-months old mice. These inclusions were verified by Resorufin stainings possibly representing cerebral amyloid angiopathy. The inclusions were also seen in non-crossbred APP_SweDI but not in wildtype and GFP_FLT1 mice. In order to characterize these inclusions Flow Cytometry (FACS) analysis demonstrated that platelets were specifically stained by Thiazine Red(+), more pronounced when aggregated. In conclusion, our data show that Thiazine Red(+) inclusions representing aggregated platelets are a first pathological sign in AD before plaque development and may become important therapeutic targets in early AD.

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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem

 

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Convenient Structural Diversity-Guided Synthesis of Functionalized Sulfur-Containing Heterocycles via alpha-Substituted Cyanoacetamides

A convenient molecular diversity-oriented synthesis of various functional sulfur-containing heterocyclic scaffolds mainly including isothiazole, 2H-1,3-thiazine, and thiazolidine via different methods from-substituted cyanoacetamides is described. The target molecules have been identified on the basis of analytical spectral data, which may serve as useful structural subunits in the fields of drug discovery.

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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem

 

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A Highly Efficient Copper(I)-Catalyzed Cascade Reaction of o-Alkenylphenyl Isothiocyanates with Isocyanides Leading to 5H-Benzo[d]imidazo[5,1-b][1,3]thiazines

The highly efficient copper(I)-catalyzed cascade reaction of (E)-3-(2-isothiocyanatophenyl)acrylates and (E)-3-(2-isothiocyanatophenyl)acrylonitriles with isocyanides was explored. The method provides an expedient route for the synthesis of 5H-benzo[d]imidazo[5,1-b][1,3]thiazines in good to excellent yields by using CuCl (10 mol-%) as the catalyst and K3PO4 (2.0 equiv.) as the base in THF at 70 degrees C. The reaction involves [3+2] cycloaddition and subsequent intramolecular C-S bond formation.

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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem

 

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Effect of salicylates and zinc salts on leukemic cells

The prospects of the action of different types of chelating agents capable of binding to zinc, and salicylate ion comprising compounds on leukemic cells are reviewed. Survival rates and therapeutic indexes were compared.

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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem

 

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Chemoselective Synthesis of Structurally Diverse 3,4-Dihydroquinazoline-2(1H)-thiones and 4H-Benzo[d][1,3]thiazines

An efficient, mild, and substrate/catalyst-controlled chemoselective reaction of o-isothiocyanato-(E)cinnamaldehyde with amines has been established, producing three types of six-membered heterocycles: 2-(4Hbenzo[d][1,3]thiazin-4-yl)acetaldehydes, 2-(2-thioxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetaldehydes, and (E)-4-(2-methoxyvinyl)-4H-benzo[d] [1,3]thiazines. The reaction scopes were quite broad and excellent yield was achieved. This method is extremely efficient and practical and can be conducted on a gram-scale with slightly inferior reactivity under catalyst-free conditions at low cost, making it an ideal alternative to existing methods.

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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem

 

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Synthesis and Characterization of Some New Bis-Pyrazolyl-Thiazoles Incorporating the Thiophene Moiety as Potent Anti-Tumor Agents

A new series of 1,4-bis(1-(5-(aryldiazenyl)thiazol-2-yl)-5-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-3-yl)benzenes 3a-i were synthesized via reaction of 5,5-(1,4-phenylene)bis(3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide) (1) with hydrazonoyl halides 2a-i. In addition, reaction of 1 with ethyl chloroacetate afforded bis-thiazolone derivative 8 as the end product. Reaction of compound 8 with methyl glyoxalate gave bis-thiazolone derivative 10. The structures of the newly synthesized compounds were established on the basis of spectroscopic evidences and their alternative syntheses. All the synthesized compounds were evaluated for their anti-tumor activities against hepatocellular carcinoma (HepG2) cell lines, and the results revealed promising activities of compounds 3g, 5e, 3e, 10, 5f, 3i, and 3f with IC50 equal 1.37 +/- 0.15, 1.41 +/- 0.17, 1.62 +/- 0.20, 1.86 +/- 0.20, 1.93 +/- 0.08, 2.03 +/- 0.25, and 2.09 +/- 0.19 M, respectively.

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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem

 

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Synthesis of 3,4-Dihydro-2H-1,3-thiazines from alpha-Enolic Dithioesters and 1,3,5-Triazinanes via a Formal (3+3) Annulation Reaction

The synthesis of 3,4-dihydro-2H-1,3-thiazines from alpha-enolic dithioesters and 1,3,5-triazinanes has been achieved via a formal (3 + 3) annulation reaction under thermal conditions, where 1,3,5-triazinanes were utilized as three-atom synthons. This transformation is catalyst-free and additive-free.

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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem

 

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Discovery of an Extremely Potent Thiazine-Based beta-Secretase Inhibitor with Reduced Cardiovascular and Liver Toxicity at a Low Projected Human Dose

Genetic evidence points to deposition of amyloid-beta (A beta) as a causal factor for Alzheimer’s disease. A beta generation is initiated when beta-secretase (BACE1) cleaves the amyloid precursor protein. Starting with an oxazine lead 1, we describe the discovery of a thiazine-based BACE1 inhibitor 5 with robust A beta reduction in vivo at low concentrations, leading to a low projected human dose of 14 mg/day where 5 achieved sustained A beta reduction of 80% at trough level.

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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem

 

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Reaction of dithiocarbamates with 2-[bis(methylthio)-methylene]malononitrile: unexpected formation of 4-imino-6-(methylthio)-3-substituted-3,4-dihydro-2H-1,3-thiazine-2-thiones

1,3-Thiazine-2-thione derivatives were obtained from the reaction between dithiocarbamates and 2-[bis(methylthio)-methylene]malononitrile. Evidence for the structure of the obtained products was obtained by IR, mass, and NMR spectra and elemental analysis. The reaction mechanism is also discussed.

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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem