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Background: Thiadiazines are heterocyclic compounds that contain two nitrogen atoms and one sulfur atom in their structure. These synthetic molecules have several relevant pharmacological activities, such as antifungal, antibacterial, and antiparasitic. Objectives: The present study aimed to evaluate the possible in vitro and in silico interactions of compounds derived from thiadiazines. Methods: The compounds were initially synthesized, purified, and confirmed through HPLC methodology. Multi‐drug resistant bacterial strains of Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 were used to evaluate the direct and modifying antibiotic activity of thiadiazine derivatives. ADMET assays (absorption, distribution, metabolism, excretion, and toxicity) were conducted, which evaluated the influence of the compounds against thousands of macromolecules considered as bioactive targets. Results: There were modifications in the chemical synthesis in carbon 4 or 3 in one of the aromatic rings of the structure where different ions were added, ensuring a variability of products. It was possible to observe results that indicate the possibility of these compounds acting through the cyclooxygenase 2 mechanism, which, in addition to being involved in inflammatory responses, also acts by helping sodium reabsorption. The amine group present in thiadiazine analogs confers hydrophilic characteristics to the substances, but this primary characteristic has been altered due to alterations and insertions of other ligands. The characteristics of the analogs generally allow easy intestinal absorption, reduce possible hepatic toxic effects, and enable possible neurological and anti‐inflammatory action. The antibacterial activity tests showed a slight direct action, mainly of the IJ23 analog. Some compounds were able to modify the action of the antibiotics gentamicin and norfloxacin against multi‐drug resistant strains, indicating a possible synergistic action. Conclusions: Among all the results obtained in the study, the relevance of thiadiazine analogs as possible coadjuvant drugs in the antibacterial, anti‐inflammatory, and neurological action with low toxicity is clear. Need for further studies to verify these effects in living organisms is not ruled out. [ABSTRACT FROM AUTHOR]

New fluorinated 1,2,4-triazin-4-ones 2–24 have been prepared using straightforward approaches. The reaction of 4-amino-3-mercapto-6-(trifluoromethyl)-1,2,4-triazin-5(4H)-one (2) with aromatic aldehydes produced 4-((4-substitutedbenzylidene)amino)-3-mercapto-6-(trifluoromethyl)-1,2,4-triazin-5(4H)-ones (5–9), which were cyclized by thioglycolic acid to give 2-(4-subsitiutedphenyl)-3-(3-mercapto-5-oxo-6-(trifluoromethyl)-1,2,4-triazin-4(5H)-yl)thiazolidin-4-ones (10–14). 7-Methyl-3-(trifluoromethyl)-4H-[1, 3, 4]thiadiazolo[2,3-c][1, 2, 4]triazin-4-one (4) was synthesized by the condensation of 2 with acetaldehyde or by reaction with cyano compounds, followed by self-cyclization in dry benzene. Cyclization of compound 2 by reaction with aromatic acids yielded 7-substitutedphenyl-3-(trifluoromethyl)-4H-[1, 3, 4]thiadiazolo[2,3-c][1, 2, 4]triazin-4-ones (15–19). Reaction of compound 2 with cyanamide produced 1-(4-oxo-3-(trifluoromethyl)-4H-[1, 3, 4]thiadiazolo[2,3-c][1, 2, 4]triazin-7-yl)guanidine (20). Alkylation of compound 2 with phenacyl bromide produced 4-amino-3-((2-oxo-2-phenylethyl)thio)-6-(trifluoromethyl)-1,2,4-triazin-5(4H)-one (21) which upon heating in the same media furnished 7-phenyl-3-(trifluoromethyl)-4H,8H-[1, 2, 4]triazino[3,4-b][1, 3, 4]thiadiazin-4-one (22). The reaction of Schiff′s bases 5 or 6 with phenacyl bromide gave 8-benzoyl-7-(4-halophenyl)-3-(trifluoromethyl)-4H,8H-[1, 2, 4]triazino[3,4-b][1, 3, 4]thiadiazin-4-ones (23–24). All of the newly synthesized compounds were characterized by spectral measurements and elemental analysis. The biological evaluation was also described. All compounds were screened for antibacterial, antifungal, and anti-biofilm activities. The findings confirm that the fluorinated 1,2,4-triazin-4-ones appear to be promising compounds as antibacterial, antifungal, and anti-biofilm agents. [ABSTRACT FROM AUTHOR]

Based on the pharmaceutical importance of the coumarin scaffold, we decided here to synthesize and evaluate the biological activity of some new coumarins. The new coumarin derivatives were synthesized starting from 3-(2-bromoacetyl)-2H-chromen-2-one (1) and their structures were clarified by fully spectral data. Ten of the new synthesized compounds were investigated for their anticancer activity against 60 human cancer cell lines by NCI USA. All the tested compounds showed good to mild activity against the tested cancer cell lines. Compounds 5, 7, and 8 were the most active against Renal Cancer UO-31 cancer cell line with growth inhibition percentage of 38.74%, 45.09%, and 34.65%, respectively. Where, compound 12 demonstrated strong to moderate activity toward Leukemia K-562, Renal Cancer UO-31and Breast Cancer T-47D cancer cell lines with growth inhibition percentage of 27.00%, 31.59%, and 32.98%, respectively. [ABSTRACT FROM AUTHOR]

In this article, we applied ultrasonic irradiation as an ecofriendly, green, efficient approach for the synthesis of a new 1,3-thiazoles and 1,3,4-thiadiazines under solvent-free conditions. Thus, thiocarbohydrazide condenses with N-(thiazol-2-yl)acetamide (2) in different molar ratios under ultrasonic irradiation afforded mono and bis thiocarbohydrazons 3a,b, respectively. Thiocarbohydrazones were reacted with α-haloketone, α-haloester as well as hydrazonoyl halides under ultrasonic conditions afforded 1,3-thiazole 4, 1,3-thiazolinone 5 and 1,3,4-thiadiazines 6 and 11a–c, respectively. The reaction of monohydrazone 3a with phthalic anhydride derivatives afforded phthalazines 7a,b in a good yield. Ultrasonic irradiation has benefits such as greater purity, lower cost, high yields, and simple workups compared to the conventional methods. All the new compounds were screened for antimicrobial activity against different tested microbes. Most of the newly synthesized compounds exhibited potent to moderate activities toward the tested microbes. Compounds that exhibited potent antimicrobial activities were selected to measure their MIC and MBC values. The results revealed that compounds 3a, 3b, 8, 10, and 11a showed lower MIC against Staphylococcus aureus with the values of 39.06, 78.13, 9.77, 39.06 and 39.06 µg/ml, respectively. Meanwhile, the MBC values were found to be acceptable for 3a and 10 of 156 and 312, respectively. [ABSTRACT FROM AUTHOR]

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A useful strategy for the construction of spirocyclic oxindoles bearing a 1,3,4-thiadiazine skeleton is reported. The desired products were obtained in high yields under mild conditions. [ABSTRACT FROM AUTHOR]

Synthesis of [3,4-b][1,3,4]thiadiazines from the condensation of 4-amino-6-methyl-3-thioxo- 1,2,4-triazine-5(2H)-one (AMTTO) or 4-amino-1,4-dihydro-5-methyle-1,2,4-triazole-5-thione (AMTT) with phenacyl bromide in the presence of a catalytic amount of various heteropolyacids (HPAs) under refluxing conditions is reported. [ABSTRACT FROM AUTHOR]

The present work includes synthesis of several 3-aryl-4-S-benzyl-6-phenylimino-2-hepta-O-acetyl-β-D-lactosylimino-2,3-dihydro-1,3,5-thiadiazines (hydrochloride) by the interaction of N-hepta-O-acetyl-β-D-lactosyl isocyanodichloride and 1-aryl-5-phenyl-2-S-benzyl-2,4-isodithiobiurets. All these products have been characterized through the usual chemical transformations and infrared, 1H NMR, and mass spectral analysis. The compounds were also screened for their antimicrobial activities. [ABSTRACT FROM PUBLISHER]

The first synthesis of the 1,2,4-triazolo[5,1-b][1,3,5] thiadiazine and some of its analogues, possessing a thiadiazino-s-triazole bicyclic ring system was performed starting from 2-benzyltriazole-5-thiol. The title compounds 6a-g were synthesized via double Mannich reaction in one step in high yields. The route employed the nucleophilic addition of two moles of CH2O onto the NH and SH groups of the triazole ring followed by cyclocondensation with elimination of two H2O molecules to form the thiadiazine derivatives. Examination of the biological activity against the selected fungi and bacteria is the main goal of this article. The tested compounds against fungi revealed that the title compounds were active against most strains of fungi, while the tested compounds were inactive against Gram +Ve and Gram -Ve bacteria. All new synthesized compounds were confirmed using the spectral analyses and the direction of the cyclization was confirmed using the molecular mechanics calculations. [ABSTRACT FROM AUTHOR]

Novel, convenient and benign synthesis of 2-arylamino-5-(3′-arylsydnone-4-yl)-1,3,4-thiadiazines 3a-1 by the interaction of 3-substituted-4-bromoacetyl sydnones 1 with substituted thiosemicarbazides 2 under MW irradiation and solvent-free condition is described. [ABSTRACT FROM AUTHOR]

The utilities of the Mannich reaction in synthetic organic chemistry are reviewed. The behaviors of Mannich reactions on several bifunctional heterocyclic compounds have been reported. A new class of heterocyclic compounds, thiadiazino[1,3,5][3,2-a]benzimidazoles 12a–g, were obtained by reaction of 2-mercaptobenzimidazole with primary aliphatic amines in a one-step synthesis. An attempt to apply this reaction using primary aromatic amines lead to the formation of the well-known Mannich bases 11a–g rather than the N -substituted thiadiazines 13. [ABSTRACT FROM AUTHOR]

Substituted 6-chloro-pyrimido[4,5- e ][1,3,4] thiadiazine was converted to the corresponding 6-hydrazino derivative by treatment with hydrazine hydrate in DMF/Et 3 N. The latter was converted to various substituted [1,2,4]triazino[1,2- a ] pyrimido[4,5- e ][1,3,4]thiadiazines. [ABSTRACT FROM AUTHOR]