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The reaction between 2‐hydroxy‐1‐naphthaldehyde and 3‐hydrazino‐5,6‐diphenyl‐1,2,4‐triazine produced a novel hydrazone ligand (DTHMN), which reacted with Cu(II) and Zn(II) metal ion in molar ratio 1:1, giving octahedral Cu(II)‐DTHMN and tetrahedral Zn(II)‐DTHMN nanosized complexes. The structural geometries have been elucidated on the basis of elemental analysis, nuclear magnetic resonance, infrared, electronic, and electron spin resonance spectra, and magnetic and molar conductance measurements as well as x‐ray diffraction and thermal analysis. TEM analysis showed that Zn(II)‐DTHMN complex has nano‐rode morphology shape. On the other hand, Cu(II)‐DTHMN has sphere shape within nanodomain. The DTHMN ligand exhibits ONN chelating sites through N‐triazine ring, azomethine nitrogen, and deprotonated OH group, forming the mononuclear metal complexes. The synthesized compounds showed a distinct solvatochromic behavior in different polar solvents. A bathochromic alteration is observed when moving from less to high polar solvents, indicating strong solute–solvent interactions accompanied by intramolecular charge transfer (ICT). The ground and excited state dipole moments of these compounds were determined experimentally by solvatochromic shift method using Bilot–Kawski, Lippert–Mataga, Bakhshiev, and Kawski–Chamma–Viallet functions and a microscopic Reichardt's solvent polarity parameter (ETN). The dipole moment is increased significantly upon excitation referring to stabilizing the excited species includes n–π* transition by polarity of solvent. The experimental results are generally consistent with those values obtained by B3LYP/GENECP method at 6‐311G(d,p) basis set for C, H, N, and O atoms and SDD (Stuttgart/Dresden) basis set for the metal atoms. The compounds were tested for antimicrobial efficiency against Gram‐positive bacteria, Gram‐negative bacteria, and fungus strain. Finally, molecular docking was used to study the interactions between donors (the current compounds) and receptors FabH–CoA complex (PDB code: 1HNJ). [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a common condition that causes the level of glucose in the blood to become too high and α-glucosidase inhibitors are therapeutic agents in managing type 2 diabetes. In the present study, we report a new series of 3-aceto(benzo)hydrazide-1,2,4-triazine analogs as potential therapeutic agents against type 2 diabetes. In the in vitro evaluations, most compounds showed much stronger α-glucosidase inhibitory activity than the standard drug acarbose. Especially, compound 2A, (N'-(5,6-diphenyl-1,2,4-triazin-3-yl)-4-methoxybenzohydrazide) as the most active compound showed IC50 = 12.0 μM which is 60 folds more potent than acarbose. In addition, the MTT test using the three cell lines HCT-116, MDA-MB-231, and A549 showed that the target compounds have low cytotoxic effects with IC50 values in the range of 60–280 μM, therefore they can be considered as safe compounds. Molecular docking studies predicted that the strong inhibitory activity of 2A is related to the interactions generated by the three residues Asp282, Trp481, and Asp616 with the triazine core and hydrazide motif in the active site of the enzyme. The significant inhibitory effect of 2A against α-glucosidase was also confirmed in vivo, where the compound showed equivalent activity to the standard drug acarbose on reducing blood glucose in the tested mice. In conclusion, this study introduces compound 2A as a new lead compound with favorable cytotoxicity, strong α-glucosidase inhibitory activity and in vivo hypoglycemic effect, for future investigation in the treatment of diabetes mellitus.

This article discusses the synthesis and characterization of 3-triazinyl-7-aminocoumarins, which are important compounds with various applications. The authors explore different synthetic approaches and find that a C–H/C–H cross-coupling method using heptafluorobutyric acid as a catalyst is a more straightforward and environmentally-friendly approach. They optimize the reaction conditions and identify the best conditions for synthesis. The article also provides detailed information on the physical and chemical properties of various compounds, including their spectroscopic data and yields. Supporting information is available online. [Extracted from the article]

The method for the preparation of 3,6-disubstituted 1,2,4-triazines based on condensation reaction between easily available α-imino esters and isonitrosoacetophenone hydrazones was reported. The significant differences in reaction conditions, ratio of products, and yields between the developed method and the earlier reported approach were demonstrated. The corresponding 2,5-disubstituted pyridines were synthesized from the prepared 1,2,4-triazines, and their photophysical properties were studied. Studies of the photo-physical properties revealed low and moderate luminescence quantum yields, and negligible solvatochromic behavior in case of 4-methoxyphenylpyridine derivative due to the role of donating methoxy group, however, with a low linearity of a Lippert–Mataga plot. Nevertheless, 2,5-disubstituted pyridines are of interest due to simple protocols of synthesis, moderate photophysical properties, and potential applicability in different scientific and industrial areas. [ABSTRACT FROM AUTHOR]

Herein we report the first microwave‐assisted one‐pot three‐step metal‐free [4+2] procedure for the synthesis of 5,6‐substituted‐3‐hydrazinyl‐1,2,4‐triazines directly from commercially available aromatic and heteroaromatic ketones. The 3‐hydrazinyl‐1,2,4‐triazine can be isolated or further elaborated, after a simple work‐up, by direct condensation with different aldehydes or ketones to provide highly functionalized hydrazone‐derivatives. This protocol represents a rapid, efficient, and sustainable approach for the development of new highly functionalized 1,2,4‐triazine derivatives with potential biological interest. [ABSTRACT FROM AUTHOR]

A series of novel amide compounds with 1,2,4-triazine, 1,2,4-triazole and 1,3,4-oxadiazole moieties were synthesized by multistep procedure from 1,2,4-triazine-containing hydrazine-carbothioamides. Numerous synthetic compounds were tested for their ability to inhibit the growth of both gram-positive (Bacillus subtitis and Staphylococcus aureus) and gram-negative (E. coli) bacteria. All the tested compounds had no effects on fungi (Candida tropicalis). The toxicity of the synthesized chemicals was checked to guarantee their safety. The enzymic activity was studied, the enzymatic activity was not affected by the compounds under examined, and the levels of uric acid and creatine did not exceed normal limits. [ABSTRACT FROM AUTHOR]

Transformations of the various 6-[4-(methylthio)phenyl]-3-(2-pyridyl)-1,2,4-triazines in their reactions with an aryne intermediate were investigated. It was shown that the interaction of a 5-unsubstituted triazine with the aryne led to an S-arylation product, whereas there were no any transformations of the pyridyltriazine system. Introduction of the pentafluorophenyl substituent at the C(6) position of the triazine changed the pathway in this reaction with the aryne, which proceeded simultaneously at two reaction centers. In particular, there were a rearrangement of the 3-(2-pyridyl)-1,2,4-triazine into the 10-(1H-1,2,3-triazol-1-yl)pyrido[1,2-a]indole system as well as S-arylation. The product of dual functionalization, 10-{5-perfluorophenyl-4-[4-(phenylthio)phenyl]-1H-1,2,3-triazol-1-yl}pyrido[1,2-a]indole, exhibited a blue emission at λem = 395 nm and a fluorescence quantum yield comparable to the analogs obtained previously. [ABSTRACT FROM AUTHOR]

The [Ag(3ADMT)(NO3)]n complex was synthesized by the self-assembly of 3-amino-5,6-dimethyl-1,2,4-triazine (3ADMT) and AgNO3. Its molecular structure was analyzed utilizing FTIR spectra, elemental analysis, and single crystal X-ray diffraction (SC-XRD). There is one crystallographically independent Ag atom, which is tetra-coordinated by two nitrogen atoms from two 3ADMT and two oxygen atoms from two nitrate anions where all ligand groups are acting as connectors between the Ag1 sites. The geometry around the Ag(I) center is a distorted tetrahedron with a AgN2O2 coordination sphere augmented by strong argentophilic interactions between Ag atoms, which assist the aggregation of the complex units in a wavy-like and coplanar pattern to form a one-dimensional polymeric chain. The O...H (37.2%) and N...H (18.8%) intermolecular interactions contributed significantly to the molecular packing based on Hirshfeld surface analysis. The [Ag(3ADMT)(NO3)]n complex demonstrates promising cytotoxicity against lung (IC50 = 2.96 ± 0.31 μg/mL) and breast (IC50 = 1.97 ± 0.18 μg/mL) carcinoma. This remarkable cytotoxicity exceeds those of 3ADMT, AgNO3, and the anticancer medication cis-platin towards the tested cancer cell lines. In addition, the complex has a wide-spectrum antimicrobial action where the high antibacterial potency of the [Ag(3ADMT)(NO3)]n complex against P. vulgaris (MIC = 6.1 µg/mL) and B. subtilis (MIC = 17.2 µg/mL) could be comparable to the commonly used drug Gentamycin (MIC = 4.8 µg/mL). These results confirm that the components of the [Ag(3ADMT)(NO3)]n complex work together synergistically, forming a powerful multifunctional agent that could be exploited as an effective antimicrobial and anticancer agent. [ABSTRACT FROM AUTHOR]

Fourteen 1,3,5-triazine–1,2,4-triazine hybrids were designed and synthesized. Their structures were confirmed by IR, NMR, and high-resolution mass spectra, as well as by single crystal X-ray diffraction. The cholinesterase inhibitory activities of the hybrids were assayed by Ellman's method. Five of the fourteen hybrids inhibited acetylcholinesterase by more than 50% at a concentration of 50 μM. Only two hybrids inhibited butyrylcholinesterase by more than 50% at a concentration of 50 μM. Compound 5c possessed the best acetyl-cholinesterase and butyrylcholinesterase inhibitory activities with IC50 of 6.80±0.14 μM and 1.91±0.12 μM, respectively. Molecular docking showed that compound 5c interacted with both catalytic active site and peripheral anionic site of acetylcholinesterase. [ABSTRACT FROM AUTHOR]

One of the biggest problems facing contemporary medicine is cancer. New approaches to therapy are required due to the difficult and prolonged treatment, the numerous adverse properties of the medications employed, and the developing confrontation of neoplastic cells to treatment. Ten 1,2,4-triazine sulfonamide derivatives (1–10) were chosen for the first time in the current work, and their chemical structures were examined by DFT studies. The in silico flexible docking analysis of the chosen receptors involved in cancer development and metastasis (3RHK, 5GTY, 6PL2, and 7JXH) revealed that the selected compounds are the most promising. The binding affinity of compounds 10, 2, 6, and 4 is much better than the standard drug, Erlotinib, whereas compounds 9, 3, 1, and 7 showed better affinities as compared to standard drugs Neratinib and Tepotinib in the case of 3RHK receptor. The binding affinity against the 5GTY receptor of compounds 10, 5, and 3 is much better than the standard drug Tepotinib, and compounds 7, 6, 2, 4, 1, 8, and 9 showed better than Erlonitib and Neratinib. The binding affinity against the 6PL2 receptor of compounds 8, 3, 5, 4, 9, and 1 is much better than the standard drug Tepotinib. Compounds 10, 6, 7, and 2 were better than Erlotinib and Neratinib. All selected drugs showed better binding affinities than the standard anti-cancer drug Neratinib in the case of the 7JXH receptor, whereas compounds 2, 10, 5, 9, and 8 are better than Erlotinib. In silico ADME experiments supported the identified compounds' drug similarity. According to the MEP calculations, compounds 3 through 10 can interact non-covalently. The interactions might take the form of σ- and π-hole interactions. Softest compound 4 has the smallest energy gap, with an E-gap value of 3.25 Ev. Compound 4 has the largest energy gap at 3.41 eV. Compound 5 superior electron donor has the highest HOMO energy (6.5470 eV for HOMO). Compound 2 has the lowest LUMO energy, which suggests that it would be the best electron acceptor (ELUMO = 5.766364 eV). [ABSTRACT FROM AUTHOR]

Alkaline hydrolysis of 6-tert-butyl 8-ethyl 7-amino-3-tert-butyl-2-oxo-1,2-dihydropyrrolo[1,2-b][1,2,4]triazine-6,8-dicarboxylate gave the corresponding 8-carboxylic acid, and treatment of the latter with butyl bromide or N-bromosuccinimide in the presence of triethylamine resulted in decarboxylation with simultaneous alkylation at N1, or C2–O or bromination at the 8-position, respectively. Diazotization of 7-amino-3-tert-butyl-8-R1-2-R2O-pyrrolo[1,2-b][1,2,4]triazine-6-carboxylates afforded 7-azido (R1 = Br, CO2Et; R1 = H, Bu) and 7-unsubstituted (R1 = Br, CN; R2 = Bu, CH2CO2Et, CH2Boc) derivatives, and 1,3-dipolar cycloaddition of the 7-azido derivative and diethyl acetylenedicarboxylate produced 7-(1H-1,2,3-triazol-1-yl)pyrrolo[1,2-b]-[1,2,4]triazine-6,8-dicarboxylate. The structure of the synthesized compounds was confirmed by spectroscopic and X-ray diffraction data, and their antimicrobial activity was evaluated. [ABSTRACT FROM AUTHOR]

Novel 7-amino-3-tert-butyl-2-OR1-6-R2-pyrrolo[1,2-b][1,2,4]triazine-8-carbonitriles (R1 = CH2CO2Et, CH2Boc, Me, n-Bu; R2 = CO2Et, CO2n-Bu, CO2t-Bu, C6H4CO2i-Pr) have been synthesized and investigated by X-ray diffraction. Nucleophilic replacement of an alkoxy group with t-BuLi afforded sterically hindered tert-butyl 7-amino-2,3-di-tert-butyl- and 2,2,3-tri-tert-butyl-8-cyanopyrrolo[1,2-b][1,2,4]triazine-6-carboxylates. The lengths and bond angles as well as packing modes of molecules in crystals have been considered. The non-covalent interactions such as the changes in the H-bonding and close contacts were analyzed by DFT and the Hirshfeld surfaces and compared for different substituents. [ABSTRACT FROM AUTHOR]

The N-amination of 3,5-diamino-6-nitro-1,2,4-triazine via treatment with O-tosylhydroxylamine (THA) resulted in the formation of the 2,3,5-triamino-6-nitro-1,2,4-triazinium cation as the tosylate salt. The tosylate anion was easily exchanged using ion exchange resin to the chloride salt from which several energetic triazinium salts were synthesized via metathesis reaction. These energetic compounds were chemically and structurally characterized utilizing nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and single-crystal X-ray crystallography. The thermal stabilities were determined by thermal gravimetric analysis (TGA) and energetic sensitivities (impact, friction) were experimentally determined with a BAM Drophammer and BAM friction tester. The energetic performances were calculated with Explo5v6 using Gaussian09 generated heats of formation. The energetic triazinium salts were found to be sensitive high performing energetic materials that have decomposition temperatures less than 200 ​°C. These salts possessed impact sensitivities ≤5 ​J and friction sensitivities generally between 40 ​N and 48 ​N, the exception being the 5,5′-bistetrazole-1,1′-diolate salt whose sensitivity was determined to be ​

Herein, we report a convenient one-pot synthesis of 1,2,4-triazinyl derivatives of benzocoumarins. The proposed approach consists in the nucleophilic addition of tetrahydrobenzo annulated dimethoxycoumarin to 1,2,4-triazines followed by double oxidation of both dihydrotriazine and tetrahydrobenzo groups with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The nucleophilic addition of the dimethoxycoumarin to 1,2,4-triazines was carried out in the presence of three-fold excess of methanesulfonic acid in DCM at room temperature and take place between positions 4 and 5 of coumarin and 1,2,4-triazine, respectively. The double oxidation step was achieved with 3.6 equivalent of DDQ. Selective oxidation of dihydrotriazine moiety, without affecting the tetrahydrobenzo fragment, was achieved using 1.2 equivalent of tetrachlorobenzoquinone (TCQ). The differences in the oxidation with TCQ and DDQ appear to be related to the higher oxidative potential of DDQ in contrast to TCQ. The advantages of the method are the elimination of the use of transition metals, the availability of starting materials, and the simplicity of the procedure. The proposed approach provides a two-step one-pot protocol for the synthesis of triazinyl benzocoumarins, precursors for the preparation of push-pull pyridinyl chromophore.

A total of 21 novel xanthone and acridone derivatives were synthesized using the reactions of 1,2,4-triazine derivatives with 1-hydroxy-3-methoxy-10-methylacridone, 1,3-dimethoxy-, and 1,3-dihydroxanthone, followed by optional dihydrotiazine ring aromatization. The synthesized compounds were evaluated for their anticancer activity against colorectal cancer HCT116, glioblastoma A-172, breast cancer Hs578T, and human embryonic kidney HEK-293 tumor cell lines. Five compounds (7a, 7e, 9e, 14a, and 14b) displayed good in vitro antiproliferative activities against these cancer cell lines. Compounds 7a and 7e demonstrated low toxicity for normal human embryonic kidney (HEK-293) cells, which determines the possibility of further development of these compounds as anticancer agents. Annexin V assay demonstrated that compound 7e activates apoptotic mechanisms and inhibits proliferation in glioblastoma cells. [ABSTRACT FROM AUTHOR]

C-glycopyranosyl derivatives of six-membered heterocycles are scarcely represented in the chemical literature and the title 3-glycopyranosyl-1,2,4-triazines are completely unknown. In this paper, the first synthesis of this compound class is accomplished by the cyclocondensation of C-glycosyl formamidrazones and 1,2-dicarbonyl derivatives. In addition, the synthesis of C-glycopyranosyl 1,2,4-triazin-5(4H)-ones was also carried out by the transformation of the above formamidrazones with α-keto-carboxylic esters. Inverse electron demand Diels–Alder reactions of 3-glycopyranosyl-1,2,4-triazines with a bicyclononyne derivative yielded the corresponding annulated 2-glycopyranosyl pyridines. [ABSTRACT FROM AUTHOR]

Within this study, 20 2-[(5,6-diaryl-1,2,4-triazin-3-yl)thio]-N-(benzo/thiazol-2-yl)acetamide derivatives (4a-4t) were synthesized and COX inhibitory activities of the compounds were investigated. Compounds 4k-4o, which have a 4-methoxyphenyl group within their structures, showed strong inhibitory activity on COX-2 enzyme, even compound 4k, namely 2-{[5,6-bis(4-methoxyphenyl)-1,2,4-triazin-3-yl]thio}-N-(thiazol-2-yl)acetamide exhibited higher selectivity on this enzyme (IC50:3.06 µM). Molecular docking studies were performed for compound 4k on COX-1 and COX-2 enzymes and the results were found to support the molecule's COX-2 selectivity. [ABSTRACT FROM AUTHOR]

A different type of MnO2-induced oxidative cyclization of dihydrotriazines has been developed. These dihydrotriazines are considered as a "formal" Schiff's base. This method provided easy access to naphthofuro-fused triazine via the C-C/C-O oxidative coupling reaction. The reaction sequence comprised the nucleophilic addition of 2-naphthol or phenol to 1,2,4-triazine, followed by oxidative cyclization. The scope and limitations of this novel coupling reaction have been investigated. Further application of the synthesized compound has been demonstrated by synthesizing carbazole-substituted benzofuro-fused triazines. The scalability of the reaction was demonstrated at a 40 mmol load. The mechanistic study strongly suggests that this reaction proceeds through the formation of an O-coordinated manganese complex. [ABSTRACT FROM AUTHOR]

The chemistry of 1,2,4-triazine derivatives received a great deals of attention in recent year due to the use of such ring system as the core structure in many heterocyclic compound covering wide range of applications in many different field especially in industrial and biological fields. An efficient aza Diels-Alder reaction have been used in this presentation to prepare the hetero adducts represented by N2,N5-di(3,5,6-tri aryl-5,6-dihydro-1,2,4-triazine-4(3H)-yl)-1,3,4-thiadiazole-2,5-diamino (9-20)from hetero dienes and hetero dienophile. However the preparation starting form 1,3,4-thiadiazole-2,5 dithaiole (1) which converted directly to the dihydrazino derivatives(2) which then afford under condensation reaction hetero dienophile represented by 2,5-bis Schiff bases of 1,3,4-thiadiazole(3-6) by its reaction with substituted benzaldehyde. The last compound were reacted through one-pot free solvent aza Diels-Alder reaction with appropriate hetero diene (hydrazine with substituted benzaldehyde in ratio 1:2) (7&8) to afford 1,2,5-triazine derivatives (9-20) using grinding and MWI techniques as a types of green chemistry approaches. [ABSTRACT FROM AUTHOR]

A 1,2,4‐triazine based azidoxime was formed via the substitution of a chloroxime (3) with sodium azide in ethanol. This compound was characterized via single‐crystal X‐ray diffraction. This material has a calculated density of 1.746 g ⋅ cm−3 and is less sensitive to impact, spark, and friction, as compared to PETN and RDX. The dehydrated material has a calculated density of 1.823 g ⋅ cm−3 and the detonation pressure and velocity of 4 are calculated to be 29.1 GPa and 8.67 km ⋅ s−1, respectively. [ABSTRACT FROM AUTHOR]

The [Ag(3ADMT)(NO3)]n complex was synthesized by the self-assembly of 3-amino-5,6-dimethyl-1,2,4-triazine (3ADMT) and AgNO3. Its molecular structure was analyzed utilizing FTIR spectra, elemental analysis, and single crystal X-ray diffraction (SC-XRD). There is one crystallographically independent Ag atom, which is tetra-coordinated by two nitrogen atoms from two 3ADMT and two oxygen atoms from two nitrate anions where all ligand groups are acting as connectors between the Ag1 sites. The geometry around the Ag(I) center is a distorted tetrahedron with a AgN2O2 coordination sphere augmented by strong argentophilic interactions between Ag atoms, which assist the aggregation of the complex units in a wavy-like and coplanar pattern to form a one-dimensional polymeric chain. The O...H (37.2%) and N...H (18.8%) intermolecular interactions contributed significantly to the molecular packing based on Hirshfeld surface analysis. The [Ag(3ADMT)(NO3)]n complex demonstrates promising cytotoxicity against lung (IC50 = 2.96 ± 0.31 μg/mL) and breast (IC50 = 1.97 ± 0.18 μg/mL) carcinoma. This remarkable cytotoxicity exceeds those of 3ADMT, AgNO3, and the anticancer medication cis-platin towards the tested cancer cell lines. In addition, the complex has a wide-spectrum antimicrobial action where the high antibacterial potency of the [Ag(3ADMT)(NO3)]n complex against P. vulgaris (MIC = 6.1 µg/mL) and B. subtilis (MIC = 17.2 µg/mL) could be comparable to the commonly used drug Gentamycin (MIC = 4.8 µg/mL). These results confirm that the components of the [Ag(3ADMT)(NO3)]n complex work together synergistically, forming a powerful multifunctional agent that could be exploited as an effective antimicrobial and anticancer agent.

The N-amination of 3,5-diamino-6-nitro-1,2,4-triazine via treatment with O-tosylhydroxylamine (THA) resulted in the formation of the 2,3,5-triamino-6-nitro-1,2,4-triazinium cation as the tosylate salt. The tosylate anion was easily exchanged using ion exchange resin to the chloride salt from which several energetic triazinium salts were synthesized via metathesis reaction. These energetic compounds were chemically and structurally characterized utilizing nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and single-crystal X-ray crystallography. The thermal stabilities were determined by thermal gravimetric analysis (TGA) and energetic sensitivities (impact, friction) were experimentally determined with a BAM Drophammer and BAM friction tester. The energetic performances were calculated with Explo5v6 using Gaussian09 generated heats of formation. The energetic triazinium salts were found to be sensitive high performing energetic materials that have decomposition temperatures less than 200 °C. These salts possessed impact sensitivities °5 J and friction sensitivities generally between 40 N and 48 N, the exception being the 5,50-bistetrazole-1,10-diolate salt whose sensitivity was determined to be < 5 N. The calculated detonation pressures range from 26 GPa to 34 GPa while the detonation velocities range from 8247 m·s-1 to 8774 m·s-1 similar to PETN (pCJ = 30.8 GPa, vD = 8429 m·s-1) and TATB (pCJ = 32.4 GPa, vD = 8114 m·s-1). [ABSTRACT FROM AUTHOR]

Synthesis and structure elucidation of several series of new hydrazones containing 1,2,4-triazine-5-one core and their antioxidant activity are presented. The target compounds have been synthesized via interaction of either 4-amino-6-(tert-butyl)-3-hydrazinyl- 1,2,4-triazin-5(4H)-one or 6-(tert-butyl)-3-hydrazinyl-1,2,4-triazin-5(2H)-one with a wide range of compounds with a carbonyl group in moderate to high yields. Molecular structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR, and elemental analyses. The antioxidant activity of these compounds against ascorbic acid was screened to determine their potential as promising oxidative stress suppressors. Our data showed that hydrazones derived from 4-amino-6-(tert-butyl)-3-hydrazinyl-1,2,4- triazin-5(4H)-one are the most active antioxidants among all tested compounds. Furthermore, 3 compounds of this series have been proved to be twice as active as ascorbic acid does. The conclusions are substantiated for in-depth investigations of these derivatives as promising agents for the treatment of disorders accompanied by oxidative stress. [ABSTRACT FROM AUTHOR]

• The study focuses on the cyanoacylation of the sulfapyridine moiety using cyanoacetyl pyrazole as a crucial synthetic intermediate, leading to the creation of various bioactive scaffolds. • The intermediate, 2-cyano-N-(4-(N-pyridin-2-yl) sulfamoyl) phenylacetamide, was utilized to synthesize acrylamide, thiophene, thiazole, chromene, pyridone, 1,2,4-triazine, and hydrazone derivatives, all incorporating the sulfapyridine core. • The structural characterization of the synthesized compounds was conducted using IR, ¹H NMR, ¹³C NMR, and mass spectrometry techniques. • The newly synthesized compounds were tested against various microorganisms, including Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans. • The thiol derivative (compound 12), pyrazole derivative (compound 15), and 1,2,4-triazine derivatives (compound 21) showed notable antibacterial and antifungal activity, with compounds 12 and 15 exhibiting a broader spectrum of activity against all tested microbial strains. This study investigated the cyanoacylation of the sulfapyridine moiety using cyanoacetyl pyrazole as a key synthetic intermediate for the construction of diverse bioactive scaffolds. The intermediate, 2-cyano-N-(4-(N-pyridin-2-yl) sulfamoyl) phenylacetamide, served as a valuable precursor for the synthesis of acrylamide, thiophene, thiazole, chromene, pyridone, 1,2,4-triazine, and hydrazone derivatives all incorporating the sulfapyridine core. The structural elucidation of the synthesized compounds was achieved using infrared (IR), nuclear magnetic resonance (1H and 13C), and mass spectrometry techniques. The biological activity of the newly synthesized compounds was evaluated against a panel of microorganisms, including Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and the fungus Candida albicans. Notably, the thiol derivative (compound 12), the pyrazole derivative (compound 15), and the 1,2,4-triazine derivatives (compound 21) exhibited significant to good antibacterial and antifungal activity. Interestingly, compounds 12 and 15 displayed a broader spectrum of activity, demonstrating efficacy against all tested microbial strains. [ABSTRACT FROM AUTHOR]

Two series of functionalized imidazothiazolotriazine derivatives were synthesized via the condensation of imidazo[4,5-e]-1,2,4-triazine-3-thiones with acetylenedicarboxylic acid dimethyl and diethyl esters (DMAD and DEAD) and subsequent base-catalyzed rearrangement of the obtained imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazines into regioisomeric imidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine derivatives.

One of the biggest problems facing contemporary medicine is cancer. New approaches to therapy are required due to the difficult and prolonged treatment, the numerous adverse properties of the medications employed, and the developing confrontation of neoplastic cells to treatment. Ten 1,2,4-triazine sulfonamide derivatives (1–10) were chosen for the first time in the current work, and their chemical structures were examined by DFT studies. The in silico flexible docking analysis of the chosen receptors involved in cancer development and metastasis (3RHK, 5GTY, 6PL2, and 7JXH) revealed that the selected compounds are the most promising. The binding affinity of compounds 10, 2, 6, and 4 is much better than the standard drug, Erlotinib, whereas compounds 9, 3, 1, and 7 showed better affinities as compared to standard drugs Neratinib and Tepotinib in the case of 3RHK receptor. The binding affinity against the 5GTY receptor of compounds 10, 5, and 3 is much better than the standard drug Tepotinib, and compounds 7, 6, 2, 4, 1, 8, and 9 showed better than Erlonitib and Neratinib. The binding affinity against the 6PL2 receptor of compounds 8, 3, 5, 4, 9, and 1 is much better than the standard drug Tepotinib. Compounds 10, 6, 7, and 2 were better than Erlotinib and Neratinib. All selected drugs showed better binding affinities than the standard anti-cancer drug Neratinib in the case of the 7JXH receptor, whereas compounds 2, 10, 5, 9, and 8 are better than Erlotinib. In silico ADME experiments supported the identified compounds’ drug similarity. According to the MEP calculations, compounds 3 through 10 can interact non-covalently. The interactions might take the form of σ- and π-hole interactions. Softest compound 4 has the smallest energy gap, with an E-gap value of 3.25 Ev. Compound 4 has the largest energy gap at 3.41 eV. Compound 5 superior electron donor has the highest HOMO energy (6.5470 eV for HOMO). Compound 2 has the lowest LUMO energy, which suggests that it would be the best electron acceptor (ELUMO = 5.766364 eV).

A cadmium(II) complex containing dppt ligand with the formula [CdCl2(dppt)2], where dppt is 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine was synthesized, elucidated and submitted to in vitro cytotoxicity studies against human breast (MCF-7), glioblastoma (U-87), and lung (A549) cancer cell lines as well as mouse embryo normal cell line (NIH/3T3), in comparison with cisplatin employing MTT assay over 24 and 48 h. The complex exhibited the highest cytotoxic effect against MCF-7 cells among the other three cell lines with IC50 values of 8.7 ± 0.5 (24 h) and 1.2 ± 0.7 µM (48 h). Significantly, flow cytometric assessment of the complex-treated MCF-7 and U-87 cells demonstrated a dose-dependent induced apoptotic cell death. The cellular morphological changes were in concord with cytotoxicity and flow cytometric results. The results of comet assay showed that the complex is able to induce DNA damage in MCF-7 cells. These observations are of importance, as sustained damage to cellular DNA could lead to apoptotic cell death. The results of DNA-binding studies indicated that the complex fits into the DNA minor groove and interacts with DNA via a partial intercalation. Moreover, the complex was able to efficiently cleave pUC19 DNA through a hydrolytic mechanism. The binding affinity between the complex and apoptosis-relevant protein targets including APAF1, Bax, Bcl-2, Cas3, Cas7, and Cas9 was evaluated through molecular docking studies. In silico virtual studies revealed the complex's strong affinity towards apoptosis-related proteins; therefore the complex can act as a potential apoptosis inducer. Physicochemical, pharmacokinetics, lipophilicity, drug-likeness, and medicinal chemistry properties of the complex were also predicted through in silico absorption, distribution, metabolism and excretion studies. [ABSTRACT FROM AUTHOR]

A series of new clubbed aryl oxadiazole-1,2,4-triazine derivatives (6a-l) were designed and synthesized using appropriate chemical routes. The structures were designed to have the required structural elements for any compounds to be potential anticonvulsant. Preliminary screening of anticonvulsant activity was performed using maximal electroshock seizure (MES), subcutaneous pentylenetetrazole-induced seizure (scPTZ) and behavioral activity were assessed by motor impairment test and actophotometer test. The derivatives 6-((5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)amino)-1,2,4-triazine-3(2H)-thione (6f) and 6-((5-(4-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)amino)-1,2,4-triazine-3(2H)-thione (6g) revealed significant activity against both MES and scPTZ indicating that the compounds are effective against both generalized tonic-clonic and absence seizure. The lead compound (6g) was further evaluated for quantitative evaluation and emerged as the most effective anticonvulsant with median effective dose of 28.5 mg/kg (MES ED50), 76.6 mg/kg (scPTZ) and toxic dose (TD50) was found to be >500 mg/kg. In the GABA estimation study results showed significantly increased GABA concentration. [ABSTRACT FROM AUTHOR]

1,2,4-Triazine derivatives showed a significant role in the biological and pharmacological fields, which motivated us to study the biological and cytotoxicity activity of its first-row transition metal complexes. Three new complexes of Co(II), 1; Ni(II), 2; and Cu(II), 3 with 3-(2-benzylidenehydrazinyl)-5-(4-isobutylphenyl)-1,2,4-triazine, L were synthesized and characterized by standard physicochemical and theoretical methods. The structure of these complexes was evidenced by IR and 1H NMR spectroscopies, elemental analysis, magnetic measurements, molar conductance, mass spectrometry, and DFT modeling. The ligand behaved as a bidentate chelator that coordinates by triazine nitrogen-2 and azomethine nitrogen in a 2:1 (ligand : metal) ratio. The anticancer activity of the compounds was investigated against breast cancer cells (Mcf7 cell line). The antimicrobial activities of the ligand and its complexes were evaluated against different types of bacteria. Cu(II) was the most efficacious antimicrobial, with greater inhibition zones than the other complexes. The molecular docking studies were implemented to consider the binding attraction of the compounds with the receptors of breast cancer oxidoreductase (PDB:3HB5) and those of the COVID-19 main protease viral protein (PDB ID: 6LU7). The DFT calculations were used to confirm the molecular geometry of the new complexes. [ABSTRACT FROM AUTHOR]

Eight pyridine-containing and four 1,2,4-triazine-containing chiral oxazoline ligands incorporating electron-withdrawing substituents have been synthesized by two-step route including Buchwald–Hartwig amination. Enantio-inducing activity of the ligands has been assessed in the copper-catalyzed asymmetric nitroaldol reactions and the influence of the electron-withdrawing substituents on the ligands' activity has been investigated. [ABSTRACT FROM AUTHOR]

In this work, a series of novel 1,2,4-triazine-chalcone hybrids were designed through the molecular hybridization strategy, synthesized by two step chlorinations and further aldol condensation and evaluated their antiproliferative activity against MGC-803, HCT-116, PC-3, EC-109 and A549 cells. Compound 9l displayed significant antiproliferative activity against MGC-803, HCT-116, PC-3, EC-109 and A549 cell lines with IC50 values of 0.41, 0.43, 0.61, 0.78 and 0.52 μM, respectively. Subsequent mechanistic investigations suggested that compound 9l induced the generation of ROS and inhibited the activation of the ERK pathway. Compound 9l induced extrinsic cell apoptosis by up-regulating DR5 dependent on the generation of ROS, while up-regulation of DR5 caused by compound 9l relied on the inhibition of ERK. Thus, compound 9l inhibited the gastric cancer cells via an axis of ROS-ERK-DR5 in vitro. Compound 9l also showed potent activity on cell proliferation inhibition, and was effective in suppressing the growth of MGC-803 xenograft tumor in nude mice without obvious toxicity. Therefore, compound 9l is to be reported as anti-gastric cancer agent in vitro and in vivo via an axis of ROS-ERK-DR5.

A total of 21 novel xanthone and acridone derivatives were synthesized using the reactions of 1,2,4-triazine derivatives with 1-hydroxy-3-methoxy-10-methylacridone, 1,3-dimethoxy-, and 1,3-dihydroxanthone, followed by optional dihydrotiazine ring aromatization. The synthesized compounds were evaluated for their anticancer activity against colorectal cancer HCT116, glioblastoma A-172, breast cancer Hs578T, and human embryonic kidney HEK-293 tumor cell lines. Five compounds (7a, 7e, 9e, 14a, and 14b) displayed good in vitro antiproliferative activities against these cancer cell lines. Compounds 7a and 7e demonstrated low toxicity for normal human embryonic kidney (HEK-293) cells, which determines the possibility of further development of these compounds as anticancer agents. Annexin V assay demonstrated that compound 7e activates apoptotic mechanisms and inhibits proliferation in glioblastoma cells.

Alkylation of tert-butyl-7-amino-3-tert-butyl-8-R1-2-oxo-1,2-dihydropyrrolo[1,2-b][1,2,4]triazin-6-carboxylates with alkyl halides R2Br (R1 = CN, CO2Et; R2 = n-Pr, CH2Boc, CH2CO2Et) gave 2-alkoxy derivatives. The prolonged heating of the latter with alkanethiols R3SH (R3 = n-Bu, n-Pr, i-Pr, Et) in the presence of a base catalyst led to the formation of 2-alkylthiopyrrolo[1,2-b][1,2,4]triazines as the products of nucleophilic heteroaromatic substitution reaction. Further treatment with mCPBA furnished the corresponding sulfoxides. The sulfur-containing pyrrolo[1,2-b][1,2,4]triazines were obtained for the first time and studied by means of spectral methods and single crystal X-ray diffraction. The compounds were also tested for antimicrobial activities. [ABSTRACT FROM AUTHOR]

Fragmentation of the Ge–Ph bond in 2-(6-tBu-5-triphenylgermyl-2-R-4,5-dihydro-1,2,4-triazin-3(2H)-ylidene)malononitriles (R = Me, nBu) using lithium naphthalenide and further electrophile trapping with H+, Ph3SiCl or Ph3GeBr furnished the corresponding 5-Ph2HGe–, Ph3Si–Ph2Ge– or Ph3Ge–Ph2Ge– derivatives. In the case of R = CH2CO2tBu, metalation at the exocyclic methylene group was observed to give tert-butyl 7-amino-3-tBu-8-cyanopyrrolo[1,2-b][1,2,4]triazine-6-carboxylate as a result of cyclization/Ge atom elimination. Structures of the synthesized compounds were confirmed by spectral and XRD data. [ABSTRACT FROM AUTHOR]

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C-glycopyranosyl derivatives of six-membered heterocycles are scarcely represented in the chemical literature and the title 3-glycopyranosyl-1,2,4-triazines are completely unknown. In this paper, the first synthesis of this compound class is accomplished by the cyclocondensation of C-glycosyl formamidrazones and 1,2-dicarbonyl derivatives. In addition, the synthesis of C-glycopyranosyl 1,2,4-triazin-5(4H)-ones was also carried out by the transformation of the above formamidrazones with α-keto-carboxylic esters. Inverse electron demand Diels–Alder reactions of 3-glycopyranosyl-1,2,4-triazines with a bicyclononyne derivative yielded the corresponding annulated 2-glycopyranosyl pyridines.

A different type of MnO2-induced oxidative cyclization of dihydrotriazines has been developed. These dihydrotriazines are considered as a “formal” Schiff’s base. This method provided easy access to naphthofuro-fused triazine via the C-C/C-O oxidative coupling reaction. The reaction sequence comprised the nucleophilic addition of 2-naphthol or phenol to 1,2,4-triazine, followed by oxidative cyclization. The scope and limitations of this novel coupling reaction have been investigated. Further application of the synthesized compound has been demonstrated by synthesizing carbazole-substituted benzofuro-fused triazines. The scalability of the reaction was demonstrated at a 40 mmol load. The mechanistic study strongly suggests that this reaction proceeds through the formation of an O-coordinated manganese complex.

A PASE (pot, step, atom, economic) synthetic approach to 5-aryl-6-arylthio-2,2′-bipyridine and 6-arylthio-2,5-diarylpyridine ligands/fluorophores has been reported via SNH in 6-aryl-5H-1,2,4-triazines/aza-Diels-Alder reaction sequence. In this article, the "1,2,4-triazine" methodology was successfully used for the synthesis of C6-thiophenol-substituted (2,2′-bi)pyridines as it is well known that thio-substituted (bi)pyridines and their aza-analogs are of wide practical interest. The photophysical properties of the obtained compounds are studied and compared with those reported earlier for 6-substituted 2,2′-bipyridines. The influence of the nature of substituents in the 6-arylthio(bi)pyridine core on the photophysical properties is discussed. It was observed that the new compounds exhibited promising photophysical properties and could be considered as potential push-pull fluorophores. In addition, they demonstrated greater Stokes shift values compared to the previously described 6-H, 6-arylamino and 6-pentafluoro-2,2′-bipyridines and higher fluorescence quantum yields values compare to pentafluorophenyl-substituted 2,2′-bipyridines. Depending on a nature of (bi)pyridine fluorophore LE (locally excited) and/or ICT (intramolecular charge transfer) state were prevailing in emission spectra. [ABSTRACT FROM AUTHOR]

Efforts toward further closure of the nuclear fuel cycle are contingent, in part, on chemoselective removal of the minor An from Ln within spent nuclear fuel. Liquid-liquid extraction has been demonstrated as an effective vehicle to further irradiate daughter nuclides of the minor An to products with shorter half-lives, lower radiotoxicity, and diminished contribution to heat load. Strategic synthetic methods to evaluate structure-activity relationships of complexants utilized in minor An separations are limited. Traditional, soft-donor complexants of bis-1,2,4-triazinyl-2,6-pyridines (BTPs) reported to date are entirely C2 -symmetric. Disruption of C2 -symmetry was hypothesized to accentuate the solubility of complexants in nonpolar diluents. In this article, a scalable synthetic strategy for the construction of unsymmetric-BTPs is described. Method development, substrate scope, a scale up reaction, and hypothesis-validating solubility data are reported herein. [Display omitted] [ABSTRACT FROM AUTHOR]

Rearrangements of 3-tert-butyl-8-methyl-4-phenylethynyl-1,4-dihydropyrazolo[5,1-c][1,2,4]triazine derivatives by the action of bases led to the formation of aromatic (E)- or (Z)-4-styryl-functionalized compounds. At the same time, 4-styryl-1,4-dihydropyrazolotriazines did not rearrange to form the expected 4-phenylethylpyrazolo[5,1-c][1,2,4]triazine. The latter was obtained via an alternative route by the addition reaction of phenylethynylmagnesium bromide to 3-tert-butyl-8-methylpyrazolo[5,1-c][1,2,4]triazine, as well as by reduction of double bonds in the ring and side chain of the 4-styryl derivative with subsequent selective oxidation by N-bromosuccinimide. The spectral and X-ray structural data as well as the antimicrobial properties of the synthesized compounds are discussed. [ABSTRACT FROM AUTHOR]

8-Hydroxy(methoxy)-substituted 2-[6-(1-methylindol-3-yl)pyridin-2-yl]quinoline ligands were synthesized by means of combination of SNH reaction between 8-methoxy-substituted 2-(6-aryl-1,2,4-triazin-3-yl)quinolones and indole and aza-Diels–Alder reaction of the obtained 1,2,4-triazines with 2,5-norbornadiene. The demethylation of quinoline moiety of 1,2,4-triazine precursor during aza-Diels–Alder reaction in autoclave was demonstrated. [ABSTRACT FROM AUTHOR]

Some new 1:1 (ML) and 1:2 (ML2) metal complexes of Co(II), Ni(II), Cu(II), and Zn(II) have been synthesized with novel ligand, that is, 4‐(3‐methylthiophene‐2‐ylmethyleneamino)‐3‐mercapto‐6‐methyl‐5‐oxo‐1,2,4‐triazine. Ligand and its metal complexes were characterized on the basis of various physicochemical techniques like elemental analysis, magnetic moment, molar conductance, cyclic voltammetry, and spectroscopic (1H‐NMR, infrared [IR], electronic, fluorescence, and electron spin resonance [ESR]) data. On the basis of these studies, octahedral and square planar geometries have been proposed for Co(II), Ni(II), Zn(II), and Cu(II) metal complexes, respectively. Thermogravimetric analysis (TGA) was carried out to study the thermal decomposition and stability of metal complexes. Electrochemical behavior of Cu(II) complexes have also been explored by cyclic voltammetry. The complexes have shown promising antimicrobial activity when checked by in vitro method against some bacterial and fungal strains. In addition to these studies, quantum mechanical approach was also performed in order to find some structural information of newly synthesized compounds. [ABSTRACT FROM AUTHOR]

Reactions of 3-tert-butyl-8-methylpyrazolo[5,1-c][1,2,4]triazine with lithium phenyldimethylsilanide and triphenylsilanide in THF media at −85 to −60 °C led to the formation of the silicon C(4)-addition products in high yields. Aromatic 3-tert-butyl-8-methyl-4-(triphenylsilyl)pyrazolo[5,1-c][1,2,4]triazine has been synthesized by oxidation of the corresponding 1,4-dihydro derivative using NBS/Et3N in pentane at −30 to −15 °C. Preferential N(1)-nucleophilic additions of silanides were observed for the sterically hindered 3,4-di-R-8-methylpyrazolo[5,1-c][1,2,4]triazines (R = t-Bu, Ph3Si). Novel C–Si derivatives of 1,2,4-triazines, as well as some other isolated compounds were characterized by IR, 1H, 13C, 29Si NMR, HRMS data and X-ray crystallography. [ABSTRACT FROM AUTHOR]

3-tert-Butyl-8-nitro-7-R-pyrazolo[5,1-c][1,2,4]triazin-4(6H)-ones (R = H, Cl, Br, NO2, N3) were prepared by nitration with HNO3/H2SO4 of the corresponding 7-R-substituted 8-carboxylic acids or their analogs with a vacant C8 position. The latter were synthesized by diazotization of 7-amino-3-tert-butyl-4-oxo-4,6-dihydropyrazolo[5,1-c][1,2,4]triazin-8-carboxylic acid. The electrophilic halogenation and cycloaddition of the 7-azido and 7-nitro derivatives of the synthesized compounds were considered. The structures of the products were confirmed by IR, heteronuclear NMR spectroscopy, HRMS, and single-crystal XRD. [ABSTRACT FROM AUTHOR]

Possible application of incorporating a well-known drug (benzocaine) with cyanoacetamide function to get a powerful synthon ethyl 4-cyanoacetamido benzoate. This synthetic intermediate was used as a precursor for the synthesis of triazine, pyridone, thiazolidinone, thiazole and thiophene scaffolds containing the benzocaine core. Facile coupling, Michael addition, condensation and nucleophilic attack reactions were used to synthesize our targets. The structural features of the synthesized scaffolds were characterized using IR, 1H NMR, 13C NMR and mass spectroscopy. The antibacterial activities against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) were evaluated using ampicillin as a reference drug. DNA/methyl–green colorimetric assay of the DNA-binding compounds was also performed. Theoretical studies of the newly synthesized compounds based on molecular docking and QSAR study were conducted. The molecular docking studies were screened by MOE software for the more potent antibacterial agent 28b and each native ligand against four of S. aureus proteins 1jij, 2xct, 2w9s and 3t07. [ABSTRACT FROM AUTHOR]

Aromatic 7-R1-8-R2-3-tert-butylpyrazolo[5,1-c][1,2,4]triazines (R1 = H, Br; R2 = H, Me, Br) reacted with lithium diphenyl- and methyl(phenyl)phosphides in THF at lower temperature to give nucleophilic addition products to the C4 atom. Further oxidation with atmospheric oxygen or N-bromosuccinimide afforded previously unknown (3-tert-butylpyrazolo[5,1-c][1,2,4]triazin-4-yl)phosphine oxides and 2,2-dibromoacetamide as a by-product. The structure of the isolated compounds was confirmed by IR, 1H, 13C, and 31P NMR, and mass spectra and X-ray analysis. [ABSTRACT FROM AUTHOR]

Novel fluorinated 1,5-disubstituted-1,3,5-triazepine-6,7-dione (4) has been obtained from the interaction between 5,6-bis(4-fluorophenyl)-1,2,4-triazine-3-thiol (1) with 2,6-diaminopyridine 2 followed by ring closer reaction with diethyl oxalate. Also, Ru-complex 7 obtained by refluxing of compound 1 with 6-(4-fluorophenyl)-1,2,4-triazine-3,5-diamine (5) to produce compound 6, the later was reacted with RuCl3.xH2O to produce the target 7. Structures of the products deduced from their elemental analysis and spectral measurements. Compounds 3, 4, 6, and 7 were evaluated as CDK2 inhibitors of tumor cells; these compounds exhibited a potential activity against CDK2, where the IC50 values were 4.5, 6.8, 4.0, and 5.0 µM respectively in comparison with Olomoucine standard (IC50=5.0 µM). [ABSTRACT FROM AUTHOR]

The work involves synthesis of new compounds derived from 2-substituted-3-thio- acetohydrazide-1,2,4-triazin. The subsituted hydrazine thiocarbothioamide [IV] was obtained via reaction of hydrazide compound [III] with ammonium thiocyanate and HCl. The cyclization of compound [IV] in 4% NaOH led to formation 1,2,4-triazoles [V], which were refluxed with chloro-ethylacetate in ethanol and sodium acetate to give compound [VI]. Condensation of ester-compound [VI] with hydrazine (80%) led to formation new hydrazide compounds [VII]. Ring closure reaction of compound [VII] with 4-aminbenzoic acid in POCl3 give 1,3,4-oxadiazoles [VIII]. Compound [VIII] was reacted with sub. benzaldehyde to form compounds of Schiff bases [IX]a-d. The synthesized compounds were diagnosed via IR, Mass and ¹HNMR spectral data. Many of synthesized compounds were examined against activity of antibacterial: gram (+) (Bacillus subtitis, staphylococcus aureus) and gram (-): (E.coli bacteria) and candida tropicalis fungial. To ensure the safety of the synthesis compounds the toxicity was examined. [ABSTRACT FROM AUTHOR]

Herein we describe our results on the synthesis of1,2,4-triazine and 1,2-diazine derivatives. This group of compounds have been synthesized by the reaction of 6-amino-1,3-dimethyluracil with chloroacetyl chloride, triethylamineusing DMF as a solvent, the product 6-(amino acetyl chloride)-1,3-dimethylpyrimidine-2,4-dione-6-yl [1] then, reacted with a hydrazine hydrate in absolute ethanol to obtain hydrazide derivative [2], which reacted with phenylisocyanate, á-naphtylisocyanate and phenylthioisocyanate, then cyclization with alkaline media of sodium hydroxide to produce six membered heterocyclic rings such as 1,2,4-triazine derivatives.In alkaline media 20%KOH compound [2] reacted with CS2 to give potassium salt [9] that cyclization with excess of hydrazine hydrate to give 1,2,4-triazine derivative compound [10].1,2-Diazine derivatives [11-16] has been synthesized by cyclization of hydrazide derivative [2] with different aromatic anhydride. All newly synthesized compounds conformation were characterized in detail by FTIR and NMR spectroscopy including 1D NMR experiments (¹H and 13C). The present study was carried out to investigate the antioxidant, anti-inflammatory by using carrageen an induced paw edema model were used in albino rats, their antimicrobial activity, antifungal and antibacterial against two Gram-positive bacteria and two Gram-negative bacteria [ABSTRACT FROM AUTHOR]

The treatment of 7-amino-8-bromo-3-tert-butylpyrazolo[5,1-c][1,2,4]triazin-4(6H)-one with an excess of NaH in THF and AlkLi (Alk = Bun, But) at -97 °C produced disodium (8-lithio-3-tert-butyl-4-oxopyrazolo[5,1-c][1,2,4]triazin-1-id-7-yl)amide unstable under ambient conditions. The chemical properties of the newly synthesized compound were studied. The electrophilic attack occurs at the N(1), C(7)—N, or C(8) ring positions depending on the nature of the electrophilic agent (PhCHO, ButCOCl, TMSBr). The treatment of the N(1)-Boc-protected derivative with BuLi resulted in the C(8)-metalation accompanied by the addition of alkyl at the carbonyl groups or at the N(2) atom. The low-temperature reaction with pivaloyl chloride was studied using deuterium labeling of the amino group, which confirmed the hydrogen atom transfer from the C(7)—NH group to the C(8) position of the heterocycle. The structures of the synthesized compounds were established by IR spectroscopy, 1H, 2H, 13C, and 2D 1H—29Si HMBC NMR spectroscopy, high-resolution mass spectrometry, and single-crystal X-ray dif raction. [ABSTRACT FROM AUTHOR]