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This work presents the synthesis and characterization of triazine heterocyclic derivatives. The spectroscopic properties like nuclear magnetic resonance [NMR, ( 1 H and 13 C)] were recorded in CDCl 3 solution and Ultraviolet–Visible (UV–vis) absorption spectrums of compounds, 5,6-diphenyl-[1,2,4]triazin-3-ylamine ( 1 ), (5,6-diphenyl-[1,2,4]triazin-3-yl)-hydrazine ( 2 ) and 5,6-diphenyl-4H-[1,2,4] triazine-3-thione ( 3 ), were recorded in the range of 200–800 nm, using chloroform as base solvent. Molecular geometry of compounds with triazine heterocyclic derivative in the ground state have been calculated using the density functional theory (DFT) with 6-31G(d,p) basis set and compared with the X-ray experimental data. The calculated results show that the optimized geometry can well reproduce the crystal structures. Total static dipole moment ( μ ), the average linear polarizability ( α ) and the first hyperpolarizability ( β ) values of the investigated molecules have been computed using the same methods. The energetic behavior of compounds in solvent media has been examined using B3LYP method with the 6-31G(d,p) basis set by applying the polarizable continuum model (PCM). The total energy of compounds decreases with increasing polarity of the solvent. Frontier molecular orbitals and the molecular electrostatic potential (MEP), 1 H NMR, and 13 C NMR of three triazine derivatives were investigated using theoretical calculations. The linear polarizabilities and first hyperpolarizabilities of the studied molecules indicate that the compounds 1 – 3 can be used as a good nonlinear optical material (NLO). Isotropic chemical shifts were calculated using the gauge-invariant atomic orbital (GIAO) method. Comparison of the NMR chemical shifts, absorption wavelengths with the experimental values revealed that DFT and time dependent-density functional theory (TD-DFT) method produce generally closer to good results. [ABSTRACT FROM AUTHOR]

A series of triazin–3(2 H )–one derivatives bearing 1,3,4–oxadiazole (4a–4o) were synthesized, characterized and evaluated for anti–inflammatory and analgesic activities. Preliminary in vitro anti–inflammatory activity was assessed using an albumin denaturation assay. The promising compounds were further evaluated in acute, sub–chronic and chronic animal models of inflammation. Derivatives 4d, 4e, 4g, 4j and 4l exhibited significant anti–inflammatory activity with reduced ulcerogenic, hepatotoxic and renotoxic liabilities compared to standard indomethacin. These potential derivatives were also evaluated for in vivo analgesic activity using a writhing model and the formalin-induced paw licking response in mice. Compounds 4d , 4e and 4g exhibited comparable analgesic activity, whereas 4j and 4l yielded moderate effects. The specificity of compounds 4d, 4e , 4g , 4j , and 4l to inhibit (cyclooxygenase–1) COX–1 and (cyclooxygenase–2) COX–2 isozymes and their kinetics were also determined via an in vitro COX inhibition assay. In silico docking studies were performed using a molecular dynamics simulation of the most active compound 4d (COX–2 IC 50 : 3.07 μM) at the COX–2 active site. The outcome of this exercise helped to verify the consensual interaction of these compounds with the enzyme. [ABSTRACT FROM AUTHOR]

Thienyl-triazine-sulphonamide conjugates were prepared from their precursor amines using triethyl orthoformate or ethyl chloroformate as cross coupling reagents. The progress of these reactions was investigated by spectral (IR, NMR, MS) and microanalytical techniques. The synthesized compounds were in vitro screened for antibacterial, antifungal, antioxidant, and anticancer activity. 4-[({[3-Mercapto-5-oxo-6-[2-(2-thienyl)vinyl]-1,2,4-triazin-4(5 H)-yl]imino}methyl)amino]-benzenesulfonamide turned out to be a powerful antibacterial agent, while all the compounds prepared were inactive against fungal species tested. 4-{[({8-Cyano-4-oxo-3-[2-(2-thienyl)vinyl]-4 H,8 H-[1,2,4]triazino[3,4- b][1,3,4]thiadiazin7-yl}amino)(ethoxy)methyl]amino}benzenesulfonamide displayed in vitro promising cytotoxicity against Ehrlich ascites carcinoma cell line with concurrent attenuation of malonodinitrile and it was unique among other compounds being unable to increase glutathione S-transferase and reduced glutathione S-transferase activities. This compound exhibited also good antioxidant properties that together with its cytotoxicity nominated it for further investigation in cancer research. [ABSTRACT FROM AUTHOR]

A new series of metal complexes have been synthesized with an imine 4-(4-cyanobenzylideneamino)-3-mercapto-5-oxo-1,2,4-triazine which has been derived by the condensation of 4-cyanobenzaldehyde and 4-amino-3-mercapto-5-oxo-1,2,4-triazine. Different techniques like IR, H NMR, electronic spectroscopy, fluorescence, ESR, thermal, conductivity and magnetic measurements were used to investigate the structural features of the synthesized compounds. Based on spectral and thermal techniques, octahedral geometry has been proposed for Co(II), Ni(II) and Zn(II) complexes and square planar for Cu(II) complexes. All the synthesized metal complexes show enhancement in fluorescence intensity in comparison to the ligand. The newly synthesized ligand and metal complexes were also screened for their antimicrobial activities against some bacterial and fungal strains to assess their inhibiting potential in vitro. The activities shown by these complexes were compared with ligand and also with standard drugs. The molar conductivity values indicate that the complexes are non-electrolytes. [ABSTRACT FROM AUTHOR]

A series of 5,6-bisaryl-1,2,4-triazine-3-thiol-substituted derivatives were synthesized by condensation of 1,2-diketones and thiosemicarbazide under microwave irradiations and subsequent alkylation of thiol group by chloromethylpyridinium chloride. Evaluation of anticonvulsant activity of compounds was performed by maximal electroshock and pentylenetetrazole-induced seizures tests. In order to evaluate their neuroprotective potential, the ability of compounds to inhibit soybean 15-lipoxygenase was also assessed. Further molecular modeling and docking study on Na+ channel and GABA receptor was performed to elucidate their mechanisms of action and necessary interactions in the active site. Compounds 2c and 2d with bis(4-bromophenyl) and pyridyl substituents showed highest protection up to 70 and 80 % in PTZ and MES-induced seizures, respectively, compared to the control group. Molecular docking study revealed their possible antiseizure mechanism of action through GABA receptor, and in silico assessment of their BBB permeability indicated them as CNS active agents. [ABSTRACT FROM AUTHOR]

[Figure not available: see fulltext.] An alternative method has been developed for the preparation of 4-R-furazan-3-carboxylic acid amidrazones (R = OMe, NH, substituted amino group) by reductive opening of 1,2,4-oxadiazole ring in 4-R derivatives of (1,2,4-oxadiazol-3-yl)furazans by the action of hydrazine. The starting 1,2,4-oxadiazoles were synthesized from 4-aminofurazan-3-carboxylic acid amidoxime. Some chemical properties of the obtained compounds were studied. [ABSTRACT FROM AUTHOR]

New unsymmetric 5,6´-diaryl-2,2´-bipyridines were synthesized in high yields using a 1,2,4-triazine methodology. Their photophysical properties were studied. [ABSTRACT FROM AUTHOR]

A new series of novel compounds 1-tert-butyl-9-substituted-12 H-indolo[2,3- c]isoquinolino[5,6-c]-1,2,4-triazoles ( 4a- 4c), 10-substituted-2-phenyl-1,13-dihydroindolo[2,3- c]isoquinolino[5,6-c]-1,2,4-triazines ( 5a- 5l), 2-(10-substituted-7 H-indolo[2,3- c]isoquinolin-5-yl)-4-phenylphthalazin-1-ones ( 6a- 6c), 2-[2-(10-substituted-7 H-indolo[2,3- c]isoquinolinyl)hydrazinecarbonyl]benzoic acid ( 7a- 7c), and 2-(10-substituted-7 H-indolo[2,3- c]isoquinolin-5-yl)phthalazine-1,4-diones ( 8a- 8c) were synthesized. The structures of these newly synthesized compounds were confirmed by their spectral studies and elemental analysis. These compounds have been screened for their antimicrobial, antitubercular, antioxidant, and cytotoxic activities. Compounds 4b, 5a, 5g, 5h, 6a, 6b, and 7b exhibited the maximum zone of inhibition against Staphylococcus aureus. Compounds 5d and 6c exhibited the maximum zone of inhibition against Pseudomonas aeruginosa. Compounds 7a and 8c showed maximum zone of inhibition against Aspergillus niger. Compounds 5k and 8c showed maximum zone of inhibition against Aspergillus flavus. Compounds 4a (MIC-1.6 µg/ml) and 5 h (MIC-0.2 µg/ml) exhibited promising antitubercular activity against Mycobacterium tuberculosis H37Rv strain. Compounds 4b, 4c, 5a, 5c, 5e, 5h, 6a, 6b, 6c, 8a, and 8b exhibited good radical scavenging activity compared with standards. Compounds 4b, 4c, 5a, 5c, 5g, 6a, and 8b exhibited maximum reducing ability. Compounds 4a and 5h exhibited 100 % cell lysis at concentration 10 µg/ml. [ABSTRACT FROM AUTHOR]

New unsymmetric 6,6´-diaryl-2,2´-bipyridines were synthesized in high yields using a '1,2,4-triazine' methodology. Their photophysical properties were studied. [ABSTRACT FROM AUTHOR]

The synthesis of 2-(trifluoromethyl)oxazoles through ring-expansion reaction of 2 H -azirine with trifluoroacetic anhydride is reported. The 2-(trifluoromethyl)oxazole compounds can be easily converted into 3-(trifluoromethyl)-1,2,4-triazines through hydrazinolysis reaction. [Display omitted] • A method for synthesis of 2-(trifluoromethyl)oxazoles and 3-(trifluoromethyl)-1,2,4-triazines was developed. • Various trifluoromethyl oxazoles and triazines were synthesized in moderate to excellent yields. • A variety of functional groups were tolerated. A ring-expansion reaction of 2 H -azirine with trifluoroacetic anhydride for the synthesis of 2-(trifluoromethyl)oxazoles is disclosed. The reaction features readily available reactants, relatively mild conditions, and high yields of products. The generated 2-(trifluoromethyl)oxazole core could be easily converted into 3-(trifluoromethyl)-1,2,4-triazines through hydrazinolysis reaction. [ABSTRACT FROM AUTHOR]

[Display omitted] • Oxidative fragmentation of 6-Bu t -2-(1,2,4-triazin-3(2 H)-ylidene)malononitriles afforded a series of 5-oxo-1,2,4-triazine-3-carboxylates. • The effects of different functional groups on the reaction path were studied. • The reactivity of novel 1,2,4-triazin-5(2 H)-ones towards N-, O-, H-, C -based nucleophiles was investigated. • Structures of the synthesized compounds were established by XRD analysis. Ring opening of 7-bromo-1,4-dihydropyrazolo[5,1- c ][1,2,4]triazin-4-ols with BuLi furnished 2-(1,2,4-triazin-3(2 H)-ylidene)malononitriles, treatment of which with m CPBA in the presence of primary alcohols gave a series of novel alkyl 6- tert -butyl-2-R1-5-oxo-2,5-dihydro-1,2,4-triazine-3-carboxylates (Alk = Me, Et, Bu n , Bui, neopentyl; R1 = Me, Bu n , CH 2 Boc) in good yields. The latter reacted with aliphatic amines, hydrazine hydrate or potassium hydroxide to afford the corresponding N -R2 3-carboxamides and hydrazide (R2 = Me, Bu t , NH 2) or 3-unsubstituted derivatives as a result of decarboxylation. Nucleophilic addition at the C3 ring position with further oxidative aromatization led to the functionalized 3-R3-1,2,4-triazin-5(2 H)-ones (R3 = H, Bu n , Bu t), which in turn can be prepared from 4-amino-6- tert -butyl-3-methylthio-1,2,4-triazin-5(4 H)-one by MeS replacement, deamination and N2 -alkylation. The structures of the synthesized compounds were established on the basis of spectral and X-ray diffraction data. [ABSTRACT FROM AUTHOR]

• New photoacid generators based on 1,2,4-triazines were synthesized. • The prepared compounds were characterized by spectroscopic methods. • According to the results of UV spectroscopy, the compounds can be used as photoacid generators in solution and polymer films. • Crystals of three PAGs were grown and X-ray diffraction analysis was carried out. • The Hirshfeld surface and conformational analysis as well as HOMO/LUMO and UV spectra DFT calculations were discussed. The title compounds 1-(3‑ tert ‑butyl‑7-R1–4‑hydroxy-8-methylpyrazolo[5,1- c ][1,2,4]triazin-1(4 H)-yl)-2‑chloro-2,2-di- and 2,2,2-trifluoroethan-1-ones (2a-d , R1 = H , Br) were prepared by interaction of 3‑ tert ‑butyl‑8-methylpyrazolo[5,1- c ][1,2,4]triazines (1a,b) with 2‑chloro-2,2-di- or 2,2,2-trifluoroacetic anhydride respectively and water. The synthesized compounds were characterized by UV/Vis, IR, NMR, HRMS, as well as X-ray diffraction analysis of 2a,с,d. The Hirshfeld surface analysis (B3LYP/6-31(d,p)), HOMO/LUMO (6-31G*), conformational analysis (iMTD-GC), DFT/B3LYP (cc-pVDZ, PCM) and UV/Vis spectra calculations were carried out. All the synthesized compounds are active as photoacid generators in solution and polymer environment during UV irradiation. [Display omitted] [ABSTRACT FROM AUTHOR]

A series of 1,2,4-triazine derivatives bearing piperazine amide moiety has been synthesized and investigated for their potential anticancer activities. 1-[4-(5,6-Bis(4-subtituted phenyl)-1,2,4-triazin-3-yl)piperazin-1-yl]-2-[4-(3-substituted phenyl)piperazin-1-yl]ethanone derivative ( 1 – 32 ) compounds were synthesized by a four step synthetic procedure. The activity studies were evaluated using XTT method, BrdU method and flow cytometric analysis on MCF-7 breast cancer cells and NIH/3T3 (mouse embryonic fibroblast cells) healthy cells. Compounds 5 with 3-chlorophenyl and compound 7 with 4-chlorophenyl substitutions were found to be promising antiproliferative agents comparing with an effective anticancer drug, cisplatin. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of novel mono- and di(substituted)-1,2,4-triazine derivatives containing thiophene and furan rings are described. Heteroaromatic rings were provided using palladium-catalyzed cross-coupling reaction between 3-alkylsulfanyl-5-acyl-1,2,4-triazines or 5-cyano-3-alkylsulfanyl-1,2,4-triazines and heteroaromatic tin compounds. New compounds bearing masked acyl groups were also obtained. These reactions were optimized to determine the scope and limitations of this methodology and were used for preparation of oligothiophenes bearing terminal heterocyclic ring. [Copyright &y& Elsevier]

Abstract: A series of 5-Aryl-6-(4-methylsulfonyl)-3-(metylthio)-1,2,4-triazine derivatives were synthesized and their COX-1/COX-2 inhibitory activity as well as in vivo anti-inflammatory and analgesic effects were evaluated. All of compounds showed strong inhibition of COX-2 with IC50 values in the range of 0.1–0.2μM and in most cases had stronger anti-inflammatory and analgesic effects than indomethacin at doses 3 and 6mg/kg. Among them, 5-(4-chlorophenyl)-6-(4-(methylsulfonyl) phenyl)-3-(methylthio)-1,2,4-triazine (9c) was the most potent and selective COX-2 compound; its selectivity index of 395 was comparable to celecoxib (SI=405). Evaluation of anti-inflammatory and analgesic effects of 9c showed its higher potency than indomethacin and hence could be considered as a promising lead candidate for further drug development. Furthermore, the affinity data of these compounds were rationalized through enzyme docking simulation and 3D-QSAR study by k-Nearest Neighbour Molecular Field Analysis. [Copyright &y& Elsevier]

A new series of 6,8-halo-substituted-2H-[1,2,4]triazino[5,6-b]indole-3(5H)-one/-thione and 6,8-halo-substituted 5-methyl-2H-[1,2,4]triazino[5,6-b]indol-3(5H)-one/-thione (5a-5l) were designed and synthesized keeping in view of the structural requirement of pharmacophore. The above compounds were characterized by thin layer chromatography and spectral analysis. Anticonvulsant activity of the synthesized compounds was evaluated by the maximal electroshock (MES) test. Neurotoxicity and CNS depressant effects were evaluated by the rotarod motor impairment and Porsolt's force swim tests, respectively. A computational study was carried out, for calculation of pharmacophore pattern, prediction of pharmacokinetic properties and toxicity properties. The above study revealed that the compounds 8-chloro-2H- [1,2,4]triazino[5,6-b]indol-3(5H)-one (5e), 6,8-dibromo-2H-[1,2,4]triazino[5,6-b]indol- 3(5H)-one (5i) and 6,8-dibromo-5-methyl-2H-[1,2,4]triazino[5,6-b]indol-3(5H)-one (5k) possess excellent anticonvulsant activity in the series with little CNS depressant effect and no neurotoxicity as compared to standard drugs phenytoin and carbamazepine. [ABSTRACT FROM AUTHOR]

Expansion of the operational capacity of soft-Lewis basic complexant scaffolds towards improved physical properties for the chemoselective sequestration of minor actinides from the electronically similar lanthanides necessitates rapid access to synthons for efficient complexant construction for downstream employment in separations assays. Pursuant to the aforementioned, we were interested in exploring the potential utility of advanced, unsymmetric heteroarene constructs for separations which required access to pyridyl carbaldehydes. Limited commercial availability of synthetic precursors inspired our effort to define a chemoselective, microwave assisted, Kornblum-type reaction via C–H functionalization. This efficient reaction sequence uses I 2 as a mild oxidant without acidic or basic additives, in concert with DMSO as the solvent and putative oxygen source to afford a diverse array of heteroaryl products devoid of competitive remote methyl group oxidation, or degradation of the heteroaryl N atom. Method development, substrate scope, and a preliminary mechanistic hypothesis supported by Density Functional Theory are presented herein. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: A series of 16 novel 1,2,4-triazine derivatives bearing hydrazone moiety (7a–7p) have been designed, synthesized and evaluated for their activity to inhibit IL-1β and TNF-α production. All compounds are reported for the first time. The chemical structures of all compounds were confirmed by spectroscopic methods and elemental analyzes. Most of the synthesized compounds were proved to have potent anti-cytokine activity and low toxicity on PBMC and MCF-7 cell lines. Compounds 7f, 7k, 7l and 7j presented simultaneously good levels of inhibition of both cytokines. Moreover, compound 7l exhibited good anti-inflammatory effect in carrageenan-induced rat paw edema. The results of Western blotting demonstrated that the anti-cytokine potential of compound 7l is mainly mediated through the inhibition of p38 MAPK signaling pathway. Molecular docking was performed to position compound 7l into p38α binding site in order to explore the potential target. The information of this work might be helpful for the design and synthesis of novel scaffold toward the development of new therapeutic agent to fight against inflammatory diseases. [Copyright &y& Elsevier]

On interacting α-bromoacetophenones with aromatic carboxylic acid hydrazides, the formation of two reaction products was observed in certain cases, the expected 1,2,4-triazine and the phenylglyoxal dihydrazone as an unexpected product. The effect of substituents in the initial substrates and of the conditions of carrying out the synthesis on the direction of the reaction have been studied. [ABSTRACT FROM AUTHOR]

Abstract: Eleven members of new ligand class incorporating a chiral oxazoline and a 1,2,4-triazine ring have been synthesized via Pd-catalyzed amination reaction of 3-halo-1,2,4-triazines with 2-(o-aminophenyl)oxazolines. Buchwald–Hartwig amination of 3-halo-1,2,4-triazines was investigated to establish the best conditions for synthesis of the title ligands. Catalytic activity of the new ligands was evaluated in the asymmetric Henry reaction of nitromethane with a variety of aromatic and aliphatic aldehydes. The β-hydroxy nitroalkanes were obtained in high yields (up to 95%), and moderate-to-good enantioselectivity (up to 82% ee). [Copyright &y& Elsevier]

Abstract: Three new cadmium(II) complexes, [Cd2(TPT)2(SCN)4]·H2O (1), [Cd(TPT)I2] (2) and [Cd(TPT)Br2] (3) (“TPT” is the abbreviation of 3,5,6-tris(2-pyridyl)-1,2,4-triazine), have been synthesized and characterized by elemental analysis, IR, 1H NMR spectroscopy, and studied by thermal gravimetric as well as X-ray single crystal diffraction. Two anions of four thiocyanate anions bridge two CdII ions to form a dinuclear complex, 1, and iodide and bromide ions produce two halide-coordinated [Cd(TPT)X2] complexes (X=I for 2 and Br for 3). Cadmium(II) in 1 is six coordinate, CdN4S2 and in 2 and 3 is five coordinate, CdN3I2 and CdN3Br2. The supramolecular features in these complexes are guided/controlled by N⋯O hydrogen bonding (in 1) and weak directional intermolecular CN, Cg⋯I, CBr and π–π interactions. [Copyright &y& Elsevier]

Abstract: The development of new HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) offers the possibility of generating novel chemical entities of increased potency. Previous investigations in our laboratory resulted in the discovery of several novel series of arylazolylthioacetanilides as potent NNRTIs. In this study, based on the structure-based bioisosterism strategy, novel 1,2,4-triazin-6-yl thioacetamide derivatives were designed, synthesized and evaluated for their anti-HIV activity in MT-4 cells. Among them, the most promising compound was 8b15 with double-digit nanomolar activity against wild-type HIV-1 (EC50 =0.018±0.007μM) and moderate activity against the double mutant strain RES056 (EC50 =3.3±0.1μM), which indicated that 1,2,4-triazin-6-yl thioacetamide can be used as a novel scaffold to develop a new class of potent NNRTIs active against both wild-type and drug-resistant HIV-1 strains. In addition, preliminary structure–activity relationship (SAR) and molecular modeling results are also briefly discussed, which provide some useful information for the further design of novel NNRTIs. [Copyright &y& Elsevier]

Abstract: The ‘triazine’ methodology for the synthesis of functionalized pyridine ligands proved to be a convenient method for the preparation of a luminescent Pt(II) complex. The key ligand can be assembled easily starting from readily accessible reagents. Further cycloplatination and post-functionalization led to the ready-to-go luminescent ‘tag’2 for peptide labeling. [Copyright &y& Elsevier]

Coordination complexes of Co(II), Ni(II), Cu(II) and Zn(II) with Schiff base derived from syringaldehyde and 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine have been synthesized. These complexes have been characterized by elemental analysis, magnetic moment, spectroscopic (IR, Electronic, H NMR, ESR) and thermogravimetric analysis. Magnetic and spectral data suggest octahedral geometry for Co(II), Ni(II) and Zn(II) complexes and square planar for Cu(II) complexes. The presence of coordinated water in metal complexes was confirmed by thermal and IR data. The Schiff base and its metal complexes have been screened for antibacterial ( Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli, Staphylococcus aureus) and antifungal activities ( Aspergillus niger, A. flavus). A comparison is made between activities of complexes with Schiff base and with the standard antibiotics. [ABSTRACT FROM AUTHOR]

Some new Schiff bases, ( Z)-4-amino-3-(( E)-( R-methoxybenzylidene)hydrazono)-6-methyl-3,4-dihydro-1,2,4-triazin-5( 2H)-one ( R = 2 ( L2), R = 3 ( L3) and R = 4 ( L4)), were synthesized by the condensation reactions of 4-amino-3-hydrazinyl-6-methyl-1,2,4-triazin-5( 4H)-one ( L1) and corresponding methoxybenzaldehyde in a molar ratio 1:1.5 in high yields. The reaction of L2 and L4 with an excess amount of the corresponding aldehydes gave the unsymmetrical bis-Schiff bases ( E)-3-(( E)-( R-methoxybenzylidene)hydrazono)-4-(( E)- R-methoxybenzylideneamino)-6-methyl-3,4-dihydro-1,2,4-triazin-5( 2H)-one ( R = 2 ( L22) and R = 4 ( L44)), respectively. Furthermore, the reaction of L2- L4 with silver(I) nitrate in a molar ratio 2:1 led to the silver(I)-complexes with the general formula [Ag( Lx)]NO ( Lx = L2 ( 2), L3 ( 3) and L4 ( 4)). All synthesized Schiff base compounds and complexes were characterized by a combination of IR-, H-NMR spectroscopy, mass spectrometry and elemental analyses. In addition, the structures of L2, L4·CHCN, L22·CHOH and L44·CHOH and complexes 2 and 4 were determined by X-ray diffraction studies. [ABSTRACT FROM AUTHOR]

Abstract: A new route to 3-heteroaryl-1,2,4-triazines possessing a keto substituent at C-5 of the 1,2,4-triazine core using a Stille cross-coupling procedure and their unexpected ring transformation into pyridyltriazines as a result of enolization of an acyl group catalyzed by metal ions, are reported. [Copyright &y& Elsevier]

B3LYP/6-311+G() and MP2/6-31G() methods are used to study the electronic structure of a 1,2,4-triazine molecule. Quantitative characteristics of the reactivity are obtained in the form of atomic charges and Fukui coefficients. Thermodynamic characteristics are determined for the protonation reaction and addition of the hydride anion to a 1,2,4-triazine molecule. [ABSTRACT FROM AUTHOR]

Two Cd(II) complexes, [Cd(PDT)2Cl2]·H2O (1) and [Cd(PDT)2Br2][image omitted]H2O (2) (PDT is the abbreviation of 3-(2-Pyridyl)-5,6-diphenyl-1,2,4-triazine), have been synthesized and characterized by elemental analysis IR, 1H NMR spectroscopy, and studied by thermal analysis as well as X-ray crystallography. The supramolecular associations with these complexes have also been analyzed. In both cases, the cadmium(II) ion is in a slightly distorted octahedral environment. The two complexes are extended into networks (2D in 1 and 3D in 2) through hydrogen bonds and weak directional intermolecular interactions. [ABSTRACT FROM AUTHOR]

The review is devoted to the use of formazans in the synthesis of azines. [ABSTRACT FROM AUTHOR]

etylcholinesterase inhibitors played significant roles in treatment of Alzheimer's disease. Based on the research foundation of our previous work and molecular modeling, twelve 3,6-diaryl-7 H-thiazolo[3,2- b][1,2,4]triazin-7-one derivatives were synthesized and characterized by mass spectra, infrared spectra, NMR and elemental analyses. The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control. All target compounds exhibited more than 40% inhibition at 10 μM. Some target compounds showed good inhibition against AChE. The preliminary structure-activity relationships were the halogen atoms at the phenyl ring at the C6 position, the hydroxy groups and the long side chains at the phenyl ring at the C3 position of the parent nucleus played significant roles in the AChE inhibitory activity of the target compounds. [ABSTRACT FROM AUTHOR]

Pb(II) and Cd(II) complexes, {[Pb2(PDTS)2(CH3OH)((H2O)2] ⋅ H2O}n (1) and [Cd(PDTS)(H2O)4] ⋅ 2H2O (2) (PDTS2- = 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine-p,p'-disulfonate), are synthesized and characterized by elemental analysis, infrared (IR), 1H-NMR spectroscopy, and thermal analysis. The single-crystal structure of 1 shows that the complex forms a 2-D polymeric network containing two types of Pb2+ with coordination number eight (PbN2O6). Both possess hemidirected coordination geometries. The single-crystal structure of 2 shows distorted octahedral geometry for cadmium(II), CdN2O4. These compounds are the first complexes of “PDTS2-”. The supramolecular features in these complexes are guided/controlled by hydrogen bonding and noncovalent intermolecular interactions. [ABSTRACT FROM AUTHOR]

Abstract: The role of novel triazine derivatives against oxidative stress exerted by hydrogen peroxide on differentiated rat pheochromocytoma (PC12) cell line was examined and a consistent protection from H2O2-induced cell death, associated with a marked reduction in caspase-3 activation, was observed. Moreover, activation of NF-κB, a known regulator of a host of genes that involves in specific stress and inflammatory responses by H2O2, was greatly impaired by triazine pretreatment in differentiated PC12 cells. Neuroprotective effect of such compounds may represent a promising approach for treatment of neurodegenerative diseases. [Copyright &y& Elsevier]

The article focuses on the synthesis of unknown compounds containing triazine and acridine fragments via the nucleophilic substitution of chlorine atom in 9-chloroacridine with amino(hydraino, thioxo)-1,2,4-triazines. Topics discussed include the yield of the reaction products during the prolonged boiling of a mixture of 9-chloroacridine and 4-amino-6-tert-butyl-3-methylthio-1,2,4-triazine-5(4H)-one and preparations of different chemicals.

Abstract: The reaction of 5,6-diphenyl-3-hydrazino-1,2,4-triazine (1) with bis(methylthio)methylene]malononitrile (2) afforded 5-amino-1-(5,6-diphenyl-1,2,4-triazin-3-yl)-3-(methylthio)-1H-pyrazole-4-carbonitrile (3). Compound 3 reacted with thiourea to give 3,4-diaminopyrazolo[3,4-d]pyrimidine 5, which was treated with benzoyl chloride to give pyrazolo[5,4,3-kl]pyrimido[4,3-d]pyrimidine 6. Treatment of 3 with acetic anhydride produced 3-methylthio-pyrazolo[3,4-d]pyrimidine derivative 7, which was allowed to react with hydrazine hydrate to give the corresponding hydrazino derivative 8. Heterocyclization of 8 with benzoyl chloride and sodium pyruvate afforded the polyfused heterocycles 9 and 10, respectively. Reaction of 3 with benzoylacetone yielded pyrazolo[3,4-b]pyridine 12, which was allowed to react with malononitrile and acetanilide to get heterocyclic systems 13 and 14, respectively. Interaction of 3 with cyanoacetone gave pyrazolo[3,4-b]pyridine 15, which was refluxed in formic acid to yield pyrazolo[4′,3′:5,6]pyrido[4,3-d]pyrimidine 16. Reaction of 3 with 2 afforded the triazinylpyrazole derivative 17, which was reacted with hydrazine hydrate to give dipyrazolo[1,5-a:3′,4′-d]pyrimidine 19. Furthermore, treatment of the latter compound with methyl anthranilate furnished tetraheterocyclic compound 21. Structures of the products have been determined by elemental analysis and spectral studies. All compounds have been screened for their antibacterial and antifungal activities. Compounds 9, 10, 13, 19 and 21 showed maximum activity comparable to the standard drugs with lower toxicity in the case of 9 and 10. [Copyright &y& Elsevier]

Two new Pb(II) complexes, [Pb(TPT)(NO3)2]n (1) and [Pb(TPT)2(ClO4)(H2O)] · ClO4 · H2O (2) (TPT is the abbreviation of 3,5,6-tris(2-pyridyl)-1,2,4-triazine), have been synthesized and characterized by single-crystal X-ray diffraction. Lead(II) in the compounds of 1 and 2 is nine coordinate (rare mode), PbN3O6 and PbN6O3, respectively. Both have hemidirected coordination geometries. The supramolecular features in these complexes are guided/controlled by hydrogen bonding and weak directional intermolecular C-H ··· O and π ··· π interactions. The thermal stabilities of 1 and 2 were investigated by thermogravimetric measurements. [ABSTRACT FROM AUTHOR]

Reaction of bis(hexafluoroacetylacetonato)copper(II) hydrate with 1,2,4-triazine (tz) in dichloromethane yields pentakis[bis(hexafluoroacetylacetonato)triazinecopper(II)] [Cu(hfac)2(tz)]5 (hfac = hexafluoroacetylacetonate) (1). The complex crystallizes in the triclinic space group P-1, with cell parameters a = 11.4124(5), b = 13.3405(5), c = 16.1794(7) Å, α = 93.360(2)°, β = 108.700(2)°, γ = 100.293(2)° at 120(1) K. In the complex, the copper(II) ions show three types of coordination polyhedra: square planar, square pyramidal, and octahedral (4 + 2). The tz ligand also shows different coordination modes (bridging and monodentate). In addition, disorder is observed in the triazine molecule, either through non-crystallographic two-fold rotation about the longitudinal N,N-axis, or with respect to a crystallographic center of symmetry. The crystal structure of 1 consists of alternating trimers and dimers. The weak coordination of the tz molecules results in negligible magnetic exchange through the ring. [ABSTRACT FROM AUTHOR]

Novel, nitrogen-containing heterocyclic chromophores based on either 1,2,4-triazine or an imidazole core were synthesized using a three-component, one-pot reaction under microwave irradiation. Structures were verified by 1H NMR, IR, MS and elemental analyses while crystal structure was determined using X-ray diffraction. The two-photon absorption and two-photon upconverted blue fluorescent emission characteristics were investigated experimentally; preliminary structure–photophysical property relationships were established. Chromophores that contained the imidazole moiety displayed more potent two-photon absorption than compounds based upon 1,2,4-triazine and also exhibited a strong two-photon upconverted blue fluorescent emission peak at around 443–476nm. Significant enhancement of the two-photon absorption cross-section was achieved by fusing a benzoxazole moiety onto the phenanthro[9,10-d]imidazole ring. [Copyright &y& Elsevier]

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 IC 50 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. [ABSTRACT FROM AUTHOR]

Novel N1-(phosphoryl moiety)-N2-(1,2,4-triazin-3-yl)hydrazines 4, 6, 8, 9 and 12, iminophosphorane 3, iminophosphane 5, 1,2,4-triazinyldiazaphospholine 7, 1,2,4,3-triazaphospholinotriazines 2, 10, 11, and 1,2,4-triazino[3,2-c][1,2,4,5] triazaphosphine 13 have been obtained via treatment 5,6-bis(4-bromophenyl)-3-hydrazino-1,2,4-triazine (1) with various polyfunctional phosphorus reagents by stirring at room temperature or refluxing for long time in tetrahydrofuran. Structures of these compounds have been deduced upon the basis of elemental and spectral data. Molluscicidal activity of the prepared compounds against Biomphalaria Alexandrina snails (the intermediate host of Schistosoma mansoni) showed considerable activities. [ABSTRACT FROM AUTHOR]

Novel 1,2,4-triazine, pyridine, and benzopyran derivatives have been synthesized from N-(2-benzothiazolyl)cyanoacetamide via its reaction with some electrophiles. The structure of the synthesized compounds was established by analytical and spectral data. [ABSTRACT FROM AUTHOR]

Abstract: A Sonogashira/copper(I)-catalyzed heteroannulation sequence was developed to convert 3,5-diamino-6-chloro-1,2,4-triazines to the corresponding 3-amino-5H-pyrrolo[2,3-e]-1,2,4-triazine derivatives in good yields. [Copyright &y& Elsevier]

The reaction of 4-amino-6-methyl-5-oxo-3-thioxo-2H-1,2,4-triazine, (AMTTO, [1]), and 4-amino-5-methyl-3-thioxo-2H-1,2,4-triazole, (AMTT, [2]), with various aldehydes under classical heating and microwave irradiation in a solvent-free system resulted in the formation of the corresponding imines 3a–e and 4a–d. The compounds were characterized by their spectroscopic data and elemental analysis. Compound 3a was also characterized by X-ray diffraction studies. Crystal data for 3a at -80°C: triclinic, space group P-1, a = 796.7(2), b = 844.8(2), c = 1073.1(2) pm, α = 88.44(2)°, β = 76.59(2)°, γ = 63.42(2)°, Z = 2. [ABSTRACT FROM AUTHOR]

Abstract: A series of 3,7-dimethyl-pyrazolo[3,4-e][1,2,4]triazin-4-yl thiosemicarbazide derivatives 3–22 were prepared and evaluated in vitro against HM1:1MSS strain of Entamoeba histolytica, to identify the compounds for antiamoebic activity. They exhibited antiamoebic activity in the range (IC50 =0.81–7.31μM). The results were compared to the activity of known drug metronidazole. It is inferred from the in vitro studies that the compounds 10, 11, 17 and 18 were found to be significantly better inhibitors of E. histolytica since IC50 values in the μM range elicited by these compounds are much lower than metronidazole. Besides, compounds 11 and 17 have shown the most promising antiamoebic activity (IC50 =0.81μM of 11, IC50 =0.84μM of 17 versus IC50 =1.81μM of metronidazole). The study suggests the possibility of developing triazine analogues as potential drug candidates for antiamoebic activity. [Copyright &y& Elsevier]

The addition of CH-active compounds to 6-aryl-1,2,4-triazine 4-oxide is reversible and occurs under conditions of kinetic control at position 5 of the heterocycle to form cyclic C(5)-σH adducts. Under conditions of thermodynamic control the nucleophilic attack is directed to position 3 of the heterocycle and is accompanied by its opening to form the more stable open chain addition products. Attack of ethylmagnesium bromide is directed exclusively to the 5 position of the 6-aryl-1,2,4-triazine 4-oxides as a result of the irreversibility of the given reaction. [ABSTRACT FROM AUTHOR]

The synthesis of a group of 1,3,4-oxadiazoles, 1,2,4-triazoles, 1,3,4-thiadiazoles and 1,2,4-triazine derived from 2-[(2,6-dichloroanilino) phenyl] acetic acid is described. The structures of new compounds are supported by IR, 1H-NMR and Mass spectral data. These compounds were tested in vivo for their anti-inflammatory activity. The compounds, which showed activity comparable to the standard drug diclofenac, were screened for their analgesic, ulcerogenic and lipid peroxidation activities. Ten new compounds, out of 28 showed very good anti-inflammatory activity in the carrageenin induced rat paw edema test, with significant analgesic activity in the acetic acid induced writhing test together with negligible ulcerogenic action. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde content (MDA), which is one of the byproduct of lipid peroxidation. The study showed that the compounds inhibited the induction of gastric mucosal lesions and it can be suggested from our results that their protective effects may be related to inhibition of lipid peroxidation in the gastric mucosa. [Copyright &y& Elsevier]

The copper(II) and nickel(II) complexes of 5,6-diphenyl-3-(2′-hydroxyphenyl)-1,2,4-triazine, noted HLH, and 5,6-bis (4-methoxyphenyl)-3-(2′-hydroxyphenyl)-1,2,4-triazine, noted HLOMe, have been synthesized from copper(II) acetate in CH2Cl2 and nickel(II) nitrate in acetone with an excess of previously deprotonated triazine. The new complexes [Cu(LH)2]·H2O (1), [Cu(LOMe)2]·2H2O (2), Na[Ni(LH)3]·2H2O·(CH3)2CO (3), and Na[Ni(LOMe)3]·2H2O (4) were isolated as pure solids and characterized by IR, UV–Vis, elemental analysis and mass spectra. Copper(II) complexes 1 and 2 were studied by EPR, in frozen solutions. In accordance with the spectroscopic data obtained by UV–Vis, the stoichiometry of the complexes was found to be 1:2 for Cu2+:LH,OMe with a square planar environment for the metal centre. Crystals of HLOMe and 3 were obtained and studied by single crystal X-ray diffraction. The structure of HLOMe exhibits a strong deviation from planarity of the two p-methoxyphenyl rings with respect to the triazine ring while the 2-hydroxyphenyl fragment is almost coplanar. Intramolecular hydrogen bonding between one of the N atoms of the triazine ring and the phenol can explain this restraint. For 3, three LH bidentate triazines are coordinated to the nickel ion in a distorted octahedral manner. [Copyright &y& Elsevier]

The gas phase far-IR spectrum of the ν20 (A″, 367.88 cm−1) and ν21 (A″, 311.28 cm−1) bands of 1,2,4-triazine, a five membered ring having the point group Cs, has been studied at a resolution ranging from 0.002 to 0.003 cm−1. From the MW spectrum 58 transitions in the ν20 level and 64 in the ν21 level have been assigned. The ν20 and ν21 modes which are due to non-planar motions of the ring system are found to be nearly unperturbed. From a simultaneous analysis of IR and MW transitions band centers, rotational constants, and the quartic centrifugal distortion constants ΔJ, ΔJK, ΔK, δJ, and δK have been obtained using the Watson Hamiltonian, A-reduction, IIIr-representation. [Copyright &y& Elsevier]

A microwave spectrum from molecules containing three nonequivalent N atoms still presents a considerable challenge for determination of the 14N quadrupole coupling constants. None the less, assisted by ab initio calculated values at the triple zeta+polarisation and MP2 level, the spectral data of 1,2,4-triazine has yielded values for the inertial and principal axis (PA) data. In general the values for the tensor elements are in good agreement with the theoretical results. This allows the calculated PA data for the whole series of known azines, calculated at the corresponding equilibrium structures, to be used to set up a group of increment effects for added N-atoms. These in turn show that very regular changes occur, which suggest that factors such as changes in aromatic character are small across the series. [Copyright &y& Elsevier]