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

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

微波辐射下1,2,4-三唑硫酮席夫碱的合成及表征

微波辐射条件下,以氨基均三唑硫醇与查尔酮为原料,通过亲核取代反应,制备了3-(4-氨基-5-硫基-3-苯基均三唑-1-氮代)-1,3-二苯-1-丙酮(Ⅳ),Ⅳ与系列芳香醛经缩合反应,合成了7种三唑硫酮席夫碱Ⅴa～Ⅴg。探讨了原料摩尔比、催化剂用量、反应时间、溶剂、微波辐射功率对收率的影响,得到了优化的工艺条件:n(芳香醛)∶n(氨基三唑硫酮)=1∶1.1,微波功率500 W,催化剂冰醋酸2 mL,反应时间5～7 min,溶剂为N,N-二甲基甲酰胺(DMF),收率为71%～87%。用IR、MS、1HNMR、元素分析对合成中间体和目标产物进行了结构表征。     

Hybridized 4-Trifluoromethyl-(1,2,3-triazol-1-yl)quinoline System: Synthesis,Photophysics, Selective DNA/HSA Bio-interactions and Molecular Docking

The synthesis, structural analysis, and evaluation of the photophysical properties of twelve novel 2-aryl(heteroaryl)-6-(4-alkyl(aryl)-1H-1,2,3-triazol-1-yl)-4-(trifluoromethyl)quinolines ( 6-8 ), where aryl(heteroaryl)=Ph, 4-Me-C₆H₄, 4-F-C₆H₄ and 2- furyl; 4-alkyl(aryl)=−CH₂OH, −(CH₂)₅CH₃ and Ph, are reported. Hybrid scaffolds 6 – 8 were synthesized at 77–95 % yields by regioselective copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction of unpublished 6-azido-4-(trifluoromethyl)quinolines ( 2 ) with selected terminal alkynes ( 3 – 5 ). Azido intermediates 2 were obtained from the reaction of 6-amino-4-(trifluoromethyl)quinolines ( 1 ) and sodium azide at good yields (78–87 %). Compounds 6 – 8 were structurally fully characterized by ¹H−, ¹³C− and ¹⁹F− and ¹H−¹³C 2D-NMR (HSQC, HMBC) spectroscopy, X-ray diffraction (SC-XRD) and HRMS analysis. Moreover, the photophysical properties, DNA- and HSA-binding experiments (bio-interactions), and molecular docking studies for compounds 6 – 8 were performed. These are discussed and compared with similar compounds from recent research.     

Lithium insertion/deinsertion properties of new layered vanadium oxides obtained by oxidation of the precursor H2V3O8

The electrochemical behavior of the three new vanadium oxides M_yH_1−yV₃^VO₈ (M=Li, Na, K; y=0.6-0.9) towards lithium insertion was studied. For each compound, the main insertion phenomena, and the lithium amount which can be inserted, were determined from galvanostatic studies performed at different rates. In order to better explain the differences between the compounds, the galvanostatic intermittent titration technique was used and chronoamperometry experiments were performed. Cyclability studies have shown that the performances of M_0.6H_0.4V₃O₈ (M=Li, K) are not better than those of H₂V₃O₈. On the contrary, Na_0.9H_0.1V₃O₈ presents very interesting lithium insertion properties, with a specific capacity of 215 mAh g⁻¹ in the 1.5-4 V voltage range at C/10, and a capacity loss at the 40th cycle remaining smaller than 2.5%. Na_0.9H_0.1V₃O₈ is therefore a good candidate as positive electrode material for rechargeable lithium batteries.     

Synthesis and Evaluation of Some Triazole Derivatives as Corrosion Inhibitors and Biocides

Three compounds namely; 5-(phenyl)-4H-1,2,4-triazole-3-thiol, 3-(decylthio)-5-phenyl-1H-1,2,4-triazole and 3-(benzylthio)-5-phenyl-1H-1,2,4-triazole) were synthesized. The chemical structure of the prepared compounds was confirmed using FTIR and ¹H-NMR analysis. The compounds were tested as corrosion inhibitors against the corrosion of carbon steel in 1 M HCl using weight loss, polarization and electrochemical impedance methods. The results revealed that these compounds have significant inhibiting effects on the corrosion of carbon steel. Polarization studies showed that the compounds act as mixed-type inhibitors which retard the anodic and the cathodic reactions with a predominant effect towards the cathodic reaction. The prepared compounds were evaluated as antimicrobial agents against sulfate-reducing bacteria using the serial dilution method, which showed good biocidal action.     

Molecular Rearrangement of Pyrazino[2,3-c]quinolin-5(6H)-ones during Their Reaction with Isocyanic Acid

New tetrahydropyrazino[2,3-c]quinolin-5(6H)-ones were prepared from 3-chloroquinoline-2,4(1H,3H)-diones and ethylene diamine. In their reaction with HNCO, an unprecedented molecular rearrangement produced new types of hydantoin derivatives. All prepared compounds were characterized on the basis of their ¹H, ¹³C, and ¹⁵N NMR and ESI mass spectra and some were authenticated by X-ray analysis of single crystalline material. A proposed mechanism for rearrangement is discussed in this essay. The CDK and ABL inhibition activity as well as in vitro cytotoxicity of the prepared compounds was also tested.     

含取代吡唑基的1,2,4-三唑并[3,4-b]-1,3,4-噻二唑类化合物的合成与波谱表征

通过3-烷基／芳基-4-氨基-5-巯基-1,2,4-三唑与1-苯基-3-甲基-5-氯吡唑甲醛进行分子内的Mannich反应,合成了12个标题化合物,并经元素分析、红外光谱、核磁共振氢谱确证结构,讨论了,其波谱性质。     

Synthesis,Characterization and Anti-Breast Cancer Activity of New 4-Aminoantipyrine-Based Heterocycles

4-Aminoantipyrine was utilized as key intermediate for the synthesis of pyrazolone derivatives bearing biologically active moieties. The newly synthesized compounds were characterized by IR, ¹H- and ¹³C-NMR spectral and microanalytical studies. The compounds were screened as anticancer agents against a human tumor breast cancer cell line MCF7, and the results showed that (Z)-4-((3-amino-5-imino-1-phenyl-1H-pyrazol-4(5H)-ylidene)methylamino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 5, 3-(4-bromophenyl) -1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 13, 1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1-Hpyrazol- 4-yl)-3-(4-iodophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 14, 3,3′-(4,4′-sulfonylbis(4,1-phenylene))bis(1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol- 4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) 16, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-hydrazono-4-oxo-3-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 17, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-3-phenyl-2-(2-phenylhydrazono)-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile 18, and (Z)-4-(3-amino-6-hydrazono-7-phenyl-6,7-dihydro pyrazolo[3,4-d]pyrimidin-5-yl)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 19 were the most active compounds with IC₅₀ values ranging from 30.68 to 60.72 μM compared with Doxorubicin as positive control with the IC₅₀ value 71.8 μM.     

Structure-Based Design,Synthesis, and Biological Evaluation of Imidazo[4,5-b]Pyridin-2-one-Based p38 MAP Kinase Inhibitors: Part 2

We identified novel potent inhibitors of p38 mitogen-activated protein (MAP) kinase using a structure-based design strategy, beginning with lead compound, 3-(butan-2-yl)-6-(2,4-difluoroanilino)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one ( 1 ). To enhance the inhibitory activity of 1 against production of tumor necrosis factor-α (TNF-α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5-b]pyridin-2-one core was successfully linked with the p-methylbenzamide fragment. Among the compounds evaluated, 3-(3-tert-butyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-4-methyl-N-(1-methyl-1H-pyrazol-3-yl)benzamide ( 25 ) exhibited potent p38 inhibition, superior suppression of TNF-α production in hWB cells, and also significant in vivo efficacy in a rat model of collagen-induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors.     

Separation and preconcentration of lead,chromium and copper by using with the combination coprecipitation-flame atomic absorption spectrometric determination

A coprecipitation method was developed for the quantitative separation and preconcentration of Pb(II), Cr(III) and Cu(II) ions. Analytes were coprecipitated using a triazole derivative (2-{4-[2-(1H-indol-3-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}-N-aryl methylidene acetohydrazid). The analytes were analyzed by flame atomic absorption spectrometry. The parameters such as sample pH, amount of reagent, sample volume, matrix effects etc. were investigated. The enrichment factor for the analyzed metal ions was obtained as 50. The relative standard deviations (RSD) were in the range of 2.8–4.1%. The accuracy of the proposed procedure was checked by the analysis of the CRM-C-Sandy Soil C. The method was successfully applied to real samples.     

A porous metal–organic framework as active catalyst for multiple C–N/C–C bond formation reactions

A 3D porous metal–organic framework {[Cu(4-tba)₂](solvent)}_n (1⋅S) is assembled via 4-(1H-1,2,4-triazol-1-yl)benzoic acid (Htba) and Cu(II) nodes, which shows the [2 + 2] roto-translational interpenetrating network. Interestingly, 1 displays high CO₂ adsorption selectivity over CH₄/H₂/O₂/Ar/N₂ gases, and acts an efficient catalyst precursor in some C–N/C–C bond formation reactions, including Chan–Lam coupling reaction of phenylboronic acid with imidazole, Suzuki–Miyoura coupling reaction of phenylboronic acids with aryl halides, and Heck coupling reaction of styrene with aryl halides.     

Synthesis,structure and properties of a novel 3D pentanuclear [Zn5(OH)2]8 + cluster-based (3,4,11)-connected coordination polymer

A novel coordination polymer based on the multidentate N-donor ligand 1-((1H-1,2,4-triazol-1-yl)methyl)-3,5-bis(3-pyridyl)-1,2,4-triazole (3,3′-tmbpt) and 1,2,4,5-benzenetetracarboxylate anion (btec), namely, [Zn₅(3,3′-tmbpt)(btec)₂(OH)₂] (1), has been synthesized hydrothermally. Compound 1 displays a rare 3D (3,4,11)-connected framework based on a [Zn₅(OH)₂]^8 + cluster. The optical band gap and photoluminescent property of compound 1 have been studied.     

4,5-二氢-3-甲基-1-(2,4-二氯苯基)-1,2,4-三唑-5(1H)酮的合成

乙酰亚氨酸甲酯盐酸盐与2,4-二氯苯肼在三乙胺的作用下生成2-(2,4-二氯苯基)酰肼乙烷亚胺酸。然后在光气中环合得到4,5-二氢-3-甲基-1-(2,4-二氯苯基)-1,2,4-三唑-5(1H)酮。反应总收率为90.6%(以2,4-二氯苯肼计),含量为98.9%。     

Characterization and conversion determination of stable PEDOT latex nanoparticles synthesized by emulsion polymerization

In this research, poly(3,4-ethylenedioxythiophene) (PEDOT) latex nanoparticles with good colloidal stability were prepared by emulsion polymerization and the conversions of EDOT were determined. Two kinds of oxidants, Iron(III) p-toluenesulfonate Fe(OTs)₃ and hydrogen peroxide H₂O₂, were introduced to decrease the use of iron salt and therefore reduce the particle coagulation. The ferrous ions (Fe²⁺) produced during the polymerization would be re-oxidized back to the reactive ferric ions (Fe³⁺) with the help of H₂O₂. This cyclic oxidation-reduction process resulted in the sustained regeneration of Fe³⁺ ions and led to a higher conversion. A dark blue PEDOT latex with long-term dispersion stability was obtained when Fe(OTs)₃ and H₂O₂ were added in sequence. The results obtained from dynamic light scattering and TEM measurements showed that the sizes of nanoparticles were around 100 nm. To determine the conversion of EDOT, two methods (gravimetric analysis and UV-visible method) were used and compared. For the first time, the UV-visible method was established to quantitatively determine the conversion of EDOT monomer. From the measurement, the conversion of EDOT in this system was determined as 74-75%. The PEDOT film prepared by drying the latex solution had conductivity up to 6.3 S/cm.     

Cyclisierungsreaktionen von 1-[2-Amino-1-cyan-2-thio-]ethylen-pyridiniumbetainen

Cyclization Reactions of 1-[2-amino-1-cyano-2-thio-]ethenepyridinium Ylides 1-[2-Amino-1-cyano-2-thio-]ethene-pyridinium ylides 1 can be alkylated with methyliodide or α-haloesters and α-haloketones, respectively, to form 1-[2-alkyl(aryl)amino-1-cyano-2-methylthio-ethene-1]pyridinium iodides 2a-–e or 1-[2-alkyl(aryl)-amino-1-cyano-2-alkoxy(aryl)-carbonylmethylthio-ethene-1] pyridinium salts 3a–f . With the exception of 3a–b the compounds 3 or 1 react with haloketones to yield 1-[4-amino-2-alkyl-(aryl)amino-5-benzoyl-thiene-3]pyridinium salts 4a–m or 3-alkyl-4-aryl-2-(1-cyano-1-pyridinium)methylene-Δ⁴-thiazoline salts 5a–f .     

4,5-二氢-3-甲基-1-(4-氯-2-氟苯基)-4-二氟甲基-1,2,4-三唑-5(1H)酮的合成方法

4,5-二氢-3-甲基-1-(4-氯-2-氟苯基)-4-二氟甲基-1,2,4-三唑-5(1H)酮是超高效含氟除草剂唑酮草酯的重要中间体,采用高温氟化的方法,通过优化反应条件,使目标化合物的合成收率达75.4%,含量达97.3%,降低了成本,更利于工业化生产.     

Nox Gene Expression and Cytochemical Localization of Hydrogen Peroxide in Polyporus umbellatus Sclerotial Formation

The effect of temperature shift on Polyporus umbellatus sclerotial development was investigated. Micromorphology of the sclerotia was observed by using scanning electron microscopy (SEM). The cytochemical localization of H₂O₂ expressed as CeCl₃ deposition at the subcellular level was observed by using transmission electron microscopy (TEM). Nox gene expression in sclerotia and mycelia was detected by quantitative real-time PCR (qRT-PCR) analysis. In addition, superoxide dismutase (SOD) and catalase (CAT) specific activities increased during sclerotial development and decreased after the antioxidant diphenyleneiodonium (DPI) was used. Results indicated that the temperature shift treatment induced P. umbellatus sclerotial formation. Compared with the mycelia, the Nox gene was respectively upregulated by 10.577-, 30.984- and 25.469-fold in the sclerotia of SI, SD and SM stages respectively. During the sclerotial formation, H₂O₂ accumulation was observed in the cell walls or around the organelle membranes of the mycelial cells. The antioxidant DPI decreased the generation of H₂O₂ in mycelial cells. The specific activity of SOD and CAT levels was decreased significantly by DPI. The activity of the two antioxidant enzymes in the mycelia increased much more during sclerotial formation (p < 0.05). Oxidative stress was closely associated with sclerotial development in P. umbellatus induced by temperature shift treatment.     

An efficient synthesis of [1,3,4]thiadiazolo[2,3-c][1,2,4] triazin-4-ones

A three-component reaction between 4-amino-6-methyl-3-thioxo-3,4-dihydro-2H-[1,2,4]triazin-5-one, ammonium thiocyanate and aroyl chlorides in the presence of N-methylimidazole to afford the [1,3,4]thiadiazolo[2,3-c][1,2,4]triazin-4-ones in excellent yields is described.