Synthesis and Cytotoxic Activity of Coumarin Derivatives Containing Benzotriazole Moieties

Three coumarin derivatives containing benzotriazole moieties, 3-(1-benzotriazolyl)-4-methyl-coumarin (BMC), 3-(1-benzotriazolyl)-4-methyl-benzo[7,8]coumarin (BMBC), and 3-(4-methyl-1-benzotriazolyl)-4-methyl-benzo[7,8]coumarin (MBMBC), were synthesized. Among them, 3-(4-methyl-1-benzotriazolyl)-4-methyl-benzo[7,8]coumarin has been structurally characterized by X-ray crystallography. The cytotoxic effect by Sulforhodamine B (SRB) assay with these compounds against the human hepatocellular carcinoma cell lines (HepG-2) was carried out in vitro. The preliminary results showed that all compounds inhibit HepG-2 growth effectively.     

Degradation of Benzotriazole UV Stabilizers in PAA/d-Electron Metal Ions Systems—Removal Kinetics,Products and Mechanism Evaluation

Benzotriazole UV stabilizers (BUVs) have gained popularity, due to their absorption properties in the near UV range (200–400 nm). They are used in the technology for manufacturing plastics, protective coatings, and cosmetics, to protect against the destructive influence of UV radiation. These compounds are highly resistant to biological and chemical degradation. As a result of insufficient treatment by sewage treatment plants, they accumulate in the environment and in the tissues of living organisms. BUVs have adverse effects on living organisms. This work presents the use of peracetic acid in combination with d-electron metal ions (Fe²⁺, Co²⁺), for the chemical oxidation of five UV filters from the benzotriazole group: 2-(2-hydroxy-5-methylphenyl)benzotriazole (UV-P), 2-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)-4-methylphenol (UV-326), 2,4-di-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)phenol (UV-327), 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV-328), and 2-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol (UV-329). The oxidation procedure has been optimized based on the design of experiments (DoE) methodology. The oxidation of benzotriazoles follows first order kinetics. The oxidation products of each benzotriazole were investigated, and the oxidation mechanisms of the tested compounds were proposed.     

Combining stir-bar sorptive extraction and large volume injection-gas chromatography-mass spectrometry for the determination of benzotriazole UV stabilizers in wastewater matrices

Stir‐bar sorptive extraction and liquid desorption followed by large volume injection‐gas chromatography coupled to mass spectrometry under selected ion monitoring mode acquisition (SBSE‐LD/LVI‐GC‐MS(SIM)) was applied for the determination of six benzotriazole UV stabilizers (Tinuvin P, Allyl‐bzt, Tinuvin 320, Tinuvin 326, Tinuvin 327 and Tinuvin 328) in wastewater matrices. Parameters affecting the performance of extraction and desorption steps were thoroughly evaluated using uni‐ and multivariate optimization strategies, based on the use of experimental factorial designs. Assays performed with stir bars, coated with 24 μL of polydimethylsiloxane, on 25 mL of ultra‐pure water samples spiked at the 0.5 ng/mL level, yielded recoveries ranging from 47.9±1.4% (Tinuvin P) to 103.1±3.6% (Tinuvin 326), under optimized experimental conditions. When applied to complex matrices (e.g. wastewater), the methodology showed also excellent linear dynamic ranges (0.02–10.00 ng/mL) for the six benzotriazole UV stabilizers studied with correlation coefficients higher than 0.9970, limits of quantification in between 0.004 and 0.015 ng/mL, suitable repeatability (RSD<12.7%) and reproducibility (RSD<4.5%). The application of the proposed methodology to urban sewage waters from Spain and Portugal wastewater plants revealed the presence of low contents of some benzotriazole UV stabilizers.     

UV stabilizers bonded to transition metals: Synthesis and X-ray structure of 2-(2′-hydroxyphenyl)benzotriazole-oxovanadium(IV) and -dioxomolybdenum(VI) complexes

The UV-stabilizer 2-(2′-hydroxy-5′-methylphenyl)benzotriazole (Tinuvin P, LH) has been used as a monoanionic bidentate ligand for complexing oxocations. Displacement of acacH from [VO(acac)₂] and [MoO₂(acac)₂] gave [*VO(acac)₂*(μ-L)] (2) and [cis-O₂Mo(acac)L] (3) respectively, as crystalline compounds. Their structure has been determined by an X-ray analysis showing the structural changes occurring upon coordination. The UV spectrum of Tinuvin P is significantly affected by complexation.     

Rapid identification and semi-quantitative determination of polymer additives by desorption electrospray ionization/time-of-flight mass spectrometry

A fast and simple method for the direct qualitative and semi-quantitative determination of a set of four polymer additives in plastic samples by desorption electrospray ionization time-of-flight mass spectrometry (DESI-TOF-MS) is presented. After evaluation of crucial DESI parameters such as composition of spray solutions and spray voltages, a series of lab-made polypropylene samples containing Chimassorb 81 (2-hydroxy-4-n-octoxybenzophenone), Tinuvin 328 (2-(2-hydroxy-3, 5-ditert-pentylphenyl)-benzotriazole), Tinuvin 326 (2-(2-hydroxy-3-tert-butyl-5-methylphenyl)-5-chloro benzotriazole), and Tinuvin 770 (bis(2,2,6,6,-tetramethyl-4-piperidyl)sebaceate) in concentrations between 0.02% and 0.2% were analyzed, resulting in calibration graphs with R ² better than 0.994. To demonstrate the applicability of the developed method for the investigation of real samples, liners for in-ground swimming pools and polypropylene granules were analyzed with respect to their content in the selected polymer additives. Two alternative methods, both well established in the fields of polymer additive analysis, namely HPLC with UV detection (after previous extraction) and thermodesorption gas chromatography/mass spectrometry have been employed for evaluation of the results from the DESI experiments.     

含4-噻唑啉酮环的新烟碱类化合物的合成及生物活性

根据生物等排原理和新烟碱类化合物与乙酰胆碱酯酶的作用机理, 以4-噻唑啉酮(4)为中间体设计合成了2-取代-3-(2-氯-5-吡啶亚甲基)-4-氰基亚胺基-1,3-噻唑烷(8a~8c)和5-芳基次甲基-2-芳基-3-(2-氯-5-吡啶亚甲基)-4-噻唑啉酮(5a~5e)两类化合物. 中间体(4)由醛、胺和巯基乙酸缩合得到. 所有化合物的结构均经元素分析和1H NMR确证. 初步生物活性试验结果表明, 部分化合物具有一定的杀菌活性和促进黄瓜子叶生根活性, 化合物8b显示出很好的抗HIV-1蛋白酶活性.     

β-Benzotriazolylethyl phosphates and phosphonic esters

β-(1-Benzotriazolyl)ethyl dibutyl phosphate and the 2-benzotriazolyl analog were prepared from dibutyl phosphite and 1- and 2-(β-hydroxyethyl)benzotriazoles, respectively. Dialkyl β-(N-benzotriazolyl) ethylphosphonates were prepared from the corresponding dialkyl β-bromoethylphosphonates. In both types of compounds, elimination of benzotriazole occurs in base; interestingly, such elimination is significantly faster in each series for the 2-substituted benzotriazole than for the corresponding 1-isomer.     

A Highly Efficient UV‐C Absorber Based on Theoretical and Experimental Studies

Based on two published UV absorbing molecules 2‐(5′‐tert‐butyl‐2′‐hydroxyl)benzotriazole (Tinuvin‐PS ) and hydroxybenzophenone (HBP ), both having characteristic absorption capability, a refined UV absorber, 2‐(3′‐benzoyl‐2′‐hydroxy‐5′‐tert‐butylphenyl)benzotriazole, has been synthesized. This new UV absorber exhibits a wider absorption range and better thermal stability compared to either Tinuvin‐PS and HBP and a higher absorption efficiency in the UV ‐C range. Theoretical studies reveal that the UV ‐C absorption arises from the electron density transfer from the Tinuvin‐PS moiety to the HBP moiety and the enhanced absorption efficiency is ascribed to the presence of the carbonyl's π system.     

N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类新化合物的合成及生物活性

以N-吡啶基吡唑甲酸和2-氨基-3-甲基苯甲酸为起始原料,经由亲核加成、环化和酰化等多步反应合成了一系列结构新颖的N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类化合物.测试了所合成化合物的杀虫及抑菌活性,结果表明,新化合物大多化合物在200 mg·L^-1浓度下对东方粘虫(Mythimna separataWalker)具有一定的杀虫活性,尤其是N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)乙酰胺(8a)和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3-氯-2,2-二甲基丙酰胺(8e)致死率可达70%;部分化合物在50 mg·L^-1浓度下对油菜菌核病菌的抑菌活性相对较好(54.5%~63.6%),优于triadimefon和chlorantraniliprole;部分化合物如N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3,3-二甲基丁酰胺80和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-4-氟苯甲酰胺(8h)对苹果轮纹病菌具有中等抑菌活性.值得注意的是,化合物8e的杀粘虫活性和对油菜菌核病菌的抑菌活性都较为突出,可用作新农药创制研究的新型参考结构.     

Convenient preparation of tert-butyl beta-(protected amino)esters

Refluxing an aldehyde 1 with benzotriazole and benzylcarbamate in the presence of a catalytic amount of p-TsOH gave the corresponding benzyloxycarbonylamino-1-(1-benzotriazolyl)alkane 2 in good yields. Compounds 2 treated with substituted tert-butyl acetates 3 using LDA as a base afford smoothly and under mild conditions the N-2-protected 3-aminoalkanoic esters 4.     

含吡唑1,2,4-三唑噻二嗪衍生物的合成及抑菌活性

1-苯基-3-甲基-5-氯-4-吡唑甲醛与4-氨基-5-取代苯基-1,2,4-三唑-3-硫酮缩合生成4-(1-苯基-3-甲基-5-氯吡唑次甲亚胺基)-5-(取代苯基)-2H-1,2,4-三唑-3(4H)-硫酮,再烷基加成化为新型含吡唑基5,6-2H-1,2,4-三唑[3,4-b][1,3,4]噻二嗪衍生物。 化合物结构经¹H NMR、IR以及元素分析确认。 初步生物活性测试结果表明,在100 mg/L浓度下,化合物8a(3-(2-甲基苯基)-6-(5-氯-2-甲基-4-苯基吡唑)-7-(4-硝基苯基)-5H-1,2,4-三唑[3,4-b][1,3,4]噻二嗪)对黄瓜炭疽病的抑制率达90%。     

新型α1受体拮抗剂先导化合物的寻找(I): 5-氯-2-(4-(芳氧烷基)哌嗪-1-基)苯并噁唑类化合物的设计、合成及生物活性研究

为寻找用于治疗良性前列腺增生的新型α1受体拮抗剂, 以本研究组发现的2-[(4-(2-(2-氯苯氧基)乙基)哌嗪-1-基)甲基]-5-甲基苯并噁唑(wb5c)为先导化合物, 结合已构建的α1-AR拮抗剂药效团模型, 通过骨架改造, 设计出以苯并噁唑-2-基哌嗪为母核的目标物, 然后以5-氯-2-氨基酚和取代苯酚为原料, 经缩合、卤代、氨化、Williamson醚合成、取代等反应共合成11个新目标化合物, 结构经ESI-MS, 1H NMR, IR及HRMS确证. 初步药理活性实验表明, 目标物具有中等强度α1受体拮抗活性, 符合我们提出的三元素药效团模型. 5-氯-2-[4-(芳氧烷基)哌嗪-1-基]类化合物是一类新的具有潜在开发价值的α1受体拮抗剂.     

Determination of midazolam and its major hydroxy metabolite in plasma by gas liquid chromatography. Application to a pharmacokinetic study

A sensitive gas liquid chromatographic (GLC) assay was developed for plasma determinations of 8-chloro-6-(2′ -fluorophenyl)-1-methyl-4H-imidazo[1,5 α][1,4]benzodiazepine (compound I) and its hydroxymethylimidazo metabolite (compound II). The internal standards used were 8-chloro-6-(2′ -chlorophenyl)-1 -methyl-4H-imidazo[1,5 α][1,4]benzodiazepine (compound VI) and 7-chloro-5-(2′ -fluorophenyl)-1, 3-dihydro-1-(hydroxyethyl)-2H-1,4-benzodiazepin-2-one (compound VII) for compounds I and II, respectively. Following extraction, and silylation for compound II, compounds I and II were analyzed by GLC using a glass column packed with 5% OV-101 on Gas-Chrom Q, and a ⁶³Ni electron-capture detector. The GLC method was validated by a CI-GC/MS technique. The detection limit of the assay is approximately 4–5 ng/ml for compound I and 3 ng/ml for compound II. The method was used in comparative pharmacokinetic studies of the distribution of the two compounds in arterial and venous blood.     

Simultaneous determination of benzotriazoles and ultraviolet filters in ground water, effluent and biosolid samples using gas chromatography-tandem mass spectrometry

A new method using gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed for the determination of four benzotriazoles, i.e. benzotriazole (BT), 5-methylbenzotriazole (5-TTri), 5-chlorobenzotriazole (CBT), 5,6-dimethylbenzotriazole (XTri), and six UV filters, i.e. benzophenone-3 (BP-3), 3-(4-methylbenzylidene)camphor (4-MBC), octyl 4-methoxycinnamate (OMC), 2-(3-t-butyl-2-hydroxy-5-methylphenyl)-5-chloro benzotriazole (UV-326), 2-(2'-hydroxy-5'-octylphenyl)-benzotriazole (UV-329), and octocrylene (OC) in ground water, effluent and biosolid samples. Solid phase extraction (SPE) and pressurized liquid extraction (PLE) were applied as the preconcentration method for water samples (ground water and effluent) and biosolid samples, respectively. The optimized method allowed us to quantify all target compounds with the method detection limits ranging from 0.29 to 11.02 ng/L, 0.5 to 14.1 ng/L and 0.33 to 8.23 ng/g in tap water, effluent and biosolid samples, respectively. The recoveries of the target analytes in tap water, effluent and biosolid samples were 70-150%, 82-127% and 81-133%, respectively. The developed analytical method was applied in the determination of these target compounds in ground water, effluent and biosolid samples collected from Bolivar sewage treatment plants in South Australia. In effluent samples, the target compounds BT, 5-TTri, CBT, XTri and BP-3 tested were detected with the maximum concentration up to 2.2 μg/L for BT. In biosolid samples, eight out of ten compounds tested were found to be present at the concentrations ranging between 18.7 ng/g (5-TTri) and 250 ng/g (4-MBC).     

Chemical constituents from the colombian medicinal plant Niphogeton ternata

Two coumarins and one polyacetylene, 5-0-(3-chloro-2-hydroxy-3-methylbutyl)-8-methoxypsoralen (1), 2',3'-dihydro-jatamansin (2), and 10-chloro-1-heptadecene-4,6-diyne-3,8,9-triol (3), along with 15 known compounds (4-18), were isolated from the methanol extract of Niphogeton ternata. Their structures were elucidated by spectroscopy.     

Synthesis and pesticidal activities of novel anthranilic diamides containing pyridylpyrazole and iminodithiocarbamate or thiosemicarbazone motifs

Abstract

A series of novel anthranilic diamide derivatives containing pyridylpyrazole and iminodithiocarbamate or thiosemicarbazone motifs were synthesized via multi-step reactions. The structures of seven title compounds (methyl 2-(2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamido)-5-chloro-3- methylbenzylidene)hydrazinecarbodithioate 7 and 3-bromo-N-(2-((2-substitutedcarbamothioylhydrazono)methyl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 8a-8f) were confirmed by melting points, IR, ¹H NMR, ¹³C NMR, and HRMS. The bioassays showed that some of the compounds exhibited modest insecticidal activities against oriental armyworm (Mythimna separata Walker), particularly, compound 8b (3-bromo-N-(4-chloro-2-methyl-6-((2-(methylcarbamothioyl)hydrazono)methyl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide) held 100% and 30% larvicidal activity at the concentration of 25?mg/L and 10?mg/L, respectively. In addition, several compounds displayed favorable fungicidal activities against Alternaria solani Sorauer and Physalospora piricola at 50?μg/mL, and were comparable with the controls Chlorothalonil and Triadimefon. The results in this paper will provide important information for further research and development of sulfur-containing heterocyclic agrochemicals.     

In vitro antioxidant properties of new thiazole derivatives

A series of novel N2-[2-chloro-4(3,4,5-trimethoxy phenyl azetidin-1-yl]-N4-(substituted aryl)-1,3-thiazole-2,4-diamine (4a–g) were synthesized starting from 3,4,5-trimethoxy benzaldehyde thiosemicarbazone (1). The compound (1) was obtained by condensing 3,4,5-trimethoxy benzaldehyde with thiosemicarbazide in methanol. 3,4,5-Trimethoxy benzaldehyde thiosemicarbazone (1) on treatment with chloracetyl chloride afforded 4-chloro-[2-(3,4,5-trimethoxy benzylidine) hydrazinyl]-1,3-thiazole (2). Compound (2) was reacted with chloracetyl chloride and triethylamine to obtain the corresponding 4-chloro-N-[2-chloro-4(3,4,5-trimethoxy phenyl) azetidin-1-yl]-1,3-thiazole-2-amine (3). Various substitutions on compound 3 with secondary amines yielded series of compounds (4a–g). The newly synthesized compounds were characterized by IR, ¹H NMR, elemental analysis and mass spectral studies. All the compounds were screened for their in vitro antioxidant properties. The IC₅₀ values of compounds 3 and 4a–g revealed that some of the synthesized compounds were showing potent antioxidant activity.     

N-甲氧基-N-{2-[2-取代-4-氯-3(2H)哒嗪酮-5-氧(硫)亚甲基]苯基}氨基甲酸甲酯的合成及其生物活性

2取代4氯5羟基(巯基)3(2H)哒嗪酮与N甲氧基N2溴甲苯氨基甲酸甲酯反应合成了一系列新型N甲氧基N{2[2取代4氯3(2H)哒嗪酮5氧(硫)亚甲基]苯基}氨基甲酸甲酯,其结构经1HNMR,IR和LCMS确认。生物活性测定表明,该类化合物在50mg·L-1下对稻瘟病菌,黄瓜灰霉,小麦赤霉病等具有较高的抑菌活性。     

Design,synthesis, and pesticidal activities of novel pyrimidin-4-amine derivatives containing trifluoroethyl sulfide moiety

In order to overcome the problem of pesticide resistance, it is necessary to discover novel pesticides with new mechanisms of action. Herein, a series of novel pyrimidin-4-amine derivatives containing trifluoroethyl sulfide moiety were designed and synthesized. Bioassays indicated that the title compounds synthesized possessed excellent acaricidal activity against Tetranychus urticae and fungicidal activity against Erysiphe graminis and Puccinia sorghi. Especially, the acaricidal activity of 5-chloro-6-(difluoromethyl)-N-(2-(2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)phenoxy)ethyl)pyrimidin-4-amine (compound T4 , LC₅₀ = 0.19 mg/L) against T. urticae was close to commercial acaricide cyenopyrafen, and the fungicidal activity of 5-chloro-6-(difluoromethyl)-2-methyl-N-(2-(3-((2,2,2-trifluoroethyl)thio)phenoxy)ethyl)pyrimidin-4-amine (compound T15 , EC₅₀ = 1.32 mg/L) against P. sorghi. was superior to commercial fungicide tebuconazole. The synthesis and characterization of these compounds were given and the structure–activity relationships were discussed.     

Synthesis and antitumor activity of novel pyridazinone derivatives containing 1,3,4-thiadiazole moiety

Abstract

A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by ¹H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)?4-chloro-5-((5-((2-ethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5?±?0.4% and 95.7?±?1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)?4-chloro-5-((5-((3-fluorophenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3?±?2.2% and 92.3?±?0.6% at a concentration of 10?μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)?4-chloro-5-((5-((2,3-dimethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5?m (2-(Tert-butyl)?4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells.