Design, synthesis and insecticidal activity of novel anthranilic diamides with benzyl sulfide scaffold

A series of novel anthranilic diamides with benzyl sulfide scaffold were synthesized,in which N-pyridylpyrazole moiety generally regarded as key pharmacophore was abandoned.The target compounds were characterized by ¹H NMR,¹³C NMR,¹⁹F NMR and HRMS.The preliminary bioassays indicated that half of the title compounds were endowed with good insecticidal activities against armyworm（Mythimna sepatara） at the concentration of 500 mg/L,Exhilaratingly,the synthesized compound 3a was also active against Tetranychus cinnabarinus at 100 mg/L.The difference in activities between the target compounds was influenced by the substituents,which provided some hints for further investigation on structure modifications.     

Design,synthesis and insecticidal activities of novel anthranilic diamides containing polyfluoroalkyl pyrazole moiety

In order to discover new molecules with good insecticidal activities, a series of anthranilic diamides containing polyfluoroalkyl pyrazole were designed and synthesized, and their structures were characterized by ¹H NMR and HRMS. Bioassays demonstrated that some of the title compound exhibited excellent insecticidal activities. The larvicidal activities of compound 8a, 8c, 8g, 8k and 8l against Mythimna separata Walker were 100% at 0.8 mg/L. The insecticidal activities of compound 8a, 8c, 8e, 8g, 8k and 8l against Plutella xylostella Linnaeus were 100% at 0.4 mg/L. Surprisingly compounds 8a and 8c still showed 100% larvicidal activities against Plutella xylostella Linnaeus at 0.08 mg/L comparable to the commercialized Chlorantraniliprole. The LC₅₀ of compound 8a and 8c against M. separata is 0.048 and 0.043 mg/L respectively.     

Design,synthesis and insecticidal activities of novel anthranilic diamides containing fluorinated groups as potential ryanodine receptors activitors

In order to search for novel potent and environmentally benign insecticides, a series of anthranilic diamides containing various fluorinated groups were designed and synthesized. Their structures were confirmed by ¹H NMR, ¹³C NMR, ¹⁹F NMR, elemental analysis, HRMS or mass spectra. Their insecticidal activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) were evaluated. The preliminary structure-activity relationship (SAR) was discussed in detail. The biological assay indicated that most of the compounds exhibited moderate to excellent insecticidal activities. Especially, Ia showed high larvicidal activity against oriental armyworm. Meanwhile, Iu had better larvicidal effects against diamondback moth than commercial chlorantraniliprole.     

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.     

Synthesis,insecticidal activities,and SAR studies of novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives

Diamide compounds such as chlorantraniliprole, a famous anthranilic diamide insecticide targeting the insect ryanodine receptor (RyR), have received continuous attention in pesticide research during the past 15 years owing to their excellent insecticidal potentials. With the aim of discovering new heterocyclic pesticides used for crop protection, based on the structural information of compound M from the reported pharmacophore-based virtual screening for RyR insecticides and diamide compound, a series of new heterocyclic mono-, di-, and tri-amide derivatives containing piperazine moiety have been synthesized in this paper. The new compounds were identified and confirmed by melting point, ¹H NMR, ¹³C NMR and HRMS. Compound M was firstly validated for insecticidal activities, and the new synthesized compounds were all made comprehensive insecticidal evaluations against diamondback moth and oriental armyworm. The bioassay results showed that some of the compounds exhibit favorable insecticidal potentials, particularly some novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives such as 8g, 14a, 15a, 15g, 15i, 15j, 15k, 15l, and 15m could be used as new insecticidal leading structures for further study (e.g., towards diamondback moth, 15i-15m LC₅₀: 0.0022−0.0081 mg/L). The structure-activity relationships of the compounds discussed in detail provide useful guidance for further design and development of new insecticides.     

The exploration of chiral N-cyano sulfiliminyl dicarboxamides on insecticidal activities

Due to new mechanism of action and ecofriendly characteristics,dicarboxamide insecticides have attracted more and more attentions in modern pest management.A series of 20 dual chiral N-cyano sulfilimines containing two centers(carbon and sulfur) were designed and synthesized.All title compounds were determined by ~1H NMR,high-resolution mass spectrometry(HRMS) and optical polarimeter.The preliminary results indicated that some of them exhibited favourable insecticidal activities against oriental armyworm(Pseudaletia separata Walker).These isomers exhibited different impact on activity following the sequence as(Sc,Ss) (Sc,Rs),and the rule of title compounds' activity against oriental armyworm was 3-CF_3≥2—CH_3—4—Cl2,3,4-trifluro in the anilide moiety.The results indicated that these groups such as 3-CF_3,2—CH_3—4—Cl or 2,3,4-trifluro were inefficient to replace heptafluoroisopropyl group for high larvicidal activity,which provided some guidance for the further modifications of sulfiliminyl dicarboxamides.     

含硫氰基邻甲酰氨基苯甲酰胺类化合物的合成与杀虫活性研究

本文合成了8个未见文献报道的类似于氯虫苯甲酰胺的化合物——含硫氰基邻甲酰氨基苯甲酰胺类化合物,并用核磁共振氢谱、碳谱以及高分辨质谱予以表征。并且对这8个化合物针对小菜蛾和斜纹夜蛾的毒力进行测试并与氯虫苯甲酰胺进行对比,发现这8个化合物均对小菜蛾和斜纹夜蛾都具有较好的杀灭活性,尽管其活性比氯虫苯甲酰胺稍弱,但也非常接近,可以作为候选农药进行进一步考察。     

Synthesis and insecticidal activities of novel bridged-neonicotinoids

A series of novel bridged-neonicotinoid analogues were designed and synthesized, which were constructed by starting material 8 with cyclopentenone or cyclohexenone in the presence of catalyst aluminium chloride. All of the compounds were characterized and confirmed by ¹H NMR, ¹³C NMR, HRMS and IR. The bioassay tests showed that compounds 5 and 6a showed higher bioactivities than imidacloprid against Aphis craccivora.     

Synthesis and insecticidal activity of new substituted N-aryl-N′-benzoylthiourea compounds

Eight new substituted N-aryl-N′-benzoylthioureas have been synthesised by a facile and mild method with high yield at room temperature. The structures of all compounds were confirmed by NMR, mass and high resolution mass spectroscopy. The preliminary bioassay tests show that two of the compounds (5b and 5e) exhibited a significant insecticidal activity on armyworm, Leucania separata Walker, at 500 mg l⁻¹.     

Synthesis and structure-insecticidal activity relationship of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety

A series of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety,i.e.,diamides 11,simple aryl-bearing amides 12 and acylthioureas 14 were successfully synthesized based on the key fluo ro-containing phe nylpyrazole acid intermediate.The new compounds were identified and confirmed by melting point,1H NMR,13C NMR and elemental analysis or HRMS.The bioassay results indicated that some of the compounds possessed excellent insecticidal activities towards oriental armyworm,diamondback moth and corn borer at low concentrations.For examples,compounds 11a,11e-g and 14b exhibited remarkable larvicidal activities with LC50 values of 0.13-0.39 mg/L and 0.0002-0.0014 mg/L against oriental armyworm and diamondback moth,respectively,were comparable with those of the control chlorantraniliprole.Particularly,lie were found superior to chlorantraniliprole in oriental armyworm tests(LC50:0.23 mg/L vs.0.26 mg/L);11a,lie,11f and 14c in diamondback moth tests with LC50 values of 0.0002 mg/L,0.0002 mg/L,0.0008 mg/L and 0.0005 mg/L,respectively,we re more effective than that of chlorantraniliprole.In addition,12 a also showed a promising insecticidal potential and development/optimization advantage.Compounds 11a,lle-g,12a,14b and 14c could be considered as possible new leading structures for further study.The SAR investigation indicated that the compounds with fluorine motif(e.g.,-F,-CF2H,-CF3)held apparently favorable insecticidal potentials,which provided useful guidance for further design/development of new phenylpyrazole-containing agrochemicals.     

Syntheses and insecticidal activities of novel 2,5-disubstituted 1,3,4-oxadiazoles

Nine novel symmetrical and asymmetrical 2,5-disubstituted 1,3,4-oxadiazoles have been synthesized by a facile and mild method with high yield. Meantime, it was found that the fluorine was easy substituted by hydrazine in polyhalogen-substituted aroyl hydrazine. The preliminary bioassay tests show that two of the compounds (D5 and D6) exhibited a significant insecticidal activity (LC₅₀=116.02 and 70.93 mg l⁻¹) on armyworm, Leucania separata Walker. Using the Drug Discovery Workbench (DDW) (Cerius²), structure-activities relationship was studied.     

Synthesis,bioactivity, action mode and 3D-QSAR of novel anthranilic diamide derivatives

Several newly synthesized anthranilic diamide derivatives were found to exhibit excellent bioactivity. The action mode test and 3D-QSAR analysis provided valuable information for evaluation and future design of anthranilic diamide insecticides.     

Design, Syntheses and Biological Activities of Novel Anthranilic Diamide Insecticides Containing N-Pyridylpyrazole

In search of environmentally benign insecticides with high activity, low toxicity and low residue, a series of novel anthranilic diamide derivatives containing N-pyridylpyrazole was designed and synthesized. All the compounds were characterized by ¹H NMR spectroscopy and elemental analysis. The single crystal structure of compound 8j was determined by X-ray diffraction. The insecticidal activities of the new compounds were evaluated. The results show that some compounds exhibited moderate insecticidal activities against Lepidoptera pests. Among this series of compounds, compounds 8o and 8p showed 100% larvicidal activity against Mythimna separate Walker, Plutella xylostella Linnaeus and Laphygma exigua Hubner at a test concentration of 200 mg/kg, which is equal to the commercial chlorantraniliprole.     

Synthesis and Insecticidal Evaluation of Novel Anthranilic Diamides Derivatives Containing 4‐Chlorine Substituted N‐Pyridylpyrazole

To search for potent insecticides targeting at ryanodine receptors (RyRs), a series of novel anthranilic diamides analogs containing 4‐chlorine N‐pyridylpyrazole were designed and synthesized. Their insecticidal activities were evaluated and the preliminary structure‐activity relationships (SARs) were discussed. The insecticidal results showed that some of the compounds (8a—8h, 8m, 8n) exhibited good larvicidal activities against oriental armyworm at 2.5 mg·L^–1, and compound 8m possessed 60% insecticidal activity at 0.5 mg·L^–1. For diamondback moth, 8m exhibited better activity than Chlorantraniliprole at a hundred fold preference. The calcium imaging technique experiment results suggested that compound 8m could increase the intracellular [Ca²⁺]_i. With the neurons preincubated experiment, the results confirmed that the target of this series of compounds could be RyRs in the central larvae neurons of oriental armyworm. The results indicated that compound 8m could respond as a potential modulator of the insect ryanodine receptor.     

Design,synthesis and insecticidal activities of novel 1-substituted-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives

A series of novel 5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives(6a–6n, 7a, 7b, and 8a-8f)were synthesised by placing the amide bond at the 4-position of the pyrazole ring. These derivatives differed from the structure of chlorantraniliprole analogues with the amide bond at the 5-position of the pyrazole ring. Preliminary bioassay results revealed that a few title compounds exhibited good insecticidal activities against lepidopteran pests, such as Plutella xylostella, Mythimna separate, Heliothis armigera, and Ostrinia nubilalis. Some title compounds also elicited broad-spectrum insecticidal activities against dipterous insects including Culex pipiens pallens after altering the amide position. Similar to pyrazole-5-carboxamide analogues, compounds 6b and 6e showed 100% insecticidal activity against P. xylostella, C. pipiens pallens, and M. separate at concentrations of 200, 2, and 200 mg/m L, respectively.This finding suggested that 5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives are potential alternative insecticides for management of agriculture pests.     

Synthesis and cytotoxic activities of a series of novel N-methylbisindolylmaleimide amino acid ester conjugates

A series of novel N-methylbisindolylmaleimides and natural amino acid conjugates were synthesized and evaluated for their inhibitory activity against six tumor cell lines.Most of the compounds exhibited moderate in vitro cytotoxic activities in the range of 10-100μmol/L.     

Design,synthesis, and insecticidal bioactivities evaluation of pyrrole- and dihydropyrrole-fused neonicotinoid analogs containing chlorothiazole ring

Chlorothiazole ring, as a substituted heterocycle, frequently occurred in structures of various insecticides, and brought positive effect on bioactivity. In purpose to find novel neonicotinoids, a series of pyrrole- and dihydropyrrole-fused neonicotinoid analogs containing chlorothiazole ring were synthesized for the first time. Results of the following biological assays showed that compounds 5a-c achieved good insecticidal activity against Aphis craccivora, and compound 5h exhibited good activity against Nilaparvata lugens.     

Synthesis of novel N-pyridylpyrazole derivatives containing 1,2,4-oxadiazole moiety via 1,3-dipolar cycloaddition and their structures and biological activities

A series of novel 1,2,4-oxadiazole-containing N-pyridylpyrazole derivatives 12a−h were efficiently synthesized with pivaldehyde, pyridylpyrazole carboxylic acid and arylamine as raw materials via 1,3-dipolar cycloaddition. Their structures were identified by melting points, ¹H NMR, ¹³C NMR and elemental analysis or HRMS. The exploration on the single-crystal structures of 12c and 12g revealed the stereochemical and substituent oriental characteristics, and the relevance of the structure and the reaction activity of this type of compounds. The preliminary bioassays indicated that several compounds had good insecticidal activities, among which 12c showed a lethality rate of 80% towards Mythimna separata Walker at 200 μg/mL; some of the compounds exhibited favorable fungicidal activities at 50 μg/mL against Physalospora piricola, Rhizoctonia cereal, Sclerotinia sclerotiorum, etc. Among which, 12a, 12b, 12c and 12h could be considered as new fungicidal leading compounds for further structural optimization. These discoveries along with the structure-activity relationship analysis in this paper will provide useful guidance for the innovative studies on new pyridylpyrazole derivatives and their applications in agrochemical area.     

Synthesis and bioactivity of novel pyrazole oxime derivatives containing oxazole ring

A series of novel pyrazole oxime derivatives containing oxazole ring were designed and synthesized. The title compounds were structurally confirmed by 1H NMR, 13C NMR spectra and elemental analyses. Preliminary bioassay results showed that some of the title compounds displayed promising fungicidal activity besides insecticidal and acaricidal activity. Particularly, compound 8c exhibited potent fungicidal activity against cucumber Pseudoperonospora cubensis beyond good insecticidal activity against Aphis craccivora and Nilaparvata lugens.     

Synthesis and biological activities of dithiocarbamates containing1,2,3-triazoles group

Twelve novel dithiocarbamates containing 1,2,3-trizaoles group were prepared via one step starting from organic halides, dithiocarbamic acid prop-2-ynyl ester, and sodium azide, using a very simple catalytic system composed of copper（I） chloride and water at 70 8C. The structures of the new compounds were characterized and screened for their in vitro anti-tumor. Four of the compounds displayed varying levels of anti-tumor activity against the CDC25 B.