First report of field resistance to cyantraniliprole, a new anthranilic diamide insecticide, on Bemisia tabaciMED in China

The Bemisia tabaci （Gennadius） cryptic species complex comprises important insect pests that cause devastating damage to agricultural crops worldwide. In China, the B. tabaci Mediterranean （MED） （or biotype Q） species is threatening agricul- tural production all over the country as resistance to commonly used insecticides has increased. This situation highlights the need for alternative pest control measures. Cyantraniliprole, a novel anthraniiic diamide insecticide, has been widely employed to control Hemipteran pests. To monitor the levels of resistance to cyantraniliprole in B. tabaci field populations in China, bioassays were conducted for 18 field samples from nine provinces over two years. Compared with median lethal concentration （LC^0） for the MED susceptible strain, all field samples had significantly higher resistance to cyantraniliprole. Furthermore, resistance factors （RFs） increased significantly in samples from Shanxi （from 5.62 in 2015 to 25.81 in 2016）, Hunan （3.30 in 2015 to 20.97 in 2016） and Hubei （from 9.81 in 2015 to 23.91 in 2016） provinces. This study indicates a considerable decrease in the efficacy of cyantraniliprole against B. tabaci and establishes a baseline of susceptibility that could serve as a reference for future monitoring and management of B. tabaci resistance to cyantraniliprole.

Discovery of Novel Anthranilic Diamide Derivatives Bearing Sulfoximine Group as Potent Insecticide Candidates

The fall armyworm,Spodoptera frugiperda(S.frugiperda),represents the most resistant insect species and poses serious threat to grain yield.Chlorantraniliprole(CHL),which targets the ryanodine receptors(RyRs)in insects,has demonstrated the efficacy in controlling S.frugiperda.Nevertheless,this has led to emerging resistance in several countries.To counter this resistance,a viable approach involves the development of novel compounds that bind against RyRs via distinct binding sites or modes.In this study,a series of 22 novel anthranilic diamide derivatives was designed and synthesized,and their insecticidal activities were evaluated.Most of these derivatives showed moderate to good insecticidal activity against S.frugiperda and Mythimna separata.Time-lapse fluorescence measurements of endoplasmic reticulum luminal calcium revealed that most derivatives elicited cellular responses similar as CHL when assessed on HEK293 cells expressing S.frugiperda ryanodine receptors(SfRyRs).The mode of action of compound 13a was studied and verified on the isolated neurons by calcium imaging technique.Finally,molecular docking analysis was employed to predict the binding mechanism of compound 13a against SfRyRs.Overall,these novel diamide derivatives hold promise as a valuable resource for guiding the future design of insecticidal compounds targeting RyRs.

Design, Synthesis and Insecticidal Activity of Novel Anthranilic Diamides Containing Oxime Ester and Diacylhydrazine Moieties

Two series of novel anthranilic diamides containing oxime ester and diacylhydrazine moieties were designed and synthesized.Their structures were characterized by melting points,1H NMR,13C NMR and high resolution mass spectrometry（HRMS）.The single crystal structure of compound 7e was determined by X-ray diffraction and their evaluated insecticidal activity against oriental armyworm（Mythimna separata） indicates that some of the compounds exhibited moderate insecticidal activities.Among the 20 compounds,6a and 6b show 100％ larvicidal activity against Mythimna separate Walker at the test concentration of 100 mg/L.

Synthesis and Biological Activities of Novel Anthranilic Diamides Analogues Containing Benzo[b]thiophene

A series of novel anthranilic diamides analogues containing benzo[b]thiophenyl ring was designed and synthesized. Their structures were characterized by melting points, 1H nuclear magnetic resonance（IH NMR） and high-resolution mass spectrometry（HRMS）. The bioassay tests indicate that their insecticidal activities were weak to moderate. Antibacterial tests indicate that some of the compounds showed favourable activity in vitro against Physa- lospora piricola, Alternaria solani, Cercospora arachidicola, Gibberella sanbinetti and Phytophthora infestans at a dosage of 50 mg/L.

Synthesis, insecticidal activities and SAR studies of novel anthranilic diamides containing trifluoroethoxyl substituent and chiral amino acid moieties

Ryanodine receptors（RyRs） activator has become one class of popular insecticide because of its unique mode of action. In order to find more new RyRs activators as insecticidal agents, a series of 18 novel chiral anthranilic diamides were designed by introducing the D-alanine acid and D-serine acid esters as well as trifluoroethoxyl group into the anthranilic diamide skeleton and synthesized successfully based on anthranilic diamide and FKI-1033 structures. The structures of the title compounds Ia–i and IIa–i were confirmed by melting points,~1H NMR,^（13）C NMR, elemental analysis and specific optical rotation analysis.The preliminary bioassay results indicated that most of the title compounds exhibited considerable larvicidal activities against oriental armyworm at 10 mg/L, especially Ib, Ie and IIh showed remarkable insecticidal activities at 0.5 mg/L. The larvicidal activity against diamondback moth of Ia and IId were 80%and 90% respectively at 0.0001 mg/L, which was similar to that of chlorantraniliprole. The relationship between structure and insecticidal activity was analyzed to reveal a possible co-regulated effect of the chiral amino acid ester, halogen atom or cyano group, and trifluoroethyloxyl group of the skeleton structures of the title compounds, which will provide useful information for guiding the design and discovery of new RyRs activators and insecticidal agrochemicals.

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,^（13）C NMR,^（19）F 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.

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 struc ture-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 activityat 0.5 mg·L^(-1).For diamondback moth,8m exhibited better activity than Chlorantraniliprole at a hundred fold preference.

Synthesis and Bioactivities Evaluation of Novel Anthranilic Diamides Containing N-(tert-Butyl)benzohydrazide Moiety as Potent Ryanodine Receptor Activator

Anthranilic diamides have been proven to be a class of efficacious and safe insecticides targeting ryanodine receptors (RyRs) during the last decade. In order to develop innovative scaffolds with high insecticidal activity, two series of N-pyridylpyrazole derivatives containing N-(tert-butyl)benzohydrazide substructures were designed and synthesized. Their insecticidal activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) were evaluated. Preliminary bioassay results revealed that some of the new compounds exhibited good insecticidal activity against the oriental armyworm and diamondback moth. The mode of action of these compounds were verified using calcium-imaging technique and the results showed that some new compounds could effectively modulate the insect cytosolic Ca^2+ level, and break the cellular calcium homeostasis, indicating some of these compounds were potent activators of the RyRs.

Design, Synthesis and Biological Activities of Novel Anthranilic Diamides Containing Dihydroisoxazoline and Isoxazole

Anthranilic diamides are one of the most important classes of modern agrochemical insecticides. To discover new structures with higher activity, lower toxicity and lower residue, a series of novel anthranilic diamides containing dihydroisoxazoline and isoxazole was designed and synthesized. Their structures were characterized by means of melting points, proton nuclear magnetic resonance（IH NMR）, 13C NMR and high resolution mass spectrometry（HRMS）. According to the bioassay data, it was found that some of the title compounds exhibit moderate insecticidal activity and good antifungal activity. In particularly, compound 15b with a concentration of 50 mg/L shows a lethality rate of 60.0% against Mythimna separata Walker and a lethality rate of 50.0% against Culex pipiens pallens with a concentration of 1 mg/L. Moreover, compound 15b showed good antifungal activities（58.8%, 77.1%, 70.7%, 55.3%, 60.7%, 65.4%） when against all the tested fungi（Cercospora araehidicola tIori, Physalospora piricola, Rhizoctonia cerealis, Bipolaris maydis, Watermelon anthracnose, Fusarium moniliforme）. The effects of compounds 14h, 14j and 15b on the concentration of intracellular calcium ion（[Ca2＋]i） in the central neurons of Mythimna separate Walker were well investigated via calcium imaging technique. The results demonstrate that the novel compounds can elevate the calcium concentration in the neurons, denoting that some new structures are potential modulators of the insect ryanodine receptor（RyR）.

Targeted Synthesis of Anthranilic Diamides Insecticides Containing Trifluoroethoxyl Phenylpyrazole

A series of novel anthranilic diamides analogues(9a-9t)containing trifluoroethoxyl pyrazole moiety was designed and synthesized and their insecticidal bioactivities against Mythimna separata(Walker,M.separata)and Plutellaxylostella(P.xylostella)were evaluated.The structures of the title compounds were confirmed by^(1)H NMR,^(13)C NMR and HRMS.Preliminary insecticidal activities showed that some of the title compounds possessed good to excellent bioactivities towards M.separata and P.xylostella.Compounds 9c and 9t exhibited 100%mortality rate against M.separate at 0.2 mg/L.For the P.xylostella,the synthesized compounds(9c-9e,9i and 9o)showed 70%,80%,75%,65%and 60%insecticidal activities at 1×10^(−6)mg/L,respectively,higher than that of chlorantraniliprole(0).Based on excellent insecticidal activities,the mode of the action was tested by the calcium-imaging technique,the results of which demonstrated that the novel compounds shared the same target with chlorantraniliprole.The binding pose of the most active compound 9t in RyRs of P.xylostella was predicted by molecular docking,which showed that compound 9t interacted with the residues Glu140(A)and His147(A)via hydrogen bond.

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,-（13）C NMR,-（19）F NMR,elemental analysis,HRMS or mass spectra.Their insecticidal activities against oriental armyworm（Mythimna separata） and diamondback moth（Plutella xyiostella）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.

Design, Synthesis and Biological Activities of Novel Anthranilic Diamide Insecticide Containing Trifluoroethyl Ether

Two series of novel anthranilic diamide insecticide containing trifluoroethyl ether were designed and synthesized, and their structures were characterized by 1H NMR spectroscopy, elemental analysis and single crystal X-ray diffraction analysis. The insecticidal activities of the new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal activities. The insecticidal activities of compounds 19a, 19b, 19d, 19g, 19k and 19m against oriental armyworm at 2.5 mg·kg-1 were 100%. The larvicidal activities of 19a, 19b, 19c, 19d, 19e, 19g and 19n against diamond-back moth were 100% at 0.1 mg·kg-1. Surprisingly, most of them still exhibited perfect insecticidal activity against diamond-back moth when the concentration was reduced to 0.05 mg·kg-1, which was higher than the commercialized Chlorantraniliprole.

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

To study the pesticide effect, action mode, structure-activity relationships (SARs) of anthranilic diamide insecticide and screen highly active pesticides, novel anthranilic diamide derivatives were synthesized.Bioassays indicated that all of the title compounds displayed 100% mortality against diamondback moth and oriental armyworm at 100 mg/L, among which 12 v and 12 w showed 100% insecticidal acitvity at 5 mg/L. Surprisingly compound 12 w exhibited better insecticidal acitvity than commercialized chlorantraniliprole against Pyrausta nubilalis (0.1 mg/L) and Cnaphalocrocis Medinalis (2 mg/L). 3 D-QSAR and SARs statistical analysis revealed that title compounds with R^2 fixed as methoxy had the highest probability possessing high activity. The calcium fluorescence measurements on neurons revealed that E series compounds containing pyrazinyl may have a molecular target different from caffeine on ryanodine receptors rather than the voltage-gated calcium channel present on cytomembran.

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 H NMR spectroscopy and elemental analysis. The single crystal structure of com pound 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 80 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.

Bioactive conformation analysis of anthranilic diamide insecticides:DFT-based potential energy surface scanning and 3D-QSAR investigations

Anthranilic diamides are fasting growing class insecticides in modern crop protection for their high activity, low ecotoxicity, and broad insecticidal spectra. However. the bioactive conformations of anthranilic diamides are still unclear until now. In the present study, DFT-based potential energy surface scanning was used to detect the low energy conformations of chlorantraniliprole, then were used respectively in the structure alignment for a series of anthranilic diamide compounds followed by detailed CoMFA and CoMSIA analyses. Finally, the bioactive conformations of anthranilic diamide insecticides were revealed from a series of low energy conformations, which might provide some clues for future insecticide design.

Design,Synthesis,Biological Evaluation and SARs of Anthranilic Diamide Derivatives Containing Pyrrole Moieties

In order to find a new variety of ryanodine receptor(RyR)regulator with greater biological activity,a se-ries of anthranilic diamide derivatives possessing pyrrole structure was designed and synthesized in this study.The pyrrole derivatives were evaluated for their insecticidal activity against Mythimna separata and Plutella xylostella.As indicated by the preliminary biological activities,compounds 12h-12j and 121-12n exhibited a remarkable in-secticidal activity against M.separata at 0.25 mg/L.Compared to control chlorantraniliprole.compound 12i exhibited more excellent insecticidal activity at 0.1 mg/L.Meanwhile,compounds 12c,12h,12i.12j.121,and 12m were selected to test the insecticidal activity against P xylostella,which led to the desirable insecticidal activity at 1x103 mg/L.Notably,compound 121 demonstrated 47%insecticidal activity at 5×10^(-6) mg/L over the control.In addition,the biological mechanism of action of compound 12i was investigated by means of insect clectrophysiology experiment.

新型邻甲酰氨基苯甲酰胺类杀虫剂的研究进展

介绍了新型邻甲酰氨基苯甲酰胺类杀虫剂的研究进展。根据具体化学结构类型不同分为五大类,概述了具有较好生物活性的化合物,介绍了氯虫酰胺的创制经纬和合成方法。

含1,2,3-噻二唑的邻甲酰胺基苯甲酰胺类化合物的合成、晶体结构与生物活性

以取代邻氨基苯甲酸为起始原料,设计并合成了一系列未见文献报道的含1,2,3-噻二唑的邻甲酰胺基苯甲酰胺类化合物.所有化合物的结构均经元素分析和1H NMR确证,并且采用X射线单晶衍射分析方法测定了化合物7g的结构.初步的生物活性试验结果表明,部分化合物具有一定的杀菌活性.

三唑Schiff碱邻甲酰胺基苯甲酰胺衍生物的合成及生物活性

以2,4-二氯苯甲酸和2-氨基-3-甲基苯甲酸为起始原料,设计合成了8个新型含2,4-二氯苯基1,2,4-三唑Schiff碱邻甲酰胺基苯甲酰胺类化合物,通过1H NMR、IR及元素分析等技术手段对目标化合物进行了结构表征。采用Airbrush喷雾法进行生物活性测试,结果表明,部分化合物具有不同程度的杀虫活性,其中化合物9a在600 mg/L浓度下对小菜蛾和粘虫的致死率均为100%。

N-[4-氯-2-取代氨基甲酰基-6-甲基苯基]-1-芳基-5-氯-3-三氟甲基-1H-吡唑-4-甲酰胺的合成及生物活性

通过改变传统氯虫酰胺中吡唑环上氨基甲酰基与吡啶环之间的相对位置,或以其它芳环取代原分子中的吡啶环,设计合成了24个结构新颖的N-[4-氯-2-取代氨基甲酰基-6-甲基苯基]-1-芳基-5-氯-3-三氟甲基-1H-吡唑-4-甲酰胺类化合物.所有目标化合物的结构均通过1H NMR谱、元素分析或高分辨质谱表征确定.初步的生物活性测试结果表明,部分化合物对东方粘虫具有较好的杀虫活性,其中化合物6m在浓度为50 mg/L时具有80%的杀虫活性.同时,在浓度为50 mg/L时目标化合物对5种常见病菌具有明显的抑制作用,其中化合物6n和6x对苹果轮纹菌的抑菌率达62.1%.