Use of diphenylpyrazoles

Abstract

This invention belongs to the field of insecticide technology, specifically providing the use of the following general formula (I) diphenylpyrazole compounds. These compounds target glutathione (GSTs) in pests and exhibit broad inhibitory activity against GSTs in various pests. They can effectively delay the metabolism of insecticides by GSTs in pests, thereby reducing the metabolic resistance of pests to insecticides, and are suitable for use as pesticides.

Description

[0001] This application is a divisional application of application number 2021107606474, filed on July 6, 2021, entitled "Diphenylpyrazole compounds and their preparation methods and uses". Technical Field

[0002] This invention belongs to the field of insecticide technology, specifically relating to the use of diphenylpyrazole compounds. Background Technology

[0003] For a long time, insecticides have been the main means of controlling agricultural pests. Among the many insecticides, ryanodine receptor modulators, represented by chlorantraniliprole, and voltage-dependent sodium ion channel blockers, represented by indoxacarb, have attracted widespread attention and become popular insecticide varieties due to their novel structures, unique mechanisms of action, rapid effects, broad insecticidal spectrum, and environmental friendliness. Chlorantraniliprole belongs to the diamide class of insecticides, while indoxacarb belongs to the oxadiazine class of insecticides. These two types of insecticides can control most chewing pests, especially Lepidoptera such as Pyralidae (rice leaf roller, corn borer, cowpea borer, etc.), Fruit borers (or peach fruit moth, etc.), Noctuidae (fall armyworm, cotton bollworm, beet armyworm, etc.), Toxascaridae (codling moth, pear fruit moth, etc.), Gramineae (cotton red bollworm, etc.), Diamondback moths (diamond moth, etc.), White butterflies (vegetable white butterfly, etc.), and Fiber moths (golden-striped leafminer, etc.). They also have high activity against Coleoptera (potato beetle, etc.), Diptera (American serpentine leafminer, etc.), and Isoptera (termites).

[0004] In recent years, the market for diamide and oxadiazine insecticides has grown rapidly and still has significant growth potential. The most widely used insecticides in these two classes are chlorantraniliprole and indoxacarb, respectively. In 2019, chlorantraniliprole held a leading position in the global insecticide market, with global sales reaching US$1.581 billion; indoxacarb's global sales also reached US$206 million. However, with the widespread use of these two insecticides, various pests have developed varying degrees of resistance, becoming a major limiting factor for their effectiveness. Resistance monitoring shows that the diamondback moth population in the field has developed high levels of resistance to chlorantraniliprole, with resistance in some areas exceeding 1000 times; resistance to indoxacarb is also generally over 10 times, with some populations reaching over 100 times. The increasing resistance of pests not only seriously affects the lifespan of pesticides but also leads to an increase in the frequency and dosage of pesticide application, causing huge economic losses. Effectively managing pesticide resistance in pests has become a pressing problem in the global plant protection field.

[0005] The mechanisms of insecticide resistance in pests can be broadly categorized into three types: metabolic resistance, penetration resistance, and target resistance, with metabolic resistance mediated by detoxification enzymes being the most common. Numerous studies have found that glutathione S-transferases (GSTs), as important detoxification enzyme systems in insects, participate in the development of resistance to various commonly used insecticides, including organochlorines, organophosphates, pyrethroids, neonicotinoids, diamides, and abamectin, through gene mutation, increased activity, and upregulated expression. For example, silencing LmGSTs5 and LmGSTu1 in the locust *Locusta migratoria* significantly increases the nymphal susceptibility to malathion and chlorpyrifos. Furthermore, there is evidence that insect GSTs can directly metabolize various insecticides. For instance, the recombinant protein of the cotton bollworm HaGST-8 exhibits good metabolic activity against chlorpyrifos, dichlorvos, and cypermethrin.

[0006] GSTs (Gastrointestinal tract inhibitors) play a crucial role in the development and progression of pesticide resistance in pests; reducing their activity significantly decreases pesticide resistance. It has been reported that compounds such as S-Hexylglutathione (GTX) and diethyl maleate (DEM) can increase efficacy by inhibiting GST activity and slowing down the rate at which pests metabolize insecticides. These compounds, as GST inhibitors, typically lack insecticidal activity themselves, but when mixed with insecticides, they can significantly enhance the toxicity or efficacy of the pesticide, making them important pesticide synergists. Developing GST inhibitors targeting insects can not only improve the control effect of insecticides but also delay or reduce resistance and extend the lifespan of insecticides, which is of great significance for controlling pesticide resistance in pests. Summary of the Invention

[0007] This invention proposes a novel inhibitor targeting GSTs in pests. This inhibitor exhibits broad-spectrum inhibitory activity against GSTs in various pests, effectively delaying the in vivo metabolism of insecticides by GSTs, thereby reducing the metabolic resistance of pests to insecticides. It effectively improves the resistance of diamondback moth resistant strains to ryanodine receptor modulators such as chlorantraniliprole and voltage-dependent sodium channel blockers such as indoxacarb, making it suitable as an insecticide synergist.

[0008] Therefore, one object of the present invention is to provide a diphenylpyrazole compound of the following general formula (I) or a pesticide-acceptable salt thereof.

[0009] Another object of the present invention is to provide a method for preparing diphenylpyrazole compounds of the following general formula (I) or pesticide-acceptable salts thereof.

[0010] Another object of the present invention is to provide the use of the following general formula (I) diphenylpyrazole compounds or their phytochemically acceptable salts in the preparation of pesticides (e.g., preferably insecticide synergists).

[0011] This invention provides diphenylpyrazole compounds of general formula (I) or pesticide-acceptable salts thereof.

[0012]

[0013] in:

[0014] R 1 It can be:

[0015] (1) An amide group that is unsubstituted or substituted by one or more of the following substituents -NH-CH(O);

[0016] (a)-C 1～6 Alkyl-R 3 -C 3～8 cycloalkyl-R 3 -C 2～6 alkenyl-R 3 -C 2～6 alkynyl-R 3 -NH-R 3 -N(R) 3 )2、-C(O)-R 3 -NH-C 1～6 Alkyl-R 3 -C 1～6 Alkyl-NH-R 3 -C 1～6 Alkyl-N(R) 3 )2、-C 1～6 Alkyl-OR 3 -C 3～8 cycloalkyl-OR 3 -OC 1～6 Alkyl-R 3 -C 1～6 Alkyl-OC 1～6 Alkyl-R 3 -C(O)-NH-R 3 -C(O)-N(R) 3 )2、-NH-C(O)-R 3 -C 1～6 Alkyl-NH-C(O)-R 3 -C 1～6 Alkyl-NH-C(O)-OR 3 -NH-C(O)-C 1～6 Alkyl-R 3 -NH-C(O)-C 1～6 Alkyl-OR 3 -C(O)-NH-C 1～6 Alkyl-R 3 or -C 1～6Alkyl-SR 3 ;

[0017] The R 3 Each group is independently selected from: H, O, S, =NH, amino, halogen, cyano, -C 1～6 Alkyl, -C 3～8 cycloalkyl, -SC 1～6 Alkyl, -S-OH, -SO2-C 1～6 Alkyl, -6 to 14-membered aryl, -5 to 14-membered heterocyclic, -5 to 14-membered heteroaryl, and -adamantyl; wherein R 3 Unsubstituted or substituted with one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1～6 Alkyl, -C 2～6 alkenyl, -C 2～6 alkynyl group, -OC 1～6 Alkyl, nitro, sulfonic acid, -C 1～6 Alkyl-halogen, -C 1～6 Alkyl-HS, -C 1～6 Alkyl-NH3 + -C 1～6 Alkyl -OH, -C 1～6 Alkyl-NH-C 1～6 Alkyl, -C 1～6 Alkyl-N(C) 1～6 Alkyl)2;

[0018] (b) -6 to 14 aryl, -5 to 14 heterocyclic or -5 to 14 heteroaryl;

[0019] The 6-14 aryl, 5-14 heterocyclic, or 5-14 heteroaryl group is unsubstituted or substituted by one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1～6 Alkyl, -OC 1～6 Alkyl, -C 1～6 Alkyl-NH-C 1～6 Alkyl, -C 1～6 Alkyl-N(C) 1～6 Alkyl)2、-C(O)-OC 1～6 Alkyl, -NH-C(O)-C 1～6 Alkyl group, -SO2-C 1～6 Alkyl group, -SO2-NH2, -SO2-NH-C 1～6 Alkyl, -SO2-N(C) 1～6 Alkyl group 2, -6 to 14 aryl group, -5 to 14 heterocyclic group, -5 to 14 heteroaryl group;

[0020] (2) The N atom of the amide group -NH-CH(O) interacts with the C atom through the -C group. 3～6 Alkylene-, -NH-C 2～6 Alkylene-, -NH-C(O)-C 1～6 alkylene-, -C 1～6 Alkylene -NH-C(O)-, -NH-C 1～6 alkylene-C(O)- or -C 1～6 Alkyl groups -C(O)- are linked to form a cyclic structure; this cyclic structure may optionally be substituted with the following substituents: -C 1～6 Alkyl, -C 3～8 cycloalkyl, -C 3～8 cycloalkyl-C 1～6 Alkyl, -OC 1～6 Alkyl, -6 to 14 aryl, -5 to 14 heterocyclic, -5 to 14 heteroaryl, -C 1～6 Alkyl-6 to 14-membered aryl, -C 1～6 Alkyl-5 to 14-membered heterocyclic groups, -C 1～6 Alkyl-5-14-membered heteroaryl, trifluoroethyl; the 6-14-membered aryl, 5-14-membered heterocyclic and 5-14-membered heteroaryl groups are optionally -OC 1～6 Alkyl substitution; or, the cyclic structure is further fused with a 5-8 membered aryl group, a 5-8 membered heterocyclic group, or a 5-8 membered heteroaryl group to form a fused ring.

[0021] The heterocyclic group (including 5-14 membered, 5-10 membered, and 5-8 membered groups) contains 1-4 heteroatoms selected from N, S, and O; the heteroaryl group (including 5-14 membered, 5-10 membered, and 5-8 membered groups) contains 1-4 heteroatoms selected from N, S, and O.

[0022] R 2 It can be: -H, -halogen, -amino, -NO2, -CF3, -C 1～6 Alkyl, -C 1～6 Alkyl-OH, -OR 4 -C(O)-R 4 -C(O)-NH2, -NH-C(O)-R 4 -C(O)-OR 4 -C(O)-ON(R) 4 )2;R 4 It can be: H or C 1～6 alkyl.

[0023] The substituent of the amide group is attached to the N atom of the amino group and / or is the same as the C atom of the carbonyl group; and when there are two substituents, the two substituents can be the same or different.

[0024] The term "halogen" refers to fluorine, chlorine, bromine, or iodine as substituents. When a halogen atom is used as a substituent, it can replace one or more atoms, including one, two, or three.

[0025] The term "alkyl" refers to a straight-chain or branched alkyl group derived from an alkane by removing a hydrogen atom.

[0026] The term "alkenyl" refers to a straight-chain, branched, or cyclic alkenyl group containing a carbon-carbon double bond.

[0027] The term "alkynyl group" refers to a straight-chain, branched, or cyclic alkynyl group containing a carbon-carbon triple bond.

[0028] The term "cycloalkyl" refers to a fully hydrogenated non-aromatic ring consisting of a mono, di, or tricyclic ring. Therefore, cycloalkyl can typically be a monocyclic ring containing 3 to 7 ring atoms. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. "Cycloalkyl" also includes bridged bicycloalkyl systems.

[0029] The term "alkyloxy group" refers to a group derived from an alkyl group by being connected to other parts via -O-.

[0030] The term "aryl" refers to a cyclic aromatic group whose ring atom is a carbon atom, including monocyclic aryl and fused-ring aryl. Monocyclic aryl refers to a completely unsaturated aryl group, while fused-ring aryl refers to a cyclic group formed by two or more cyclic structures sharing two adjacent carbon atoms, with at least one ring being a completely unsaturated aromatic ring.

[0031] The term "heterocyclic group" refers to a saturated or unsaturated non-aromatic group consisting of 1 to 3 rings and containing 1, 2, 3 or 4 heteroatoms (N, O or S).

[0032] The term "heteroaryl" refers to an aromatic ring structure, including monocyclic heteroaryl and fused-ring heteroaryl. At least one of the ring atoms is a heteroatom (N, O, or S), and the remaining ring atoms are independently selected from carbon, oxygen, nitrogen, and sulfur.

[0033] Preferably, R 1 It can be:

[0034] (1) An amide group substituted with one or more of the following substituents: -NH-CH(O),

[0035] (a)-C 1～3 Alkyl-R 3 -C 3～6 cycloalkyl-R 3 -C 2～5 alkenyl-R 3 -C 1～3 Alkyl-NH-R 3 -C 1～3Alkyl-OR 3 、or -OC 1～3 Alkyl-R 3 The R 3 Each group is independently selected from: H, O, S, =NH, amino, halogen, cyano, -C 1～3 Alkyl, -C 3～6 Cycloalkyl, -6 to 14 aryl, -5 to 14 heterocyclic, -5 to 14 heteroaryl; the R 3 Unsubstituted or substituted with one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), -S-OH, amino, -C 1～3 Alkyl, -C 2～5 alkenyl, -C 2～5 alkynyl group, -OC 1～3 Alkyl, nitro, sulfonic acid, -C 1～3 Alkyl-halogen, -C 1～3 alkyl-OH;

[0036] (b) -6-14 aryl, -5-14 heterocyclic, or -5-14 heteroaryl; wherein the 6-14 aryl, 5-14 heterocyclic, or 5-14 heteroaryl is unsubstituted or substituted by one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1～3 Alkyl, -OC 1～3 Alkyl, -C 1～3 Alkyl-NH-C 1～3 Alkyl, -C 1～3 Alkyl-N(C) 1～3 Alkyl)2、-C(O)-OC 1～3 Alkyl, -NH-C(O)-C 1～3 Alkyl group, -SO2-C 1～3 Alkyl group, -SO2-NH2, -SO2-NH-C 1～3 Alkyl, -SO2-N(C) 1～3 Alkyl)2;

[0037] (2) The N atom of the amide group -NH-CH(O) interacts with the C atom through the -C group. 3～6 Alkylene-, -NH-C 2～4 Alkylene-, -NH-C(O)-C 1～3 alkylene-, -C 1～3 Alkylene -NH-C(O)-, -NH-C 1～3 alkylene-C(O)- or -C 1～3 Alkyl groups -C(O)- are linked to form a cyclic structure, which may optionally be substituted with the following substituents: -C 1～3 Alkyl, -C 3～6 cycloalkyl, -C3～6 cycloalkyl-C 1～3 Alkyl, -6 to 14 aryl, -5 to 14 heterocyclic, -5 to 14 heteroaryl, -C 1～3 Alkyl-6 to 14-membered aryl, -C 1～3 Alkyl-5 to 14-membered heterocyclic groups, -C 1～3 Alkyl-5-14-membered heteroaryl, trifluoroethyl; the 6-14-membered aryl, 5-14-membered heterocyclic, and 5-14-membered heteroaryl are optionally substituted with -OC 1～3 Alkyl substitution;

[0038] The heterocyclic group contains 1 to 3 heteroatoms selected from N, S and O; the heteroaryl group contains 1 to 3 heteroatoms selected from N, S and O.

[0039] R 2 It is: -H or halogen.

[0040] More preferably, R 1 It can be:

[0041] (1)-NH-C(O)-C 1～3 Alkyl-R 3 The R 3 Selected from: -6-10 aryl, -5-10 heterocyclic, -5-10 heteroaryl; the R 3 Unsubstituted or substituted with one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), -S-OH, amino, -C 1～3 Alkyl, -OC 1～3 Alkyl, nitro, sulfonic acid, -C 1～3 Alkyl-halogen, -C 1～3 Alkyl-HS, -C 1～3 Alkyl-NH3 + -C 1～3 alkyl-OH;

[0042] (2) -NH-C(O)-6~10 aryl, -NH-C(O)-5~10 heterocyclic or -NH-C(O)-5~10 heteroaryl; wherein the 6~10 aryl, 5~10 heterocyclic or 5~10 heteroaryl is unsubstituted or substituted by one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1～3 Alkyl, -OC 1～3 alkyl;

[0043] The heterocyclic group contains 1 to 3 heteroatoms selected from N, S, and O; the heteroaryl group contains 1 to 3 heteroatoms selected from N, S, and O;

[0044] R 2It can be: -H.

[0045] R 1 Specifically, it can be:

[0046]

[0047]

[0048]

[0049]

[0050]

[0051]

[0052]

[0053]

[0054]

[0055]

[0056]

[0057]

[0058]

[0059]

[0060]

[0061]

[0062]

[0063]

[0064]

[0065]

[0066]

[0067] Preferably, R 1 Specifically, it can be:

[0068]

[0069]

[0070]

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077] More preferably, R 1 Specifically, it can be:

[0078]

[0079]

[0080]

[0081]

[0082]

[0083]

[0084]

[0085]

[0086] More preferably, R 1 Specifically, it can be:

[0087]

[0088]

[0089] More preferably, R 1 Specifically, it can be:

[0090]

[0091] In a specific implementation scheme, the general formula (I) diphenylpyrazole compound or its pesticide-acceptable salt is the following compound or its pesticide-acceptable salt:

[0092]

[0093]

[0094]

[0095]

[0096]

[0097]

[0098]

[0099] In the most preferred embodiment, the general formula (I) diphenylpyrazole compound or its agrochemically acceptable salt is the following compound or its agrochemically acceptable salt:

[0100]

[0101] This invention provides a method for preparing diphenylpyrazole compounds of general formula (I) or pesticide-acceptable salts thereof, comprising the following methods:

[0102]

[0103] Compound A is hydrolyzed to its carboxylic acid form, compound B. Then, compound B reacts with compound H2N-R. 1 Compound (I) is condensed into a solvent by adding an organic or inorganic base to a solvent using a condensing agent, and by stirring or heating at room temperature; wherein, R 1 and R 2 The definition is the same as above;

[0104] or,

[0105]

[0106] Compound A is reacted with hydrazine hydrate to generate acylhydrazine compound C, or compound A is hydrolyzed to form compound B, compound B reacts with hydrazine hydrate to generate acylhydrazine compound C, and then compound C reacts with compound COOH-R. 5 Compound (I) is synthesized by adding an organic or inorganic base to a solvent using a condensing agent and by stirring or heating at room temperature; wherein, R 2 The definition is the same as above, R 5 For: (a)-C 1～6 Alkyl-R 3 -C 3～8 cycloalkyl-R 3 -C 2～6 alkenyl-R 3 -C 2～6 alkynyl-R 3-NH-R 3 -N(R) 3 )2、-C(O)-R 3 -NH-C 1～6 Alkyl-R 3 -C 1～6 Alkyl-NH-R 3 -C 1～6 Alkyl-N(R) 3 )2、-C 1～6 Alkyl-OR 3 -C 3～8 cycloalkyl-OR 3 -OC 1～6 Alkyl-R 3 -C 1～6 Alkyl-OC 1～6 Alkyl-R 3 -C(O)-NH-R 3 -C(O)-N(R) 3 )2、-NH-C(O)-R 3 -C 1～6 Alkyl-NH-C(O)-R 3 -C 1～6 Alkyl-NH-C(O)-OR 3 -NH-C(O)-C 1～6 Alkyl-R 3 -NH-C(O)-C 1～6 Alkyl-OR 3 -C(O)-NH-C 1～6 Alkyl-R 3 or -C 1～6 Alkyl-SR 3 ;

[0107] The R 3 Each group is independently selected from: H, O, S, =NH, amino, halogen, cyano, -C 1～6 Alkyl, -C 3～8 cycloalkyl, -SC 1～6 Alkyl, -S-OH, -SO2-C 1～6 Alkyl, -6 to 14 aryl, -5 to 14 heterocyclic, -5 to 14 heteroaryl, -adamantyl; the R 3 Unsubstituted or substituted with one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1～6 Alkyl, -C 2～6 alkenyl, -C 2～6 alkynyl group, -OC 1～6 Alkyl, nitro, sulfonic acid, -C 1～6 Alkyl-halogen, -C1～6 Alkyl-HS, -C 1～6 Alkyl-NH3 + -C 1～6 Alkyl -OH, -C 1～6 Alkyl-NH-C 1～6 Alkyl, -C 1～6 Alkyl-N(C) 1～6 (a) Alkyl group 2; (b) -6 to 14 aryl group, -5 to 14 heterocyclic group or -5 to 14 heteroaryl group; wherein the 6 to 14 aryl group, 5 to 14 heterocyclic group or 5 to 14 heteroaryl group is unsubstituted or substituted by one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1～6 Alkyl, -OC 1～6 Alkyl, -C 1～6 Alkyl-NH-C 1～6 Alkyl, -C 1～6 Alkyl-N(C) 1～6 Alkyl)2、-C(O)-OC 1～6 Alkyl, -NH-C(O)-C 1～6 Alkyl group, -SO2-C 1～6 Alkyl group, -SO2-NH2, -SO2-NH-C 1～6 Alkyl, -SO2-N(C) 1～6 Alkyl group 2, -6 to 14 aryl group, -5 to 14 heterocyclic group, -5 to 14 heteroaryl group; wherein the heterocyclic group contains 1 to 4 heteroatoms selected from N, S and O; wherein the heteroaryl group contains 1 to 4 heteroatoms selected from N, S and O.

[0108] The condensing agents include, but are not limited to: active esters, carbodiimides, onium salts, organophosphorus compounds, and other condensing agents.

[0109] The solvents include, but are not limited to: N,N-dimethylformamide, dichloromethane, acetonitrile, and tetrahydrofuran.

[0110] The organic bases include, but are not limited to, triethylamine, diisopropylethylamine, etc.

[0111] The inorganic bases include, but are not limited to: sodium carbonate, potassium carbonate, sodium hydroxide, sodium bicarbonate, etc.

[0112] The synthesis of compound A was obtained from the reference (J.Org.Chem.2010,75,3,984–987).

[0113] The present invention provides a composition comprising a diphenylpyrazole compound of general formula (I) or a pesticide-acceptable salt thereof, and a pesticide-acceptable excipient.

[0114] Preferably, the composition contains one or more insecticides.

[0115] The present invention also provides the use of a compound of general formula (I) diphenylpyrazole or a pesticide-acceptable salt thereof in the preparation of GST inhibitors.

[0116] Preferably, the GSTs include: PxGSTδ1, PxGSTε3, PxGSTσ1, PxGSTσ2, PxGSTω4, PxGSTθ1, PxGSTζ1 and PxGSTμ1; preferably, the GSTs include: PxGSTδ1, PxGSTσ1, PxGSTσ2 and PxGSTε3; more preferably, the GSTs include: PxGSTδ1 and PxGSTε3.

[0117] The present invention also provides the use of general formula (I) diphenylpyrazole compounds or pesticide-acceptable salts thereof in the preparation of pesticides, preferably insecticide synergists.

[0118] The insecticide synergist delays or reduces the insecticide resistance of pests.

[0119] The insecticides include: ryanodine receptor modulator insecticides (e.g., diamide insecticides); voltage-dependent sodium channel blockers insecticides (e.g., oxadiazine insecticides).

[0120] Specifically, the insecticides include chlorantraniliprole and indoxacarb.

[0121] The pests mentioned include: pests of field crops and pests of economic crops.

[0122] Specifically, the pests include: diamondback moth (Plutella xylostella), armyworm (Mythimna separata), corn borer (Pyrausta nubilalis), rice stem borer (Chilo suppressalis), brown planthopper (Nilaparvata lugens), fall armyworm (Spodoptera frugiperda), cotton bollworm (Helicoverpa armigera), peach fruit borer (Carposinasasakii), and beet armyworm (Spodoptera litura).

[0123] This invention provides a class of insect GST inhibitors with novel structures. It has been found that compounds with such structures have broad inhibitory activity against GSTs in insects, significantly improving the sensitivity and effectiveness of resistant insect strains to various insecticides, and playing an important role in the management of insect resistance. Attached Figure Description

[0124] Figure 1 This is the mass spectrum of compound PXG1 prepared in this invention.

[0125] Figure 2 This is the mass spectrum of compound PXG2 prepared in this invention.

[0126] Figure 3 This is the mass spectrum of compound PXG3 prepared in this invention.

[0127] Figure 4 The compound PXG3 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0128] Figure 5 This is the mass spectrum of compound PXG4 prepared in this invention.

[0129] Figure 6 The compound PXG4 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0130] Figure 7 This is the mass spectrum of compound PXG5 prepared in this invention.

[0131] Figure 8 This is the mass spectrum of compound PXG6 prepared in this invention.

[0132] Figure 9 The compound PXG6 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0133] Figure 10 This is the mass spectrum of compound PXG7 prepared in this invention.

[0134] Figure 11 This is the mass spectrum of compound PXG8 prepared in this invention.

[0135] Figure 12 This is the mass spectrum of compound PXG9 prepared in this invention.

[0136] Figure 13 This is the mass spectrum of compound PXG10 prepared in this invention.

[0137] Figure 14 The compound PXG10 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0138] Figure 15 This is the mass spectrum of compound PXG11 prepared in this invention.

[0139] Figure 16 The compound PXG11 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0140] Figure 17 This is the mass spectrum of compound PXG12 prepared in this invention.

[0141] Figure 18 This is the mass spectrum of compound PXG13 prepared in this invention.

[0142] Figure 19 This is the mass spectrum of compound PXG14 prepared in this invention.

[0143] Figure 20 This is the mass spectrum of compound PXG15 prepared in this invention.

[0144] Figure 21 This is the mass spectrum of compound PXG16 prepared in this invention.

[0145] Figure 22 The compound PXG16 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0146] Figure 23 This is the mass spectrum of compound PXG17 prepared in this invention.

[0147] Figure 24 This is the mass spectrum of compound PXG18 prepared in this invention.

[0148] Figure 25 The compound PXG18 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0149] Figure 26 This is the mass spectrum of compound PXG19 prepared in this invention.

[0150] Figure 27 The compound PXG19 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0151] Figure 28 This is the mass spectrum of compound PXG20 prepared in this invention.

[0152] Figure 29 This is the mass spectrum of compound PXG21 prepared in this invention.

[0153] Figure 30This is the mass spectrum of compound PXG22 prepared in this invention.

[0154] Figure 31 The compound PXG22 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0155] Figure 32 This is the mass spectrum of compound PXG23 prepared in this invention.

[0156] Figure 33 The compound PXG23 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0157] Figure 34 This is the mass spectrum of compound PXG24 prepared in this invention.

[0158] Figure 35 The compound PXG24 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0159] Figure 36 This is the mass spectrum of compound PXG25 prepared in this invention.

[0160] Figure 37 This is the mass spectrum of compound PXG26 prepared in this invention.

[0161] Figure 38 The compound PXG26 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0162] Figure 39 This is the mass spectrum of compound PXG27 prepared in this invention.

[0163] Figure 40 The compound PXG27 prepared in this invention is dissolved in deuterated DMSO. 1 H-NMR spectrum.

[0164] Figure 41 This is the mass spectrum of compound PXG28 prepared in this invention.

[0165] Figure 42 This is the mass spectrum of compound PXG29 prepared in this invention.

[0166] Figure 43 The image shows the inhibition curves of some of the compounds of this invention on the total enzymes of GSTs in diamondback moth.

[0167] Figure 44The inhibition curves of some compounds of this invention on total GSTs enzymes of *Prunus persica* are shown.

[0168] Figure 45 This is the inhibition curve of some compounds of the present invention on the total enzymes of GSTs in Spodoptera litura.

[0169] Figure 46 The image shows the inhibition curves of some of the compounds of this invention on the total enzymes of GSTs in armyworms.

[0170] Figure 47 The figures show the inhibition curves of some of the compounds of this invention on the total enzymes of GSTs in corn borers.

[0171] Figure 48 The figures show the inhibition curves of some of the compounds of this invention on the total enzymes of GSTs from rice stem borer.

[0172] Figure 49 The image shows the inhibition curves of some of the compounds of this invention on the total enzymes of GSTs in brown planthoppers.

[0173] Figure 50 The image shows the inhibition curves of some of the compounds of this invention on the total enzymes of GSTs in fall armyworm.

[0174] Figure 51 The image shows the inhibition curves of some of the compounds of this invention on the total enzymes of GSTs in cotton bollworm.

[0175] Figure 52 The enzyme kinetics curve of the PxGSTs recombinant protein from the diamondback moth.

[0176] Figure 53 The figures show the inhibition curves of some of the compounds of this invention on PxGSTδ1.

[0177] Figure 54 The figures show the inhibition curves of some of the compounds of this invention on PxGSTε3.

[0178] Figure 55 The figures show the inhibition curves of some of the compounds of this invention on PxGSTσ1.

[0179] Figure 56 The figures show the inhibition curves of some of the compounds of this invention on PxGSTσ2. Detailed Implementation

[0180] The present invention will be described below through examples, but the invention is not limited thereto. Unless otherwise specified, the experimental methods shown in the following examples are conventional methods. The reagents and materials shown are all commercially available products.

[0181] Preparation of Compound PXG1 in Example 1

[0182]

[0183] Method 1:

[0184] (1) Preparation of hydrazide compound C1: Compound A1 (preparation of A1: J.Org.Chem.2010,75,3,984–987. HNMR (400MHz,CDCl3):δ3.83(s,3H),7.33–7.36(m,2H),7.41–7.50(m,7H),7.87(m,2H). The same applies below) 10 g of compound A1 was added to 100 ml of anhydrous ethanol and 20 ml of hydrazine hydrate. The mixture was heated under reflux overnight, cooled and filtered to obtain compound C1, 9.5 g, yield 95%.

[0185] (2) Add compound F1 (carboxylic acid) (2.5 g, 1 eq), DMF 10 ml, EDCI (4.14 g, 1.2 eq), and potassium carbonate (6.21 g, 2.5 eq) to a 100 ml three-necked flask. After stirring for 10 minutes, add compound C1 (acylhydrazine) (5.5 g, 1.1 eq). Stir overnight at room temperature. After the reaction is complete by TLC, the product is post-processed, diluted with water, filtered out the precipitate and dried. The crude compound is purified by reversed-phase HPLC without additional treatment with methanol-water eluent. Combine the selected fractions and concentrate to obtain the target product PXG1.

[0186] Alternatively, method 2:

[0187] (1) Preparation of compound B1: 10 g of compound A1, 100 ml of anhydrous ethanol, and 28.7 ml (2 eq) of 10% NaOH were added to a 100 ml three-necked flask. The mixture was heated under reflux for 5 hours. After the reaction was completely cooled, the pH was adjusted to 2-3 with 10% hydrochloric acid. The mixture was then filtered to obtain 8 g of compound B1, with a yield of 85%.

[0188] (2) Add compound B1 (carboxylic acid) (6.5 g, 1 eq), DMF 10 ml, EDCI (5.75 g, 1.2 eq), and potassium carbonate (8.63 g, 2.5 eq) to a 100 ml three-necked flask. After stirring for 10 minutes, add compound G1 (acylhydrazine) (4.21 g, 1.1 eq). Stir overnight at room temperature. After the reaction is complete by TLC, the product is diluted with water, the precipitate is filtered out and dried. The crude compound is purified by reversed-phase HPLC without the need for further treatment with methanol-water eluent. Combine the selected fractions and concentrate to obtain the target product PXG1.

[0189] MS(ES-API)cacld.for C 22 H 17 N5O3 found at 400.2 [M+1] + .( Figure 1 )

[0190] Preparation Example 2: Preparation of compound PXG2

[0191]

[0192] Method 1: Except for step (2), where compound F2 (carboxylic acid) (2.83 g, 1 eq) is added to a 100 ml three-necked flask, compound PXG2 is prepared using the same method and steps as in Example 1. Alternatively,

[0193] Method 2: Except for adding compound G2 (acylhydrazine) (4.70 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG2 was prepared using the same method and steps as in Preparation Example 1.

[0194] MS(ES-API)cacld.for C 22 H 19 N5O2S found 418.2 [M+1] + .( Figure 2 )

[0195] Preparation of compound PXG3 in Example 3

[0196]

[0197] Method 1: Except for step (2), where compound F3 (carboxylic acid) (2.72 g, 1 eq) is added to a 100 ml three-necked flask, compound PXG3 was prepared using the same method and steps as in Example 1. Alternatively,

[0198] Method 2: Except for adding compound G3 (acylhydrazine) (4.54 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG3 was prepared using the same method and steps as in Preparation Example 1.

[0199] MS(ES-API)cacld.for C 24 H 21 N5O2 found at 412.2 [M+1] + .( Figure 3 )

[0200] HNMR (400MHz, DMSO): δ3.6(s,2H),2.45(m,5H),5.65(s,1H),6.6(m,3H),7.05-7.2(m,3H),7.4-7.5(m,12H),10.0(s,2H).( Figure 4 )

[0201] Preparation of compound PXG4 in Example 4

[0202]

[0203] Method 1: Except for step (2), where compound F4 (carboxylic acid) (3.81 g, 1 eq) is added to a 100 ml three-necked flask, compound PXG4 is prepared using the same method and steps as in Example 1. Alternatively,

[0204] Method 2: Except for adding compound G4 (acylhydrazine) (6.22 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG4 was prepared using the same method and steps as in Example 1.

[0205] MS(ES-API)cacld.for C 26 H 24 N4O5 was found at 473.2 [M+1]. + .( Figure 5 )

[0206] HNMR (400MHz, DMSO): δ3.75(s,3H),3.9(s,6H),7.05(s,1H),7.2-7.5(m,12H),8.05(s,1H),10.0(s,1H),10.4(s,1H).( Figure 6 )

[0207] Preparation of compound PXG5 in Example 5

[0208]

[0209] Method 1: Except for step (2), where compound F5 (carboxylic acid) (2.74 g, 1 eq) is added to a 100 ml three-necked flask, compound PXG5 is prepared using the same method and steps as in Preparation Example 1. Alternatively,

[0210] Method 2: Except for adding compound G5 (acylhydrazide) (4.57 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG5 was prepared using the same method and steps as in Preparation Example 1.

[0211] MS(ES-API)cacld.for C 24 H 20 N4O3 was found at 413.2 [M+1]. + .( Figure 7 )

[0212] Preparation of compound PXG6 in Example 6

[0213]

[0214] Method 1: Except for step (2) adding compound G6 (acylhydrazine) (5.04 g, 1 eq) to a 100 ml three-necked flask, compound PXG6 was prepared using the same method and steps as in Preparation Example 1.

[0215] MS(ES-API)cacld.for C 24 H 23 N5O3 was found at 430.2 [M+1]. + .( Figure 8 )

[0216] HNMR (400MHz, DMSO): δ1.4(m,1H),1.5-1.9(m,9H),7.05(s,1H),7.2-7.4(m,10H),8.8(s,1H),10.6(s,1H).( Figure 9 )

[0217] Preparation of compound PXG7 in Example 7

[0218]

[0219] Method 1:

[0220] (1) Preparation of hydrazide compound C2: Compound A2 (preparation of A2 reference: J.Org.Chem.2010,75,3,984–987), 10 g, 100 ml of anhydrous ethanol, and 20 ml of hydrazine hydrate were added to a 100 ml three-necked flask. The mixture was heated under reflux overnight, cooled, and filtered to obtain compound C2, 7.5 g, yield 75%.

[0221] (2) Add compound F7 (carboxylic acid) (2.10 g, 1 eq), DMF 10 ml, EDCI (4.14 g, 1.2 eq), and potassium carbonate (6.21 g, 2.5 eq) to a 100 ml three-necked flask. After stirring for 10 minutes, add compound C2 (acylhydrazine) (6.0 g, 1.1 eq). Stir overnight at room temperature. After the reaction is complete by TLC, dilute with water, filter out the precipitate and dry it. The crude compound is purified by reversed-phase HPLC without additional treatment with methanol-water eluent. Combine the selected fractions and concentrate to obtain the target product PXG7.

[0222] Method 2:

[0223] (1) Preparation of compound B2: 10 g of compound A2, 100 ml of anhydrous ethanol, and 28.7 ml (2 eq) of 10% NaOH were added to a 100 ml three-necked flask. The mixture was heated under reflux for 5 hours. After the reaction was completely cooled, the pH was adjusted to 2-3 with 10% hydrochloric acid. The mixture was then filtered to obtain 6.8 g of compound B2, with a yield of 70%.

[0224] (2) Add compound B2 (carboxylic acid) (7.0 g, 1 eq), DMF 10 ml, EDCI (5.75 g, 1.2 eq), and potassium carbonate (8.63 g, 2.5 eq) to a 100 ml three-necked flask. After stirring for 10 minutes, add compound G7 (acylhydrazine) (3.48 g, 1.1 eq). Stir overnight at room temperature. After the reaction is complete by TLC, the product is diluted with water, the precipitate is filtered out and dried. The crude compound is purified by reversed-phase HPLC without additional treatment with methanol-water eluent. The selected fractions are combined and concentrated to obtain the target product PXG7.

[0225] MS(ES-API)cacld.for C 22 H 16 ClN5O2 found 418.0 [M+1] + .( Figure 10 )

[0226] Preparation of compound PXG8 in Example 8

[0227]

[0228] Method 1: Except for step (2) adding compound F8 (carboxylic acid) (3.24 g, 1 eq) to a 100 ml three-necked flask, compound PXG8 was prepared using the same method and steps as in Preparation Example 1.

[0229] Method 2: Except for adding compound G8 (acylhydrazine) (5.34 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG8 was prepared using the same method and steps as in Preparation Example 1.

[0230] MS(ES-API)cacld.for C 25 H 20 N4O4 found 441.0 [M+1] + .( Figure 11 )

[0231] Preparation of compound PXG9 in Example 9

[0232]

[0233] Method 1: Except for step (2) adding compound F9 (carboxylic acid) (4.12 g, 1 eq) to a 100 ml three-necked flask, compound PXG9 was prepared using the same method and steps as in Preparation Example 1.

[0234] Method 2: Except for adding compound G9 (acylhydrazide) (6.68 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG9 was prepared using the same method and steps as in Preparation Example 1.

[0235] MS(ES-API)cacld.for C 25 H 23 N5O4S found 490.2 [M+1] + .( Figure 12 )

[0236] Preparation of compound PXG10 in Example 10

[0237]

[0238] Method 1: Except for step (2) adding compound F10 (carboxylic acid) (3.00 g, 1 eq) to a 100 ml three-necked flask, compound PXG10 was prepared using the same method and steps as in Preparation Example 1.

[0239] Method 2: Except for adding compound G10 (acylhydrazide) (4.95 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG10 was prepared using the same method and steps as in Preparation Example 1.

[0240] MS(ES-API)cacld.for C 25 H 22 N4O3 was found at 427.2 M+1. + .( Figure 13 )

[0241] HNMR (400MHz, DMSO): δ3.5(s,2H),3.8(s,3H),6.8(m,2H),7.05(s,1H),7.2-7.6(m,12H),10.0(dd,2H).( Figure 14 )

[0242] Preparation of Compound PXG11 in Example 11

[0243]

[0244] Method 1: Except for step (2) adding compound F11 (carboxylic acid) (2.20 g, 1 eq) to a 100 ml three-necked flask, compound PXG11 was prepared using the same method and steps as in Preparation Example 1.

[0245] Method 2: Except for adding compound G11 (acylhydrazine) (3.74 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG11 was prepared using the same method and steps as in Preparation Example 1.

[0246] MS(ES-API)cacld.for C 23 H 18 N4O2 was found at 383.2 [M+1]. + .( Figure 15 )

[0247] HNMR (400MHz, DMSO): δ7.05(s,1H),7.2-7.6(m,13H),7.95(s,2H),10.05(s,1H),10.45(s,1H).( Figure 16 )

[0248] Preparation of compound PXG12 in Example 12

[0249]

[0250] Method 1: Except for step (2) adding compound G12 (acylhydrazine) (5.64 g, 1 eq) to a 100 ml three-necked flask, compound PXG12 was prepared using the same method and steps as in Preparation Example 1.

[0251] MS(ES-API)cacld.for C 26 H 21 N5O3 found at 452.2 [M+1] + .( Figure 17 )

[0252] Preparation of compound PXG13 in Example 13

[0253]

[0254] Method 1: Except for step (2) adding compound G13 (acylhydrazine) (4.32 g, 1 eq) to a 100 ml three-necked flask, compound PXG13 was prepared using the same method and steps as in Preparation Example 1.

[0255] MS(ES-API)cacld.for C 22 H 21 N5O3 found at 404.2 [M+1] + .( Figure 18 )

[0256] Preparation of compound PXG14 in Example 14

[0257]

[0258] Method 1: Except for step (2) adding compound G14 (acylhydrazine) (6.47 g, 1 eq) to a 100 ml three-necked flask, compound PXG14 was prepared using the same method and steps as in Preparation Example 1.

[0259] MS(ES-API)cacld.for C 27 H 23 N5O4 was found at 482.2 [M+1]. + .( Figure 19 )

[0260] Preparation of compound PXG15 in Example 15

[0261]

[0262] Method 1: Except for step (2) adding compound G15 (acylhydrazine) (6.41 g, 1 eq) to a 100 ml three-necked flask, compound PXG15 was prepared using the same method and steps as in Preparation Example 1.

[0263] MS(ES-API)cacld.for C 28 H 25 N5O3 found at 480.2 [M+1] + .( Figure 20 )

[0264] Preparation of compound PXG16 in Example 16

[0265]

[0266] Method 1: Except for step (2) adding compound G16 (acylhydrazine) (5.42 g, 1 eq) to a 100 ml three-necked flask, compound PXG16 was prepared using the same method and steps as in Preparation Example 1.

[0267] MS(ES-API)cacld.for C 25 H 25 N5O3 was found at 444.2 [M+1]. + .( Figure 21 )

[0268] HNMR (400MHz, DMSO): δ1.0(s,3H),1.1-1.8(m,8H),7.05(s,1H),7.2-7.4(m,10H),9.05(s,1H),10.5(s,1H).( Figure 22 )

[0269] Preparation of compound PXG17 in Example 17

[0270]

[0271] Method 1: Except for step (2) adding compound G17 (acylhydrazine) (6.47 g, 1 eq) to a 100 ml three-necked flask, compound PXG17 was prepared using the same method and steps as in Preparation Example 1.

[0272] MS(ES-API)cacld.for C 27 H 23 N5O4 was found at 482.2 [M+1]. + .( Figure 23 )

[0273] Preparation of compound PXG18 in Example 18

[0274]

[0275] Method 1: Except for step (2) adding compound F18 (carboxylic acid) (3.28 g, 1 eq) to a 100 ml three-necked flask, compound PXG18 was prepared using the same method and steps as in Preparation Example 1.

[0276] Method 2: Except for adding compound G18 (acylhydrazine) (5.39 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG18 was prepared using the same method and steps as in Preparation Example 1.

[0277] MS(ES-API)cacld.for C 25 H 22 N4O4 was found at 443.2 [M+1]. + .( Figure 24 )

[0278] HNMR (400MHz, DMSO): δ3.85(s,3H),4.45(s,2H),6.8-7.25(m,5H),7.2-7.5(m,10H),8.05(s,1H),10.25(s,1H).( Figure 25 )

[0279] Preparation of compound PXG19 in Example 19

[0280]

[0281] Method 1: Except for step (2) adding compound F19 (carboxylic acid) (3.19 g, 1 eq) to a 100 ml three-necked flask, compound PXG19 was prepared using the same method and steps as in Preparation Example 1.

[0282] Method 2: Except for adding compound G19 (acylhydrazine) (5.25 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG19 was prepared using the same method and steps as in Preparation Example 1.

[0283] MS(ES-API)cacld.for C 25 H 19 N5O3 was found at 438.2 m². + .( Figure 26 )

[0284] HNMR (400MHz, DMSO): δ4.75(s,2H),7.05-7.5(m,15H),7.8(dd,2H),8.05(s,1H),10.5(s,1H).( Figure 27 )

[0285] Preparation Example 20: Preparation of Compound PXG20

[0286]

[0287] Method 1: Except for step (2) adding compound F20 (carboxylic acid) (2.09 g, 1 eq) to a 100 ml three-necked flask, compound PXG20 was prepared using the same method and steps as in Preparation Example 7.

[0288] Method 2: Except for adding compound G20 (acylhydrazide) (3.47 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG20 was prepared using the same method and steps as in Example 7.

[0289] MS(ES-API)cacld.for C 22 H 16 ClN5O2 was found at 418.2 [M+1]. + .( Figure 28 )

[0290] Preparation Example 21: Preparation of Compound PXG21

[0291]

[0292] Method 1: Except for step (2) adding compound F21 (carboxylic acid) (3.67 g, 1 eq) to a 100 ml three-necked flask, compound PXG21 was prepared using the same method and steps as in Preparation Example 1.

[0293] Method 2: Except for adding compound G21 (acylhydrazine) (6.00 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG21 was prepared using the same method and steps as in Preparation Example 1.

[0294] MS(ES-API)cacld.for C 22 H 16 ClN5O2 was found at 465.2 [M+1]. + .( Figure 29 )

[0295] Preparation Example 22: Preparation of Compound PXG22

[0296]

[0297] Method 1: Except for step (2) adding compound F22 (carboxylic acid) (3.40 g, 1 eq) to a 100 ml three-necked flask, compound PXG22 was prepared using the same method and steps as in Preparation Example 1.

[0298] Method 2: Except for adding compound G22 (acylhydrazine) (5.58 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG22 was prepared using the same method and steps as in Preparation Example 1.

[0299] MS(ES-API)cacld.for C 26 H 19 N5O3 found at 450.2 [M+1] + .( Figure 30 )

[0300] HNMR (400MHz, DMSO): δ1.05(s,1H),2.45(m,5H),3.2(s,5H),6.6(s,1H),7.05-7.5(m,15H),8.05(s,1H),10.0(s,1H),10.4(s,1H),12.05(s,1H).( Figure 31 )

[0301] Preparation of compound PXG23 in Example 23

[0302]

[0303] Method 1: Except for step (2) adding compound F23 (carboxylic acid) (3.19 g, 1 eq) to a 100 ml three-necked flask, compound PXG23 was prepared using the same method and steps as in Preparation Example 1.

[0304] Method 2: Except for adding compound G23 (acylhydrazide) (5.25 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG23 was prepared using the same method and steps as in Preparation Example 1.

[0305] MS(ES-API)cacld.for C 25 H 19 N5O3 was found at 438.2 m². + .( Figure 32 )

[0306] HNMR (400MHz, DMSO): δ4.8(s,2H),7.05-7.8(m,17H),10.3(s,1H).( Figure 33 )

[0307] Preparation of Compound PXG24 in Example 24

[0308]

[0309] Method 1: Except for step (2) adding compound F24 (carboxylic acid) (1.62 g, 1 eq) to a 100 ml three-necked flask, compound PXG24 was prepared using the same method and steps as in Preparation Example 1.

[0310] Method 2: Except for adding compound G24 (acylhydrazine) (2.86 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG24 was prepared using the same method and steps as in Preparation Example 1.

[0311] MS(ES-API)cacld.for C 19 H 18 N4O3 was found at 351.2 M+1. + .( Figure 34 )

[0312] HNMR (400MHz, DMSO): δ1.25(s,3H),4.05(s,2H),7.05(s,1H),7.2-7.4(m,10H).( Figure 35 Preparation of Compound PXG25 in Example 25

[0313]

[0314] Method 1: Except for step (2) adding compound F25 (carboxylic acid) (2.50 g, 1 eq) to a 100 ml three-necked flask, compound PXG25 was prepared using the same method and steps as in Preparation Example 1.

[0315] Method 2: Except for adding compound G25 (acylhydrazide) (4.21 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG25 was prepared using the same method and steps as in Preparation Example 1.

[0316] MS(ES-API)cacld.for C 22 H 17 N5O3 found at 400.2 [M+1] + .( Figure 36 )

[0317] Preparation Example 26: Preparation of Compound PXG26

[0318]

[0319] Method 1: Except for step (2) adding compound F26 (carboxylic acid) (3.49 g, 1 eq) to a 100 ml three-necked flask, compound PXG26 was prepared using the same method and steps as in Preparation Example 1.

[0320] Method 2: Except for adding compound G26 (acylhydrazide) (5.72 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG26 was prepared using the same method and steps as in Preparation Example 1.

[0321] MS(ES-API)cacld.for C 28 H 30 N4O2 found at 455.2 [M+1] + .( Figure 37 )

[0322] HNMR (400MHz, DMSO): δ1.6-2.0(m,19H),7.1(s,1H),7.2-7.4(m,10H),9.6(d,2H).( Figure 38 )

[0323] Preparation Example 27: Preparation of Compound PXG27

[0324]

[0325] Method 1: Except for step (2) adding compound F27 (carboxylic acid) (2.52 g, 1 eq) to a 100 ml three-necked flask, compound PXG27 was prepared using the same method and steps as in Preparation Example 1.

[0326] Method 2: Except for adding compound G27 (acylhydrazide) (4.24 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG27 was prepared using the same method and steps as in Preparation Example 1.

[0327] MS(ES-API)cacld.for C 21 H 16 N6O3 found at 455.2 [M+1] + .( Figure 39 )

[0328] HNMR (400MHz, DMSO): δ6.8-7.3(m,13H),7.8(m,1H),10.2(m,2H),13.5(s,1H).( Figure 40 )

[0329] Preparation of compound PXG28 in Example 28

[0330]

[0331] Method 1: Except for step (2) adding compound F28 (carboxylic acid) (2.05 g, 1 eq) to a 100 ml three-necked flask, compound PXG28 was prepared using the same method and steps as in Preparation Example 1.

[0332] Method 2: Except for adding compound G28 (acylhydrazine) (3.52 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG28 was prepared using the same method and steps as in Preparation Example 1.

[0333] MS(ES-API)cacld.for C 22 H 22 N4O2 found at 375.2 [M+1] + .( Figure 41 )

[0334] Preparation of compound PXG29 in Example 29

[0335]

[0336] Method 1: Except for step (2) adding compound F29 (carboxylic acid) (4.12 g, 1 eq) to a 100 ml three-necked flask, compound PXG29 was prepared using the same method and steps as in Preparation Example 1.

[0337] Method 2: Except for adding compound G29 (acylhydrazide) (6.68 g, 1.1 eq) after stirring for 10 minutes in step (2), compound PXG29 was prepared using the same method and steps as in Example 1.

[0338] MS(ES-API)cacld.for C 25 H 23 N5O4S found 490.2 [M+1] + .( Figure 42 )

[0339] Experimental Example 1: Detection of the inhibitory activity of compounds PXG1-PXG29 (29 compounds) of the present invention against the total enzymes of GSTs in 6 field crop pests and 3 economic crop pests.

[0340] Experiment: Approximately 50 mg of larvae / nymphs of nine major pests, including the diamondback moth (Plutella xylostella), armyworm (Mythimna separata), corn borer (Pyraustanubilalis), rice stem borer (Chilo suppressalis), brown planthopper (Nilaparvata lugens), fall armyworm (Spodoptera frugiperda), cotton bollworm (Helicoverpa armigera), peach fruit moth (Carposina sasakii), and beet armyworm (Spodoptera litura), were ground in a pre-cooled mortar at -80℃. Then, 1 mL of 100 mM sodium phosphate buffer (1 mM EDTA, pH 7.2) was added and the mixture was thoroughly homogenized. The homogenate was transferred to a 1.5 mL centrifuge tube at 4℃ and centrifuged at 14,000 g for 30 minutes. The supernatant was transferred to a new centrifuge tube as the total GSTs enzymes. The protein concentration of the total enzymes was determined using the BCA method.

[0341] 100 μL of PBS buffer (100 mM, pH 7.2) containing 1 mM GSH was added to each well of a 96-well plate. 5 μg of total insect GSTs enzymes and appropriate concentrations of compounds PXG1-PXG29 (29 compounds) of this invention were added to each well. After thorough mixing, the plate was incubated at 30°C for 10 min. Then, 100 μL of PBS buffer (100 mM, pH 7.2) containing 1 mM CDNB was added to each well. After mixing, the plate was immediately placed in a microplate reader, and the absorbance (A) was measured at 340 nm every 1 min. 340The absorbance values ​​at each measurement point were recorded for 5 minutes, and the in vitro inhibition rate of different concentrations of compounds against insect GSTs total enzymes was calculated. Each measurement was repeated three times, with GSTs total enzymes inactivated at 100℃ for 5 minutes as a negative control and GTX as a positive control. The IC50 was calculated using GraphPad Prism5 software. 50 The relative inhibition rate is calculated using the following formula:

[0342]

[0343] Where, ΔA 340c Control group A 340 The change over 5 minutes, ΔA 340t For experimental group A 340 Changes over 5 minutes.

[0344] Results: The experimental results are shown in Table 1 and Table 2. Figures 43-51 As shown, the compounds PXG1-PXG29 (29 compounds) of this invention exhibit certain inhibitory activity against the total GSTs enzymes of both field crop pests and economic crop pests. Specifically, compound PXG1 of this invention shows a high IC50 value against the total GSTs enzymes of field crop pests such as armyworm, corn borer, rice stem borer, brown planthopper, fall armyworm, and cotton bollworm, as well as economic crop pests such as diamondback moth, peach fruit moth, and beet armyworm. 50 The concentrations of the compound PXG2 were 27.57 μM, 7.2 μM, 12.11 μM, 8.24 μM, 3.62 μM, 62.38 μM, 52.78 μM, 52.63 μM, and 17.67 μM, respectively. The IC50 values ​​of the compound PXG2 against total GSTs of field crop pests such as armyworm, corn borer, rice stem borer, brown planthopper, fall armyworm, and cotton bollworm, as well as economic crop pests such as diamondback moth, were also observed. 50 The concentrations were 18.09 μM, 15.69 μM, 42.01 μM, 47.88 μM, 2.18 μM, 40.16 μM, and 52.13 μM, respectively. The IC50 values ​​of compound PXG2 of this invention against the total GSTs of economic crop pests such as the peach fruit borer and the beet armyworm were also measured. 50 Both were greater than 100 μM, with inhibition rates of 35.12% and 57.13% at 100 μM, respectively. The compound PXG22 of this invention exhibited an IC50 value greater than 100 μM against total GSTs enzymes of field crop pests such as armyworm, rice stem borer, brown planthopper, fall armyworm, and cotton bollworm, as well as economic crop pests such as diamondback moth and beet armyworm. 50 The concentrations were 52.98 μM, 19.01 μM, 59.29 μM, 1.72 μM, 77.05 μM, 32.8 μM, and 43.1 μM, respectively. The IC50 values ​​of compound PXG22 of this invention against the total enzymes of GSTs in field crop pests *Cornus spp.* and *Cornus officinalis* pests are also shown. 50Both were greater than 100 μM, with inhibition rates of 42.38% and 42.76% at 100 μM, respectively. The positive control GSTs inhibitor GTX (S-Hexylglutathione) showed an IC50 value greater than 100 μM for total GSTs enzymes in field crop pests such as armyworm, corn borer, rice stem borer, brown planthopper, fall armyworm, and cotton bollworm, as well as economic crop pests such as diamondback moth, peach fruit moth, and beet armyworm. 50 The corresponding values ​​were 12.9 μM, 16.33 μM, 23.46 μM, 6.65 μM, 2.31 μM, 14.41 μM, 14.05 μM, 6.87 μM, and 15.19 μM.

[0345] Table 1. Inhibitory effects of compounds PXG1-PXG29 of the present invention on total GSTs enzymes of three economic crop pests.

[0346]

[0347]

[0348] Table 2. Inhibitory effects of compounds PXG1-PXG29 of the present invention on total GSTs enzymes of nine field crop pests.

[0349]

[0350] Conclusion: Compounds PXG1, PXG2, and PXG22 of this invention exhibit significant inhibitory activity against the total GST enzymes of various field crop and economic crop pests. They can reduce the metabolic activity of insecticides on the total GST enzymes of field crop pests such as armyworm, corn borer, rice stem borer, brown planthopper, fall armyworm, and cotton bollworm, as well as economic crop pests such as diamondback moth, peach fruit moth, and beet armyworm. Example 2: Enzyme kinetics detection of 8 known GST recombinant proteins from diamondback moth.

[0351] Experiment: Currently, eight known PxGSTs (Gastropod Species Scales) from the diamondback moth are identified: PxGSTδ1, PxGSTε3, PxGSTσ1, PxGSTσ2, PxGSTω4, PxGSTθ1, PxGSTζ1, and PxGSTμ1. Recombinant proteins of these eight PxGSTs were obtained through prokaryotic expression, and the enzyme kinetics of the recombinant PxGSTs proteins were detected using the CDNB method. 1 μg of recombinant PxGST protein was added to 200 μL of PBS buffer (100 mM, pH 7.2) containing gradient concentrations of CDNB (0.05–1.60 mM) and 1 mM GSH. The absorbance (A) was measured at 340 nm every 1 min at 30°C using a microplate reader. 340The absorbance was measured continuously for 5 minutes. The obtained absorbance values ​​were converted to molar CDNB conjugated / min / mg, with an extinction coefficient ε340 = 9600M. -1 cm -1 Michaelis-Menten models were generated based on different concentrations of CDNB to obtain enzyme kinetic parameters.

[0352] Results: Enzyme kinetics of recombinant proteins were detected using CDNB as a substrate. Only PxGSTδ1, PxGSTσ1, PxGSTσ2, and PxGSTε3 showed catalytic activity towards CDNB, while the other four PxGSTs (PxGSTω4, PxGSTθ1, PxGSTζ1, and PxGSTμ1) did not show catalytic activity towards CDNB. The experimental results are shown in Table 3. Figure 52 As shown, the Kc of recombinant proteins PxGSTδ1, PxGSTε3, PxGSTσ1, and PxGSTσ2 is... m The concentrations were 0.032 mM, 0.37 mM, 0.12 mM, and 0.19 mM, respectively. max The concentrations were 7.64 mM / min / mg, 0.49 mM / min / mg, 1.70 mM / min / mg, and 0.26 mM / min / mg, respectively.

[0353] Table 3. Kinetic parameters of PxGSTs recombinant protease from Diamondback moth.

[0354]

[0355] Conclusion: Among the eight PxGSTs, only four PxGSTs, namely PxGSTδ1, PxGSTσ1, PxGSTσ2 and PxGSTε3, have GSH binding sites and belong to the GST types that have metabolic activity against insecticides in the diamondback moth.

[0356] Experimental Example 3: Detection of the inhibitory activity of compounds PXG1-PXG29 of the present invention against four GSTs with GSH binding sites in diamondback moth.

[0357] Experiment: 100 μL of PBS buffer (100 mM, pH 7.2) was added to each well of a 96-well plate. 1 μg of recombinant PxGSTs protein and an appropriate concentration of the compound PXG1-PXG29 of this invention were added to each well. After thorough mixing, the plate was incubated at 30°C for 10 min. Then, 100 μL of PBS buffer (100 mM, pH 7.2) containing 1 mM CDNB and 1 mM GSH was added to each well. After mixing, the plate was immediately placed in a microplate reader, and the absorbance (A) was measured at 340 nm every 1 min. 340The absorbance values ​​at each measurement point were recorded for 5 minutes, and the in vitro inhibition rates of different concentrations of compounds PXG1-PXG29 against recombinant PxGSTs protein were calculated. Each measurement was repeated three times, with PxGSTs recombinant protein inactivated at 100°C for 5 minutes as a negative control and GTX as a positive control. The IC50 was calculated using GraphPad Prism 5 software. 50 The relative inhibition rate is calculated using the following formula:

[0358]

[0359] Where, ΔA 340c Control group A 340 The change over 5 minutes, ΔA 340t For experimental group A 340 Changes over 5 minutes.

[0360] Results: The experimental results are shown in Table 4. Figures 53-56 As shown. The compounds PXG1, PXG2, PXG3, PXG4, PXG5, PXG7, PXG8, PXG10, PXG18, PXG20, PXG22, PXG23, and PXG28 of this invention exhibit IC50 inhibition against the PxGSTδ1 recombinant protein of *Plutella xylostella*. 50 The concentrations of these compounds were 40.25 μM, 31.41 μM, 31.58 μM, 50.56 μM, 17.78 μM, 65.37 μM, 30.64 μM, 24.25 μM, 29.9 μM, 40.79 μM, 25.03 μM, 32.92 μM, and 63.53 μM, respectively. The IC50 values ​​of the remaining compounds of this invention against the PxGSTδ1 recombinant protein were... 50 All were greater than 100 μM; the IC50 values ​​of compounds PXG 11, PXG 14, PXG 15, PXG 16, PXG 19, PXG22, PXG 26 and PXG 29 of this invention against the PxGSTσ1 recombinant protein of diamondback moth were... 50 The concentrations were 38.25 μM, 53.23 μM, 62.13 μM, 49.3 μM, 82.12 μM, 80.61 μM, 35.95 μM, and 54.96 μM, respectively. The IC50 values ​​of the remaining compounds of this invention against the PxGSTσ1 recombinant protein were... 50 Both are greater than 100 μM; the IC50 values ​​of compounds PXG1 and PXG22 of this invention against the PxGSTσ2 recombinant protein of diamondback moth are... 50 The concentrations were 57.77 μM and 27.15 μM, respectively. The IC50 values ​​for the remaining compounds of this invention against the PxGSTσ2 recombinant protein were... 50 All values ​​are greater than 100 μM; the IC50 of compound PXG22 of this invention against the recombinant protein PxGSTε3 of diamondback moth is greater than 100 μM.50 The concentration was 36.89 μM, and the IC50 of the remaining compounds of this invention against the PxGSTε3 recombinant protein was... 50 All values ​​were greater than 100 μM. The positive control GSTs inhibitor GTX showed IC50 values ​​for recombinant PxGSTδ1, PxGSTσ1, PxGSTσ2, and PxGSTε3 proteins. 50 The values ​​were 36.02 μM, 66.85 μM, 7.75 μM, and 95.41 μM, respectively.

[0361] Table 4. Inhibitory effects of compounds PXG1-PXG29 of the present invention on four recombinant PxGST proteins.

[0362]

[0363] Conclusion: Compound PXG22 of this invention exhibits significant inhibitory activity against all four recombinant PxGSTs proteins possessing GSH binding sites. Among them, compound PXG22's inhibitory activity against PxGSTδ1 and PxGSTε3 recombinant proteins exceeds that of the positive control GSTs inhibitor GTX. The other compounds of this invention show varying degrees of inhibitory activity against PxGSTδ1 and PxGSTσ1 recombinant proteins, with only compound PXG1 showing significant inhibitory activity against PxGSTσ2 recombinant protein. Experimental Example 4: Detection of the insecticidal synergistic activity of compound PXG22 against chlorantraniliprole.

[0364] Experiment: A stock solution of 96% chlorantraniliprole (Chl) technical grade was prepared at a concentration of 50,000 mg / L. Six treatment concentrations were set up for the experiment: 500, 250, 125, 62.5, 31.25, and 15.63 mg / L. 200 mg / L of the compound PXG22 of this invention was added to each treatment concentration. 200 mg / L of diethyl maleate (DEM) was used as the control synergist. A water control was also included. The diamondback moth (Plutella xylostella (Linnaeus)) was collected from a vegetable field in Yunnan Province. Healthy 3rd instar larvae of the same instar were selected for indoor bioactivity testing.

[0365] Cut clean cabbage leaves into 6.5cm diameter circles (avoiding the main vein). Soak the leaves in the pesticide solution for 10 seconds, then remove and air dry at 25℃. Place them in 6.5cm diameter petri dishes. Inoculate each dish with 10 early-stage 3rd instar diamondback moth resistant larvae, cover with double layers of absorbent paper, and then cover with the petri dish lid. Place the dishes face up in an incubator at 25±1℃, 65%-70% relative humidity, and a light-to-dark ratio (L:D) of 16:8h. Each treatment is repeated 4 times, with 10 larvae per replicate. Check mortality after 48 hours and calculate LC50. 50And the resistance multiple. During observation, gently touch the insect with a small brush or sharp tweezers; if the insect does not react or cannot move in a coordinated manner, it is considered dead. The experimental procedure is strictly performed in accordance with the standard: NY / T 1154.7-2006.

[0366] The experimental data analysis was conducted on the Practical Statistical Analysis and Computer Processing Platform (DPS) (Tang Qiyi et al., 1997). Toxicity regression equations for each agent were established, and LC ratios were calculated. 50 Value and 95% confidence limit.

[0367] Results: The experimental results are shown in Table 5. The LC50 of chlorantraniliprole solution against diamondback moth resistant strains after the addition of compound PXG22 of this invention... 50 The concentration of chlorantraniliprole decreased from 110.17 mg / L to 14.04 mg / L, and the resistance multiple of the diamondback moth resistant strain to chlorantraniliprole also decreased from 479 to 61.04. For chlorantraniliprole solutions containing the control synergist DEM, the LC50... 50 The resistance folds decreased to 50.02 mg / L and 217.48, respectively.

[0368] Table 5. Synergistic effect of the compounds of this invention and DEM on chlorantraniliprole

[0369]

[0370] Note: Chlorantraniliprole

[0371] Conclusion: The compound PXG22 of this invention has significant insecticidal synergistic activity against chlorantraniliprole, and its synergistic activity exceeds that of the control synergist DEM.

[0372] Experimental Example 5: Detection of the insecticidal synergistic activity of compounds PXG1, PXG2, and PXG22 against indoxacarb.

[0373] Experiment: A stock solution of 95% indoxacarb (Ind) technical grade was prepared at a concentration of 50,000 mg / L. Six treatment concentrations were set up: 500, 250, 125, 62.5, 31.25, and 15.63 mg / L. For each treatment concentration, 200 mg / L of the compounds PXG1, PXG2, and PXG22 of this invention were added. A control synergist of 200 mg / L diethyl maleate (DEM) was used. A water control was also included. The diamondback moth (Plutella xylostella (Linnaeus)) was collected from a vegetable field in Huizhou City, Guangdong Province. Healthy 3rd instar larvae of the same instar were selected for indoor bioactivity testing.

[0374] Cut clean cabbage leaves into 6.5cm diameter circles (avoiding the main vein). Soak the leaves in the pesticide solution for 10 seconds, then remove and air dry at 25℃. Place them in 6.5cm diameter petri dishes. Inoculate each dish with 10 early-stage 3rd instar diamondback moth resistant larvae, cover with double layers of absorbent paper, and then cover with the petri dish lid. Place the dishes face up in an incubator at 25±1℃, 65%-70% relative humidity, and a light-to-dark ratio (L:D) of 16:8h. Each treatment is repeated 4 times, with 10 larvae per replicate. Check mortality after 48 hours and calculate LC50. 50 And the resistance multiple. During observation, gently touch the insect with a small brush or sharp tweezers; if the insect does not react or cannot move in a coordinated manner, it is considered dead. The experimental procedure is strictly performed in accordance with the standard: NY / T 1154.7-2006.

[0375] The experimental data analysis was conducted on the Practical Statistical Analysis and Computer Processing Platform (DPS) (Tang Qiyi et al., 1997). Toxicity regression equations for each agent were established, and LC ratios were calculated. 50 Value and 95% confidence limit.

[0376] Results: The experimental results are shown in Table 6. After adding the compound PXG1 of this invention, the LC50 of indoxacarb against diamondback moth-resistant lines was [not specified]. 50 The concentration of indoxacarb decreased from 74.72 mg / L to 59.13 mg / L, and the resistance multiple of the diamondback moth resistant strain to indoxacarb decreased from 143.70 to 113.71. After the addition of compound PXG2 of this invention, the LC50 of indoxacarb to the diamondback moth resistant strain decreased. 50 The concentration of indoxacarb decreased from 74.72 mg / L to 39.93 mg / L, and the resistance multiple of the diamondback moth resistant strain to indoxacarb decreased from 143.70 to 76.78. After the addition of compound PXG22 of this invention, the LC50 of indoxacarb to the diamondback moth resistant strain decreased. 50 The LC50 of the diamondback moth resistant strain against indoxacarb decreased from 74.72 mg / L to 51.21 mg / L, and the resistance multiple of indoxacarb to the control strain decreased from 143.70 to 98.48. Meanwhile, for indoxacarb solution containing the control synergist DEM, the LC50... 50 The resistance folds decreased to 54.11 mg / L and 104.06, respectively.

[0377] Table 6. Synergistic effect of the compounds of this invention and DEM on indoxacarb

[0378]

[0379] Note: Ind: Indoxorubicin

[0380] Conclusion: The compounds PX1, PXG2 and PXG22 of this invention all have significant insecticidal synergistic activity against indoxacarb. PXG2 and PXG22 are particularly effective, and can change the resistance of diamondback moth resistant strains to indoxacarb from high resistance to medium resistance.

[0381] Experimental Example 6: Using the diamondback moth super-resistant strain (Huizhou insect source) as the test insect, the insecticidal synergistic activity of compound PXG22 of this invention against chlorantraniliprole was tested.

[0382] Experiment: The method was the same as in Experiment Example 4. The tested diamondback moth was a chlorantraniliprole-resistant strain (Huizhou insect source). The concentration of compound PXG22 of this invention was 200 mg / L, and the concentration of diethyl maleate (DEM) as the control synergist was 200 mg / L.

[0383] Results: The experimental results are shown in Table 7. After adding the compound PXG22 of this invention, the LC50 of chlorantraniliprole solution against the highly resistant diamondback moth strain (Huizhou source) was [not specified]. 50 The LC50 of the diamondback moth super-resistant strain (Huizhou source) against chlorantraniliprole decreased from 503.38 mg / L to 148.45 mg / L, and the resistance multiple of chlorantraniliprole also decreased from 2188.61 to 645.43. For chlorantraniliprole solutions with added control synergist DEM, the LC50... 50 The resistance multiples decreased to 442.81 mg / L and 1925.26, respectively.

[0384] Table 7. Synergistic effect of compounds PXG22 and DEM of the present invention on chlorantraniliprole

[0385]

[0386] Note: Chlorantraniliprole

[0387] Conclusion: The compound PXG22 of this invention significantly enhances the insecticidal activity of chlorantraniliprole against the highly resistant strain of diamondback moth (Huizhou insect source), and its synergistic activity against chlorantraniliprole is significantly higher than that of the control synergist DEM.

[0388] Experimental Example 7: Using the diamondback moth highly resistant strain I (Lianzhou insect source) as the test insect, the insecticidal synergistic activity of different concentrations of the compound PXG22 of this invention against chlorantraniliprole was detected.

[0389] Experiment: The method was the same as in Experiment Example 4. The tested diamondback moth was a highly resistant strain I of chlorantraniliprole (Lianzhou insect source). The concentrations of compound PXG22 of this invention were 200 mg / L, 100 mg / L and 50 mg / L, while the concentration of the control synergist diethyl maleate (DEM) was maintained at 200 mg / L.

[0390] Results: The experimental results are shown in Table 8. The LC-releasing capacity of chlorantraniliprole solutions against the highly resistant diamondback moth strain I (Lianzhou source) was determined after adding 200 mg / L, 100 mg / L, and 50 mg / L of the compound PXG22 of this invention.50 The LC50 concentrations of chlorantraniliprole decreased from 134.26 mg / L to 40.44 mg / L, 21.16 mg / L, and 49.89 mg / L, respectively. The resistance multiples of the diamondback moth resistant strain I (from Lianzhou) to chlorantraniliprole also decreased from 583.74 to 175.82, 92, and 216.91, respectively. For chlorantraniliprole solutions containing the control synergist DEM, the LC50 concentrations... 50 The resistance folds decreased to 53.36 mg / L and 232 mg / L, respectively.

[0391] Table 8. Synergistic effect of compounds PXG22 and DEM of the present invention on chlorantraniliprole

[0392]

[0393] Note: Chlorantraniliprole

[0394] Conclusion: The compound PXG22 of this invention significantly enhances the insecticidal activity of chlorantraniliprole against the highly resistant strain I of diamondback moth (Lianzhou insect source). Moreover, when the concentration of compound PXG22 is 100 mg / L, its synergistic activity against chlorantraniliprole is the strongest, which is significantly higher than that of the control synergist DEM.

[0395] Experimental Example 8: Using the diamondback moth highly resistant strain II (Lianzhou insect source) as the test insect, the insecticidal synergistic activity of different concentrations of the compound PXG22 of this invention against chlorantraniliprole was detected.

[0396] Experiment: The method was the same as in Experiment Example 4. The tested diamondback moth was a chlorantraniliprole-resistant strain II (Lianzhou insect source). The concentrations of compound PXG22 of this invention were 200 mg / L, 100 mg / L, 50 mg / L and 25 mg / L, while the concentration of the control synergist diethyl maleate (DEM) was maintained at 200 mg / L.

[0397] Results: The experimental results are shown in Table 9. The LC-index of chlorantraniliprole solutions against the highly resistant diamondback moth strain II (Lianzhou source) was determined after adding 200 mg / L, 100 mg / L, 50 mg / L, and 25 mg / L of the compound PXG22 of this invention. 50 The concentrations of chlorantraniliprole decreased from 145.19 mg / L to 55.92 mg / L, 44.86 mg / L, 71.88 mg / L, and 78.54 mg / L, respectively. The resistance multiples of the highly resistant diamondback moth strain II (from Lianzhou) to chlorantraniliprole also decreased from 631.26 to 243.13, 195.04, 312.52, and 341.48, respectively. For chlorantraniliprole solutions containing the control synergist DEM, the LC50 values... 50 The resistance folds decreased to 107.99 mg / L and 469.52, respectively.

[0398] Table 9. Synergistic effect of compounds PXG22 and DEM of the present invention on chlorantraniliprole

[0399]

[0400] Note: Chlorantraniliprole

[0401] Conclusion: The compound PXG22 of this invention significantly enhances the insecticidal activity of chlorantraniliprole against the highly resistant strain II of diamondback moth (Lianzhou insect source). Moreover, when the concentration of compound PXG22 is 100 mg / L, its synergistic activity against chlorantraniliprole is the strongest, which is significantly higher than that of the control synergist DEM.

[0402] Based on the above description of the invention, those skilled in the art can fully apply the present invention, and all modifications based on the same principles or similar modifications should be considered to be included within the scope of the present invention.

Claims

1. The use of diphenylpyrazole compounds of general formula (I) or their pesticide-acceptable salts as insecticide synergists, General Formula (I) in: R 1 for: (1) An amide group that is unsubstituted or whose C is substituted by one or more of the following substituents: -NH-CH(O); (a)-C 1~6 Alkyl-R 3 -C 3~8 cycloalkyl-R 3 -C 2~6 alkenyl-R 3 -C 1~6 Alkyl-NH-R 3 -C 1~6 Alkyl-N(R) 3 )2、-C 1~6 Alkyl-OR 3 -C 3~8 cycloalkyl-OR 3 -OC 1~6 Alkyl-R 3 -C 1~6 Alkyl-OC 1~6 Alkyl-R 3 -C 1~6 Alkyl-NH-C(O)-R 3 -C 1~6 Alkyl-NH-C(O)-OR 3 or -C 1~6 Alkyl-SR 3 ; The R 3 Each group is independently selected from: H, amino, halogen, cyano, -C 1~6 Alkyl, -C 3~8 cycloalkyl, -SC 1~6 Alkyl, -S-OH, -SO2-C 1~6 Alkyl, -6 to 14 aryl, -5 to 14 heterocyclic, -5 to 14 heteroaryl, and -adamantyl; wherein the 6 to 14 aryl, 5 to 14 heterocyclic, or 5 to 14 heteroaryl is unsubstituted or substituted by one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1~6 Alkyl, -C 2~6 alkenyl, -C 2~6 alkynyl group, -OC 1~6 Alkyl, sulfonic acid group, -C 1~6 Alkyl-halogen, -C 1~6 Alkyl -OH, -C 1~6 Alkyl-NH-C 1~6 Alkyl or -C 1~6 Alkyl-N(C) 1~6 Alkyl)2; (b) -6~14 aryl, -5~14 heterocyclic or -5~14 heteroaryl; The 6-14 aryl, 5-14 heterocyclic, or 5-14 heteroaryl group is unsubstituted or substituted by one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1~6 Alkyl, -OC 1~6 Alkyl, -C 1~6 Alkyl-NH-C 1~6 Alkyl, -C 1~6 Alkyl-N(C) 1~6 Alkyl)2、-C(O)-OC 1~6 Alkyl, -NH-C(O)-C 1~6 Alkyl group, -SO2-C 1~6 Alkyl, -SO2-NH2, -SO2-NH-C 1~6 Alkyl or -SO2-N(C) 1~6 Alkyl)2; (2) The N atom of the amide group -NH-CH(O) interacts with the C atom through -NH-C 2~6 Alkylene-, -NH-C(O)-C 1~6 alkylene-, -C 1~6 Alkylene -NH-C(O)-, -NH-C 1~6 alkylene-C(O)- or -C 1~6 Alkyl groups -C(O)- are linked to form a cyclic structure; this cyclic structure may optionally be substituted with the following substituents: -C 1~6 Alkyl, -C 3~8 cycloalkyl, -C 3~8 cycloalkyl-C 1~6 Alkyl, -6~14 aryl, -5~14 heterocyclic, -5~14 heteroaryl, -C 1~6 Alkyl-6~14-membered aryl, -C 1~6 Alkyl-5 to 14-membered heterocyclic groups or -C 1~6 Alkyl-5-14-membered heteroaryl; the 6-14-membered aryl, 5-14-membered heterocyclic and 5-14-membered heteroaryl groups are optionally -OC 1~6 Alkyl substitution; The heterocyclic group contains 1 to 4 heteroatoms selected from N, S, and O; the heteroaryl group contains 1 to 4 heteroatoms selected from N, S, and O; R 2 Selected from: -H, halogen, amino, -NO2, -CF3, -C 1~6 Alkyl, -C 1~6 Alkyl-OH, -OR 4 -C(O)-R 4 -C(O)-NH2, -NH-C(O)-R 4 -C(O)-OR 4 -C(O)-ON(R) 4 )2;R 4 Selected from: H or C 1~6 alkyl.

2. The use according to claim 1, wherein, R 1 for: (1) The amide group C is substituted by one or more of the following substituents: -NH-CH(O), (a)-C 1~3 Alkyl-R 3 -C 3~6 cycloalkyl-R 3 -C 2~5 alkenyl-R 3 -C 1~3 Alkyl-NH-R 3 -C 1~3 Alkyl-OR 3 or -OC 1~3 Alkyl-R 3 The R 3 Each group is independently selected from: H, amino, halogen, cyano, -C 1~3 Alkyl, -C 3~6 Cycloalkyl, -6-14 aryl, -5-14 heterocyclic, and -5-14 heteroaryl; wherein the 6-14 aryl, 5-14 heterocyclic, or 5-14 heteroaryl is unsubstituted or substituted by one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1~3 Alkyl, -C 2~5 alkenyl, -C 2~5 alkynyl group, -OC 1~3 Alkyl, sulfonic acid group, -C 1~3 Alkyl-halogen or -C 1~3 alkyl-OH; (b) -6~14 aryl, -5~14 heterocyclic or -5~14 heteroaryl; wherein the 6~14 aryl, 5~14 heterocyclic or 5~14 heteroaryl is unsubstituted or substituted by one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1~3 Alkyl, -OC 1~3 Alkyl, -C 1~3 Alkyl-NH-C 1~3 Alkyl, -C 1~3 Alkyl-N(C) 1~3 Alkyl)2、-C(O)-OC 1~3 Alkyl, -NH-C(O)-C 1~3 Alkyl group, -SO2-C 1~3 Alkyl, -SO2-NH2, -SO2-NH-C 1~3 Alkyl or -SO2-N(C) 1~3 Alkyl)2; (2) The N atom of the amide group -NH-CH(O) interacts with the C atom through -NH-C 2~4 Alkylene-, -NH-C(O)-C 1~3 alkylene-, -C 1~3 Alkylene -NH-C(O)-, -NH-C 1~3 alkylene-C(O)- or -C 1~3 Alkyl groups -C(O)- are linked to form a cyclic structure, which may optionally be substituted with the following substituents: -C 1~3 Alkyl, -C 3~6 cycloalkyl, -C 3~6 cycloalkyl-C 1~3 Alkyl, -6~14 aryl, -5~14 heterocyclic, -5~14 heteroaryl, -C 1~3 Alkyl-6~14-membered aryl, -C 1~3 Alkyl-5~14-membered heterocyclic groups, -C 1~3 Alkyl-5-14-membered heteroaryl; the 6-14-membered aryl, 5-14-membered heterocyclic and 5-14-membered heteroaryl groups are optionally -OC 1~3 Alkyl substitution; The heterocyclic group contains 1 to 3 heteroatoms selected from N, S, and O; the heteroaryl group contains 1 to 3 heteroatoms selected from N, S, and O; R 2 It is: -H or halogen.

3. The use according to claim 1, wherein, R 1 for: (1) -NH-C(O)-C 1~3 Alkyl-R 3 The R 3 Selected from: -6~10 aryl, -5~10 heterocyclic and -5~10 heteroaryl; the R 3 Unsubstituted or substituted with one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1~3 Alkyl, -OC 1~3 Alkyl, sulfonic acid group, -C 1~3 Alkyl-halogen or -C 1~3 alkyl-OH; (2) -NH-C(O)-6~10 aryl, -NH-C(O)-5~10 heterocyclic or -NH-C(O)-5~10 heteroaryl; wherein the 6~10 aryl, 5~10 heterocyclic or 5~10 heteroaryl is unsubstituted or substituted by one or more of the following substituents: O, -OH, halogen, cyano, nitro, -CH(O), amino, -C 1~3 Alkyl or -OC 1~3 alkyl; The heterocyclic group contains 1 to 3 heteroatoms selected from N, S, and O; the heteroaryl group contains 1 to 3 heteroatoms selected from N, S, and O; R 2 For: -H.

4. The use according to claim 1, wherein, R 1 Specifically: ， ， 。 5. The use according to claim 1, wherein, The general formula (I) diphenylpyrazole compounds or their pesticide-acceptable salts are the following compounds or their pesticide-acceptable salts: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 6. The use according to claim 1, wherein, The general formula (I) diphenylpyrazole compounds or their pesticide-acceptable salts are the following compounds or their pesticide-acceptable salts: 、 、 。 7. The use according to claim 1, wherein, The insecticide synergist delays or reduces the insecticide resistance of pests.

8. The use according to claim 1, wherein, The insecticide is selected from: ryanodine receptor modulator insecticides or voltage-dependent sodium ion channel blocker insecticides.

9. The use according to claim 1, wherein, The insecticide is selected from: diamide insecticides or oxadiazine insecticides.

10. The use according to claim 1, wherein, The insecticide is selected from chlorantraniliprole or indoxacarb.

11. The use according to claim 7, wherein, The pests mentioned are selected from: pests of field crops or pests of economic crops.

12. The use according to claim 7, wherein, The pest mentioned was selected from: diamondback moth. Plutella xylostella Armyworms Mythimna separata Corn borer Pyrausta nubilalis , borer Chilo suppressalis Brown planthopper Nilaparvata lugens fall armyworm Spodoptera frugiperda , cotton bollworm Helicoverpa armigera Peach fruit moth Carposina sasakii Or beet armyworm Spodoptera litura .

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