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CN-117658918-B - Application of diphenylpyrazole compound

CN117658918BCN 117658918 BCN117658918 BCN 117658918BCN-117658918-B

Abstract

The invention belongs to the technical field of pesticides, and particularly provides application of a diphenylpyrazole compound shown in a general formula (I). The compound targets the pest GSTs, has wide inhibition activity on the GSTs in various pests, can effectively delay the in-vivo metabolism of the pest GSTs on pesticides, thereby reducing the metabolic resistance of the pests on the pesticides, and is suitable for being used as pesticides.

Inventors

  • LIU JIYUAN
  • ZHANG YALIN

Assignees

  • 西北农林科技大学

Dates

Publication Date
20260505
Application Date
20210706
Priority Date
20210105

Claims (12)

  1. 1. The application of the diphenyl pyrazole compound shown in the following general formula (I) or the pharmaceutically acceptable salt thereof as an insecticide synergist, General formula (I) Wherein R 1 is: (1) An amido-NH-CH (O) unsubstituted or substituted with one or more substituents selected from the group consisting of; (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-O-R 3 、-C 3~8 cycloalkyl-O-R 3 、-O-C 1~6 alkyl-R 3 、-C 1~6 alkyl-O-C 1~6 alkyl-R 3 、-C 1~6 alkyl-NH-C (O) -R 3 、-C 1~6 alkyl-NH-C (O) -O-R 3 or-C 1~6 alkyl-S-R 3 ; the R 3 is independently selected from H, amino, halogen, cyano, -C 1~6 alkyl, -C 3~8 cycloalkyl, -S-C 1~6 alkyl, -S-OH, -SO 2 -C 1~6 alkyl, -6-14 membered aryl, -5-14 membered heterocyclyl, -5-14 membered heteroaryl and-adamantyl, the 6-14 membered aryl, 5-14 membered heterocyclyl or 5-14 membered heteroaryl being unsubstituted or substituted with one or more substituents O, -OH, halogen, cyano, nitro, -CH (O), amino, -C 1~6 alkyl, -C 2~6 alkenyl, -C 2~6 alkynyl, -O-C 1~6 alkyl, sulfo, -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) -a 6-14 membered aryl, -a 5-14 membered heterocyclyl or-a 5-14 membered heteroaryl; The 6-14 membered aryl, 5-14 membered heterocyclyl or 5-14 membered heteroaryl is unsubstituted or substituted with one or more substituents selected from O, -OH, halogen, cyano, nitro, -CH (O), amino, -C 1~6 alkyl, -O-C 1~6 alkyl, -C 1~6 alkyl-NH-C 1~6 alkyl, -C 1~6 alkyl-N (C 1~6 alkyl) 2 、-C(O)-O-C 1~6 alkyl, -NH-C (O) -C 1~6 alkyl, -SO 2 -C 1~6 alkyl, -SO 2 -NH 2 、-SO 2 -NH-C 1~6 alkyl or-SO 2 -N(C 1~6 alkyl) 2 ; (2) The N atom and the C atom of the amido-NH-CH (O) are connected into a cyclic structure 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 alkylene-C (O) -, wherein the cyclic structure is optionally substituted by-C 1~6 alkyl, -C 3~8 cycloalkyl, -C 3~8 cycloalkyl-C 1~6 alkyl, -6-14 membered aryl, -5-14 membered heterocyclyl, -5-14 membered heteroaryl, -C 1~6 alkyl-6-14 membered aryl, -C 1~6 alkyl-5-14 membered heterocyclyl or-C 1~6 alkyl-5-14 membered heteroaryl, and the 6-14 membered aryl, 5-14 membered heterocyclyl and 5-14 membered heteroaryl are optionally substituted by-O-C 1~6 alkyl; The heterocyclic group contains 1-4 hetero atoms selected from N, S and O, and the heteroaryl group contains 1-4 hetero atoms selected from N, S and O; R 2 is selected from-H, halogen, amino, -NO 2 、-CF 3 、-C 1~6 alkyl, -C 1~6 alkyl -OH、-O-R 4 、-C(O)-R 4 、-C(O)-NH 2 、-NH-C(O)-R 4 、-C(O)-O-R 4 、-C(O)-O-N(R 4 ) 2 ;R 4 is selected from H or C 1~6 alkyl.
  2. 2. The use according to claim 1, wherein, R 1 is: (1) C is an amido-NH-CH (O) substituted with one or more substituents, (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-O-R 3 or-O-C 1~3 alkyl-R 3 , each of said R 3 being independently selected from the group consisting of H, amino, halogen, cyano, -C 1~3 alkyl, -C 3~6 cycloalkyl, -6-14 membered aryl, -5-14 membered heterocyclyl and-5-14 membered heteroaryl, said 6-14 membered aryl, 5-14 membered heterocyclyl or 5-14 membered heteroaryl being unsubstituted or substituted with one or more substituents selected from the group consisting of O, -OH, halogen, cyano, nitro, -CH (O), amino, -C 1~3 alkyl, -C 2~5 alkenyl, -C 2~5 alkynyl, -O-C 1~3 alkyl, sulfo, -C 1~3 alkyl-halogen or-C 1~3 alkyl-OH; (b) -a 6-14 membered aryl, -a 5-14 membered heterocyclyl or-a 5-14 membered heteroaryl, said 6-14 membered aryl, 5-14 membered heterocyclyl or 5-14 membered heteroaryl being unsubstituted or substituted by one or more substituents O, -OH, halogen, cyano, nitro, -CH (O), amino, -C 1~3 alkyl, -O-C 1~3 alkyl, -C 1~3 alkyl-NH-C 1~3 alkyl, -C 1~3 alkyl-N (C 1~3 alkyl) 2 、-C(O)-O-C 1~3 alkyl, -NH-C (O) -C 1~3 alkyl, -SO 2 -C 1~3 alkyl, -SO 2 -NH 2 、-SO 2 -NH-C 1~3 alkyl or-SO 2 -N(C 1~3 alkyl) 2 ; (2) The N atom and the C atom of the amido-NH-CH (O) are connected into a cyclic structure 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 alkylene-C (O) -, the cyclic structure is optionally substituted by-C 1~3 alkyl, -C 3~6 cycloalkyl, -C 3~6 cycloalkyl-C 1~3 alkyl, -6-14 membered aryl, -5-14 membered heterocyclyl, -5-14 membered heteroaryl, -C 1~3 alkyl-6-14 membered aryl, -C 1~3 alkyl-5-14 membered heterocyclyl, -C 1~3 alkyl-5-14 membered heteroaryl, and the 6-14 membered aryl, 5-14 membered heterocyclyl and 5-14 membered heteroaryl are optionally substituted by-O-C 1~3 alkyl; the heterocyclic group contains 1-3 hetero atoms selected from N, S and O, and the heteroaryl group contains 1-3 hetero atoms selected from N, S and O; R 2 is-H or halogen.
  3. 3. The use according to claim 1, wherein, R 1 is: (1) -NH-C (O) -C 1~3 alkyl-R 3 , said R 3 being selected from the group consisting of-6-10 membered aryl, -5-10 membered heterocyclyl and-5-10 membered heteroaryl, said R 3 being unsubstituted or substituted by one or more substituents O, -OH, halogen, cyano, nitro, -CH (O), amino, -C 1~3 alkyl, -O-C 1~3 alkyl, sulfonic, -C 1~3 alkyl-halogen or-C 1~3 alkyl-OH; (2) -NH-C (O) -6-10 membered aryl, -NH-C (O) -5-10 membered heterocyclyl or-NH-C (O) -5-10 membered heteroaryl, said 6-10 membered aryl, 5-10 membered heterocyclyl or 5-10 membered heteroaryl being unsubstituted or substituted by one or more substituents O, -OH, halogen, cyano, nitro, -CH (O), amino, -C 1~3 alkyl or-O-C 1~3 alkyl; the heterocyclic group contains 1-3 hetero atoms selected from N, S and O, and the heteroaryl group contains 1-3 hetero atoms selected from N, S and O; R 2 is-H.
  4. 4. The use according to claim 1, wherein, R 1 is specifically: , , 。
  5. 5. The use according to claim 1, wherein the diphenylpyrazole compound of general formula (I) or an agropharmaceutically acceptable salt thereof is the following compound or an agropharmaceutically acceptable salt thereof: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。
  6. 6. The use according to claim 1, wherein the diphenylpyrazole compound of general formula (I) or an agropharmaceutically acceptable salt thereof is the following compound or an agropharmaceutically acceptable salt thereof: 、 、 。
  7. 7. The use according to claim 1, wherein the pesticide synergist delays or reduces the resistance of the pest to the pesticide.
  8. 8. The use according to claim 1, wherein the insecticide is selected from the group consisting of a ryanodine receptor modulator insecticide or a voltage dependent sodium ion channel blocker insecticide.
  9. 9. The method according to claim 1, wherein the insecticide is selected from bisamide insecticides or oxadiazine insecticides.
  10. 10. The method according to claim 1, wherein the pesticide is selected from chlorantraniliprole or indoxacarb.
  11. 11. The method according to claim 7, wherein the pest is selected from the group consisting of field crop pests and cash crop pests.
  12. 12. The use according to claim 7, wherein the pest is selected from plutella xylostella Plutella xylostella, armyworm MYTHIMNA SEPARATA, corn borer Pyrausta nubilalis, chilo suppressalis Chilo suppressalis, brown planthopper NILAPARVATA LUGENS, spodoptera frugiperda Spodoptera frugiperda, cotton bollworm Helicoverpa armigera, peach fruit borer Carposina sasakii or prodenia litura Spodoptera litura.

Description

Application of diphenylpyrazole compound The application relates to a split application of application number 2021107606474 and the application name of diphenyl pyrazole compound, a preparation method and application thereof, which are filed on the year 2021, month 07 and year 06. Technical Field The invention belongs to the technical field of pesticides, and particularly relates to application of a diphenylpyrazole compound. Background For a long time, pesticides have been the primary means of agricultural pest control. Among the various pesticides, the ryanodine receptor modulator represented by chlorantraniliprole and the voltage-dependent sodium ion channel blocker represented by indoxacarb have the characteristics of novel structure, unique action mechanism, quick response, broad insecticidal spectrum, environmental friendliness and the like, and are widely focused on, so that the ryanodine receptor modulator is a popular variety of pesticides. Chlorantraniliprole belongs to bisamide pesticides, and indoxacarb belongs to oxadiazine pesticides. The two pesticides can control most chewing mouthpart pests, especially have good control effects on lepidoptera (cnaphalocrocis medinalis, corn borers, cowpea borers and the like), fruit moth (spodoptera frugiperda, cotton bollworms, prodenia litura and the like), spodoptera (codling moth, piroplasmosa and the like), horrida (pink bollworm and the like), plutella xylostella (plutella xylostella and the like), pinctada (cabbage butterflies and the like), lepidoptera (golden moth and the like) and the like, and have higher activity on coleoptera (potato beetles and the like), diptera (liriomyza sativa and the like) and other wing pests. In recent years, the market for bisamides and oxadiazines pesticides has grown rapidly, and there is still a great growing potential in the future. The most widely used of these two classes of pesticides are chlorantraniliprole and indoxacarb, respectively. In 2019, chlorantraniliprole is in the army of the global pesticide market, the global sales rate reaches up to 15.81 hundred million dollars, and the global sales rate of indoxacarb reaches up to 2.06 hundred million dollars. However, with the widespread use of these two pesticides, there are a variety of pests to which resistance has been developed to varying degrees, which become the main limiting factor for these two pesticides. The drug resistance monitoring shows that the field plutella xylostella population has high-level resistance to chlorantraniliprole, the population resistance in partial areas is even more than 1000 times, the resistance to indoxacarb is also generally more than 10 times, and the population resistance in partial areas is more than 100 times. The aggravation of the drug resistance of the pests not only seriously affects the service life of the pesticides, but also causes the increase of the using times and the dosage of the pesticides, thereby causing huge economic loss. Effective management of pest resistance has become a challenge to be addressed in the field of global plant protection. The mechanisms of pest resistance to pesticides can be broadly categorized into three categories, metabolic resistance, penetration resistance and target resistance, with detoxified enzyme-mediated metabolic resistance being common. A plurality of researches show that Glutathione S Transferase (GSTs) can be used as an important detoxification enzyme system in insects to participate in the drug resistance of the insects to various common pesticides such as organochlorine, organophosphorus, pyrethroid, neonicotinoid, diamide, abamectin and the like through the modes of gene mutation, activity increase, up-regulation expression and the like. For example, silencing LmGSTs and LmGSTu1 in migratory locust Locusta migratoria can significantly increase the sensitivity of its nymphs to malathion and chlorpyrifos. There is also evidence that insect GSTs can directly metabolize a variety of pesticides. For example, the recombinant protein of cotton bollworm HaGST-8 has better metabolic activity on chlorpyrifos, dichlorvos, cypermethrin and the like. GSTs play an important role in the development and progression of pest resistance, and decreasing their activity significantly reduces pest resistance. Compounds such as S-Hexylglutathione (GTX) and diethyl maleate (DEM) have been reported to increase control by inhibiting GSTs activity and retarding the rate of metabolism of pesticides by pests. These compounds are used as GSTs inhibitor, generally have no insecticidal activity per se, but can obviously improve the toxicity or efficacy of the pesticide when mixed with the pesticide, and are important pesticide synergists. The research and development of the inhibitor for targeting insect GSTs can not only improve the control effect of the pesticide, but also delay or reduce the drug resistance, prolong the service life of the pesticide, and has important significance for the treatm