A γ-aminobutyric acid-gated chloride channel allosteric modulator compound and its use

Abstract

The present invention discloses a γ-aminobutyric acid-gated chloride channel allosteric modulator compound and its use, namely (S)-4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide. The compound has excellent control effects on pests such as Thysanoptera, Acarina, and Lepidoptera, is very friendly to bees, has high environmental and ecological safety, can be used to prepare high-efficiency, low-toxic, and safe insecticides, and has broad application prospects in agricultural production.

Description

Technical Field

[0001] The present invention relates to a γ-aminobutyric acid-gated chloride ion channel allosteric modulator compound and its application, belonging to the technical field of pesticide compounds. Background Art

[0002] Currently, the use of pesticides remains the most effective method for controlling agricultural pests worldwide. However, the most common problem with pest control in agricultural production is the development of pesticide resistance. To maintain the advantages of modern pesticides in terms of high efficiency, low toxicity, pesticide resistance, environmental friendliness, and economic viability, the continuous discovery and development of new products is essential.

[0003] These novel insecticides are specific for γ-aminobutyric acid (GABA) receptors and possess broad-spectrum, high activity, and high selectivity. They exhibit strong biological activity against agricultural pests such as Hemiptera, Thysanoptera, Diptera, Lepidoptera, and mites. Currently, marketed pesticides of this class include Fluxametamide.

[0004] Currently, pesticide application is a crucial tool for preventing and controlling plant pests and diseases in agricultural production. However, with the repeated and extensive use of existing pesticides, coupled with inappropriate application by some farmers, some pests are gradually developing resistance to common pesticides, making pesticide control increasingly difficult. Developing and researching new pesticides is an effective way to address this pest resistance problem. Therefore, developing new, highly effective, low-toxic, and safe pesticides for pest control is crucial. Summary of the Invention

[0005] The purpose of the present invention is to overcome the deficiencies of the above-mentioned prior art and to provide a γ-aminobutyric acid-gated chloride channel allosteric modulator compound and its use.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] 1. A γ-aminobutyric acid-gated chloride channel allosteric modulator compound or an agrochemically acceptable salt thereof, wherein the compound is (S)-4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide (abbreviated as: S-configuration CCMO-88), and the chemical structure is as follows:

[0008]

[0009] 2. A pharmaceutical composition comprising the aforementioned γ-aminobutyric acid-gated chloride channel allosteric modulator compound or an agrochemically acceptable salt thereof.

[0010] 3. Use of the aforementioned γ-aminobutyric acid-gated chloride channel allosteric modulator compound or an agrochemically acceptable salt thereof in the preparation of agricultural pesticides.

[0011] Preferably, the agricultural insecticide is used to control the following insects: Thysanoptera, Acarina, and Lepidoptera.

[0012] More preferably, the agricultural insecticide is used to control the following insects: Thripidae, Tetranychus, and Pyralidae.

[0013] More preferably, the agricultural insecticide is used to control palm thrips, flower thrips, two-spotted spider mite, and striped stem borer.

[0014] 4. Use of the aforementioned pharmaceutical composition in the preparation of agricultural pesticides.

[0015] Preferably, the agricultural insecticide is used to control the following insects: Thysanoptera, Acarina, and Lepidoptera.

[0016] More preferably, the agricultural insecticide is used to control the following insects: Thripidae, Tetranychus, and Pyralidae.

[0017] More preferably, the agricultural insecticide is used to control palm thrips, flower thrips, two-spotted spider mite, and striped stem borer.

[0018] 5. An agricultural insecticide, the active ingredient of which is the aforementioned γ-aminobutyric acid-gated chloride channel allosteric modulator compound or an agrochemically acceptable salt thereof.

[0019] 6. An agricultural insecticide comprising the aforementioned pharmaceutical composition.

[0020] Beneficial effects of the present invention:

[0021] The present invention discloses a γ-aminobutyric acid-gated chloride channel allosteric modulator compound, namely (S)-4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, referred to as S-configuration CCMO-88. This compound has excellent control effects on pests such as Thysanoptera, Acarina, and Lepidoptera, is very friendly to bees, has high environmental and ecological safety, can be used to prepare high-efficiency, low-toxicity, and safe insecticides, and has broad application prospects in agricultural production.

[0022] Indoor toxicity tests against palm thrips showed that the S-configuration CCMO-88 was 2.38 times more potent than CCMO-88, over 326 times more potent than R-configuration CCMO-88, and 410 times more potent than flurelana. Indoor toxicity tests against flower thrips showed that the S-configuration CCMO-88 was approximately twice as potent as CCMO-88, approximately 500 times more potent than R-configuration CCMO-88, and approximately 200 times more potent than flurelana. Indoor toxicity tests against spider mites showed that the S-configuration CCMO-88 was 2.03 times more potent than CCMO-88, over 39 times more potent than R-configuration CCMO-88, and 9.2 times more potent than flurelana. Indoor toxicity tests against the striped stem borer showed that the S-configuration CCMO-88 was approximately twice as potent as CCMO-88, approximately 133 times more potent than R-configuration CCMO-88, and approximately 167 times more potent than flurelana. The above data all show that CCMO-88 with S configuration is more effective in killing pests of Thripidae, Tetranychus, and Pyralidae than CCMO-88, and is significantly better than CCMO-88 with R configuration and Flurelana.

[0023] At present, in order to protect the health of the ecosystem and control the potential adverse effects of high-risk pesticides on the environment and ecology from the source, Europe and the United States have proposed a complete pesticide biosafety evaluation system for bees. my country's Ministry of Environmental Protection and Ministry of Agriculture have also listed the biotoxicity and safety evaluation of pesticides on bees as an important part of pesticide registration management and pesticide use environmental safety management. Therefore, the safety evaluation of bees is an indispensable part of the research on the drugability of innovative pesticides. The applicant conducted an oral toxicity test on bees with reference to GB / T31270.10-2014 "Test Guidelines for Environmental Safety Evaluation of Chemical Pesticides Part 10: Acute Toxicity Test for Bees". The results showed that the acute oral toxicity test results of S-configuration CCMO-88 Italian honey bees were: LD 50 (48 hours)>11μg ai / bee, which is low toxic according to the acute toxicity classification standard of pesticides to bees in the "Chemical Pesticide Environmental Safety Evaluation Test Guidelines"; CCMO-88 Italian honey bee acute oral toxicity test results: LD 50 (48 hours) 1.8μg ai / bee, according to the "Chemical Pesticide Environmental Safety Evaluation Test Guidelines" classification standard for the acute toxicity of pesticides to bees, it is highly toxic; R-configuration CCMO-88 Italian honey bee acute oral toxicity test results: LD 50 (48 hours) 0.12μg ai / bee, according to the "Chemical Pesticide Environmental Safety Evaluation Test Guidelines" classification standard for the acute toxicity of pesticides to bees, it is highly toxic; the results of the toxicity test of flurelana on Italian honey bees showed that the acute toxicity was highly toxic (LD 50The above data show that the toxicity of CCMO-88 with S configuration to bees is significantly lower than that of CCMO-88, CCMO-88 with R configuration, and flurellan. It is more bee-friendly, has greater potential for drug development and practical agricultural application, and has broader prospects for agricultural application. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is the hydrogen spectrum of CCMO-88 in S configuration;

[0025] Figure 2 This is the hydrogen spectrum of racemic CCMO-88;

[0026] Figure 3 This is the hydrogen spectrum of CCMO-88 in R configuration. DETAILED DESCRIPTION

[0027] The present invention will be further described below with reference to the accompanying drawings and embodiments. It should be noted that the following description is only for explaining the present invention and does not limit its contents.

[0028] Example 1: CCMO-88 in S configuration

[0029] (S)-4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, the chemical structure is as follows:

[0030]

[0031] The preparation method is as follows:

[0032]

[0033] (1) Preparation of intermediate 1:

[0034] Take 4-acetyl-2-methylbenzoic acid (CAS: 55860-35-0, supplier: Dezhou Hanhua Pharmaceutical Chemical Co., Ltd.) (150 g, 841.8 mmol), 1-[3-chloro-5-(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone (CAS: 1125812-58-9, supplier: Dezhou Hanhua Pharmaceutical Chemical Co., Ltd.) (232.8 g, 841.8 mmol), and triethylamine (170.3 g, 1683 mmol) into a 2000 ml three-necked flask, add 1000 mL of toluene, and start stirring. The mixture was heated under reflux for 24 hours, then the heat was turned off and the temperature was cooled to room temperature. 193 g of 35% concentrated hydrochloric acid was added and stirred for 1 hour. The layers were separated and the toluene layer was concentrated to dryness to obtain (4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluoro-3-hydroxybutyryl)-2-methylbenzoic acid) as a white solid (345 g) in a 90% yield. [MH] - =453.0333

[0035] (2) Preparation of intermediate 2:

[0036] To a 2000 mL three-necked flask, add (4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluoro-3-hydroxybutyryl)-2-methylbenzoic acid) (345 g, 758.6 mmol), 1380 mL of toluene, acetic anhydride (93 g, 910 mmol), and DMAP (4-dimethylaminopyridine, 18.5 g, 151.7 mmol). Heat to reflux and stir for 12 hours. Cool to room temperature, add 35% hydrochloric acid (79 g, 757.62 mmol), stir for 1 hour, and separate the layers. The toluene layer is concentrated to dryness to obtain 315 g of a yellow-green solid (4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-2-enoyl)-2-methylbenzoic acid) in a 95% yield. [MH]- = 435.0227

[0037] (3) Preparation of intermediate 3:

[0038] Take (4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-2-enoyl)-2-methylbenzoic acid) intermediate di (315 g, 721 mmol) and put it into a 2000 mL three-necked flask. Add 1575 mL of toluene and add thionyl chloride (128 g, 1082 mmol) under stirring. Heat and reflux for 2 hours. Concentrate the reaction solution to dryness to obtain an acid chloride concentrate for standby use.

[0039] (2-Amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride) (CAS: 1171331-39-7, supplier: Dezhou Hanhua Pharmaceutical Chemical Co., Ltd.) (166.6 g, 866 mmol), triethylamine (109.5 g, 1082 mmol), and 945 ml of toluene were placed in a 2000 ml three-necked flask and stirred for 1 hour. The concentrated acyl chloride solution from the previous step was added and stirring continued for 12 hours. A large amount of solid precipitated. After TLC, the acyl chloride reaction was complete. 1 L of purified water was added and stirred for 1 hour. The mixture was filtered and the filter cake was placed in a 50°C forced air oven and dried for 12 hours to obtain 331.7 g of a yellow-green solid (4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-2-enoyl)-2-methyl-N-(2-oxo-2-((2,2-trifluoroethyl)amino)ethyl)benzamide) with a yield of 80%. [M+H] + =575.0774, [MH] - =573.0634

[0040] (4) Preparation of CCMO-88 with S configuration:

[0041] (4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-2-enoyl)-2-methyl-N-(2-oxo-2-((2,2-trifluoroethyl)amino)ethyl)benzamide) (57.5 g, 100 mmol) and N-(acridin-9-ylmethyl)quinine bromide (CAS: 466639-23-6, supplier: Dezhou Hanhua Pharmaceutical Chemical Co., Ltd.) (5.96 g, 10 mmol) were added to 500 mL of dichloromethane, and 200 ml of a 10% aqueous sodium hydroxide solution was added under stirring. Hydrochloric acid was added in portions. Hydroxylamine (20.85 g, 300 mmol) was added and stirred for 12 hours. The mixture was separated and allowed to stand for 5 minutes. The dichloromethane layer was washed with 100 ml of 2M hydrochloric acid and then concentrated under reduced pressure to gradually precipitate a solid. 200 mL of water was added and the dichloromethane was dried. The mixture was stirred for 1 hour, filtered, and the filter cake was washed with water and dried to give 50 g of (S)-4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide in a yield of 85%.

[0042] The product hydrogen spectrum is shown Figure 1 .

[0043] 1H NMR(400MHz, CDCl3)δ7.82(s,1H),7.76(s,1H),7.69(s,1H),7.45–7.54(m,2H),7.46(d,1H) ,7.11(t,1H),6.82(t,1H),4.21(d,2H),4.16(d,1H),3.94(m,2H),3.75(d,1H),2.46(s,3H)C 23 H 17 ClF9N3O3, [M+H] + =590.0884, [MH] - =588.0743

[0044] Comparative Example 1: CCMO-88

[0045] The racemic form of 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide has the following chemical structure:

[0046]

[0047] The preparation method is as follows:

[0048]

[0049] (1) Preparation of Intermediate 3 is the same as in Example 1.

[0050] (2) Preparation of racemic CCMO-88:

[0051] (4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-2-enoyl)-2-methyl-N-(2-oxo-2-((2,2-trifluoroethyl)amino)ethyl)benzamide) (57.5 g, 100 mmol) was added to 500 mL of dichloromethane, and 200 ml of a 10% aqueous sodium hydroxide solution was added under stirring. Hydroxylamine hydrochloride (20.85 g, 300 mmol) was added in portions and the mixture was stirred for 12 hours. The layers were separated and the mixture was allowed to stand for 12 hours. The mixture was allowed to stand for 2 hours, and the dichloromethane layer was washed with 100 ml of 2M hydrochloric acid, then concentrated under reduced pressure to gradually precipitate a solid. 200 mL of water was added and the dichloromethane was continued to be dried. The mixture was stirred for 1 hour, filtered, and the filter cake was washed with water and dried to give 52 g of 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide in a yield of 88.4%.

[0052] The product hydrogen spectrum is shown Figure 2 .

[0053] 1 H NMR (600MHz, CDCl3) δ7.82(s,1H),7.76(s,1H),7.69(s,1H),7.55(s,1H),7.52(d,1H),7.47(d,1 H),6.93(t,1H),6.72(t,1H),4.21(d,2H),4.16(d,1H),3.95(qd,2H),3.74(d,1H),2.47(s,3H).C 23 H 17 ClF9N3O3, [M+H] + =590.0884, [MH] - =588.0743

[0054] Comparative Example 2: CCMO-88 with R configuration

[0055] The compound (R)-4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide has the following chemical structure:

[0056]

[0057] The preparation method is as follows:

[0058]

[0059] (1) Preparation of Intermediate 3 is the same as in Example 1.

[0060] (2) Preparation of CCMO-88 with R configuration:

[0061] (4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-2-enoyl)-2-methyl-N-(2-oxo-2-((2,2-trifluoroethyl)amino)ethyl)benzamide) (57.5 g, 100 mmol), (1S,2R,4S,5R)-1-(acridin-9-ylmethyl)-2-((S)-hydroxy(6-methoxyquinolin-4-yl)methyl)-5-vinylquinin-1-ammonium bromide (supplier: Dezhou Hanhua Pharmaceutical Chemical Co., Ltd.) (5.96 g, 10 mmol) were added to 500 mL of dichloromethane, and 10% mass concentration of hydroxide was added under stirring. To 200 ml of sodium aqueous solution, hydroxylamine hydrochloride (20.85 g, 300 mmol) was added portionwise, and stirring was continued for 12 hours. The layers were allowed to stand, and the dichloromethane layer was washed with 100 ml of 2M hydrochloric acid. The mixture was then concentrated under reduced pressure to gradually precipitate a solid. 200 mL of water was added and the dichloromethane was dried. The mixture was stirred for 1 hour, filtered, and the filter cake was washed with water and dried to give 48 g of (R)-4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide in a yield of 81.6%.

[0062] The product hydrogen spectrum is shown Figure 3 .

[0063] 1 H NMR (400MHz, DMSO) δ8.62(s,2H),8.09(s,1H),7.98(s,1H),7.87(s,1H),7.63(s,2H),7.52(d,1H),4.43(q,2H),3.96(m,4H),2.41(s,3H).C 23 H 17 ClF9N3O3, [M+H] + =590.0884, [MH] - =588.0727

[0064] Comparative Example 3: Flurella (CAS: 864731-61-3, supplier: Dezhou Hanhua Pharmaceutical Chemical Co., Ltd.)

[0065] The chemical structure is as follows:

[0066]

[0067] Test example

[0068] 1. Toxicology studies

[0069] According to Part 10 "Acute Toxicity Test for Bees" of the "Test Guidelines for Environmental Safety Assessment of Chemical Pesticides" (GB / T 31270.10-2014), the acute toxicity of pesticides to bees is measured according to the LD500. 50 The size of (48h) is divided into four levels:

[0070] LD 50 >11.0μg ai / bee is low toxicity,

[0071] 2.00 μg ai / bee <LD 50 ≤11.0μg ai / bee is considered poisoning,

[0072] 0.001 μg ai / bee <LD 50 ≤2.00μg ai / bee is highly toxic,

[0073] LD 50 ≤0.001μg ai / bee is highly toxic.

[0074] The toxicity test results of each compound are shown in Table 1.

[0075] Table 1. Toxicity test results

[0076]

[0077] As shown in Table 1, the toxicity of the compound in Example 1 to the beneficial insect bees is significantly lower than that of the compounds in Comparative Examples 1 to 3, making it more friendly to bees, having greater potential for drug development and practical agricultural application, and having broader prospects for agricultural application.

[0078] 2. Agricultural pest control effect

[0079] The compounds of Example 1 and Comparative Examples 1 to 3 were respectively used for controlling various agricultural pests.

[0080] This test was conducted in accordance with the agricultural industry standard of the People's Republic of China, "Guidelines for Indoor Bioassay Tests of Pesticides - Insecticides Part 8: Filter Paper Film Method" (NY / T 1154.8-2007), to determine the indoor toxicity of four technical pesticides to Thrips palmi and Thrips flower.

[0081] This test was conducted in accordance with the agricultural industry standard of the People's Republic of China, "Guidelines for Indoor Bioassay Tests of Pesticides - Insecticides Part 12: Slide Dipping Method for Spider Mites" (NY / T 1154.12-2008), to determine the indoor toxicity of four technicals to Tetranychus urticae.

[0082] This test was conducted in accordance with the agricultural industry standard of the People's Republic of China, "Guidelines for Indoor Bioassays of Pesticides - Insecticides Part 16: Activity Tests against Whiteflies - Agar Moisturized Leaf Dip Method" (NY / T 1154.16-2013), to determine the indoor toxicity of four technicals to Bemisia tabaci.

[0083] This test was conducted in accordance with the agricultural industry standard of the People's Republic of China, "Guidelines for Indoor Bioassay Tests of Pesticides - Insecticides Part 6: Activity Test - Insect Dipping Method" (NY / T 1154.6-2006), to determine the indoor toxicity of four technicals to Chilo suppressalis.

[0084] The indoor toxicity test data of the compounds of Example 1 and Comparative Examples 1 to 3 against Thrips palmi are shown in Tables 2-1 to 2-4.

[0085] Table 2-1. Indoor toxicity test data of the compound of Example 1 against Thrips palmi

[0086]

[0087]

[0088] Table 2-2. Comparative Example 1 compound indoor toxicity test data on Thrips palmi

[0089]

[0090]

[0091] Table 2-3. Comparative Example 2 compound indoor toxicity test data on Thrips palmi

[0092]

[0093]

[0094] Table 2-4. Comparative Example 3 compound indoor toxicity test data on Thrips palmi

[0095]

[0096]

[0097] The insecticidal rates of the compounds of Example 1 and Comparative Examples 1 to 3 against flower thrips are shown in Table 3.

[0098] Table 3. Insecticidal rate of compounds against flower thrips

[0099]

[0100]

[0101] The indoor toxicity test data of the compounds of Example 1 and Comparative Examples 1 to 3 against Tetranychus urticae are shown in Tables 4-1 to 4-4.

[0102] Table 4-1. Indoor toxicity test data of the compound of Example 1 against spider mite

[0103]

[0104]

[0105] Table 4-2. Indoor toxicity test data of the compound of Comparative Example 1 against Tetranychus urticae

[0106]

[0107] Table 4-3. Indoor toxicity test data of the compound of Comparative Example 2 against Tetranychus urticae

[0108]

[0109]

[0110] Table 4-4. Comparative Example 3 compound indoor toxicity test data on spider mites

[0111]

[0112]

[0113] The indoor toxicity test data of the compounds of Example 1 and Comparative Examples 1 to 3 against Bemisia tabaci are shown in Tables 5-1 to 5-4.

[0114] Table 5-1. Indoor toxicity test data of the compound of Example 1 against Bemisia tabaci

[0115]

[0116]

[0117] Table 5-2. Indoor toxicity test data of the compound of Comparative Example 1 against Bemisia tabaci

[0118]

[0119] Table 5-3. Indoor toxicity test data of the compound of Comparative Example 2 against Bemisia tabaci

[0120]

[0121]

[0122] Table 5-4. Comparative Example 3 compound indoor toxicity test data on Bemisia tabaci

[0123]

[0124]

[0125] The insecticidal rates of the compounds of Example 1 and Comparative Examples 1 to 3 against Chilo suppressalis are shown in Table 6.

[0126] Table 6. Insecticidal rate of compounds against Chilo suppressalis

[0127]

[0128]

[0129] The comparison of the control effects of various compounds on agricultural pests is shown in Table 7.

[0130] Calculation method:

[0131]

[0132] Using the logarithm of the drug concentration (mg / L) as the independent variable X and the probability of corrected mortality as the dependent variable Y, the LC of the toxicity regression line was calculated using DPS software. 50 value.

[0133] Table 7. Comparison of the control effects of compounds on agricultural pests

[0134]

[0135] As shown in Table 8, compared with Comparative Examples 1-3, the compound of Example 1 has significantly better control effects against Thrips palmi, Thrips ursinus, Tetranychus ursinus, and Chilo suppressalis. Regarding Bemisia tabaci, the compound of Example 1 has comparable control effects to the compounds of Comparative Examples 1 and 2, and slightly better effects than the compound of Comparative Example 3. Thrips palmi and Thrips ursinus are typical representatives of Thysanoptera pests, Tetranychus ursinus is a typical representative of Acarina pests, and Chilo suppressalis is a typical representative of Lepidoptera pests. Therefore, it can be concluded that the compound of Example 1 has significantly better control effects against Thysanoptera, Acarina, and Lepidoptera pests.

[0136] Although the above describes the specific embodiments of the present invention in conjunction with the accompanying drawings, it does not limit the scope of protection of the present invention. Based on the technical solution of the present invention, various modifications or variations that can be made by those skilled in the art without creative work are still within the scope of protection of the present invention.

Claims

1. Use of a pharmaceutical composition comprising a γ-aminobutyric acid-gated chloride channel allosteric modulator compound or an agrochemically acceptable salt thereof in the preparation of an agricultural insecticide, characterized in that: The compound is (S)-4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, and its chemical structure is as follows: The agricultural insecticide is used to control Thrips palmi, and the dosage of the compound is 0.06250 mg / L; The agricultural insecticide is used to control flower thrips, and the dosage of the compound is 0.08 ppm.

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