A p-tolylsulfonanilide derivative, its preparation method and application

Abstract

The present application relates to a kind of substituted p-methyl sulfone aniline derivatives and its preparation method and application, belong to the technical field of drug synthesis. Specifically, the present application discloses a kind of substituted p-methyl sulfone aniline derivatives shown in general formula (I) and the application of pharmaceutical composition containing the derivative in the preparation of antiparasitic drugs.The structure general formula (I) of the substituted p-methyl sulfone aniline derivative is as follows:(I);The effect of the substituted p-methyl sulfone aniline derivative of the present application in the prevention and treatment of parasitic infection, vector insects, forest pests, etc., has broad application prospects.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical synthesis technology, specifically relating to a methyl sulfone aniline derivative, its preparation method, and its application. Background Technology

[0002] Solving pest problems has always been a key focus, but pesticides used for pest control often have limited mechanisms of action, leading to increasingly serious pesticide resistance issues. Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the mammalian central nervous system. Glutamate-gated chloride channels are ligand-gated ion channels unique to invertebrates; therefore, developing agricultural and veterinary drugs targeting glutamate-gated chloride channels offers high safety for mammals. Drugs marketed targeting this channel include lindane, dieldrin, and endosulfan, which were introduced in the mid-to-late 20th century, as well as isoxazoline and resorcinolone insecticides introduced in recent years.

[0003] Phthalic acid amides, as a novel class of diamide compounds acting on GABA-gated chloride ion channels, have shown great promise due to their unique mechanism of action. Currently marketed drugs include brofenoxuron-methyl and cyprofenoflavone for controlling agricultural pests. However, both of these drugs contain more than 10 fluorine atoms in their molecular structures, posing a potential environmental risk. To address these issues, this invention introduces a sulfone group with strong insecticidal activity and an acetaldehyde ethylene glycol group to regulate the drug molecule's lipid solubility into the molecular structure, thereby improving both the insecticidal activity and broadening the insecticidal spectrum.

[0004] The compounds involved in this invention have been studied in the fields of veterinary drug and pesticide insecticide applications, and compounds with good activity have been obtained, which have the potential to become new insecticides and are expected to achieve great economic benefits in the treatment of parasites. Summary of the Invention

[0005] The present invention aims to solve the technical problems in the prior art and provide a methyl sulfone aniline derivative, its preparation method and application.

[0006] The technical solution of this invention is as follows:

[0007] In a first aspect, the present invention provides a p-methylsulfonyl aniline derivative, the general structural formula of which is shown in formula (I): (Ⅰ);

[0008] R1 is selected from hydrogen, bromine, fluorine, chlorine, hydroxyl, methyl, ethyl, and methoxy.

[0009] R2 can be hydrogen, bromine, fluorine, chlorine, hydroxyl, or trifluoromethyl.

[0010] R3 can be hydrogen, bromine, fluorine, chlorine, or methyl.

[0011] R4 represents hydrogen, bromine, fluorine, or chlorine.

[0012] Preferably, the p-methylsulfonyl aniline derivative is selected from compounds with the following structures:

[0013] , , , , , , , , , , , , , , , , , , , .

[0014] Preferably, the salt of the p-methylsulfonyl aniline derivative is a salt formed by the p-methylsulfonyl aniline derivative and the following acids: hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, acetic acid, trifluoroacetic acid, pyruvic acid, citric acid, tartaric acid, lactic acid, maleic acid, benzenesulfonic acid, succinic acid, methanesulfonic acid, p-toluenesulfonic acid, fumaric acid, salicylic acid, or phenylacetic acid.

[0015] In a third aspect, the present invention also provides a synthetic route for compounds having the general formula (I):

[0016] .

[0017] The compound of general formula I of the present invention can be obtained by the preparation method described above or similar to the above method, and the corresponding starting material can be selected according to the different substituents and the different positions of the substituents.

[0018] The synthesis steps of the synthetic route include:

[0019] Step 1: Starting materials 1 and 2 react in a certain proportion to obtain intermediate 3 through condensation reaction.

[0020] Step 2: Intermediate 3 and bromoacetaldehyde ethylene glycol react in a certain proportion to obtain intermediate 4 through a substitution reaction. The pure intermediate 4 is obtained by column chromatography.

[0021] Step 3: Intermediate 4 and the substituted p-methylsulfonyl aniline are condensed to obtain the target compound (p-methylsulfonyl aniline derivative), which is then purified by column chromatography to obtain the pure target compound.

[0022] Those skilled in the art should recognize that the above approach helps to understand the present invention, but is not limited to the content of the present invention, and unless otherwise specified, variables are defined as mentioned in general formula (I).

[0023] A fourth aspect of the present invention provides a pharmaceutical composition comprising a sulfaniline derivative of general formula (I) or a salt thereof, and a pharmaceutically acceptable carrier and / or excipient.

[0024] The pharmaceutical compositions of the present invention can be used to prepare various pharmaceutical formulations, such as oral formulations, injections, and topical formulations. The pharmaceutical compositions of the present invention can be administered alone or in combination with other active pharmaceutical ingredients.

[0025] The oral preparations include, but are not limited to, tablets, granules, capsules, emulsions, suspensions, and oral solutions.

[0026] The topical preparations include, but are not limited to, drops, pour-over solutions, ointments, and sprays.

[0027] Pharmaceutically acceptable carriers or excipients include stabilizers, diluents, surfactants, lubricants, antioxidants, binders, colorants, fillers, emulsifiers, flavoring agents, etc.

[0028] Injectable formulations can be prepared using suitable dispersants or wetting agents and suspending agents in accordance with techniques known in the art.

[0029] In a fifth aspect, the invention provides the use of p-methylsulfonyl aniline derivatives of general formula (I) or salts thereof in the preparation of medicaments for preventing and controlling the infestation of parasites, vector insects, and agricultural pests.

[0030] Preferably, the parasite is a zoonotic parasite or a parasite that is susceptible to non-human mammals.

[0031] More preferably, the parasite is one or more of Cryptosporidium, nematodes, fleas, ticks, Demodex mites, scabies mites, ear mites, and lice.

[0032] Preferably, the vector insect is selected from mosquitoes and flies.

[0033] Preferably, the agricultural pests are one or more of the following: diamondback moth, armyworm, fall armyworm, cotton bollworm, corn borer, mosquito larvae, aphids, spider mites, whiteflies, psyllids, leafhoppers, scale insects, and beetles.

[0034] Beneficial effects:

[0035] 1. This invention introduces a sulfone group with strong insecticidal activity and an acetaldehyde ethylene glycol group that regulates the lipid solubility of drug molecules into the molecular structure, providing a novel sulfone aniline derivative that not only improves the insecticidal activity of the drug molecule but also expands the insecticidal spectrum. This novel sulfone aniline derivative exhibits strong insecticidal activity against animal parasites, insects, and agricultural pests.

[0036] 2. The sulfone aniline derivatives of this invention have a strong killing effect on animal parasites such as ticks and nematodes, agricultural pests such as diamondback moths and scale insects, as well as zoonotic cryptosporidia.

[0037] 3. The preparation process of this invention is simple, energy-saving and environmentally friendly, and easy to industrialize. Detailed Implementation

[0038] The preparation method of the compound of general formula (I) of the present invention is described below with reference to specific embodiments, but these specific methods do not constitute any limitation on the present invention. The compounds of the present invention can also be conveniently prepared by optionally combining various synthetic methods described in this specification or known in the art, and such combinations can be easily performed by those skilled in the art.

[0039] The starting materials and reaction reagents used in the specific embodiments of this invention are all commercially available. Experimental methods in the embodiments of this invention that do not specify specific conditions are generally performed under conventional conditions or according to the conditions recommended by the raw material or product manufacturer.

[0040] The structures of all compounds in the examples were obtained by Waters QDa mass spectrometry and proton nuclear magnetic resonance spectroscopy (1H NMR). 1 Characterization by H-NMR.

[0041] Example 1

[0042] Preparation of compound 1:

[0043] .

[0044] Step 1:

[0045] 0.35 g of starting material 1 was dissolved in 10 mL of dichloromethane. 0.34 g of starting material 2 and 0.30 g of triethylamine were added under ice bath conditions, and the reaction was carried out at room temperature for 1 hour. 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white intermediate 3. [M+H] + 292.1, 1H-NMR (DMSO-d6, 300MHz) δ: 9.31 (s, 1H), 8.17 (d, 1H), 8.12(m, 2H), 7.84 (d, 1H), 7.37 (m, 2H), 7.24 (t, 1H), 3.90 (s, 3H).

[0046] Step 2:

[0047] 0.29 g of intermediate 3 was dissolved in 10 mL of tetrahydrofuran, and 0.27 g of potassium carbonate and 0.18 g of bromoacetaldehyde ethylene glycol condensate were added. The mixture was refluxed for 4 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was purified by column chromatography to obtain the pure, off-white intermediate 4. [M+H] + 378.1, 1 H-NMR (DMSO-d6, 300MHz) δ: 8.12 (m, 2H), 7.83 (m,2H), 7.37 (m, 2H), 7.24 (t, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.90 (s, 3H), 3.85 (m, 2H), 3.50 (d, 2H).

[0048] Step 3:

[0049] 0.38 g of intermediate 4 was dissolved in 10 mL of tetrahydrofuran, and 0.28 g of potassium tert-butoxide and 0.19 g of 2-fluoro-4-methylsulfonylaniline were added. The mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to give the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 1. [M+H] + 535.1, 1 H-NMR (DMSO-d6, 300MHz) δ: 9.31 (s, 1H), 8.12 (m, 2H), 7.98 (m, 2H), 7.90 (m, 3H), 7.37 (m, 2H), 7.28 (t, 1H), 6.71 (d, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H).

[0050] Example 2

[0051] Preparation of compound 2:

[0052] .

[0053] Step 1:

[0054] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.21 g of 2-chloro-4-methylsulfonylaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 2. [M+H] + :551.1, 1 H-NMR(DMSO-d6,300MHz) δ: 9.31 (s, 1H), 8.33 (s, 1H),8.12 (m, 2H), 7.98 (m, 2H), 7.90 (d,1H), 7.37 (m, 2H), 7.28 (t, 1H), 6.71 (d, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H).

[0055] Example 3

[0056] Preparation of compound 3:

[0057] .

[0058] Step 1:

[0059] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.25 g of 2-bromo-4-methylsulfonylaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 3. [M+H] + 595.1, 1H-NMR (DMSO-d6,300MHz) δ: 9.31 (s, 1H),8.33 (s, 1H),8.12 (m, 2H), 7.98 (m, 2H), 7.90 (d,1H), 7.37 (m, 2H), 7.28 (t, 1H), 6.88 (d, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H).

[0060] Example 4

[0061] Preparation of compound 4:

[0062] .

[0063] Step 1:

[0064] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.19 g of 2-hydroxy-4-methylsulfonylaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 4. [M+H] + 533.1, 1 H-NMR (DMSO-d6,300MHz) δ: 10.11 (s, 1H), 9.31 (s, 1H), 8.12 (m, 2H), 7.98 (m, 2H), 7.90 (d,1H), 7.63 (s, 1H), 7.37 (m, 2H), 7.28 (t, 1H), 6.50 (d, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H).

[0065] Example 5

[0066] Preparation of compound 5:

[0067] .

[0068] Step 1:

[0069] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.19 g of 2-methyl-4-methylsulfonylaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 5. [M+H] + 531.1, 1 H-NMR(DMSO-d6,300MHz) δ: 9.61 (s, 1H), 8.12 (m, 2H), 7.98 (m, 2H), 7.90 (d, 1H), 7.63 (s,1H), 7.37 (m, 2H), 7.28 (t, 1H), 6.84 (d, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H), 2.12 (s, 3H).

[0070] Example 6

[0071] Preparation of compound 6:

[0072] .

[0073] Step 1:

[0074] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.20 g of 2-ethyl-4-methylsulfonylaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 6. [M+H] + 545.1, 1H-NMR(DMSO-d6,300MHz) δ: 9.61 (s, 1H), 8.12 (m, 2H), 7.98 (m, 2H), 7.90 (d, 1H), 7.63 (s,1H), 7.37 (m, 2H), 7.28 (t, 1H), 6.84 (d, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H), 2.58 (m, 2H), 1.12 (t, 3H).

[0075] Example 7

[0076] Preparation of compound 7:

[0077] .

[0078] Step 1:

[0079] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.22 g of 2-methoxy-4-methylsulfonylaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 7. [M+H] + 547.1, 1 H-NMR(DMSO-d6,300MHz) δ: 9.61 (s, 1H), 8.12 (m, 2H), 7.98 (m, 2H), 7.90 (d, 1H), 7.63 (s,1H), 7.37 (m, 2H), 7.28 (t, 1H), 6.84 (d, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.76 (s, 3H), 3.50 (d, 2H), 3.32 (s, 3H), 2.12 (s, 3H).

[0080] Example 8

[0081] Preparation of compound 8:

[0082] .

[0083] Step 1:

[0084] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran, and 0.28 g of potassium tert-butoxide and 0.17 g of 4-methylsulfonyl aniline were added. The mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 8. [M+H] + 517.1, 1 H-NMR (DMSO-d6, 300MHz)δ: 9.61 (s, 1H), 8.12 (m, 2H), 7.98 (m, 2H), 7.74 (m, 2H), 7.63 (s, 1H), 7.37(m, 2H), 7.28 (t, 1H), 6.84 (m, 2H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m,2H), 3.50 (d, 2H), 3.39 (s, 3H).

[0085] Example 9

[0086] Preparation of compound 9:

[0087] .

[0088] Step 1:

[0089] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.21 g of 2-hydroxy-4-methylsulfonyl-6-fluoroaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 9. [M+H] + 517.1, 1 H-NMR(DMSO-d6, 300MHz) δ: 10.21 (s, 1H), 9.81 (s, 1H), 8.12 (m, 2H), 7.98 (m, 1H), 7.74 (m, 2H), 7.41 (s, 1H), 7.37 (m, 2H), 7.28 (t, 1H), 6.84 (m, 2H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.39 (s, 3H).

[0090] Example 10

[0091] Preparation of compound 10:

[0092] .

[0093] Step 1:

[0094] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.26 g of 2-hydroxy-4-methylsulfonyl-6-trifluoromethylaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white compound 10. [M+H] + 601.1, 1 H-NMR (DMSO-d6, 300MHz) δ: 10.21 (s, 1H), 9.81 (s, 1H), 8.12 (m, 2H), 7.96 (m,2H), 7.67 (m, 2H), 7.37 (m, 2H), 7.28 (t, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H).

[0095] Example 11

[0096] Preparation of compound 11:

[0097] .

[0098] Step 1:

[0099] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.21 g of 2-fluoro-4-methylsulfonyl-6-fluoroaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white compound 11. [M+H] + 553.1, 1H-NMR(DMSO-d6, 300MHz) δ: 9.81 (s, 1H), 8.12 (m, 2H), 7.96 (m, 2H), 7.67 (m, 2H), 7.37 (m, 2H), 7.28 (t, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H).

[0100] Example 12

[0101] Preparation of compound 12:

[0102] .

[0103] Step 1:

[0104] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.24 g of 2-fluoro-4-methylsulfonyl-6-chloroaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white compound 12. [M+H] + 569.1, 1 H-NMR(DMSO-d6, 300MHz) δ: 9.81 (s, 1H), 8.12 (m, 2H), 8.08 (s, 1H), 7.96 (m, 2H), 7.67(s, 1H), 7.37 (m, 2H), 7.28 (t, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H).

[0105] Example 13

[0106] Preparation of compound 13:

[0107] .

[0108] Step 1:

[0109] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.21 g of 2-fluoro-4-methylsulfonyl-6-methylaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white compound 13. [M+H] + 549.1, 1 H-NMR(DMSO-d6, 300MHz) δ: 9.81 (s, 1H), 8.12 (m, 2H), 7.96 (m, 2H), 7.67 (m, 2H), 7.37 (m, 2H), 7.28 (t, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H), 2.12 (s, 3H).

[0110] Example 14

[0111] Preparation of compound 14:

[0112] .

[0113] Step 1:

[0114] 0.38 g of intermediate 4 (prepared as described in steps 1 and 2 of Example 1) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.27 g of 2-fluoro-4-methylsulfonyl-6-bromoaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white compound 14. [M+H] + 613.1, 1 H-NMR(DMSO-d6, 300MHz) δ: 9.81 (s, 1H), 8.12 (m, 2H), 7.96 (m, 2H), 7.67 (m, 2H), 7.37(m, 2H), 7.28 (t, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H), 2.12 (s, 3H).

[0115] Example 15

[0116] Preparation of compound 15:

[0117] .

[0118] Step 1:

[0119] 0.35 g of starting material 1 was dissolved in 10 mL of dichloromethane. 0.31 g of starting material 5 and 0.30 g of triethylamine were added under ice bath conditions, and the reaction was carried out at room temperature for 1 hour. 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white intermediate 6. [M+H] + 274.1, 1 H-NMR (DMSO-d6, 300MHz) δ: 9.31 (s, 1H), 8.43 (s, 1H), 8.12(m, 2H), 7.84 (m, 2H), 7.50 (t, 1H), 7.37 (m, 2H), 3.90 (s, 3H).

[0120] Step 2:

[0121] 0.29 g of intermediate 6 was dissolved in 10 mL of tetrahydrofuran, and 0.27 g of potassium carbonate and 0.18 g of bromoacetaldehyde ethylene glycol condensate were added. The mixture was refluxed for 4 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white intermediate 7. [M+H] + 360.1 1 H-NMR (DMSO-d6, 300MHz) δ: 8.20 (s, 1H),8.12 (m,2H), 7.84 (m, 2H), 7.48 (t, 1H), 7.37 (m, 2H), 6.18 (t, 2H), 4.01 (m, 2H)3.90 (s, 3H), 3.85 (m, 2H), 3.50 (d, 2H).

[0122] Step 3:

[0123] 0.36 g of intermediate 7 was dissolved in 10 mL of tetrahydrofuran, and 0.28 g of potassium tert-butoxide and 0.28 g of 2-fluoro-4-methylsulfonyl-6-bromoaniline were added. The mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to give the crude product, which was then purified by column chromatography to obtain a pure, off-white compound 15. [M+H]+ 595.1, 1 H-NMR (DMSO-d6, 300MHz) δ: 9.80 (s, 1H), 8.18 (s, 1H), 8.12 (m, 2H), 7.98 (m, 2H), 7.83 (m, 2H), 7.48 (t, 1H), 7.37(m, 2H), 6.18 (t, 2H), 4.01 (m, 2H) 3.90 (s, 3H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H).

[0124] Example 16

[0125] Preparation of compound 16:

[0126] .

[0127] Step 1:

[0128] 0.36 g of intermediate 7 (prepared as described in steps 1 and 2 of Example 15) was dissolved in 10 mL of tetrahydrofuran. 0.28 g of potassium tert-butoxide and 0.19 g of 2-fluoro-4-methylsulfonylaniline were added, and the mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white compound 16. [M+H] + 517.1, 1 H-NMR(DMSO-d6,300MHz) δ: 9.80 (s, 1H), 8.18 (s, 1H), 8.12 (m, 2H), 7.98 (m, 2H), 7.83 (m,2H), 7.48 (t, 1H), 7.37 (m, 2H), 6.71 (d, 1H), 6.18 (t, 2H), 4.01 (m, 2H) 3.90 (s, 3H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H).

[0129] Example 17

[0130] Preparation of compound 17:

[0131] .

[0132] Step 1:

[0133] 0.35 g of starting material 1 was dissolved in 10 mL of dichloromethane. 0.46 g of starting material 8 and 0.30 g of triethylamine were added under ice bath conditions, and the reaction was carried out at room temperature for 1 hour. 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white intermediate 9. [M+H] + 352.1, 1 H-NMR (DMSO-d6, 300MHz) δ: 9.31 (s, 1H), 8.12 (m, 2H), 7.90 (m, 2H), 7.50 (t, 1H), 7.37 (m, 2H), 3.90 (s, 3H).

[0134] Step 2:

[0135] 0.36 g of intermediate 9 was dissolved in 10 mL of tetrahydrofuran, and 0.27 g of potassium carbonate and 0.18 g of bromoacetaldehyde ethylene glycol condensate were added. The mixture was refluxed for 4 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white intermediate 10. [M+H] + 438.2, 1 H-NMR(DMSO-d6, 300MHz) δ: 8.12 (m, 2H), 7.70 (m,2H), 7.50 (t, 1H),7.37 (m, 2H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.90 (s, 3H), 3.50 (d, 2H).

[0136] Step 3:

[0137] 0.44 g of intermediate 10 was dissolved in 10 mL of tetrahydrofuran, and 0.28 g of potassium tert-butoxide and 0.19 g of 2-fluoro-4-methylsulfonylaniline were added. The mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 17. [M+H] + 595.4 1H-NMR(DMSO-d6, 300MHz) δ: 9.82 (s, 1H), 8.12(m, 2H), 7.90 (m, 2H), 7.79 (d, 1H), 7.50 (t, 1H), 7.37 (m, 2H), 6.18 (t,1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.90 (s, 3H), 3.50 (d, 2H), 3.32 (s, 3H).

[0138] Example 18

[0139] Preparation of compound 18:

[0140] .

[0141] Step 1:

[0142] 0.44 g of starting material 11 was dissolved in 10 mL of dichloromethane. 0.37 g of starting material 12 and 0.30 g of triethylamine were added under ice bath conditions, and the reaction was carried out at room temperature for 1 hour. 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white intermediate 13. [M+H] + 368.6 1 H-NMR(DMSO-d6, 300MHz) δ: 9.31 (s, 1H), 8.25 (m, 1H), 7.90 (m, 2H), 7.79 (d, 1H), 7.70 (m, 2H), 7.35 (t, 1H), 3.90 (s, 3H).

[0143] Step 2:

[0144] 0.37 g of intermediate 13 was dissolved in 10 mL of tetrahydrofuran, and 0.27 g of potassium carbonate and 0.18 g of bromoacetaldehyde ethylene glycol condensate were added. The mixture was refluxed for 4 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white intermediate 14. [M+H] + 454.7 1H-NMR(DMSO-d6, 300MHz) δ: 8.01 (m, 2H), 7.80 (m,2H), 7.69 (m, 2H), 7.35 (t, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.92 (s, 3H), 3.50 (d, 2H).

[0145] Step 3:

[0146] 0.46 g of intermediate 14 was dissolved in 10 mL of tetrahydrofuran, and 0.28 g of potassium tert-butoxide and 0.19 g of 2-fluoro-4-methylsulfonylaniline were added. The mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 18. [M+H] + 611.8 1 H-NMR(DMSO-d6, 300MHz) δ: 9.80 (s, 1H), 8.01(m, 2H), 7.80 (m, 3H), 7.69 (m, 2H), 7.42 (t, 1H), 7.27 (d, 1H), 6.71 (d,1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.92 (s, 3H), 3.50 (d, 2H), 3.32 (s, 3H).

[0147] Example 19

[0148] Preparation of compound 19:

[0149] .

[0150] Step 1:

[0151] 0.36 g of starting material 15 was dissolved in 10 mL of dichloromethane. 0.33 g of starting material 16 and 0.30 g of triethylamine were added under ice bath conditions, and the reaction was carried out at room temperature for 1 hour. 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white intermediate 17. [M+H] + 303.7, 1H-NMR(DMSO-d6, 300MHz) δ: 9.31 (s, 1H), 7.90 (m, 2H), 7.55 (m, 3H), 7.45 (d, 1H), 7.35 (t, 1H), 3.90 (s, 3H), 2.25 (s, 3H).

[0152] Step 2:

[0153] 0.31 g of intermediate 17 was dissolved in 10 mL of tetrahydrofuran, and 0.27 g of potassium carbonate and 0.18 g of bromoacetaldehyde ethylene glycol condensate were added. The mixture was refluxed for 4 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask. The mixture was extracted separately, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white intermediate 18. [M+H] + 390.1, 1 H-NMR(DMSO-d6, 300MHz) δ: 7.90 (m, 2H), 7.55 (m,3H), 7.45 (d, 1H), 7.35 (t, 1H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.90 (s, 3H), 3.50 (d, 2H), 2.25 (s, 3H).

[0154] Step 3:

[0155] 0.39 g of intermediate 18 was dissolved in 10 mL of tetrahydrofuran, and 0.28 g of potassium tert-butoxide and 0.19 g of 2-fluoro-4-methylsulfonylaniline were added. The mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 19. [M+H] + 547.1, 1 H-NMR(DMSO-d6, 300MHz) δ: 9.81 (s, 1H), 7.90(m, 2H), 7.85 (m, 2H), 7.60 (m, 3H), 7.44 (t, 1H), 6.71 (d, 1H), 6.18 (t,1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H), 2.25 (s, 3H).

[0156] Example 20

[0157] Preparation of compound 20:

[0158] .

[0159] Step 1:

[0160] 0.28 g of starting material 19 was dissolved in 10 mL of dichloromethane. 0.33 g of starting material 16 and 0.30 g of triethylamine were added under ice bath conditions, and the reaction was carried out at room temperature for 1 hour. 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain a pure, off-white intermediate 20. [M+H] + 270.1, 1 H-NMR(DMSO-d6, 300MHz) δ: 9.31 (s, 1H), 7.90 (m, 2H),7.62 (t, 1H), 7.55 (m, 3H), 7.45 (d, 1H), 7.35 (t, 1H), 3.90 (s, 3H), 2.25(s, 3H).

[0161] Step 2:

[0162] 0.27 g of intermediate 20 was dissolved in 10 mL of tetrahydrofuran, and 0.27 g of potassium carbonate and 0.18 g of bromoacetaldehyde ethylene glycol condensate were added. The mixture was refluxed for 4 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was purified by column chromatography to obtain the pure, off-white intermediate 21. [M+H] + 356.1, 1 H-NMR (DMSO-d6, 300MHz) δ: 7.62 (m, 2H), 7.55 (d,1H), 7.35 (m, 5H), 6.18 (t, 1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.90 (s, 3H), 3.50 (d, 2H), 2.25 (s, 3H).

[0163] Step 3:

[0164] 0.36 g of intermediate 21 was dissolved in 10 mL of tetrahydrofuran, and 0.28 g of potassium tert-butoxide and 0.19 g of 2-fluoro-4-methylsulfonylaniline were added. The mixture was refluxed for 5 hours. After cooling to room temperature, 30 mL of water was added to the reaction flask, and the mixture was extracted separately. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were washed once with saturated brine. The organic phase was dried under vacuum to obtain the crude product, which was then purified by column chromatography to obtain the pure, off-white compound 20. [M+H]+ 513.1, 1 H-NMR(DMSO-d6, 300MHz) δ: 7.98 (d, 1H), 7.88(s, 1H), 7.62 (m, 2H), 7.55 (d, 1H), 7.35 (m, 5H), 6.71 (d, 1H), 6.18 (t,1H), 4.01 (m, 2H), 3.85 (m, 2H), 3.50 (d, 2H), 3.32 (s, 3H), 2.25 (s, 3H).

[0165] Example 21 In vitro insecticidal activity test

[0166] 1. In vitro tick larval toxicity test

[0167] The drugs from compounds 1-20 of Examples were weighed out. Using brofenoxam and cyprofenoflavone as positive control groups, compounds 1-20, brofenoxam, and cyprofenoflavone were dissolved in appropriate amounts of dimethyl sulfoxide, and diluted with water to obtain six different concentration gradients (100 μg / mL, 25 μg / mL, 6.25 μg / mL, 1.56 μg / mL, 0.39 μg / mL, and 0.097 μg / mL). A blank control group was also set up. In vitro tick larval toxicity tests were conducted. The in vitro tick larval toxicity results of compounds 1-20 are shown in Table 1.

[0168] Table 1. Results of in vitro insecticidal activity tests of compounds 1-20

[0169] .

[0170] 2. In vitro mosquito larvae toxicity test

[0171] Rearing of mosquito larvae: Temperature 25±2℃, relative humidity 75±5%, natural light. The experiment begins when the mosquito larvae reach the 4th instar.

[0172] Toxicity testing: Compounds from Examples 1-20 were weighed. Using brofenoxam and cyprofen as positive control groups, compounds from Examples 1-20, brofenoxam, and cyprofen were dissolved in appropriate amounts of dimethyl sulfoxide. The solutions were then diluted with hatching water to obtain six different concentration gradients (100 μg / mL, 25 μg / mL, 6.25 μg / mL, 1.56 μg / mL, 0.39 μg / mL, and 0.097 μg / mL). 20 mL of each solution was prepared for use. A blank control group was also set up. In vitro drug activity tests were conducted on mosquito larvae. The in vitro mosquito larval toxicity results of compounds 1-20 are shown in Table 2.

[0173] Table 2. Results of in vitro insecticidal activity tests of compounds 1-20

[0174] .

[0175] 3. In vitro toxicity test of *Ostomyces toothedis*

[0176] The drugs from compounds 1-20 of Examples were weighed. Avermectin and brombutazone were used as positive control groups. Compounds 1-20, avermectin, and brombutazone were dissolved in appropriate amounts of dimethyl sulfoxide, and diluted with water to obtain six different concentration gradients (100 μg / mL, 25 μg / mL, 6.25 μg / mL, 1.56 μg / mL, 0.39 μg / mL, and 0.097 μg / mL). A blank control group was also set up. In vitro drug activity tests were conducted against *Osteophytic esophagitis*. The in vitro toxicity results of compounds 1-20 against *Osteophytic esophagitis* are shown in Table 3.

[0177] 4. In vitro toxicity test of Strongyloides nematodes

[0178] The drugs from compounds 1-20 of Examples were weighed. Avermectin and brombutazone were used as positive control groups. Compounds 1-20, avermectin, and brombutazone were dissolved in appropriate amounts of dimethyl sulfoxide, and diluted with water to obtain six different concentration gradients (100 μg / mL, 25 μg / mL, 6.25 μg / mL, 1.56 μg / mL, 0.39 μg / mL, and 0.097 μg / mL). A blank control group was also set up. In vitro drug activity against *Strongyloides nematodes* was tested. The in vitro *Strongyloides nematodes* toxicity results of compounds 1-20 are shown in Table 3.

[0179] Table 3. Results of in vitro insecticidal activity tests of compounds 1-20

[0180] .

[0181] The results show that the compounds in the embodiments of the present invention have better in vitro toxicity than first-line clinical drugs against tick larvae, mosquito larvae, toothed esophageal nematodes, and strongyloides, and have certain development value.

[0182] Example 22: Efficacy evaluation of in vivo tick expellent

[0183] Half male and half female beagles were used in a control group and a bromfenac-based positive control group. The bromfenac dosage was 50 mg / kg, and the dosage of the compound of this invention (Examples 1-20) was 50 mg / kg. The experimental dogs were infested with 50 adult ticks that had not yet ingested food. Dogs received treatment on day 0. The average detection rate of ticks in vitro for each group was recorded on days 0, 2, and 4 after treatment. Any immediate response to treatment was observed, as well as adverse reactions and skin irritation. The in vivo tick detection rate of the compound is shown in Table 4.

[0184] Table 4. Detection rate of the compound in vivo against ticks

[0185] .

[0186] The results show that the compounds in the embodiments of the present invention have tick-repellent activity in vivo, and their efficacy is superior to that of the control drug bromfenacin, making them suitable for anti-parasitic drugs.

[0187] Example 23 In vitro toxicity test of diamondback moth

[0188] Diamondback moth larvae were randomly divided into three groups: a blank control group, a bromfenac-methyl control group, and an experimental group (compounds from Examples 1-20). The test drugs (bromfenac-methyl and compounds from Examples 1-20) were administered at a concentration of 50 μg / mL. Thirty diamondback moth larvae were placed on 12-day-old radish plants in each experimental group, and the drugs were sprayed onto each plant. Plant damage was assessed and moth mortality was recorded at 12, 24, and 48 hours based on the condition of the leaves consumed. The diamondback moth toxicity results are shown in Table 5.

[0189] Table 5 Detection rate of drug toxicity to diamondback moth

[0190] .

[0191] The results show that the compound of the present invention has the activity of killing the diamondback moth, an agricultural pest.

[0192] Example 24 In vitro scale insect toxicity test

[0193] Greenhouse mealybugs were randomly divided into three groups: a blank control group, a bromfenac-methyl control group, and experimental groups (compounds from Examples 1-20). The test drugs (bromfenac-methyl and compounds from Examples 1-20) were set at a concentration of 100 μg / mL. Thirty greenhouse mealybug larvae were placed on 12-day-old radish plants in each experimental group, and the drugs were administered to each group of radish plants via spraying. Plant feeding damage was assessed at 12, 24, and 48 hours based on the condition of the leaves consumed, and the mortality rate of the greenhouse mealybugs was counted. The toxicity results are shown in Table 6.

[0194] Table 6. Detection rate of drug toxicity to greenhouse mealybugs

[0195] .

[0196] The results show that the compound of the present invention has the activity of killing the agricultural pest, greenhouse mealybug.

[0197] Example 25: In vitro activity test of human colon cancer (HCT-8) cells against Cryptosporidium.

[0198] HCT-8 cells were cultured in RPMI-1640 medium containing 5% fetal bovine serum (FCS) and grown in a 37°C, 5% CO2 cell culture incubator. After the cells reached confluence with the culture dish, they were digested with cell digestion solution, transferred to new 6-well plates, and cultured for 48 hours in a 37°C, 5% CO2 cell culture incubator. After changing the medium, cells were cultured at a rate of 1×10⁻⁶ cells / well. 3 A number of decapitated oocysts were added and cultured for 8 hours, followed by incubation in complete culture medium for 48 hours. Using brofenoxuron-methyl as a positive control, a blank control group and experimental groups (compounds from Examples 1-20) were set up. The test compounds (brofenoxuron-methyl, compounds from Examples 1-20) were added to infected HCT-8 cells at six concentration gradients (50 μM / mL, 12.5 μM / mL, 3.12 μM / mL, 0.78 μM / mL, 0.20 μM / mL, 0.05 μM / mL), and incubated for 48 hours. The morphology of the parasites was observed under a fluorescence microscope using Crypt-a-Glo and Sporo-Glo staining to evaluate the drug activity. The results of the in vitro activity test of HTC-8 cells against Cryptosporidium are shown in Table 7.

[0199] Table 7 Results of in vitro activity test of HTC-8 cells against Cryptosporidium

[0200] .

[0201] The results show that the compound of the present invention has zoonotic activity against Cryptosporidium.

[0202] The above experiments verified that the p-methyl sulfone aniline derivatives represented by general formula (I) of this invention have strong antiparasitic, insecticidal, and agricultural pest-killing activities, and show better effects than existing compounds, with great application prospects.

Claims

1. A p-methylsulfonyl aniline derivative, characterized in that, Its structure is shown in general formula (Ⅰ): (Ⅰ); where R1 is selected from hydrogen, bromine, fluorine, chlorine, hydroxyl, methyl, ethyl, methoxy; R2 is hydrogen, bromine, fluorine, chlorine, hydroxyl, trifluoromethyl; R3 is hydrogen, bromine, fluorine, chlorine, methyl; R4 is hydrogen, bromine, fluorine, chlorine.

2. The p-methylsulfonyl aniline derivative according to claim 1, characterized in that, The p-methylsulfonyl aniline derivative has one of the following structures: , , , , , , , , , , , , , , , , , , , .

3. A salt of a p-methylsulfonyl aniline derivative as described in any one of claims 1-2, characterized in that, The salts of the p-methylsulfonyl aniline derivatives are salts formed by the p-methylsulfonyl aniline derivatives and the following acids: hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, acetic acid, trifluoroacetic acid, pyruvic acid, citric acid, tartaric acid, lactic acid, maleic acid, benzenesulfonic acid, succinic acid, methanesulfonic acid, p-toluenesulfonic acid, fumaric acid, salicylic acid, or phenylacetic acid.

4. A pharmaceutical composition, characterized in that, The pharmaceutical composition comprises a salt of a sulfaniline derivative as described in any one of claims 1-2 or a sulfaniline derivative as described in claim 3, and one or more excipients.

5. A pharmaceutical composition, characterized in that, The pharmaceutical composition comprises a salt of a sulfaniline derivative as described in any one of claims 1-2 or a sulfaniline derivative as described in claim 3, and one or more pharmaceutical carriers.

6. The use of a sulfonylurea derivative as described in any one of claims 1-2, a salt of a sulfonylurea derivative as described in claim 3, or a pharmaceutical composition as described in any one of claims 4-5 in the preparation of a medicament for preventing and controlling the infestation of parasites, vector insects, and agricultural pests.

7. The application according to claim 6, characterized in that, The parasite is one or more of the following: Cryptosporidium, nematodes, fleas, ticks, Demodex mites, scabies mites, ear mites, and lice.

8. The application according to claim 6, characterized in that, The vector insects are selected from mosquitoes and flies.

9. The application according to claim 6, characterized in that, The agricultural pests mentioned are one or more of the following: diamondback moth, armyworm, fall armyworm, cotton bollworm, corn borer, mosquito larvae, aphids, spider mites, whiteflies, psyllids, leafhoppers, scale insects, and beetles.

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