Piperazine-containing structural derivative and use thereof

Abstract

The present application relates to a kind of containing piperazine derivative structure and its application.The compound has the structure as one of general formula (I-III) shown: The compound is as rice bacterial leaf blight, tobacco bacterial wilt, cucumber bacterial leaf blight, konjac bacterial leaf blight, citrus bacterial wilt, grape bacterial wilt, tomato bacterial wilt, kiwi bacterial wilt, apple bacterial wilt, cucumber bacterial wilt, pepper wilt pathogen, sclerotinia sclerotiorum, fusarium graminearum, potato late blight pathogen, blueberry root rot pathogen and the like has good inhibitory effect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical chemistry, and particularly relates to a piperazine derivative and application thereof. BACKGROUND

[0002] The outbreak of plant diseases results in huge yield and economic losses of agricultural production every year. However, due to the drug resistance of pathogens, the effectiveness of antibacterial drugs is continuously reduced, which is one of the challenges faced by chemical drugs. Long-term use also has common potential side effects, such as unsatisfactory field curative effect, harm to the environment and plant health, etc. Therefore, efficient, low-risk and environmentally friendly antibacterial drugs are urgently needed to be developed.

[0003] Among the nitrogen-containing heterocyclic compounds, piperazine derivatives exhibit a wide range of pharmacological properties, such as antibacterial activity against drug-resistant pathogens, antimalarial activity, dual calcium channel blockade, antipsychotic activity, antifungal activity, and antituberculosis, anticancer activity, antiviral and antioxidant properties. Many commercial drugs, such as the antiviral protease inhibitor indinavir, also contain piperazine structures. In five-membered and six-membered nitrogen heterocyclic compounds, such compounds with high enzyme induction activity have also been found.

[0004] The research progress of the biological activity of piperazine derivatives is as follows:

[0005] In 2020, Ding et al. synthesized a series of furan piperazine ketone compounds, and some of the compounds exhibited effective cytotoxic activity at the nanomolar level against various human cancer cell lines. In particular, the 5-position methyl or methoxymethyl substituent of the furan group can replace the alkyl group at the 5-position of the imidazole to maintain the cytotoxic activity. Immunofluorescence detection showed that the compounds could effectively inhibit microtubule polymerization. Furan-diketopiperazine derivatives can be considered as potential scaffolds for the development of anticancer drugs.

[0006] In 2017, Gu et al. synthesized a series of novel aralkyl piperazine derivatives and evaluated their serotonin reuptake inhibition and 5-HT1A / 5-HT7 receptor affinity activity. The in vivo antidepressant activity of the compounds was screened using forced swimming test (FST) and tail suspension test (TST). The results showed that the compounds exhibited high affinity for 5-HT1A / 5-HT7 receptors and effective serotonin reuptake inhibition.

[0007] In 2017, Aslam et al. synthesized a new class of bi (phthalimide) piperazine and its derivative bioactive molecules, and tested their antibacterial activity, showing high safety and effectiveness. The bacterial strains tested by the compounds had good antibacterial activity, with the highest active inhibition diameter of 31.5 mm. The inhibition of Pseudomonas aeruginosa was the strongest, followed by the inhibition of Haemophilus influenzae of 30 mm.

[0008] In 2018, Khanam et al. synthesized 2-azetidinone phenylpiperazine derivatives to evaluate their in vitro antiproliferative activity and induction of apoptosis. The compounds induced apoptosis, phosphatidylserine externalization, DNA fragmentation, and cell cycle arrest in HeLa cancer cells in a concentration-dependent manner. In addition, the compounds caused the production of intracellular ROS and a decrease in mitochondrial membrane potential, causing oxidative stress, thus leading to apoptosis through a mitochondria-mediated pathway. The elevation of cytochrome levels and the upregulation of caspase-3 expression clearly indicated the involvement of the intrinsic pathway in programmed cell death.

[0009] In 2018, Shallal et al. synthesized a series of novel piperazinylpyrimidine compounds and tested their potential to selectively inhibit the growth of certain tumor cell lines in the NCI-60 cell line panel. The compounds were more effective in inhibiting oncogenic mutant forms of the PDGFR family kinases, which is of great importance in developing drugs against drug resistance or antitumor studies driven by such mutations. The clinical need for drugs against triple-negative breast cancer demonstrated that this class of compounds 15 is an effective inhibitor of MDA-MB-468 cell line growth. SUMMARY

[0010] One of the purposes of the present application is to provide a piperazine structure derivative or a stereoisomer thereof, or a salt or a solvate thereof.

[0011] Another purpose of the present application is to provide a composition containing the above-mentioned compound or a stereoisomer thereof, or a salt or a solvate thereof.

[0012] Another purpose of the present application is to provide the use of the above-mentioned compound or a stereoisomer thereof, or a salt or a solvate thereof, or the composition.

[0013] Another purpose of the present application is to provide a method for controlling agricultural pests and diseases using the above-mentioned compound or a stereoisomer thereof, or a salt or a solvate thereof, or the composition.

[0014] To achieve the above-mentioned purposes, the present application adopts the following technical solutions:

[0015] A piperazine structure derivative or a stereoisomer thereof, or a salt or a solvate thereof, the compound having a structure as shown in one of general formulae (I-III):

[0016]

[0017] wherein,

[0018] R1 is halogen, alkoxy, alkyl, or nitro; R2 is halogen; R3 is hydrogen, alkoxy, or halogen; R4 is halogen; R5 is monosubstituted or more than one substituted by halogen and alkyl.

[0019] The alkyl is C1-C6 alkyl.

[0020] The alkyl is C1-C6 alkyl.

[0021] The piperazine-containing structural derivative or its stereoisomer, or its salt or its solvate is selected from the following compounds:

[0022]

[0023] The present application also provides a preparation method of the piperazine-containing structural derivative or its stereoisomer, or its salt or its solvate, which comprises the following steps:

[0024]

[0025] The present application also provides a composition containing the compound or its stereoisomer, or its salt or its solvate, and an agriculturally acceptable adjuvant or a bactericide, an insecticide or a herbicide; preferably, the dosage form of the composition is selected from the group consisting of an emulsifiable concentrate (EC), a powder (DP), a wettable powder (WP), a granule (GR), an aqueous solution (AS), a suspension concentrate (SC), an ultra-low volume spray (ULV), a soluble powder (SP), a microcapsule (MC), a fumigant (FU), an emulsion in water (EW), and a water dispersible granule (WG).

[0026] The compound or its stereoisomer, or its salt or its solvate, or the composition can be used for preventing and treating agricultural pests, preferably, the agricultural pests are bacterial or fungal diseases of plants; more preferably, the agricultural pests are leaf blight of plants and bacterial wilt of plants; most preferably, the agricultural pests are Xanthomonas oryzae pv. oryzae, Xanthomonas campestris pv. campestris, Xanthomonas yamadae, Xanthomonas axonopodis pv. citri, Xanthomonas axonopodis pv. vesicatoria, Xanthomonas axonopodis pv. glycines, Pseudomonas syringae pv. actinidiae, Pseudomonas syringae pv. syringae, Botrytis cinerea, Phytophthora infestans, and Phytophthora cactorum.

[0027] The present application also provides a method for preventing and treating agricultural pests. The compound or its stereoisomer, or its salt or its solvate, or the composition is applied to the pests or their living environment; preferably, the agricultural pests are bacterial or fungal diseases of plants; more preferably, the agricultural pests are Xanthomonas oryzae pv. oryzae, Xanthomonas campestris pv. campestris, Xanthomonas yamadae, Xanthomonas axonopodis pv. citri, Xanthomonas axonopodis pv. vesicatoria, Xanthomonas axonopodis pv. glycines, Pseudomonas syringae pv. actinidiae, Pseudomonas syringae pv. syringae, Botrytis cinerea, Phytophthora infestans, and Phytophthora cactorum.

[0028] The present application also provides a method for protecting a plant from agricultural pests and diseases, comprising the method step of contacting the plant with the compound or a stereoisomer thereof, or a salt or solvate thereof, or the composition.

[0029] The term "alkyl" as used herein includes both branched and straight-chain saturated hydrocarbon groups having the specified number of carbon atoms. For example "C 1-10 The term "alkyl" (or alkylene) is intended to include C1, C2, C3, C4, C5, C6, C7, C8, C9, and C10alkyl groups. Additionally, for example "C 1-6 alkyl" means an alkyl group having from 1 to 6 carbon atoms. The alkyl group can be unsubstituted or substituted, such that one or more of its hydrogen atoms are replaced by other chemical groups. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (such as n-propyl and i-propyl), butyl (such as n-butyl, i-butyl, t-butyl), pentyl (such as n-pentyl, i-pentyl, neopentyl), and the like. Also, when referring to hexyl, heptyl, octyl groups, this is intended to include all isomers thereof, in addition to the normal (straight-chain) isomers.

[0030] The term "alkenyl" is intended to include both branched and straight-chain hydrocarbons having one or more carbon-carbon double bonds and having the specified number of carbon atoms. For example "C 2-6 The term "alkenyl" (or alkenylene) is intended to include C2, C3, C4, C5, and C6alkenyl groups. Examples of alkenyl groups include, but are not limited to, ethenyl, 1- propenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl, and the like.

[0031] The term "alkynyl" is intended to include both branched and straight-chain hydrocarbons having one or more carbon-carbon triple bonds and having the specified number of carbon atoms. For example "C 2-6 The term "alkynyl" (or alkynylene) is intended to include C2, C3, C4, C5, and C6alkynyl groups; such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0032] The term "substituted" as used herein means that any one or more hydrogen atoms on the designated atom or group is replaced with a selection of the designated substituents, provided that the designated atom's normal valence is not exceeded. If not otherwise stated, substituents are named to the point of attachment to the central structure. For example, it is understood that when (cycloalkyl)alkyl is a possible substituent, the point of attachment to the central structure is in the alkyl portion. A ring double bond as used herein is a double bond formed between two adjacent ring atoms (e.g., C=C, C=N or N=N). When referring to substitution, especially polysubstitution, it is meant that multiple substituents are substituted on various positions on the designated group, e.g., dichlorophenyl means 1,2-dichlorophenyl, 1,3-dichlorophenyl and 1,4-dichlorophenyl.

[0033] Combinations of substituents and / or variables are permissible only if such combinations result in stable compounds or useful synthetic intermediates. A stable compound or stable structure is one that is sufficiently robust to survive isolation from a reaction mixture and subsequent formulation into an efficacious therapeutic agent. Preferably, the compound does not contain N-halogen, S(O)2H or S(O)H groups.

[0034] The term "aryl" means a monocyclic or bicyclic aromatic hydrocarbon group having from 6 to 12 carbon atoms in the ring portion, such as phenyl and naphthyl, each of which can be substituted.

[0035] The term "halogen" or "halo" means chlorine, bromine, fluorine and iodine.

[0036] The term "heteroaryl" means substituted and unsubstituted aromatic 5- or 6-membered monocyclic, 9- or 10-membered bicyclic, and 11- to 14-membered tricyclic groups having at least one heteroatom (O, S or N) in at least one ring, with the heteroatom-containing rings preferably having 1, 2 or 3 heteroatoms selected from O, S and N. Each ring of the heteroatom-containing heteroaryl group can contain one or two oxygen or sulfur atoms and / or from 1 to 4 nitrogen atoms, provided that the total number of heteroatoms in each ring is 4 or less, and each ring has at least one carbon atom. The fused rings completing the bicyclic and tricyclic groups can contain only carbon atoms and can be saturated, partially saturated or unsaturated. Nitrogen and sulfur atoms can optionally be oxidized and nitrogen atoms can optionally be quaternized. The bicyclic or tricyclic heteroaryl must include at least one fully aromatic ring, and the other fused rings can be aromatic or nonaromatic. The heteroaryl group can be attached at any available nitrogen or carbon atom of any ring. When valence permits, the other ring, if it is a cycloalkyl or heterocycloalkyl, is additionally optionally substituted with =O (oxo).

[0037] Exemplary monocyclic heteroaryl groups include pyrrolyl, pyrazolyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, furanyl, thiophenyl, oxadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl and the like.

[0038] Exemplary bicyclic heteroaryl groups include indolyl, benzothiazolyl, benzodioxolyl, benzoxazolyl, benzothienyl, quinolinyl, tetrahydroisoquinolyl, isoquinolyl, benzimidazolyl, benzofuranyl, indolizynyl, benzofuranyl, chromonyl, coumarinyl, benzofuranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, fluoropyridyl, dihydroisoindolyl, tetrahydroquinolinyl and the like.

[0039] If not otherwise stated, the compounds of the present application are understood to include the free form and salts thereof. The term "salt" denotes an acid and / or a base addition salt. In addition, the term "salt" can include zwitterions (inner salts), for example when a compound of Formula I contains both a basic fragment, such as an amine or a pyridine or imidazole ring, and an acidic fragment such as a carboxylic acid. Pharmaceutically acceptable (i.e. non-toxic, physiologically acceptable) salts are preferred, such as acceptable metal and amine salts, where the cation does not contribute significant toxicity or biological activity to the salt. However, other salts can be useful, e.g. in isolation or purification steps, and are included within the scope of the application.

[0040] Preferably, C1-C 10 Alkyl refers to methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and the isomers thereof; C1-C5alkyl refers to methyl, ethyl, propyl, butyl, pentyl and the isomers thereof; C1-C5alkoxy refers to methoxy, ethoxy, propoxy, butoxy, pentoxy and the isomers thereof; 10 Alkyl refers to methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and the isomers thereof; C1-C5alkyl refers to methyl, ethyl, propyl, butyl, pentyl and the isomers thereof; C1-C5alkoxy refers to methoxy, ethoxy, propoxy, butoxy, pentoxy and the isomers thereof;

[0041] When referring to substituents, such as alkenyl, alkynyl, alkyl, halo, aryl, heteroaryl, alkoxy, cycloalkyl, hydroxy, amino, mercapto, phosphino, or these substituents specifically to a certain specific alkenyl, alkynyl, alkyl, halo, aryl, heteroaryl, alkoxy, cycloalkyl, hydroxy, amino, mercapto, phosphino, it refers to one to three of the above substituents. As methylphenyl refers to phenyl substituted with one to three methyl groups.

[0042] By adopting the technical scheme, the present application synthesizes a series of compounds containing the piperazine structure, and finds that the compounds have good inhibiting effect on pathogenic bacteria, such as Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and P. syringae pv. Actinidiae (PSA), etc., and provides an important scientific basis for research and development of new pesticides. DETAILED DESCRIPTION

[0043] EMBODIMENT

[0044] The present application is further described below by examples. It should be understood that the method described in the examples of the present application is only used to illustrate the present application, but is not a limitation of the present application, and simple improvement of the preparation method of the present application under the concept of the present application belongs to the scope of the present application. All raw materials and solvents used in the examples are commercially available products.

[0045] Substituted anthranilic acid (0.01 m) is refluxed in acetic anhydride (0.01 m) for 2 hours. The solvent is evaporated under reduced pressure, and the product A is recrystallized with ethanol. Compound A (13.0 mmol) and 4-aminophenol (13.7 mmol) are added to 5 ml of glacial acetic acid. After heating, the liquid is completely reacted and refluxed for 4 hours, cooled and poured into ice water to obtain solid compound B (67% yield). B (0.0396 mol) is dissolved in a potassium hydroxide (0.107 mol) ethanol solution, and epichlorohydrin (0.0913 mol) is added, and stirred at room temperature for 10 hours. The solid product is collected, dried and column chromatography to obtain white solid C (65%). Compound C (1.0 mol) is dissolved in an EtOH solution, and the appropriate amine (2.0 mol) is added. The reaction mixture is stirred at 65°C overnight. Then EtOH is evaporated under vacuum, and the crude solution is purified by crystallization or flash chromatography to obtain sulfonamide piperazine derivatives D1-D8 (I) and benzopiperazine derivatives D9-D20 (II).

[0046] wherein D1-D8 (I): D1: R1=4-CH3, R2=Cl, D2: R1=3-F, R2=Cl, D3: R1=4-F, R2=Cl, D4: R1=3-Cl, R2=Cl, D5: R1=4-Cl, R2=Cl, D6: R1=4-OCH3, R2=Cl, D7: R1=4-Br, R2=Cl, D8: R1=4-NO2, R2=Cl,;

[0047] D9-D20 (II): D9: R3= H, R4= 6-Cl, D10: R3= 3-OCH3, R4= 6-Cl, D11:

[0048] R3= 2-F, R4= 6-Cl, D12: R3= 2-Cl, R4= 6-Cl, D13: R3= 4-F, R4= 6-Cl, D14: R3= 4-OCH3, R4= 6-Cl, D15: R3= 4-Cl, R4= 6-Cl, D16: R3= 2-Cl, R= 6-Br, D17: R3= 4-Cl, R4= 6-F, D18: R3= 4-OCH3, R4= 6-Br, D19: R3= 4-Cl, R4= 6-Br, D20: R3= 2-OCH3, R4= 6-Cl.

[0049] Phenol (1 g, 7.69 mmol) was dissolved in 3 ml H2O, NaOH aqueous solution (made from 0.185 g NaOH dissolved in 1.5 ml H2O) was added, the reaction system became clear immediately. After stirring at room temperature for 40 min, epichlorohydrin (2.13 g, 23.06 mmol) was added dropwise, and the system was heated to reflux at 35 °C for 8 h. After the reaction was completed, the reaction solution was poured into a 50 ml separatory funnel, and the lower oil layer was taken into a 25 ml flask. Then 3 ml H2O and NaOH aqueous solution (made from 0.64 g NaOH dissolved in 2 ml H2O) were added successively, and the system was stirred at room temperature overnight. After the reaction was completed, the reaction solution was poured into a 50 ml separatory funnel, and the lower layer was taken and dissolved in dichloromethane, and then the organic layer was washed with H2O (3 x 20 ml). After washing, the organic layer was transferred into a 50 ml conical flask, and anhydrous sodium sulfate was added. After standing for 8 h, the mixture was filtered, and the solvent was removed under vacuum to obtain an oil. The oil was reacted with 1-(3,4-dichlorophenyl)piperazine (0.36 g, 1.55 mmol) in ethanol, and the system was heated to 80 °C. The reaction was monitored by TLC, and the reaction was completed after 2 h. The reaction system was cooled to room temperature, and the solvent was removed under vacuum at 45 °C to obtain a colorless oil. The oil was placed in the refrigerator overnight, and no solid was precipitated. The oil was dissolved in dichloromethane, and column chromatography (ethyl acetate: petroleum ether = 1:2) was used to separate the target compounds 3,4-Cl2-benzopiperazine derivatives F1-F14 (III).

[0050] F1-F14 (III): F1: R5=3-F, 4-CH3, F2: R5=3-CH3, 4-F, F3: R5=2-F, 4-CH3, F4: R5=2-CH3, 4,6-Cl2, F5: R5=2-F, 5-CH3, F6: R5=2-F, 3-CH3, F7: R5=3-Cl, 4-CH3, F8: R5=2, 4-F2, F9: R5=2, 5-F2, F10: R5=3, 4-F2, F11: R5=3, 5-F2, F12: R5=2, 5-Br2, F13: R5=2-CH3, 3-F, F14: R5=3-F, 5-CH3.

[0051] The physicochemical properties and NMR data of the synthesized partial piperazine structure derivatives are shown in Table 1, and the physicochemical properties are shown in Table 2.

[0052] Table 1 Physicochemical properties and NMR data of target compound D

[0053]

[0054]

[0055]

[0056]

[0057]

[0058]

[0059] Table 2 NMR data of target compound F

[0060]

[0061]

[0062]

[0063]

[0064]

[0065] Pharmacological Example 1:

[0066] The turbidity method is used to test the inhibition rate of the target compound on plant pathogenic bacteria, and the test objects are Xoo, Xac and PSA. DMSO dissolved in the culture medium is used as a blank control. The Xoo (rice bacterial blight pathogen on M210 solid medium) is placed in NB medium and cultured in a constant temperature shaker at 28°C and 180 rpm to the logarithmic growth phase for standby; the Xac (on M210 solid medium) is placed in NB medium and cultured in a constant temperature shaker at 28°C and 180 rpm to the logarithmic growth phase for standby; the PSA (on M210 solid medium) is placed in NB medium and cultured in a constant temperature shaker at 28°C and 180 rpm to the logarithmic growth phase for standby. The drug (compound) is configured into different concentrations (for example: 100, 50 μg / mL) of NB liquid medium containing poison 5 mL, and 40 μL of NB liquid medium containing plant disease bacteria is added respectively, and oscillated in a constant temperature shaker at 28-30°C and 180 rpm, and the Xoo is cultured for 36 h, the Xac is cultured for 48 h, and the PSA is cultured for 36 h. The OD 595 value of each concentration of bacterial liquid is determined on a spectrophotometer, and the OD 595 value of the corresponding concentration of sterile NB liquid medium containing poison is determined.

[0067] The turbidity method is used to test the effective concentration of the target compound on plant pathogenic bacteria, and the test objects are Xoo, Xac and PSA. DMSO dissolved in the culture medium is used as a blank control. The Xoo (rice bacterial blight pathogen on M210 solid medium) is placed in NB medium and cultured in a constant temperature shaker at 28°C and 180 rpm to the logarithmic growth phase for standby; the Xac (on M210 solid medium) is placed in NB medium and cultured in a constant temperature shaker at 28°C and 180 rpm to the logarithmic growth phase for standby; the PSA (on M210 solid medium) is placed in NB medium and cultured in a constant temperature shaker at 28°C and 180 rpm to the logarithmic growth phase for standby. The drug (compound) is configured into different concentrations (for example: 80, 40, 20, 10, 5 μg / mL) of NB liquid medium containing poison 5 mL, and 40 μL of NB liquid medium containing plant disease bacteria is added respectively, and oscillated in a constant temperature shaker at 28-30°C and 180 rpm, and the Xoo is cultured for 48 h, the Xac is cultured for 36 h, and the PSA is cultured for 36 h. The OD 595 value of each concentration of bacterial liquid is determined on a spectrophotometer, and the OD595 Values.

[0068] Corrected OD value = OD value of bacterial culture medium - OD value of sterile culture medium

[0069] Inhibition rate % = [(corrected OD value of control medium bacterial solution - corrected OD value of toxic culture medium) / corrected OD value of control medium bacterial solution] x 100

[0070] The embodiments of the present application are used to illustrate the technical solutions of the present application, but the contents of the embodiments are not limited thereto, and the experimental results of some target compounds are shown in Tables 3 and 4.

[0071] Table 3 Inhibitory activity of piperazine structure derivative D on three plant pathogens

[0072]

[0073]

[0074] Table 4 Inhibitory activity of piperazine structure derivative F on three plant pathogens

[0075]

[0076] In the in vitro test, the marketed drug anilozole and the positive control drug thiodiazole copper were used as the positive control drugs, and the activities of some compounds on rice bacterial leaf blight, kiwi bacterial wilt and citrus bacterial wilt were tested. As shown in Table 3, the target compounds D9, D11, D12, D13, D15, D17, D18 and D19 were better than the control drug anilozole (64.9%) at a concentration of 50 μg / mL. As shown in Table 3, the inhibition rate of the target compounds on kiwi bacterial wilt at a concentration of 50 μg / mL was better than or close to the control drug anilozole and thiodiazole copper. As shown in Table 3, the target compounds D9, D11, D13, D14, D17 and D20 were better than the control drug anilozole (46.1%) in inhibiting citrus bacterial wilt.

[0077] Compounds F1, F2, F8, F9, F10, F11 and F14 have good activity against Xoo, and the bacteriostatic activities at a concentration of 25 μg / mL are 94.8%, 90.5%, 91.7%, 96.3%, 90.9%, 96.9% and 96.5%, respectively. (5) Compounds F1, F2, F6, F9 and F11 have good activity against Xac, and the bacteriostatic activities at a concentration of 50 μg / mL are 94.4%, 93.4%, 93.2%, 95.9% and 95.8%, respectively.

Claims

1. A piperazine derivative, characterized in that: The derivative has a structure as shown in one of general formulae (II-III): wherein R3 is hydrogen, alkoxy or halogen; R4 is halogen; R5 is one or more than one substituted halogen and alkyl; the alkoxy is C1-C6 alkoxy; the alkyl is C1-C6 alkyl.

2. A composition characterized in that: The piperazine derivative-containing agent according to claim 1, and an agriculturally acceptable adjuvant or a bactericide, insecticide or herbicide.

3. Use of the piperazine derivative according to claim 1 or the composition according to claim 2 for controlling agricultural pests; the agricultural pests are rice bacterial leaf blight, cucumber bacterial leaf blight, taro bacterial leaf blight, citrus canker, grape canker, tomato canker, kiwifruit canker, apple canker.

4. A method of controlling agricultural pests and diseases, characterized by: The piperazine derivative according to claim 1 or the composition according to claim 2 is allowed to act on pests or their living environment; the agricultural pests are rice bacterial leaf blight, cucumber bacterial leaf blight, taro bacterial leaf blight, citrus canker, grape canker, tomato canker, kiwifruit canker, apple canker.

Images