A class of substituted phenyl isopropanolamine compounds and their preparation method and application

Abstract

The present invention relates to a class of substituted phenyl isopropanolamine compounds, their preparation methods, and applications. The compounds have a structure as shown in the general formula (I): #imgabs0#. Based on low-chlorophenol, the present invention introduces nitrogen-containing fragments into this system to synthesize a series of substituted phenyl isopropanolamine compounds. These compounds have excellent inhibitory effects on plant pathogenic bacteria and plant pathogenic fungi.

Description

Technical Field

[0001] The present invention relates to the technical field of medicinal chemistry, in particular to a substituted phenyl isopropanolamine compound and a preparation method and application thereof. Background Art

[0002] Bacterial plant diseases are a major factor impacting global agricultural production, severely affecting the yield and quality of agricultural products. They not only cause significant economic losses but also threaten human health. Diseases such as rice bacterial blight, citrus canker, kiwifruit canker, and tobacco bacterial wilt occur annually to varying degrees, causing significant economic losses to farmers. The long-term use of traditional fungicides such as thiophanate-methyl, chlorothiazolinone, and streptomycin sulfate not only increases drug resistance in plant pathogens but also has detrimental effects on the ecological environment and plant safety. Therefore, there is an urgent need to develop new pesticides with high activity and selectivity.

[0003] In order to find active compounds with high efficiency and fungicidal effect, the present invention uses substituted phenyl as the parent ring, connects to propylene oxide, and then uses amine compounds to open the ring to obtain the target compound containing isopropanolamine structure. A series of novel substituted phenyl isopropanolamine compounds are synthesized and their biological activities are tested, providing an important scientific basis for the research and development and creation of new pesticides.

[0004] The research progress on the biological activity of substituted phenyl compounds is as follows:

[0005] In 2019, Zhao et al. [Zhao, Yong Liang; Huang, Xing; Liu, Li Wei; Wang, Pei Yi; Long, Qing Su; Tao, Qing Qing; Li, Zhong; Yang, Song. Identification of Racemic and ChiralCarbazole Derivatives Containing an Isopropanolamine Linker as ProspectiveSurrogates against Plant Pathogenic Bacteria: In Vitro and In Vivo Assays and Quantitative Proteomics [J]. J. Agric. Food Chem., 2019, 67(26), 7512-7525.] designed and synthesized a class of racemic chiral carbazole derivatives. The antibacterial activity test results showed that compound 26 could significantly inhibit the growth of the tested plant pathogens Xanthomonas oryzae, Xanthomonas citri var. citri var. and Xanthomonas kiwifruit. Its EC 50The values ​​were 2.04, 2.42, and 0.603 μg / mL, respectively, significantly outperforming existing commercially available drugs. In vivo studies confirmed their promising application in controlling plant bacterial diseases. Label-free quantitative proteomics analysis demonstrated that compound 27 significantly induced the upregulation and downregulation of 247 differentially expressed proteins, a finding further validated by parallel reaction monitoring technology.

[0006] In 2019, Xiang et al. [Xiang, Meng; Zhou, Xiang; Luo, Ting Rong; Wang, Pei Yi; Liu, Li Wei; Li, Zhong; Wu, Zhi Bing; Yang, Song. Design, Synthesis, Antibacterial Evaluation, and Induced Apoptotic Behaviors of Epimeric and Chiral 18β-Glycyrrhetinic Acid Ester Derivatives with an Isopropanolamine Bridge against Phytopathogens [J]. J. Agric. Food Chem., 2019, 67(48), 13212-13220.] designed and synthesized a series of 18β-glycyrrhetinic acid ester derivatives with different tertiary amines and screened their pharmacological activities. The results showed that compounds 28 and 29 had active effects on plant pathogens Xanthomonas oryzae and Xanthomonas citri (EC 50 3.81 and 2.76 μg / mL respectively) were more active than GA (EC 50 >400μg / mL), thiophanate-methyl, and chlorpyrifos. Pharmacophore studies indicate that the synergistic combination of the GA backbone and the tertiary amine scaffold contributes to biological effects. In vivo experiments demonstrate their promising application in controlling bacterial infections. Mechanistic studies demonstrate that the title compound can induce apoptosis in the tested pathogens, with significant bacterial morphological changes observed in scanning electron microscopy images. This finding will facilitate the development of various apoptosis inducers.

[0007] 2020, Liu et al [Liu, Hong Wu; Ji, Qing Tian; Ren, Gang Gang; Wang, Fang; Su, Fen; Wang, Pei Yi; Zhou, Xiang; Wu, Zhi Bing; Li, Zhong; Yang, Song. Antibacterial Functions and Proposed Modes of Action of Novel 1, 2, 3, 4-Tetrahydro-β-carbolineDerivatives that Possess an Attractive 1,3-Diaminopropan-2-ol Pattern againstRice Bacterial Blight, Kiwifruit Bacterial Canker, and Citrus Bacterial Canker[J].J.Agric.Food Chem., 2020, 68(45), 12558-12568.] A series of new THC derivatives of 1,3-diaminopropane-2-ol were prepared and their biological activity was evaluated. The target compound 30 showed excellent activity against three plant pathogens: rice bacterial blight fungus, citrus canker fungus and kiwifruit canker fungus. The relevant EC50 values ​​were 1.69, 4.05 and 2.39 μg / mL, respectively. The effect was better than the parent structure 1,2,3,4-THC and the positive control. The antibacterial mechanism showed that tetrahydrocannabinol compounds can induce an increase in bacterial reactive oxygen species, thereby causing the bacteria to have obvious apoptotic behavior. In addition, compound 30 can reduce the hypersensitivity and pathogenicity of kiwifruit canker fungus.

[0008] In 2021, Huang et al. [Huang, Xing; Liu, Hong Wu; Long, Zhou Qing; Li, Zhen Xing; Zhu, Jian Jun; Wang, Pei Yi; Qi, Pu Ying; Liu, Li Wei; Yang, Song. Rational Optimization of 1,2,3-Triazole-Tailored Carbazoles As Prospective Antibacterial Alternatives with Significant In Vivo Control Efficiency and Unique Mode of Action [J]. J. Agric. Food Chem., 2021, 69(16), 4615-4627.] prepared 1,2,3-triazole-tailored carbazoles. These compounds inhibited the growth of rice bacterial blight, citrus canker, and kiwifruit canker with EC50 values ​​of 3.36(31), 2.87(31), and 4.57μg / mL(32), respectively. Potted plant tests showed that compound 31, at a concentration of 200 μg / mL, exhibited 53.23% and 50.78% efficacy against rice bacterial blight, respectively. Interestingly, the addition of 0.1% silicone and orange oil adjuvants significantly enhanced the surface wettability of compound 31 on rice leaves, increasing the control efficacy by 65.50% and 61.38%, respectively. Compound 32 also demonstrated a significant inhibitory effect on the white purulent discharge caused by kiwifruit canker infection, achieving 79.42% (protective activity) and 78.74% (curative activity) efficacy at 200 μg / mL, significantly outperforming the commercial pesticide thiophanate-methyl. Summary of the Invention

[0009] One of the purposes of the present invention is to provide a substituted phenyl isopropanolamine compound or its stereoisomer, or its salt or solvate.

[0010] Another object of the present invention is to provide an intermediate compound for preparing the above-mentioned compound or its stereoisomer, or its salt or solvate and a preparation method thereof.

[0011] Another object of the present invention is to provide a composition containing the above compound or its stereoisomer, or its salt or solvate.

[0012] Another object of the present invention is to provide the use of the above compound or its stereoisomer, or its salt or solvate, or the composition.

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

[0014] To achieve the above object, the present invention adopts the following technical solutions:

[0015] A substituted phenyl isopropanolamine compound or its stereoisomer, or its salt or solvate, wherein the compound has a structure as shown in general formula (I):

[0016]

[0017] wherein R1, R2 and R3 are each independently selected from hydrogen and chlorine; R4 and R5 are each independently selected from one or more of hydrogen, optionally substituted or unsubstituted alkyl, amino, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl;

[0018] The present invention also provides a method for preparing the substituted phenyl isopropanolamine compound or its stereoisomer, or its salt or solvate, comprising the following steps:

[0019]

[0020] 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 "alkyl" (or alkylene) refers to C1, C2, C3, C4, C5, C6, C7, C8, C9 and C10 alkyl. In addition, for example, "C 1-6 "Alkyl" means an alkyl group having 1 to 6 carbon atoms. The alkyl group may 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 isopropyl), butyl (such as n-butyl, isobutyl, tert-butyl), pentyl (such as n-pentyl, isopentyl, neopentyl), and the like.

[0021] As used herein, the term "substituted" refers to the replacement of any one or more hydrogen atoms on a designated atom or group with a selected designated group, provided that the general valence of the designated atom is not exceeded. Unless otherwise specified, substituents are named relative to the central structure. For example, it is understood that when (cycloalkyl)alkyl is a possible substituent, the point of attachment of the substituent 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, particularly polysubstitution, it is meant that multiple substituents are substituted at various positions on the designated group, e.g., dichlorobenzyl refers to 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 2,5-dichlorobenzyl, 2,6-dichlorobenzyl, 3,4-dichlorobenzyl, and 3,5-dichlorobenzyl.

[0022] Combinations of substituents and variables are permissible only if such combinations result in stable compounds or useful synthetic intermediates.A stable compound or stable structure implies that the compound is sufficiently stable when isolated to a useful degree of purity from a reaction mixture, and then formulated into an efficacious therapeutic agent.

[0023] The term "heteroaryl" refers to substituted and unsubstituted aromatic 5- or 6-membered monocyclic groups, 9- or 10-membered bicyclic groups, and 11- to 14-membered tricyclic groups having at least one heteroatom (O, S, or N) in at least one ring, preferably one, two, or three heteroatoms selected from O, S, and N. Each ring of a heteroaryl group containing a heteroatom may contain one or two oxygen or sulfur atoms and / or from one to four nitrogen atoms, provided that the total number of heteroatoms in each ring is four or fewer and each ring has at least one carbon atom. The fused rings completing the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated, or unsaturated. The nitrogen may optionally be oxidized and quaternized. A bicyclic or tricyclic heteroaryl group must include at least one fully aromatic ring; the nitrogen and other fused rings may be aromatic or non-aromatic. The heteroaryl group may be attached at any available nitrogen or carbon atom in any ring.

[0024] Exemplary monocyclic heteroaryl groups include pyrrolyl, pyrazolyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, furanyl, thienyl, oxadiazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, and the like.

[0025] If not otherwise indicated, the compounds of the present invention are understood to include both the free form and salts thereof. The term "salt" refers to acidic and / or basic salts formed with inorganic and / or organic acids and bases. In addition, the term "salt" may include zwitterions (inner salts), such as when the compound of formula I contains 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, in which the cation does not significantly contribute to the toxicity or biological activity of the salt. However, other salts may be useful, such as when separation or purification steps are employed during the preparation process, and are therefore also included in the scope of the present invention.

[0026] Preferably, C1-C 10 Alkyl refers to methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and isomers thereof;

[0027] When a substituent is referred to as an alkynyl, alkyl, aryl, or benzyl group, or when these substituents are specifically referred to as a specific alkynyl, alkyl, aryl, benzyl, or cycloalkyl group, it refers to one to three of the above substituents. For example, chlorobenzyl refers to one to three chlorine-substituted benzyl groups.

[0028] By adopting the above technical scheme, the present invention uses substituted phenyl groups as starting materials to synthesize a series of substituted phenyl-containing isopropanolamine compounds, and it is found that the compounds have a good inhibitory effect on pathogenic plant pathogens, especially pathogenic bacteria [such as rice bacterial blight pathogen (Xanthomonas oryzae pv.oryzae, Xoo), citrus canker pathogen (Xanthomonas axonopodis pv.citri, Xac) and kiwifruit canker pathogen (Pseudomonas syringaepv.actinidiae, Psa)], and have a good inhibitory effect on pathogenic fungi [such as Botrytis cinerea and rice sheath blight pathogen, etc.], providing an important scientific basis for the research and development and creation of new pesticides. Example

[0029] The present invention is further illustrated by the following examples. It should be understood that the methods described in the examples are merely illustrative of the present invention and are not intended to limit the present invention. Simple modifications to the preparation methods of the present invention within the scope of the present invention fall within the scope of the present invention. All raw materials and solvents used in the examples are commercially available products.

[0030] Example 1: Preparation of intermediate 2-(2-chlorophenoxy)methyl oxirane

[0031] 2-Chlorophenol (15.56 mmol) and K2CO3 (18.67 mmol) were added to a 100 mL round-bottom flask. 20 mL of DMF was added and the mixture was stirred at 60°C for 15 minutes. Epibromohydrin (23.34 mmol) was then slowly added dropwise. The reaction was stopped after 5 hours. Ethyl acetate (60 mL) was added and the mixture was washed with saturated aqueous NH4Cl (3 × 30 mL). The organic phase was collected, dried over anhydrous Na2SO4, desolvated, and purified by column chromatography (PE:EA = 10:1, V / V) to give a colorless liquid in an 87.74% yield. Its NMR data were: 1 H NMR (400MHz, CDCl3) δ7.36 (dd, J=1.6Hz, 1H, phenyl-H), 7.22-7.18 (m, 1H, phenyl-H), 6.96-6.89 (m, 2H, phenyl-H), 4.29 (dd, J=2.8Hz, 1H, phenyl-O -CH2-), 4.05 (dd, J=5.6Hz, 1H, phenyl-O-CH2-), 3.41-3.37 (m, 1H, -O-CH-), 2.93-2.90 (t, J=4.8Hz, 1H, -O-CH2-), 2.83 (dd, J=2.8Hz, 1H, -O-CH2-). 13 C NMR (101MHz, CDCl3) δ154.1, 130.5, 127.8, 123.2, 122.2, 114.0, 69.7, 50.2, 44.8.

[0032] Example 2: Preparation of the intermediate 4-(3-(2-chlorophenoxy)-2-hydroxypropyl)-1-tert-butyloxycarbonylpiperazine

[0033] 2-(2-Chlorophenoxy)methyloxirane (2.71 mmol) and K2CO3 (18.67 mmol) were dissolved in 4 mL of isopropanol solution, followed by the addition of 1-tert-butyloxycarbonylpiperazine (2.98 mmol) and the reaction was carried out at 60°C. TLC was followed until the reaction was complete. Dichloromethane (20 mL) was added, and the mixture was washed with water (3 x 15 mL). The organic phase was collected, dried over anhydrous Na2SO4, desolvated, and column chromatography (DCM:M=50:1, V / V) afforded a yellow oil in a yield of 96.15%. Its NMR data were as follows: 1H NMR (400MHz, CDCl3) δ7.33 (dd, J=7.9, 1.6Hz, 1H, phenyl-H), 7.19 (ddd, J=8.3, 7.6, 1.6Hz, 1H, phenyl-H) yl-H), 6.93 (dd, J=8.3, 1.2Hz, 1H, phenyl-H), 6.89 (td, J=7.7, 1.3Hz, 1H, phenyl-H), 4.14 (td, J=9. 3, 4.7Hz, 1H, -O-CH-), 4.04 (d, J=4.9Hz, 2H, -CH-CH2-piperazinyl), 3.46-3.40 (m, 4H, piperazinyl -H), 2.64-2.55(m, 4H, piperazinyl-H), 2.45-2.37(m, 2H, phenyl-O-CH2-), 1.44(s, 9H, -C(CH3)3). 13 C NMR (101MHz, CDCl3) δ154.8, 154.3, 130.3, 127.8, 123.1, 121.9, 113.9, 79.8, 71.3, 65.8, 60.7, 53.3, 28.5, 25.4.

[0034] Example 3: Preparation of Intermediate 1-(2-chlorophenoxy)-3-(piperazin-1-yl)propanol

[0035] 4-(3-(2-chlorophenoxy)-2-hydroxypropyl)-1-tert-butyloxycarbonylpiperazine (5.39 mmol) was dissolved in 10 mL of DCM and placed in a 50 mL round-bottom flask. Concentrated hydrochloric acid (5.39 mmol) was slowly added dropwise to the reaction system and stirred at room temperature for 2 h. TLC was performed. After the reaction was complete, the solvent was removed and 10 mL of water was added. The pH was then adjusted to 9-10 with KCO and the solvent was removed to obtain a yellow solid in a yield of 95.88%. Its NMR data were: 1H NMR (400MHz, CDCl3) δ7.35 (dd, J=7.9, 1.5Hz, 1H, phenyl-H), 7.22-7.17 (m, 1H, phenyl-H), 6.9 5 (dd, J=8.3, 1.2Hz, 1H, phenyl-H), 6.93-6.86 (m, 1H, phenyl-H), 4.17-4.10 (m, 1H, -O-CH-), 4 .04(d, J=5.0Hz, 2H, -CH-CH2-piperazinyl), 3.03-2.77(m, 4H, piperazinyl-H), 2.74-2.64(m , 2H, piperazinyl-H), 2.61-2.57 (m, 2H, phenyl-O-CH2-), 2.49-2.37 (m, 2H, piperazinyl-H). 13 C NMR (101MHz, CDCl3) δ154.4, 130.4, 127.8, 123.2, 121.9, 113.9, 71.6, 65.5, 61.2, 51.6, 46.2.

[0036] Example 4: Preparation of the target compound 3,3′-ethylazadiylbis(1-(2-chlorophenoxy)propan-2-ol)

[0037] 2-(2-Chlorophenoxy)methyloxirane (1.62 mmol) and K2CO3 (0.81 mmol) were dissolved in 4 mL of isopropanol, followed by the addition of ethylamine (0.81 mmol) and the reaction at 60°C. TLC was followed until completion. The reaction was quenched by the addition of water (15 mL), followed by extraction with CH2Cl2 (30 mL) and washing with water (2 x 30 mL). The organic phase was dried over anhydrous Na2SO4, desolvated, and purified by column chromatography (DCM:M=60:1, V / V) to afford a white solid in a yield of 79.28%.

[0038] Example 5: Target compound: 1-(2-chlorophenoxy)-3-(4-(3-trifluoromethylphenyl)piperazin-1-yl)propanol 1-(2-chlorophenoxy)-3-(piperazin-1-yl)propanol (1.11 mmol) and Cs2CO3 (1.33 mmol) were dissolved in 4 mL of DMSO solution, and then 2-chloro-6-trifluoromethylpyridine (1.11 mmol) was added and reacted at 105°C. TLC was followed until the reaction was completed, and then the mixture was extracted with ethyl acetate (30 mL) and washed with water (4×15 mL). The organic phase was dried over anhydrous Na2SO4, desolvated, and purified by column chromatography (DCM:M=100:1, V / V) to obtain a white solid in a yield of 53.17%.

[0039] Other target compounds were synthesized by using corresponding raw materials or substituents according to the steps of the above examples.

[0040] The structures, hydrogen and carbon nuclear magnetic resonance (HNMR) spectra of the synthesized substituted phenyl isopropanolamine compounds are shown in Table 1, and their physicochemical properties are shown in Table 2.

[0041] Table 1 Nuclear magnetic resonance hydrogen spectrum and carbon spectrum data of the compounds of the present application

[0042]

[0043]

[0044]

[0045]

[0046]

[0047]

[0048]

[0049]

[0050]

[0051]

[0052]

[0053] Table 2 Physicochemical properties of the compounds of this application

[0054]

[0055]

[0056] Pharmacological Example 1:

[0057] EC 50 Median effective concentration (MEC) is an important indicator for evaluating the sensitivity of plant pathogens to compounds. It is also an important parameter for setting compound concentration when studying the mechanism of action of target compounds. In the concentration gradient experiment, the two-fold dilution method was used to set 5 appropriate concentrations. Finally, the inhibition rate of the agent on plant pathogens and the agent concentration were converted into logarithmic values. The toxicity curve was obtained through regression analysis using SPSS software, and the EC was calculated. 50 .

[0058] The effective medium concentration EC of target compounds against plant pathogens was tested by turbidimetric method.50 The test subjects were Xanthophyllotoxin (Xoo), Xanthophyllotoxin (Xac), and Xanthophyllotoxin (Psa). DMSO was dissolved in the culture medium as a blank control. Xanthophyllotoxin (Xoo) was cultured in NB medium (M210 solid medium) and shaken in a constant temperature shaker at 28°C and 180 rpm until the logarithmic growth phase. Xanthophyllotoxin (Psa) was cultured in NB medium and shaken in a constant temperature shaker at 28°C and 180 rpm until the logarithmic growth phase. 5 mL of NB liquid medium containing different concentrations of the drug (compound) (e.g., 100, 50, 25, 12.5, 6.25 μg / mL) was added to a test tube, and 40 μL of NB liquid medium containing plant pathogens was added to each test tube. The mixture was shaken in a constant temperature shaker at 28°C and 180 rpm. The rice bacterial blight pathogen was cultured for 36 hours, the citrus canker pathogen was cultured for 48 hours, and the kiwifruit canker pathogen was cultured for 36 hours. The OD values ​​of the bacterial solutions at each concentration were measured on a spectrophotometer. 595 The OD of the corresponding concentration of toxic sterile NB liquid culture medium was also measured. 595 value.

[0059] Corrected OD value = OD value of bacterial culture medium - OD value of sterile culture medium

[0060] Inhibition rate % = [(corrected OD value of control culture medium bacteria liquid - corrected OD value of poisonous culture medium) / corrected OD value of control culture medium bacteria liquid] × 100

[0061] The examples of the present invention are used to illustrate the technical solutions of the present invention, but the contents of the examples are not limited thereto. The experimental results of the target compounds are shown in Table 3.

[0062] Table 3 Inhibitory activity of the compounds of the present application against plant pathogenic bacteria

[0063]

[0064]

[0065] Table 4 EC values ​​of the compounds of this application against plant pathogenic bacteria 50

[0066]

[0067]

[0068] "NT" means not tested

[0069] As can be seen from Table 4, in the in vitro test, the target compounds showed good inhibitory activity against plant pathogens (such as Xanthoceras oryzae, Xanthoceras citri, and Xanthoceras kiwifruit). Among them, most of the compounds containing benzyl and phenyl groups in their structures had good EC values ​​against Xanthoceras oryzae and Xanthoceras citri. 50 All of them are within 20, especially compound 28 has excellent activity against rice bacterial blight and citrus canker, EC 50 The concentrations of these compounds were 3.57 and 1.70 μg / mL, respectively. Therefore, it can be seen that this type of compound has great research prospects and can be used to prepare pesticides against plant pathogenic bacteria.

[0070] Pharmacological Example 2:

[0071] EC 50 Median effective concentration (MEC) is an important indicator for evaluating the sensitivity of plant pathogens to compounds. It is also an important parameter for setting compound concentration when studying the mechanism of action of target compounds. In the concentration gradient experiment, the two-fold dilution method was used to set 5 appropriate concentrations. Finally, the inhibition rate of the agent on plant pathogens and the agent concentration were converted into logarithmic values. The toxicity curve was obtained through regression analysis using SPSS software, and the EC was calculated. 50 .

[0072] The mycelial growth rate method was used to test the effective medium concentration EC of the target compound against plant pathogens. 50 The test subjects were Botrytis cinerea (Bd), Fusarium wilt of pepper (Fo), and Rhizoctonia solani (Rs). Botrytis cinerea (Bd on PDA solid medium) was placed on PDA medium and cultured in a 28°C incubator for 48 hours before use; Fusarium wilt of pepper (on PDA solid medium) was placed on PDA medium and cultured in a 28°C incubator for 48 hours before use; Rhizoctonia solani (on PDA solid medium) was placed on PDA medium and cultured in a 28°C incubator for 48 hours before use; The drug (compound) was prepared into drug dilutions of different concentrations (e.g., 50, 25, 12.5, 6.25, 3.125 μg / mL), and the drug-containing plates were prepared with the drug dilutions of different concentrations at a ratio of 9:1. The treatment without drug was used as the control. A bacterial cake was prepared at the edge of the activated colony using a 5mm inner diameter borer. This cake was then inoculated with an inoculating loop into the center of the PDA culture medium containing each concentration of the drug and the control. The culture was then placed in a constant temperature incubator for 2-3 days. When the control colony almost filled the entire culture dish, the diameter of each colony was measured using the cross-hatch method. The inhibition rate of each drug against different fungi was calculated.

[0073] Mycelial growth inhibition rate % = [(control colony diameter - drug-treated colony diameter) / control colony diameter - 5] × 100

[0074] The examples of the present invention are used to illustrate the technical solutions of the present invention, but the contents of the examples are not limited thereto. The experimental results of the target compounds are shown in Table 5.

[0075] Table 5 Inhibitory activity of the compounds of the present application against plant pathogenic fungi

[0076]

[0077]

[0078] As shown in Table 5, the target compounds exhibited poor inhibitory activity against plant pathogenic fungi (Botrytis cinerea, Fusarium wilt, and Rhizoctonia solani) in in vitro experiments. Compounds 11 and 46 exhibited 78.50% and 83.95% inhibitory activity against Botrytis cinerea at 50 μg / mL, respectively; compounds 13 and 18 exhibited 72.99% and 70.08% inhibitory activity against Rhizoctonia solani at 50 μg / mL, respectively. These compounds can be used to prepare pesticides against plant pathogenic fungi.

Claims

1. A class of substituted phenyl isopropanolamine compounds or their salts, characterized in that Selected from the following compounds:

2. A composition characterized in that The invention relates to a composition comprising the compound or salt thereof according to claim 1, and an agriculturally usable adjuvant or fungicide, insecticide or herbicide; wherein the composition is in the form of an emulsifiable concentrate, a powder, a granule, an aqueous solution, a suspension, an ultra-low volume spray, a microcapsule, a smoke agent, and an aqueous emulsion.

3. Use of the compound or salt thereof according to claim 1, or the composition according to claim 2, in preventing and controlling agricultural pests and diseases, wherein the agricultural pests and diseases are Xanthoceras oryzae or Xanthoceras citri.

4. A method for preventing and controlling agricultural pests and diseases, characterized in that: The compound or salt thereof according to claim 1, or the composition according to claim 2, is allowed to act on a pest or its living environment; the pest is Xanthoceras oryzae or Xanthoceras citri.

5. A method for protecting plants from agricultural pests and diseases, comprising a method step in which the plant is contacted with the compound or salt thereof according to claim 1, or the composition according to claim 2.

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