Chalcone-containing isopropanolamine compounds, preparation method and application thereof

Abstract

The application relates to a kind of chalcone structure-containing isopropanolamine compounds and a preparation method and application thereof.The compound has the structure as shown in general formula (I):The application introduces nitrogen-containing fragment into the system based on chalcone compounds, and synthesizes a series of chalcone isopropanolamine compounds, and the compound has good inhibitory effect on plant pathogenic bacteria and plant pathogenic fungi.

Description

Technical Field

[0001] This invention relates to the field of medicinal chemistry, and in particular to an isopropanolamine compound containing chalcone, its preparation method, and its application. Background Technology

[0002] In recent years, plant bacteria and fungi have severely impacted the yield and quality of crops worldwide, causing significant economic losses for farmers. For example, *Xanthomonas oryzae* pv. Oryzae, the bacterium that causes rice bacterial blight, is a rod-shaped, Gram-negative bacterium that causes rice leaves to wilt and turn white, resulting in yield reductions of at least 10-50% annually in rice-growing countries. Furthermore, *Xanthomonas axonopodis* pv. Citri, the causal agent of citrus canker, causes citrus rot, affecting citrus production globally. In agricultural production, the long-term use of traditional pesticides has led to the development of resistance in plant pathogens. Therefore, the development of novel, highly effective, low-toxicity, and safe green pesticides is of paramount importance.

[0003] Natural products are an important resource for the creation of new pesticides. Chalcones are natural products found in a variety of natural medicinal plants and have broad development potential. According to literature reports, chalcones possess a wide range of biological activities, such as antibacterial, antiviral, anti-inflammatory, and anticancer effects. To find compounds with highly efficient antibacterial activity, this invention uses the chalcone structure as a base and isopropanol as a linking chain to introduce a series of nitrogen-containing saturated aliphatic heterocyclic or aliphatic secondary amine groups into this system, synthesizing a series of chalcone-containing isopropanolamine compounds. Their biological activities were investigated, providing an important scientific basis for the research and creation of new pesticides.

[0004] The progress in research on the bioactivity of chalcone compounds is as follows:

[0005] In 2013, Liu et al. [Liu, YT., Sun, XM., Yin, DW. et al. Syntheses and biological activity of chalcones-imidazole derivatives. Res Chem Intermed., 2013, 39, 1037-1048.] reported the synthesis of a new batch of 13-membered chalcone-imidazole derivatives, and synthesized them by IR spectroscopy, 1 H NMR, 13 The structure was characterized by C10 NMR and elemental analysis, and the results were consistent with the expected structure. Several chalcones exhibited in vitro antibacterial activity against Gram-negative bacteria. Compounds 5b, 5k, and 5g showed higher antibacterial activity against Gram-negative bacteria than standard drugs. These results indicate that these are potential antibacterial compounds.

[0006] In 2017, Shaik et al. [Afzal Basha Shaik, Rajendra Prasad Yejella, Shahanaaz Shaik. Synthesis, Antimicrobial, and Computational Evaluation of Novel Isobutylchalcones as Antimicrobial Agents. International Journal of Medicinal Chemistry., vol. 2017, Article ID 6873924, 14 pages.] synthesized 25 new chalcones using the Claisen-Schmidt condensation method, characterized them by spectroscopic data, and evaluated their antibacterial and antifungal activities using a serial tube dilution method. Among the tested compounds, A3 and A6 contained 2,4-dichlorobenzene and 2,4-difluorobenzene moieties, respectively, with MIC values ​​of 16 μg / mL against bacterial and fungal strains, respectively.

[0007] In 2019, Wang et al. [Yi-Hui Wang, Shi-Chun Jiang1, Ying Chen1, Tao Guo1, Rong-Jiao Xia1, Xu Tang1, Ming He, Wei Xue. Synthesis and antibacterial activity of novel chalcone derivatives bearing a coumarin moiety. Chem Boil Drug Des., 2015, 86, 272-283.] reported the synthesis of a series of novel chalcone derivatives with a coumarin moiety, and through... 1 HNMR, 13 The structures were verified by C10 NMR and HRMS. Bioassays showed that most of the title compounds exhibited significant antibacterial activity. Compound 3a showed the highest antibacterial activity against *Bacillus oryzae*, the causal agent of rice bacterial blight, with an EC50 value of 49.77 μg / mL, significantly superior to thiabendazole copper (179.93 μg / mL). Meanwhile, compound 3n was considered the most promising antibacterial agent against *Citrus canker*, with an EC50 value of 48.04 μg / mL, much higher than thiabendazole copper (162.48 μg / mL). This study indicates that chalcone hybrids containing coumarin moieties warrant further investigation as potential antibacterial agents.

[0008] In 2020, Lagu et al. [Lagu, SB; Yejella, RP; Bhandare, RR; Shaik, AB] reported the design, synthesis, and evaluation of the antibacterial and antifungal activities of novel fluorinated compounds containing trifluoromethyl (A1-A10) and trifluoromethoxy (B1-B10) substituents. These compounds were characterized using spectroscopic techniques, and their antibacterial activity against four pathogenic Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Bacillus subtilis) bacteria and fungi (Candida albicans and Aspergillus niger) strains was assessed. The results of this study indicate that the trifluoromethoxy compounds are more effective than the trifluoromethyl compounds. Among 20 fluorinated chalcones, compound A3 / B3, with an indole ring attached to an olefinic carbon, has been shown to have the greatest antibacterial activity compared to the standard drug, without exhibiting cytotoxicity against the normal human hepatocyte cell line (L02). Furthermore, the minimum inhibitory concentration (MIC) of A3 / B3 was determined by a tandem tube dilution method, demonstrating potential activity.

[0009] In 2015, Chen et al. [Chen, Y, Li, P, Chen, M, et al. Synthesis and antibacterial activity of chalcone derivatives containing thioether triazole. J Heterocyclic Chem. 2020; 57: 983-990.] reported the design and synthesis of a series of novel chalcone derivatives containing thioether triazoles. Through... 1 H NMR, 13 The structures of the new compounds were systematically characterized by C10 NMR and HRMS. Antibacterial activity results showed that E10, E11, E15, and E16 all exhibited good antibacterial activity against Xoo, Rs, and Xac. Among them, E15 showed a significant inhibitory effect on Xac, with EC... 50 It was 9.1 μg / mL, which is superior to the commercial formulation tebuconazole (54.9 μg / mL). Summary of the Invention

[0010] One of the objectives of this invention is to provide an isopropanolamine compound containing chalcone, or its stereoisomer, or its salt or solvate.

[0011] Another object of the present invention is to provide intermediate compounds for preparing the above-mentioned compounds or their stereoisomers, their salts or their solvates, and methods thereof.

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

[0013] Another object of the present invention is to provide the use of the above-mentioned compound or its stereoisomer, its salt or its solvate, or the composition thereof.

[0014] 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, its salt or its solvate, or the composition thereof.

[0015] To achieve the above objectives, the present invention adopts the following technical solution:

[0016] A chalcone isopropanolamine compound or its stereoisomer, its salt or its solvate, having a structure as shown in general formula (I):

[0017]

[0018] in

[0019] R1 is selected from one or more of unsubstituted furanyl, substituted or unsubstituted aryl;

[0020] R2 and R3 are each independently selected from one or more of hydrogen, alkyl or unsubstituted, amino, aryl or unsubstituted, and piperazine.

[0021] Preferably, R1, R2, and R3 are each independently selected from hydrogen, C1-C6 alkyl, C6 ... 15 Aromatic group, C6-C 15 One or more of the heteroaryl groups;

[0022] Preferably, R1 is selected from furanyl, phenyl, fluorophenyl, and chlorophenyl;

[0023] Preferably, R2 and R3 are each independently selected from hydrogen, methyl, ethyl, propyl, butyl, phenyl, benzyl, fluorobenzyl, chlorobenzyl, trifluoromethylbenzyl, trifluoromethoxybenzyl, methylbenzyl, dichlorobenzyl, methoxybenzyl, dimethoxybenzyl, pyridinepiperazinyl, tert-butylbenzyl, and trifluoroethyl.

[0024] The present invention also provides an intermediate compound for preparing the chalcone-containing isopropanolamine compound or its stereoisomer, its salt or its solvate:

[0025]

[0026] The present invention also provides a method for preparing a class of isopropanolamine compounds containing chalcone, or their stereoisomers, or their salts or solvates, comprising the following steps:

[0027]

[0028] R1, R2, and R3 are as described above.

[0029] The present invention also provides a composition comprising the said compound or its stereoisomer, its salt or its solvate, and agriculturally usable adjuvants or fungicides, insecticides or herbicides; preferably, the formulation of the composition is selected from emulsifiable concentrates (EC), powders (DP), wettable powders (WP), granules (GR), aqueous solutions (AS), suspensions (SC), ultra-low volume sprays (ULV), soluble powders (SP), microcapsules (MC), fumigants (FU), emulsions (EW), and water-dispersible granules (WG).

[0030] The compound or its stereoisomer, its salt or its solvate, or the composition thereof can be used to prevent and control agricultural pests and diseases. Preferably, the agricultural pests and diseases are bacterial or fungal plant diseases; more preferably, the agricultural pests and diseases are plant leaf blight and plant canker; most preferably, the agricultural pests and diseases are rice bacterial leaf blight, cucumber bacterial leaf blight, konjac bacterial leaf blight, citrus canker, grape canker, tomato canker, kiwifruit canker, apple canker, cucumber gray mold, pepper wilt pathogen, rapeseed sclerotinia rot, wheat scab, potato late blight, and blueberry root rot.

[0031] This invention also provides a method for preventing and controlling agricultural pests and diseases, wherein the compound or its stereoisomer, its salt or its solvate, or the composition thereof acts on the harmful substance or its living environment; preferably, the agricultural pests and diseases are bacterial or fungal plant diseases; more preferably, the agricultural pests and diseases are rice bacterial blight, tobacco bacterial wilt, cucumber bacterial blight, konjac bacterial blight, citrus canker, grape canker, tomato canker, kiwi canker, apple canker, cucumber gray mold, pepper wilt pathogen, rapeseed sclerotinia rot, wheat scab, potato late blight, and blueberry root rot.

[0032] The present invention also provides a method for protecting plants from agricultural pests and diseases, comprising the method steps of contacting the plant with the compound or its stereoisomer, its salt or its solvate, or the composition thereof.

[0033] The term "alkyl" as used here refers to both branched and straight-chain saturated hydrocarbon groups having a specific 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 groups. Additionally, for example, "C 1-6 "Alkyl" means an alkyl group having 1 to 6 carbon atoms. Alkyl groups can be unsubstituted or substituted, such that one or more of their 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.

[0034] The term "substituted" as used herein refers to the substitution of one or more hydrogen atoms on a specified atom or group by a chosen specified group, provided that the substitution does not exceed the general valence of the specified atom. Unless otherwise specified, substituents are named to the central structure. For example, it can be understood that when (cycloalkyl)alkyl is a possible substituent, the substituent's connection point to the central structure is within the alkyl moiety. Cyclic double bonds as used herein are double bonds formed between two adjacent ring atoms (e.g., C=C, C=N, or N=N). When substitution is mentioned, especially polysubstitution, it refers to the substitution of multiple substituents at various positions on a specified group, such as dichlorophenyl referring to 1,2-dichlorophenyl, 1,3-dichlorophenyl, and 1,4-dichlorophenyl.

[0035] Combinations of substituents and / or variables are permitted only when these combinations yield stable compounds or useful synthetic intermediates. A stable compound or stable structure implies that the compound is sufficiently stable to be isolated from the reaction mixture with useful purity, subsequently formulated to form an effective therapeutic agent. Preferably, the compound currently does not contain N-halogens, S(O)₂H, or S(O)H groups.

[0036] The term "aryl" refers to a monocyclic or bicyclic aromatic hydrocarbon group, such as phenyl and naphthyl, having 6 to 12 carbon atoms in the ring moiety, each of which can be substituted.

[0037] 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, wherein the heteroatom-containing ring preferably has 1, 2, or 3 heteroatoms selected from O, S, and N. Each ring of a heteroatom-containing heteroaryl may contain one or two oxygen or sulfur atoms and / or 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 may contain only carbon atoms and may be saturated, partially saturated, or unsaturated. Nitrogen and sulfur atoms may optionally be oxidized, and nitrogen atoms may optionally be quaternized. Bicyclic or tricyclic heteroaryl groups must include at least one fully aromatic ring, and the other fused rings may be aromatic or non-aromatic. Heteroaryl groups may be attached to any available nitrogen or carbon atom in any ring. Where valence permits, if the other ring is a cycloalkyl or heterocyclic ring, it may optionally be substituted with =O (oxygen).

[0038] Exemplary monocyclic heteroaryl groups include furanyl, thiophene, pyridyl, and their analogues.

[0039] Unless otherwise specified, the compounds of this invention are understood to include both their free state and their salts. The term "salt" refers to an acidic and / or basic salt formed from inorganic and / or organic acids and bases. Additionally, the term "salt" may include zwitterions (internal salts), such as when a compound of formula I contains a basic fragment such as an amine. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred, such as acceptable metal and amine salts, wherein the cation does not significantly contribute to toxicity or the biological activity of the salt. However, other salts may be useful, such as those prepared using separation or purification steps, and are therefore also included within the scope of this invention.

[0040] When referring to substituents as alkylaryl or heteroarylamino, or specifically as a particular alkylaryl or heteroarylamino group, it means one to three of the aforementioned substituents. For example, methylphenyl refers to a phenyl group with one to three methyl-substituted groups.

[0041] By adopting the above technical solution, this invention synthesizes a series of chalcone compounds containing isopropanolamine substructures based on chalcone compounds. It was found that these compounds have good inhibitory effects on pathogenic bacteria, including Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac), and also have good inhibitory effects on pathogenic fungi. This provides an important scientific basis for the research and development of new pesticides. Example

[0042] The present invention will be further illustrated below through examples. It should be understood that the methods described in the examples are merely illustrative and not intended to limit the invention. Simple modifications to the preparation methods of the present invention within the framework of the present invention's concept are all within the scope of protection claimed by the present invention. All raw materials and solvents used in the examples are commercially available products.

[0043] Example 1: Preparation of intermediate 3-furan-2-yl-1-(4-hydroxyphenyl)prop-2-en-1-one

[0044] p-Hydroxyacetophenone (3.67 mmol) and furfural (3.67 mmol) were added to a 15 mL pressure-resistant tube, followed by 2 mL of anhydrous ethanol. Then, an aqueous solution of sodium hydroxide (20% NaOH, 4.59 mmol) was added to the reaction system. The mixture was stirred at room temperature for 20 hours. The reaction process was observed by thin-layer chromatography. After the reaction was complete, the reaction system was poured into ice water and acidified with hydrochloric acid (pH to 2). The solid precipitate was filtered and dried to give intermediate 1 (yellow solid, yield 72.45%). Its NMR data are as follows: 1 HNMR (400MHz, DMSO-d6) δ10.46 (s, 1H, phenyl-OH), 8.02-7.98 (m, 1H, phenyl-H), 7.98-7.96 (m, 1H, phenyl-H), 7.89 (d, J=1.5Hz, 1H, furan-H), 7.57- 7.47 (m, 2H, phenyl-H), 7.08-7.03 (m, 1H, furan-CH=), 6.92-6.89 (m, 1H, furan-H), 6.89-6.86 (m, 1H, CH-C=O), 6.67 (dd, J=3.4, 1.8Hz, 1H, furan-H).

[0045] Example 2: Preparation of intermediate 3-(furan-2-yl)-1-(4-(epoxy-2-ylmethoxy)phenyl)prop-2-en-1-one

[0046] 1.40 mmol of 3-furan-2-yl-1-(4-hydroxyphenyl)prop-2-en-1-one, 2.10 mmol of K₂CO₃, and 8 mL of DMF were added to a 50 mL round-bottom flask and stirred at 60 °C for 10 minutes. Then, 1.68 mmol of epoxybromopropane was added, and the reaction was stopped after 8 hours. 30 mL of ethyl acetate was added, and the mixture was washed with saturated NH₄Cl₃ (4 x 15 mL). The organic phase was collected, dried over anhydrous Na₂SO₄, dissolved, and subjected to column chromatography (dichloromethane) to give a yellow solid in 55.19% yield. The NMR data are as follows: 1H NMR (400MHz, CDCl3) δ8.03-8.00 (m, 1H, phenyl-H), 8.00-7.98 (m, 1H, phenyl-H), 7.55 (d, J=15.3Hz, 1H, furan-H), 7.49 (d, J=1. 4Hz, 1H, furan-CH=), 7.42 (d, J=15.3Hz, 1H, furan-H), 6.98-6.95 (m, 1H, phenyl-H), 6.95-6.93 (m, 1H, CH-C=O), 6.67 (d, J=3.4H z, 1H, furan-H), 6.47 (dd, J=3.4, 1.8Hz, 1H, phenyl-H), 4.29 (dd, J=11.0, 2.9Hz, 1H, phenyl-O-CH2), 3.95 (dd, J=11.0, 5.9Hz, 1 H, phenyl-O-CH2), 3.34 (ddt, J=5.7, 4.2, 2.8Hz, 1H, O-CH), 2.90-2.84 (m, 1H, O-CH-CH2), 2.74 (ddt, J=4.9, 2.6Hz, 1H, O-CH-CH2).

[0047] Example 3: Preparation of intermediate 1-(4-(epoxyethylene-2-ylmethoxy)phenyl)ethane-1-one

[0048] 14.69 mmol of p-hydroxyacetophenone, 17.63 mmol of K₂CO₃, and 20 mL of DMF were added to a 100 mL round-bottom flask and stirred at 60 °C for 10 minutes. Then, 22.03 mmol of epichlorohydrin was added, and the reaction was stopped after 6 hours. 50 mL of ethyl acetate was added, and the mixture was collected with saturated NH₄Cl₃ (4 x 30 mL). The organic phase was dried over anhydrous Na₂SO₄, dissolved, and subjected to column chromatography (dichloromethane) to give a colorless solid in 73.29% yield. The NMR data are as follows: 1H NMR (400MHz, CDCl3) δ7.89 (d, J=2.8Hz, 1H, phenyl-H), 7.87 (d, J=2.0Hz, 1H, phenyl-H), 6.91 ( d, J=2.9Hz, 1H, phenyl-H), 6.89 (d, J=2.0Hz, 1H, phenyl-H), 4.28 (dd, J=11.1, 2.8Hz, 1H, pheny l-O-CH2-), 3.92 (dd, J=11.1, 5.9Hz, 1H, phenyl-O-CH2-), 3.33 (ddt, J=5.8, 4.2, 2.8Hz, 1H, -O- CH-), 2.88 (t, J=4.5Hz, 1H, -O-CH2-), 2.73 (dd, J=4.8, 2.7Hz, 1H, -O-CH2-), 2.50 (s, 3H, -CH3).

[0049] Example 4: Preparation of intermediate 1-(4-(2-hydroxy-3-(methyl(4-methylbenzyl)amino)propoxy)phenyl)ethane-1-one

[0050] 1-(4-(epoxyethylene-2-ylmethoxy)phenyl)ethane-1-one (5.20 mmol), K₂CO₃ (5.20 mmol), and isopropanol (8 mL) were added to a 15 mL pressure-resistant tube and stirred at 60 °C for 10 minutes. Then, N-methyl-4-methylbenzylamine (5.72 mmol) was added, and the reaction was stopped after 5 hours. 30 mL of ethyl acetate was added, and the mixture was extracted with water (3 x 15 mL). The organic phase was collected, dried over anhydrous Na₂SO₄, dissolved, and subjected to column chromatography (DCM:M 100:1) to give a white solid in 89.49% yield. Its NMR data are as follows: 1H NMR (500MHz, CDCl3) δ7.93-7.92 (m, 1H, phenyl-H), 7.91-7.90 (m, 1H, phenyl-H), 7.18 (d, J=8.0Hz, 2H, phenyl-H), 7.13 ( d, J=7.9Hz, 2H, phenyl-H), 6.94-6.93 (m, 1H, phenyl-H), 6.92-6.91 (m, 1H, phenyl-H), 4.15-4.09 (m, 1H, -O-CH-), 4.04- 3.97 (m, 2H, phenyl-O-CH2-), 3.65 (d, J=12.9Hz, 1H, -N-CH2-phenyl), 3.49 (d, J=12.9Hz, 1H, -N-CH2-phenyl), 2.64 (dd, J=12.3, 9.8Hz, 1H, -N-CH2-), 2.54 (s, -CH3), 2.53-2.49 (m, 1H, -N-CH2-), 2.33 (s, 3H, -N-CH3), 2.28 (s, 3H, phenyl-CH3). 13 C NMR (101MHz, CDCl3) δ196.9, 162.7, 137.0, 135.0, 130.6, 130.4, 129.1, 129.0, 114.2, 70.5, 66.0, 62.2, 59.2, 42.2, 26.4, 21.2.

[0051] Example 5: Preparation of (E)-1-(4-(4-fluorobenzylmethyl)amino)-2-hydroxypropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one

[0052] 3-(furan-2-yl)-1-(4-(epoxyethylene-2-ylmethoxy)phenyl)prop-2-en-1-one (0.74 mmol), K2CO3 (0.74 mmol), and isopropanol (4 mL) were added to a 15 mL pressure-resistant tube and stirred at 60 °C for 10 minutes. Then, N-methyl-4-fluorobenzylamine (0.81 mmol) was added, and the reaction was stopped after 10 h. 30 mL of ethyl acetate was added, and the mixture was extracted with water (3 × 15 mL). The organic phase was collected, dried over anhydrous Na2SO4, dissolved, and subjected to column chromatography (DCM:M 80:1) to give a yellow solid with a yield of 93.44%.

[0053] Example 6: Preparation of (E)-3-(4-fluorophenyl)-1-(4-hydroxy-3-methyl(4-methylbenzyl)amino)propoxy)phenyl)prop-2-en-1-one

[0054] 1.53 mmol of p-1-(4-(2-hydroxy-3-(methyl(4-methylbenzyl)amino)propoxy)phenyl)ethane-1-one and 1.53 mmol of p-fluorobenzaldehyde were added to a 15 mL pressure-resistant tube, followed by 2 mL of anhydrous ethanol. Then, an aqueous solution of sodium hydroxide (20% NaOH, 1.91 mmol) was added to the reaction mixture. The mixture was stirred at room temperature for 5 hours. The reaction was observed by thin-layer chromatography. After the reaction was complete, the reaction mixture was poured into ice water and acidified with hydrochloric acid (pH to 2). The solid precipitate was collected, filtered, and dried to give the target compound (white solid, yield 79.27%).

[0055] The structures and 1H and 1C NMR spectra of the synthesized substituted phenyl isopropanolamine compounds are shown in Table 1, and their physicochemical properties are shown in Table 2.

[0056] Table 1. 1H and 1C NMR spectra of the compounds

[0057]

[0058]

[0059]

[0060]

[0061]

[0062]

[0063]

[0064] Table 2 Physicochemical properties of the target compounds

[0065]

[0066] Pharmacological Example 1:

[0067] EC 50 Median effective concentration (MEC) is an important indicator for evaluating the sensitivity of plant pathogens to compounds, and it is also a crucial parameter for setting the compound concentration when studying the mechanism of action of target compounds. In concentration gradient experiments, five appropriate concentrations were set using the two-fold dilution method. Finally, the inhibition rate of the agent against the plant pathogen and the agent concentration were converted into logarithmic values, and the toxicity curve was obtained through regression analysis using SPSS software to calculate the EC50. 50 .

[0068] The effective medium concentration (EC) of the target compound against plant pathogens was determined using a turbidimetric method. 50The experimental subjects were *Xoo*, the pathogen of rice bacterial blight, and *Xac*, the pathogen of citrus canker. DMSO was dissolved in the culture medium as a blank control. *Xoo* (the pathogen of rice bacterial blight was on M210 solid medium) was placed in NB medium and cultured in a shaker at 28℃ and 180 rpm until the logarithmic growth phase. *Xac* (the pathogen of citrus canker) was placed in NB medium on M210 solid medium and cultured in a shaker at 28℃ and 180 rpm until the logarithmic growth phase. 5 mL of NB liquid medium containing different concentrations of the agent (compound) (e.g., 100, 50, 25, 12.5, 6.25 μg / mL) was added to test tubes, followed by 40 μL of NB liquid medium containing the pathogenic bacteria. The tubes were cultured in a shaker at 28-30℃ and 180 rpm for 36 h for *Xoo* and 48 h for *Xac*. The OD values ​​of bacterial solutions at various concentrations were measured using a spectrophotometer. 595 The value was also measured, and the OD of the corresponding concentration of sterile NB liquid culture medium containing the toxin was also determined. 595 value.

[0069] Corrected OD value = OD value of bacterial culture medium - OD value of sterile culture medium

[0070] Inhibition rate % = [(OD value of bacterial suspension in the corrected control medium - OD value of the corrected virus-containing medium) / OD value of bacterial suspension in the corrected control medium] × 100

[0071] The embodiments of this invention are provided to illustrate the technical solutions of this invention, but the content of the embodiments is not limited thereto. The experimental results of the target compound are shown in Tables 3 and 4.

[0072] Table 3. Preliminary screening of the activity of chalcone-containing isopropanolamine compounds against plant pathogenic bacteria.

[0073]

[0074]

[0075] Table 4. EC50 of isopropanolamine compounds containing chalcone against plant pathogenic bacteria. 50

[0076]

[0077]

[0078] "NT" indicates that it has not been tested.

[0079] As shown in Tables 3 and 4, the target compounds exhibited good inhibitory activity against plant pathogens (such as *Xanthomonas oryzae* pv. oryzae, citrus canker) in in vitro experiments. The compounds showed excellent inhibitory activity against *Xanthomonas oryzae* pv. oryzae (Xoo), with an EC50 value of [missing information]. 50 The concentrations ranged from 2.04 to 10.15 μg / mL; compounds 4, 7, and 11 had EC values ​​of 2.04-10.15 μg / mL. 50 The concentrations were 2.61, 2.97, and 2.04 μg / mL, respectively. It also exhibited excellent inhibitory activity against *Xanthomonas axonopodis* pv. citri (Xac), the causal agent of citrus canker, with EC50 values ​​of 2.61, 2.97, and 2.04 μg / mL, respectively. 50 The EC values ​​ranged from 1.43 to 9.82 μg / mL; compounds 1, 7, 11, and 30 had EC values ​​of 1.43–9.82 μg / mL. 50 The concentrations are 2.62, 2.41, 1.43, and 2.88 μg / mL, respectively, and can be used to prepare pesticides against plant pathogenic bacteria.

[0080] Pharmacological Example 2:

[0081] EC 50 Median effective concentration (MEC) is an important indicator for evaluating the sensitivity of plant pathogens to compounds, and it is also a crucial parameter for setting the compound concentration when studying the mechanism of action of target compounds. In concentration gradient experiments, five appropriate concentrations were set using the two-fold dilution method. Finally, the inhibition rate of the agent against the plant pathogen and the agent concentration were converted into logarithmic values, and the toxicity curve was obtained through regression analysis using SPSS software to calculate the EC50. 50 .

[0082] The effective medium concentration (EC) of the target compound against plant pathogens was determined using the mycelial growth rate method. 50The experimental subjects were *Botrytis cinerea* (Bd), *Fusarium wilt* (Fo), and *Rhizoctonia solani* (Rs). *Botrytis cinerea* (in PDA solid medium) was placed in PDA medium and incubated at 28°C for 48 hours before use. *Fusarium wilt* (in PDA solid medium) was placed in PDA medium and incubated at 28°C for 48 hours before use. *Rhizoctonia solani* (in PDA solid medium) was placed in PDA medium and incubated at 28°C for 48 hours before use. The agents (compounds) were prepared into different concentrations (e.g., 50, 25, 12.5, 6.25, 3.125 μg / mL). PDA plates containing the agent were prepared with the different concentrations of the agent at a ratio of 9:1. The treatment without agent served as a control. Using a 5mm inner diameter punch, create mycelial cakes at the edge of the activated colonies. Inoculate these cakes with an inoculation loop into the center of PDA medium containing each drug concentration and the control. Incubate in a constant temperature incubator for 2–3 days. When the control colonies nearly cover the entire culture dish, measure the diameter of each colony using the cross-sectional method. Calculate the inhibition rate of each drug against different fungi.

[0083] Mycelial growth inhibition rate % = [(Control colony diameter - Agent-treated colony diameter) / Control colony diameter - 5] × 100

[0084] The embodiments of this invention are provided to illustrate the technical solutions of this invention, but the content of the embodiments is not limited thereto. The experimental results of the target compound are shown in Table 5.

[0085] Table 5. Inhibitory activity of chalcone-containing isopropanolamine compounds against plant pathogenic fungi.

[0086]

[0087] As shown in Table 5, the target compounds exhibited poor inhibitory activity against plant pathogenic fungi (Botrytis cinerea, Fusarium wilt of pepper, and Rhizoctonia solani of rice) in in vitro experiments. At a concentration of 50 μg / mL, compounds 29 and 31 showed inhibitory activities of 76.72% and 79.22% against Botrytis cinerea, respectively; and at a concentration of 50 μg / mL, compound 30 showed an inhibitory activity of 77.17% against Rhizoctonia solani of rice. These compounds can be used to prepare pesticides against plant pathogenic fungi.

Claims

1. A compound containing chalcone isopropanolamine or its salt, characterized in that... Selected from the following compounds:

2. A composition, characterized in that... The composition contains the compound of claim 1 or a salt thereof, and agriculturally available adjuvants or fungicides, insecticides or herbicides; the formulation of the composition is selected from emulsifiable concentrates, powders, granules, aqueous suspensions, ultra-low volume sprays, microcapsules, fumigants, and water-in-oil emulsions.

3. Use of the compound of claim 1 or its salt, or the composition of claim 2, in the prevention and control of agricultural pests and diseases, wherein the agricultural pests and diseases are rice bacterial blight fungus and rice sheath blight fungus.

4. A method for preventing and controlling agricultural pests and diseases, characterized in that: The compound of claim 1 or its salt, or the composition of claim 2, is applied to a harmful substance or its living environment; the harmful substance is rice bacterial blight fungus or rice sheath blight fungus.

5. A method for protecting plants from agricultural pests and diseases, comprising the step of contacting the plant with the compound of claim 1 or a salt thereof, or the composition of claim 2.

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