Application of imidazo [1, 2-a] pyridine derivatives in prevention and treatment of plant diseases

Abstract

The invention discloses application of imidazo [1, 2-a] pyridine derivatives in prevention and treatment of plant diseases, and a series of imidazo [1, 2-a] pyridine skeleton-containing derivatives are synthesized. The compound has excellent inhibitory activity on botryosphaeria dothidea, colletotrichum gloeosporioides, colletotrichum kaoliforme, colletotrichum frutescens, alternaria solani, fusarium oxysporum, pepper fusarium wilt and rhizoctonia solani. Wherein the EC50 value of a part of the compounds for resisting colletotrichum frutescens, colletotrichum gloeosporioides and capsicum oxysporum is close to that of the positive control drug, namely, partheneine, the EC50 value of the part of the compounds for resisting fusarium oxysporum is superior to that of the positive control drug, namely, partheneine, and the compound also shows good inhibitory activity on plant pathogenic bacteria. In conclusion, the compound disclosed by the invention can be used for preparing a plant fungicide, and has potential application value for plant fungal or bacterial diseases.

Description

Technical Field

[0001] The present invention belongs to the field of pesticide chemistry, and specifically relates to the application of imidazo[1,2-a]pyridine derivatives in controlling plant diseases, effectively inhibiting plant pathogenic fungi or bacteria, and the use of such compounds in controlling agricultural plant diseases. Background Art

[0002] Plant fungal or bacterial diseases not only cause a decrease in the yield of agricultural crops, but also toxins accumulate in grains, affecting food safety and further endangering the health of humans and animals. Diseases caused by plant pathogenic fungi account for about 70-80% of plant diseases. Among them, Colletotrichum is one of the world's recognized top ten important plant pathogenic fungal groups. Many species or even the entire genus Colletotrichum are listed as key objects for quarantine inspection when entering multiple countries. Fungi of this genus can cause anthracnose of agricultural and forestry crops and post-harvest fruit rot, resulting in serious economic losses.

[0003] Pesticides, as substances with special biological activities, can control and regulate the growth and reproduction processes of various agricultural pests, thereby playing a role in preventing and controlling diseases, ensuring the yield and safety of global food and cash crops, and are essential production materials for modern agriculture. According to relevant information, stopping the use of pesticides will lead to a 30% reduction in crop yields and a 50-70% increase in the prices of agricultural products, while the use of pesticides can recover unnecessary losses. However, due to the ban on highly toxic pesticides and drug resistance, etc., we have to continuously develop new green pesticides with high efficiency, low toxicity, and low residues. Biogenic pesticides have the characteristics of low toxicity, low pollution, low cost, easy degradation, and unique action modes that are not prone to generating resistance, providing many ideal molecules for the research and development of drugs.

[0004] In recent years, fused heterocyclic compounds have gradually emerged as a bright spot in the development of new drugs. Heterocyclic compounds are important molecular structural units and have a variety of applications, including in agriculture, medicine, and veterinary medicine. These substances are also present in disinfectants, antioxidants, copolymers, corrosion inhibitors, dyes, etc. Vitamins, hormones, and antibiotics are just a small part of the many heterocyclic compounds present in organisms. In medicinal chemistry, nitrogen-containing heterocyclic analogs have a unique position in therapeutic drugs, and currently, the nitrogen-containing heterocyclic moieties of marketed drugs account for more than 75% of FDA-approved drugs. Quinoline, imidazole, pyrrole, indole, pyridine, and pyrrolidine are among these nitrogen-containing heterocyclic compounds, and they are of great significance in various research fields including chemical synthesis and medicine. Due to the diversity of applications, heterocyclic compound synthesis has gained a prominent position in organic synthesis. Imidazopyridines are divided into isomeric forms, such as imidazo[4,5-c]pyridine, imidazo[4,5-b]pyridine, imidazo[1,5-a]pyridine, and imidazo[1,2-a]pyridine. Among the isomeric forms of imidazopyridines, imidazo[1,2-a]pyridine has received a lot of attention, but its application in preventing and controlling plant diseases has not been reported. Summary of the Invention

[0005] In view of the deficiencies in the above problems, the purpose of the present invention is to explore a class of novel and highly efficient heterocyclic imidazo[1,2-a]pyridine fungicides, and to provide heterocyclic imidazo[1,2-a]pyridine derivatives with anti-plant pathogenic fungal or bacterial diseases. The compound has a structure shown in General Formula I:

[0006]

[0007] Wherein, R1 is selected from one or more of: hydrogen, hydroxyl, halogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted amino or heterocyclic amino, optionally substituted or unsubstituted heteroaryl;

[0008] R2 is selected from one or more of hydrogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted amino or heterocyclic amino, optionally substituted or unsubstituted heteroaryl.

[0009] Preferably, the substitution refers to substitution by one or more of: hydrogen, amino, hydroxyl, halogen, methyl, methoxy, cyclopropyl, cyclohexyl, alkyl, aryl.

[0010] The present invention also provides a method for preparing the imidazo[1,2-a]pyridine skeleton-containing compound as described above, comprising the following steps:

[0011] (1) Take 2-aminopyridine and 2-bromoacetophenone and add them into a round-bottom flask; weigh sodium bicarbonate and add it into the flask; measure absolute ethanol and add it into the round-bottom flask, fix it on an iron stand, add a magnetic stirrer and stir; stir at room temperature.

[0012] (2) Take a small amount of the reaction solution from the reaction solution in step (1) for TCL monitoring of the reaction.

[0013] (3) After determining that the reaction is complete in step (2), filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography to obtain the target compound.

[0014] The specific synthetic chemical equation is as follows:

[0015]

[0016] Correspondingly, the derivative includes an imidazo[1,2-a]pyridine derivative or its stereoisomer, or its salt or its solvate.

[0017] And the application of the composition containing the derivative in preventing and controlling agricultural pests and diseases.

[0018] The dosage form of the required derivative or the composition containing the derivative is selected from: emulsifiable concentrate, powder, wettable powder, granule, aqueous solution, suspension, ultra-low volume spray, soluble powder, microcapsule, smoke agent, emulsion in water or water dispersible granule.

[0019] Preferably, the agricultural pests and diseases are plant fungal or bacterial diseases.

[0020] Preferably, the bacterial disease is any one of Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. citri, Pseudomonas syringae pv. actinidiae, Ralstonia solanacearum.

[0021] Preferably, the fungal disease is any one of Botryosphaeria dothidea, Fusarium oxysporum, Colletotrichum coccodes, Colletotrichum gloeosporioides, Colletotrichum fructicola, Colletotrichum sublineolum, Alternaria alternata, Verticillium dahliae, Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. nicotianae, Fusarium solani, Alternaria solani, Rhizoctonia solani.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] A series of derivatives containing the imidazo[1,2-a]pyridine skeleton were synthesized with 2-aminopyridine. These compounds have excellent inhibitory effects on plant pathogenic fungi such as *Colletotrichum gloeosporioides*, *Colletotrichum sublineolum*, *Colletotrichum camelliae*, and *Fusarium oxysporum*. It can be seen from in vitro experiments that the target compounds have excellent inhibitory activities against plant pathogenic fungi such as *Botryosphaeria dothidea*, *Colletotrichum gloeosporioides*, *Colletotrichum sublineolum*, *Colletotrichum fructicola*, *Alternaria solani*, *Fusarium oxysporum*, *Fusarium oxysporum f. sp. vasinfectum*, and *Rhizoctonia solani*. Among them, the EC 50 values of compound 5 against *Colletotrichum fructicola*, *Colletotrichum gloeosporioides*, and *Fusarium oxysporum f. sp. vasinfectum* are 1.281±0.012 μg / mL, 1.560±0.049 μg / mL, and 10.141±0.290 μg / mL, respectively, which are close to the EC 50 values of the positive control drug fenarimol, which are 0.77±0.0073 μg / mL, 0.75±0.0.149 μg / mL, and 9.436±0.437 μg / mL, respectively; the EC 50 value of compound 5 against *Fusarium oxysporum* is 7.565 μg / mL, which is better than the EC 50 = 9.529 μg / mL of the positive control drug fenarimol. In addition, some of the target compounds show good inhibitory activities against plant pathogenic bacteria such as *Xanthomonas oryzae pv. oryzae* and *Xanthomonas axonopodis pv. citri*. At a concentration of 50 μg / mL, the inhibitory activity of compound 5 against *Xanthomonas oryzae pv. oryzae* is 67.6%, which is better than 32.6% of the control drug thiodiazole copper and 54.6% of bismerthiazol; the inhibitory activity of compound 5 against *Xanthomonas axonopodis pv. citri* is 46.8%, which is better than 18.6% of the control drug thiodiazole copper and 25.1% of bismerthiazol. In summary, the compounds disclosed in the present invention have potential application value for combating plant fungal or bacterial diseases. Detailed implementation manners

[0024] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention. If not specifically specified, the technical means used in the implementation examples are conventional means well known to those skilled in the art.

[0025] Example 1

[0026] Preparation of the target compound 2-phenylimidazo[1,2-a]pyridine (1).

[0027] The preparation route is as follows:

[0028]

[0029] The preparation process is as follows:

[0030] Weigh 2-aminopyridine (243 mg, 1.00 mmol) and 2-bromoacetophenone (170.22 mg, 1.81 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (101.29 mg, 1.21 mmol) and add it to the flask; measure 5 mL of absolute ethanol and add it to the round-bottom flask. Fix the flask on an iron stand, add a magnetic stir bar and stir; stir at room temperature for 12 h and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography eluted with petroleum ether:ethyl acetate = 10:1 to 1:1 to obtain the target product 1.

[0031] Example 2

[0032] Preparation of the target compound 2-(4-fluorophenyl)imidazo[1,2-a]pyridine (2).

[0033]

[0034] The preparation process is as follows:

[0035] Weigh 2-aminopyridine (3 g, 13.82 mmol) and 2-bromo-4'-fluoroacetophenone (2.21 g, 23.50 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (1.39 g, 16.59 mmol) and add it to the flask; measure 25 mL of absolute ethanol and add it to the round-bottom flask. Fix the flask on an iron stand, add a magnetic stir bar and stir; stir at room temperature for 12 h and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography eluted with petroleum ether:ethyl acetate = 10:1 to 1:1 to obtain the target product 2.

[0036] Example 3

[0037] Preparation of the target compound 2-(4-methylphenyl)imidazo[1,2-a]pyridine (3).

[0038]

[0039] The preparation process is as follows:

[0040] Weigh 2-aminopyridine (2 g, 9.39 mmol) and 2-bromo-4'-methylacetophenone (1.5 g, 15.96 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (946.22 mg, 11.26 mmol) and add it to the flask; measure 15 mL of absolute ethanol and add it to the round-bottom flask, fix it on an iron stand, add a magnetic stir bar and stir; stir at room temperature for 12 h, and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography eluting with petroleum ether:ethyl acetate = 10:1 to 2:1 to obtain the target product 3.

[0041] Example 4

[0042] Preparation of the target compound 2-(thiophen-2-yl)imidazo[1,2-a]pyridine (4).

[0043]

[0044] The preparation process is as follows:

[0045] Weigh 2-aminopyridine (2 g, 9.75 mmol) and 2-(2-bromoacetyl)thiophene (1.65 g, 17.56 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (983.15 mg, 11.70 mmol) and add it to the flask; measure 15 mL of absolute ethanol and add it to the round-bottom flask, fix it on an iron stand, add a magnetic stir bar and stir; stir at room temperature for 12 h, and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography eluting with petroleum ether:ethyl acetate = 10:1 to 3:1 to obtain the target product 4.

[0046] Example 5

[0047] Preparation of the target compound 2-(furan-2-yl)imidazo[1,2-a]pyridine (5).

[0048]

[0049] The preparation process is as follows:

[0050] Weigh 2-aminopyridine (2 g, 10.58 mmol) and 2-(2-bromoacetyl)furan (1.79 g, 19.05 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (1.07 g, 12.70 mmol) and add it to the flask; measure 15 mL of absolute ethanol and add it to the round-bottom flask, fix it on an iron stand, add a magnetic stir bar and stir; stir at room temperature for 12 h, and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography eluting with petroleum ether:ethyl acetate = 10:1 to 1:1 to obtain the target product 5.

[0051] Example 6

[0052] Preparation of the target compound 2-(3-fluorophenyl)imidazo[1,2-a]pyridine (6).

[0053]

[0054] The preparation process is as follows:

[0055] Weigh 2-aminopyridine (2 g, 9.22 mmol) and 2-bromo-3'-fluoroacetophenone (1.39 g, 14.74 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (928.94 mg, 1.06 mmol) and add it to the flask; measure 15 mL of absolute ethanol and add it to the round-bottom flask, fix it on an iron stand, add a magnetic stir bar and stir; stir at room temperature for 12 h, and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography with petroleum ether:ethyl acetate = 10:1 to 1:1 elution to obtain the target product 6.

[0056] Example 7

[0057] Preparation of the target compound 2-(2-fluorophenyl)imidazo[1,2-a]pyridine (7).

[0058]

[0059] The preparation process is as follows:

[0060] Weigh 2-aminopyridine (2 g, 9.22 mmol) and 2-bromo-2'-fluoroacetophenone (1.39 g, 14.74 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (928.94 mg, 1.06 mmol) and add it to the flask; measure 15 mL of absolute ethanol and add it to the round-bottom flask, fix it on an iron stand, add a magnetic stir bar and stir; stir at room temperature for 12 h, and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography with petroleum ether:ethyl acetate = 10:1 to 1:1 elution to obtain the target product 7.

[0061] Example 8

[0062] Preparation of the target compound 2-methylimidazo[1,2-a]pyridine (8).

[0063]

[0064] The preparation process is as follows:

[0065] Weigh 2-aminopyridine (2.47 g, 26.28 mmol) and bromoacetone (4 g, 29.20 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (2.7 g, 32.12 mmol) and add it to the flask; measure 25 mL of absolute ethanol and add it to the round-bottom flask. Fix the flask on an iron stand, add a magnetic stir bar and stir. Stir at room temperature for 12 h and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography eluting with dichloromethane:methanol = 500:1 to 50:1 to obtain the target product 8.

[0066] Example 9

[0067] Preparation of the target compound 2-cyclopropylimidazo[1,2-a]pyridine (9).

[0068]

[0069] The preparation process is as follows:

[0070] Weigh 2-aminopyridine (2.8 g, 17.18 mmol) and bromoacetone (4 g, 29.20 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (2.1 g, 22.33 mmol) and add it to the flask; measure 25 mL of absolute ethanol and add it to the round-bottom flask. Fix the flask on an iron stand, add a magnetic stir bar and stir. Stir at room temperature for 12 h and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography eluting with petroleum ether:ethyl acetate = 10:1 to 1:1 to obtain the target product 9.

[0071] Example 10

[0072] Preparation of the target compound 2-methylimidazo[1,2-a]pyridin-8-ol (10).

[0073]

[0074] The preparation process is as follows:

[0075] Weigh 2-amino-3-hydroxypyridine (1.99 g, 8.09 mmol) and 2-bromoacetophenone (2 g, 10.05 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (1.01 g, 12.06 mmol) and add it to the flask; measure 20 mL of absolute ethanol and add it to the round-bottom flask. Fix the flask on an iron stand, add a magnetic stir bar and stir. Stir at room temperature for 12 h and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography eluting with petroleum ether:ethyl acetate = 10:1 to 1:1 to obtain the target product 10.

[0076] Example 11

[0077] Preparation of the target compound 7-fluoro-2-methylimidazo[1,2-a]pyridine (11).

[0078]

[0079] The preparation process is as follows:

[0080] Weigh bromoacetone (2 g, 14.6 mmol) and 2-amino-4-fluoropyridine (1.64 g, 14.6 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (1.47 g, 17.52 mmol) and add it to the flask; measure 20 mL of absolute ethanol and add it to the round-bottom flask. Fix the flask on an iron stand, add a magnetic stir bar and stir. Stir at room temperature for 12 h and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography. Elute with petroleum ether:ethyl acetate = 10:1 to 1:1 to obtain the target product 11.

[0081] Example 12

[0082] Preparation of the target compound 8-fluoro-2-methylimidazo[1,2-a]pyridine (12).

[0083]

[0084] The preparation process is as follows:

[0085] Weigh bromoacetone (2 g, 14.6 mmol) and 2-amino-3-fluoropyridine (1.64 g, 14.6 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (1.35 g, 16.06 mmol) and add it to the flask; measure 20 mL of absolute ethanol and add it to the round-bottom flask. Fix the flask on an iron stand, add a magnetic stir bar and stir. Stir at room temperature for 12 h and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography. Elute with petroleum ether:ethyl acetate = 10:1 to 1:1 to obtain the target product 12.

[0086] Example 13

[0087] Preparation of the target compound 6-fluoro-2-methylimidazo[1,2-a]pyridine (13).

[0088]

[0089] The preparation process is as follows:

[0090] Weigh bromoacetone (2 g, 14.6 mmol) and 2-amino-5-fluoropyridine (1.64 g, 14.6 mmol) and add them to a round-bottom flask; weigh sodium bicarbonate (1.47 g, 17.52 mmol) and add it to the flask; measure 20 mL of absolute ethanol and add it to the round-bottom flask, fix it on an iron stand, add a magnetic stir bar and stir; stir at room temperature for 12 h and monitor the reaction by TLC. Filter the reacted mixture by suction filtration, distill the filtrate under reduced pressure, and purify it by column chromatography with petroleum ether:ethyl acetate = 10:1 to 1:1 elution to obtain the target product 13.

[0091] The compounds in the present invention can all be prepared by the above or similar methods. Just select the corresponding raw materials according to the differences in substituents and the positions of substituents.

[0092] The structures, 1H NMR and 13C NMR data of the synthesized imidazo[1,2-a]pyridine skeleton compounds are shown in Table 1, and the physical and chemical properties are shown in Table 2.

[0093] Table 1: 1H NMR, 13C NMR and high-resolution mass spectrometry data of the compounds

[0094]

[0095]

[0096]

[0097]

[0098] Table 2: Physical and chemical properties of the target compounds

[0099]

[0100]

[0101] Example 14

[0102] Applications of the target compounds

[0103] The mycelial growth rate method, also known as the toxic medium method, is one of the conventional methods for determining the toxicity of fungicides. The main principle is to mix the test agent with the culture medium, and measure the toxicity of the agent by the growth rate of the colony on the toxic culture medium. In this example, Rhizoctonia solani, Colletotrichum graminicola, and Alternaria solani were used as test objects, and DMSO was used as the blank control. The specific operations are as follows: 1) Weigh an appropriate amount of the drug according to the test concentration, dissolve it with DMSO (the dosage does not exceed 1% of the final toxic culture medium), then add 0.1% Tween 20 solution to make up to 10 mL, pour it into 90 mL of melted PDA culture medium, mix well and pour it into 9 petri dishes for standby; 2) Sterilize the punch (inner diameter 5 mm) by burning, and after it cools down, punch the mycelium at the edge of the pre-activated strain, and use an inoculation needle to stick its mycelial surface in the center of the toxic culture medium. After the treatment is completed, place them in an incubator at 25 °C for cultivation; 3) After the colony diameter of the control group grows to 5.5 - 6.6 cm, use the cross method to measure the colony diameter of the control group and each agent treatment group; 4) Use the following formula to calculate the inhibition rate (%): Inhibition rate % = (C - T) / (C - 0.5) × 100; where C is the colony diameter of the control group, T is the colony diameter of the agent treatment group, and 0.5 is the diameter of the inoculated fungal cake. According to the above method, the experimental results of the target compounds in Table 1 above are shown in Table 3.

[0104] Table 3 Inhibitory activities of compounds against phytopathogenic fungi (25 μg / mL)

[0105]

[0106] As can be seen from Table 3, some of the target compounds at a concentration of 25 μg / mL have significant inhibitory effects on Botryosphaeria dothidea, Colletotrichum gloeosporioides, Fusarium oxysporum, and Fusarium oxysporum f. sp. vasinfectum, which are significantly better than the positive control drug fenarimol.

[0107] EC 50 is an important indicator for evaluating the sensitivity of phytopathogens to compounds, and is also an important parameter for setting the compound concentration when studying the mechanism of action of compounds. In the concentration gradient experiment, five appropriate concentrations were set by the two-fold dilution method. Finally, the inhibition rate of the agent on phytopathogens and the agent concentration were converted into logarithmic values, and the toxicity curve was obtained by regression analysis using SPSS software, and the EC50 value was calculated. The experimental results are shown in Table 4.

[0108] Table 4 EC 50 values of some compounds against phytopathogens

[0109]

[0110] As can be seen from Table 4, the EC50 The values were 1.281±0.012 μg / mL, 1.560±0.049 μg / mL and 10.141±0.290 μg / mL respectively, which were close to the EC 50 values of 0.77±0.0073 μg / mL, 0.75±0.0.149 μg / mL and 9.436±0.437 μg / mL of the positive control fungicide fuberidazole; Compound 5 had good antibacterial activity against Fusarium oxysporum, and its EC 50 value was 7.565 μg / mL, which was better than the EC 50 value of 9.529 μg / mL of the positive control fungicide fuberidazole. In summary, Compound 5 had excellent inhibitory effects on Colletotrichum fructicola, Colletotrichum gloeosporioides, Fusarium oxysporum f. sp. vasinfectum and Fusarium oxysporum causing anthracnose of tea tree, fusarium wilt of pepper; Therefore, the compound disclosed in the present invention has potential application value in antifungal, and can prevent and control fungal diseases such as anthracnose of tea tree caused by Colletotrichum fructicola and Colletotrichum gloeosporioides, anthracnose of sorghum caused by Colletotrichum sublineolum, etc.

[0111] Example 15

[0112] Antibacterial application of imidazo[1,2-a]pyridine skeleton derivatives to plants, taking the activities against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas citri subsp. citri (Xac) as examples below.

[0113] The turbidimetric method was used to test the antibacterial activities of imidazo[1,2-a]pyridine skeleton compounds against Xanthomonas citri subsp. citri and Xanthomonas oryzae pv. oryzae. NA solid medium was used: 10 g glucose, 5 g peptone, 1 g yeast, 3 g beef extract, 15 g agar and 1000 mL secondary water. Xanthomonas citri subsp. citri and Xanthomonas oryzae pv. oryzae were activated and placed in a constant temperature incubator at 28 °C until single colonies grew. An appropriate amount of yellow single colonies were selected with an inoculation loop and placed into a conical flask containing NB medium: 10 g glucose, 5 g peptone, 1 g yeast, 3 g beef extract and 1000 mL secondary water, and shaken and cultured in a constant temperature shaker until the logarithmic growth phase for standby.

[0114] The drugs to be tested were formulated to the specified concentrations. 1 mL of each was taken and added to a test tube containing 4 mL of NB medium, and then 40 μL of NB medium containing Xanthomonas oryzae pv. oryzae and Xanthomonas citri subsp. citri was added to the test tube, and shaken and cultured in a constant temperature shaker at 26-28 °C and 180 r / min. When the OD 595 value of the blank control NB liquid medium was 0.6-0.8, the OD 595 values of the bacterial suspensions at each concentration were measured on a spectrophotometer.

[0115] Corrected OD 595 value = OD of the medium containing bacteria 595 - OD of the sterile medium595

[0116] Inhibition rate (%) = (OD of the control culture medium after correction - OD of the culture medium containing the drug after correction 595 - OD of the control culture medium after correction 595 ) / OD value of the control culture medium after correction × 100%.

[0117] Table 5 In vitro antibacterial activities of target compound 5 against plant pathogenic bacteria Xoo and Xac (50 μg / mL)

[0118]

[0119] As can be seen from Table 5, at a concentration of 50 μg / mL, the inhibitory activity of compound 5 against Xanthomonas oryzae pv. oryzae (Xoo) was 67.6%, superior to that of the control drugs thiodiazole copper (32.6%) and bismerthiazol (54.6%). In addition, the inhibitory activity of compound 5 against Xanthomonas citri subsp. citri (Xac) was 46.8%, superior to that of the control drugs thiodiazole copper (18.6%) and bismerthiazol (25.1%). From the above, it can be known that the imidazo[1,2-a]pyridine skeleton-containing derivatives of the present invention have good antibacterial activity and have good applications in preventing and controlling agricultural plant diseases.

[0120] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered by the scope of the claims of the present invention. The protection scope of this application should be subject to the protection scope of the claims.

Claims

1. Use of a class of imidazo[1,2-a]pyridine derivatives in preventing and controlling agricultural pests and diseases, characterized in that: This class of derivatives has the structure shown in General Formula I: Wherein, R1 is selected from one or more of: hydrogen, hydroxyl, halogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted amino or heterocyclic amino, optionally substituted or unsubstituted heteroaryl; R2 is selected from one or more of hydrogen, halogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted amino or heterocyclic amino, optionally substituted or unsubstituted heteroaryl.

2. Use of a class of imidazo[1,2-a]pyridine derivatives according to claim 1 in the prevention and control of agricultural pests and diseases, characterized in that: The so-called "substituted" means substituted by one or more of hydrogen, amino, hydroxyl, halogen, methyl, methoxy, cyclopropyl, cyclohexyl, alkyl, aryl.

3. Use of a class of imidazo[1,2-a]pyridine derivatives according to claim 1 in controlling agricultural pests and diseases, characterized in that: The preparation method of this derivative comprises the following steps: (1) Take 2-aminopyridine and 2-bromoacetophenone and add them into a round-bottom flask; weigh sodium bicarbonate and add it into the flask; measure 5 mL of absolute ethanol and add it into the round-bottom flask, fix it on an iron stand, add a magnetic stirrer and stir; stir at room temperature for 12 h; (2) Take a small amount of the reaction solution in the reaction solution of step (1) for TCL monitoring of the reaction; (3) After determining that the reaction in step (2) is complete, filter the reacted mixture by suction, distill the filtrate under reduced pressure, and purify and elute it by column chromatography to obtain the target compound.

4. Use of a class of imidazo[1,2-a]pyridine derivatives according to claim 1 in preventing and controlling agricultural pests and diseases, characterized in that: The derivative includes imidazo[1,2-a]pyridine derivatives or their stereoisomers, or their salts or their solvates.

5. The application of a class of imidazo[1,2-a]pyridine derivatives according to claim 1 in controlling agricultural pests and diseases: the application of a composition containing the said derivative in controlling agricultural pests and diseases.

6. Use of a class of imidazo[1,2-a]pyridine derivatives according to claim 4 or 5 in preventing and controlling agricultural pests and diseases, characterized in that: The dosage form of the required derivative or the composition containing the derivative is selected from: emulsifiable concentrate, powder, wettable powder, granule, aqueous solution, suspending agent, ultra-low volume spray, soluble powder, microcapsule, smoke agent, emulsion in water or water dispersible granule.

7. Use of a class of imidazo[1,2-a]pyridine derivatives according to claim 4 or 5 in controlling agricultural pests and diseases, characterized in that: The said agricultural pests and diseases are plant bacterial or fungal diseases.

8. Use of a class of imidazo[1,2-a]pyridine derivatives according to claim 7 in the prevention and control of agricultural pests and diseases, characterized in that: The said fungal diseases are any one of Botryosphaeria dothidea, Fusarium oxysporum, Colletotrichum coccodes, Colletotrichum gloeosporioides, Colletotrichum camelliae, Colletotrichum graminicola, Alternaria alternata, Verticillium dahliae, Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. nicotianae, Alternaria solani, Rhizoctonia solani.

9. Use of a class of imidazo[1,2-a]pyridine derivatives according to claim 7 in the prevention and control of agricultural pests and diseases, characterized in that: The said bacterial diseases are any one of Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. citri, Pseudomonas syringae pv. actinidiae, Ralstonia solanacearum.

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