A compound containing 1-((piperidin-4-yl)amino)propan-2-ol, its preparation and application

Abstract

The present invention discloses a 1-((piperidin-4-yl)amino)propan-2-ol compound, its preparation and application. The structural formula of the 1-((piperidin-4-yl)amino)propan-2-ol compound is shown in Formula I. The compound of the present invention has a low cost and is easy to synthesize, and can be used as an inhibitor of trehalose-6-phosphate synthase in the prevention and control of crop diseases, especially the prevention and control of crop pathogenic bacteria represented by Magnaporthe oryzae, Fusarium graminearum and Botrytis cinerea.

Description

Technical Field

[0001] The present invention belongs to the technical field of agricultural disease control, and particularly relates to the preparation of 1-((piperidin-4-yl)amino)propan-2-ol compounds and their application in the control of crop diseases. Background Art

[0002] Rice blast is one of the devastating diseases of rice, which can occur throughout the growth period of rice and damage almost all parts of the rice plant. When Magnaporthe oryzae infects rice, it can cause a reduction in yield of about 30%, and in severe cases, even result in no harvest at all. [1] Therefore, rice blast was included in the List of Major Crop Diseases and Pests in September 2020. At present, chemical control is one of the important means for controlling rice blast, but the long-term and unreasonable use of fungicides has also caused serious resistance problems and ecological environment problems. Therefore, it is of great significance to develop new fungicides based on new targets for controlling rice blast.

[0003] Trehalose-6-phosphate synthase (MoTPS1) of Magnaporthe oryzae is a key protein in the process of trehalose synthesis. In recent years, many scholars have conducted in-depth studies on its biological functions. The results show that MoTPS1 plays a key role in the infection process of Magnaporthe oryzae. The spore production of the mutant strain lacking MoTPS1 decreases significantly, and its appressorium cannot generate enough turgor pressure to complete the infection, resulting in the loss of pathogenic ability of Magnaporthe oryzae. [2 -4]. It can be seen that MoTPS1 plays an important role in the infection and pathogenic process of Magnaporthe oryzae. In addition, this protein does not exist in mammals. Therefore, MoTPS1 is considered an effective and safe candidate target for developing new fungicides. In 2019, Wang et al. used X-ray crystallography to analyze the crystal structures of the apo-MoTPS1 and its complexes with substrates UDPG and G6P. [5] This laid an important structural biology foundation for the screening and design of new fungicides targeting MoTPS1.

[0004] At present, certain progress has also been made in the research on trehalose-6-phosphate synthase inhibitors. Researchers at home and abroad have reported dozens of trehalose-6-phosphate synthase inhibitors, including jinggangmycin A-6-phosphate, phenylthiopyran compounds, reduced nicotinamide adenine dinucleotide phosphate, trehalose-6-phosphate, 5-aminoindole, etc. [6-10] In addition, Xue et al. used a homology-modeled MoTPS1 model and found through virtual screening that the compound Lead25 can be used as a potential inhibitor of MoTPS1.

[11] However, the above inhibitors generally have problems such as complex structures and difficulty in synthesis, especially the lack of reports on agricultural fungicidal activities. Therefore, it provides an opportunity for screening and designing new fungicide candidates based on the structure of MoTPS1.

[0005] References

[0006] [1] Dean, R.; Van Kan, J. A. L.; Pretorius, Z. A.; Hammond-Kosack, K. E.; DiPietro, A.; Spanu, P. D.; Rudd, J. J.; Dickman, M.; Kahmann, R.; Ellis, J.; Foster, G. D., The top 10 fungal pathogens in molecular plant pathology. Mol. Plant Pathol. 2012, 13(4), 414 - 430.

[0007] [2] Foster, A. J.; Jenkinson, J. M.; Talbot, N. J., Trehalose synthesis and metabolism are required at different stages of plant infection by Magnaporthe grisea. Embo J. 2003, 22(2), 225 - 235.

[0008] [3] Wilson, R. A.; Jenkinson, J. M.; Gibson, R. P.; Littlechild, J. A.; Wang, Z.; Talbot, N. J., Tps1 regulates the pentose phosphate pathway, nitrogen metabolism and fungal virulence. Embo J. 2007, 26(15), 3673 - 3685.

[0009] [4] Wilson, R. A.; Gibson, R. P.; Quispe, C. F.; Littlechild, J. A.; Talbot, N. J., An NADPH-dependent genetic switch regulates plant infection by the rice blast fungus. Proc. Natl. Acad. Sci. U.S.A. 2010, 107(50), 21902 - 21907.

[0010] [5]Wang, S. S.; Zhao, Y. X.; Yi, L.; Shen, M. H.; Wang, C.; Zhang, X.; Yang, J.; Peng, Y. L.; Wang, D. L.; Liu, J. F., Crystal structures of Magnaporthe oryzae trehalose-6-phosphate synthase (MoTps1) suggest a model for catalytic process of Tps1. Biochem. J. 2019, 476(21), 3227 - 3240.

[0011] [6]Errey, J. C.; Lee, S. S.; Gibson, R. P.; Martinez Fleites, C.; Barry, C. S.; Jung, P. M.; O'Sullivan, A. C.; Davis, B. G.; Davies, G. J., Mechanistic insight into enzymatic glycosyl transfer with retention of configuration through analysis of glycomimetic inhibitors. Angew. Chem. Int. Ed. 2010, 122(7), 1256 - 1259.

[0012] [7]Kern, C.; Wolf, C.; Bender, F.; Berger, M.; Noack, S.; Schmalz, S.; Ilg, T., Trehalose-6-phosphate synthase from the cat flea Ctenocephalides felis and Drosophila melanogaster: Gene identification, cloning, heterologous functional expression and identification of inhibitors by high throughput screening. Insect Mol. Biol. 2012, 21(4), 456 - 471.

[0013] [8] R.S.;De Lima, K.C.;de Almeida, D.S.;De Mesquita, J.F.;Eleutherio, E.C., Trehalose-6-phosphate as a potential lead candidate for the development of Tps1 inhibitors: insights from the trehalose biosynthetic pathway in diverse yeast species. Appl. Biochem. Biotechnol. 2017, 181(3), 914-924.

[0014] [9] L.M.;Trevisol, E.T.V.;de Azevedo Abrahim Vieira, B.;De Mesquita, J.F., Trehalose synthesis inhibitor: a molecular in silico drug design. J. Cell. Biochem. 2020, 121(2), 1114-1125.

[0015]

[10] Verma, N. Targeting trehalose and methylglucose lipopolysaccharide biosynthetic pathways in M. tuberculosis - structural and functional characterisation, and early-stage drug discovery of OtsA and Rv3030. University of Cambridge, Doctoral Thesis, 2016, doi:10.17863 / CAM.13754.

[0016]

[11] Xue, Y.K.;Shui, G.H.;Wenk, M.R., TPS1 drug design for rice blast disease in Magnaporthe oryzae. SpringerPlus, 2014, 3(1), doi:10.1186 / 2193-1801-3-18. Summary of the Invention

[0017] The object of the present invention is to provide a preparation method of a trehalose-6-phosphate synthase inhibitor, namely a compound containing 1-((piperidin-4-yl)amino)propan-2-ol, and its application in the control of agricultural diseases, which is of great significance for screening and developing novel fungicides with a completely new mechanism of action.

[0018] The present invention first provides a compound containing 1-((piperidin-4-yl)amino)propan-2-ol, and its structural formula is shown as formula (I):

[0019]

[0020] In the formula: X is methylene or carbonyl; R 1 and R 2 are each independently selected from optionally substituted or unsubstituted six-membered aryl or heteroaryl, and the heteroatoms in the heteroaryl are one or more of N, O, and S. The aryl or heteroaryl is selected from any of the following rings: benzene, pyridine, benzodioxolane, benzodioxane, 2H-chromenone, 4H-chromene, quinoline, isoquinoline, etc. The substituents in the substituted aryl and heteroaryl are each independently selected from any one or more of the following groups and can be at different positions of the aryl or heteroaryl: H, halogen, hydroxyl, amino, cyano, nitro, C1-C12 alkyl, halo-C1-C12 alkyl, C1-C12 alkoxy, halo-C1-C12 alkoxy, C3-C12 cycloalkyl, C1-C12 alkylamino, di(C1-C12 alkyl)amino, C1-C12 alkylthio, halo-C1-C12 alkylthio, C2-C12 alkenyl, C2-C12 alkynyl, C2-C12 alkenyloxy, C2-C12 alkynyloxy, C1-C12 alkylsulfonyl, C1-C12 alkylsulfinyl, C1-C12 alkylcarbonyl, C1-C12 alkoxycarbonyl, C1-C12 alkylaminocarbonyloxy, or C1-C12 alkylsulfonyloxy; wherein, the halogen in the halogen or the halo is each independently selected from F, Cl, Br, and I.

[0021] The present invention also provides a preparation method of the above-mentioned compound containing 1-((piperidin-4-yl)amino)propan-2-ol. The preparation process of the compound containing 1-((piperidin-4-yl)amino)propan-2-ol shown in formula (I) is as follows:

[0022] Using compound 1 and differently substituted benzyl halides (benzoyl chloride) as raw materials, dichloromethane as the solvent, and triethylamine as the acid-binding agent, intermediate 2 was synthesized at room temperature. Using intermediate 2 and trifluoroacetic acid as reactants, the tert-butoxycarbonyl protecting group of intermediate 2 was removed by reaction at room temperature. Subsequently, the pH of the reaction solution was adjusted to alkaline using an aqueous sodium hydroxide solution to obtain intermediate 3. Using compound 4 and 2-(chloromethyl)oxirane as raw materials, acetonitrile as the solvent, and potassium carbonate to provide an alkaline environment, intermediate 5 was synthesized at 75 °C. Using intermediate 3 and intermediate 5 as raw materials, isopropanol as the solvent, the structure shown in formula (I) was synthesized at 75 °C.

[0023] The synthesis route of formula (I) is as follows:

[0024]

[0025] The 1-((piperidin-4-yl)amino)propan-2-ol-containing compounds described in the present invention can be applied to the prevention and control of agricultural diseases, especially the prevention and control of rice blast, wheat head blight, and tomato gray mold.

[0026] Specifically, the present invention provides a trehalose-6-phosphate synthase inhibitor, the component of which is the above-mentioned 1-((piperidin-4-yl)amino)propan-2-ol-containing compound. In addition, the present invention also provides an agricultural fungicide, the active ingredient of which is the above-mentioned 1-((piperidin-4-yl)amino)propan-2-ol-containing compound, and its dosage form is a pharmaceutically acceptable dosage form, including at least one of emulsifiable concentrate, wettable powder, suspension concentrate, powder, soluble powder, aqueous solution, water dispersible powder, smoke agent, granule, and seed coating agent.

[0027] The compounds described in the present invention have a low cost and are easy to synthesize, and can be used as inhibitors of trehalose-6-phosphate synthase in the prevention and control of crop diseases, especially the prevention and control of crop pathogens represented by Magnaporthe oryzae, Fusarium graminearum, and Botrytis cinerea. Detailed implementation mode

[0028] The present invention will be further described below in conjunction with examples, but the protection scope of the present invention is not limited thereto. The methods in the following examples are all conventional methods unless otherwise specified; the materials used can all be obtained from public commercial channels unless otherwise specified.

[0029] Example 1: Preparation of 5-(oxiran-2-yloxy)benzo[d][1,3]dioxole

[0030]

[0031] Take compound 8 (10 mmol, 1.0 e.q.) in a 500 mL reaction flask, add 50 mL of acetonitrile to dissolve it, and add compound 6 (25 mmol, 2.5 e.q.) and anhydrous potassium carbonate (12 mmol, 1.2 e.q.). React at 75 °C for about 12 h. After the reaction is completed, most of the solvent is removed by distillation under reduced pressure, and it is extracted 3 times with water and ethyl acetate. The organic phase is collected, and after adding anhydrous sodium sulfate for drying and filtering, the filtrate is distilled under reduced pressure to obtain the crude product of intermediate 9. It is purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to finally obtain the pure product of intermediate 9 with a yield of 94.5%.

[0032] Example 2: Preparation of 7-(oxiran-2-ylmethoxy)-2H-chromen-2-one

[0033]

[0034] Take compound 10 (10 mmol, 1.0 e.q.) in a 500 mL reaction flask, add 50 mL of acetonitrile to dissolve it, and add compound 6 (25 mmol, 2.5 e.q.) and anhydrous potassium carbonate (12 mmol, 1.2 e.q.). React at 75 °C for about 8 h. After the reaction is completed, most of the solvent is removed by distillation under reduced pressure, and it is extracted 3 times with water and ethyl acetate. The organic phase is collected, and after adding anhydrous sodium sulfate for drying and filtering, the filtrate is distilled under reduced pressure to obtain the crude product of intermediate 11. It is purified by silica gel column chromatography (petroleum ether: ethyl acetate = 20:1) to finally obtain the pure product of intermediate 11 with a yield of 86.7%.

[0035] Example 3: Preparation of 1-(4-(trifluoromethyl)benzyl)piperidin-4-amine

[0036]

[0037] Take compound 1 (10 mmol, 1.0 e.q.) in a 100 mL reaction flask, add 20 mL of dichloromethane and triethylamine (12 mmol, 1.2 e.q.). Weigh compound 12 (12 mmol, 1.2 e.q.), dissolve it in 10 mL of dichloromethane, and slowly drip it into the reaction solution under ice bath conditions. After dropping, remove the ice bath, and place the reaction solution at room temperature to react for about 6 h.

[0038]

[0039] After the reaction was completed, 5 mL of trifluoroacetic acid was added dropwise to the reaction solution of Compound 13, and the reaction was carried out at room temperature for about 6 h. After the reaction was completed, the reaction solution was concentrated to near dryness under reduced pressure, and then 20% aqueous sodium hydroxide solution was added until the pH of the system was about 10. Extraction was carried out 3 times with water and dichloromethane, the organic phase was collected, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain Intermediate 14 with a yield of about 85.0%.

[0040] Example 4: Preparation of 4-(4-aminopiperidine-1-carbonyl)benzonitrile

[0041]

[0042] Compound 1 (10 mmol, 1.0 e.q.) was taken in a 100 mL reaction flask, and 20 mL of dichloromethane and triethylamine (12 mmol, 1.2 e.q.) were added. After weighing Compound 15 (12 mmol, 1.5 e.q.) and dissolving it in 10 mL of dichloromethane, it was slowly added dropwise to the reaction solution under ice bath conditions. After the addition was completed, the ice bath was removed, and the reaction solution was allowed to react at room temperature for about 4 h.

[0043]

[0044] After the reaction was completed, 5 mL of trifluoroacetic acid was added dropwise to the reaction solution of Compound 16, and the reaction was carried out at room temperature for about 8 h. After the reaction was completed, the reaction solution was concentrated to near dryness under reduced pressure, and then 20% aqueous sodium hydroxide solution was added until the pH of the system was about 10. Extraction was carried out 3 times with water and dichloromethane, the organic phase was collected, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain Intermediate 14 with a yield of about 72.7%.

[0045] Example 5: Preparation of 1-benzylpiperidin-4-amine

[0046]

[0047] Compound 1 (10 mmol, 1.0 e.q.) was taken in a 100 mL reaction flask, and 20 mL of dichloromethane and triethylamine (12 mmol, 1.2 e.q.) were added. After weighing Compound 18 (12 mmol, 1.2 e.q.) and dissolving it in 10 mL of dichloromethane, it was slowly added dropwise to the reaction solution under ice bath conditions. After the addition was completed, the ice bath was removed, and the reaction solution was allowed to react at room temperature for about 6 h.

[0048]

[0049] After the reaction was completed, 5 mL of trifluoroacetic acid was added dropwise to the reaction solution of Compound 19, and the reaction was carried out at room temperature for about 6 h. After the reaction was completed, the reaction solution was rotary-evaporated to near dryness under reduced pressure, and then 20% aqueous sodium hydroxide solution was added until the pH of the system was about 10. It was extracted 3 times with water and dichloromethane, the organic phase was collected, dried over anhydrous sodium sulfate and filtered, and the filtrate was distilled under reduced pressure to obtain Intermediate 14 with a yield of about 66.4%.

[0050] Example 6: Preparation of 1-(benzo[d][1,3]dioxol-5-yloxy)-3-((1-(4-(trifluoromethyl)benzyl)piperidin-4-yl)amino)propan-2-ol

[0051]

[0052] Take Intermediate 14 (12 mmol, 1.2 e.q.) in a 50 mL reaction flask, dissolve it with 20 mL of isopropanol, weigh Intermediate 9 (10 mmol, 1.0 e.q.), dissolve it in 5 mL of isopropanol and slowly add it dropwise to the reaction solution, and react at 75 °C for about 4 h. After the reaction was completed, most of the solvent was removed by distillation under reduced pressure to obtain the crude product of IA-08. It was purified by recrystallization with ethyl acetate and n-hexane to finally obtain the pure product of IA-08 with a yield of 72.3%.

[0053] Example 7: Preparation of 4-(4-((3-(benzo[d][1,3]dioxol-5-yloxy)-2-hydroxypropyl)amino)piperidine-1-carbonyl)benzonitrile

[0054]

[0055] Take Intermediate 17 (12 mmol, 1.2 e.q.) in a 50 mL reaction flask, dissolve it with 20 mL of isopropanol, weigh Intermediate 9 (10 mmol, 1.0 e.q.), dissolve it in 5 mL of isopropanol and slowly add it dropwise to the reaction solution, and react at 75 °C for about 3 h. After the reaction was completed, most of the solvent was removed by distillation under reduced pressure to obtain the crude product of IB-06. It was purified by recrystallization with ethyl acetate and n-hexane to finally obtain the pure product of IB-06 with a yield of 80.4%.

[0056] Example 8: Preparation of 6-(3-((1-benzylpiperidin-4-yl)amino)-2-hydroxypropoxy)-2H-chromen-2-one

[0057]

[0058] Take intermediate 20 (12 mmol, 1.2 e.q.) in a 50 mL reaction flask, add 20 mL of isopropanol to dissolve it, weigh intermediate 11 (10 mmol, 1.0 e.q.), dissolve it in 5 mL of isopropanol, and slowly add it dropwise to the reaction solution. React at 75 °C for about 4 h. After the reaction is completed, most of the solvent is removed by distillation under reduced pressure to obtain the crude product of IC-01. Purify it by silica gel column chromatography (methylene chloride:methanol = 120:1) to finally obtain the pure product of IC-01 with a yield of 62.3%.

[0059] Other 1-((piperidin-4-yl)amino)propan-2-ol compounds (Formula I) involved in the present invention can be synthesized by referring to the methods described in Examples 1 to 8. The properties, molecular weights and yields of Formula I in the present invention are shown in Table 1.

[0060] Table 1 Properties and yields of 1-((piperidin-4-yl)amino)propan-2-ol compounds (Formula I)

[0061]

[0062]

[0063]

[0064] Example 9: Inhibitory activity of 1-((piperidin-4-yl)amino)propan-2-ol compounds against MoTPS1

[0065] The inhibitory activity of 1-((piperidin-4-yl)amino)propan-2-ol compounds against MoTPS1 was tested using the ion-pair liquid chromatography (IPC) method. The volume of the enzyme inhibition activity test solution was 100 μL, which included: 50 μg / mL MoTPS1, 5 mM UDPG, 10 mM G6P, 25 mM Tris-HCl, and 200 μmol / L of the compound. The reaction mixture without the compound was used as a blank control, and all experiments were repeated three times. First, recombinant MoTPS1 and the inhibitor were added successively to a 0.5 mL EP tube and incubated at 25 °C for 10 minutes. Subsequently, the substrate solutions of UDPG and G6P were added successively and incubated at 25 °C for 20 minutes. Thereafter, the mixture was heated at 100 °C for 5 minutes to terminate the enzymatic reaction. The mixture was centrifuged (12,000 rpm, 10 min), and 20 μL of the supernatant was diluted 50-fold to prepare the test solution. The content of UDP catalyzed and generated in the mixture was directly detected using an LC-20AT workstation (Shimadzu, Kyoto, Japan), and the chromatographic column was a ZORBAX StableBond AQ column (250 mm × 0.46 mm, 0.25 μm, Agilent, California, USA). During the analysis, the eluent used was an aqueous solution of 50 mM potassium dihydrogen phosphate (containing 8 mM tetrabutylammonium hydrogen sulfate, pH 7.20). Before analysis, both the diluted test solution and the eluent should be purified through a 0.22 μm filter. The parameters for high-performance liquid chromatography analysis were set as follows: the injection volume was 10 μL, the flow rate of the eluent was 1 mL / min, and the wavelength of the ultraviolet detector was 260 nm. The peak areas of UDP in the blank group and the test group were denoted as Ab and At respectively, and the inhibitory activity of the compound against MoTPS1 was calculated using the following formula.

[0066] Inhibition rate (%) = [(Ab - At) / (Ab)] × 100%

[0067] The inhibitory activity of 1-((piperidin-4-yl)amino)propan-2-ol compounds against MoTPS1 is shown in Table 2.

[0068] Table 2 Inhibitory activity of 1-((piperidin-4-yl)amino)propan-2-ol compounds against MoTPS1 (200 μmol / L)

[0069]

[0070]

[0071] The results showed that when the concentration was 200 μmol / L, almost all 1-((piperidin-4-yl)amino)propan-2-ol compounds showed certain inhibitory activities against MoTPS1, and the inhibition rates were in the range of 13.78% - 76.81%, indicating that 1-((piperidin-4-yl)amino)propan-2-ol compounds were inhibitors of MoTPS1.

[0072] Example 10: In vitro antibacterial activities of 1-((piperidin-4-yl)amino)propan-2-ol compounds against Magnaporthe oryzae, Fusarium graminearum, and Botrytis cinerea

[0073] The mycelial growth rate method was used to determine the in vitro antibacterial activities of 1-((piperidin-4-yl)amino)propan-2-ol compounds against Magnaporthe oryzae, Fusarium graminearum, and Botrytis cinerea. The specific method was as follows: Weigh the above 1-((piperidin-4-yl)amino)propan-2-ol compounds and the positive control fungicide carbendazim respectively, and prepare a stock solution with a concentration of 2500 μg / mL using dimethyl sulfoxide. Then, transfer the above stock solutions respectively, add them to the sterilized and cooled potato dextrose agar medium (PDA) at about 55 °C, mix well, and then pour the medium mixed with the compounds into petri dishes with a diameter of 9 cm, 15 mL per dish. The medium added with an equal amount of dimethyl sulfoxide was used as the blank control, and the above treatments were all set with 3 replicates. After the medium in the dishes cooled and solidified, prepare 5-mm-diameter fungal discs along the edge of the mycelia of the in vitro amplified Magnaporthe oryzae, and inoculate them in the center of the media with different treatments respectively. Invert the petri dishes and culture them in the dark at 28 °C in an incubator. After the mycelial diameter of the blank control group was about 8 cm, use the cross method to measure the mycelial diameters of different treatments.

[0074] The following formula was used to calculate the inhibition rate of 1-((piperidin-4-yl)amino)propan-2-ol compounds on the mycelial growth of three phytopathogenic fungi:

[0075] Inhibition rate (%) = [(diameter of the control group - diameter of the treatment group) / (diameter of the control group - 5 mm)] × 100%

[0076] The in vitro antibacterial activities of 1-((piperidin-4-yl)amino)propan-2-ol compounds against Magnaporthe oryzae, Fusarium graminearum, and Botrytis cinerea are shown in Table 3.

[0077] Table 3 In vitro antibacterial activities of 1-((piperidin-4-yl)amino)propan-2-ol compounds against Magnaporthe oryzae, Fusarium graminearum, and Botrytis cinerea (50 μg / mL)

[0078]

[0079]

[0080]

[0081] The results showed that: at a concentration of 50 μg / mL, the 1-((piperidin-4-yl)amino)propan-2-ol compounds had a certain inhibitory effect on the mycelial growth of Magnaporthe oryzae, Fusarium graminearum, and Botrytis cinerea in vitro. The inhibition rates of the above compounds on Magnaporthe oryzae were in the range of 4.78% - 46.47%; the inhibition rates on Fusarium graminearum were in the range of 3.79% - 82.32%; the inhibition rates on Botrytis cinerea were in the range of 18.11% - 86.47%. The above experiments proved that the 1-((piperidin-4-yl)amino)propan-2-ol compounds provided by the present invention had certain inhibitory activities against Magnaporthe oryzae, Fusarium graminearum, and Botrytis cinerea. And as described in Example 9, the 1-((piperidin-4-yl)amino)propan-2-ol compounds showed certain protein-binding activities against MoTPS1. Therefore, it was speculated that the 1-((piperidin-4-yl)amino)propan-2-ol compounds further showed antibacterial activities by inhibiting MoTPS1, which was of great significance for screening and discovering novel fungicides with a brand-new mechanism of action.

[0082] The description of the above embodiments is only used to help understand the method and its core idea of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. Use of a 1-((piperidin-4-yl)amino)propan-2-ol compound in the preparation of a trehalose-6-phosphate synthase inhibitor, wherein the 1-((piperidin-4-yl)amino)propan-2-ol compound has a structural formula as shown in Formula I: Wherein: X is methylene or carbonyl; R 1 is selected from optionally substituted or unsubstituted benzene, pyridine, benzodioxole, 2H-chromenone; R 2 is selected from optionally substituted or unsubstituted benzene; R 1 and R 2 the substituents in are each independently selected from any one or more of the following groups: halogen, cyano, nitro, C1-C5 alkyl, halogenated C1-C5 alkyl, C1-C5 alkoxy, halogenated C1-C5 alkoxy; wherein, The halogen in the halogen or the halogenation is selected from F, Cl, Br, and I.

2. Use of a 1-((piperidin-4-yl)amino)propan-2-ol compound in the prevention and control of crop diseases such as rice blast, wheat scab, and tomato gray mold, wherein the 1-((piperidin-4-yl)amino)propan-2-ol compound has a structural formula as shown in Formula I: Wherein: X is methylene or carbonyl; R 1 is selected from optionally substituted or unsubstituted benzene, pyridine, benzodioxole, 2H-chromenone; R 2 is selected from optionally substituted or unsubstituted benzene; R 1 and R 2 The substituents in are each independently selected from any one or more of the following groups: halogen, cyano, nitro, C1-C5 alkyl, halo-C1-C5 alkyl, C1-C5 alkoxy, halo-C1-C5 alkoxy; wherein, The halogen in the halogen or the halogenation is selected from F, Cl, Br, and I.

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