1,3,4-oxadiazole sulfide compounds containing isopropanolamine structure, preparation method and application thereof

Abstract

The application discloses a 1,3,4-oxadiazole sulfide compound containing an isopropanolamine structure and a preparation method and application thereof. The preparation method of the 1,3,4-oxadiazole sulfide compound containing the isopropanolamine structure is simple in operation, does not involve a noble metal in the reaction, and is efficient. The 1,3,4-oxadiazole sulfide compound containing the isopropanolamine structure has good bactericidal activity, and the 1,3,4-oxadiazole sulfide compound containing the isopropanolamine structure shows efficient and / or broad-spectrum bacteriostatic activity, and can be effectively used in the prevention and treatment of crop pathogenic bacteria.

Description

Technical Field

[0001] This invention belongs to the field of compound technology, specifically relating to 1,3,4-oxadiazole thioether compounds containing isopropanolamine structures, their preparation methods, and applications. Background Technology

[0002] 1,3,4-Oxadiazole is the scaffold for many important active substances and is known to have a wide range of biological activities, including antibacterial, herbicidal, insecticidal, nematicidal, acaricidal and antiviral effects, and has attracted widespread attention from pesticide developers.

[0003] Using isopropanolamine structures as multifunctional starting materials and linking units is a common synthetic strategy for developing novel antibacterial agents. This method connects pharmacologically active head groups to variable terminal amine groups via an isopropanolamine skeleton, enabling modular assembly of structurally diverse molecules. Therefore, developing 1,3,4-oxadiazole thioether compounds containing isopropanolamine structures has significant positive implications and extremely important value.

[0004] Currently, there are no reports on 1,3,4-oxadiazole thioether compounds containing isopropanolamine structures, their synthetic routes, and their antibacterial properties. Summary of the Invention

[0005] Purpose of the invention: The technical problem to be solved by the present invention is to construct a series of 1,3,4-oxadiazole thioether compounds with antibacterial and bacteriostatic activities by using a strategy of splicing substructures of active units to connect isopropanolamine with a 1,3,4-oxadiazole skeleton.

[0006] Another technical problem to be solved by the present invention is to provide a series of methods for preparing 1,3,4-oxadiazole thioether compounds containing isopropanolamine structures.

[0007] The final technical problem to be solved by this invention is to provide the application of 1,3,4-oxadiazole thioether compounds containing isopropanolamine in the preparation of products that inhibit or kill pathogens.

[0008] Technical solution: To solve the above-mentioned technical problems, the first aspect of the present invention provides 1,3,4-oxadiazole thioether compounds containing an isopropanolamine structure, the structure of which is shown in Formula I:

[0009] Among them, R 1 Selected from Me, Et, Pr, i -Pr, Bn, (2-CF3)-Bn, (3-CF3)-Bn, (4-CF3)-Bn, (4-F)-Bn, (3,4-diF)-Bn, (2,4,5-triF)-Bn, (4-( t-bu))-Bn or (4-( i -Pr))-Bn;R 2 Selected from Ph, (3-Br)-Ph, (3-CH3)-Ph, (3-OCH3)-Ph, (4-F)-Ph, (4-Cl)-Ph, (4-CF3)-Ph, (4-CH3)-Ph, 1,2,4-triazole, Bn, (4-I)-Bn, (4-Cl)-Bn, (4-F)-Bn, (4-OCH3)-Bn, (4-CF3)-Bn, thiophene-2-methyl, furan-2-methyl, thiophene-2-methyl, furan-2-methyl, N , N -Dibutyl, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0010] The compounds of the present invention include 1-(phenylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((3-bromophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((3-bromophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((3-bromophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((4-fluorophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-fluorophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 4-Oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((4-chlorophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-((4-(trifluoromethyl)phenyl)amino)prop-2-ol, 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(4- (5-(ethylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(4-(5-(propanethio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(4-(5-(isopropylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(4-(5-(benzylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(benzylamino)-3-(4-(5-(propanethio)- 1,3,4-Oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((4-iodobenzyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((4-chlorobenzyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((4-fluorobenzyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-methoxybenzyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-(5-(propylthio)-1,3,4-Oxadiazol-2-yl)phenoxy)-3-((4-(trifluoromethyl)benzyl)amino)prop-2-ol, 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-((thiophen-2-ylmethyl)amino)prop-2-ol, 1-((furan-2-ylmethyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(dibutylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclopropylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl) Phenoxy)propane-2-ol, 1-(cyclobutylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclopentylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclohexylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclohexylamino)-3-(4-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclohexylamino)-3-(4-(5-(ethylthio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclohexylamino)-3-(4-(5-(ethylthio)-1,3,4-oxadiazol-2-yl) 1-(cyclohexylamino)-3-(4-(5-(isopropylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-(5-(phenylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(cyclohexylamino)prop-2-ol, 1-(cyclohexylamino)-3-(4-(5-((2-(trifluoromethyl)phenyl)thio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(cyclohexylamino)-3-(4-(5-((3-(trifluoromethyl)phenyl)thio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(cyclohexylamino)-3- (4-(5-((4-(trifluoromethyl)phenylthio)-1,3,4-oxadiazol-2-yl)phenoxy))propane-2-ol, 1-(cyclohexylamino)-3-(4-(5-((4-fluorophenyl)thio-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclohexylamino)-3-(4-(5-((3,4-difluorothio-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclohexylamino)-3-(4-(5-((2,4,5-trifluorophenyl)thio-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(4-(5-((4-(tert-butyl)phenylthio)-1,3,One or more of 4-thiadiazol-2-yl)phenoxy)-3-(cyclohexylamino)prop-2-ol or 1-(cyclohexylamino)-3-(4-(5-((4-isopropylphenyl)thio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol.

[0011] A second aspect of this invention provides a method for preparing 1,3,4-oxadiazole thioether compounds containing an isopropanolamine structure, comprising the following steps: (1) 4-hydroxybenzoyl hydrazine was prepared by adding ethanol and hydrazine hydrate sequentially to ethyl 4-hydroxybenzoate as raw material; (2) 4-hydroxybenzoylhydrazine was added to ethanol, followed by sodium hydroxide and carbon disulfide. The solvent was removed by vacuum distillation, and then an appropriate amount of ice water was added to dissolve it. The pH was then adjusted to 3-4 to prepare 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol. (3) Add to 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol N , N - Dimethylformamide (DMF) was dissolved and stirred, followed by the addition of triethylamine and a haloalkane to prepare the intermediate 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted sulfide; (4) Add 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted sulfide and potassium carbonate to N , N Dissolve it in dimethylformamide (DMF) solution, then add epichlorohydrin dropwise to the reactor to prepare intermediate 5-(4-epoxypropyl)phenyl-1,3,4-oxadiazole-2-substituted sulfide; (5) The intermediate 5-(4-epoxypropyl)phenyl-1,3,4-oxadiazole-2-substituted thioether was dissolved in isopropanol, the substituted amine was added, the mixture was heated and stirred, and the reaction progress was monitored by TLC. After the reaction was complete, the mixture was purified by column chromatography to prepare a series of target compounds containing isopropanolamine structure 1,3,4-oxadiazole thioether compounds.

[0012] The method for preparing the 1,3,4-oxadiazole sulfide compounds containing the isopropanolamine structure of the present invention uses ethyl 4-hydroxybenzoate (1) as a raw material, and obtains the 1,3,4-oxadiazole sulfide compounds containing the isopropanolamine structure shown in Formula I through hydrazolysis, cyclization, substitution, substitution, and epoxide ring-opening reaction. The specific steps include: Step (1): Add ethyl 4-hydroxybenzoate (1) to a flask, then add anhydrous ethanol as a solvent to dissolve it. Then, add hydrazine hydrate under ice bath conditions, followed by evacuation to ensure the system is in dry N2. The reaction temperature is 85℃, and the reaction time is 24 h. After the reaction is complete, remove the solvent by vacuum distillation to obtain the intermediate 4-hydroxybenzoylhydrazine (2); wherein the molar ratio of ethyl 4-hydroxybenzoate (1) to hydrazine hydrate is 1:5-1:10. Preferably, the molar ratio of ethyl 4-hydroxybenzoate to hydrazine hydrate is 1:5.

[0013] Step (2): Add 4-hydroxybenzoyl hydrazine (2) to a round-bottom flask, add anhydrous ethanol to the flask to dissolve the substrate, and then add solid sodium hydroxide. Keep the system temperature at 0-5℃, measure out water-sealed carbon disulfide and add it dropwise to the reaction flask, and react at 85℃ for 12 hours. After the reaction is complete, remove the solvent by vacuum distillation to obtain a large amount of yellow solid, dissolve it in ice water, adjust the pH to 3-4, and a large amount of white flocculent matter appears. After filtration, the obtained filter cake is the intermediate 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol (3); wherein, the molar ratio of 4-hydroxybenzoyl hydrazine (2) to sodium hydroxide and carbon disulfide is 1:1.4:2-1:2:4. Preferably, the molar ratio of 4-hydroxybenzoyl hydrazine to sodium hydroxide and carbon disulfide is 1:1.4:2.

[0014] Step (3): Add 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol (3) to the round-bottom flask, and then add anhydrous... N , N Dissolve dimethylformamide (DMF), then weigh anhydrous triethylamine and add it to the solution, stirring for 5-10 min. Add the haloalkane dropwise to a round-bottom flask and react for 12 h. After the reaction is complete, extract the system with ethyl acetate and wash with saturated ammonium chloride. N , N -Dimethylformamide (DMF) was then removed under reduced pressure, followed by purification by silica gel column chromatography using ethyl acetate-petroleum ether (V:V:Petrol = 1:3) to yield intermediate 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted thioether (4); wherein the molar ratio of 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol (3) to triethylamine and haloalkanes is 1:1.5:1.2-1:2:1.5. Preferably, the molar ratio of 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol to triethylamine and haloalkanes is 1:1.5:1.2.

[0015] Step (4): The intermediate 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted thioether (4) was added to a round-bottom flask, and anhydrous N,N-dimethylformamide DMF was added to dissolve it. Potassium carbonate was weighed into the flask and stirred for 5-10 min. Epichlorohydrin was added dropwise to the round-bottom flask, and the reaction was carried out at 85℃ for 6 h. After the reaction was completed, the system was extracted with ethyl acetate and washed with saturated ammonium chloride. N , N -Dimethylformamide (DMF) was then removed under reduced pressure, followed by purification by silica gel column chromatography using ethyl acetate-petroleum ether (V:V:Petrol = 1:4) to yield intermediate 5-(4-epoxypropyl)phenyl-1,3,4-oxadiazole-2-substituted sulfide (5); wherein the molar ratio of 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted sulfide (4) to potassium carbonate and epichlorohydrin is 1:1.5:2-1:2:5. Preferably, the molar ratio of the 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted sulfide to potassium carbonate and epichlorohydrin is 1:1.5:2.

[0016] Step (5): 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted thioether (4) and the substituted amine were added to a round-bottom flask and dissolved thoroughly in isopropanol solution. The reaction temperature was 75°C. After the reaction was completed, the solvent was removed under reduced pressure, and the mixture was purified by silica gel column chromatography. The developing solvent was methanol-dichloromethane (V methanol:V dichloromethane = 1:40), yielding a series of target compounds containing 1,3,4-oxadiazole thioethers with isopropanolamine structures; wherein the molar ratio of 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted thioether (4) to the substituted amine was 1:1.2-1:3. Preferably, the molar ratio of 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted thioether to the substituted amine was 1:1.2.

[0017] The preparation method of the 1,3,4-oxadiazole thioether compound containing the isopropanolamine structure described in this invention also includes the purification of the target compound. There are no special requirements for the purification method. Those skilled in the art can use various conventional purification methods, such as extraction with an extractant, drying with a drying agent, and removing impurities by column chromatography to obtain the target compound with high purity.

[0018] The third aspect of the present invention provides the use of the 1,3,4-oxadiazole thioether compounds containing the isopropanolamine structure in the preparation of products that inhibit or kill pathogens.

[0019] The pathogens include, but are not limited to, crop pathogens, including, but are not limited to, rice bacterial blight pathogens (…). Xanthomonas oryzae pv. oryzae ), rice bacterial leaf streak ( Xanthomonas oryzae pv. oryzicola ), Citrus canker pathogen ( Xanthomonas citri subsp. citri ) and the soft rot pathogen of Chinese cabbage ( Pectobacterium carotovorum subsp. carotovorum One or more of them.

[0020] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: 1. This invention uses ethyl 4-hydroxybenzoate, various substituted benzyl groups, epichlorohydrin, and various substituted amines as starting materials to obtain 1,3,4-oxadiazole sulfide compounds containing the isopropanolamine structure through a simple five-step reaction. The preparation method of the 1,3,4-oxadiazole sulfide compounds containing the isopropanolamine structure of this invention is simple to operate, involves no precious metals in the reaction, and is highly efficient.

[0021] 2. The 1,3,4-oxadiazole sulfide compounds containing the isopropanolamine structure of this invention have good bactericidal activity. The 1,3,4-oxadiazole sulfide compounds containing the isopropanolamine structure exhibit highly efficient antibacterial activity against a wider variety of crop pathogens and can be effectively used to control multiple pathogenic bacteria in crops at the same time. Detailed Implementation

[0022] The technical solution of the present invention will be further described below. The technical solution of the present invention will be described in detail through embodiments.

[0023] Me represents methyl, Et represents ethyl, and Pr represents propyl. i -Pr represents isopropyl, Bn represents benzyl, (2-CF3)-Bn represents 2-trifluoromethylbenzyl, (3-CF3)-Bn represents 3-trifluoromethylbenzyl, (4-CF3)-Bn represents 4-trifluoromethylbenzyl, (4-F)-Bn represents 4-fluorobenzyl, (3,4-diF)-Bn represents 3,4-fluorobenzyl, (2,4,5-triF)-Bn represents 2,4,5-trifluorobenzyl, (4-( t -bu))-Bn represents 4-tert-butylbenzyl, (4-( i-Pr))-Bn represents 4-isopropylbenzyl, Ph represents phenyl, (3-Br)-Ph represents 3-bromophenyl, (3-CH3)-Ph represents 3-methylphenyl, (3-OCH3)-Ph represents 3-methoxyphenyl, (4-F)-Ph represents 4-fluorophenyl, (4-Cl)-Ph represents 4-chlorophenyl, (4-CF3)-Ph represents 4-trifluoromethylphenyl, (4-CH3)-Ph represents 4-methylphenyl, 1,2,4-triazole represents triazole, (4-I)-Bn represents 4-iodobenzyl, (4-Cl)-Bn represents 4-chlorobenzyl, (4-OCH3)-Bn represents 4-methoxybenzyl, 2-methylthiophene represents thiophene-2-methyl, 2-methylfuran represents furan-2-methyl. N , N -diBu means N , N -Dibutyl, cyclopropane represents cyclopropyl, cyclobutane represents cyclobutyl, cyclopentane represents cyclopentyl, and cyclohexane represents cyclohexyl.

[0024] Example 1: Preparation of 1,3,4-oxadiazole thioether compounds containing isopropanolamine structure

[0025] Among them, R 1 Selected from Me, Et, Pr, i -Pr, Bn, (2-CF3)-Bn, (3-CF3)-Bn, (4-CF3)-Bn, (4-F)-Bn, (3,4-diF)-Bn, (2,4,5-triF)-Bn, (4-( t -bu))-Bn or (4-( i -Pr))-Bn;R 2 Selected from Ph, (3-Br)-Ph, (3-CH3)-Ph, (3-OCH3)-Ph, (4-F)-Ph, (4-Cl)-Ph, (4-CF3)-Ph, (4-CH3)-Ph, 1,2,4-triaz ole, Bn, (4-I)-Bn, (4-Cl)-Bn, (4-F)-Bn, (4-OCH3)-Bn, (4-CF3)-Bn, 2-methylthiophene, 2-methylfuran, N , N - diBu, cyclopropane, cyclobutane or cyclopentane, cyclohexane.

[0026] The specific steps are as follows: 1. Hydrazolysis reaction: Ethyl 4-hydroxybenzoate (50 mmol, 8003 mg) (1) was added to a 250 mL Shlenk reaction flask and dissolved in 120 mL of anhydrous ethanol. Then, hydrazine hydrate (250 mmol, 12515 mg) was added under ice bath conditions. The system was then evacuated to ensure that it was in dry N2. The apparatus was heated to 85 °C in an oil bath and reacted for 24 h. After the reaction was completed, the apparatus was cooled to room temperature and excess hydrazine hydrate and solvent were removed by vacuum distillation. The intermediate 4-hydroxybenzoylhydrazine (2) was obtained.

[0027] 2. Cyclization reaction: Weigh 20 mmol (3880 mg) of 4-hydroxybenzoyl hydrazine (2) and add it to a 250 mL round-bottom flask. Dissolve it in 120 mL of anhydrous ethanol and add 28 mmol (1120 mg) of sodium hydroxide solid. After the sodium hydroxide solid is completely dissolved, keep the system temperature at 0-5℃ and slowly add 40 mmol (3046 mg) of carbon disulfide to the reaction flask. The reaction temperature is 85℃ and the reaction is carried out for 12 h. After the reaction is completed, let the apparatus cool to room temperature and remove the solvent by vacuum distillation to obtain a large amount of yellow solid. Dissolve it in 150 mL of ice water and adjust the pH to 3-4. A large amount of white flocculent matter appears. After filtration, the filter cake obtained is the intermediate 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol (3). A series of intermediates 3 are shown in Table 1.

[0028] 3. Substitution reaction: Weigh 20 mmol of 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol (3) and add it to a 250 mL round-bottom flask. Add 120 mL of anhydrous... N , N Dissolve dimethylformamide (DMF), then add anhydrous triethylamine (30 mmol) dropwise, stirring for 5–10 min. Next, measure 24 mmol of haloalkanes (iodomethane, bromoethane, bromopropane, 2-iodopropane, benzyl bromide, 2-trifluoromethylbenzyl bromide, 3-trifluoromethylbenzyl bromide, 4-trifluoromethylbenzyl bromide, 4-fluorobenzyl bromide, 3,4-difluorobenzyl bromide, 2,4,5-trifluorobenzyl bromide, 4-tert-butylbenzyl bromide, and 4-isopropylbenzyl bromide) into a round-bottom flask and react for 12 h. After the reaction is complete, extract the system with ethyl acetate and wash with saturated ammonium chloride. N , N -Dimethylformamide (DMF) was then removed under reduced pressure, and purified by silica gel column chromatography with ethyl acetate-petroleum ether (V ethyl acetate:V petroleum ether = 1:3) to obtain intermediate 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted thioether (4). A series of intermediates 4 were obtained as shown in Table 1.

[0029] 4. Substitution reaction: Weigh 10 mmol of 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted sulfide (4) and add it to a 250 mL round-bottom flask. Add 10 mL of anhydrous N,N-dimethylformamide to dissolve it. Then weigh 15 mmol of potassium carbonate and add it to the flask. Stir for 5-10 min. Then measure 20 mmol of epichlorohydrin and add it to the round-bottom flask. The reaction temperature is 85℃ and the reaction is carried out for 6 h. After the reaction is completed, extract the system with ethyl acetate and wash with saturated ammonium chloride. N , N -Dimethylformamide (DMF), then the organic phase was removed under reduced pressure, purified by silica gel column chromatography, with ethyl acetate-petroleum ether as the developing solvent (V ethyl acetate:V petroleum ether = 1:4), to give intermediate 5-(4-epoxypropyl)phenyl-1,3,4-oxadiazole-2-substituted thioether (5).

[0030] 5. Epoxy ring-opening reaction: Weigh substituted amines (1.2 mmol) (cyclopropylamine, cyclobutylamine, cyclopentylamine, cyclohexylamine, aniline, 3-bromoaniline, 3-methylaniline, 3-methoxyaniline, 4-fluoroaniline, 4-chloroaniline, 4-trifluoromethylaniline, 4-methylaniline, benzylamine, 4-iodobenzylamine, 4-chlorobenzylamine, 4-fluorobenzylamine, 4-methoxybenzylamine, 4-trifluoromethylbenzylamine, 2-thiophene methylamine, 2-furan methylamine, di-n-butylamine and 1,2,4-triazole) and 5-(4-epoxypropyl)phenyl-1,3,4-oxadiazole-2-substituted sulfide (1 mmol) (5) into a 100 mL round-bottom flask, add 5 mL of isopropanol solution to dissolve completely, and react at 75℃. After the reaction was completed, the solvent was removed under reduced pressure, and the mixture was purified by silica gel column chromatography with methanol-dichloromethane (V methanol:V dichloromethane = 1:40) as the developing solvent. A series of 1,3,4-oxadiazole thioether compounds containing isopropanolamine structures were obtained, as shown in Table 2.

[0031] Table 1. Intermediates 4 and 5 of the target compound

[0032] Table 2. Compounds containing isopropanolamine structure of 1,3,4-oxadiazole sulfides

[0033] The synthetic routes and products of intermediates 4-4, 4-5, 4-6, 4-7, 4-8, 4-9, 4-10, 4-11, 4-12, and 4-13 are known routes and products.

[0034] The structural characterization data of intermediates 4-1, 4-2, 4-3, 4-4, 5-1, 5-2, 5-3, 5-4, 5-5, 5-6, 5-7, 5-8, 5-9, 5-10, 5-11, 5-12, 5-13, and the target compounds containing the isopropanolamine structure (1-38) are as follows: Intermediate 4-1: 4-(5-(isopropylthio)-1,3,4-oxadiazol-2-yl)phenol: White solid, yield: 56%. 1 H NMR (400 MHz, CDCl3- d ) δ 8.57 (s, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.9 Hz, 2H), 3.94 (hept, J = 6.8 Hz, 1H), 1.51(d, J = 6.7 Hz, 6H). 13 C NMR (101 MHz, CDCl3- d ) δ 166.07, 163.57, 160.22,128.84, 116.49, 114.89, 39.21, 23.42. HR-MS (ESI): m / z calcd for C 11 H 12 N₂O₂S([M + H]) + ) 237.0697, Found 237.0704. Intermediate 4-2: 4-(5-((3,4-difluorobenzyl)thio)-1,3,4-oxadiazol-2-yl)phenol: White solid, yield: 78%. 1 H NMR (400 MHz, DMSO- d 6) δ 10.33 (s, 1H), 7.77 (d, J = 8.7 Hz, 2H), 7.56 (ddd, J = 11.6, 7.8, 2.1 Hz, 1H), 7.39 (dt, J = 10.6, 8.4Hz, 1H), 7.35 – 7.29 (m, 1H), 6.92 (d, J= 8.8 Hz, 2H), 4.53 (s, 2H). 13 C NMR (101 MHz, DMSO-) d 6) δ 166.04, 162.26, 161.33, 151.34 – 150.09 (m), 149.17 –147.49 (m), 135.26 – 135.09 (m), 128.84, 126.47 (dd, J = 6.8, 3.4 Hz), 118.58(d, J = 17.6 Hz), 117.97 (d, J = 17.2 Hz), 116.62, 114.17, 35.22. HR-MS (ESI): m / z calcd for C 15 H 10 F2N2O2S ([M + H) + ) 321.0509, Found 321.0519. Intermediate 4-3: 4-(5-((2,4,5-trifluorobenzyl)thio)-1,3,4-oxadiazol-2-yl)phenol: White solid, yield: 49%. 1 H NMR (400 MHz, DMSO- d 6) δ 10.36 (s, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.68 (ddd, J = 11.0, 9.0, 7.0 Hz, 1H), 7.58 (td, J = 10.8, 6.7Hz, 1H), 6.94 (d, J = 8.8 Hz, 2H), 4.52 (s, 2H). 13 C NMR (101 MHz, DMSO- d 6) δ166.27, 161.73, 161.39, 145.35 – 144.68 (m), 128.83, 122.29 – 121.18 (m), 119.59 (dd, J = 20.1, 4.8 Hz), 116.61, 114.14, 106.58 (dd, J = 28.3, 21.5 Hz),29.59. HR-MS (ESI): m / z calcd for C15 H9F3N2O2S ([M + H) + ) 339.0415, Found339.0426. Intermediate 4-4: 4-(5-((4-isopropylbenzyl)thio)-1,3,4-oxadiazol-2-yl)phenol White solid, yield: 82%. 1 H NMR (400 MHz, DMSO- d 6) δ 10.34 (s, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 7.21 (d, J = 8.1 Hz, 2H), 6.94 (d, J =8.8 Hz, 2H), 4.51 (s, 2H), 2.85 (p, J = 6.8 Hz, 1H), 1.16 (d, J = 7.0 Hz, 6H). 13 CNMR (101 MHz, DMSO- d 6) δ 165.91, 162.60, 161.30, 148.45, 134.35, 129.48,128.86, 126.97, 116.64, 114.22, 36.25, 33.59, 24.25. HR-MS (ESI): m / z calcdfor C 18 H 18 N₂O₂S ([M + H)) + ) 327.1167, Found 327.1178. Intermediate 5-1: 2-(methylthio)-5-(4-(ethylene oxide-2-ylmethoxy)phenyl)-1,3,4-oxadiazole White solid, yield: 63%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.92 (d, J = 9.0 Hz, 2H), 7.00 (d, J = 9.0 Hz, 2H), 4.31 (dd, J = 11.0, 2.9 Hz, 1H), 4.02 – 3.92 (m,1H), 3.37 (ddd, J= 7.0, 5.7, 2.8 Hz, 1H), 2.97 – 2.89 (m, 1H), 2.77 (dd, J =4.9, 2.7 Hz, 1H), 2.75 (s, 3H). 13 C NMR (101 MHz, CDCl3- d ) δ 165.52, 163.69,161.04, 128.46, 116.80, 115.08, 68.91, 49.93, 44.61, 27.06, 14.78. HR-MS(ESI): m / z calcd for C 12 H 12 N₂O₃S ([M + H)) + ) 265.0647, Found 265.0655. Intermediate 5-2: 2-Ethylthio-5-(4-(ethylene oxide-2-ylmethoxy)phenyl)-1,3,4-oxadiazole White solid, yield: 71%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.91 (d, J = 9.0 Hz, 2H), 6.99 (d, J = 9.0 Hz, 2H), 4.30 (dd, J = 11.0, 2.9 Hz, 1H), 3.97 (dd, J = 11.1,5.8 Hz, 1H), 3.36 (ddd, J = 6.9, 5.7, 2.8 Hz, 1H), 3.24 (t, J = 7.2 Hz, 2H), 2.91(t, J = 4.5 Hz, 1H), 2.76 (dd, J = 4.9, 2.7 Hz, 1H), 1.85 (h, J = 7.4 Hz, 2H), 1.06(t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl3- d) δ 165.47, 163.91, 161.03,128.44, 116.79, 115.07, 68.91, 49.92, 44.59, 34.54, 22.76, 13.18. HR-MS(ESI): m / z calcd for C 13 H 14 N₂O₃S ([M + H)) + ) 279.0803, Found 279.0811. Intermediate 5-3: 2-(4-(ethylene oxide-2-ylmethoxy)phenyl)-5-propenthio-1,3,4-oxadiazole White solid, yield: 59%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.91 (d, J = 9.0 Hz, 2H), 6.99 (d, J = 9.0 Hz, 2H), 4.30 (dd, J = 11.0, 2.9 Hz, 1H), 3.97 (dd, J = 11.1,5.8 Hz, 1H), 3.36 (ddd, J = 6.9, 5.7, 2.8 Hz, 1H), 3.24 (t, J = 7.2 Hz, 2H), 2.91(t, J = 4.5 Hz, 1H), 2.76 (dd, J = 4.9, 2.7 Hz, 1H), 1.85 (h, J = 7.4 Hz, 2H), 1.06(t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, CDCl3- d ) δ 165.47, 163.91, 161.03,128.44, 116.79, 115.07, 68.91, 49.92, 44.59, 34.54, 22.76, 13.18. HR-MS(ESI): m / z calcd for C 14 H 16 N₂O₃S ([M + H)) + ) 293.0960, Found 293.0969. Intermediate 5-4: 2-(isopropylthio)-5-(4-(ethylene oxide-2-ylmethoxy)phenyl)-1,3,4-oxadiazole White solid, yield: 47%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.92 (d, J = 9.0 Hz, 2H), 6.99 (d, J = 8.9 Hz, 2H), 4.30 (dd, J = 11.0, 2.9 Hz, 1H), 4.01 – 3.86 (m,2H), 3.41 – 3.32 (m, 1H), 2.91 (t, J = 4.5 Hz, 1H), 2.76 (dd, J = 4.9, 2.6 Hz, 1H), 1.50 (d, J = 6.7 Hz, 6H). 13 C NMR (101 MHz, CDCl3- d ) δ 165.45, 163.31,161.06, 116.79, 115.08, 68.91, 49.92, 44.59, 39.09, 23.40. HR-MS (ESI): m / zcalcd for C 14 H 16 N₂O₃S ([M + H)) + ) 293.0960, Found 293.0971. Intermediate 5-5: 2-(benzylthio)-5-(4-(ethylene oxide-2-ylmethoxy)phenyl)-1,3,4-oxadiazole White solid, yield: 80%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.91 (d, J = 8.9 Hz, 2H), 7.45 (d, J = 6.6 Hz, 2H), 7.38 – 7.26 (m, 3H), 7.00 (d, J = 8.9 Hz, 2H), 4.50 (s, 2H), 4.31 (dd, J = 11.0, 2.9 Hz, 1H), 3.98 (dd, J= 11.1, 5.9 Hz, 1H), 3.37 (dq, J = 5.7, 2.8 Hz, 1H), 2.92 (t, J = 4.5 Hz, 1H), 2.77 (dd, J = 4.9, 2.7Hz, 1H). 13 C NMR (101 MHz, CDCl3- d ) δ 165.68, 161.10, 135.69, 129.16, 128.82,128.50, 128.10, 116.69, 115.10, 68.92, 49.93, 44.60, 36.88. HR-MS (ESI): m / zcalcd for C 18 H 16 N₂O₃S ([M + H)) + ) 341.0960, Found 341.0972. Intermediate 5-6: 2-(4-(ethylene oxide-2-ylmethoxy)phenyl)-5-((2-(trifluoromethyl)benzyl)thio)-1,3,4-oxadiazole White solid, yield: 67%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.92 (d, J = 9.0 Hz, 2H), 7.79 (d, J = 7.7 Hz, 1H), 7.67 (d, J = 6.6 Hz, 1H), 7.52 (t, J = 7.6 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 8.9 Hz, 2H), 4.70 (d, J = 1.1 Hz, 2H), 4.32(dd, J = 11.0, 2.9 Hz, 1H), 3.99 (dd, J = 11.0, 5.9 Hz, 1H), 3.45 – 3.31 (m, 1H), 2.93 (t, J = 4.5 Hz, 1H), 2.78 (dd, J = 4.9, 2.7 Hz, 1H). 13C NMR (101 MHz, CDCl3- d ) δ 165.92, 163.18, 161.17, 134.59 (d), 132.41 (d), 132.04, 128.80, 128.51,128.32, 126.39 (q, J = 5.6 Hz), 122.87, 116.57, 115.12, 68.92, 49.92, 44.59,33.24. HR-MS (ESI): m / z calcd for C 19 H 15 F3N2O3S ([M + H) + ) 409.0833, Found409.0845. Intermediate 5-7: 2-(4-(ethylene oxide-2-ylmethoxy)phenyl)-5-((3-(trifluoromethyl)benzyl)thio)-1,3,4-oxadiazole White solid, yield: 53%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.86 (d, J = 8.9 Hz, 3H), 7.80 (d, J = 7.3 Hz, 1H), 7.63 (d, J = 8.1 Hz, 1H), 7.57 (t, J = 7.7 Hz, 1H), 7.13 (d, J = 8.9 Hz, 2H), 4.65 (s, 2H), 4.44 (dd, J = 11.4, 2.6 Hz, 1H), 3.92(dd, J = 11.4, 6.6 Hz, 1H), 2.86 (t, J = 4.7 Hz, 1H), 2.73 (dd, J = 5.1, 2.6 Hz, 1H). 13 C NMR (101 MHz, DMSO- d 6) δ 165.72, 162.72, 161.50, 139.12, 133.64,130.08, 129.82, 129.50, 128.72, 126.13 (q, J = 3.9 Hz), 124.85 (q, J= 4.0 Hz),116.09, 115.81, 49.98, 44.20, 35.61. HR-MS (ESI): m / z calcd for C 19 H 15 F3N2O3S([M + H)) + ) 409.0833, Found 409.0845. Intermediate 5-8: 2-(4-(ethylene oxide-2-ylmethoxy)phenyl)-5-((4-(trifluoromethyl)benzyl)thio)-1,3,4-oxadiazole White solid, yield: 74%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.88 (d, J = 8.9 Hz,2H), 7.57 (s, 4H), 6.98 (d, J = 8.9 Hz, 2H), 4.50 (s, 2H), 4.34 – 4.27 (m, 1H), 3.96 (dd, J = 11.1, 5.9 Hz, 1H), 3.39 – 3.33 (m, 1H), 2.91 (d, J = 4.8 Hz, 1H), 2.76 (dd, J = 4.9, 2.6 Hz, 1H). 13 C NMR (101 MHz, CDCl3- d ) δ 165.90, 162.60,161.20, 140.11, 130.18 (d, J = 32.6 Hz), 128.48, 125.70 (q, J = 3.7 Hz), 125.32,122.62, 116.48, 115.13, 68.94, 49.91, 44.54, 36.02. HR-MS (ESI): m / z calcdfor C 19 H 15 F3N2O3S ([M + H) + ) 409.0833, Found 409.0845. Intermediate 5-9: 2-((4-fluorobenzyl)thio)-5-(4-(ethylene oxide-2-ylmethoxy)phenyl)-1,3,4-oxadiazole White solid, yield: 61%. 1H NMR (400 MHz, CDCl3- d ) δ 7.89 (d, J = 9.0 Hz, 2H), 7.42 (dd, J = 8.7, 5.2 Hz, 2H), 7.04 – 6.96 (m, 4H), 4.45 (s, 2H), 4.30(dd, J = 11.1, 2.9 Hz, 1H), 3.97 (dd, J = 11.1, 5.8 Hz, 1H), 3.36 (ddt, J = 5.6,4.2, 2.8 Hz, 1H), 2.95 – 2.85 (m, 1H), 2.76 (dd, J = 4.9, 2.7 Hz, 1H). 13 C NMR (101 MHz, CDCl3-) d ) δ 165.75, 163.67, 162.99, 161.18 (d, J = 7.1 Hz), 131.63 (d, J = 3.3 Hz), 130.92 (d, J = 8.3 Hz), 128.48, 116.59, 115.71 (d, J = 21.7 Hz),115.12, 68.93, 49.92, 44.57, 36.05. HR-MS (ESI): m / z calcd for C 18 H 15 FN2O3S ([M+ H) + ) 359.0865, Found 359.0876. Intermediate 5-10: 2-((3,4-difluorobenzyl)thio)-5-(4-(ethylene oxide-2-ylmethoxy)phenyl)-1,3,4-oxadiazole White solid, yield: 50%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.87 (d, J = 8.8 Hz, 2H), 7.56 (t, J = 8.7 Hz, 1H), 7.41 – 7.31 (m, 2H), 7.14 (d, J= 8.9 Hz, 2H), 4.55 (s, 2H), 4.44 (dd, J = 11.4, 2.7 Hz, 1H), 3.93 (dd, J = 11.4, 6.6 Hz, 1H), 2.87 (t, J = 4.7 Hz, 1H), 2.74 (dd, J = 5.1, 2.7 Hz, 1H). 13 C NMR (101 MHz, DMSO- d 6) δ 165.70, 162.74, 161.50, 150.71 (dd, J = 16.6, 12.6 Hz), 148.27 (dd, J =16.7, 12.6 Hz), 135.18 (dd, J = 5.9, 3.6 Hz), 128.72, 126.50 (dd, J = 6.7, 3.4Hz), 118.60 (d, J = 17.7 Hz), 117.99 (d, J = 17.2 Hz), 116.11, 115.82 (d, J = 3.9Hz), 69.73, 49.98, 44.21, 35.21. HR-MS (ESI): m / z calcd for C 18 H 14 F2N2O3S ([M +H) + ) 377.0771, Found 377.0782. Intermediate 5-11: 2-(4-(ethylene oxide-2-ylmethoxy)phenyl)-5-((2,4,5-trifluorobenzyl)thio)-1,3,4-oxadiazole White solid, yield: 55%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.89 (d, J = 9.0 Hz, 2H), 7.45 (ddd, J = 10.3, 8.6, 6.8 Hz, 1H), 6.99 (d, J = 9.0 Hz, 2H), 6.93 (td, J=9.6, 6.5 Hz, 1H), 4.43 (s, 2H), 4.31 (dd, J = 11.1, 2.9 Hz, 1H), 3.97 (dd, J =11.0, 5.9 Hz, 1H), 3.40 – 3.31 (m, 1H), 2.92 (t, J = 4.5 Hz, 1H), 2.76 (dd, J =4.9, 2.6 Hz, 1H). 13 C NMR (101 MHz, CDCl3- d ) δ 166.02, 162.50, 161.22, 157.25(dd, J = 9.6, 2.8 Hz), 151.22 (dd), 145.38 (d, J = 16.0 Hz), 128.50, 119.97 (dd, J = 16.9, 4.8 Hz), 119.14 (dd, J = 20.0, 4.5 Hz), 116.46, 115.14, 105.73 (dd, J =27.5, 21.1 Hz), 68.94, 49.91, 44.56, 29.15 (d, J = 2.6 Hz). HR-MS (ESI): m / zcalcd for C 18 H 13 F3N2O3S ([M + H) + ) 395.0677, Found 395.0689. Intermediate 5-12: 2-((4-tert-butylbenzyl)thio)-5-(4-(ethylene oxide-2-ylmethoxy)phenyl)-1,3,4-oxadiazole White solid, yield: 60%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.90 (d, J = 9.0 Hz, 2H), 7.36 (d, J = 1.6 Hz, 4H), 6.98 (d, J = 9.0 Hz, 2H), 5.12 – 5.00 (m, 1H), 4.63 (t, J= 8.5 Hz, 1H), 4.53 (dd, J = 8.7, 5.9 Hz, 1H), 4.47 (s, 2H), 4.31 (dd, J = 10.8, 3.7 Hz, 1H), 4.19 (dd, J = 10.7, 3.6 Hz, 1H), 1.29 (s, 9H). 13 C NMR (101 MHz, CDCl3-) d ) δ 165.43, 163.64, 160.33, 154.67, 151.20, 132.45, 128.86,128.58, 125.79, 117.38, 115.13, 74.04, 67.11, 65.91, 36.59, 34.61, 31.29. HR-MS (ESI): m / z calcd for C 22 H 24 N₂O₃S ([M + H)) + ) 397.1586, Found 397.1598. Intermediate 5-13: 2-((4-isopropylbenzyl)thio)-5-(4-(ethylene oxide-2-ylmethoxy)phenyl)-1,3,4-oxadiazole White solid, yield: 51%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.90 (d, J = 9.0 Hz, 2H), 7.36 (d, J = 8.2 Hz, 2H), 7.19 (d, J = 8.1 Hz, 2H), 6.99 (d, J = 8.9 Hz, 2H), 4.47 (s, 2H), 4.30 (dd, J = 11.0, 2.9 Hz, 1H), 3.97 (dd, J = 11.1, 5.9 Hz, 1H), 3.41 – 3.30 (m, 1H), 2.93 – 2.89 (m, 1H), 2.76 (dd, J = 4.8, 2.6 Hz, 1H), 1.22(d, J = 7.0 Hz, 6H). 13 C NMR (101 MHz, CDCl3-d ) δ 165.62, 163.37, 161.10,148.86, 132.91, 129.15, 128.48, 126.89, 116.71, 68.94, 49.93, 44.58, 36.72,33.85, 23.93. HR-MS (ESI): m / z calcd for C 21 H 22 N₂O₃S ([M + H)) + ) 383.1429, Found383.1440. Compound A1: 1-(phenylamino)-3-(4-(5-(propanethio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 47%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.94 (d, J = 9.0 Hz,2H), 7.24 – 7.15 (m, 2H), 7.01 (d, J = 8.9 Hz, 2H), 6.75 (t, J = 7.3 Hz, 1H), 6.69 (d, J = 7.6 Hz, 2H), 4.30 (s, 1H), 4.19 – 4.11 (m, 2H), 4.10 (d, J = 6.1 Hz, 1H), 3.46 (dd, J = 13.1, 4.3 Hz, 1H), 3.33 (dd, J = 13.1, 7.1 Hz, 1H), 3.26 (t, J =7.2 Hz, 2H), 1.87 (h, J = 7.3 Hz, 2H), 1.08 (t, J = 7.4 Hz, 3H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.51, 163.60, 161.97, 149.30, 129.42, 128.73, 116.26, 115.91 (d, J= 6.0 Hz), 112.64, 71.19, 67.88, 46.59, 34.47, 22.99, 13.37. HR-MS (ESI): m / z calcd for C 20 H 23 N3O3S ([M + H)) + ) 386.1538, Found 386.1520. Compound A2: 1-((3-bromophenyl)amino)-3-(4-(5-(propanethio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 65%. 1 H NMR (500 MHz, DMSO- d 6) δ 7.86 (d, J = 8.9 Hz, 2H), 7.10 (d, J = 9.0 Hz, 2H), 6.95 (t, J = 8.0 Hz, 1H), 6.75 (t, J = 2.1 Hz, 1H),6.65 – 6.54 (m, 2H), 5.98 (t, J = 6.0 Hz, 1H), 5.28 (d, J = 4.9 Hz, 1H), 4.06 (dd, J = 9.6, 4.2 Hz, 1H), 4.03 – 3.93 (m, 2H), 3.23 (t, J = 7.1 Hz, 2H), 3.13 –3.02 (m, 1H), 1.74 (h, J = 7.3 Hz, 2H), 0.96 (t, J = 7.3 Hz, 3H). 13 C NMR (126MHz, DMSO- d 6) δ 165.50, 163.60, 161.91, 151.03, 131.19, 128.74, 122.93,118.37, 115.94 (d, J = 9.8 Hz), 114.57, 111.63, 70.95, 67.76, 46.26, 34.47,22.99, 13.37. HR-MS (ESI): m / z calcd for C 20 H22 BrN3O3S ([M + H] + ) 464.0643,Found 464.0621. Compound A3: 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-((3-methylphenyl)amino)prop-2-ol: White solid, yield: 44%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.94 (d, J = 8.9 Hz, 2H), 7.08 (t, J = 8.0 Hz, 1H), 7.01 (d, J = 8.9 Hz, 2H), 6.58 (d, J = 7.5 Hz, 1H), 6.50 (d, J = 7.3 Hz, 2H), 4.29 (s, 1H), 4.19 – 4.08 (m, 2H), 4.03 (s, 1H), 3.45(dd, J = 13.1, 4.4 Hz, 1H), 3.32 (dd, J = 13.1, 7.0 Hz, 1H), 3.26 (t, J = 7.2 Hz,2H), 2.27 (s, 3H), 1.87 (h, J = 7.3 Hz, 2H), 1.08 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, DMSO-) d 6) δ 165.50, 163.59, 161.96, 149.27, 138.38, 129.27, 128.73,117.20, 115.92 (d), 113.18, 110.05, 71.14, 67.87, 46.57, 34.46, 22.99, 21.89,13.37. HR-MS (ESI): m / z calcd for C 21 H 25 N3O3S ([M + H)) + ) 400.1695, Found400.1687. Compound A4: 1-((3-methoxyphenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 48%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.93 (d, J = 8.9 Hz, 2H), 7.10 (t, J = 8.1 Hz, 1H), 7.00 (d, J = 8.9 Hz, 2H), 6.30 (td, J = 8.9, 8.9 Hz, 2H), 6.24 (t, J = 2.3 Hz, 1H), 4.29 (s, 1H), 4.20 – 4.12 (m, 1H), 4.12 – 4.01 (m, 2H), 3.77 (s, 3H), 3.44 (dd, J = 13.1, 4.3 Hz, 1H), 3.32 (t, 1H), 3.26 (t, J = 7.2 Hz, 2H), 1.87 (h, J = 7.3 Hz, 2H), 1.08 (t, J = 7.4 Hz, 3H). 13 C NMR (126MHz, DMSO- d 6) δ 165.50, 163.60, 161.97, 160.89, 150.66, 130.11, 128.73,115.91 (d, J = 6.1 Hz), 105.68, 101.90, 98.30, 71.15, 67.86, 55.12, 46.61,34.46, 22.99, 13.36. HR-MS (ESI): m / z calcd for C 21 H 25 N3O4S ([M + H)) + 416.1644, Found 416.1628. Compound A5: 1-((4-fluorophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 51%. 1H NMR (400 MHz, DMSO- d 6) δ 7.90 (d, J = 8.9 Hz, 2H), 7.15 (d, J = 8.9 Hz, 2H), 6.91 (t, J = 8.9 Hz, 2H), 6.61 (dd, J = 9.0, 4.6 Hz, 2H), 5.54 (t, J = 6.2 Hz, 1H), 5.27 (d, J = 4.8 Hz, 1H), 4.11 (dd, 1H), 4.08 –3.96 (m, 2H), 3.27 (t, J = 7.1 Hz, 2H), 3.21 (dd, J = 6.5, 5.6 Hz, 1H), 3.14 –3.02 (m, 1H), 1.78 (h, J = 7.3 Hz, 2H), 1.00 (t, J = 7.3 Hz, 3H). 13 C NMR (126MHz, DMSO- d 6) δ 165.50, 163.59, 161.95, 155.71, 153.87, 146.05, 128.72,115.89 (t), 115.66, 113.36 (d, J = 7.2 Hz), 71.16, 67.88, 47.15, 34.46, 22.98,13.35. HR-MS (ESI): m / z calcd for C 20 H 22 FN3O3S ([M + H) + 404.1444, Found404.1428. Compound A6: 1-((4-chlorophenyl)amino)-3-(4-(5-(propanethio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 49%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.89 (d, J = 8.9 Hz, 2H), 7.11 (dd, J= 27.0, 8.9 Hz, 4H), 6.63 (d, J = 8.9 Hz, 2H), 5.85 (t, J = 5.9Hz, 1H), 5.29 (d, J = 4.9 Hz, 1H), 4.16 – 4.07 (m, 1H), 4.07 – 3.91 (m, 2H), 3.27 (t, J = 7.1 Hz, 2H), 3.22 (t, J = 5.9 Hz, 1H), 3.15 – 3.02 (m, 1H), 1.78 (h, J = 7.3 Hz, 2H), 1.00 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.50,163.61, 161.94, 148.28, 129.08, 128.74, 119.37, 115.93 (d, J = 8.0 Hz), 113.94,71.07, 67.81, 46.59, 34.47, 22.99, 13.37. HR-MS (ESI): m / z calcd forC 20 H 22 ClN3O3S ([M + H)) + 420.1148, Found 420.1130. Compound A7: 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-((4-(trifluoromethyl)phenyl)amino)prop-2-ol: White solid, yield: 39%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.89 (d, J = 8.9 Hz, 2H), 7.36 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.9 Hz, 2H), 6.73 (d, J = 8.7 Hz, 2H), 6.44 (t, J = 5.9 Hz, 1H), 5.33 (d, J= 4.9 Hz, 1H), 4.15 – 4.07 (m, 1H), 4.07 –3.96 (m, 2H), 3.27 (t, J = 7.2 Hz, 2H), 3.22 – 3.12 (m, 1H), 1.78 (h, J = 7.3 Hz, 2H), 1.00 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.51, 163.68,161.88, 152.28, 128.73, 126.72 (d), 115.89 (q), 111.91, 70.88, 67.75, 45.98,34.45, 22.96, 13.31. HR-MS (ESI): m / z calcd for C 21 H 22 F3N3O3S ([M + H) + )454.1412, Found 454.1391. Compound A8: 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol: White solid, yield: 40%. 1 H NMR (500 MHz, CDCl3- d ) δ 7.91 (d, J = 8.9 Hz, 2H), 6.99 (t, J = 9.1 Hz, 4H), 6.61 (d, J = 8.4 Hz, 2H), 4.34 – 4.24 (m, 1H), 4.15 – 4.06 (m, 2H), 3.43 (dd, J = 13.0, 4.3 Hz, 1H), 3.29 (t, 1H), 3.25 (t,2H), 2.24 (s, 3H), 1.86 (h, J = 7.4 Hz, 2H), 1.07 (t, J = 7.4 Hz, 3H). 13 C NMR (126MHz, DMSO- d6) δ 165.46, 163.65, 161.66, 151.88, 145.47, 128.76, 116.18,115.90, 70.43, 67.71, 52.38, 34.47, 22.98, 13.36. HR-MS (ESI): m / z calcd forC 21 H 25 N3O3S ([M + H)) + 400.1695, Found 400.1687. Compound A9: 1-(4-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol: White solid, yield: 33%. 1 H NMR (400 MHz, CDCl3- d ) δ 8.18 (s, 1H), 7.93 (t, 3H), 6.98 (d, J = 8.9 Hz, 2H), 4.52 (dd, J = 13.0, 2.5 Hz, 1H), 4.48 – 4.34 (m,2H), 4.12 – 3.98 (m, 2H), 3.92 (s, 1H), 2.76 (s, 3H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.47, 164.44, 161.64, 151.88, 145.47, 128.75, 116.19, 115.87 (d, J =7.0 Hz), 70.39 (d, J = 13.0 Hz), 67.72, 52.38, 14.86. HR-MS (ESI): m / z calcdfor C 14 H 15 N5O3S ([M + H)) + ) 334.0974, Found 334.0964. Compound A10: 1-(4-(5-(ethylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol: White solid, yield: 35%. 1 H NMR (400 MHz, CDCl3-d ) δ 8.17 (s, 1H), 7.95 –7.88 (m, 3H), 6.98 (d, J = 8.9 Hz, 2H), 4.52 (dd, J = 13.0, 2.5 Hz, 1H), 4.47 –4.36 (m, 2H), 4.12 (d, J = 4.6 Hz, 1H), 4.05 (qd, J = 9.6, 5.1 Hz, 2H), 3.29 (q, J = 7.3 Hz, 2H), 1.50 (t, J = 7.4 Hz, 3H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.48,163.54, 161.66, 151.88, 145.47, 128.77, 116.18, 115.90, 70.44, 67.71, 52.38,27.20, 15.43. HR-MS (ESI): m / z calcd for C 15 H 17 N5O3S ([M + H)) + ) 348.1130, Found348.1120. Compound A11: 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol: White solid, yield: 48%. 1 H NMR (500 MHz, CDCl3- d ) δ 8.17 (s, 1H), 7.86 (s,2H), 7.85 (s, 1H), 6.94 (d, J = 9.0 Hz, 2H), 5.01 (d, J = 5.3 Hz, 1H), 4.49 (dd, J = 13.5, 2.9 Hz, 1H), 4.45 – 4.33 (m, 2H), 4.10 – 3.99 (m, 2H), 3.21 (t, J = 7.2Hz, 2H), 1.82 (h, J = 7.3 Hz, 2H), 1.03 (t, J= 7.3 Hz, 3H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.46, 163.65, 161.66, 151.88, 145.47, 128.76, 116.18, 115.90,70.43, 67.71, 52.38, 34.47, 22.98, 13.36. HR-MS (ESI): m / z calcd forC 16 H 19 N5O3S ([M + H)) + ) 362.1287, Found 362.1271. Compound A12: 1-(4-(5-(isopropylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol: White solid, yield: 44%. 1 H NMR (400 MHz, CDCl3- d ) δ 8.17 (s, 1H), 7.93 (d, J = 8.7 Hz, 3H), 6.98 (d, J = 9.0 Hz, 2H), 4.52 (dd, J = 13.1, 2.7 Hz, 1H), 4.48 –4.43 (m, 1H), 4.43 – 4.35 (m, 1H), 4.14 – 3.99 (m, 2H), 3.99 – 3.89 (m, 2H),1.51 (d, J = 6.8 Hz, 6H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.57, 162.76, 161.72,151.87, 145.46, 128.83, 116.16, 115.91, 70.44, 67.72, 52.38, 23.60. HR-MS(ESI): m / z calcd for C 16 H 19 N5O3S ([M + H)) + ) 362.1287, Found 362.1271. Compound A13: 1-(4-(5-(benzylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol: White solid, yield: 58%. 1 H NMR (400 MHz, CDCl3- d ) δ 8.48 (s, 1H), 7.97 (s, 1H), 7.88 (d, J = 9.0 Hz, 2H), 7.45 (d, J = 6.9 Hz, 2H), 7.32 (t, J = 7.4 Hz, 2H), 7.26 (t, J = 7.3 Hz, 2H), 7.12 (d, J = 9.0 Hz, 2H), 5.59 (d, J = 5.4 Hz, 1H), 4.55(s, 2H), 4.38 (dd, J = 13.9, 4.1 Hz, 1H), 4.29 (dd, J = 13.8, 7.5 Hz, 1H), 4.24 –4.16 (m, 1H), 4.10 – 3.97 (m, 2H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.68,163.02, 161.74, 151.88, 145.48, 137.19, 129.58, 129.12, 128.82, 128.30,116.00 (d, J = 16.0 Hz), 70.44, 67.70, 52.36, 36.45, 34.67. HR-MS (ESI): m / zcalcd for C 20 H 19 N5O3S ([M + H)) + ) 410.1287, Found 410.1265. Compound A14: 1-(benzylamino)-3-(4-(5-(propanethio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 69%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.89 (d, J= 8.9 Hz,2H), 7.38 – 7.27 (m, 4H), 7.23 (t, J = 6.8 Hz, 1H), 7.13 (d, J = 9.0 Hz, 2H),4.14 – 4.03 (m, 1H), 4.02 – 3.89 (m, 2H), 3.75 (s, 2H), 3.28 (t, J = 7.1 Hz,2H), 2.74 – 2.55 (m, 2H), 1.78 (h, J = 7.3 Hz, 2H), 1.01 (t, J = 7.4 Hz, 3H). 13 CNMR (126 MHz, CDCl3- d ) δ 165.61, 163.97, 161.38, 139.90, 128.62, 128.49,128.21, 127.29, 116.57, 115.08, 70.72, 68.29, 53.90, 51.21, 34.60, 22.83,13.29. HR-MS (ESI): m / z calcd for C 21 H 25 N3O3S ([M + H)) + ) 400.1695, Found400.1686. Compound A15: 1-((4-iodobenzyl)amino)-3-(4-(5-(propanethio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 47%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.89 (d, J = 8.9 Hz, 2H), 7.65 (d, J = 8.3 Hz, 2H), 7.13 (dd, J = 15.1, 8.6 Hz, 4H), 5.07 (s, 1H), 4.07 (d, J = 9.7 Hz, 1H), 4.01 – 3.87 (m, 2H), 3.68 (s, 2H), 3.27 (d, J = 7.2 Hz,2H), 2.71 – 2.53 (m, 2H), 1.78 (h, J= 7.3 Hz, 2H), 1.01 (t, J = 7.3 Hz, 3H). 13 CNMR (126 MHz, DMSO- d 6) δ 165.53, 163.58, 162.02, 141.32, 137.34, 130.86,128.73, 115.88 (d), 92.71, 71.50, 68.60, 52.88, 51.96, 34.47, 23.00, 13.38.HR-MS (ESI): m / z calcd for C 21 H 24 IN3O3S ([M + H)) + ) 526.0661, Found 526.0646. Compound A16: 1-((4-chlorobenzyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 76%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.89 (d, J = 9.0 Hz,2H), 7.35 (s, 4H), 7.12 (d, J = 8.9 Hz, 2H), 5.07 (d, J = 4.8 Hz, 1H), 4.16 –4.04 (m, 1H), 4.02 – 3.85 (m, 2H), 3.72 (s, 2H), 3.27 (t, J = 7.2 Hz, 2H), 2.74– 2.54 (m, 2H), 1.78 (h, J = 7.3 Hz, 2H), 1.01 (t, J = 7.3 Hz, 3H). 13 C NMR (126MHz, DMSO- d 6) δ 165.53, 163.57, 162.03, 140.51, 131.51, 130.24, 128.72,128.55, 115.87 (d), 71.51, 68.61, 52.73, 51.98, 34.47, 22.99, 13.36. HR-MS(ESI): m / z calcd for C 21H 24 ClN3O3S ([M + H)) + 434.1305, Found 434.1294. Compound A17: 1-((4-fluorobenzyl)amino)-3-(4-(5-(propanethio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 68%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.89 (d, J = 8.9 Hz, 2H), 7.36 (dd, J = 8.7, 5.7 Hz, 2H), 7.20 – 6.89 (m, 4H), 5.07 (d, J = 4.9 Hz, 1H), 4.09 (dd, J = 9.5, 3.9 Hz, 1H), 4.03 – 3.86 (m, 2H), 3.71 (s, 2H), 3.28(t, J = 7.1 Hz, 2H), 2.75 – 2.54 (m, 2H), 1.78 (h, J = 7.3 Hz, 2H), 1.01 (t, J =7.3 Hz, 3H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.52, 163.57, 162.53, 162.03,160.61, 137.59 (d), 130.23 (d, J = 7.8 Hz), 128.72, 115.87 (d), 115.36, 115.20,71.54, 68.61, 52.74, 52.01, 34.47, 22.99, 13.36. HR-MS (ESI): m / z calcd forC 21 H 24 FN3O3S ([M + H) + ) 418.1600, Found 418.1591. Compound A18: 1-((4-methoxybenzyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 72%. 1H NMR (400 MHz, DMSO- d 6) δ 7.88 (d, J = 8.9 Hz, 2H), 7.23 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 8.9 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 5.05 (d, J = 5.0 Hz, 1H), 4.16 – 4.03 (m, 1H), 4.01 – 3.83 (m, 2H), 3.72 (s, 3H), 3.64 (s, 2H), 3.26 (t, J = 7.1 Hz, 2H), 2.70 – 2.53 (m, 2H), 1.77 (h, J =7.3 Hz, 2H), 1.00 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.53,163.57, 162.04, 158.53, 133.30, 129.60, 128.71, 115.86 (d, J = 4.1 Hz), 114.01,71.61, 68.61, 55.49, 53.03, 52.03, 34.47, 22.99, 13.36. HR-MS (ESI): m / zcalcd for C 22 H 27 N3O4S ([M + H)) + ) 430.1800, Found 430.1794. Compound A19: 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-((4-(trifluoromethyl)benzyl)amino)prop-2-ol: White solid, yield: 50.8%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.88 (d, J = 8.9 Hz, 2H), 7.65 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 8.2 Hz, 2H), 7.11 (d,J = 9.0 Hz, 2H), 5.08 (d, J = 4.8 Hz, 1H), 4.09 (dd, J = 9.5, 4.0 Hz, 1H), 4.02 – 3.88 (m, 2H), 3.82 (s, 2H), 3.26 (d, J = 7.2 Hz, 2H), 2.73 – 2.54 (m, 2H), 1.78 (h, J = 7.3 Hz, 2H), 1.00 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.51, 163.56,162.02, 146.49, 129.01, 128.69, 125.43 (d, J = 4.0 Hz), 115.84 (q), 71.46,68.64, 52.95, 52.03, 34.45, 22.98, 13.33. HR-MS (ESI): m / z calcd forC 22 H 24 F3N3O3S ([M + H) + 468.1568, Found 468.1557. Compound A20: 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-((thiophen-2-ylmethyl)amino)prop-2-ol: White solid, yield: 49%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.94 (d, J = 8.9 Hz, 2H), 7.24 (d, J = 4.8 Hz, 1H), 7.02 (s, 1H), 6.99 (d, J = 4.9 Hz, 1H), 6.97 (d, J = 5.0Hz, 2H), 4.15 – 4.08 (m, 1H), 4.07 (d, J = 2.2 Hz, 3H), 4.03 (d, J = 4.6 Hz, 1H), 3.28 (t, J= 7.3 Hz, 2H), 3.02 – 2.89 (m, 1H), 2.89 – 2.78 (m, 1H), 1.88 (h, J =7.3 Hz, 3H), 1.09 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, CDCl3- d ) δ 165.59,164.00, 161.34, 143.23, 128.49, 126.87, 125.47, 124.85, 116.54, 115.08,70.65, 68.30, 50.90, 48.27, 34.59, 22.82, 13.29. HR-MS (ESI): m / z calcd forC 19 H 23 N3O3S2([M + H)) + ) 406.1259, Found 406.1250. Compound A21: 1-((furan-2-ylmethyl)amino)-3-(4-(5-(propanethio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 65%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.94 (d, J = 9.0 Hz, 2H), 7.38 (d, J = 2.8 Hz, 1H), 7.01 (d, J = 8.9 Hz, 2H), 6.39 – 6.30 (m, 1H), 6.21 (d, J = 3.2 Hz, 1H), 4.79 (s, 1H), 4.14 – 4.07 (m, 1H), 4.06 – 3.98 (m, 2H), 3.85(s, 2H), 3.27 (t, J = 7.2 Hz, 2H), 2.95 – 2.87 (m, 1H), 2.84 – 2.74 (m, 1H), 1.88 (h, J = 7.4 Hz, 3H), 1.09 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, CDCl3- d) δ165.59, 163.98, 161.33, 153.22, 142.15, 128.48, 116.54, 115.07, 110.32,107.50, 70.65, 68.23, 50.92, 46.00, 34.58, 22.81, 13.28. HR-MS (ESI): m / zcalcd for C 19 H 23 N3O4S ([M + H)) + ) 390.1487, Found 390.1475. Compound A22: 1-(dibutylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol Yellow oily liquid, yield: 48%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.89 (d, J = 8.9 Hz, 2H), 7.12 (d, J = 9.0 Hz, 2H), 4.84 (s, 1H), 4.14 – 4.04 (m, 1H), 4.03 – 3.94(m, 1H), 3.86 (s, 1H), 3.27 (t, J = 7.1 Hz, 2H), 2.67 – 2.53 (m, 1H), 2.46 –2.28 (m, 4H), 1.85 – 1.70 (m, 2H), 1.42 – 1.29 (m, 4H), 1.28 – 1.14 (m, 4H),1.00 (t, J = 7.3 Hz, 3H), 0.82 (t, J = 7.3 Hz, 6H). 13 C NMR (126 MHz, CDCl3- d ) δ165.67, 163.93, 161.55, 128.47, 116.42, 115.08, 70.67, 65.82, 56.99, 54.08,34.58, 29.33, 22.83, 20.64, 14.15, 13.27. HR-MS (ESI): m / z calcd forC 22 H 35 N3O3S ([M + H)) +) 422.2477, Found 422.2460. Compound A23: 1-(cyclopropylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol White solid, yield: 73%. 1 H NMR (500 MHz, CDCl3- d ) δ 7.89 (d, J = 9.0 Hz, 2H), 6.98 (d, J = 9.0 Hz, 2H), 4.14 – 4.06 (m, 1H), 4.05 – 3.91 (m, 2H), 3.24 (t, J =7.2 Hz, 2H), 2.95 (dd, J = 12.3, 3.7 Hz, 1H), 2.83 (dd, J = 12.3, 8.3 Hz, 1H),2.23 – 2.10 (m, 1H), 1.84 (h, J = 7.3 Hz, 2H), 1.05 (t, J = 7.4 Hz, 3H), 0.52 –0.41 (m, 2H), 0.41 – 0.26 (m, 2H). 13 C NMR (126 MHz, CDCl3- d ) δ 165.60,163.98, 161.41, 128.48, 116.51, 115.07, 70.77, 67.99, 51.79, 34.58, 30.56,22.81, 13.27, 6.52 (d, J = 78.5 Hz). HR-MS (ESI): m / z calcd for C 17 H 23 N3O3S ([M +H)) + ) 350.1538, Found 350.1528. Compound A24: 1-(cyclobutylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 41%. 1 H NMR (500 MHz, CDCl3- d ) δ 7.88 (d, J= 8.9 Hz, 2H), 6.96 (d, J = 8.9 Hz, 2H), 4.07 (td, J = 8.7, 5.2 Hz, 1H), 4.00 (dd, J = 5.2, 2.1Hz, 2H), 3.28 (q, J = 7.3 Hz, 1H), 3.23 (t, J = 7.2 Hz, 2H), 2.83 – 2.75 (m, 1H), 2.67 (dd, J = 12.2, 8.2 Hz, 1H), 2.28 – 2.15 (m, 2H), 1.84 (h, J = 7.3 Hz, 2H),1.78 – 1.67 (m, 3H), 1.67 – 1.59 (m, 1H), 1.05 (t, J = 7.4 Hz, 3H). 13 C NMR (126MHz, CDCl3- d ) δ 165.59, 163.99, 161.36, 128.48, 116.51, 115.06, 70.74, 68.13,53.99, 48.96, 34.58, 30.76 (d, J = 7.5 Hz), 22.81, 14.79, 13.27. HR-MS (ESI): m / z calcd for C 18 H 25 N3O3S ([M + H)) + ) 364.1695, Found 364.1687. Compound A25: 1-(cyclopentylamino)-3-(4-(5-(propanethio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 38%. 1 H NMR (500 MHz, CDCl3- d ) δ 7.89 (d, J = 9.0 Hz, 2H), 6.97 (d, J = 9.0 Hz, 2H), 4.11 – 4.04 (m, 1H), 4.04 – 3.96 (m, 2H), 3.24 (t, J =7.2 Hz, 2H), 3.09 (p,J = 6.7 Hz, 1H), 2.86 (dd, J = 12.0, 3.7 Hz, 1H), 2.76 –2.69 (m, 2H), 1.84 (h, J = 7.4 Hz, 4H), 1.71 – 1.62 (m, 2H), 1.58 – 1.46 (m,2H), 1.42 – 1.26 (m, 2H), 1.05 (t, J = 7.4 Hz, 3H). 13 C NMR (126 MHz, CDCl3- d ) δ165.60, 163.97, 161.40, 128.48, 116.51, 115.06, 70.84, 68.27, 59.99, 50.59,34.58, 33.18 (d, J = 21.1 Hz), 24.01 (d, J = 6.9 Hz), 22.81, 13.27. HR-MS (ESI): m / z calcd for C 19 H 27 N3O3S ([M + H)) + ) 378.1851, Found 378.1843. Compound A26: 1-(cyclohexylamino)-3-(4-(5-(propanethio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol Pale yellow solid, yield: 44%. 1 H NMR (500 MHz, CDCl3- d ) δ 7.88 (d, J = 8.9 Hz, 1H), 6.96 (d, J = 8.9 Hz, 1H), 4.07 (td, J = 8.7, 5.1 Hz, 1H), 4.03 – 3.96 (m,1H), 3.23 (t, J = 7.2 Hz, 1H), 2.92 (dd, J = 12.1, 3.6 Hz, 1H), 2.75 (dd, J = 12.1, 8.4 Hz, 1H), 2.45 (tt, J= 10.5, 3.8 Hz, 1H), 1.95 – 1.89 (m, 1H), 1.84 (h, J =7.3 Hz, 1H), 1.75 – 1.67 (m, 1H), 1.65 – 1.55 (m, 1H), 1.29 – 1.07 (m, 2H), 1.05 (t, J = 7.4 Hz, 2H). 13 C NMR (126 MHz, CDCl3- d ) δ 165.60, 163.97, 161.40,128.47, 116.48, 115.06, 70.80, 68.11, 57.02, 48.85, 34.58, 33.45 (d, J = 22.0Hz), 26.02, 25.07, 22.81, 13.27. HR-MS (ESI): m / z calcd for C 20 H 29 N3O3S ([M +H)) + ) 392.2008, Found 392.1999. Compound A27: 1-(cyclohexylamino)-3-(4-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol Yellow solid, yield: 66%, mp: 169.1-170.0 ℃ 1 H NMR (500 MHz, CDCl3- d ) δ7.92 (d, J = 9.0 Hz, 2H), 7.00 (d, J = 9.0 Hz, 2H), 4.09 – 4.04 (m, 1H), 4.04 –4.00 (m, 2H), 2.96 (dd, J = 12.2, 3.7 Hz, 1H), 2.81 – 2.77 (m, 1H), 2.76 (s,3H), 2.51 – 2.45 (m, 2H), 1.93 (d, J = 8.9 Hz, 2H), 1.78 – 1.69 (m, 2H), 1.62(d, J = 12.3 Hz, 1H), 1.40 – 1.01 (m, 6H). 13C NMR (126 MHz, CDCl3- d ) δ 165.76,164.46, 161.40, 128.49, 116.47, 115.08, 70.72, 68.04, 57.05, 48.76, 33.47,25.99, 25.05, 14.74. HR-MS (ESI): m / z calcd for C 18 H 25 N3O3S ([M + H)) + )364.1695, Found 364.1685. Compound A28: 1-(cyclohexylamino)-3-(4-(5-(ethylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 64%. 1 H NMR (400 MHz, CDCl3- d ) δ 7.92 (d, J = 8.9 Hz, 2H), 7.00 (d, J = 9.0 Hz, 2H), 4.14 – 4.06 (m, 1H), 4.06 – 3.99 (m, 2H), 3.29 (q, J =7.3 Hz, 2H), 3.08 – 2.75 (m, 2H), 2.55 – 2.44 (m, 1H), 1.95 (d, J = 9.8 Hz, 2H), 1.75 (d, J = 10.0 Hz, 2H), 1.62 (d, J = 9.5 Hz, 1H), 1.50 (t, J = 7.4 Hz, 3H), 1.23 (td, J = 27.3, 12.7 Hz, 5H). 13 C NMR (126 MHz, CDCl3- d ) δ 165.62, 163.72,161.39, 128.47, 116.48, 115.06, 70.76, 67.97, 57.10, 48.83, 33.25 (d, J = 21.5Hz), 27.11, 25.96, 25.04, 14.85. HR-MS (ESI): m / z calcd for C 19 H27 N3O3S ([M +H)) + ) 378.1851, Found 378.1842. Compound A29: 1-(cyclohexylamino)-3-(4-(5-(isopropylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol White solid, yield: 58%. 1 H NMR (500 MHz, CDCl3- d ) δ 7.92 (d, J = 9.0 Hz, 2H), 6.99 (d, J = 8.9 Hz, 2H), 4.11 – 4.05 (m, 1H), 4.03 (dd, J = 5.1, 3.1 Hz, 2H),3.93 (p, 1H), 2.97 (dd, J = 12.2, 3.7 Hz, 1H), 2.79 (dd, J = 12.2, 8.3 Hz, 1H),2.56 – 2.44 (m, 1H), 1.94 (d, J = 12.9 Hz, 2H), 1.80 – 1.70 (m, 2H), 1.67 –1.57 (m, 1H), 1.51 (d, J = 6.7 Hz, 6H), 1.33 – 1.04 (m, 5H). 13 C NMR (126 MHz, CDCl3-) d ) δ 165.59, 163.36, 161.43, 128.53, 116.56, 115.08, 70.74, 68.12,56.98, 48.75, 39.15, 33.57 (d, J = 29.2 Hz), 26.04, 25.07, 23.48. HR-MS (ESI): m / z calcd for C 20 H 29 N3O3S ([M + H)) + ) 392.2008, Found 392.1992. Compound A30: 1-(4-(5-(phenylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(cyclohexylamino)prop-2-ol: White solid, yield: 72%. 1H NMR (400 MHz, CDCl3- d ) δ 7.90 (d, J = 8.7 Hz, 2H), 7.45 (d, J = 7.3 Hz, 2H), 7.38 – 7.27 (m, 3H), 6.99 (d, J = 8.8 Hz, 2H), 4.50 (s,2H), 4.10 – 4.05 (m, 1H), 4.03 (s, 2H), 3.03 – 2.91 (m, 1H), 2.84 – 2.71 (m,1H), 2.52 – 2.46 (m, 2H), 1.93 (d, J = 12.1 Hz, 2H), 1.74 (d, J = 12.8 Hz, 2H), 1.62 (d, J = 12.1 Hz, 1H), 1.34 – 1.02 (m, 5H). 13 C NMR (126 MHz, DMSO- d 6) δ165.72, 162.95, 162.11, 137.19, 129.57, 129.11, 128.77, 128.29, 115.90,115.75, 71.62, 68.75, 56.72, 49.77, 36.44, 33.43, 26.36, 24.95. HR-MS (ESI):m / z calcd for C 24 H 29 N3O3S ([M + H)) + 440.2008, Found 440.1993. Compound A31: 1-(cyclohexylamino)-3-(4-(5-((2-(trifluoromethyl)phenyl)thio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol: White solid, yield: 56%. 1 H NMR (500 MHz, DMSO- d 6) δ 7.81 (d, J = 8.9 Hz, 2H), 7.72 (d, J = 4.0 Hz, 2H), 7.64 (t, J = 7.6 Hz, 1H), 7.50 (t, J= 7.7 Hz, 1H), 7.08 (d, J = 8.9 Hz, 2H), 4.98 (s, 1H), 4.65 (s, 2H), 4.01 (dd, J = 9.9, 4.3 Hz, 1H), 3.90 (dd, J = 9.9, 6.2 Hz, 1H), 3.80 (t, J = 6.2 Hz, 1H), 2.64 (dd, J = 11.7, 5.1Hz, 1H), 2.54 (dd, J = 11.7, 6.7 Hz, 1H), 2.35 – 2.21 (m, 1H), 1.74 (dd, J =12.8, 4.0 Hz, 2H), 1.59 (dt, J = 12.5, 3.7 Hz, 2H), 1.48 (dt, J = 12.4, 3.9 Hz, 2H), 1.23 – 0.85 (m, 5H). 13 C NMR (126 MHz, DMSO- d 6) δ 166.05, 162.28, 162.18,134.99, 132.61, 129.27, 128.81, 126.86 (q), 115.91, 115.68, 33.69, 33.20 (d), 26.32, 24.93. HR-MS (ESI): m / z calcd for C 25 H 28 F3N3O3S ([M + H) + 508.1881, Found 508.1855. Compound A32: 1-(cyclohexylamino)-3-(4-(5-((3-(trifluoromethyl)phenyl)thio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol: White solid, yield: 47%. 1 H NMR (500 MHz, DMSO- d 6) δ 7.83 (d, J = 8.9 Hz, 3H), 7.77 (d, J = 7.6 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.56 (t,J = 7.7 Hz, 1H), 7.08 (d, J = 9.0 Hz, 2H), 5.08 (s, 1H), 4.62 (s, 2H), 4.03 (dd, J = 9.9, 4.4 Hz, 1H), 3.98 – 3.89 (m, 1H), 3.89 – 3.76 (m, 1H), 2.70 (dd, J = 11.8, 4.9 Hz, 1H), 2.60(dd, J = 11.9, 6.8 Hz, 1H), 2.40 – 2.34 (m, 1H), 1.79 (d, J = 12.2 Hz, 2H), 1.72– 1.57 (m, 2H), 1.57 – 1.43 (m, 1H), 1.31 – 0.88 (m, 5H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.85, 162.68, 162.15, 139.17, 133.70, 130.11, 128.71, 126.20,124.89, 115.74 (d, J = 13.9 Hz), 71.68, 68.91, 56.72, 49.91, 35.64, 33.64,26.40, 24.96. HR-MS (ESI): m / z calcd for C 25 H 28 F3N3O3S ([M + H) + ) 508.1881,Found 508.1858. Compound A33: 1-(cyclohexylamino)-3-(4-(5-((4-(trifluoromethyl)phenylthio)-1,3,4-oxadiazol-2-yl)phenoxy))prop-2-ol: White solid, yield: 42%. 1 H NMR (500 MHz, DMSO- d 6) δ 7.82 (d, J = 8.9 Hz, 2H),7.68 (s, 4H), 7.08 (d, J = 9.0 Hz, 2H), 5.00 (s, 1H), 4.61 (s, 2H), 4.02 (dd, J=9.9, 4.3 Hz, 1H), 3.92 (dd, J = 9.9, 6.2 Hz, 1H), 3.81 (s, 1H), 2.65 (dd, J =11.7, 5.1 Hz, 1H), 2.55 (dd, J = 11.7, 6.7 Hz, 1H), 2.29 (tt, J = 10.1, 3.7 Hz, 1H), 1.76 (d, J = 10.7 Hz, 2H), 1.61 (dt, J = 12.7, 3.8 Hz, 2H), 1.50 (dt, 2H), 1.21 – 0.89 (m, 5H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.85, 162.67, 162.15,142.48, 130.39, 128.77, 125.93 (q), 115.88, 115.67, 71.67, 56.71, 49.89,35.65, 33.63, 26.41, 24.96. HR-MS (ESI): m / z calcd for C 25 H 28 F3N3O3S ([M + H) + 508.1881, Found 508.1848. Compound A34: 1-(cyclohexylamino)-3-(4-(5-((4-fluorophenyl)thio-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol: White solid, yield: 52%. 1 H NMR (500 MHz, DMSO- d 6) δ 7.87 (d, J = 8.9 Hz, 1H), 7.51 (dd, J = 8.6, 5.6 Hz, 1H), 7.16 (t, J = 8.9 Hz, 1H), 7.12 (d, J = 9.0 Hz, 1H), 4.55 (s, 1H), 4.06 (dd, J= 9.9, 4.4 Hz, 1H), 4.00 – 3.93 (m, 1H), 3.93 – 3.85(m, 1H), 2.78 – 2.70 (m, 1H), 2.63 (dd, J = 11.8, 7.0 Hz, 1H), 2.47 – 2.37 (m,1H), 1.82 (d, J = 12.3 Hz, 1H), 1.65 (dt, J = 12.6, 3.7 Hz, 1H), 1.53 (dt, J =12.4, 3.7 Hz, 1H), 1.25 – 0.97 (m, 3H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.76,163.10, 162.87, 162.13, 161.16, 133.59 (d), 131.68 (d, J = 8.4 Hz), 128.77,116.00, 115.86 (d, J = 8.1 Hz), 115.71, 71.66, 68.88, 56.71, 49.88, 35.58,33.60, 26.40, 24.97. HR-MS (ESI): m / z calcd for C 24 H 28 FN3O3S ([M + H) + 458.1913, Found 458.1887. Compound A35: 1-(cyclohexylamino)-3-(4-(5-((3,4-difluorothio-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol: White solid, yield: 67%. 1 H NMR (500 MHz, DMSO- d 6) δ 7.87 (d, J = 8.9 Hz, 2H),7.67 – 7.50 (m, 1H), 7.46 – 7.36 (m, 1H), 7.37 – 7.28 (m, 1H), 7.12 (d, J = 8.9Hz, 2H), 4.54 (s, 2H), 4.06 (dd, J = 9.9, 4.4 Hz, 1H), 3.96 (dd,J = 9.9, 6.1 Hz,1H), 3.88 (p, 1H), 2.73 (dd, J = 11.7, 4.9 Hz, 1H), 2.62 (dd, J = 11.8, 6.9 Hz, 1H), 2.37 (t, J = 12.0 Hz, 1H), 1.81 (d, J = 12.2 Hz, 2H), 1.65 (dt, J = 12.7, 3.8Hz, 2H), 1.53 (dt, 1H), 1.30 – 0.90 (m, 6H). 13 C NMR (126 MHz, DMSO- d 6) δ165.84, 162.71, 162.13, 128.78, 126.63, 118.69 (d, J = 17.5 Hz), 118.08 (d, J =17.2 Hz), 115.89, 115.71, 71.62, 68.75, 56.72, 49.76, 35.22, 26.36, 24.94.HR-MS (ESI): m / z calcd for C 24 H 27 F2N3O3S ([M + H) + 476.1819, Found 476.1793. Compound A36: 1-(cyclohexylamino)-3-(4-(5-((2,4,5-trifluorophenyl)thio-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol: White solid, yield: 61%. 1 H NMR (500 MHz, DMSO- d 6) δ 7.87 (d, J = 7.3 Hz, 2H), 7.69 (q, J = 10.2 Hz, 1H), 7.59 (q, 1H), 7.13 (d, J = 7.3 Hz, 2H), 5.03 (s, 1H), 4.53 (s, 2H), 4.06 (dd, J = 10.0, 4.2 Hz, 1H), 3.96 (dd, J= 9.9, 6.3 Hz, 1H), 3.86 (p, J = 5.8 Hz, 1H), 2.69 (dd, J = 11.6, 5.1 Hz, 1H), 2.59 (dd, J = 11.7, 6.7Hz, 1H), 2.33 (t, J = 10.2 Hz, 1H), 1.79 (d, J = 9.2 Hz, 2H), 1.64 (d, J = 13.2 Hz, 2H), 1.53 (d, J = 12.6 Hz, 1H), 1.27 – 0.92 (m, 6H). 13 C NMR (101 MHz, DMSO- d 6) δ165.99, 162.12 (d, J = 3.6 Hz), 157.45 (dd), 155.01 (dd), 150.69 (t, J = 14.2Hz), 148.08 (t, J = 13.5 Hz), 147.44 (dd, J = 13.4 Hz), 145.06 (dd), 128.69,121.53 (dt, J = 17.6 Hz), 119.64 (dd, J = 20.0, 4.9 Hz), 115.80, 115.60, 106.64(dd, J = 28.2, 21.5 Hz), 71.62, 68.83, 56.64, 49.83, 33.56, 29.57, 26.33,24.89. HR-MS (ESI): m / z calcd for C 24 H 26 F3N3O3S ([M + H) + 494.1725, Found494.1698. Compound A37: 1-(4-(5-((4-(tert-butyl)phenylthio)-1,3,4-thiadiazol-2-yl)phenoxy)-3-(cyclohexylamino)prop-2-ol: Yellowish-brown solid, yield: 66%. 1 H NMR (400 MHz, DMSO- d6) δ 7.90 (d, J = 8.8 Hz,2H), 7.37 (q, 4H), 7.15 (d, J = 8.9 Hz, 2H), 6.20 (s, 1H), 5.95 (s, 1H), 4.53(s, 2H), 4.41 (d, J = 6.3 Hz, 1H), 4.27 (s, 1H), 4.19 – 4.05 (m, 3H), 3.74 (t, J = 8.8 Hz, 1H), 3.16 (d, J = 12.4 Hz, 1H), 3.08 – 2.93 (m, 3H), 2.06 (d, 2H), 1.87 (d, 1H), 1.74 (d, 4H), 1.60 (t, J = 12.7 Hz, 2H), 1.42 – 1.28 (m, 3H), 1.25 (s, 9H), 1.21 – 1.08 (m, 6H). 13 C NMR (126 MHz, DMSO- d 6) δ 165.63, 163.16,161.65, 150.76, 134.04, 129.30, 128.80, 125.90, 116.12, 115.96, 70.57, 65.54,56.93, 47.02, 36.13, 34.80, 28.99, 28.61, 26.89, 25.32, 24.94, 24.52 (d),24.02. HR-MS (ESI): m / z calcd for C 28 H 37 N3O3S ([M + H)) + 496.2634, Found496.2614. Compound A38: 1-(cyclohexylamino)-3-(4-(5-((4-isopropylphenyl)thio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol: Yellowish-brown solid, yield: 58%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.91 (d, J = 6.7 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.21 (d,J = 6.1 Hz, 2H), 7.16 (d, J = 8.9 Hz, 2H), 5.95 (s, 1H), 4.53 (s, 2H), 4.39 (s, 2H), 4.28 (s, 1H), 4.10 (d, J = 5.2 Hz, 2H), 3.44 (q, J = 7.2 Hz, 3H), 3.17 (d, J = 12.9 Hz, 1H), 3.08 – 2.96 (m, 2H), 2.85 (p, 1H), 2.07 (d, 2H), 1.76 (d, J = 13.2 Hz, 3H), 1.60 (t, J = 13.0 Hz, 2H),1.46 – 1.20 (m, 6H), 1.17 (d, J = 6.8 Hz, 6H). 13 C NMR (126 MHz, DMSO- d 6) δ165.63, 163.14, 161.64, 148.53, 134.40, 129.57, 128.80, 127.04, 116.12,115.96, 70.57, 65.55, 56.93, 47.02, 36.25, 33.65, 29.02, 28.62, 25.32, 24.54(d, J = 5.4 Hz), 24.33. HR-MS (ESI): m / z calcd for C 27 H 35 N3O3S ([M + H)) + 482.2417, Found 482.2458. Example 2: Detection of the antibacterial activity of the target compound Rice bacterial blight pathogen ( Xanthomonas oryzae pv. oryzae ), rice bacterial leaf streak ( Xanthomonas oryzae pv. oryzicola ), Citrus canker pathogen ( Xanthomonas citri subsp. citri ) and the soft rot pathogen of Chinese cabbage ( Pectobacterium carotovorum subsp. carotovorum Four common agricultural plant pathogenic bacteria were used as experimental subjects. A broth dilution method was employed to preliminarily screen the antibacterial activity of the target compounds. 8-hydroxyquinoline copper, a commonly used commercial antibacterial agent for controlling corresponding crop diseases, was selected as a control agent.

[0035] Experimental instruments and equipment: petri dishes (Haimen Chuangxin Consumables Co., Ltd.), 24-well plates (Haimen Chuangxin Consumables Co., Ltd.), autoclave (TOMY SX-700), IS-RDS3 stacked constant temperature shaker (Suzhou Jiemei Electronics Co., Ltd.), electric thermostatic biochemical incubator (Shanghai Jinghong Experimental Equipment Co., Ltd.), eppendrof pipette, double-sided clean bench for two people (Suzhou Purification Equipment Co., Ltd.), ELISA reader, etc.

[0036] Experimental methods: (I) Preliminary screening of the antibacterial activity of 38 target compounds using the broth dilution method. Preparation of nutrient broth (NB) medium: Weigh 3g of beef extract (Beijing Aoboxing Biotechnology Co., Ltd.), 1g of yeast extract (Thermo Fisher Scientific Co., Ltd.), 5g of polypeptone (Beijing Solarbio Science & Technology Co., Ltd.), and 10g of sucrose (Sinopharm Chemical Reagent Co., Ltd.) into a beaker, add 1L of deionized water, and wait for the weighed substances to dissolve completely. Then, adjust the pH of the medium to 7.0-7.4 with 1mol / mL NaOH solution, dispense into Erlenmeyer flasks, and sterilize at 121℃ and 1 MPa for 20 min.

[0037] Preparation of Nutrient Agar (NA) medium: Weigh 3 g of beef extract, 1 g of yeast extract, 5 g of peptone, 10 g of sucrose and 16 g of agar into a beaker, add 1 L of deionized water, and wait for the weighed substances to dissolve completely. Then, adjust the pH of the medium to 7.0-7.4 with 1 mol / mL NaOH solution, dispense into Erlenmeyer flasks, and sterilize at 121℃ and 1 MPa for 20 min.

[0038] EC 50 Toxicity assay: Based on the initial screening activity test data, a concentration gradient was set, and 5 mg of the test compound was weighed, dissolved in DMSO, and then serially diluted to five concentrations (50 μg / mL, 25 μg / mL, 12.5 μg / mL, 6.25 μg / mL, and 3.125 μg / mL). The inhibition rate at each concentration was calculated, and the linear equation and EC50 were obtained using the statistical software DPS. 50 Values ​​and confidence intervals.

[0039] The drug treatment group and the blank group were set up. The treatment method and the amount of solvent added were the same as those of the drug treatment group. The specific experimental data are shown in Table 4.

[0040] Inoculation and activity assay: Preserved strain: *Bacterium tumefaciens*, the pathogen of bacterial blight in rice (… Xanthomonas oryzae pv. oryzae ), rice bacterial leaf streak ( Xanthomonas oryzae pv. oryzicola ), Citrus canker pathogen ( Xanthomonas citri subsp. citri ) and the soft rot pathogen of Chinese cabbage ( Pectobacterium carotovorum subsp. carotovorum (The above strains have been published in the following articles: Study on the mechanism of action of thiabendazole in the control of rice bacterial blight and citrus canker, Doctoral Dissertation, 2016.5; Research progress on bacterial leaf streak of rice, Journal of Nanjing Agricultural University, 2025, 48(1): 46-57; Cloning and functional analysis of gene expression induced by calla lily tissue extract in *Pectinobacter carotenoides*, Chinese Society for Plant Pathology, 2012-07-20). From -80 o Remove from the refrigerator and streak onto a pre-prepared NA plate. Incubate at 28°C in the dark until single colonies grow. Select healthy, pure, single colonies and repeat the above steps. Once the colonies on the plate have fully grown, store at 4°C. Add 1% of an OD = 1.0 bacterial suspension to a certain volume of NB medium to prepare a new bacterial suspension. Then, dilute the suspension with 1000 ml of ... μ 990 μL of the compound stock solution was transferred to a 24-well plate using a pipette of L. After transfer, 10 μL of the stock solution was transferred to three parallel wells using a 10 μL pipette, with three wells in each 24-well plate serving as blank controls (i.e., only DMSO added). Since the logarithmic growth phases of different bacteria are not entirely consistent, the culture time for different bacteria was controlled differently based on the reported growth cycle data in the literature. *Bacillus thuringiensis*, *Bacillus streak*, and *Citrus canker* were cultured for 24 h (starting from the preparation of the drug-containing culture solution), while *Bacillus thuringiensis* was cultured for 12 h. After the pre-set culture time, the wells were removed and placed in a microplate reader to measure the OD595 value of the liquid in each well. The growth inhibition rate after drug treatment was calculated using the following formula:

[0041] Where: ΔOD 空白组 The absorbance value of the blank group; ΔOD 用药组 The absorbance value is for the drug-treated group.

[0042] Table 3. Initial screening results of the antibacterial activity of the target compound [inhibition rate η (%)] (test concentration 50) μ g / mL)

[0043] Table 3 shows the antibacterial test results for common agricultural bacteria, from which the following conclusions can be drawn: 1. 1,3,4-oxadiazole thioether compounds containing isopropanolamine structure have shown certain antibacterial activity against common agricultural bacteria, with some inhibitory effects similar to those of the control drug.

[0044] 2. Overall, when the amine part is cyclohexyl, it has a better inhibitory effect on rice bacterial blight, rice bacterial leaf streak, citrus canker, and Chinese cabbage soft rot.

[0045] For compounds exhibiting inhibition rates above 80% in the initial in vitro activity screening, the EC50 of the tested pathogens was further determined using concentration gradients of 50, 25, 12.5, 6.25, and 3.125 µg / mL. 50 The values ​​obtained are calculated using the DPS data processing system, EC 50 The values ​​are shown in Table 4-7.

[0046] Table 4. Antibacterial activity of some compounds against *Bacterium tumefaciens*, the pathogen of rice bacterial blight (EC). 50 ( μ (g / mL) results

[0047] Table 5. Antibacterial activity of some compounds against *Bacterium streakum*, the pathogen causing bacterial leaf streak in rice. 50 ( μ (g / mL) results

[0048] Table 6. Antibacterial activity of some compounds against *Citrus canker* (EC) 50 ( μ (g / mL) results

[0049] Table 7. Antibacterial activity of some compounds against *Bacillus subtilis*, the pathogen causing soft rot in Chinese cabbage (EC) 50 ( μ (g / mL) results

[0050] Table 4-7 shows the test results for common agricultural bacteria, from which the following conclusions can be drawn: 1. In the thioether substituent R 1 Introducing a benzyl group at the 0.5 position is beneficial for enhancing the inhibitory activity of compounds against rice bacterial blight pathogens. For example, compound A26(R 1 = Pr, R 2 = Cyclohexane) inhibitory activity against rice bacterial blight pathogen EC 50 The value was 10.99 μg / mL, compound A30 (R 1 = Bn, R 2= Cyclohexane; anti-Xanthomonas oryzae pv.oryzae EC, resistant to rice bacterial blight. 50 Value = 4.25 μg / mL.

[0051] 2. Introducing a cyclohexyl group at the amine site is beneficial for enhancing the inhibitory activity of compounds against rice bacterial blight pathogens. For example, compound A26(R 1 = Pr; R 2 =Cyclohexane; Anti-Xanthomonas oryzae pv. oryzaeEC, resistant to rice bacterial blight. 50 Value = 10.99 μg / mL), superior to compounds A14, A20, and A22-A25 (R 1 = Pr, R 2 EC50 of Bn, 2-methylthiophene, N,N-dibutyl, cyclopropane, cyclobutene, and cyclopentane (Bn, 2-methylthiophene, N,N-dibutyl, cyclopropane, cyclobutene, cyclopentane) inhibiting the bacterial blight pathogen of rice. 50 The values ​​were 18.99, 15.77, 30.35, 49.08, 13.24, and 15.24 μg / mL, respectively.

[0052] 3. Compound A31 exhibits certain inhibitory effects against four pathogenic bacteria (rice bacterial blight pathogen, rice bacterial leaf streak pathogen, citrus canker pathogen, and Chinese cabbage soft rot pathogen) (EC). 50 The values ​​were 2.14, 1.68, 4.60, and 11.04 μg / mL, respectively.

Claims

1. A 1,3,4-oxadiazole sulfide compound containing an isopropanolamine structure, characterized in that, The structure of the compound is shown in Formula I: Among them, R 1 Selected from Me, Et, Pr, i-Pr, Bn, (2-CF3)-Bn, (3-CF3)-Bn, (4-CF3)-Bn, (4-F)-Bn, (3,4-diF)-Bn, (2,4,5-triF)-Bn, (4-(t-bu))-Bn or (4-(i-Pr))-Bn; R 2 Selected from Ph, (3-Br)-Ph, (3-CH3)-Ph, (3-OCH3)-Ph, (4-F)-Ph, (4-Cl)-Ph, (4-CF3)-Ph, (4-CH3)-Ph, 1,2,4-triazole, Bn, (4-I)-Bn, (4-Cl)-Bn, (4-F)-Bn, (4-OCH3)-Bn, (4-CF3)-Bn, thiophene-2-methyl, furan-2-methyl, thiophene-2-methyl, furan-2-methyl, N,N-dibutyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

2. The 1,3,4-oxadiazole sulfide compound containing an isopropanolamine structure according to claim 1, characterized in that, The compounds include 1-(phenylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((3-bromophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((3-bromophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((3-methoxyphenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, and 1-((4-fluorophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol. -2-yl)phenoxy)prop-2-ol, 1-((4-chlorophenyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-((4-(trifluoromethyl)phenyl)amino)prop-2-ol, 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(4-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(4-(5-( 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(4-(5-(isopropylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(4-(5-(isopropylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(4-(5-(benzylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(1H-1,2,4-triazol-1-yl)prop-2-ol, 1-(benzylamino)-3-(4-(5-(propylthio)-1,3 ... ,4-Oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((4-iodobenzyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((4-chlorobenzyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-((4-fluorobenzyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-methoxybenzyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-(5-(propylthio)-1,3,4-Oxadiazol-2-yl)phenoxy)-3-((4-(trifluoromethyl)benzyl)amino)prop-2-ol, 1-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-((thiophen-2-ylmethyl)amino)prop-2-ol, 1-((furan-2-ylmethyl)amino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(dibutylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclopropylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy) 1-(cyclohexylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(cyclopentylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(cyclohexylamino)-3-(4-(5-(propylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(cyclohexylamino)-3-(4-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(cyclohexylamino)-3-(4-(5-(ethylthio)-1,3,4-oxadiazol-2-yl) 1-(cyclohexylamino)-3-(4-(5-(isopropylthio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(4-(5-(phenylthio)-1,3,4-oxadiazol-2-yl)phenoxy)-3-(cyclohexylamino)prop-2-ol, 1-(cyclohexylamino)-3-(4-(5-((2-(trifluoromethyl)phenyl)thio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(cyclohexylamino)-3-(4-(5-((3-(trifluoromethyl)phenyl)thio)-1,3,4-oxadiazol-2-yl)phenoxy)prop-2-ol, 1-(cyclohexylamino)-3-( 4-(5-((4-(trifluoromethyl)phenylthio)-1,3,4-oxadiazol-2-yl)phenoxy))propane-2-ol, 1-(cyclohexylamino)-3-(4-(5-(((4-fluorophenyl)thio-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclohexylamino)-3-(4-(5-((3,4-difluorothio-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(cyclohexylamino)-3-(4-(5-((2,4,5-trifluorophenyl)thio-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol, 1-(4-(5-((4-(tert-butyl)phenylthio)-1,3,One or more of 4-thiadiazol-2-yl)phenoxy)-3-(cyclohexylamino)prop-2-ol or 1-(cyclohexylamino)-3-(4-(5-((4-isopropylphenyl)thio)-1,3,4-oxadiazol-2-yl)phenoxy)propane-2-ol.

3. The method for preparing the 1,3,4-oxadiazole sulfide compound containing the isopropanolamine structure as described in claim 1 or 2, characterized in that, Includes the following steps: (1) Using ethyl 4-hydroxybenzoate as a raw material, ethanol and hydrazine hydrate were added sequentially, and hydrazide was used to prepare 4-hydroxybenzoylhydrazine by hydrazide hydrolysis; (2) 4-hydroxybenzoyl hydrazide was added to ethanol, followed by sodium hydroxide and carbon disulfide. The solvent was removed by vacuum distillation, and then an appropriate amount of ice water was added to dissolve it. The pH was then adjusted to 3-4 to prepare 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol. (3) N,N-dimethylformamide was added to 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol, dissolved and stirred, and then triethylamine and haloalkanes were added to prepare the intermediate 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted thioether. (4) Dissolve 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted sulfide and potassium carbonate in N,N-dimethylformamide solution, and then add epichlorohydrin dropwise to the reactor to prepare intermediate 5-(4-epoxypropyl)phenyl-1,3,4-oxadiazole-2-substituted sulfide. (5) The intermediate 5-(4-epoxypropyl)phenyl-1,3,4-oxadiazole-2-substituted thioether was dissolved in isopropanol, the substituted amine was added, the mixture was heated and stirred, and the reaction progress was monitored by TLC. After the reaction was complete, the mixture was purified by column chromatography to prepare a series of target compounds containing isopropanolamine structure 1,3,4-oxadiazole thioether compounds.

4. The method for preparing 1,3,4-oxadiazole sulfide compounds containing an isopropanolamine structure according to claim 3, characterized in that, In step (1), the molar ratio of ethyl 4-hydroxybenzoate to hydrazine hydrate is 1:5-1:

10.

5. The method for preparing 1,3,4-oxadiazole sulfide compounds containing an isopropanolamine structure according to claim 3, characterized in that, In step (2), the molar ratio of 4-hydroxybenzoyl hydrazine to sodium hydroxide and carbon disulfide is 1:1.4:2-1:2:

4.

6. The method for preparing 1,3,4-oxadiazole sulfide compounds containing an isopropanolamine structure according to claim 3, characterized in that, In step (3), the molar ratio of 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-thiol to triethylamine and haloalkanes is 1:1.5:1.2-1:2:1.

5.

7. The method for preparing 1,3,4-oxadiazole sulfide compounds containing an isopropanolamine structure according to claim 3, characterized in that, In step (4), the molar ratio of 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted sulfide to potassium carbonate and epichlorohydrin is 1:1.5:2-1:2:

5.

8. The method for preparing 1,3,4-oxadiazole sulfide compounds containing an isopropanolamine structure according to claim 3, characterized in that, In step (5), the molar ratio of 5-(4-hydroxy)phenyl-1,3,4-oxadiazole-2-substituted thioether to substituted amine is 1:1.2-1:

3.

9. The use of the 1,3,4-oxadiazole thioether compound containing the isopropanolamine structure according to any one of claims 1 or 2 in the preparation of products that inhibit or kill pathogens.

10. The application according to claim 9, characterized in that, The pathogens include crop pathogens, including one or more of the following: Xanthomonas oryzae pv. oryzae (bacterial leaf blight of rice), Xanthomonas oryzae pv. oryzicola (bacterial leaf streak of rice), Xanthomonas citri subsp. citri (citrus canker), and Pectobacterium carotovorum subsp. carotovorum (soft rot of Chinese cabbage).

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