Compound containing amido benzoselenazole and triazole biheterocycle as well as preparation and application thereof

Abstract

The invention discloses a compound containing amido benzoselenazole and triazole biheterocycle, the compound has a structural formula shown as a formula (I), R1, R2 and R3 are respectively and independently selected from hydrogen, alkyl, halogen, nitryl, methoxyl, trifluoromethyl, trifluoromethoxyl, cyano, aryl, substituted aryl, ester group, acyl, aliphatic heterocycle and aromatic heterocycle, and n is the number of separated carbon. The compound containing the amino benzoselenazole and the triazole biheterocycle, which is disclosed by the invention, shows relatively high inhibitory activity on cancer cells, particularly human gastric cancer cells MGC803, and a new choice is provided for development and application of gastric cancer treatment medicines. The preparation method disclosed by the invention is simple to operate, mild in system, low in cost and high in yield, and has great popularization and application values.

Description

Technical Field

[0001] The invention relates to the field of biopharmaceuticals, and specifically discloses a compound containing aminobenzoselenazole and triazole biheterocycle, and the preparation and application thereof. Background Art

[0002] Selenazole heterocyclic structures containing aminobenzoselenazoles are widely present in drug molecules and natural products, and they show significant biological activities, such as antibacterial, antifungal, antiviral and antitumor. Triazole heterocyclic rings and their derivative structures have significant pharmacological and biological activities, and have attracted much attention as pharmacophores in new drug research, playing an important role in some cancer treatment drugs, such as letrozole, anastrozole and vorozole.

[0003] However, to date, compounds containing aminobenzoselenazole and triazole biheterocyclic rings and their synthesis methods have not been disclosed in the prior art. Summary of the invention

[0004] One of the purposes of the present invention is to provide a new compound, which contains an aminobenzoselenazole and a triazole bicyclic heterocyclic structure, and at the same time, the compound introduces a substituent group on the benzene ring containing the aminobenzoselenazole, and can further introduce a new substituent group on the triazole ring.

[0005] The second object of the present invention is to provide a method for preparing the above compound.

[0006] The third object of the present invention is to provide an application method of the above-mentioned compound.

[0007] To achieve one of the above purposes, the present invention first provides the following technical solution:

[0008] A compound containing an oxazole and a triazole bicyclic heterocycle, having a structural formula as shown in formula (I):

[0009] in:

[0010] R 1 Selected from: hydrogen, hydrocarbon, halogen, nitro, methoxy, trifluoromethyl, trifluoromethoxy, cyano, aryl, substituted aryl, ester, acyl, aliphatic heterocycle and aromatic heterocycle;

[0011] R 2 Selected from: hydrogen, hydrocarbon, halogen, nitro, methoxy, trifluoromethyl, trifluoromethoxy, cyano, aryl, substituted aryl, ester, acyl, aliphatic heterocycle and aromatic heterocycle;

[0012] R 3 Selected from: hydrogen, hydrocarbon, halogen, nitro, methoxy, trifluoromethyl, trifluoromethoxy, cyano, aryl, substituted aryl, ester, acyl, aliphatic heterocycle and aromatic heterocycle;

[0013] n is the number of carbon atoms.

[0014] The hydrocarbon group in the above scheme refers to a saturated or unsaturated, chain and / or cyclic organic group containing only carbon and hydrogen elements.

[0015] The substituted hydrocarbon group refers to a hydrocarbon group having a substituent on the main chain or the branched chain.

[0016] The aryl group refers to a group containing a benzene ring structure on the main chain and / or the side chain.

[0017] The substituted aryl group refers to an aryl group having a substituent on the main chain and / or the side chain.

[0018] The aromatic heterocycle refers to an aromatic group having a ring structure composed of heteroelements (elements other than carbon and hydrogen) and carbon elements on the main chain or side chain;

[0019] The aliphatic heterocycle refers to other heterocyclic compounds except aromatic heterocycles.

[0020] As shown in formula (I), the compound of the present invention has a triazole and an amino-containing benzoselenazole bicyclic heterocycle, and a substituent group is introduced on the benzene ring of the amino-containing benzoselenazole, and multiple substitutions can be achieved on the triazole ring, thereby obtaining a new amino-containing benzoselenazole-triazole derivative.

[0021] According to some specific embodiments of the present invention, in the structural formula (I):

[0022] R 1 Any one selected from H, 5-F, 6-F, 4-Cl, 5-Cl, 7-Cl, 5-Br, 6-Br, 6-NO2, 6-CF3, 6-CN, 6-COOCH3, 6-CH3 or 6-OCH3;

[0023] and / or, R 2 Selected from H, CH 3、 PhC=O, Any of the following:

[0024] and / or, R 3 Selected from 4-CH3Ph, 4-(CH3)3CPh, 4-OCH3Ph, 4-OCF3Ph, 4-CF3Ph, 4-NO2Ph,

[0025] or -C7H 15 Any of the following:

[0026] And / or, n is selected from any one of 1, 2, 3, 4 or 5.

[0027] Among them, Ph represents phenyl, and the number before the group represents the position of the substituent on the phenyl, such as 4-CH3Ph represents phenyl after the fourth position on the benzene ring is substituted by -CH3, 4-OCH3Ph represents phenyl after the fourth position on the benzene ring is substituted by -OCH3, 4-CF3Ph represents phenyl after the fourth position on the benzene ring is substituted by -CF3, and so on.

[0028] According to some specific embodiments of the present invention, the structural formula (I) is selected from any one of the following (1)-(31):

[0029] (1)R 1 =H, R 2 =H, R 3 =Ph, n=1;

[0030] (2)R 1 =5-F, R 2 =H, R 3 =Ph, n=1;

[0031] (3)R 1 =6-F, R 2 =H, R 3 =Ph, n=1;

[0032] (4)R 1 =5-Cl, R 2 =H, R 3 =Ph, n=1;

[0033] (5)R 1 =6-Cl, R 2 =H, R 3 =Ph, n=1;

[0034] (6)R 1 =4-Cl, R2=H, R 3 =Ph, n=1;

[0035] (7)R 1 =4-Br, R 2 =H, R 3 =Ph, n=1;

[0036] (8)R 1 =6-Br, R 2 =H,,R 3 =Ph, n=1;

[0037] (9)R 1 =6-NO2, R 2 =H, R 3 =Ph, n=1;

[0038] (10)R1 =6-CF3,R 2 =H,R 3 =Ph,n=1;

[0039] (11)R 1 =6-COOCH3,R 2 =H,R 3 =Ph,n=1;

[0040] (12)R 1 =6-CN,R 2 =H,R 3 =Ph,n=1;

[0041] (13)R 1 =6-CH3,R 2 =H,R 3 =Ph,n=1;

[0042] (14)R 1 =6-OCH3,R 2 =H,R 3 =Ph,n=1;

[0043] (15)R 1 =H,R 2 =CH3,R 3 =Ph,n=1;

[0044] (16)R 1 =H,R 2 =COPh,R 3 =Ph,n=1;

[0045] (17)R 1 =H, R 3 =Ph,n=1;

[0046] (18)R 1 =H,R 2 =H,R 3 =Ph,n=2;

[0047] (19)R 1 =H,R 2 =H,R 3 =Ph,n=3;

[0048] (20)R 1 =H,R 2 =H,R 3 =4-CH3Ph,n=1;

[0049] (21)R 1 =H,R 2=H, R 3 =4-(CH3)3Ph, n=1;

[0050] (22)R 1 =H, R 2 =H, R 3 =4-OCH3Ph, n=1;

[0051] (23)R 1 =H, R 2 =H, R 3 =4-OCH3Ph, n=1;

[0052] (24)R 1 =H, R 2 =H, R 3 =4-CF3Ph, n=1;

[0053] (25)R 1 =HR 2 =H, R 3 =4-NO2Ph, n=1;

[0054] (26)R 1 =H, R 2 =H, n = 1;

[0055] (27)R 1 =H, R 2 =H, R 3 =C7H 15 , n = 1;

[0056] (28)R 1 =H, R 2 =H, n = 1;

[0057] (29)R 1 =H, R 2 =H, n = 1;

[0058] (30)R 1 =H, R 2 =H, n = 1;

[0059] (31)R 1 =H, R 2 =H, n=1.

[0060] To achieve the second of the aforementioned objectives, the present invention provides the following technical solutions:

[0061] A method for preparing a compound containing aminobenzoselenazole and triazole biheterocyclic ring according to any one of the above items comprises:

[0062] The compound represented by formula (II), the compound represented by formula (III) and the compound represented by formula (IV) are subjected to a cycloaddition reaction in the presence of a catalyst to obtain a compound containing aminobenzoselenazole and triazole biheterocyclic ring;

[0063]

[0064] Among them, R 1 , R 2 , R 3 , n is selected from any of the above R 1 and / or R 2 and / or R 3 and / or n;

[0065] The molar ratio of the compound represented by formula (II), the compound represented by formula (III) and the compound represented by formula (IV) is 1:(1-5):(1-1.5), preferably 1:(1-1.2):(1-1.2).

[0066] In the above scheme, the reaction of the compound represented by formula (II) with the compound represented by formula (III) can insert an alkynyl functional group into the formed amino-containing benzoselenazole ring, thereby efficiently introducing an alkynyl group and a secondary amine group into the amino-containing benzoselenazole ring at the same time, and the alkynyl bond is effectively converted into a triazole ring through a [3+2] cyclization reaction with the compound represented by formula (IV). The whole process can be prepared by a one-pot method without the need to separate the intermediates.

[0067] Furthermore, the compound represented by formula (III) is an alkynylamine, preferably propargylamine.

[0068] According to some specific embodiments of the present invention, the preparation method comprises the following steps:

[0069] (1) reacting the compound represented by formula (II) with the compound represented by formula (III) at elevated temperature in the presence of a solvent and a catalyst to obtain a mixture containing an intermediate;

[0070] (2) Adding the compound represented by formula (IV) to the mixture, heating and reacting, thereby obtaining a compound containing aminobenzoselenazole and triazole biheterocyclic ring.

[0071] The above implementation method can be completed in two steps under the premise of a one-pot process, and the intermediate still does not need to be separated.

[0072] Furthermore, the solvent in step (1) is selected from aprotic solvents.

[0073] Furthermore, the solvent is selected from one or more of dimethylformamide (DMF), acetonitrile (CH3CN) and dimethyl sulfoxide (DMSO).

[0074] Furthermore, the reaction temperature in step (1) is 20-80°C, preferably 25-45°C; the reaction time is 0.5-5h, preferably 1-2h.

[0075] Furthermore, step (1) is performed in an air environment.

[0076] Furthermore, the reaction temperature in step (2) is 20-80°C, preferably 25-45°C; the reaction time is 0.5-5h, preferably 1-2h.

[0077] Furthermore, the catalyst in step (1) is selected from monovalent copper salts, including: monovalent copper salts of cuprous iodide and / or cuprous bromide, preferably cuprous iodide CuI.

[0078] Furthermore, the catalyst ligand is selected from nitrogen-containing organic matter.

[0079] Furthermore, the nitrogen-containing organic compound is selected from 1,10-phenanthroline and / or bipyridine, preferably 1,10-phenanthroline.

[0080] Furthermore, the amount of the catalyst used in step (1) is 5-40 mol%, preferably 10-20 mol%, of the total amount of the compound represented by formula (II) and the compound represented by formula (III).

[0081] Furthermore, the amount of the catalyst ligand used is 10-80 mol%, preferably 20-40 mol%, of the total amount of the compound represented by formula (II) and the compound represented by formula (III).

[0082] According to some specific embodiments of the present invention, the compound represented by formula (II) can be purchased or prepared by selenization.

[0083] If R 1 =H, compound (II) 1-iodo-2-isoselenocyanatobenzene can be prepared by the following preparation process:

[0084]

[0085] The specific process is as follows: add N-formyl-2-iodoaniline and dichloromethane into a reaction container, then add dichloromethane to dissolve triphosgene, add into a constant pressure dropping funnel, dropwise react at room temperature for 1-2 hours, then raise the temperature to 40-55°C, add selenium powder to continue the reaction, take out the container after the reaction is completed, then extract, wash and dry to obtain benzene 1-iodo-2-isoselenocyanate benzene.

[0086] According to some specific embodiments of the present invention, the compound represented by formula (IV) can be purchased or prepared by reacting a halogenated raw material with an azide.

[0087] If R 3 When it is phenyl, compound (IV) benzyl azide can be prepared by the following preparation process:

[0088]

[0089] The specific process is as follows: benzyl bromide and solvent acetone are added into a reaction container, and then an equal amount of NaN3 is added after stirring, and then water is added, and refluxed at 50-70°C. After the reaction is completed, the solvent is dried, and water is added, and the aqueous phase is extracted with chloroform. The chloroform is dried to obtain benzyl azide.

[0090] To achieve the third of the aforementioned objectives, the present invention provides the following technical solutions:

[0091] The above-mentioned compound containing aminobenzoselenazole and triazole biheterocyclic ring or the compound containing aminobenzoselenazole and triazole biheterocyclic ring prepared according to any of the above-mentioned preparation methods is applied to the production of gastric cancer therapeutic drugs.

[0092] Furthermore, the gastric cancer therapeutic drug is a therapeutic drug that inhibits gastric cancer cells.

[0093] Furthermore, the gastric cancer cell is MGC803.

[0094] The present invention has the following beneficial effects:

[0095] (1) The present invention obtains a new benzoselenazole-triazole compound containing a secondary amine group;

[0096] (2) The preparation method of the present invention can be realized by a one-pot process without the need to separate intermediates, and the product yield can reach 55-90%, which is economical and efficient;

[0097] (3) The compounds of the present invention exhibit high inhibitory activity against human gastric cancer cell MGC803, and provide an important opportunity for the discovery of amino-containing benzoselenazole-triazole lead compounds for the treatment of gastric cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0098] Figure 1 This is a unit structure diagram of the product of Example 13 obtained by X-ray single crystal diffraction. DETAILED DESCRIPTION

[0099] The present invention is described in detail below in conjunction with the embodiments and drawings, but it should be understood that the embodiments and drawings are only used to exemplify the present invention and do not constitute any limitation on the protection scope of the present invention. All reasonable changes and combinations within the scope of the inventive concept of the present invention fall within the protection scope of the present invention.

[0100] The following examples are prepared by the following preparation process:

[0101] 1-iodo-2-isoselenocyanatobenzene (II) and alkynylamine (III) are used as substrates, 10-20 mol% of a divalent copper salt catalyst such as Cu(OTf)2 is used as a catalyst, 20-40 mol% of a nitrogen-containing organic matter is used as a ligand of the catalyst such as 1,10-o-phenanthroline, and an aprotic solvent such as acetonitrile is used as a solvent. The reaction is carried out in an air environment at a reaction temperature of 25-45° C. After reacting for 1-2 hours, an azide (IV) is added, and the reaction is carried out at 25-45° C. for 1-2 hours to obtain a product (I) through a cycloaddition process;

[0102]

[0103] Example 1

[0104] R was prepared by the following process 1 =H, R 2 =H, R 3 =Ph, bicyclic heterocyclic compounds with n=1:

[0105] (1) Add 10 mmol of N-(2-iodophenyl)formamide and 25-30 mL of dichloromethane to a 100 mL reaction bottle, then add 5 mmol of triphosgene and 20-35 mL of dichloromethane to a constant pressure dropping funnel, place the reaction bottle in a 25°C water bath, slowly drip the triphosgene solution into the reaction bottle, react for 1-1.5 hours, connect a spherical condenser, heat to 45°C and react for 6-9 hours, then add selenium powder and react overnight. Then take out the reaction bottle and stir at room temperature to room temperature. After the reaction is completed, filter, then rinse with ethyl acetate (2×20 mL), and spin dry at low pressure to obtain the product 2-iodo-1-isoselenocyanobenzene;

[0106] (2) Add 0.5 mmol of benzyl bromide and 20 mL of acetone to a 100 mL round-bottom flask, stir at room temperature, add 0.5 mmol of NaN3, then add 10 mL of water, and reflux the reaction at 60°C overnight for 10-14 h (TLC monitoring). After cooling to room temperature, spin dry the solvent, then add 30 mL of water, extract the aqueous phase with chloroform (3×30 mL), combine the organic phases, dry with anhydrous Na2SO4, and then spin dry the chloroform to obtain the product benzyl azide without further purification;

[0107] (3) 0.5 mmol of 2-iodo-1-isoselenocyanobenzene, 0.5 mmol of propargylamine, 0.5 mmol of benzyl azide, 0.05 mmol of copper trifluoromethanesulfonate (0.1 equiv) and 0.1 mmol of 1,10-phenanthroline were added to a reaction tube in sequence, and 4.0 mL of acetonitrile as a solvent was placed in a water bath at 25° C. in air for 2-4 hours. After the reaction was completed, the solvent acetonitrile was removed under reduced pressure, and the product N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)benzo[d][1,3]selenazol-2-amine (A) was separated by column chromatography as a white solid with a yield of 91%;

[0108]

[0109] The obtained product was a white solid, and its melting point was measured by a SGW X-4 digital melting point instrument to be 155.3-156.7.

[0110] The product A was subjected to NMR ( 1 H NMR and 13 C NMR) characterization, the results are as follows:

[0111] 1 H NMR(400MHz,DMSO)δ8.47(s,1H),8.14(s,1H),7.77–7.65(m,1H),7.48–7.27(m,6H),7 .25–7.18(m,1H),6.96(td,J=7.7,1.0Hz,1H),5.60(s,2H),4.65(d,J=4.4Hz,2H)ppm; 13 C NMR (100MHz, DMSO) δ166.0,154.6,144.9,136.6,133.7,129.2,128.6,128.4,126.2,124.9,123.8,121.6,119.8,53.2,39.9ppm.

[0112] The product A was characterized by high-resolution mass spectrometry, and the results were as follows:

[0113] HRMS(ESI)m / z:[M+H] + Calculate for C 17 H 16 N5Se 370.0565; found 370.0567.

[0114] according to 1 HNMR, 13 Comparison of C NMR and high-resolution mass spectrometry data revealed that the product had the structural formula shown in Formula A.

[0115] (29)R 1 =H, R 2 =H, n = 1;

[0116] (30)R 1 =H, R 2 =H, n = 1;

[0117] (31)R 1 =H, R 2 =H, n=1.

[0118] Example 2-31

[0119] Referring to the specific process of Example 1, the target products (I) of Examples 2-31 can be prepared respectively through the aforementioned preparation process as shown in Table 1 below:

[0120] Table 1 Target product (I) of Example 2-31

[0121]

[0122]

[0123] The product can be verified by nuclear magnetic resonance and high-resolution mass spectrometry to have a structure as shown in formula (I), and the yield of the obtained product is between 55-91%.

[0124] Taking the product of Example 13 as an example, it is a light yellow solid, and its melting point is 158.3-160.1 as measured by a SGW X-4 digital melting point instrument.

[0125] The results of NMR characterization are:

[0126] 1 H NMR (500MHz, CDCl3) δ7.51 (s, 1H), 7.45–7.31 (m, 5H), 7.25–7.23 (m, 3H), 7.08 (d, J = 7.6Hz, 1H), 5.47 (s, 2H), 4.72 (s, 2H), 2.36 (s, 3H) ppm; 13 C NMR (125MHz, CDCl3) δ166.0,151.3,144.9,134.5,133.4,131.9,129.2,128.8,128.1,127.3,124.3,122.2,119.8,54.3,41.0,21.1ppm

[0127] The high-resolution mass spectrometry characterization results are:

[0128] HRMS(ESI)m / z:[M+H] + Calculate for C 18 H 18 N5Se 384.0722; found 384.0726.

[0129] according to 1 HNMR, 13 By comparing the data of C NMR and high-resolution mass spectrometry, its structural formula is determined as follows:

[0130]

[0131] The product was further characterized by X-ray single crystal diffraction, and the results showed that the product had Figure 1 The unit structure diagram shown in the figure confirms that it has the above structure. The characterization results are shown in Table 2:

[0132] Table 2

[0133]

[0134] Example 21 The product was subjected to tumor inhibition test:

[0135] MGC-803 (human gastric cancer cells), T24 (human bladder cancer cells), HepG-2 (liver cancer cells), and A549 (human non-small cell lung cancer cells) were cultured in DMEM medium containing 10% fetal bovine serum and 1% double antibody in a CO2 incubator at 37°C, 5% CO2, and 95% air. Cells in the logarithmic growth phase were washed 3 times with PBS, and then digested with 0.25% trypsin and 10% serum culture medium were used to terminate the digestion of cells. The cells were suspended in a culture medium containing 10% serum, and the cells were gently blown to make a single cell suspension. By counting the cells, an appropriate amount of the cell suspension was taken and diluted with 10% culture medium, and inoculated into a 96-well plate, 180 μL per well, and the number of cells per well was 2×10 4 -4×10 4 . Add the sample to be tested to a 96-well plate with different tumor cells, 20 μL per well, so that the final concentration of the drug is 20 μM, for preliminary screening. After the preliminary screening, select the samples with better effects and select different concentration gradients for screening, and calculate the IC 50, each group has 9 replicate wells. 20μL of culture medium containing 10% DMSO was added to each well of the control group and cultured for 48 hours. After 48 hours of MTT drug action, 10μL of 5mg / mL MTT solution was added to each well and cultured in a CO2 incubator for another 4 hours. Carefully discard the culture medium in the wells, and add 100μL DMSO to each well, shake on a shaker for 10 minutes to completely dissolve the formazan crystals. Then use an enzyme reader (490nm) to measure the absorbance value of each well. The inhibition rate of each sample on tumor cells was calculated according to the following formula: Inhibition rate (%) = 1-A 样品 / A 对照 ×100%. The dose-response curve can be obtained by plotting the tumor cell growth inhibition rate at different concentrations of the same sample, and the half-maximal inhibitory concentration IC of the sample can be calculated according to the linear regression equation. 50 , and the results shown in Table 3 are obtained (the average + positive and negative standard deviation of each data is taken):

[0136] Table 3 IC values ​​of different samples for different cancer cells 50 value

[0137]

[0138] From the biological activity test data in Table 3, it can be seen that the compounds obtained in Examples 9, 15, 17 and 19 of the present invention all exhibited high inhibitory activity against human gastric cancer cell MGC803, and the same test conducted on the compounds in other Examples showed that they also had similar anti-tumor effects. Therefore, the compounds obtained in Examples 1-31 can all be used in the preparation of cancer therapeutic drugs.

[0139] The above embodiments are only preferred implementations of the present invention, and the protection scope of the present invention is not limited to the above embodiments. All technical solutions under the concept of the present invention belong to the protection scope of the present invention. It should be pointed out that for ordinary technicians in this technical field, improvements and modifications without departing from the principle of the present invention should also be regarded as the protection scope of the present invention.

Claims

1. A compound containing an aminobenzoselenazole and a triazole bicyclic heterocycle, which has a structural formula as shown in formula (I): in: R 1 Selected from: hydrogen, hydrocarbon, halogen, nitro, methoxy, trifluoromethyl, trifluoromethoxy, cyano, aryl, substituted aryl, ester, acyl, aliphatic heterocycle and aromatic heterocycle; R 2 Selected from: hydrogen, hydrocarbon, halogen, nitro, methoxy, trifluoromethyl, trifluoromethoxy, cyano, aryl, substituted aryl, ester, acyl, aliphatic heterocycle and aromatic heterocycle; R 3 Selected from: hydrogen, hydrocarbon, halogen, nitro, methoxy, trifluoromethyl, trifluoromethoxy, cyano, aryl, substituted aryl, ester, acyl, aliphatic heterocycle and aromatic heterocycle; n is the number of carbon atoms.

2. The compound according to claim 1, wherein: The R 1 Selected from: any one of H, 5-F, 6-F, 4-Cl, 5-Cl, 7-Cl, 5-Br, 6-Br, 6-NO2, 6-CF3, 6-CN, 6-COOCH3, 6-CH3 or 6-OCH3; and / or, R 2 Selected from: H, CH3, PhC=O, Any of the following: and / or, R 3 Selected from: 4-MePh, 4-(CH3)3CPh, 4-OCH3Ph, 4-OCF3Ph, 4-CF3Ph, 4-NO2Ph, or -C7H 15 Any of the following: And / or, n is selected from any one of 1, 2, 3, 4, and 5.

3. The compound according to claim 1 or 2, wherein: The structural formula (I) is selected from any one of the following (1)-(31): (1)R 1 =H,R 2 =H,R 3 =Ph,n=1; (2)R 1 =5-F,R 2 =H,R 3 =Ph,n=1; (3)R 1 =6-F,R 2 =H,R 3 =Ph,n=1; (4)R 1 =5-Cl,R 2 =H,R 3 =Ph,n=1; (5)R 1 =6-Cl,R 2 =H,R 3 =Ph,n=1; (6)R 1 =4-Cl,R2=H,R 3 =Ph,n=1; (7)R 1 =4-Br,R 2 =H,R 3 =Ph,n=1; (8)R 1 =6-Br,R 2 =H,,R 3 =Ph,n=1; (9)R 1 =6-NO2,R 2 =H,R 3 =Ph,n=1; (10)R 1 =6-CF3,R 2 =H,R 3 =Ph,n=1; (11)R 1 =6-COOCH3,R 2 =H,R 3 =Ph,n=1; (12)R 1 =6-CN,R 2 =H,R 3 =Ph,n=1; (13)R 1 =6-CH3,R 2 =H,R 3 =Ph,n=1; (14)R 1 =6-OCH3,R 2 =H,R 3 =Ph,n=1; (15)R 1 =H,R 2 =CH3,R 3 =Ph,n=1; (16)R 1 =H,R 2 =COPh,R 3 =Ph,n=1; (17)R 1 =H, R 3 =Ph,n=1; (18)R 1 =H,R 2 =H,R 3 =Ph,n=2; (19)R 1 =H,R 2 =H,R 3 =Ph,n=3; (20)R 1 =H,R 2 =H,R 3 =4-CH3Ph,n=1; (21)R 1 =H,R 2 =H,R 3 =4-(CH3)3Ph,n=1; (22)R 1 =H, R 2 =H, R 3 =4-OCH3Ph, n=1; (23)R 1 =H,R 2 =H,R 3 =4-OCF3Ph,n=1; (24)R 1 =H,R 2 =H,R 3 =4-CF3Ph,n=1; (25)R 1 =H,R 2 =H,R 3 =4-NO2Ph,n=1; (26)R 1 =H,R 2 =H, n=1; (27)R 1 =H,R 2 =H,R 3 =C7H 15 ,n=1; (28)R 1 =H,R 2 =H, n=1;(29)R 1 =H,R 2 =H, n=1; (30)R 1 =H,R 2 =H, n=1; (31)R 1 =H,R 2 =H, n=1。 4. A method for preparing a compound containing aminobenzoselenazole and triazole biheterocyclic ring according to any one of claims 1 to 3, comprising: The compound represented by formula (II), the compound represented by formula (III) and the compound represented by formula (IV) are subjected to a cycloaddition reaction in the presence of a catalyst to obtain a compound containing aminobenzoselenazole and triazole biheterocyclic ring; Among them, R 1 , R 2 , R 3 , n is selected from R in any one of claims 1 to 3 1 and / or R 2 and / or R 3 and / or n; The molar ratio of the compound represented by formula (II), the compound represented by formula (III) and the compound represented by formula (IV) is 1:(1-5):(1-1.5).

5. The preparation method according to claim 4, comprising: (1) reacting the compound represented by formula (II) with the compound represented by formula (III) at elevated temperature in the presence of a solvent and a catalyst to obtain a mixture containing an intermediate; (2) Adding a compound represented by formula (IV) to the mixture containing the intermediate, and reacting after heating to obtain a compound containing aminobenzoselenazole and triazole biheterocyclic ring.

6. The preparation method according to claim 5, wherein: The solvent in step (1) is selected from aprotic solvents; The catalyst is selected from copper salts; The amount of the catalyst used is 5-40 mol% of the total amount of the compound represented by formula (II) and the compound represented by formula (III); The reaction temperature is 20-80°C, and the reaction time is 0.5-5h.

7. The preparation method according to claim 6, wherein: The solvent is selected from: one or more of dimethylformamide, acetonitrile and dimethyl sulfoxide; The copper salt is selected from: monovalent or divalent copper salts of copper trifluoromethanesulfonate and / or cuprous iodide; The amount of the catalyst used is 10-20 mol% of the total amount of the compound represented by formula (II) and the compound represented by formula (III). The reaction temperature is 25-45°C, and the reaction time is 1-2h.

8. The preparation method according to claim 5, wherein: The reaction temperature of step (2) is 20-80°C, preferably 25-45°C, and / or the reaction time of step (2) is 0.5-5h, preferably 1-2h.

9. The preparation method according to claim 5, wherein: The catalyst ligand is selected from nitrogen-containing organic substances, including: 1,10-phenanthroline and / or bipyridine; The amount of the catalyst ligand used is 10-80 mol% of the total amount of the compound represented by formula (II) and the compound represented by formula (III).

10. Use of a compound containing aminobenzoselenazole and a triazole biheterocyclic ring according to any one of claims 1 to 3 or a compound containing aminobenzoselenazole and a triazole biheterocyclic ring prepared according to any one of claims 4 to 9 in the preparation of a gastric cancer drug.

Images