5-substituted-3-(arylaminoethyl) benzoxazolone compound as well as preparation method and application thereof

Abstract

The invention discloses a 5-substituted-3-(arylaminoethyl) benzoxazolone compound and a preparation method and application thereof.The compound takes CO2 as a carbonyl source, the preparation method is simple, raw materials are easy to obtain, and the compound has a good anti-cancer effect on the activity of cancer cells and particularly has a remarkable anti-cancer effect on the cancer cells such as HCCLM3 (human hepatoma carcinoma cells) and MCF-7 (human breast cancer cells).

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical drugs. Specifically, it relates to a 5-substituted-3-(arylaminoethyl)benzoxazolone compound, a preparation method thereof, and uses thereof. Background Art

[0002] Most heterocyclic compounds have very broad biological activities, among which heterocyclic compounds containing nitrogen and oxygen elements are particularly important. For example, benzoxazolone compounds contain nitrogen and oxygen heteroatoms and are generally considered important skeletons for drug discovery, showing excellent biological activities such as anti-tumor, anti-inflammatory, and bactericidal activities. They are widely used in the pharmaceutical field and have good research value and application prospects. For example, in 2000, Han Baolai et al. reported that 5-chloro-2-benzoxazolone (chlorzoxazone) can be used as a central relaxant, capable of treating pain caused by various sprains, contusions, etc., as well as diseases such as chronic fasciitis. In 2007, Ceccarelli et al. reported that 7-amidobenzoxazolone compounds can be used as highly efficient and stable mGlu5 receptor antagonists, showing good pharmacokinetic properties and efficacy in in vivo anxiety models. In 2013, Fukaya et al. reported that 3-amidobenzoxazolone derivatives can be used as effective and highly selective TSPO ligands, having an oral anti-anxiety effect and high affinity for human translocator protein (TSPO) (Ki = 8.0 nM). In 2020, Tang et al. reported a series of disubstituted benzoxazolone derivatives with in vitro nitric oxide synthase (iNOS) inhibitory activity, having anti-inflammatory activity and being able to treat LPS-induced acute lung injury.

[0003] Currently, the synthesis cost of benzoxazolone compounds in the publicly available materials is generally high, which poses a great resistance to the popular application of drugs. From the perspectives of economy, greenness, and environmental protection, we designed and synthesized 5-substituted-3-(arylaminoethyl)benzoxazolone compounds by using easily available carbon dioxide as a carbonyl source, and studied the anti-cancer activities of these compounds to reduce the high cost problem of existing benzoxazolone compounds. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and provide a 5-substituted-3-(arylaminoethyl)benzoxazolone compound, a preparation method thereof, and uses thereof. This compound uses CO2 as a carbonyl source, the preparation method is simple, the raw materials are easily available, and at the same time it has good anti-cancer activity against cancer cells, especially significant anti-cancer activity effects against cancer cells such as HCCLM3 and MCF-7.

[0005] To solve the above technical problems, the basic concept of the technical solution adopted by the present invention is:

[0006] On the one hand, the present invention provides a 5-substituted-3-(arylaminoethyl)benzoxazolone compound, which is a compound having the general structural formula (V).

[0007]

[0008] In formula (V), R 1 is hydrogen, C1-C2 alkyl, C1-C2 alkoxy or halogen; R 2 is hydrogen or alkyl;

[0009] Preferably, R 1 is H, 4-CH3O, 4-Cl, 3-CH3 or 3-CH3O; R 2 is H or CH3.

[0010] Preferably, the 5-substituted-3-(arylaminoethyl)benzoxazolone compound having the general structural formula (V) is specifically selected from one or more of the following compounds:

[0011] 3-((phenylamino)ethyl)benzoxazolone:

[0012]

[0013] 3-((4-methoxyphenylamino)ethyl)benzoxazolone:

[0014]

[0015] 3-((4-chlorophenylamino)ethyl)benzoxazolone:

[0016]

[0017] 3-((3-methylphenylamino)ethyl)benzoxazolone:

[0018]

[0019] 3-((3-methoxyphenylamino)ethyl)benzoxazolone:

[0020]

[0021] 5-methyl-3-((4-chlorophenylamino)ethyl)benzoxazolone:

[0022]

[0023] 5-methyl-3-((3-methylphenylamino)ethyl)benzoxazolone:

[0024]

[0025] 5-Methyl-3-((3-methoxyphenylamino)ethyl)benzoxazolone:

[0026]

[0027] On the other hand, the present invention provides a method for synthesizing 5-substituted-3-(arylaminoethyl)benzoxazolone compounds with the structural general formula (IV), and the method specifically comprises the following steps:

[0028] S1) An N-aryl-2-bromoacetamide with the structural formula (I) and a 2-aminophenol compound with the structural formula (II) are subjected to an alkylation reaction under the condition of a base to obtain an N-aryl-2-((2-hydroxyphenyl)amino)acetamide compound with the structural formula (III); finally, the N-aryl-2-((2-hydroxyphenyl)amino)acetamide compound with the structural formula (III) is reduced under the action of a reducing agent lithium aluminum hydride to obtain a 2-((2-(arylamino)ethyl)amino)phenol compound with the structural formula (IV):

[0029]

[0030] S2) A 2-((2-(arylamino)ethyl)amino)phenol compound with the structural formula (V) is reacted with a mixed system of an organic solvent of an alkali and CO2 under the action of phenyl chloroformate to obtain a 5-substituted-3-(arylaminoethyl)benzoxazolone compound with the structural general formula (V):

[0031]

[0032] In the formula, R 1 is hydrogen, C1-C2 alkyl, C1-C2 alkoxy or halogen; R 2 is hydrogen or alkyl.

[0033] Preferably, R 1 is H, 4-CH3O, 4-Cl, 3-CH3 or 3-CH3O; R 2 is H or CH3.

[0034] Preferably, step S1) is specifically as follows: N-aryl-2-bromoacetamide with the structural formula (I) and 2-aminophenol compounds with the structural formula (II) are alkylated with K2CO3 as the base and tetrahydrofuran and N,N-dimethylformamide as solvents to obtain N-aryl-2-((2-hydroxyphenyl)amino)acetamide compounds with the structural formula (III). Finally, the N-aryl-2-((2-hydroxyphenyl)amino)acetamide compounds with the structural formula (III) are reduced with lithium aluminum hydride (LiAlH4) in a tetrahydrofuran solvent to obtain 2-((2-(arylamino)ethyl)amino)phenol compounds with the structural formula (IV).

[0035] In the present invention, in step S1): The molar ratio of N-aryl-2-bromoacetamide having the general structural formula (I), 2-aminophenol compounds with the structural formula (II), and K2CO3 added to the reaction is 1:1 - 1.5:1 - 2, preferably 1:1.2:1.5. The molar ratio of N-aryl-2-((2-hydroxyphenyl)amino)acetamide compounds with the structural formula (III) to the reducing agent lithium aluminum hydride (LiAlH4) added to the reaction is 1:1 - 5, preferably 1:3. The reaction temperature is 30 to 80 °C, preferably 50 to 60 °C. The reaction time is 2 - 24 h, preferably 2 - 5 h.

[0036] Preferably, step S2) is specifically as follows: 2-((2-(arylamino)ethyl)amino)phenol compounds with the structural formula (IV) are added to an organic solvent, then a base is added, CO2 gas is introduced and stirred in the system for a certain time, and finally phenyl chloroformate is added to the mixed system for reaction and separation to obtain 5-substituted-3-(arylaminoethyl)benzoxazolone compounds with the general structural formula (V).

[0037] Preferably, the base is triethylamine, triethylenediamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, or 4-dimethylaminopyridine, preferably 4-dimethylaminopyridine.

[0038] Preferably, the organic solvent is dichloromethane, N,N-dimethylformamide, toluene, dimethyl sulfoxide, or acetonitrile, preferably acetonitrile.

[0039] In the present invention, in step S2): The molar ratio of 2-((2-(arylamino)ethyl)amino)phenol compounds with the general structural formula (IV) to 4-dimethylaminopyridine and phenyl chloroformate is 1:1.0 - 2.0:1.0 - 2.0, preferably 1:1.5 - 2.0:1.5 - 2.0, more preferably 1:1.9 - 2.0:1.8 - 2.0.

[0040] Preferably, the temperature selected for the entire reaction process is 15 - 55°C, more preferably 20 - 25°C, such as 21°C, 23°C, 25°C.

[0041] Preferably, the reaction time after adding phenyl chloroformate to the reaction system is 10 - 60 min, more preferably 30 - 40 min, such as 30 min, 35 min, 40 min.

[0042] In the present invention, the separation is filtration, suction filtration or extraction; preferably, extraction separation is carried out using brine.

[0043] Preferably, the present invention further includes drying the extracted organic phase, preferably drying with anhydrous Na2SO4.

[0044] Preferably, the present invention further includes a desolvation process for the dried product, preferably by vacuum desolvation.

[0045] Preferably, step S2) is specifically as follows: Dissolve the 2 - ((2 - (arylamino)ethyl)amino)phenol compound with the general structural formula (IV) in acetonitrile at room temperature, add 4 - dimethylaminopyridine, continuously introduce CO2 gas into the mixed system, and finally add phenyl chloroformate and react for 30 minutes to obtain the 5 - substituted - 3 - (arylaminoethyl)benzoxazolone compound with the general structural formula (V). After the reaction is completed, quench with saturated brine, and extract the aqueous phase with ethyl acetate. Combine the organic phases, dry with anhydrous Na2SO4, and carry out vacuum desolvation. The product is obtained through a chromatography column.

[0046] On the other hand, the present invention provides the use of a 5 - substituted - 3 - (arylaminoethyl)benzoxazolone compound with the general structural formula (V) or a 5 - substituted - 3 - (arylaminoethyl)benzoxazolone compound prepared by the above method, and uses the 5 - substituted - 3 - (arylaminoethyl)benzoxazolone compound with the general structural formula (V) to prepare anticancer drugs; specifically used to prepare drugs against one or more of cancer cells such as HCCLM3 and MCF - 7.

[0047] Preferably, the 5 - substituted - 3 - (arylaminoethyl)benzoxazolone compound with the general structural formula (V) is used to prepare drugs against HCCLM3 and MCF - 7 cancer cells.

[0048] After adopting the above technical solutions, the present invention has the following beneficial effects compared with the prior art.

[0049] The present invention provides a method using CO2 as a carbonyl source for preparing a 5-substituted-3-(arylaminoethyl)benzoxazolone compound for anti-cancer in medicine. The preparation method of this compound is simple, and the raw materials are easily available. At the same time, it has good anti-cancer activity against cancer cells, especially significant anti-cancer effects on cancer cells such as HCCLM3 (human liver cancer cells) and MCF-7 (human breast cancer cells).

[0050] The following further describes in detail the specific embodiments of the present invention with reference to the accompanying drawings. Description of the Drawings

[0051] As part of this application, the accompanying drawings are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention, but do not constitute an improper limitation to the present invention. Obviously, the accompanying drawings in the following description are only some embodiments. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings. In the drawings:

[0052] Figure 1 It is a structural diagram of the 5-substituted-3-(arylaminoethyl)benzoxazolone compound with the general structural formula (IV) described in the present invention.

[0053] Figure 2 It is a synthetic route diagram of the 5-substituted-3-(arylaminoethyl)benzoxazolone compound with the general structural formula (IV) described in the present invention.

[0054] It should be noted that these drawings and textual descriptions are not intended to limit the scope of the concept of the present invention in any way, but to illustrate the concept of the present invention to those skilled in the art by referring to specific embodiments. Specific Embodiments

[0055] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. The following embodiments are used to illustrate the present invention, but are not used to limit the scope of the present invention.

[0056] The sources of the chemical reagents used in the embodiments of the present invention are as shown in Table 1 below:

[0057] Table 1 Sources of Chemical Reagents

[0058]

[0059]

[0060] Example 1

[0061] Synthesis of 3-((phenylamino)ethyl)-benzoxazolone

[0062]

[0063] Weigh 0.34 g (1.49 mmol) of 2-((2-(phenylamino)ethyl)amino)phenol and add it to a round-bottom flask containing 15 mL of acetonitrile. Then add 0.364 g (2.98 mmol) of 4-dimethylaminopyridine. Continuously fill the mixed solution system with CO2. Finally, add 0.466 g (2.98 mmol) of phenyl chloroformate and react for 35 min. Then, perform suction filtration. After decompressing and evaporating the solvent from the filtrate, the residue is separated by column chromatography to obtain a white solid, yield: 68%.

[0064] 1 H NMR (400 MHz, CDCl3) δ 7.19 (ddd, J = 7.5, 5.3, 3.4 Hz, 3H), 7.16 - 7.07 (m, 2H), 6.88 (dd, J = 7.6, 1.1 Hz, 1H), 6.74 (t, J = 7.3 Hz, 1H), 6.62 (d, J = 7.8 Hz, 2H), 4.05 (t, J = 6.0 Hz, 2H), 3.58 (t, J = 6.0 Hz, 2H).

[0065] 13 C NMR (101 MHz, CDCl3) δ 154.99, 147.06, 142.70, 131.30, 129.48 (2C), 123.96, 122.60, 118.06, 112.81 (2C), 110.16, 108.35, 42.12, 41.59.

[0066] Example 2

[0067] Synthesis of 3-((4-methoxyphenylamino)ethyl)benzoxazolone

[0068]

[0069] According to the process conditions of Example 1, use 0.36 g (1.49 mmol) of 2-((2-(4-methoxyphenylamino)ethyl)amino)phenol, 0.364 g (2.98 mmol) of 4-dimethylaminopyridine, and 0.467 g (2.98 mmol) of phenyl chloroformate, and the yield is: 74%, a brown solid.

[0070] 11H NMR (400 MHz, CDCl3) δ 7.21 - 7.17 (m, 1H), 7.11 (ddd, J = 8.7, 7.4, 1.3 Hz, 2H), 6.90 - 6.85 (m, 1H), 6.80 - 6.75 (m, 2H), 6.60 - 6.55 (m, 2H), 4.03 (t, J = 6.0 Hz, 2H), 3.74 (s, 3H), 3.53 (t, J = 6.0 Hz, 2H).

[0071] 13 13C NMR (101 MHz, CDCl3) δ 155.03, 152.65, 142.78, 141.14, 131.39, 123.99, 122.64, 115.15 (2C), 114.28 (2C), 110.24, 108.40, 55.90, 43.08, 41.78.

[0072] Example 3

[0073] Synthesis of 3 - ((4 - chlorophenylamino)ethyl)benzoxazolone

[0074]

[0075] According to the process conditions of Example 1, 0.39 g (1.48 mmol) of 2 - ((2 - (4 - chlorophenylamino)ethyl)amino)phenol, 0.363 g (2.97 mmol) of 4 - dimethylaminopyridine, and 0.465 g (2.97 mmol) of phenyl chloroformate, the yield was: 71%, a brown solid.

[0076] 1 1H NMR (400 MHz, CDCl3) δ 7.21 - 7.17 (m, 1H), 7.17 - 7.08 (m, 4H), 6.87 (dd, J = 7.5, 1.2 Hz, 1H), 6.55 - 6.49 (m, 2H), 4.04 (t, J = 5.9 Hz, 2H), 3.54 (t, J = 5.9 Hz, 2H).

[0077] 13 13C NMR (101 MHz, CDCl3) δ 155.08, 145.65, 142.74, 131.20, 129.33 (2C), 124.07, 122.77, 122.71, 113.93 (2C), 110.31, 108.23, 42.34, 41.50.

[0078] Example 4

[0079] Synthesis of 3 - ((3 - methylphenylamino)ethyl)benzoxazolone

[0080]

[0081] Under the process conditions of Example 1, 0.36 g (1.49 mmol) of 2-((2-(3-methylphenylamino)ethyl)amino)phenol, 0.364 g (2.98 mmol) of 4-dimethylaminopyridine, and 0.465 g (2.98 mmol) of phenyl chloroformate, the yield was: 74%, a yellowish-brown solid.

[0082] 1 H NMR (400 MHz, DMSO) δ 7.31 (d, J = 7.7 Hz, 1H), 7.21 - 7.06 (m, 3H), 6.94 (t, J = 8.1 Hz, 1H), 6.37 (d, J = 3.2 Hz, 3H), 5.66 (s, 1H), 3.94 (t, J = 6.1 Hz, 2H), 3.44 - 3.39 (m, 2H), 2.15 (s, 3H).

[0083] 13 C NMR (101 MHz, CDCl3) δ 155.03, 144.96, 142.48, 131.11, 130.28, 127.02, 123.80, 122.43, 122.35 (d, J = 7.6 Hz), 117.36, 109.92, 108.99, 108.10, 41.96, 41.20, 17.29.

[0084] Example 5

[0085] Synthesis of 3-((3-methoxyphenylamino)ethyl)benzoxazolone

[0086]

[0087] Under the process conditions of Example 1, 0.36 g (1.49 mmol) of 2-((2-(3-methoxyphenylamino)ethyl)amino)phenol, 0.364 g (2.98 mmol) of 4-dimethylaminopyridine, and 0.467 g (2.98 mmol) of phenyl chloroformate, the yield was: 73%, a brown solid.

[0088] 1 H NMR (400 MHz, DMSO) δ 7.32 (d, J = 7.7 Hz, 1H), 7.21 - 7.06 (m, 3H), 6.95 (t, J = 8.0 Hz, 1H), 6.19 - 6.10 (m, 3H), 5.79 (t, J = 6.3 Hz, 1H), 3.93 (t, J = 6.1 Hz, 2H), 3.64 (s, 3H), 3.41 (d, J = 6.2 Hz, 2H).

[0089] 13 C NMR (101 MHz, DMSO) δ 160.40, 153.90, 149.55, 142.02, 131.38, 129.70, 123.76, 122.06, 109.56, 109.10, 105.20, 101.81, 97.64, 54.61, 41.17, 40.37.

[0090] Example 6

[0091] Synthesis of 5-Methyl-3-((4-chlorophenylamino)ethyl)-benzoxazolone

[0092]

[0093] According to the process conditions of Example 1, 0.415 g (1.50 mmol) of 4-Methyl-2-((2-(4-chlorophenylamino)ethyl)amino)phenol, 0.367 g (3.00 mmol) of 4-dimethylaminopyridine, and 0.470 g (3.00 mmol) of phenyl chloroformate, the yield was: 73%, yellow solid.

[0094] 1 H NMR (400 MHz, DMSO) δ 7.16 (d, J = 8.1 Hz, 1H), 7.09 (d, J = 8.8 Hz, 2H), 6.91 - 6.84 (m, 2H), 6.57 (d, J = 8.8 Hz, 2H), 5.97 (t, J = 6.3 Hz, 1H), 3.90 (t, J = 6.0 Hz, 2H), 3.47 - 3.40 (m, 2H), 2.28 (s, 3H).

[0095] 13 C NMR (101 MHz, DMSO) δ 154.12, 147.05, 140.04, 133.09, 131.22, 128.63 (2C), 122.24, 119.30, 113.56 (2C), 109.53, 109.04, 40.60, 40.27, 21.01.

[0096] Example 7

[0097] Synthesis of 5-Methyl-3-((3-methylphenylamino)ethyl)-benzoxazolone

[0098]

[0099] Under the process conditions of Example 1, 0.385 g (1.50 mmol) of 4-methyl-2-((2-(3-methylphenylamino)ethyl)amino)phenol, 0.367 g (3.00 mmol) of 4-dimethylaminopyridine, and 0.470 g (3.00 mmol) of phenyl chloroformate, the yield was: 76%, a brown solid.

[0100] 1 H NMR (400 MHz, DMSO) δ 7.17 (d, J = 8.0 Hz, 1H), 6.96 (t, J = 8.0 Hz, 1H), 6.92 - 6.85 (m, 2H), 6.38 (d, J = 8.7 Hz, 3H), 3.90 (t, J = 6.1 Hz, 2H), 3.40 (t, J = 6.1 Hz, 2H), 2.28 (s, 3H), 2.16 (s, 3H).

[0101] 13 C NMR (101 MHz, DMSO) δ 154.11, 147.94, 140.02, 137.94, 133.06, 131.29, 128.81, 122.20, 117.11, 112.96, 109.60 (2C), 109.03, 40.87, 40.43, 21.31, 20.98.

[0102] Example 8

[0103] Synthesis of 5-methyl-3-((3-methoxyphenylamino)ethyl)-benzoxazolone

[0104]

[0105] Under the process conditions of Example 1, 0.405 g (1.49 mmol) of 4-methyl-2-((2-(3-methoxyphenylamino)ethyl)amino)phenol, 0.363 g (2.97 mmol) of 4-dimethylaminopyridine, and 0.466 g (2.97 mmol) of phenyl chloroformate, the yield was: 78%, a yellowish-brown solid.

[0106] 1 H NMR (400 MHz, DMSO) δ 7.17 (d, J = 8.0 Hz, 1H), 6.98 (t, J = 8.0 Hz, 1H), 6.92 - 6.84 (m, 2H), 6.21 - 6.10 (m, 3H), 5.77 (t, J = 6.3 Hz, 1H), 3.90 (t, J = 6.1 Hz, 2H), 3.66 (s, 3H), 3.41 (q, J = 6.1 Hz, 2H), 2.28 (s, 3H).

[0107] 1313C NMR (101 MHz, DMSO) δ 160.44, 154.14, 149.50, 140.04, 133.10, 131.29, 129.68, 122.22, 109.60, 109.04, 105.26, 101.82, 97.75, 54.60, 40.84, 40.37, 20.99.

[0108] Activity effect test

[0109] Antitumor activity effect test

[0110] The antitumor activities of 3 - ((phenylamino)ethyl)benzoxazolone, 3 - ((4 - methoxyphenylamino)ethyl)benzoxazolone, 3 - ((4 - chlorophenylamino)ethyl)benzoxazolone, 3 - ((3 - methylphenylamino)ethyl)benzoxazolone, 3 - ((3 - methoxyphenylamino)ethyl)benzoxazolone, 5 - methyl - 3 - ((4 - chlorophenylamino)ethyl)benzoxazolone, 5 - methyl - 3 - ((3 - methylphenylamino)ethyl)benzoxazolone, and 5 - methyl - 3 - ((3 - methoxyphenylamino)ethyl)benzoxazolone were tested by the CCK8 method.

[0111] Using HCCLM3 (human hepatocarcinoma cells) and MCF - 7 (human breast cancer cells) as test materials for antitumor activity testing, the test agents were dissolved in dimethyl sulfoxide and diluted with complete medium to a 50 μmol / L drug solution. The formula of the complete medium was 45 mL of basal medium, 5 mL of fetal bovine serum, and 0.5 mL of double antibiotics.

[0112] Open a 96 - well plate in a sterile workbench, inoculate the cultured HCCLM3 (human hepatocarcinoma cells) or MCF - 7 (human breast cancer cells) into the 96 - well plate. The cell density was 5000 cells / 100 μL of complete medium, and the total inoculation amount was 60 wells × 5000 hepatocarcinoma cells, a total of 300,000 hepatocarcinoma cells. Transfer to a constant - temperature incubator for culture. After 24 hours, in a sterile workbench, use a pipette to aspirate 100 μL of the compound solution and add it to the 96 - well plate inoculated with HCCLM3 (human hepatocarcinoma cells) or MCF - 7 (human breast cancer cells). Use the complete medium without the drug as a blank control and the cell solution without the drug but with the same concentration as a negative control. Incubate each treatment in an incubator at 24 ± 1 °C. After 24 hours, add 10 μL of CCK8 staining agent to each well of the 96 - well plate for staining. After staining for 2 hours, measure the absorbance of each well. Remove the absorbance data with an error greater than 10% of the total sample to obtain the average absorbance values of the experimental group, negative control group, and blank control group.

[0113] Inhibitory rate of cell survival (%) = (Absorbance of negative control group - Absorbance of experimental group) × 100% / (Absorbance of negative control group - Absorbance of blank control group)

[0114] The drug concentration was 50 μmol / L. The results of the anti-tumor activity test are shown in Table 2.

[0115] Table 2 Results of anti-tumor activity test of 5-substituted-3-(arylaminoethyl)benzoxazolone compounds

[0116]

[0117] It can be seen from the table that 5-methyl-3-((3-methylphenylamino)ethyl)benzoxazolone has the best inhibitory rate on human liver cancer cells, up to 94.67%; followed by 3-((4-chlorophenylamino)ethyl)benzoxazolone, with an inhibitory rate of 94.31%; and the inhibitory rate of 3-((4-methoxyphenylamino)ethyl)benzoxazolone is 90.08%. The one with the best inhibitory rate on human breast cancer cells is 3-((3-methoxyphenylamino)ethyl)benzoxazolone, at 96.70%, followed by 3-((4-chlorophenylamino)ethyl)benzoxazolone, at 94.99%, and then 5-methyl-3-((3-methylphenylamino)ethyl)benzoxazolone, at 93.91%.

[0118] The above are only the preferred embodiments of the present invention, and do not impose any formal restrictions on the present invention. Although the present invention has been disclosed above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art of this patent, without departing from the scope of the technical solution of the present invention, can make some changes or modifications using the technical content prompted above into equivalent embodiments of equivalent changes. However, as long as it does not depart from the content of the technical solution of the present invention, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention still fall within the scope of the present invention's solution.

Claims

1. A 5-substituted-3-(arylaminoethyl)benzoxazolone compound, characterized in that, The compound has the general structural formula (V). In formula (V), R 1 is hydrogen, C1-C2 alkyl, C1-C2 alkoxy or halogen; R 2 is hydrogen or alkyl.

2. The 5-substituted-3-(arylaminoethyl)benzoxazolone compound according to claim 1, characterized in that, R 1 is H, 4-CH3O, 4-Cl, 3-CH3 or 3-CH3O; R 2 is H or CH3.

3. A 5-substituted-3-(arylaminoethyl)benzoxazolone compound, characterized in that, The compound is selected from one or more of the following compounds: 3-((phenylamino)ethyl)benzoxazolone: 3-((4-methoxyphenylamino)ethyl)benzoxazolone: 3-((4-chlorophenylamino)ethyl)benzoxazolone: 3-((3-methylphenylamino)ethyl)benzoxazolone: 3-((3-methoxyphenylamino)ethyl)benzoxazolone: 5-methyl-3-((4-chlorophenylamino)ethyl)benzoxazolone: 5-methyl-3-((3-methylphenylamino)ethyl)benzoxazolone: 5-methyl-3-((3-methoxyphenylamino)ethyl)benzoxazolone:

4. A preparation method of 5-substituted-3-(arylaminoethyl)benzoxazolone compounds with structural general formula (IV), characterized in that, The general structural formula (V) is: The preparation method specifically includes the following steps: S1. Using N-aryl-2-bromoacetamide with the structural formula (I) and 2-aminophenol compounds with the structural formula (II) as starting materials, with K2CO3 as the base, under the condition that tetrahydrofuran and N,N-dimethylformamide are used as solvents, alkylation reaction is carried out to obtain N-aryl-2-((2-hydroxyphenyl)amino)acetamide compounds with the structural formula (III). Finally, the N-aryl-2-((2-hydroxyphenyl)amino)acetamide compounds with the structural formula (III) are reduced with lithium aluminum hydride in tetrahydrofuran solvent to obtain 2-((2-(arylamino)ethyl)amino)phenol compounds with the structural formula (IV): S2. Dissolve the 2-((2-(arylamino)ethyl)amino)phenol compounds with the general structural formula (IV) in an organic solvent at room temperature, add a base, and continuously introduce CO2 gas into the mixed system. Finally, phenyl chloroformate is added and reacted for 30 minutes to obtain 5-substituted-3-(arylaminoethyl)benzoxazolone compounds with the general structural formula (V). After the reaction is completed, it is quenched with saturated brine, the aqueous phase is extracted with ethyl acetate, the organic phases are combined, dried with anhydrous Na2SO4, solvent is removed under reduced pressure, and 5-substituted-3-(arylaminoethyl)benzoxazolone compounds with the general structural formula (V) are obtained through a chromatography column: In the formula, R 1 is hydrogen, a C1-C2 alkyl group, a C1-C2 alkoxy group or a halogen; R 2 is hydrogen or an alkyl group.

5. The preparation method according to claim 4, wherein R 1 is H, 4-CH3O, 4-Cl, 3-CH3 or 3-CH3O; R 2 is H or CH3.

6. The preparation method according to claim 4, wherein in step S2, the organic solvent is dichloromethane, N,N-dimethylformamide, toluene, dimethyl sulfoxide or acetonitrile.

7. The preparation method according to claim 6, wherein in step S2, the base is triethylamine, triethylenediamine, 1,8-diazabicyclo[5.4.0]undec-7-ene or 4-dimethylaminopyridine.

8. The preparation method according to claim 6, wherein in step S1, the molar ratio of N-aryl-2-bromoacetamide with the general structural formula (I), 2-aminophenol compounds with the structural formula (II) and K2CO3 added to the reaction is 1:1 - 1.5:1 - 2; the molar ratio of N-aryl-2-((2-hydroxyphenyl)amino)acetamide compounds with the structural formula (III) to the reducing agent lithium aluminum hydride added to the reaction is 1:1 - 5. In step S2, the molar ratio of the 2-((2-(arylamino)ethyl)amino)phenol compound of structural general formula (IV), 4-dimethylaminopyridine, and phenyl chloroformate is 1:1.0 - 2.0:1.0 - 2.

0.

9. Use of a 5-substituted-3-(arylaminoethyl)benzoxazolone compound having the structural general formula (IV) as described in any one of claims 1-3 or a 5-substituted-3-(arylaminoethyl)benzoxazolone compound having the structural general formula (IV) prepared by the method as described in any one of claims 4-8, characterized in that, For preparing anticancer drugs.

10. The use according to claim 9, wherein For preparing drugs against HCCLM3 and MCF-7 cancer cells.

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