Dibenzo-1,3-oxazocinisoquinolin-1(2h)-one compounds, methods of making and antitumor applications thereof

Abstract

The application discloses a kind of dibenzo-1,3-oxazolocyclopentane and isoquinoline-1 (2H) -ketone compound and its preparation method and antitumor application, the structural formula of the compound is or, in formula R 1 , R 2 , R 3 Each independently represent any one of H, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, fluorine, chlorine.The preparation method is as follows: 3-biphenyl-1-hydroxyethyl pyridine-2 (1H) -ketone compound and hydrochloric acid are dissolved in toluene and other organic solvents, under argon protection, irradiated with ultraviolet light, after reaction is finished, separation and purification, the pure product of target compound is obtained.The synthesis method has the advantages of simple process, simple operation, high product yield and low production cost, and the obtained compound has good antitumor cell activity effect, and can be developed as a new type of medical product with antitumor cell activity.

Description

Technical Field

[0001] This invention belongs to the field of heterocyclic compound technology, specifically relating to a class of dibenzo-1,3-oxazolidinyl pentanoisoquinoline-1(2H)-one compounds, as well as the preparation method of the compound and its application in the preparation of antitumor drugs. Background Technology

[0002] Isoquinoline-1(2H)-ones are generally considered to be important biologically active skeletal structures in natural product chemistry. Some natural products contain structural fragments of isoquinoline-1(2H)-one compounds, which possess a wide range of physiological activities, acting as NK3 antagonists, melatonin MT1 and MT2 receptor agonists, Rho kinase inhibitors, JNK inhibitors, HT3 antagonists, and thymidine synthase (TS) inhibitors, and exhibiting good antitumor activity. In 1995, Monroe Wall et al. first discovered an alkaloid called Camptothecin from plants. This alkaloid contains the isoquinoline-1(2H)-one skeleton and was found to inhibit topoisomerase I activity. It also showed strong antitumor activity against colorectal cancer, breast cancer, lung cancer, and ovarian cancer, and can be used for antitumor drug research. In addition, roserin also has significant inhibitory activity against topoisomerase I (top1) and antihypertensive activity; the isoquinoline-1(2H)-one structural fragment is also found in drugs for treating gastric tumors and human brain cell diseases. The biological properties of isoquinoline-1(2H)-one compounds have inspired researchers to develop various synthetic methods.

[0003] In 2013, Fan's group developed a method for the efficient synthesis of 3-cyanoisoquinoline-1(2H)-one compounds via copper-catalyzed N-arylation of amides using 2-bromobenzyl bromide and cyanoacetamide as starting materials and ethylene glycol as a solvent at 100 °C. In 2014, Jeganmohan's group developed a ruthenium-catalyzed oxidative cyclization reaction of naphthylamine and propynyl ester. This reaction uses naphthylamine and propynyl ester as starting materials, a ruthenium complex as a catalyst, and silver hexafluoroantimonate and dimethylpropionic acid as catalysts, with isopropanol as a solvent, at 130 °C for 24 hours to induce cyclization and yield benzisoquinoline-1(2H)-one compounds. In 2018, Cho's group synthesized benzisoquinoline-1(2H)-one compounds via a weak base-promoted microwave-induced lactam cyclization reaction. This method uses lactam compounds as raw materials, potassium carbonate as a base, and N,N-dimethylformamide as a solvent, and proceeds through a free radical cyclization reaction under microwave irradiation at 150 °C. These methods require expensive transition metals or strong acids as catalysts, are difficult to recycle, and can cause environmental pollution.

[0004] Cancer is a disease that harms health, damages body tissues, causes pain and infection, leads to organ dysfunction, and can even be life-threatening. Cancers are classified as benign or malignant. Benign tumors are relatively less harmful, generally causing compression and obstruction. However, malignant tumors are much more dangerous, severely damaging tissue structure, causing organ dysfunction, weakening the immune system, leading to pain, fever, infection, cachexia, extreme emaciation, and ultimately, death due to the failure of various systems. Cancers cause immense harm to the human body; therefore, scientists have continuously developed many anti-cancer drugs. However, some drugs produce numerous side effects that harm the body, making it urgent to find new, safer, and more effective anti-cancer drugs to replace them. Summary of the Invention

[0005] The purpose of this invention is to provide a class of dibenzo-1,3-oxazinecyclopentanoisoquinoline-1(2H)-one compounds with anti-tumor cell activity.

[0006] Another object of the present invention is to provide a method for preparing dibenzo-1,3-oxazacyclopentaneisoquinoline-1(2H)-one compounds from 3-biphenyl-1-hydroxyethylpyridine-2(1H)-one compounds.

[0007] A further object of the present invention is to provide an application of dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compounds.

[0008] To achieve the above objectives, the structural formula of the dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compounds provided by the present invention is shown below:

[0009] or

[0010] In the formula R 1 R 2 R 3 Each of these can be independently represented by any one of H, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, fluorine, or chlorine. R is preferred. 1 R represents any one of hydrogen, methyl, methoxy, chlorine, or trifluoromethyl. 2 R represents any one of hydrogen, methyl, methoxy, trifluoromethyl, or fluorine. 3 It represents any one of hydrogen, trifluoromethyl, or methoxy.

[0011] The dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compounds of the present invention are further preferred. Any one of them.

[0012] The preparation method of the above-mentioned dibenzo-1,3-oxazacyclopentanisoquinoline-1(2H)-one compounds is as follows: 3-biphenyl-1-hydroxyethylpyridine-2(1H)-one compounds of Formula I and hydrochloric acid are dissolved in an organic solvent and reacted under argon protection and ultraviolet light radiation of 300-365 nm for 30-90 minutes. After the reaction is completed, the reaction solution is distilled under reduced pressure and purified by column chromatography to obtain dibenzo-1,3-oxazacyclopentanisoquinoline-1(2H)-one compounds.

[0013]

[0014] In the above preparation method, the preferred molar ratio of 3-biphenyl-1-hydroxyethylpyridine-2(1H)-one compound to HCl in hydrochloric acid is 1:1 to 2.

[0015] In the above preparation method, the preferred organic solvent is any one of toluene, dichloromethane, or dioxane.

[0016] The dibenzo-1,3-oxazacyclopentanoquinoline-1(2H)-one compounds of this invention exhibit good inhibitory effects on leukemia cells HL-60, lung cancer cells A549, liver cancer cells SMMC-7721, and breast cancer cells MDA-MB-231. They can be used to prepare antitumor drugs, manufactured according to conventional pharmaceutical preparation methods with pharmaceutically acceptable carriers, and can be in the form of tablets, granules, capsules, etc. The tumors mentioned are any one of leukemia, lung cancer, liver cancer, and breast cancer.

[0017] The beneficial effects of this invention are as follows:

[0018] 1. The dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compounds of this invention all exhibit strong anti-tumor cell activity. Using commercial cisplatin as a control, compounds 2b-α and 2b-β of this invention showed good inhibitory effects on HL-60 leukemia cells, A549 lung cancer cells, and SMMC-7721 liver cancer cells; 2j-β showed significant inhibitory effects on SMMC-7721 liver cancer cells and MDA-MB-231 breast cancer cells; and 2k-α showed inhibitory effects on MDA-MB-231 breast cancer cells. Furthermore, experimental data show that some compounds in the dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compounds of this invention exhibit inhibitory activity higher than or similar to cisplatin against these four tumor cell types. If these compounds are used to prepare anti-tumor cell drugs, they are expected to have good therapeutic effects on tumors.

[0019] 2. This invention uses inexpensive and readily available 3-biphenyl-1-hydroxyethylpyridine-1(2H)-one compounds as raw materials and inexpensive hydrochloric acid as a catalyst to synthesize a series of dibenzo-1,3-oxazacyclopentaneisoquinoline-1(2H)-one compounds through photochemical reaction. It has the advantages of short synthesis route, simple process, simple equipment, high product yield, low production cost and environmental protection. Detailed Implementation

[0020] The present invention will be further described in detail below with reference to the embodiments, but the scope of protection of the present invention is not limited to these embodiments. Example 1

[0021] 59.2 g (0.2 mol) of 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one, 0.3 L of 1 mol / L hydrochloric acid aqueous solution, and 40 L of toluene were added to a photoreaction tube. The reaction was carried out under argon protection and stirring with 313 nm ultraviolet light for 1 hour. After the reaction was completed, the reaction solution was distilled under reduced pressure and purified by column chromatography (the eluent was a mixture of CH2Cl2 and CH3OH in a volume ratio of 20:1) to obtain pure compounds 2a-α and 2a-β, with yields of 38% and 36%, respectively.

[0022]

[0023] Compound 2a-α is a white powder with a melting point of 198.5–199.0 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.79 (dd, J = 17.2,7.6 Hz, 2H), 7.40 – 7.34 (m, 3H), 7.34 – 7.27 (m, 3H), 4.62 (dd, J = 5.2, 4.1Hz, 1H), 4.27 – 7.15 (m, 1H), 4.12 – 4.04 (m, 1H), 3.92 (d, J = 5.4 Hz, 1H), 3.80 (q, J = 8.4 Hz, 1H), 3.56 – 3.43 (m, 1H), 3.35 – 3.31 (m, 1H), 2.41 –2.29 (m, 1H), 2.10 (dt, J = 14.7, 4.3 Hz, 1H); 13C NMR (151 MHz, Chloroform- d )δ 169.3, 136.1, 133.3, 132.9, 131.6, 128.4, 128.2, 128.1, 128.0, 127.9,127.1, 124.4, 123.8, 85.2, 63.9, 46.8, 42.8, 33.5, 28.9; HRMS (ESI): m / z [M+Na] + Theoretical value C 19 H 17 NO2Na: 314.1152; Measured value: 314.1158.

[0024] Compound 2a-β is a white powder with a melting point of 175.6–176.3 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.78 (t, J = 6.9 Hz, 2H), 7.63 (d, J = 7.7 Hz, 1H), 7.43 – 7.32 (m, 2H), 7.32 – 7.22 (m, 3H), 4.83(dd, J = 9.4, 4.9 Hz, 1H), 4.16 – 4.05 (m, 1H), 4.03 – 3.93 (m, 2H), 3.89 (q, J = 8.3 Hz, 1H), 3.57 – 3.46 (m, 1H), 3.36 – 3.21 (m, 1H), 2.14 – 2.00 (m,1H), 1.82 – 1.69 (m, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 167.5, 136.7,133.1, 132.8, 131.4, 128.4, 128.2, 128.1, 127.9, 127.7, 127.5, 124.1, 124.0,86.7, 64.7, 44.7, 42.3, 36.0, 29.7; HRMS (ESI): m / z [M+Na] + Theoretical value C 19 H 17 NO2Na: 314.1152; Measured value: 314.1156. Example 2

[0025] In this embodiment, 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one was replaced with an equimolar amount of 3-(4'-methoxy-[1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one in Example 1, and the other steps were the same as in Example 1, to obtain pure compounds 2b-α and 2b-β, both in 34% yield.

[0026]

[0027] Compound 2b-α is a white powder with a melting point of 167.8–168.4 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.74 (dd, J = 23.0, 8.1 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.1 Hz, 1H), 6.92 (dd, J = 8.6, 2.4 Hz, 1H), 6.88 (d, J = 2.3 Hz, 1H), 4.70 – 4.62 (m, 1H), 4.28 –4.20 (m, 1H), 4.14 – 4.05 (m, 1H), 3.93 (d, J = 5.2 Hz, 1H), 3.90 – 3.81 (m,4H), 3.48 – 3.40 (m, 1H), 3.36 – 3.28 (m, 1H), 2.36 – 2.27 (m, 1H), 2.15 –2.06 (m, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 169.5, 159.6, 137.8, 132.9,130.7, 128.2, 127.9, 127.3, 126.0, 125.7, 123.1, 113.2, 112.6, 85.1, 63.8,55.3, 46.8, 42.7, 33.9, 28.8; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H19 NO3Na: 344.1258; Measured value: 344.1255.

[0028] Compound 2b-β is a white powder with a melting point of 150.2–150.8 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.64 (dd, J = 15.3, 7.9 Hz, 2H), 7.52 (d, J = 7.2 Hz, 1H), 7.28 – 7.14 (m, 2H), 6.84 (d, J = 7.3Hz, 1H), 6.71 (s, 1H), 4.88 – 4.68 (m, 1H), 4.14 – 4.00 (m, 1H), 3.96 – 3.68(m, 6H), 3.50 – 3.39 (m, 1H), 3.16 (d, J = 10.7 Hz, 1H), 1.99 (d, J = 10.7Hz, 1H), 1.70 (q, J = 12.3 Hz, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 167.6,159.6, 138.3, 132.8, 130.6, 127.7, 127.5, 127.4, 126.0, 125.5, 123.3, 113.6,113.1, 86.7, 64.7, 55.4, 44.8, 42.3, 36.5, 29.7; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H 19 NO3Na: 344.1258; Measured value: 344.1254. Example 3

[0029] In this embodiment, equimolar amounts of 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one were used to replace 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one in Example 1, and the other steps were the same as in Example 1, to obtain pure compounds 2c-α and 2c-β in yields of 30% and 32%, respectively.

[0030]

[0031] Compound 2c-α is a white powder with a melting point of 178.8–179.5 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.90 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 7.4 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.58 (s, 1H), 7.44 –7.35 (m, 3H), 4.67 – 4.56 (m, 1H), 4.27 – 4.15 (m, 1H), 4.09 (q, J = 8.1 Hz, 1H), 3.94 (d, J = 5.1 Hz, 1H), 3.83 (q, J = 7.8 Hz, 1H), 3.59 – 3.50 (m, 1H), 3.34 – 3.25 (m, 1H), 2.42 – 2.30 (m, 1H), 2.13 (d, J = 14.8 Hz, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 168.7, 136.8 (q, J = 8.8Hz), 132.1, 131.6, 129.7(q, J = 33.4Hz), 129.4, 128.7, 128.3, 128.0 (q, J = 25.8Hz), 124.8 (q, J =3.4Hz), 124.7, 124.4, 124.1, 124.0 (q, J = 272.3Hz), 85.0, 63.9, 46.5, 42.8,33.5, 28.6; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H 16 F3NO2Na: 382.1026; Measured value: 382.1022.

[0032] Compound 2c-β is a white powder with a melting point of 187.2–187.7 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.89 (d, J = 8.2 Hz, 1H), 7.81 (d, J = 7.4 Hz, 1H), 7.67 (d, J = 7.5 Hz, 1H), 7.62 (d, J = 7.9 Hz,1H), 7.53 (s, 1H), 7.43 – 7.33 (m, 2H), 4.87 (dd, J = 9.3, 4.9 Hz, 1H), 4.15– 4.07 (m, 1H), 4.02 – 3.95 (m, 2H), 3.92 (q, J = 8.1 Hz, 1H), 3.58 – 3.47(m, 1H), 3.43 – 3.33 (m, 1H), 2.15 – 2.05 (m, 1H), 1.87 – 1.72 (m, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 167.0, 137.2, 136.6, 132.0, 131.6, 130.0 (q, J =33.0Hz), 129.6, 128.1, 127.9, 125.0 (q, J = 3.9Hz), 124.9 (q, J = 4.1Hz),124.6, 124.5, 124.0 (q, J = 271.9Hz), 86.6, 64.8, 44.5, 42.4, 36.0, 29.5; HRMS(ESI): m / z [M+Na] + Theoretical value C 20 H 16 F3NO2Na: 382.1026; Measured value: 382.1024. Example 4

[0033] In this embodiment, 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one was replaced with an equimolar amount of 3-(4'-chloro-[1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one in Example 1, and the other steps were the same as in Example 1, to obtain pure compounds 2d-α and 2d-β in yields of 32% and 31%, respectively.

[0034]

[0035] Compound 2d-α is a white powder with a melting point of 159.7–160.5℃. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.73 (d, J = 7.6 Hz,2H), 7.40 – 7.30 (m, 5H), 4.63 (t, J = 4.7 Hz, 1H), 4.24 – 4.15 (m, 1H), 4.11– 4.06 (m, 1H), 3.90 (d, J = 5.4 Hz, 1H), 3.82 (q, J = 8.3 Hz, 1H), 3.49 –3.42 (m, 1H), 3.33 – 3.25 (m, 1H), 2.39 – 2.29 (m, 1H), 2.10 (dt, J = 14.6, 4.4 Hz, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 168.8, 137.8, 133.7, 132.0,131.9, 131.5, 128.7, 128.5, 128.2, 128.1, 127.1, 125.8, 123.8, 85.0, 64.0,46.5, 42.8, 33.4, 28.7; HRMS (ESI): m / z [M+Na] + Theoretical value C 19 H 16 ClNO2Na: 348.0762; Measured value: 348.0753.

[0036] Compound 2d-β is a white powder with a melting point of 145.5–146.0 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows:1 H NMR (600 MHz, Chloroform- d ) δ 7.65 (t, J = 8.0 Hz, 2H), 7.56 (d, J = 7.6 Hz, 1H), 7.32 – 7.20 (m, 3H), 7.19 (s, 1H), 4.77 (dd, J = 9.3, 4.8 Hz, 1H), 4.08 – 4.00 (m, 1H), 3.96 – 3.81 (m, 3H), 3.49 – 3.40 (m,1H), 3.27 – 3.17 (m, 1H), 2.10 – 1.98 (m, 1H), 1.77 – 1.67 (m, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 167.2, 138.3, 133.7, 131.91, 131.7, 131.2, 128.8,128.3, 127.9, 127.8, 127.7, 125.6, 124.0, 86.6, 64.8, 44.6, 42.4, 35.9, 29.5; HRMS (ESI): m / z [M+Na] + Theoretical value C 19 H 16 ClNO2Na: 348.0762; Measured value: 348.0753. Example 5

[0037] In this embodiment, equimolar amounts of 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one were used to replace 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one in Example 1, and the other steps were the same as in Example 1, to obtain pure compounds 2e-α and 2e-β in yields of 34% and 32%, respectively.

[0038]

[0039] Compound 2e-α is a white powder with a melting point of 131.2–131.8 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.67 (d, J= 7.7 Hz,1H), 7.31 – 7.28 (m, 2H), 7.27 – 7.24 (m, 2H), 7.18 (d, J = 9.0 Hz, 1H), 6.80– 6.76 (m, 1H), 4.56 (t, J = 4.5 Hz, 1H), 4.14 – 4.08 (m, 1H), 4.04 – 3.98 (m, 1H), 3.80 (s, 3H), 3.73 (d, J = 7.9 Hz, 1H), 3.58 (s, 1H), 3.42 – 3.34(m, 1H), 3.27 – 3.17 (m, 1H), 2.33 – 2.25 (m, 1H), 2.03 – 1.97 (m, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 169.4, 159.4, 134.5, 132.9, 132.8, 132.0, 128.7,128.3, 128.0, 127.9, 123.8, 113.5, 110.0, 85.2, 63.9, 55.4, 47.0, 42.8, 32.8,29.1; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H 19 NO3Na: 344.1258; Measured value: 344.1260.

[0040] Compound 2e-β is a white powder with a melting point of 129.2–129.8 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.75 (d, J = 7.3 Hz, 1H), 7.62 (d, J = 7.3 Hz, 1H), 7.40 – 7.27 (m, 3H), 7.18 (d, J = 8.0 Hz, 1H), 6.86 (d, J = 7.8 Hz, 1H), 4.83 (dd, J= 8.0, 4.2 Hz, 1H), 4.11 (s, 1H), 4.02– 3.96 (m, 1H), 3.95 – 3.89 (m, 1H), 3.88 (s, 3H), 3.65 (s, 1H), 3.55 – 3.48(m, 1H), 3.25 (d, J = 14.2 Hz, 1H), 2.03 (d, J = 11.7 Hz, 1H), 1.73 (q, J =12.3 Hz, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 167.7, 159.6, 134.2, 132.8,131.7, 129.1, 128.9, 128.6, 127.7, 127.6, 124.1, 113.9, 109.5, 86.8, 64.7,55.4, 45.0, 42.4, 35.4, 30.0; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H 19 NO3Na: 344.1258; Measured value: 344.1260. Example 6

[0041] In this embodiment, equimolar amounts of 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one were used to replace 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one in Example 1, and the other steps were the same as in Example 1, to obtain pure compounds 2f-α and 2f-β with yields of 29% and 27%, respectively.

[0042]

[0043] Compound 2f-α is a white powder with a melting point of 208.4–208.9 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.01 (d, J = 7.5 Hz,1H), 7.64 – 7.59 (m, 1H), 7.40 (dd, J= 9.9, 2.5 Hz, 1H), 7.35 – 7.27 (m,2H), 7.20 – 7.16 (m, 1H), 6.97 (td, J = 8.4, 2.5 Hz, 1H), 4.86 (dd, J = 9.5, 3.9 Hz, 1H), 4.22 (td, J = 8.2, 2.9 Hz, 1H), 4.03 – 3.93 (m, 1H), 3.93 – 3.86(m, 1H), 3.47 – 3.93 (m, 1H), 3.23 (d, J = 13.7 Hz, 1H), 2.92 – 2.84 (m, 2H), 1.71 – 1.64 (m, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 166.8, 162.5 (d, J =244.7 Hz), 137.0 (d, J = 7.8 Hz), 134.9, 133.9, 133.1 (d, J = 2.6 Hz), 128.5,127.6, 125.5, 124.7, 124.4 (d, J = 21.8 Hz), 114.2 (d, J = 21.8 Hz), 111.6(d, J = 22.7 Hz), 87.3, 65.2, 46.3, 43.1, 35.3, 30.1; HRMS (ESI): m / z [M+Na] + Theoretical value C 19 H 16 FNO2Na: 332.1058; Measured value: 332.1056.

[0044] Compound 2f-β is a white powder with a melting point of 191.4–191.9 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (400 MHz, Chloroform- d ) δ 7.71 (d, J = 7.5 Hz, 1H), 7.64 (d, J = 7.3 Hz, 1H), 7.47 (d,J = 9.5 Hz, 1H), 7.40 – 7.39 (m, 2H), 7.25 – 7.18 (m, 1H), 6.99 (t, J = 7.6 Hz, 1H), 4.84 (dd, J = 9.2, 4.8 Hz,1H), 4.23 – 4.06 (m, 1H), 4.05 – 3.84 (m, 3H), 3.52 (t, J = 10.7 Hz, 1H), 3.36 – 3.21 (m, 1H), 2.04 (d, J = 13.3 Hz, 1H), 1.75 (q, J = 12.7 Hz, 1H); 13 CNMR (151 MHz, Chloroform- d ) δ 167.4, 162.8 (d, J = 245.2 Hz), 135.2 (d, J =7.7 Hz), 132.3 (d, J = 2.6 Hz), 132.0 (d, J = 2.1 Hz), 131.5, 129.4 (d, J =8.3 Hz), 129.1, 127.9, 127.7, 124.2, 115.0 (d, J = 21.9 Hz), 110.9 (d, J =22.7 Hz), 86.7, 64.7, 44.8, 42.4, 35.4, 29.8; HRMS (ESI): m / z [M+Na] + Theoretical value C 19 H 16 FNO2Na: 332.1058; Measured value: 332.1057. Example 7

[0045] In this embodiment, equimolar amounts of 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one were used to replace 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one in Example 1, and the other steps were the same as in Example 1, yielding 2 g of pure compounds -α and 2 g of -β, with yields of 28% and 27%, respectively.

[0046]

[0047] Compound 2g-α is a white powder with a melting point of 187.1–187.7 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.04 (s, 1H), 7.81 (d, J = 7.6 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.45 (d, J = 7.9 Hz, 1H), 7.44 –7.33 (m, 3H), 4.62 (t, J = 4.3 Hz, 1H), 4.27 – 4.17 (m, 1H), 4.14 – 4.04 (m,1H), 3.94 (d, J = 5.3 Hz, 1H), 3.82 (q, J = 8.3 Hz, 1H), 3.60 – 3.50 (m, 1H), 3.38 – 3.17 (m, 1H), 2.41 – 3.27 (m, 1H), 2.17 – 2.07 (m, 1H); 13 C NMR (151MHz, Chloroform- d ) δ 168.8, 139.8, 134.1, 131.7, 131.6, 130.4 (q, J = 32.1Hz), 129.2, 128.6, 128.3, 127.6, 124.7 (q, J = 4.0 Hz), 124.1 (q, J = 272.3Hz), 124.0, 121.3 (q, J = 3.7 Hz), 85.0, 63.9, 46.4, 42.8, 33.5, 28.5; HRMS(ESI): m / z [M+Na] + Theoretical value C 20 H 16 F3NO2Na: 382.1026; Measured value: 382.1025.

[0048] Compound 2g-β is a white powder with a melting point of 168.2–168.9 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.96 (s, 1H), 7.74 (d, J = 7.2 Hz, 1H), 7.59 (d, J = 7.4 Hz, 1H), 7.48 (d, J = 7.1 Hz, 1H), 7.34 -7.29 (m, 2H), 7.19 (s, 1H), 4.80 (dd, J = 8.6, 4.5 Hz, 1H), 4.05 (q, J = 7.7Hz, 1H), 3.94 – 83 (m, 3H), 3.51 – 3.41 (m, 1H), 3.31 (d, J = 11.7 Hz, 1H), 2.01 (d, J = 12.0 Hz, 1H), 1.74 (q, J = 12.2 Hz, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 167.0, 140.3, 134.0, 131.6 (q, J = 3.2 Hz), 130.7 (q, J =31.0 Hz), 129.4, 128.5, 128.1, 127.9, 124.7 (q, J = 3.2 Hz), 124.3, 124.1 (q, J = 272.1 Hz), 121.1 (q, J = 3.2 Hz), 121.1, 86.6, 64.8, 44.5, 42.4, 36.0,29.4; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H 16 F3NO2Na: 382.1026; Measured value: 382.1026. Example 8

[0049] In this embodiment, 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one was replaced with an equimolar amount of 3-(4-methoxy-[1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one in Example 1, and the other steps were the same as in Example 1, to obtain pure compounds 2h-α and 2h-β, both in 31% yield.

[0050]

[0051] Compound 2h-α is a white powder with a melting point of 149.7–150.3 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.71 (dd, J = 11.4,8.7 Hz, 2H), 7.36 – 7.31 (m, 1H), 7.29 (d, J = 7.2 Hz, 1H), 7.25 – 7.22 (m,1H), 6.97 – 6.87 (m, 2H), 4.64 (dd, J = 5.3, 3.8 Hz, 1H), 4.25 – 4.16 (m,1H), 4.10 – 4.04 (m, 1H), 3.90 (d, J = 5.4 Hz, 1H), 3.84 (s, 3H), 3.81 (q, J = 8.4 Hz, 1H), 3.49 – 3.42 (m, 1H), 3.38 – 3.23 (m, 1H), 2.37 – 2.29 (m, 1H), 2.13 – 1.96 (m, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 169.3, 159.7, 135.2,133.3, 133.2, 127.9, 127.2, 127.0, 125.8, 125.2, 123.7, 113.7, 113.6, 85.2,63.9, 55.4, 47.1, 42.8, 33.6, 28.8; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H 19 NO3Na: 344.1258; Measured value: 344.1248.

[0052] Compound 2h-β is a white powder with a melting point of 159.5–160.3℃. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.64 (d, J = 8.7 Hz,2H), 7.30 – 7.25 (m, 1H), 7.20 – 7.15 (m, 3H), 6.81 (dd, J = 8.6, 2.3 Hz, 1H), 4.77 (dd, J = 9.4, 4.8 Hz, 1H), 4.09 – 4.03 (m, 1H), 3.94 – 3.81 (m,3H), 3.76 (s, 3H), 3.49 – 3.41 (m, 1H), 3.26 – 3.15 (m, 1H), 1.99 (d, J =11.4 Hz, 1H), 1.78 – 1.67 (m, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 167.6,159.9, 135.8, 133.1, 133.0, 128.2, 127.9, 127.3, 125.7, 125.3, 123.4, 113.3,113.2, 86.8, 64.7, 55.3, 44.9, 42.4, 36.2, 29.8; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H 19 NO3Na: 344.1258; Measured value: 344.1251. Example 9

[0053] In this embodiment, equimolar amounts of 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one were used to replace 3-(4-trifluoromethyl-[1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one in Example 1, and the other steps were the same as in Example 1, to obtain pure compounds 2i-α and 2i-β with yields of 36% and 34%, respectively.

[0054]

[0055] Compound 2i-α is a white powder with a melting point of 177.7–178.5 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 7.87 (d, J = 8.2 Hz, 1H), 7.83 (d, J = 7.4 Hz, 1H), 7.64 (s, 1H), 7.62 (d, J = 8.2 Hz, 1H), 7.45 –7.34 (m, 3H), 4.66 (t, J = 4.8 Hz, 1H), 4.24 – 4.14 (m, 1H), 4.13 – 4.06 (m,1H), 3.93 (d, J = 5.6 Hz, 1H), 3.82 (q, J = 8.3 Hz, 1H), 3.61 – 3.50 (m, 1H), 3.38 – 3.20 (m, 1H), 2.52 – 2.35 (m, 1H), 2.19 – 2.07 (m, 1H); 13 C NMR (151MHz, Chloroform- d ) δ 168.2, 136.3, 136.2, 132.5, 132.1, 129.9 (q, J = 32.4Hz), 129.3, 128.2, 127.1, 125.8 (q, J = 4.0 Hz), 125.0 (q, J = 4.0 Hz),124.9, 124.1, 124.0 (q, J = 280.4 Hz), 85.0, 64.0, 46.5, 43.0, 33.2, 28.8; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H 16 F3NO2Na: 382.1026; Measured value: 382.1020.

[0056] Compound 2i-β is a white powder with a melting point of 183.4–183.9 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1H NMR (600 MHz, Chloroform- d ) δ 7.95 (s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 7.5 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.47 –7.35 (m, 2H), 7.30 (d, J = 7.1 Hz, 1H), 4.87 (dd, J = 8.9, 4.5 Hz, 1H), 4.23– 4.08 (m, 1H), 4.07 – 3.87 (m, 3H), 3.59 – 3.47 (m, 1H), 3.42 – 3.25 (m,1H), 2.11 (d, J = 12.0 Hz, 1H), 1.72 (q, J = 12.7 Hz, 1H); 13 C NMR (151 MHz, Chloroform- d ) δ 166.8, 137.0, 136.3, 132.2, 131.8, 130.2 (q, J = 32.7 Hz),129.4, 128.5, 128.2, 124.8 (q, J = 2.1 Hz), 124.7, 124.4, 124.1 (q, J = 272.0Hz), 86.7, 64.8, 44.4, 42.4, 35.8, 30.0; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H 16 F3NO2Na: 382.1026; Measured value: 382.1018. Example 10

[0057] In this embodiment, 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one was replaced with an equimolar amount of 3-(4'-methyl-[1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one in Example 1, and the other steps were the same as in Example 1, to obtain pure compounds 2j-α and 2j-β in yields of 34% and 35%, respectively.

[0058]

[0059] Compound 2j-α is a white powder with a melting point of 137.7–138.5 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.67 (d, J = 7.5 Hz,1H), 7.63 (d, J = 7.9 Hz, 1H), 7.30 – 7.25 (m, 1H), 7.21 (d, J = 7.3 Hz, 1H), 7.19 (s, 1H), 7.10 (d, J = 7.8 Hz, 1H), 7.06 (s, 1H), 4.55 (s, 1H), 4.14 (q,J = 8.0 Hz, 1H), 4.01 (q, J = 8.1 Hz, 1H), 3.84 (d, J = 4.9 Hz, 1H), 3.74 (q,J = 7.9 Hz, 1H), 3.42 – 3.29 (m, 1H), 3.29 – 3.18 (m, 1H), 2.31 (s, 3H), 2.27- 2.20 (m, 1H), 2.01 (d, J = 14.6 Hz, 1H); 13 C NMR (151 MHz, Chloroform-d)δ 169.8, 138.3, 136.4, 133.3, 131.6, 130.8, 128.9, 128.5, 128.2, 128.1,128.0, 124.6, 123.8, 85.5, 64.1, 47.2, 43.0, 33.8, 29.2, 21.5; HRMS (ESI): m / z[M+H] + Theoretical value C 20 H 20 NO2: 306.1489; Measured value: 306.1489.

[0060] Compound 2j-β is a white powder with a melting point of 155.2–155.9 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1H NMR (600 MHz, Chloroform-d) δ 7.67 (d, J = 7.7 Hz,1H), 7.60 (d, J = 7.9 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.25 (t, J = 7.5 Hz,1H), 7.18 (t, J = 7.4 Hz, 1H), 7.10 (d, J = 7.9 Hz, 1H), 6.98 (s, 1H), 4.75 (dd, J = 9.4, 4.8 Hz, 1H), 4.07 – 3.98 (m, 1H), 3.94 – 3.87 (m, 1H), 3.87 –3.75 (m, 2H), 3.49 – 3.39 (m, 1H), 3.19 – 3.10 (m, 1H), 2.30 (s, 3H), 1.96 (d, J = 12.6 Hz, 1H), 1.71 – 1.62 (m, 1H); 13 C NMR (151 MHz, Chloroform-d) δ167.9, 138.4, 136.9, 133.2, 131.4, 130.6, 129.2, 128.8, 128.3, 127.9, 127.7,124.3, 124.0, 87.0, 65.0, 45.1, 42.6, 36.4, 30.0, 21.4; HRMS (ESI): m / z [M+Na] + Theoretical value C 20 H 19 NO2Na: 328.1308; Measured value: 328.1306. Example 11

[0061] In this embodiment, equimolar amounts of 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one were used to replace 3-([1,1'-biphenyl]-2-yl)-1-(3-hydroxyethyl)pyridin-1(2H)-one in Example 1, and the other steps were the same as in Example 1, to obtain pure compounds 2k-α and 2k-β in yields of 34% and 35%, respectively.

[0062]

[0063] Compound 2k-α is a white powder with a melting point of 142.8–143.5 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1H NMR (600 MHz, Chloroform-d) δ 7.68 (d, J = 7.8 Hz,1H), 7.50 (s, 1H), 7.26 (d, J = 7.0 Hz, 2H), 7.19 (t, J = 7.1 Hz, 1H), 7.01(s, 1H), 4.55 (t, J = 4.4 Hz, 1H), 4.17 – 4.05 (m, 1H), 4.05 – 3.94 (m, 1H), 3.80 (d, J = 5.2 Hz, 1H), 3.72 (q, J = 8.1 Hz, 1H), 3.39 – 3.27 (m, 1H), 3.25– 3.17 (m, 1H), 2.27 (d, J = 5.8 Hz, 1H), 2.24 (s, 3H), 2.21 (s, 3H), 2.02 –1.95 (m, 1H); 13 C NMR (151 MHz, Chloroform-d) δ 169.8, 137.0, 136.3, 133.8,133.3, 131.7, 131.0, 128.7, 128.5, 128.1, 127.9, 125.8, 123.7, 85.5, 64.1,47.2, 43.0, 33.3, 29.3, 19.9, 19.8; HRMS (ESI): m / z [M+Na] + Theoretical value C 21 H 21 NO2Na: 342.1465; Measured value: 342.1461.

[0064] Compound 2k-β is a white powder with a melting point of 166.9–167.5 °C. It is readily soluble in organic solvents such as methanol, ethanol, and dichloromethane. The structural characterization results are as follows: 1H NMR (600 MHz, Chloroform-d) δ 7.66 (d, J = 7.5 Hz, 1H), 7.52 (d, J = 7.7 Hz, 1H), 7.47 (s, 1H), 7.23 (t, J = 7.5 Hz, 1H), 7.18 –7.14 (m, 1H), 6.92 (s, 1H), 4.72 (dd, J = 9.5, 4.8 Hz, 1H), 4.05 - 3.97 (m,1H), 3.92 - 3.85 (m, 1H), 3.82 - 3.75 (m, 2H), 3.46 - 3.88 (m, 1H), 3.14 –3.05 (m, 1H), 2.23 (s, 3H), 2.19 (s, 3H), 1.93 (d, J = 12.4 Hz, 1H), 1.69 –1.59 (m, 1H); 13 C NMR (151 MHz, Chloroform-d) δ 168.0, 137.0, 136.6, 134.4, 133.2, 131.4, 130.8, 129.3, 128.1, 127.8, 127.7, 125.4, 123.8, 87.0, 64.9, 45.1, 42.5, 35.8, 30.1, 19.9, 19.6; HRMS (ESI): m / z [M+Na]+ Theoretical value C 21 H 21 NO2Na: 342.1465; Measured value: 342.1460. Example 12

[0065] Application of compounds in Examples 1-11 in the preparation of antitumor drugs

[0066] The compounds from Examples 1 to 11 were used as active ingredients in efficacy tests, and the specific test results are as follows:

[0067] 1. Test drug

[0068] Cisplatin, paclitaxel (positive control compound), and compounds from Examples 1 to 11.

[0069] 2. Test cells

[0070] Leukemia HL-60, Lung cancer A549, Liver cancer SMMC-7721, Breast cancer MDA-MB-231.

[0071] 3. Assay for antitumor cell activity

[0072] Cell seeding: Prepare a single-cell suspension using culture medium (DMEM or RMPI1640) containing 10% fetal bovine serum, and seed 3,000 to 15,000 cells per well into a 96-well plate with a volume of 100 μL per well. The cells should be seeded and cultured 12 to 24 hours in advance.

[0073] Add the solution of the compound to be tested: Dissolve the compound in DMSO, and screen the compound at a concentration of 40 μmol / L. The final volume of each well is 200 μL, and each treatment has 3 replicates.

[0074] Color development: After incubation at 37℃ for 48 hours, discard the culture medium in the wells of adherent cells, and add 20 μL of MTS solution and 100 μL of culture medium to each well; discard 100 μL of culture supernatant in the wells of HL-60 suspension cells, and add 20 μL of MTS solution to each well; set up 3 blank replicates (a mixture of 20 μL of MTS solution and 100 μL of culture medium), and continue incubation for 2-4 hours to allow the reaction to proceed fully before measuring the absorbance.

[0075] Colorimetric analysis: A wavelength of 492 nm was selected, and the absorbance values ​​of each well were read using a multi-functional microplate reader (MULTISKAN FC). The results were recorded, and after data processing, a cell inhibition rate graph was plotted with the compound number as the x-axis and the cell inhibition rate as the y-axis. The results are shown in Table 1.

[0076] Table 1. Antitumor activity inhibition rate

[0077]

[0078] As shown in Table 1, compounds 2b-α, 2b-β, 2j-β, and 2k-α exhibited good inhibition rates (>60%), therefore their IC50 values ​​were further tested. 50 The half-maximal inhibitory concentration (IC50) was calculated. Cisplatin (DDP) was included as a positive compound in each experiment. Cell growth curves were plotted with concentration on the x-axis and cell viability on the y-axis. The IC50 of the compound was calculated using the Reed-Muench method. 50 Values. The results are shown in Table 2.

[0079] Table 2 IC50 of antitumor activity 50 Value (IC50±SD(µM))

[0080]

[0081] In the table, "--" indicates that it has not been tested.

[0082] As shown in Table 2, the compounds 2b-α, 2b-β, 2j-β, and 2k-α of this invention exhibit good inhibitory activity against four tested cancer cell lines. Specifically, 2b-α and 2b-β show good inhibitory effects against HL-60 leukemia cells, A549 lung cancer cells, and SMMC-7721 liver cancer cells. 2b-β shows significant inhibitory effects against SMMC-7721 liver cancer cells and MDA-MB-231 breast cancer cells, while 2k-α shows inhibitory effects against MDA-MB-231 breast cancer cells. Therefore, the dibenzo-1,3-oxazacyclopentanoquinoline-1(2H)-one compounds of this invention possess good antitumor activity.

Claims

1. A class of dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compounds, characterized in that... The structural formula of this compound is: or In the formula R 1 R 2 R 3 Each can be independently represented by any one of H, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, fluorine, or chlorine.

2. The dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compound according to claim 1, characterized in that: The R 1 R represents any one of hydrogen, methyl, methoxy, chlorine, or trifluoromethyl. 2 R represents any one of hydrogen, methyl, methoxy, trifluoromethyl, or fluorine. 3 It represents any one of hydrogen, trifluoromethyl, or methoxy.

3. The dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compound according to claim 1, characterized in that... The compound is or , or , or , or , or , or , or , or , or , or , or Any one of them.

4. A method for preparing the dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compound according to claim 1, characterized in that: The 3-biphenyl-1-hydroxyethylpyridine-2(1H)-one compound shown in Formula I was dissolved in an organic solvent and hydrochloric acid. The reaction was carried out under argon protection and ultraviolet light irradiation of 300-365 nm for 30-90 minutes. After the reaction was completed, the reaction solution was distilled under reduced pressure and purified by column chromatography to obtain dibenzo-1,3-oxazacyclopentanisoquinoline-1(2H)-one compound. In the formula R 1 R 2 R 3 Each can be independently represented by any one of H, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, fluorine, or chlorine.

5. The method for preparing dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compounds according to claim 4, characterized in that: The molar ratio of the 3-biphenyl-1-hydroxyethylpyridine-2(1H)-one compound to HCl in hydrochloric acid is 1:1 to 2.

6. The method for preparing dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compounds according to claim 4, characterized in that: The organic solvent is any one of toluene, dichloromethane, and dioxane.

7. The use of the dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compound of claim 1 in the preparation of antitumor drugs.

8. The use of the dibenzo-1,3-oxazacyclopentanoisoquinoline-1(2H)-one compound according to claim 7 in the preparation of antitumor cell drugs, characterized in that: The tumor can be any one of leukemia, lung cancer, liver cancer, or breast cancer.

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