2'-acetyl-2',3'-dihydro-4'h-spiro[cyclohexane-1,1'-isoquinoline]-4'-ketone compounds, processes for their preparation and uses thereof

Abstract

The application belongs to the technical field of medicines, and particularly relates to 2'-acetyl-2',3'-dihydro-4' H -[cyclohexane-1,1'-isoquinoline]-4'-ketone compounds, a preparation method and uses thereof. The application patent first synthesizes a six-membered spiro ring structure containing an acetyl group, and obtains a novel compound with more antitumor effect. Pharmacological research shows that the compound has certain inhibitory activity on human breast cancer MCF-7 cells.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to a class of compounds with specific chemical structures possessing antitumor activity, specifically 2'-acetyl-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one compounds, their preparation methods and uses. Background Technology

[0002] Malignant tumors seriously endanger human health, with their incidence and mortality rates constantly rising. Their defining characteristic is the uncontrolled division and spread of abnormal cells within the body. Therefore, the synthesis of effective new anticancer drugs is one of the most important goals of modern medicinal chemistry. Breast cancer, as one of the most common malignant tumors in women, has the highest incidence rate among female malignant tumors. Currently, the main clinical treatment for breast cancer is chemotherapy. While current antitumor drugs have good efficacy, they also suffer from problems such as drug resistance, poor selectivity, and significant toxic side effects.

[0003] Therefore, the discovery of novel, previously unreported antitumor compounds can provide new options and possibilities for the development of new anticancer drugs, thus providing a new direction for new drug research and development in my country. Summary of the Invention

[0004] The object of this invention is to provide 2'-acetyl-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one compounds and their preparation methods were described. The prepared compounds showed good results in in vitro antitumor activity tests.

[0005] The 2'-acetyl-2',3'-dihydro-4' provided by this invention H The general structural formulas of spiro[cyclohexane-1,1'-isoquinoline]-4'-one compounds are as follows:

[0006]

[0007] general formula

[0008] Wherein: R group is alkyl, chloro-substituted alkyl, bromo-substituted alkyl, alkenyl, alkenyl, ester or ether.

[0009] The compounds, isomers, and pharmaceutically acceptable salts, hydrates, or prodrugs of the general formulas described in this invention are particularly preferred, but these compounds do not imply any limitation on the invention:

[0010] 2'-(2-chloroacetyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-1);

[0011] Ethyl 2-oxo-2-(4'-oxo-3',4'-dihydro-2') H 1-spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)acetate (T-2);

[0012] 3-Oxo-3-(4'-Oxo-3', 4'-Dihydro-2') H methyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)propionate (T-3);

[0013] 2'-(but-2-enyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-4);

[0014] 2'-Acryloyl-2',3'-Dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-5);

[0015] 2'-(4-chlorobutyryl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-6);

[0016] 4-Oxo-4-(4'-Oxo-3', 4'-Dihydro-2') H ethyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl]butyrate (T-7);

[0017] 2'-(2-methoxyacetyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-8);

[0018] 2'-(2-bromoacetyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-9);

[0019] 2'-(4-bromobutyryl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-10);

[0020] 2'-(pent-4-enyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-11);

[0021] 2'-(6-bromohexanoyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-12);

[0022] 2-Oxo-2-(4'-Oxo-3', 4'-Dihydro-2') H ethyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl]ethyl acetate (T-13);

[0023] 2'-(3-methylbutyryl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-14);

[0024] 2'-(4-methylpentanoyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-15);

[0025] 4-Oxo-4-(4'-Oxo-3', 4'-Dihydro-2') H methyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)butyrate (T-16);

[0026] 2'-(3-cyclopentylpropionyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-17).

[0027] To achieve the above objectives, the present invention also provides the 2'-acetyl-2',3'-dihydro-4' H Preparation method of -spiro[cyclohexane-1,1'-isoquinoline]-4'-one compounds.

[0028] The preparation method of the compound specifically includes the following steps:

[0029] Step 1: Add bromobenzene and magnesium strip to the reaction flask and dissolve them in an appropriate amount of diethyl ether. After the classic Grignard reagent reaction, 1-phenylcyclohexanol is obtained.

[0030] Step 2: Add 1-phenylcyclohexanol and an appropriate amount of dichloromethane as solvent to the reaction flask, and obtain 1-azido-1-phenylcyclohexane through the azidation reaction;

[0031] Step 3: Add 1-azido-1-phenylcyclohexane to the reaction flask, using tetrahydrofuran as a solvent, and reduce it to obtain 1-amino-1-phenylcyclohexane.

[0032] Step 4: Add 1-amino-1-phenylcyclohexane to the reaction flask, using acetonitrile as the solvent, and proceed with the alkylation reaction to obtain (1-phenylcyclohexyl)glycine ethyl ester;

[0033] Step 5: Add ethyl ester of (1-phenylcyclohexyl)glycine to the reaction flask, with an appropriate amount of water as a solvent, and obtain (1-phenylcyclohexyl)glycine through hydrolysis reaction;

[0034] Step 6: Add (1-phenylcyclohexyl)glycine and an appropriate amount of dichloromethane as solvent to the reaction flask, and halogenate to obtain (1-phenylcyclohexyl)glycyl chloride;

[0035] Step 7: Add (1-phenylcyclohexyl)glycyl chloride and an appropriate amount of dichloromethane as solvent to the reaction flask, and proceed with the Friedel-Crafts acylation reaction to obtain 2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one;

[0036] Step 8: Add 2',3'-dihydro-4' to the reaction flask H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one, using tetrahydrofuran as solvent and triethylamine as acid-binding agent, with the addition of an R-substituted acyl chloride, followed by an acylation reaction, yields the target compound with the general structural formula described above.

[0037] Furthermore, the present invention also includes prodrugs derived from the present invention. These prodrugs are derivatives of a general formula, which may themselves have weak or no activity, but are converted into their corresponding biologically active forms under physiological conditions (e.g., through metabolism, solvation, or other means) after administration.

[0038] This invention may contain the general formula 2'-acetyl-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one compounds, and their pharmaceutically acceptable salts and solvates as active ingredients, are mixed with pharmaceutically acceptable carriers or excipients to prepare pharmaceutical compositions and clinically acceptable dosage forms. The aforementioned pharmaceutically acceptable excipients refer to any diluent, adjuvant, and / or carrier that can be used in the pharmaceutical field. The derivatives of this invention can be used in combination with other active ingredients, provided they do not produce other adverse effects, such as allergic reactions.

[0039] The pharmaceutical compositions of the present invention can be formulated into several dosage forms, containing some commonly used excipients in the pharmaceutical field. The dosage forms described above can be injections, tablets, capsules, aerosols, suppositories, films, pellets, topical liniments, ointments, and other dosage forms.

[0040] The carriers used in the pharmaceutical compositions of this invention are common types available in the pharmaceutical field, including: binders, lubricants, disintegrants, solubilizers, diluents, stabilizers, suspending agents, colorants, flavoring agents, preservatives, solvents, and matrices, etc.

[0041] This invention comprises any of the 2'-acetyl-2',3'-dihydro-4' described above. H The use of spiro[cyclohexane-1,1'-isoquinoline]-4'-one compounds, isomers, pharmaceutically acceptable salts, hydrates, and pharmaceutical compositions in the preparation of antitumor drugs; said pharmaceutical composition comprising any of the 2'-acetyl-2',3'-dihydro-4'-ones described herein. H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one compounds, their pharmaceutically acceptable salts, hydrates or solvates and pharmaceutically acceptable carriers.

[0042] The anti-tumor drug mentioned is an anti-human breast cancer cell (MCF-7) drug.

[0043] Compared with the prior art, the beneficial effects of the present invention are as follows.

[0044] In the design process of this invention, 2'-acetyl-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one compounds significantly improved antitumor effects and were found to exhibit superior anti-proliferative activity against human breast cancer cells (MCF-7). The synthetic steps were optimized, making future industrial production possible. Detailed Implementation

[0045] The present invention will be further described below with reference to specific embodiments. These embodiments are merely illustrative and do not limit the scope of the present invention.

[0046] Example 1.

[0047] 2'-(2-chloroacetyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-1).

[0048] a. Preparation of 1-phenylcyclohexanol

[0049] Bromobenzene (50 g, 0.31 mol) and magnesium ribbon (8.13 g, 0.33 mol) were added to a 1000 mL three-necked flask and dissolved in an appropriate amount of diethyl ether. The reaction was initiated at 35 °C. After the reaction was complete, cyclohexanone (34.38 g, 0.35 mol) was added, and the reaction was carried out at 35 °C for 5 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the reaction solution was added to a saturated ammonium chloride aqueous solution and extracted with diethyl ether. The extract was dried and evaporated under reduced pressure to obtain the product, with a yield of 95.9%.

[0050] b. Preparation of 1-azido-1-phenylcyclohexane

[0051] 1-Phenylon (20.00 g, 0.11 mol), 500 mL of dichloromethane, sodium azide (8.11 g, 0.12 mol), and trifluoroacetic acid (25.88 g, 0.23 mol) were added to a 1000 mL reaction flask. The reaction was carried out at room temperature for 15 hours, and the reaction progress was monitored by thin-layer chromatography. After the reaction was completed, a saturated sodium carbonate aqueous solution was added to the reaction solution, and the mixture was extracted with dichloromethane. The extract was dried and evaporated under reduced pressure to obtain the product, with a yield of 97.8%.

[0052] c. Preparation of 1-amino-1-phenylcyclohexane

[0053] 1-Azide-1-phenylcyclohexane (13 g, 0.064 mol), tetrahydrofuran (500 mL), and lithium aluminum hydride (4.77 g, 0.13 mol) were added to a 1000 mL reaction flask. After reacting at room temperature for 4 hours, the temperature was increased to 40-60℃ to continue the reaction, and the reaction progress was monitored by thin-layer chromatography. After the reaction was completed, aqueous solution and sodium hydroxide solution were added to the reaction solution in sequence, filtered, and the filtrate was evaporated under reduced pressure. Then, a small amount of water was added and the pH was adjusted to acidic. Impurities were extracted with diethyl ether, and the pH was adjusted to alkaline after extraction. Dichloromethane was extracted, and the extract was dried and evaporated under reduced pressure to obtain the product. The yield was 90.43%.

[0054] d. Preparation of (1-phenylcyclohexyl)glycine ethyl ester

[0055] 1-Amino-1-phenylcyclohexane (20.00 g, 0.11 mol), ethyl bromoacetate (17.15 g, 0.10 mol), and K₂CO₃ (31.54 g, 0.23 mol) were added to a 500 mL reaction flask. The reaction was carried out at 90 °C for 17 hours, and the reaction progress was monitored by thin-layer chromatography. After the reaction was completed, an appropriate amount of water was added to dissolve the product, and the product was extracted with ethyl acetate. The extract was dried, evaporated under reduced pressure, and then purified by column chromatography to obtain the product. The yield was 80.5%.

[0056] e. Preparation of (1-phenylcyclohexyl)glycine

[0057] (1-Phenylonyl)glycine ethyl ester (15.00 g, 0.057 mol), sodium hydroxide (4.59 g, 0.115 mol), and 300 mL of water were added to a 500 mL reaction flask. The reaction was carried out at 50 °C for 1.5 hours, and the reaction progress was monitored by thin-layer chromatography. After the reaction was completed, impurities were extracted with ethyl acetate, the pH of the aqueous layer was adjusted to 5, and the solvent was removed by vacuum evaporation until solid precipitates. A large amount of dichloromethane was added to dissolve the solid, and the filtrate was filtered. The filtrate was dried and evaporated under reduced pressure to obtain the product. The yield was 98.15%.

[0058] f. Preparation of (1-phenylcyclohexyl)glycyl chloride

[0059] (1-Phenylonyl)glycine (20.00 g, 0.086 mol), thionyl chloride (20.39 g, 0.171 mol), and 300 mL of dichloromethane were added to a 500 mL reaction flask. The reaction was carried out at 40 °C, and the reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the product was obtained by evaporation under reduced pressure, yield: 100%.

[0060] g. 2',3'-dihydro-4' H Preparation of spiro[cyclohexane-1,1'-isoquinoline]-4'-one

[0061] (1-Phenylonyl)glycyl chloride (9 g, 0.036 mol) and 200 mL of dichloromethane were added to a 500 mL reaction flask. The reaction was carried out at 70 °C until dissolved, then the temperature was lowered to 45 °C, and aluminum trichloride (14.30 g, 0.107 mol) was added to continue the reaction. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the reaction solution was added to a mixture of hydrochloric acid and ice water. Impurities were extracted with diethyl ether, and the aqueous layer was collected to adjust the pH to alkaline. The solution was extracted with ethyl acetate, dried, evaporated under reduced pressure, and then purified by column chromatography to obtain the product. Yield: 38.2%.

[0062] h. 2'-(2-chloroacetyl)-2',3'-dihydro-4' H Preparation of spiro[cyclohexane-1,1'-isoquinoline]-4'-one

[0063] Add 2',3'-dihydro-4' to a 100 mL reaction flask H Spiro[cyclohexane-1,1'-isoquinoline]-4'-one (300 mg, 1.19 mmol), triethylamine (315.52 mg, 3.10 mmol), and a suitable amount of tetrahydrofuran were dissolved in the solution. Chloroacetyl chloride (161.50 mg, 1.43 mmol) was slowly added dropwise at -10°C until no smoke was observed. The reaction was then allowed to proceed at room temperature for 8 hours, and the reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was filtered, and the filtrate was evaporated under reduced pressure and then purified by column chromatography to obtain the product 2'-(2-chloroacetyl)-2',3'-dihydro-4'-one. H 1-spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-1), off-white solid, yield: 47.4%.

[0064] 1 H NMR (600 MHz, DMSO- d 6) d 7.83 (dd, J= 7.7, 1.4 Hz, 1H), 7.65 (td, J =7.6, 1.5 Hz, 1H), 7.49 – 7.43 (m, 2H), 4.44 (s, 2H), 4.42 (s, 2H), 2.76 (s,2H), 1.72 – 1.64 (m, 5H), 1.43 (qt, J = 13.1, 3.5 Hz, 2H), 1.31 (tdt, J = 13.3, 9.0, 4.1 Hz, 1H); 13 C NMR (151 MHz, DMSO- d 6) d 194.24, 169.19, 150.01, 134.65, 130.31, 127.93, 127.63, 123.58, 60.66, 53.59, 44.85, 36.71, 25.23, 22.82.

[0065] Example 2.

[0066] Ethyl 2-oxo-2-(4'-oxo-3',4'-dihydro-2') H -spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)acetate (T-2).

[0067] 2',3'-Dihydro-4' H The preparation of spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out according to the steps in Example 1g, using monoethyl oxalyl chloride as a raw material, and following the steps in Example 1h to obtain 2-oxo-2-(4'-oxo-3',4'-dihydro-2'-) H ethyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl] (T-2), off-white solid, yield: 48.2%.

[0068] 1 H NMR (600 MHz, DMSO- d 6) d 7.90 (dd, J = 7.7, 1.4 Hz, 1H), 7.70 (td, J =7.6, 1.5 Hz, 1H), 7.51 (dt, J = 15.1, 7.7 Hz, 2H), 4.38 (s, 2H), 4.26 (q, J= 7.1Hz, 2H), 2.77 (s, 2H), 1.83 – 1.68 (m, 5H), 1.44 (dtd, J = 16.8, 9.4, 6.6, 3.3Hz, 2H), 1.35 (qt, J = 12.4, 4.2 Hz, 1H), 1.22 (t, J = 7.1 Hz, 3H); 13 C NMR (151MHz, DMSO- d 6) d 192.88, 163.73, 162.69, 149.45, 135.12, 129.69, 128.39, 127.95, 123.90, 62.54, 62.16, 53.15, 36.41, 24.91, 23.06, 14.07.

[0069] Example 3.

[0070] 3-Oxo-3-(4'-Oxo-3', 4'-Dihydro-2') H methyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)propionate (T-3).

[0071] 2',3'-Dihydro-4' H The preparation of 3-spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out as per the steps of Example 1g, using methyl malonate chloride as a starting material, and following the steps of Example 1h to obtain 3-oxo-3-(4'-oxo-3',4'-dihydro-2'-) H methyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)propionate (T-3), yellow solid, yield: 40.7%.

[0072] 1 H NMR (600 MHz, DMSO- d 6) d 7.83 (dd, J = 7.7, 1.5 Hz, 1H), 7.64 (td, J =7.6, 1.5 Hz, 1H), 7.49 – 7.41 (m, 2H), 4.40 (s, 2H), 3.65 (s, 2H), 3.53 (s, 3H), 2.77 (s, 2H), 1.71 – 1.62 (m, 5H), 1.46 (dtd, J= 14.5, 11.1, 10.3, 3.6 Hz,2H), 1.32 (tdt, J = 13.4, 9.3, 4.3 Hz, 1H); 13 C NMR (151 MHz, DMSO- d 6) d 194.31, 168.80, 168.67, 150.22, 134.53, 130.43, 127.81, 127.52, 123.60, 60.84, 53.83, 52.21, 44.08, 25.25, 22.77, 14.54.

[0073] Example 4.

[0074] 2'-(but-2-enyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-4).

[0075] 2',3'-Dihydro-4' H The preparation of spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out according to the steps in Example 1g, using 2-butenoyl chloride as a starting material, and following the steps in Example 1h to obtain 2'-(but-2-enyl)-2',3'-dihydro-4'-one. H 1-spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-4), pale yellow solid, yield: 56.6%.

[0076] 1 H NMR (600 MHz, DMSO- d 6) d 7.82 (ddd, J = 16.2, 7.7, 1.5 Hz, 1H), 7.65(qd, J = 7.7, 1.5 Hz, 1H), 7.49 (ddd, J = 14.5, 7.9, 1.1 Hz, 1H), 7.45 – 7.40 (m,1H), 6.53 (dq, J = 15.1, 6.8 Hz, 1H), 6.33 (dq, J = 15.1, 1.6 Hz, 1H), 4.47 (s,2H), 2.79 (s, 2H), 1.80 (dd, J = 6.8, 1.6 Hz, 3H), 1.73 – 1.61 (m, 5H), 1.43(pt,J = 13.1, 3.4 Hz, 2H), 1.31 (tdt, J = 12.6, 8.5, 3.8 Hz, 1H); 13 C NMR (151MHz, DMSO- d 6) d 194.60, 170.05, 151.12, 141.47, 134.75, 130.05, 127.59, 127.51, 126.30, 123.73, 59.43, 54.12, 25.34, 22.65, 18.04, 15.41.

[0077] Example 5.

[0078] 2'-Acryloyl-2',3'-Dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-5).

[0079] 2',3'-Dihydro-4' H The preparation of -spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out according to the steps in Example 1g, using 3-chloropropionyl chloride as a starting material, and 2'-acryloyl-2',3'-dihydro-4'-one was prepared according to the steps in Example 1h. H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-5), gray solid, yield: 45.8%.

[0080] 1 H NMR (600 MHz, DMSO- d 6) d 7.81 (dd, J = 7.7, 1.5 Hz, 1H), 7.66 (td, J =7.6, 1.5 Hz, 1H), 7.49 (dd, J = 7.8, 1.1 Hz, 1H), 7.43 (td, J = 7.5, 1.1 Hz, 1H), 6.63 (dd, J = 16.9, 10.5 Hz, 1H), 5.96 (dd, J = 16.9, 1.9 Hz, 1H), 5.65 (dd, J =10.4, 1.9 Hz, 1H), 4.48 (s, 2H), 2.80 (s, 2H), 1.75 – 1.62 (m, 5H), 1.43(dtd,J = 13.2, 9.6, 3.0 Hz, 2H), 1.32 (tdt, J = 12.7, 8.6, 4.0 Hz, 1H); 13 C NMR (151 MHz, DMSO-) d 6) d 194.38, 169.93, 150.85, 134.79, 132.56, 130.07, 127.81, 127.71, 127.59, 123.76, 59.74, 54.04, 36.35, 25.29, 22.69.

[0081] Example 6.

[0082] 2'-(4-chlorobutyryl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-6).

[0083] 2',3'-Dihydro-4' H The preparation of 2'-(4-chlorobutyryl)-2',3'-dihydro-4'-one was carried out according to the steps in Example 1g, using 4-chlorobutyryl chloride as a starting material, following the steps in Example 1h. H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-6), brown solid, yield: 50.2%.

[0084] 1 H NMR (600 MHz, DMSO- d 6) d 7.81 (dd, J = 7.7, 1.4 Hz, 1H), 7.64 (td, J =7.6, 1.5 Hz, 1H), 7.47 (d, J = 7.8 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H), 4.45 (s,2H), 3.60 (t, J = 6.6 Hz, 2H), 2.80 (s, 2H), 2.54 (t, J = 7.2 Hz, 2H), 1.86 (p, J =6.9 Hz, 2H), 1.72 – 1.62 (m, 5H), 1.41 (dtd, J= 14.0, 10.5, 3.4 Hz, 2H), 1.32(tt, J = 13.2, 4.0 Hz, 1H); 13 C NMR (151 MHz, DMSO- d 6) d 194.71, 174.62, 150.78, 134.62, 130.32, 127.70, 127.59, 123.63, 60.39, 53.26, 45.28, 36.97, 33.31, 28.76, 25.30, 22.90.

[0085] Example 7.

[0086] 4-Oxo-4-(4'-Oxo-3', 4'-Dihydro-2') H ethyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)butyrate (T-7).

[0087] 2',3'-Dihydro-4' H The preparation of 4-spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out according to the steps in Example 1g, using monoethyl succinate chloride as a raw material, and following the steps in Example 1h to obtain 4-oxo-4-(4'-oxo-3',4'-dihydro-2'-) H ethyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)butyrate (T-7), brown solid, yield: 46.2%.

[0088] 1 H NMR (600 MHz, DMSO- d 6) d 7.81 (dd, J = 7.6, 1.4 Hz, 1H), 7.63 (td, J =7.6, 1.5 Hz, 1H), 7.50 – 7.39 (m, 2H), 4.48 (s, 2H), 3.97 (q, J = 7.1 Hz, 2H),2.84 – 2.74 (m, 2H), 2.65 (dd, J = 7.4, 5.1 Hz, 2H), 2.42 (dd, J = 7.4, 5.2 Hz, 2H), 1.64 (dq, J = 20.0, 7.4, 5.7 Hz, 5H), 1.45 (dtd, J= 13.4, 9.8, 3.1 Hz, 2H),1.30 (tdt, J = 12.9, 8.7, 4.1 Hz, 1H), 1.17 (q, J = 6.9 Hz, 3H); 13 C NMR (151 MHz, DMSO- d 6) d 207.84, 194.73, 174.17, 172.72, 150.77, 134.57, 130.37, 127.68, 127.55, 123.59, 53.17, 36.91, 31.06, 29.79, 28.03, 25.33, 22.74, 21.20.

[0089] Example 8.

[0090] 2'-(2-methoxyacetyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-8).

[0091] 2',3'-Dihydro-4' H The preparation of 2'-spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out according to the steps in Example 1g, using methoxyacetyl chloride as a starting material, following the steps in Example 1h to obtain 2'-(2-methoxyacetyl)-2',3'-dihydro-4'-one. H 1-spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-8), off-white solid, yield: 54.4%.

[0092] 1 H NMR (600 MHz, DMSO- d 6) d 7.81 (dd, J = 7.7, 1.4 Hz, 1H), 7.64 (td, J =7.6, 1.5 Hz, 1H), 7.48 (d, J = 7.8 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 4.41 (s,2H), 4.06 (s, 2H), 3.27 (s, 3H), 2.79 (s, 2H), 1.72 – 1.65(m, 5H), 1.44 (dtd, J = 14.0, 10.6, 3.4 Hz, 2H), 1.32 (tdt, J= 13.4, 9.0, 3.9 Hz, 1H); 13 C NMR (151MHz, DMSO- d 6) d 194.70, 172.50, 150.47, 134.57, 130.31, 127.80, 127.60, 123.59, 73.68, 60.49, 58.66, 52.65, 36.57, 25.18, 22.92.

[0093] Example 9.

[0094] 2'-(2-bromoacetyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-9).

[0095] 2',3'-Dihydro-4' H The preparation of 2'-spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out according to the steps in Example 1g, using bromoacetyl chloride as a starting material, following the steps in Example 1h to obtain 2'-(2-bromoacetyl)-2',3'-dihydro-4'-one. H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-9), gray solid, yield: 50.8%.

[0096] 1 H NMR (600 MHz, DMSO- d 6) d 7.84 – 7.81 (m, 1H), 7.66 (td, J = 7.6, 1.4Hz, 1H), 7.49 – 7.42 (m, 2H), 4.47 (s, 2H), 4.21 (s, 2H), 2.77 (s, 2H), 1.75 –1.62 (m, 5H), 1.44 (dqd, J = 13.2, 10.1, 3.2 Hz, 2H), 1.31 (tdt, J = 13.3, 8.9, 4.1 Hz, 1H); 13 C NMR (151 MHz, DMSO- d 6) d 194.22, 169.13, 149.98, 134.69, 130.30, 127.95, 127.62, 123.64, 60.73, 54.19, 44.85, 31.65, 25.25, 22.82.

[0097] Example 10.

[0098] 2'-(4-bromobutyryl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-10).

[0099] 2',3'-Dihydro-4' H The preparation of 2'-(4-bromobutyryl)-2',3'-dihydro-4'-one was carried out according to the steps in Example 1g, using 4-bromobutyryl chloride as a starting material, following the steps in Example 1h. H 1-spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-10), pale yellow solid, yield: 53.2%.

[0100] 1 H NMR (600 MHz, DMSO- d 6) d 7.94 (dd, J = 7.7, 1.4 Hz, 1H), 7.84 – 7.80(m,1H), 7.76 (td, J = 7.7, 1.5 Hz, 1H), 7.64 (td, J = 7.6, 1.5 Hz, 1H), 4.93 (t, J =7.5 Hz, 2H), 4.89 (s, 2H), 4.45 (s, 2H), 2.80 (s, 2H), 2.62 (d, J = 14.3 Hz,2H), 2.01 – 1.91 (m, 5H), 1.54 (qt, J = 13.4, 3.1 Hz, 2H), 1.24 (d, J = 4.0 Hz, 1H); 13 C NMR (151 MHz, DMSO- d 6) d 194.70, 184.58, 150.77, 145.78, 135.37, 134.64, 82.05, 69.30, 60.41, 58.17, 53.26, 34.92, 28.97, 25.29, 22.85, 21.24.

[0101] Example 11.

[0102] 2'-(pent-4-enyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-11).

[0103] 2',3'-Dihydro-4' H The preparation of -spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out according to the steps in Example 1g, using 4-pentenoyl chloride as a starting material, and 2'-(pent-4-enyl)-2',3'-dihydro-4'-one was prepared according to the steps in Example 1h. H 1-spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-11), yellow solid, yield: 51.9%.

[0104] 1 H NMR (600 MHz, DMSO- d 6) d 7.81 (dd, J = 7.7, 1.4 Hz, 1H), 7.63 (td, J =7.6, 1.5 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.42 (t, J = 7.5 Hz, 1H), 5.77 (ddt, J = 16.8, 10.2, 6.4 Hz, 1H), 5.00 (dq, J = 17.2, 1.8 Hz, 1H), 4.92 (dd, J = 10.2,1.9 Hz, 1H), 4.45 (s, 2H), 2.80 (s, 2H), 2.55 – 2.45 (m, 2H), 2.18 (q, J = 6.9Hz, 2H), 1.72 – 1.61 (m, 5H), 1.48 – 1.37 (m, 2H), 1.31 (tt, J = 12.8, 4.1 Hz, 1H); 13 C NMR (151 MHz, DMSO- d 6) d 194.87, 174.97, 150.91, 138.12, 134.58, 130.35, 127.66, 127.55, 123.63, 115.61, 60.26, 53.34, 36.95, 35.38, 29.65, 25.29, 22.82.

[0105] Example 12.

[0106] 2'-(6-bromohexanoyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-12).

[0107] 2',3'-Dihydro-4' H The preparation of 2'-(6-bromohexanoyl)-2',3'-dihydro-4'-one was carried out according to the steps in Example 1g, using 6-bromohexanoyl chloride as a starting material, following the steps in Example 1h. H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-12), gray solid, yield: 43.2%.

[0108] 1 H NMR (600 MHz, DMSO- d 6) d 7.81 (dd, J = 7.7, 1.5 Hz, 1H), 7.63 (td, J =7.6, 1.5 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.42 (td, J = 7.5, 1.1 Hz, 1H), 4.45(s, 2H), 3.48 (t, J = 6.7 Hz, 2H), 2.80 (s, 2H), 2.38 (t, J = 7.3 Hz, 2H), 1.77(p, J = 6.8 Hz, 2H), 1.71 – 1.60 (m, 5H), 1.43 (ddd, J = 13.1, 8.3, 5.3 Hz, 4H),1.37 – 1.29 (m, 3H); 13 C NMR (151 MHz, DMSO- d 6) d 194.90, 175.56, 150.97, 134.59, 130.31, 127.64, 127.55, 123.63, 60.21, 53.37, 36.97, 36.01, 35.50, 32.48, 27.68, 25.33, 24.74, 22.88.

[0109] Example 13.

[0110] 2-Oxo-2-(4'-Oxo-3', 4'-Dihydro-2') H ethyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl] (T-13).

[0111] 2',3'-Dihydro-4' H The preparation of -spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out as per the steps of Example 1g, using acetoxyacetyl chloride as a starting material, and following the steps of Example 1h to obtain 2-oxo-2-(4'-oxo-3',4'-dihydro-2'-) H ethyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl] (T-13), brown solid, yield: 47.9%.

[0112] 1 H NMR (600 MHz, DMSO- d 6) d 7.82 (dd, J = 7.7, 1.5 Hz, 1H), 7.64 (td, J =7.6, 1.5 Hz, 1H), 7.49 – 7.43 (m, 2H), 4.75 (s, 2H), 4.38 (s, 2H), 2.75 (s, 2H), 2.04 (s, 3H), 1.72 – 1.58 (m, 5H), 1.44 (dtd, J = 13.1, 9.7, 2.9 Hz, 2H),1.34 – 1.23 (m, 1H); 13 C NMR (151 MHz, DMSO- d 6) d 194.32, 170.33, 169.43, 150.27, 134.61, 130.32, 127.85, 127.62, 123.53, 63.66, 60.63, 52.15, 25.23, 22.71, 20.81, 14.55.

[0113] Example 14.

[0114] 2'-(3-methylbutyryl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-14).

[0115] 2',3'-Dihydro-4' HThe preparation of -spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out according to the steps in Example 1g, using isovaleryl chloride as a starting material, and 2'-(3-methylbutyryl)-2',3'-dihydro-4'-one was prepared according to the steps in Example 1h. H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-14), brown solid, yield: 44.2%.

[0116] 1 H NMR (600 MHz, DMSO- d 6) d 7.80 (dd, J = 7.6, 1.5 Hz, 1H), 7.64 (td, J =7.6, 1.5 Hz, 1H), 7.50 – 7.46 (m, 1H), 7.42 (td, J = 7.5, 1.1 Hz, 1H), 4.45 (s,2H), 2.81 (s, 2H), 2.26 (d, J = 6.9 Hz, 2H), 1.92 (m, J = 6.7 Hz, 1H), 1.70 –1.62 (m, 5H), 1.43 (dtd, J = 14.1, 10.5, 3.4 Hz, 2H), 1.36 – 1.26 (m, 1H), 0.84(d, J = 6.6 Hz, 6H); 13 C NMR (151 MHz, DMSO- d 6) d 194.86, 175.26, 151.05, 134.62, 130.28, 127.64, 127.53, 123.69, 60.26, 53.42, 45.10, 36.97, 29.70, 25.76, 25.32, 22.82.

[0117] Example 15.

[0118] 2'-(4-methylpentanoyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-15).

[0119] 2',3'-Dihydro-4' HThe preparation of -spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out according to the steps in Example 1g, using isohexanoyl chloride as a starting material, and 2'-(4-methylpentanoyl)-2',3'-dihydro-4'-one was prepared according to the steps in Example 1h. H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-15), gray solid, yield: 50.2%.

[0120] 1 H NMR (600 MHz, DMSO- d 6) d 8.08 (d, J = 7.8 Hz, 1H), 7.95 (dd, J = 7.6, 1.2Hz, 1H), 7.80 (td, J = 7.6, 1.3 Hz, 1H), 7.65 (t, J = 7.6 Hz, 1H), 2.65 (td, J =13.3, 4.8 Hz, 2H), 2.04 – 1.96 (m, 2H),1.88 (ddd, J = 13.7, 8.0, 3.7 Hz, 2H),1.79 (ddd, J = 14.1, 6.6, 3.5 Hz, 2H), 1.50 (dq, J = 13.2, 2.3 Hz, 5H), 1.36 (dt, J = 13.6, 3.9 Hz, 1H), 1.24 (d, J = 5.7 Hz, 2H), 1.17 (t, J = 7.1 Hz, 1H), 0.91(t, J = 7.4 Hz, 3H), 0.85 (t, J = 6.9 Hz, 3H); 13 C NMR (151 MHz, DMSO- d 6) d 168.70, 160.99, 152.55, 135.15, 129.47, 127.91, 125.48, 125.17, 66.16, 60.22, 32.22, 31.75, 27.02, 24.54, 22.06, 14.42, 0.58.

[0121] Example 16.

[0122] 4-Oxo-4-(4'-Oxo-3', 4'-Dihydro-2') H methyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)butyrate (T-16).

[0123] 2',3'-Dihydro-4' H The preparation of 4-spiro[cyclohexane-1,1'-isoquinoline]-4'-one was carried out according to the steps in Example 1g, using monomethyl succinate chloride as a raw material, and 4-oxo-4-(4'-oxo-3',4'-dihydro-2') was prepared according to the steps in Example 1h. H 1-spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)methyl butyrate (T-16), yellow solid, yield: 57.3%.

[0124] 1 H NMR (600 MHz, DMSO- d 6) d 7.81 (dd, J = 7.7, 1.5 Hz, 1H), 7.63 (td, J =7.6, 1.5 Hz, 1H), 7.48 – 7.40 (m, 2H), 4.48 (s, 2H), 3.51 (s, 3H), 2.78 (dh, J = 15.2, 6.8 Hz, 2H), 2.69 – 2.62 (m, 2H), 2.46 – 2.38 (m, 2H), 1.72 – 1.60 (m,5H), 1.44 (qt, J = 11.1, 2.6 Hz, 2H), 1.31 (ddt, J = 12.7, 8.1, 4.1 Hz, 1H); 13 CNMR (151 MHz, DMSO- d 6) d 194.74, 174.17, 173.22, 150.77, 134.59, 130.37, 127.70, 127.57, 123.60, 60.49, 53.18, 51.68, 36.96, 31.05, 29.61, 25.32, 22.73.

[0125] Example 17.

[0126] 2'-(3-cyclopentylpropionyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-17).

[0127] 2',3'-Dihydro-4' H The preparation of 2'-(3-cyclopentylpropionyl)-2',3'-dihydro-4'-one was carried out according to the steps in Example 1g, using 3-cyclopentylpropionyl chloride as a starting material, following the steps in Example 1h. H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one (T-17), brown solid, yield: 48.7%.

[0128] 1 H NMR (600 MHz, DMSO- d 6) d 7.81 (dd, J = 7.7, 1.5 Hz, 1H), 7.63 (td, J =7.6, 1.5 Hz, 1H), 7.48 – 7.45 (m, 1H), 7.42 (td, J = 7.5, 1.1 Hz, 1H), 4.44 (s,2H), 2.79 (s, 2H), 2.40 – 2.35(m, 2H), 1.71 – 1.62 (m, 8H), 1.58 – 1.50 (m,2H), 1.47 – 1.39 (m, 6H), 1.31 (tdt, J = 13.7, 9.0, 4.3 Hz, 1H), 1.08 – 1.00(m, 2H); 13 C NMR (151 MHz, DMSO- d 6) d 194.93, 175.87, 175.04, 150.99, 134.61, 130.30, 127.65, 127.54, 123.66, 60.13, 53.43, 36.95, 35.58, 32.48, 31.89, 25.32, 25.12, 22.86.

[0129] Experiments to inhibit tumor cell proliferation.

[0130] The compounds of the present invention were subjected to tumor cell proliferation inhibition experiments using the conventional MTT assay.

[0131] Tumor cell culture: The cell line used was MCF-7 (human breast cancer cells) cultured in McCoy's 5A + 10% FBS + double antibiotics (penicillin 100 units / ml, streptomycin 100 μg / ml).

[0132] Sample preparation: Dissolve the sample in DMSO (Merck), then add it to culture medium to prepare a 1000 μg / ml solution or a homogeneous suspension. Dilute with DMSO-containing culture medium. The final concentrations were 50 µM, 25 µM, 12.5 µM, 6.25 µM, and 3.125 µM. Rucaparib was used as a control.

[0133] Assay for cell proliferation inhibition: Add 4–5 × 10⁻⁵ cells per well of a 96-well plate. 4 100 μl of cell suspension per cell / ml was incubated at 37°C in a 5% CO2 incubator. After 24 hours, 10 μl of sample solution and control solution were added to each well, with duplicate wells, and incubated at 37°C in a 5% CO2 incubator for 24 hours. 20 μl of 5 mg / ml MTT (3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide) solution was added to each well, and after incubation for 4 hours, 150 μl of DMSO dissolving solution was added to each well. After dissolution, the OD value was measured at 490 nm using an MK-2 automated microplate reader, and the IC50 inhibitory concentration was calculated. 50 value.

[0134] The experimental results are shown in Table 1.

[0135] Table 1. In vitro inhibitory activity (IC50) of the samples against human tumor cells 50 value.

[0136]

[0137] The experimental data above show that most of the compounds in this invention have good in vitro antitumor activity, and are of great value for further research and development of new antitumor drugs, and also provide a broader perspective for new drug development.

[0138] This invention relates to 2'-acetyl-2',3'-dihydro-4' H This invention relates to spiro[cyclohexane-1,1'-isoquinoline]-4'-one compounds and their preparation methods, belonging to the field of pharmaceutical technology, specifically relating to a class of compounds with specific chemical structures possessing antitumor activity; these compounds are pharmaceutically acceptable salts, hydrates, or solvates of the general formula. Based on tumor cell line testing (human breast cancer cells), this invention demonstrates that the compounds possess tumor-inhibiting activity. The compounds provided by this invention are readily available, and experiments have shown that they have good anticancer effects, exhibiting promising application prospects in the design and development of antitumor drugs.

Claims

1. A compound, characterized in that, The structure of the compound is selected from any of the following: 2'-(2-chloroacetyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; Ethyl 2-oxo-2-(4'-oxo-3',4'-dihydro-2') H 1-spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)acetate; 3-Oxo-3-(4'-Oxo-3', 4'-Dihydro-2') H methyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)propionate; 2'-(but-2-enyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; 2'-Acryloyl-2',3'-Dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; 2'-(4-chlorobutyryl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; 4-Oxo-4-(4'-Oxo-3', 4'-Dihydro-2') H ethyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)butyrate; 2'-(2-methoxyacetyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; 2'-(2-bromoacetyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; 2'-(4-bromobutyryl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; 2'-(pent-4-enyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; 2'-(6-bromohexanoyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; 2-Oxo-2-(4'-Oxo-3', 4'-Dihydro-2') H ethyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl]; 2'-(3-methylbutyryl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; 2'-(4-methylpentanoyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; 4-Oxo-4-(4'-Oxo-3', 4'-Dihydro-2') H methyl spiro[cyclohexane-1,1'-isoquinoline]-2'-yl)butyrate; 2'-(3-cyclopentylpropionyl)-2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one.

2. The method for preparing the compound according to claim 1, characterized in that, Specifically, the following steps are included: Step 1: Add bromobenzene and magnesium strip to the reaction flask and dissolve them in an appropriate amount of diethyl ether. After the classic Grignard reagent reaction, 1-phenylcyclohexanol is obtained. Step 2: Add 1-phenylcyclohexanol and an appropriate amount of dichloromethane as solvent to the reaction flask, and obtain 1-azido-1-phenylcyclohexane through the azidation reaction; Step 3: Add 1-azido-1-phenylcyclohexane to the reaction flask, using tetrahydrofuran as a solvent, and reduce it to obtain 1-amino-1-phenylcyclohexane. Step 4: Add 1-amino-1-phenylcyclohexane to the reaction flask, using acetonitrile as the solvent, and proceed with the alkylation reaction to obtain (1-phenylcyclohexyl)glycine ethyl ester; Step 5: Add ethyl ester of (1-phenylcyclohexyl)glycine to the reaction flask, with an appropriate amount of water as a solvent, and obtain (1-phenylcyclohexyl)glycine through hydrolysis reaction; Step 6: Add (1-phenylcyclohexyl)glycine and an appropriate amount of dichloromethane as solvent to the reaction flask, and halogenate to obtain (1-phenylcyclohexyl)glycyl chloride; Step 7: Add (1-phenylcyclohexyl)glycyl chloride and an appropriate amount of dichloromethane as solvent to the reaction flask, and proceed with the Friedel-Crafts acylation reaction to obtain 2',3'-dihydro-4' H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one; Step 8: Add 2',3'-dihydro-4' to the reaction flask H -spiro[cyclohexane-1,1'-isoquinoline]-4'-one, using tetrahydrofuran as solvent and triethylamine as acid-binding agent, is given by adding a substituted acyl chloride and undergoing an acylation reaction to obtain the compound.

3. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

4. The use of the compound according to claim 1 or the pharmaceutical composition according to claim 3 in the preparation of an antitumor drug that inhibits human breast cancer MCF-7 cells.

5. The application as described in claim 4, characterized in that, The dosage form of the drug is a pharmacologically acceptable dosage form.

6. The application as described in claim 4, characterized in that, The dosage of the drug is a pharmacologically acceptable dosage.

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