An anti-tumor compound, a preparation method, a pharmaceutical composition containing the compound, and applications thereof

Abstract

The present invention discloses an anti-tumor compound, a preparation method, a pharmaceutical composition containing the compound and an application, belonging to the field of biomedical technology. The compound of the present invention has remarkable effects in in vitro anti-tumor activity tests. During the design process of the present invention, N 3 -((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-((R)-[1,1'-biphenyl]-3,3'-dicarboxamide compounds are designed and synthesized, which improve the anti-tumor effect, and it is found that they have good anti-proliferation ability against human melanoma cell line A375. During the synthesis process, the synthesis steps are optimized, providing a possibility for future industrial production.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to an anti-tumor compound, a preparation method, a pharmaceutical composition containing the compound, and an application thereof. Background Art

[0002] Melanoma is a highly malignant tumor derived from melanocytes, mostly occurring in the skin, and also visible in mucous membranes and internal organs. In recent years, the incidence and mortality of malignant melanoma have been increasing year by year. Compared with other solid tumors, its lethal age is lower. Except for early surgical resection, there is a lack of effective treatment for malignant melanoma, and the prognosis is poor. Therefore, the synthesis of effective new anti-melanoma drugs is one of the most important goals in modern medicinal chemistry. At present, the main clinical treatment methods for cancer mostly use chemotherapy drugs. Although current anti-tumor drugs have certain curative effects, there are also problems such as drug resistance, poor selectivity, and large toxic and side effects. Therefore, many researchers at home and abroad have tried to explore anti-melanoma compounds with completely new structures in order to obtain a completely new compound with better anti-tumor effects. Summary of the Invention

[0003] Aiming at the problems existing in the prior art, the present invention provides an anti-tumor compound, a preparation method, a pharmaceutical composition containing the compound, and an application thereof. The compound has good anti-proliferation ability against human melanoma cells (A375).

[0004] In order to achieve the above technical objectives, the technical solutions adopted by the present invention are as follows:

[0005] An anti-tumor compound, the compound is: N 3 -((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(R)-[1,1'-biphenyl]-3,3'-dicarboxamide compound, the structure of which is shown in general formula (I) or stereoisomers, geometric isomers, tautomers, prodrugs, crystal forms, metabolites, pharmaceutically acceptable salts, hydrates or solvates of the compound shown in formula (I):

[0006] Wherein the R group is one or more of 2-fluoro-9H-purin-6-yl, 7H-pyrrolo[2,3-d]pyrimidin-4-yl, 7H-purin-6-yl, 1H-pyrazolo[3,4-d]pyrimidin-4-yl, and 3-methyl-3H-purin-6-yl.

[0007] The compound, isomers, and pharmaceutically acceptable salts, hydrates or prodrugs of the general formula of the present invention: The following compounds are particularly preferred, but these compounds do not mean any limitation to the present invention:

[0008] N3 -(4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '- (2-Fluoro-9H-purin-6-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-1);

[0009] N 3 -((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-2);

[0010] N 3 -((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(7H-Purin-6-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-3);

[0011] N 3 -((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(1H-Pyrazolo[3,4-d]pyrimidin-4-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-4);

[0012] N 3 -(4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(3-Methyl-3H-purin-6-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-5).

[0013] A method for preparing an anti-tumor compound, comprising the following steps:

[0014] (1) Add 3-bromobenzoic acid, 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one, 1-hydroxybenzotriazole HOBt, carbodiimide EDCI and 4-methylmorpholine to a container, dissolve in organic solvent a, and carry out an acylation reaction to obtain the key intermediate 3-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide;

[0015] (2) Add 3-carboxyphenylboronic acid, the key intermediate 3-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide obtained in step (1), and tetrakis(triphenylphosphine)palladium into a container, and add them into organic solvent b to obtain a mixed solution A; then dissolve potassium carbonate in solvent c to obtain a mixed solution B; mix the mixed solutions A and B, and carry out a Suzuki reaction under nitrogen protection to obtain the key intermediate 3'-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid;

[0016] (3) Add the key intermediate 3'-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid, the substituent component, 1-hydroxybenzotriazole HOBt, carbodiimide EDCI and 4-methylmorpholine into a container, and dissolve them in organic solvent d, and carry out an acylation reaction to obtain the target compound.

[0017] The different dosages of the raw materials in the present invention only affect the yield of the final product and do not affect the structure and synthesis of the product.

[0018] Furthermore, the organic solvent a in step (1), the organic solvent b in step (2), and the organic solvent d in step (3) are all N,N-dimethylformamide DMF, the volume of solvent c is 1 / 5 of that of organic solvent b, and solvent c is water.

[0019] Furthermore, the substituent component in step (3) is one or more of 2-fluoro-9H-purin-6-amine, 7H-pyrrolo[2,3-d]pyrimidin-4-amine, 7H-purin-6-amine, 1H-pyrazolo[3,4-d]pyrimidin-4-amine, 3-methyl-3H-purin-6-amine.

[0020] A pharmaceutical composition, which contains a pharmaceutically acceptable carrier and the compound of general formula (I) in the present application, or stereoisomers, geometric isomers, tautomers, prodrugs, crystal forms, metabolites, pharmaceutically acceptable salts, hydrates or solvates.

[0021] In addition, the present invention also includes prodrugs of the derivatives of the present invention. The prodrugs of the derivatives of the present invention are derivatives of the general formula, and they may have weak activity or even no activity by themselves, but after administration, they are converted into the corresponding bioactive forms under physiological conditions (such as through metabolism, solvolysis or other means).

[0022] The present invention may contain N of the general formula 3 -((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3'-(R)-[1,1'-Biphenyl]-3,3'-dicarboxamides, and pharmaceutically acceptable salts and solvates thereof as active ingredients, are mixed with pharmaceutically acceptable carriers or excipients to prepare a pharmaceutical composition, which is prepared into a clinically acceptable dosage form. The above-mentioned pharmaceutically acceptable excipients refer to any diluents, adjuvants, and / or carriers that can be used in the pharmaceutical field. The derivatives of the present invention can be used in combination with other active ingredients as long as they do not produce other adverse effects, such as allergic reactions.

[0023] The pharmaceutical composition of the present invention can be formulated into several dosage forms, which contain some commonly used excipients in the pharmaceutical field. The above-mentioned several dosage forms can be injection, tablet, capsule, aerosol, suppository, film, dropping pill, external liniment, ointment and other dosage form drugs.

[0024] The carriers used in the pharmaceutical composition of the present invention are common types available in the pharmaceutical field, including: binders, lubricants, disintegrants, solubilizers, diluents, stabilizers, suspending agents, colorless agents, flavoring agents, preservatives, solubilizing agents and matrices, etc.

[0025] The application of an anti-tumor compound, the compound of the present invention, for preparing an anti-tumor drug.

[0026] Furthermore, the compound of the present invention is used for preparing an anti-melanoma drug.

[0027] Beneficial effects:

[0028] The compound of the present invention has a significant effect in the in vitro anti-tumor activity test. In the design process of the present invention, N 3 -((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(R)-[1,1'-biphenyl]-3,3'-dicarboxamides were designed and synthesized, which improved the anti-tumor effect, and it was found that it has good anti-proliferative ability against human melanoma cells (A375). During the synthesis process, the synthesis steps were optimized, providing possibilities for future industrial production. Specific embodiments

[0029] The technical solutions of the present invention will be further described below in conjunction with specific embodiments, but not limited thereto.

[0030] Example 1

[0031] N 3 -(4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(2-Fluoro-9H-purin-6-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-1) preparation method:

[0032] a. Preparation of 3-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide:

[0033] Add 3-bromobenzoic acid (5 g, 24.87 mmol), 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one (5.68 g, 37.31 mmol), HOBt (4.03 g, 29.85 mmol), EDCI (5.72 g, 29.85 mmol) and 4-methylmorpholine (16.35 g, 161.68 mmol) into a 250 mL eggplant-shaped flask, and dissolve them in an appropriate amount of DMF. Stir the reaction at room temperature for 30 minutes, and monitor the reaction progress by thin-layer chromatography. After the reaction is completed, add ice water to precipitate a white solid, filter it by suction, and dry it to obtain the product 3-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide, a white solid, yield: 87.9%.

[0034] b. Preparation of 3'-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid:

[0035] Add 3-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide (2 g, 5.97 mmol), 3-carboxyphenylboronic acid (1.49 g, 8.95 mmol) and tetrakis(triphenylphosphine)palladium (689.49 mg, 596.66 μmol) into a 100 mL eggplant-shaped flask and dissolve them in 100 mL of DMF. Separately, dissolve potassium carbonate (3.30 g, 23.87 mmol) in 20 mL of water. Mix the two solutions, displace with nitrogen three times, and react at 90 °C for 8 hours under nitrogen protection, and monitor the reaction progress by thin-layer chromatography. After the reaction is completed, filter off the palladium salt by suction. Add ice water to the filtrate to precipitate a white solid, filter it by suction, and dry it to obtain the product 3'-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid, a purple-black solid, yield: 89.7%.

[0036] c.N 3 -(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(2-fluoro-9H-purin-6-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide Preparation:

[0037] To a 100 mL eggplant-shaped flask, add 3'-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid (300 mg, 797.00 μmol), 2-fluoro-9H-purin-6-amine (183.06 mg, 1.20 mmol), HOBt (129.23 mg, 956.40 μmol), EDCI (183.34 mg, 956.40 μmol), and 4-methylmorpholine (524.00 mg, 5.18 mmol). Dissolve them in an appropriate amount of DMF and stir at room temperature for 2 hours, monitoring the reaction progress by thin-layer chromatography. After the reaction is completed, add ice water to precipitate the solid, filter by suction. The filter cake is purified by column chromatography to obtain the product N 3 -(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(2-fluoro-9H-purin-6-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-1), a yellow solid, yield: 82.08%.

[0038] Product A-1: 1 H NMR (600 MHz, DMSO-d6) δ 11.56 (s, 1H), 8.63 (t, J = 5.0 Hz, 1H), 8.15 (d, J = 1.9 Hz, 1H), 7.88 (d, J = 7.6 Hz, 1H), 7.85–7.79 (m, 2H), 7.78–7.74 (m, 1H), 7.55 (dt, J = 10.5, 7.7 Hz, 2H), 7.44–7.38 (m, 1H), 5.88 (s, 1H), 4.35 (d, J = 4.8 Hz, 2H), 2.20 (s, 3H), 2.13 (s, 3H). 13 C NMR (151 MHz, DMSO-d6) δ 170.41, 166.31, 150.26, 143.31, 140.12, 139.74, 137.76, 135.61, 129.79, 129.45, 129.42, 128.18, 127.46, 126.55, 125.94, 125.69, 122.06, 108.01, 35.84, 19.42, 18.66.

[0039] Example 2

[0040] N 3 -((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)

[0041] - Preparation method of [1,1'-biphenyl]-3,3'-dicarboxamide (A-2):

[0042] The preparation of 3-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide was carried out as in Example 1a, and the preparation of 3'-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid was carried out as in Example 1b. Using 7H-pyrrolo[2,3-d]pyrimidin-4-amine as the raw material, N 3 -((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-2) was obtained as a yellow solid with a yield of 83.76%.

[0043] Product A-2: 1 H NMR (600 MHz, DMSO-d6) δ 11.55 (s, 1H), 8.65–8.62 (m, 1H), 8.26 (s, 1H), 8.17 (s, 1H), 8.01 (m, 2H), 7.90 (d, J = 7.7 Hz, 1H), 7.84 (d, J = 7.7 Hz, 1H), 7.65 (t, J = 8.0 Hz, 1H), 7.57 (t, J = 7.7 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 5.88 (s, 1H), 4.35 (d, J = 5.0 Hz, 2H), 2.20 (s, 3H), 2.13 (s, 3H). 13 C NMR (151 MHz, DMSO-d6) δ 166.62, 166.24, 163.56, 150.25, 143.31, 140.64, 139.41, 135.66, 132.25, 130.83, 130.00, 129.84, 129.54, 128.82, 127.74, 126.05, 122.05, 107.99, 52.77, 35.84, 19.42, 18.66.

[0044] Example 3

[0045] N 3 -((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '- (7H-purin-6-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-3) preparation method:

[0046] The preparation of 4-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide was carried out as in Example 1a, and the preparation of 3'-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid was carried out as in Example 1b. Using 7H-purin-6-amine as the raw material, N 3 -((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(7H-purin-6-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-3), a yellow solid, yield: 82.05%.

[0047] Product A-3: 1 H NMR (600 MHz, DMSO-d6) δ 11.56 (s, 1H), 8.65–8.62 (m, 1H), 8.26 (s, 1H), 8.17 (s, 1H), 8.01 (m, 2H), 7.90 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 7.6 Hz, 1H), 7.65 (t, J = 7.7 Hz, 1H), 7.60–7.50 (m, 1H), 7.41 (t, J = 7.6 Hz, 1H), 5.88 (s, 1H), 4.35 (d, J = 4.8 Hz, 2H), 2.22–2.19 (s, 3H), 2.13 (s, 3H). 13 C NMR (151 MHz, DMSO-d6) δ 166.62, 166.24, 150.25, 143.31, 140.64, 139.42, 135.66, 132.25, 130.84, 130.00, 129.84, 129.55, 128.83, 127.74, 126.05, 122.05, 108.00, 52.77, 35.84, 19.42, 18.66.

[0048] Example 4

[0049] The preparation method of N3-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N3'-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-4):

[0050] The preparation of 3-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide was carried out as in Example 1a, and the preparation of 3'-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid was carried out as in Example 1b. Using 1H-pyrazolo[3,4-d]pyrimidin-4-amine as the raw material, N 3 -((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-4), yellow solid, 83.88%.

[0051] Product A-4: 1 H NMR (600 MHz, DMSO-d6) δ 8.65 (q, J = 5.2 Hz, 1H), 8.27 (dt, J = 7.4, 1.8 Hz, 1H), 8.18 (q, J = 1.7 Hz, 1H), 8.00–7.97 (m, 2H), 7.91 (ddt, J = 7.7, 4.8, 1.4 Hz, 1H), 7.84 (dt, J = 7.7, 1.4 Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.64 (dt, J = 13.6, 7.7 Hz, 1H), 7.59–7.53 (m, 2H), 7.45–7.40 (m, 1H), 5.88 (s, 1H), 4.37 (d, J = 4.8 Hz, 2H), 2.21 (s, 3H), 2.13 (s, 3H). 13 C NMR (151 MHz, DMSO-d6) δ 166.66, 162.54, 149.22, 142.26, 134.62, 131.19, 130.95, 130.76, 129.79, 128.94, 128.75, 127.78, 127.31, 126.91, 126.70, 121.02, 106.97, 51.72, 34.81, 18.38, 17.61.

[0052] Example 5

[0053] Preparation method of N3-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N3'-(3-methyl-3H-purin-6-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-5):

[0054] The preparation of 4-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide was carried out as in Example 1a, and the preparation of 3'-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid was carried out as in Example 1b. Using 3-methyl-3H-purin-6-amine as the raw material, N 3 -(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '- (3-methyl-3H-purin-6-yl)-[1,1'-biphenyl]-3,3'-dicarboxamide (A-5), white solid, 84.2%.

[0055] Product A-5: 1 H NMR (600 MHz, DMSO-d6) δ 11.54 (s, 1H), 8.62 (t, J = 5.0 Hz, 1H), 8.26 (t, J = 1.9 Hz, 1H), 8.17 (d, J = 1.9 Hz, 1H), 8.02 (dt, J = 7.8, 1.5 Hz, 1H), 7.98 (dt, J = 7.8, 1.4 Hz, 1H), 7.90 (dt, J = 7.8, 1.4 Hz, 1H), 7.84 (dt, J = 7.8, 1.4 Hz, 1H), 7.65 (t, J = 7.7 Hz, 1H), 7.57 (t, J = 7.7 Hz, 1H), 5.88 (s, 1H), 4.36 (d, J = 4.8 Hz, 2H), 3.91 (s, 3H), 2.21 (s, 3H), 2.13 (s, 3H). 13 C NMR (151 MHz, DMSO-d6) δ 166.61, 166.24, 150.23, 143.30, 140.64, 139.42, 135.68, 132.23, 130.84, 129.99, 129.83, 129.53, 128.82, 127.74, 127.59, 126.06, 122.06, 108.00, 52.76, 35.85, 19.42, 18.66.

[0056] Anti-tumor cell proliferation experiment

[0057] The anti-tumor cell proliferation experiment of the compounds of the present invention was carried out, and the conventional CCK8 method was used for the test method.

[0058] Cell culture: The cell line A375 (human melanoma cells) was selected, diluted with DMEM high-glucose medium, and the above cells were resuspended with DMEM high-glucose nutrient solution. Finally, the cells were cultured in an incubator at 37 °C with 5% CO2 and saturated humidity.

[0059] After culturing the cells according to the manufacturer's instructions, they were digested with 0.25% trypsin and finally diluted to a single-cell suspension using phosphate-buffered saline (PBS). The above cells were seeded in a 96-well plate at a concentration of 5×10 3 cells per well and cultured in an incubator containing 5% CO2 at 37°C. After the cells adhered, the nutrient solution was discarded and 100 μL of serum-free medium containing different concentrations of the compound was added to the cells. After incubating the compound with the cells for 24 hours, the hypersensitive CCK-8 solution (5 μL) was added to each well. Next, after incubating it at 37°C for 4 hours, the optical density value (OD) was analyzed at 490 nm. The compound concentration that caused a 50% inhibition rate was used as the IC 50 value.

[0060] The experimental results are shown in Table 1:

[0061] Table 1 IC 50 values of the in vitro proliferation inhibitory activity of the samples against human tumor cells

[0062]

[0063]

[0064] The above experimental data show that the compounds in the present invention have relatively good in vitro anti-tumor activity, have the value of in-depth research and development of new anti-tumor drugs, and also provide a broader idea for the research and development of new drugs.

[0065] It should be noted that the above embodiments are only some of the preferred embodiments for implementing the present invention, rather than all embodiments. Obviously, based on the above embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

Claims

1. An anti-tumor compound, characterized in that, The compound is: N 3 -((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-N 3 '-((R)-[1,1'-biphenyl]-3,3'-dicarboxamide) compound or a pharmaceutically acceptable salt thereof, wherein the R group is one of 2-fluoro-9H-purin-6-yl, 7H-pyrrolo[2,3-d]pyrimidin-4-yl, 7H-purin-6-yl, 1H-pyrazolo[3,4-d]pyrimidin-4-yl, and 3-methyl-3H-purin-6-yl.

2. A method for preparing the anti-tumor compound according to claim 1, characterized in that, Comprising the following steps: (1) Add 3-bromobenzoic acid, 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one, 1-hydroxybenzotriazole (HOBt), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDCI), and 4-methylmorpholine into a container, dissolve them in organic solvent a, and obtain the key intermediate 3-bromo-N-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide through acylation reaction; (2) Add 3-carboxyphenylboronic acid, the key intermediate 3-bromo-N-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzamide obtained in step (1), and tetrakis(triphenylphosphine)palladium into a container, then add them into organic solvent b to obtain a mixed solution A; dissolve potassium carbonate in solvent c to obtain a mixed solution B; mix the mixed solutions A and B, and obtain the key intermediate 3'-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid through Suzuki reaction under nitrogen protection; (3) Add the key intermediate 3'-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-[1,1'-biphenyl]-3-carboxylic acid, a substituent component, 1-hydroxybenzotriazole (HOBt), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDCI), and 4-methylmorpholine into a container, and dissolve them in organic solvent d, and obtain the target compound through acylation reaction; wherein, the substituent component is one of 2-fluoro-9H-purin-6-amine, 7H-pyrrolo[2,3-d]pyrimidin-4-amine, 7H-purin-6-amine, 1H-pyrazolo[3,4-d]pyrimidin-4-amine, 3-methyl-3H-purin-6-amine.

3. The preparation method of the anti-tumor compound according to claim 2, wherein, The organic solvent a in step (1), the organic solvent b in step (2), and the organic solvent d in step (3) are all N,N-dimethylformamide (DMF), the volume of solvent c is 1 / 5 of that of organic solvent b, and solvent c is water.

4. A pharmaceutical composition, which contains a pharmaceutically acceptable carrier and the compound or pharmaceutically acceptable salt according to claim 1.

5. Use of the anti-tumor compound according to claim 1, characterized in that, The compound is used for preparing an anti-melanoma tumor drug.

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