A sym-triazine-based LSD1 inhibitor, its preparation method and application

Abstract

The present invention belongs to the technical field of compound synthesis, and particularly relates to a s-triazine-based LSD1 inhibitor, its preparation method and application. The s-triazine-based LSD1 inhibitor of the present invention is a compound represented by formula I or a pharmaceutically acceptable salt thereof: The present invention introduces characteristic aliphatic amines, aromatic amines, phenols or benzenethiols at the 2-position of s-triazine, and at the same time introduces characteristic aromatic rings, heteroaromatic-aliphatic rings or fused ring groups at its 4-position and 6-position for modification, obtaining a s-triazine-based compound with a novel skeleton, high efficiency and low toxicity. It is confirmed by the LSD1 inhibitory activity test that the s-triazine-based compound with the above characteristic structure has good inhibitory activity against LSD1, shows good potential for drug development, can provide a new design direction and skeleton selection for the research and development of new LSD1 inhibitors, and is also of great significance for the research and treatment of related diseases based on the LSD1 target.

Description

Technical Field

[0001] The present invention belongs to the technical field of compound synthesis, and particularly relates to a s-triazine-based LSD1 inhibitor, a preparation method thereof, and an application thereof. Background Art

[0002] Lysine Specific Demethylase 1 (LSD1), the first histone lysine demethylase discovered by Professor Shi Yang of Harvard University in 2004, mainly functions to specifically remove the mono- and dimethylation of histone H3K4, thereby inhibiting gene transcription and regulating gene expression. LSD1 can also interact with estrogen receptor or androgen receptor to specifically remove the methylation of H3K9me1 / 2, leading to the activation of hormone receptor-dependent gene transcription. In addition, LSD1 can also demethylate non-histone substrates such as E2F1, DNMT1, p53, and STAT3, and further regulate the functions of their downstream proteins. Studies have shown that LSD1 is overexpressed in various tumor cells such as small cell lung cancer, gastric cancer, prostate cancer, and leukemia, and is related to tumor proliferation, differentiation, metastasis, and poor prognosis. Using LSD1 inhibitors or RNAi to downregulate LSD1 expression can significantly inhibit the occurrence and development of tumors. Therefore, LSD1 is a highly potential anti-tumor target. The research and development of efficient LSD1 inhibitors for effective use in the research of tumor targets and the prevention and treatment of tumors have become a hot topic in current anti-tumor drug research and an important research direction in the future.

[0003] At present, studies have confirmed that a few reported s-triazine-based compounds have biological and pharmacological activities such as antibacterial, antimalarial, and anticancer activities. As a new type of compound with biological activity and development potential, s-triazine-based compounds have become a hot topic and focus in drug research and development. However, the biological activities and application directions of s-triazine-based compounds with different structures vary greatly. There is currently no research report on the inhibition of LSD1 target protein by s-triazine-based compounds, nor has the role of s-triazine-based compounds in the inhibition of LSD1 target protein been disclosed, and the effective structure of s-triazine-based compounds with high inhibitory activity against LSD1 protein and capable of being developed as LSD1 inhibitors has not been made public. In addition, the existing reported LSD1 inhibitors, such as TCP, ORY-1001, CC-90011, and SP-2577, do not belong to the type of s-triazine-based compounds.

[0004] Therefore, the development of new and effective s-triazine-based LSD1 inhibitor compounds can provide more compound structures and skeletons for the research and use of LSD1 target-related inhibitory drugs, and also has important significance for the in-depth research and treatment of diseases related to the LSD1 target. Summary of the Invention

[0005] The object of the present invention is to provide a s-triazine-based LSD1 inhibitor, which has good inhibitory activity against the LSD1 protein and has the potential to be developed into a novel LSD1 inhibitor.

[0006] The present invention also aims to provide a preparation method of a s-triazine-based LSD1 inhibitor, which is simple in operation and mild in reaction conditions, and can effectively prepare s-triazine compounds with strong inhibitory activity against LSD1.

[0007] The present invention also aims to provide an application of a s-triazine-based LSD1 inhibitor.

[0008] To achieve the above object, the technical solution adopted for the s-triazine-based LSD1 inhibitor of the present invention is as follows:

[0009] A s-triazine-based LSD1 inhibitor is a compound represented by formula I or a pharmaceutically acceptable salt thereof:

[0010]

[0011] In formula I, X is selected from O, NH or S;

[0012] R1 is selected from one of them;

[0013] R2 is selected from one of them;

[0014] R3 is selected from one of them.

[0015] Advantageous effects: The s-triazine-based compound of the present invention introduces characteristic aliphatic amines, aromatic amines, phenols or benzenethiols at the 2-position of s-triazine, and at the same time introduces characteristic aromatic rings, heteroaromatic rings or fused ring groups at its 4-position and 6-position for modification, which is a s-triazine-based compound with a novel skeleton, high efficiency and low toxicity. It is confirmed by the LSD1 inhibitory activity test that the s-triazine-based compound with the above characteristic structure has good inhibitory activity against LSD1, is suitable for use as an LSD1 inhibitor, and can also provide a brand-new structural skeleton for the development of highly efficient LSD1 target-based inhibitory drugs.

[0016] Further preferably, according to the different requirements for the preparation cost and inhibitory activity of s-triazine-based compounds, in the actual application of drug preparation, X, R1, R2, and R3 can be selected from the following typical X, R1, R2, and R3 groupings, so as to construct s-triazine-based compounds numbered 1 to 51. Specifically, X, R1, R2, and R3 are selected from the following groupings:

[0017]

[0018]

[0019]

[0020] After X, R1, R2, and R3 are selected from the above group of groups, the formed s-triazine LSD1 inhibitors are sequentially denoted as Compounds 1 to 51.

[0021] To further optimize the inhibitory activity of s-triazine compounds against LSD1, preferably, X, R1, R2, and R3 are selected from the group of groups 12-14, 17-18, 21-26, 28, 30-39, 41-42, 44 to obtain s-triazine compounds 12-14, 17-18, 21-26, 28, 30-39, 41-42, 44, and the inhibition rate against LSD1 can reach more than 50%.

[0022] More preferably, X, R1, R2, and R3 are selected from the group of groups 17, 25-26, 30, 35, 41-42, 51 to obtain s-triazine compounds 17, 25-26, 30, 35, 41-42, 51, and the inhibition rate against LSD1 can reach more than 80%.

[0023] Most preferably, to maximize the inhibitory activity of s-triazine compounds against LSD1, X, R1, R2, and R3 are selected from the group of groups 25, 30, 35, 41, 51 to obtain s-triazine compounds 25, 30, 35, 41, 51, and the inhibition rate against LSD1 can reach more than 90%. Specifically, the corresponding group types of s-triazine compounds 25, 30, 35, 41, 51 are as follows: In Formula I, X is NH, R1 is R2 is R3 is Or, X is NH, R1 is R2 is R3 is Or, X is NH, R1 is R2 is R3 is Or, X is NH, R1 is R2 is R3 is Or, X is NH, R1 is R2 is R3 is The above limitation of the X, R1, R2, and R3 groups can effectively improve the inhibitory activity of s-triazine compounds against LSD1, and the inhibition rate against LSD1 can reach more than 90%, IC50 The values are only 0.1 - 0.8 μM, all lower than 1 μM. The concentration at which this group of compounds exhibit effective inhibitory activity is relatively low, with stronger targeting effects, and is very suitable for use as LSD1 inhibitors.

[0024] The preparation method of the s-triazine-based LSD1 inhibitor of the present invention adopts the following technical solution:

[0025] The preparation method of the above s-triazine-based LSD1 inhibitor is prepared by adopting the following synthetic route ① or synthetic route ②;

[0026]

[0027] Synthetic route ① includes the following steps: React compound Ⅱ, phenylboronic acid, basic substance A, and a catalyst in organic solvent A to obtain compound Ⅲ; React compound Ⅲ, R2B(OH)2, basic substance A, and a catalyst in organic solvent B to obtain compound Ⅳ; React compound Ⅳ, R1XH, and basic substance B in organic solvent C to obtain the s-triazine-based compound shown in formula Ⅰ;

[0028] Synthetic route ② includes the following steps: React compound Ⅱ and a Grignard reagent in organic solvent D to obtain compound Ⅴ; React compound Ⅴ, N,N-diethyl-p-phenylenediamine, and basic substance C in organic solvent E to obtain compound Ⅵ; React compound Ⅵ, 1-methylpyrazole-4-boronic acid, basic substance D, and a catalyst in organic solvent F to obtain the s-triazine-based compound shown in formula Ⅰ.

[0029] Advantageous effects: The preparation method of the present invention has the characteristics of mild reaction conditions, simple operation, and high yield. The present invention uses easily available cyanuric chloride as the starting material, first synthesizes disubstituted s-triazine intermediates with different substituents at the 4,6-positions, and modifies the groups at the 2-position of the s-triazine ring with different aliphatic amines, aromatic amines, phenols, or benzenethiols, etc. to design and synthesize the compounds of the present invention. While retaining the activity of s-triazine, these compounds also have the characteristics of the modified groups, improving the biological activity of the original molecule, showing good inhibition of LSD1, and enhancing the inhibitory activity of the target molecule against the LSD1 target protein.

[0030] To improve the synthesis efficiency, as a further preferred solution, the organic solvents A, B, C, D, E, and F are each independently selected from one or more of N,N-dimethylformamide, N-methylpyrrolidone, tetrahydrofuran, acetonitrile, dioxane, methanol, ethanol, a dioxane-water mixed solution with a volume ratio of 4:1, and toluene.

[0031] To better reduce the occurrence of side reactions and further improve the selectivity of the reaction, as a further preferred embodiment, the catalyst is one or more of tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride, and bis(dibenzylideneacetone)palladium.

[0032] To further promote the conversion of raw materials and reduce the occurrence of side reactions, as a further preferred embodiment, the basic substances A, B, C, and D are each independently selected from one or more of potassium carbonate, cesium carbonate, sodium bicarbonate, sodium tert-butoxide, triethylamine, pyridine, sodium hydroxide, and potassium hydroxide.

[0033] Considering reducing the reaction energy consumption and ensuring the conversion effect, as a further preferred embodiment, in synthetic route ①, the reaction temperature between compound Ⅱ and phenylboronic acid is 50 - 150 °C; the reaction temperature between compound Ⅲ and R2B(OH)2 is 50 - 150 °C; the reaction temperature between compound Ⅳ and R1XH is 20 - 80 °C.

[0034] Considering reducing the reaction energy consumption and ensuring the conversion effect, as a further preferred embodiment, in synthetic route ②, the reaction temperature between compound Ⅱ and Grignard reagent is -10 - 30 °C; the reaction temperature between compound Ⅴ and N,N-diethyl-p-phenylenediamine is 0 - 50 °C; the reaction temperature between compound Ⅵ and 1-methylpyrazole-4-boronic acid is 60 - 120 °C.

[0035] The application of the s-triazine-based LSD1 inhibitor of the present invention adopts the following technical solution:

[0036] For the above application of the s-triazine-based LSD1 inhibitor, the s-triazine-based LSD1 inhibitor is used as an active ingredient in the preparation of an inhibitor targeting the LSD1 target.

[0037] Beneficial effects: For the application of the s-triazine-based LSD1 inhibitor provided by the present invention, the s-triazine-based compound involved is a novel s-triazine-based drug specifically developed by the present invention with good inhibitory activity against LSD1. Experiments have confirmed that this type of compound exhibits good inhibitory activity against LSD1, showing good potential for drug development, and can provide a new design direction and skeleton selection for the research and development of inhibitory drugs based on the LSD1 target. At the same time, it also has important significance for the research and treatment of related diseases based on the LSD1 target. Specific embodiments

[0038] The technical solution of the present invention will be further described below in conjunction with specific embodiments, but it does not constitute a limitation to the present invention. The chemical raw materials involved in the following embodiments can all be obtained through conventional commercial channels.

[0039] Among them, the s-triazine-based compounds 1 - 51 involved in the following embodiments of the present invention all conform to the structural general formula shown in Formula Ⅰ For the sake of convenience of description, in the following examples, only the substituent groups X, R1, R2, and R3 of the s-triazine compounds in Formula I are specifically defined.

[0040] In addition, for the s-triazine compounds 1 to 51 involved in the following examples of the present invention, the preparation routes all conform to Routes ① and ②.

[0041]

[0042] Among them, Compounds 1 to 45 are prepared by Synthetic Route ①; Compounds 46 to 51 are prepared by Synthetic Route ②.

[0043] Example 1

[0044] The structure and preparation method of the s-triazine compound in this example are as follows:

[0045] The s-triazine compound 1 conforms to the general formula Formula I, wherein X = NH, R1 = R2 = R3 =

[0046] The preparation method of the s-triazine compound 1 includes the following steps:

[0047] 1) Dissolve the compound of Formula II (1.84 g, 10 mmol) and phenylboronic acid (1.46 g, 12 mmol) in anhydrous 1,4-dioxane (50 mL), then successively add anhydrous potassium carbonate (3.45 g, 25 mmol) and bis(triphenylphosphine)palladium dichloride (0.175 g, 0.25 mmol), and react at 60 °C under nitrogen protection, monitoring the reaction progress by TLC. After the reaction is completed, remove the solvent by distillation under reduced pressure, add dichloromethane (50 mL) to the obtained reaction system, wash the organic phase with saturated brine (3 × 50 mL), dry with anhydrous magnesium sulfate, and distill under reduced pressure to obtain the crude product of the intermediate compound of Formula III;

[0048] 2) Dissolve the intermediate compound of Formula III (224 mg, 1 mmol) and phenylboronic acid (1.46 g, 12 mmol) in an aqueous solution of 1,4-dioxane (V 1,4-二氧六环 :V 水 = 4:1, 10 mL), then successively add anhydrous potassium carbonate (345 mg, 2.5 mmol) and bis(triphenylphosphine)palladium dichloride (17.5 mg, 0.025 mmol), and react at 100 °C under nitrogen protection, monitoring the reaction progress by TLC. After the reaction is completed, remove the solvent by distillation under reduced pressure, add dichloromethane (10 mL) to the obtained reaction system, wash the organic phase with saturated brine (3 × 10 mL), dry with anhydrous magnesium sulfate, and purify by column chromatography to obtain the intermediate compound of Formula IV.

[0049] 3) Dissolve the compound of formula Ⅳ (134 mg, 0.5 mmol) and 4-methyl-1-piperazineethanamine (86 mg, 0.6 mmol) in anhydrous acetonitrile (10 mL), then add sodium hydroxide (24 mg, 0.6 mmol), and react at room temperature. Monitor the reaction progress by TLC. After the reaction is completed, remove the solvent by distillation under reduced pressure. Add dichloromethane (10 mL) to the obtained reaction system, wash the organic phase with saturated brine (3 × 10 mL), dry over anhydrous magnesium sulfate, and purify by column chromatography to obtain the s-triazine compound 1 with a yield of 43.5%. The structure characterization is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 7.1 Hz, 2H), 8.54 (d, J = 6.9 Hz, 2H), 7.51 - 7.48 (m, 6H), 6.09 (s, 1H), 3.73 (dd, J = 11.4, 5.7 Hz, 2H), 2.67 (t, J = 6.0 Hz, 2H), 2.54 (d, J = 32.8 Hz, 8H), 2.32 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 171.40, 171.18, 166.30, 136.82, 136.73, 131.86, 131.75, 128.67, 128.53, 128.37, 56.66, 55.08, 52.90, 46.02, 37.54. 13 C NMR (100 MHz, CDCl3) δ 173.58, 171.44, 135.63, 132.71, 129.04, 128.58, 65.10, 56.54, 54.73, 53.05, 45.60. HR-MS (ESI): Calcd. C 22 H 26 N6, [M + H] + m / z: 375.2297, found: 375.2291.

[0050] Example 2

[0051] The structure and preparation method of the s-triazine compound in this example are as follows:

[0052] The s-triazine compound 2 conforms to the general formula Ⅰ, where X = NH, R1 = R2 = R3 =

[0053] The preparation method of the s-triazine compound 2 is basically the same as that of Example 1, except that: replace 4-methyl-1-piperazineethanamine in step 3) with N,N-dimethylethylenediamine to prepare compound 2 with a yield of 40.0%. The structure characterization is as follows:1 1H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 7.1 Hz, 2H), 8.54 (d, J = 7.0 Hz, 2H), 7.51 (d, J = 7.4 Hz, 6H), 6.10 (s, 1H), 3.71 (dd, J = 11.5, 5.8 Hz, 2H), 2.60 (t, J = 6.1 Hz, 2H), 2.32 (s, 6H). 13 13C NMR (100 MHz, CDCl3) δ 171.39, 171.12, 166.34, 136.89, 136.71, 131.81, 131.72, 128.66, 128.53, 128.34, 57.89, 45.26, 38.41. HRMS (ESI) calcd for C 19 H 21 N5 [M + H] + , 320.1870; found, 320.1873.

[0054] Example 3

[0055] The structure and preparation method of the s-triazine compound in this example are as follows:

[0056] The s-triazine compound 3 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0057] The preparation method of the s-triazine compound 3 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethanamine in step 3) is replaced with 4-aminopiperidine, and compound 3 is prepared with a yield of 78.2%. The structure characterization is as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 8.52 (d, J = 7.2 Hz, 4H), 7.60 (dt, J = 14.5, 7.0 Hz, 6H), 4.83 (d, J = 13.1 Hz, 2H), 3.23 (t, J = 11.6 Hz, 2H), 3.03 - 2.98 (m, 1H), 1.92 (d, J = 10.8 Hz, 2H), 1.36 - 1.27 (m, 2H). 13 13C NMR (100 MHz, DMSO-d6) δ 170.17, 164.17, 136.24, 132.06, 128.53, 128.20, 47.97, 41.60, 34.30. HRMS (ESI) calcd for C 20 H 21 N5 [M + H] +,332.1870; found, 332.1874.

[0058] Example 4

[0059] The structure and preparation method of the s-triazine compound in this example are as follows:

[0060] The s-triazine compound 4 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0061] The preparation method of the s-triazine compound 4 is basically the same as that of Example 1, except that: 4-Methyl-1-piperazineethanamine in step 3) is replaced with 1-aminopiperidine to prepare compound 4, and the yield is 81.8%. The structure characterization is as follows: 1 HNMR(400MHz, DMSO-d6) δ9.22(s, 1H), 8.51(d, J = 18.5Hz, 4H), 7.64 - 7.57(m, 6H), 2.92(t, J = 5.0Hz, 4H), 1.68(t, J = 5.1Hz, 4H), 1.43(s, 2H). 13 C NMR(100MHz, DMSO-d6) δ170.79, 169.94, 165.74, 136.37, 136.13, 132.00, 128.52, 128.22, 127.99, 55.06, 25.37, 23.13. HR-MS(ESI) calcd for C 20 H 21 N5[M + H] + ,332.1870; found, 332.1871.

[0062] Example 5

[0063] The structure and preparation method of the s-triazine compound in this example are as follows:

[0064] The s-triazine compound 5 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0065] The preparation method of the s-triazine compound 5 is basically the same as that of Example 1, except that: 4-Methyl-1-piperazineethanamine in step 3) is replaced with morpholineamine to prepare compound 5, and the yield is 46.4%. The structure characterization is as follows: 11H NMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 8.51 (d, J = 14.5 Hz, 4H), 7.65 - 7.56 (m, 6H), 3.75 (t, J = 4.2 Hz, 4H), 2.99 (t, J = 4.3 Hz, 4H). 13 13C NMR (100 MHz, DMSO-d6) δ 165.91, 136.21, 132.09, 128.55, 128.20, 66.07, 54.31. HRMS (ESI) calcd for C 19 H 19 N5O [M + H] + , 334.1663; found, 334.1665.

[0066] Example 6

[0067] The structure and preparation method of the s-triazine compound in this example are as follows:

[0068] The s-triazine compound 6 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0069] The preparation method of the s-triazine compound 6 is basically the same as that of Example 1, except that: 4-Methyl-1-piperazineethanamine in step 3) is replaced with 1-Amino-4-methylmorpholine to prepare the compound 6, and the yield is 70.4%. The structural characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 5.3 Hz, 4H), 7.57 - 7.48 (m, 6H), 6.37 (s, 1H), 3.09 (s, 4H), 2.69 (s, 4H), 2.38 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 166.51, 136.45, 132.04, 128.77, 128.39, 55.01, 54.63, 45.81. HRMS (ESI) calcd for C 20 H 22 N6 [M + H] + , 347.1975; found, 347.1978.

[0070] Example 7

[0071] The structure and preparation method of the s-triazine compound in this example are as follows:

[0072] The s-triazine compound 7 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0073] The preparation method of the s-triazine compound 7 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethanamine in step 3) is replaced by aniline to obtain compound 7, and the yield is 30.2%. The structural characterization is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 6.8 Hz, 4H), 7.78 (d, J = 7.7 Hz, 2H), 7.58 - 7.51 (m, 6H), 7.43 (dd, J = 14.1, 5.8 Hz, 3H), 7.16 (t, J = 7.4 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 171.79, 164.86, 138.34, 136.36, 132.22, 129.06, 128.79, 128.53, 123.69, 120.32. HRMS (ESI) calcd for C 21 H 16 N4[M + H] + , 325.1448; found, 325.1449.

[0074] Example 8

[0075] The structure and preparation method of the s-triazine compound in this example are as follows:

[0076] The s-triazine compound 8 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0077] The preparation method of the s-triazine compound 8 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethanamine in step 3) is replaced by p-toluidine to obtain compound 8, and the yield is 31.3%. The structural characterization is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 6.8 Hz, 4H), 7.65 (d, J = 8.4 Hz, 2H), 7.59 - 7.50 (m, 7H), 7.23 (d, J = 10.0 Hz, 2H), 2.37 (s, 3H). 1313C NMR (100 MHz, CDCl3) δ 171.71, 164.84, 136.42, 135.68, 133.36, 132.13, 129.54, 128.76, 128.48, 120.47, 20.90. HRMS (ESI) calcd for C 22 H 18 N4 [M + H] + , 339.1604; found, 339.1607.

[0078] Example 9

[0079] The structure and preparation method of the s-triazine compound in this example are as follows:

[0080] The s-triazine compound 9 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0081] The preparation method of the s-triazine compound 9 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethanamine in step 3) is replaced with 4-cyanoaniline to prepare compound 9, and the yield is 34.9%. The structural characterization is as follows: 1 1H NMR (400 MHz, DMSO-d6) δ 10.82 (s, 1H), 8.58 (d, J = 7.2 Hz, 4H), 8.13 (d, J = 8.6 Hz, 2H), 7.89 (d, J = 8.5 Hz, 2H), 7.74 - 7.61 (m, 6H). 13 13C NMR (100 MHz, DMSO-d6) δ 171.01, 164.58, 143.57, 135.61, 133.19, 132.66, 128.81, 128.42, 120.19, 119.20, 104.38. HRMS (ESI) calcd for C 22 H 15 N5 [M + H] + , 350.1400; found, 350.1403.

[0082] Example 10

[0083] The structure and preparation method of the s-triazine compound in this example are as follows:

[0084] The s-triazine compound 10 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0085] The preparation method of the s-triazine compound 10 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethylamine in step 3) is replaced with p-methoxyaniline to obtain compound 10 with a yield of 38.0%. The structural characterization is as follows: 1 HNMR(400MHz,CDCl3)δ8.58(d,J=6.7Hz,4H),7.65(d,J=9.0Hz,2H),7.60-7.47(m,6H),7.28(s,1H),6.97(d,J=9.0Hz,2H),3.85(s,3H). 13 C NMR(100MHz,CDCl3)δ164.91,156.23,136.46,131.32,128.47,122.34,114.24,55.59.HRMS(ESI)calcd C 22 H 18 N4O[M+H] + ,355.1554;found,355.1557.

[0086] Example 11

[0087] The structure and preparation method of the s-triazine compound in this example are as follows:

[0088] The s-triazine compound 11 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0089] The preparation method of the s-triazine compound 11 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethylamine in step 3) is replaced with p-methylthioaniline to obtain compound 11 with a yield of 42.2%. The structural characterization is as follows: 1 HNMR(400MHz,CDCl3)δ8.56(d,J=6.9Hz,4H),7.62(d,J=8.6Hz,2H),7.56-7.47(m,7H),7.28(d,J=8.6Hz,2H),2.47(s,3H). 13 C NMR(100MHz,CDCl3)δ171.73,164.72,136.32,136.03,132.77,132.26,128.82,128.54,128.10,120.92,16.85.HRMS(ESI)calcd forC 22 H 18 N4S[M+H] + ,371.1325;found,371.1324.

[0090] Example 12

[0091] The structure and preparation method of the s-triazine compound in this example are as follows:

[0092] The s-triazine compound 12 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0093] The preparation method of the s-triazine compound 12 is basically the same as that of Example 1, except that: 4-Methyl-1-piperazineethanamine in step 3) is replaced with p-phenylenediamine to prepare compound 12, and the yield is 51.2%. The structure characterization is as follows: 1 HNMR(400MHz,CDCl3)δ8.58(d,J = 6.8Hz,4H),7.56 - 7.49(m,8H),7.22(s,1H),6.76(d,J = 8.7Hz,2H),3.66(s,2H). 13 C NMR(100MHz,CDCl3)δ164.95,143.03,136.54,132.01,129.50,128.72,128.43,122.68,115.49.HRMS(ESI)calcd for C 21 H 17 N5[M + H] + ,340.1557; found,340.1561.

[0094] Example 13

[0095] The structure and preparation method of the s-triazine compound in this example are as follows:

[0096] The s-triazine compound 13 conforms to the general formula I, wherein X = O, R1 = R2 = R3 =

[0097] The preparation method of the s-triazine compound 13 is basically the same as that of Example 1, except that: 4-Methyl-1-piperazineethanamine in step 3) is replaced with p-aminophenol to prepare compound 13, and the yield is 46.2%. The structure characterization is as follows: 1HNMR(400MHz, DMSO-d6) δ 8.47 (d, J = 8.5Hz, 4H), 7.68 (t, J = 7.3Hz, 2H), 7.60 (t, J = 7.4Hz, 4H), 7.04 (d, J = 8.7Hz, 2H), 6.67 (d, J = 8.7Hz, 2H), 5.15 (s, 2H). 13 C NMR(100MHz, DMSO-d6) δ 172.98, 171.93, 146.49, 141.97, 134.89, 133.11, 128.72, 122.65, 121.75, 115.10, 114.13. HRMS(ESI) calcd for C 21 H 16 N4O [M+H] + , 341.1397; found, 341.1400.

[0098] Example 14

[0099] The structure and preparation method of the s-triazine compound in this example are as follows:

[0100] The s-triazine compound 14 conforms to the general formula I, where X = S, R1 = R2 = R3 =

[0101] The preparation method of the s-triazine compound 14 is basically the same as that of Example 1, except that: in step 3), 4-methyl-1-piperazineethanamine is replaced with p-aminothiophenol to prepare the compound 14, and the yield is 51.1%. The structure characterization is as follows: 1 HNMR(400MHz, CDCl3) δ 8.48 (d, J = 7.6Hz, 4H), 7.55 (t, J = 7.2Hz, 2H), 7.47 (t, J = 8.2Hz, 6H), 6.79 (d, J = 8.3Hz, 2H), 3.93 (s, 2H). 13 C NMR(100MHz, CDCl3) δ 184.08, 170.33, 147.88, 137.07, 135.63, 132.55, 129.03, 128.55, 115.46. HRMS(ESI) calcd for C 21 H 16 N4S [M+H] + , 357.1169; found, 357.1176.

[0102] Example 15

[0103] The structure and preparation method of the s-triazine compound in this embodiment are as follows:

[0104] The s-triazine compound 15 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0105] The preparation method of the s-triazine compound 15 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethanamine in step 3) is replaced with m-phenylenediamine to prepare the compound 15, and the yield is 42.4%. The structure characterization is as follows: 1 HNMR(400MHz,CDCl3)δ8.60(d,J = 6.8Hz,4H),7.60 - 7.51(m,6H),7.34(s,1H),7.25(d,J = 2.0Hz,1H),7.20(t,J = 7.9Hz,1H),7.13(d,J = 8.0Hz,1H),6.49(dd,J = 7.8,1.3Hz,1H),3.78(s,2H). 13 C NMR(100MHz,CDCl3)δ171.73,164.82,147.14,139.35,136.41,132.17,129.86,128.77,128.51,110.61,106.92.HRMS(ESI)calcd for C 21 H 17 N5[M + H] + ,340.1557; found,340.1560.

[0106] Example 16

[0107] The structure and preparation method of the s-triazine compound in this embodiment are as follows:

[0108] The s-triazine compound 16 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0109] The preparation method of the s-triazine compound 16 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethanamine in step 3) is replaced with 1,3-diaminotriazole to prepare the compound 16, and the yield is 36.0%. The structure characterization is as follows: 1 H NMR(400MHz,DMSO-d6)δ8.55(d,J = 7.2Hz,4H),7.73 - 7.63(m,6H),5.85(s,2H). 13CNMR(100MHz,DMSO-d6)δ171.46,162.63,161.29,157.26,135.03,133.12,128.95,128.60.HRMS(ESI)calcd for C 17 H 14 N8[M+H] + ,331.1414;found,331.1418.

[0110] Example 17

[0111] The structure and preparation method of the s-triazine compound in this example are as follows:

[0112] The s-triazine compound 17 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0113] The preparation method of the s-triazine compound 17 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-dimethyl-p-phenylenediamine to prepare the compound 17, and the yield is 38.4%. The structure characterization is as follows: 1 H NMR(400MHz,DMSO-d6)δ10.10(s,1H),8.54(s,4H),7.70-7.59(m,8H),6.82(d,J = 8.8Hz,2H),2.91(s,6H). 13 C NMR(100MHz,DMSO-d6)δ170.65,170.20,164.16,147.13,136.18,132.25,128.63,128.37,128.24,128.12,122.05,112.63,40.48.HRMS(ESI)calcdfor C 23 H 21 N5[M+H] + ,368.1870;found,368.1873.

[0114] Example 18

[0115] The structure and preparation method of the s-triazine compound in this example are as follows:

[0116] The s-triazine compound 18 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0117] The preparation method of the s-triazine compound 18 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethanamine in step 3) is replaced by N,N-diethyl-p-phenylenediamine to obtain compound 18 with a yield of 55.6%. The structure characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.59(d,J=7.0Hz,4H),7.57-7.49(m,8H),7.21(s,1H),6.76(d,J=9.0Hz,2H),3.38(q,J=7.1Hz,4H),1.19(t,J=7.1Hz,6H). 13 C NMR(100MHz,CDCl3)δ164.86,145.01,136.65,131.92,128.72,128.40,126.84,122.61,112.45,44.62,12.62.HRMS(ESI)calcd for C 25 H 25 N5[M+H] + ,396.2183;found,396.2194.

[0118] Example 19

[0119] The structure and preparation method of the s-triazine compound in this example are as follows:

[0120] The s-triazine compound 19 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0121] The preparation method of the s-triazine compound 19 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethanamine in step 3) is replaced by 4-piperazinylaniline to obtain compound 19 with a yield of 48.0%. The structure characterization is as follows: 1 HNMR(400MHz,DMSO-d6)δ8.55(d,J=7.2Hz,4H),7.64-7.56(m,6H),6.79(d,J=8.2Hz,2H),6.54(d,J=8.2Hz,2H),4.67(s,2H),4.14(s,4H),3.06(s,4H). 13 C NMR(100MHz,DMSO-d6)δ170.14,164.30,136.05,132.11,128.50,128.19,118.72,114.80,50.56,43.05.HRMS(ESI)calcd for C 25 H24 N6[M+H] + , 431.1955; found, 431.1956.

[0122] Example 20

[0123] The structure and preparation method of the s-triazine compound in this example are as follows:

[0124] The s-triazine compound 20 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0125] The preparation method of the s-triazine compound 20 is basically the same as that of Example 1, except that: 4-methyl-1-piperazineethanamine in step 3) is replaced with 4-morpholinoaniline, and compound 20 is prepared with a yield of 45.1%. The structural characterization is as follows: 1 HNMR(400MHz, DMSO-d6) δ10.17(s, 1H), 8.54(d, J = 6.4Hz, 4H), 7.74(d, J = 9.0Hz, 2H), 7.67 - 7.59(m, 6H), 7.03(d, J = 9.0Hz, 2H), 3.76(t, J = 4.4Hz, 4H), 3.11(t, J = 4.6Hz, 4H). 13 CNMR(100MHz, DMSO-d6) δ164.22, 147.26, 136.06, 132.30, 130.91, 128.66, 128.24, 121.70, 115.36, 66.11, 48.85. HRMS(ESI) calcd for C 25 H 23 N5O[M+H] + , 410.1976; found, 410.1970.

[0126] Example 21

[0127] The structure and preparation method of the s-triazine compound in this example are as follows:

[0128] The s-triazine compound 21 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0129] The preparation method of the s-triazine compound 21 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with p-tolylboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine, and the compound 21 is prepared with a yield of 34.3%. The structural characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.58(d,J=6.5Hz,2H),8.48(d,J=7.7Hz,2H),7.57-7.51(m,5H),7.31(d,J=8.1Hz,2H),7.18(s,1H),6.76(d,J=9.0Hz,2H),3.38(q,J=7.1Hz,4H),2.45(s,3H),1.19(t,J=7.0Hz,6H). 13 C NMR(100MHz,CDCl3)δ164.82,144.92,142.43,136.77,133.94,131.88,129.21,128.74,128.41,127.01,122.57,112.49,44.65,21.71,12.65.HRMS(ESI)calcd for C 26 H 27 N5[M+H] + ,410.2339;found,410.2340.

[0130] Example 22

[0131] The structure and preparation method of the s-triazine compound in this example are as follows:

[0132] The s-triazine compound 22 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0133] The preparation method of the s-triazine compound 22 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with p-isopropylphenylboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine, and the compound 22 is prepared with a yield of 62.4%. The structural characterization is as follows: 11H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 6.4 Hz, 2H), 8.50 (d, J = 7.5 Hz, 2H), 7.57 - 7.48 (m, 5H), 7.37 (d, J = 8.3 Hz, 2H), 7.24 (s, 1H), 6.75 (d, J = 9.0 Hz, 2H), 3.37 (q, J = 7.0 Hz, 4H), 3.06 - 2.94 (m, 1H), 1.31 (s, 3H), 1.29 (s, 3H), 1.18 (t, J = 7.0 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ 164.79, 153.23, 144.89, 136.74, 134.30, 131.83, 128.76, 128.37, 126.98, 126.54, 122.51, 112.45, 44.62, 34.25, 23.84, 12.61. HRMS (ESI) calcd for C 28 H 31 N5[M + H] + , 438.2650; found, 438.2656.

[0134] Example 23

[0135] The structure and preparation method of the s-triazine compound in this example are as follows:

[0136] The s-triazine compound 23 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0137] The preparation method of the s-triazine compound 23 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with p-methoxyphenylboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine to prepare the compound 23 with a yield of 34.4%. The structure characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 8.0 Hz, 4H), 7.57 - 7.49 (m, 5H), 7.17 (s, 1H), 7.01 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 9.0 Hz, 2H), 3.90 (s, 3H), 3.38 (q, J = 7.0 Hz, 4H), 1.19 (t, J = 7.0 Hz, 6H). 1313C NMR (100 MHz, CDCl3) δ 164.77, 162.89, 144.95, 136.81, 131.80, 130.57, 128.37, 127.06, 122.57, 113.73, 112.53, 55.41, 44.64, 12.63. HRMS (ESI) calcd for C 26 H 27 N5O [M+H] + , 426.2287; found, 426.2295.

[0138] Example 24

[0139] The structure and preparation method of the s-triazine compound in this example are as follows:

[0140] The s-triazine compound 24 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0141] The preparation method of the s-triazine compound 24 is basically the same as that in Example 1, except that: the phenylboronic acid in step 2) is replaced with 4-hydroxyphenylboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine, to obtain compound 24 with a yield of 56.6%. The structure characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, J = 12.9, 7.6 Hz, 2H), 7.50 (t, J = 7.2 Hz, 1H), 7.43 (t, J = 7.3 Hz, 5H), 7.27 (t, J = 6.8 Hz, 3H), 7.20 (d, J = 8.3 Hz, 1H), 6.69 (d, J = 8.3 Hz, 1H), 6.50 (d, J = 8.3 Hz, 1H), 3.35 - 3.28 (m, 3H), 1.17 - 1.10 (m, 6H). 13 13C NMR (100 MHz, CDCl3) δ 174.07, 173.19, 171.88, 171.21, 165.74, 152.52, 152.26, 145.15, 144.91, 135.83, 135.70, 132.34, 132.25, 129.39, 129.26, 129.04, 128.66, 128.42, 126.31, 125.54, 125.36, 122.88, 122.21, 122.03, 112.27, 44.59, 12.62. HRMS (ESI) calcd for C 25 H 25N5O[M+H] + , 412.2132; found, 412.2134.

[0142] Example 25

[0143] The structure and preparation method of the s-triazine compound in this example are as follows:

[0144] The s-triazine compound 25 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0145] The preparation method of the s-triazine compound 25 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with 4-aminophenylboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine to prepare the compound 25 with a yield of 46.2%. The structure characterization is as follows: 1 H NMR(400MHz, CDCl3) δ8.40(d, J = 6.8Hz, 2H), 7.63(d, J = 7.9Hz, 2H), 7.56 - 7.45(m, 4H), 7.36(s, 1H), 7.30(s, 2H), 7.05(t, J = 7.3Hz, 1H), 6.68(d, J = 8.1Hz, 2H), 3.34(q, J = 7.0Hz, 4H), 1.16(t, J = 7.0Hz, 6H). 13 CNMR(100MHz, CDCl3) δ171.54, 164.99, 164.67, 147.66, 147.12, 145.11, 138.78, 136.72, 131.66, 128.79, 128.38, 124.49, 124.02, 123.11, 120.30, 119.14, 112.39, 44.67, 12.61. HRMS(ESI) calcd for C 25 H 26 N6[M+H] + , 411.2290; found, 411.2296.

[0146] Example 26

[0147] The structure and preparation method of the s-triazine compound in this example are as follows:

[0148] The s-triazine compound 26 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0149] The preparation method of the s-triazine compound 26 is basically the same as that of Example 1, with the only difference being that: the phenylboronic acid in step 2) is replaced with p-toluenesulfonylphenylboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine, to obtain compound 26 with a yield of 46.2%. The structural characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.75(d,J=8.4Hz,2H),8.57(d,J=4.4Hz,2H),8.08(d,J=8.4Hz,2H),7.55(dt,J=21.0,7.1Hz,5H),7.30(s,1H),6.76(d,J=8.9Hz,2H),3.39(q,J=7.0Hz,4H),3.10(s,3H),1.20(t,J=7.0Hz,2H). 13 C NMR(100MHz,CDCl3)δ164.88,145.33,143.06,141.87,136.16,132.26,129.57,128.73,128.50,127.40,126.29,122.87,112.34,44.59,44.49,12.62.HRMS(ESI)calcd for C 26 H 27 N5O2S[M+H] + ,474.1958;found,474.1962.

[0150] Example 27

[0151] The structure and preparation method of the s-triazine compound in this example are as follows:

[0152] The s-triazine compound 27 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0153] The preparation method of the s-triazine compound 27 is basically the same as that of Example 1, with the only difference being that: the phenylboronic acid in step 2) is replaced with 2-isopropylphenylboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine, to obtain compound 27 with a yield of 66.1%. The structural characterization is as follows: 11H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 7.0 Hz, 2H), 7.80 (d, J = 48.1 Hz, 1H), 7.56 - 7.43 (m, 7H), 7.36 - 7.28 (m, 1H), 6.73 (s, 2H), 3.85 (d, J = 48.5 Hz, 1H), 3.36 (s, 4H), 1.33 - 1.28 (m, 6H), 1.18 (s, 6H). 13 13C NMR (100 MHz, CDCl3) δ 145.11, 136.66, 136.55, 131.96, 130.21, 128.42, 126.58, 126.18, 125.58, 122.67, 112.43, 44.61, 31.44, 24.36, 12.59. HRMS (ESI) calcd for C 28 H 31 N5[M + H] + , 438.2652; found, 438.2651.

[0154] Example 28

[0155] The structure and preparation method of the s-triazine compound in this example are as follows:

[0156] The s-triazine compound 28 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0157] The preparation method of the s-triazine compound 28 is basically the same as that of Example 1, with the only difference being that: the phenylboronic acid in step 2) is replaced by 3-fluorophenylboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced by N,N-diethyl-p-phenylenediamine, to obtain the compound 28 with a yield of 33.8%. The structure characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 6.1 Hz, 2H), 8.38 (d, J = 7.1 Hz, 1H), 8.27 (d, J = 10.0 Hz, 1H), 7.58 - 7.45 (m, 6H), 7.25 - 7.22 (m, 2H), 6.76 (d, J = 9.0 Hz, 2H), 3.39 (q, J = 7.1 Hz, 4H), 1.20 (t, J = 7.1 Hz, 6H). 1313C NMR(100MHz,CDCl3)δ164.83,164.22,161.79,145.12,132.09,129.92,129.84,128.45,126.53,124.47,122.72,118.88,118.67,112.36,44.60,12.62.HRMS(ESI)calcd for C 25 H 24 FN5[M+H] + ,414.2089;found:414.2091.

[0158] Example 29

[0159] The structure and preparation method of the s-triazine compound in this example are as follows:

[0160] The s-triazine compound 29 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0161] The preparation method of the s-triazine compound 29 is basically the same as that in Example 1, except that: the phenylboronic acid in step 2) is replaced with 3-acetylphenylboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine to prepare the compound 29, and the yield is 56.9%. The structure characterization is as follows: 1 1H NMR(400MHz,CDCl3)δ9.14(s,1H),8.78(d,J = 7.7Hz,1H),8.59(d,J = 5.5Hz,2H),8.15(d,J = 7.7Hz,1H),7.61(t,J = 7.8Hz,1H),7.57 - 7.51(m,5H),7.27(s,1H),6.76(d,J = 8.9Hz,2H),3.39(q,J = 7.0Hz,4H),2.72(s,3H),1.19(t,J = 7.0Hz,6H). 13 13C NMR(100MHz,CDCl3)δ197.92,164.80,145.12,137.35,137.16,132.12,131.28,128.79,128.47,122.92,122.70,112.28,44.60,12.60.HRMS(ESI)calcd for C 27 H 27 N5O[M+H] + ,438.2289;found,438.2288.

[0162] Example 30

[0163] The structure and preparation method of the s-triazine compound in this example are as follows:

[0164] The s-triazine compound 30 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0165] The preparation method of the s-triazine compound 30 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced by 3-acetamidophenylboronic acid, and the 4-methyl-1-piperazineethanamine in step 2) is replaced by N,N-diethyl-p-phenylenediamine to obtain the compound 30 with a yield of 43.1%. The structure characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.56(d,J = 6.9Hz,2H),8.49(s,1H),8.31(d,J = 7.8Hz,1H),7.97(d,J = 35.6Hz,1H),7.57 - 7.52(m,4H),7.50 - 7.47(m,2H),7.44(d,J = 1.9Hz,1H),7.24(s,1H),6.76(d,J = 8.9Hz,2H),3.38(q,J = 7.1Hz,4H),2.21(s,3H),1.19(t,J = 7.0Hz,6H).HRMS(ESI)calcd for C 27 H 28 N6O[M + H] + ,453.2398; found,453.2402.

[0166] Example 31

[0167] The structure and preparation method of the s-triazine compound in this example are as follows:

[0168] The s-triazine compound 31 conforms to the general formula I, wherein X = NH, R1 = , R2 = , R3 = .

[0169] The preparation method of the s-triazine compound 31 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced by 3-fluoro-4-methoxyphenylboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced by N,N-diethyl-p-phenylenediamine to obtain the compound 31 with a yield of 50.2%. The structure characterization is as follows: 11H NMR (400 MHz, CDCl3) δ 8.61 - 8.56 (m, 4H), 7.57 - 7.49 (m, 5H), 7.20 - 7.16 (m, 3H), 6.75 (d, J = 9.0 Hz, 2H), 3.38 (q, J = 7.1 Hz, 4H), 1.19 (t, J = 7.0 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ 165.43, (J = 250.35 Hz), 164.78, 164.19, 145.05, 136.53, 132.80, 131.99, 130.89, 128.62, 128.42, 126.64, 122.71, 115.39 (J = 21.6 Hz), 112.36, 44.60, 12.61. HRMS (ESI) calcd for C 25 H 24 FN5[M + H] + , 414.2089; found, 414.2090.

[0170] Example 32

[0171] The structure and preparation method of the s - triazine compound in this example are as follows:

[0172] The s - triazine compound 32 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0173] The preparation method of the s - triazine compound 32 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with 3,4,5 - trimethoxyphenylboronic acid, and the 4 - methyl - 1 - piperazineethanamine in step 3) is replaced with N,N - diethyl - p - phenylenediamine, and the compound 32 is prepared with a yield of 59.2%. The structure characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 6.5 Hz, 2H), 8.36 (d, J = 7.8 Hz, 1H), 8.31 (dd, J = 12.6, 2.0 Hz, 1H), 7.57 - 7.49 (m, 5H), 7.19 (s, 1H), 7.06 (t, J = 8.5 Hz, 1H), 6.75 (d, J = 9.0 Hz, 2H), 3.97 (s, 2H), 3.38 (q, J = 7.1 Hz, 4H), 1.19 (t, J = 7.1 Hz, 6H). 1313C NMR (100 MHz, CDCl3) δ 164.73, 153.38, 150.97, 150.86, 145.02, 136.54, 131.97, 128.42, 126.72, 124.48, 123.99, 122.66, 112.50, 112.40, 56.27, 44.62, 12.62. HRMS (ESI) calcd for C 26 H 26 FN5O [M+H] + , 443.2194; found, 443.2201.

[0174] Example 33

[0175] The structure and preparation method of the s-triazine compound in this example are as follows:

[0176] The s-triazine compound 33 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0177] The preparation method of the s-triazine compound 33 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with 2-thiopheneboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine to prepare the compound 33 with a yield of 30.2%. The structure characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 6.3 Hz, 2H), 8.19 (d, J = 2.9 Hz, 1H), 7.56 - 7.48 (m, 6H), 7.18 (t, J = 4.7 Hz, 2H), 6.74 (d, J = 9.0 Hz, 2H), 3.38 (q, J = 7.0 Hz, 4H), 1.19 (t, J = 7.0 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ 164.37, 144.95, 136.32, 131.99, 131.14, 130.61, 128.67, 128.38, 128.15, 126.77, 124.46, 123.98, 122.45, 119.09, 112.41, 44.61, 12.60. HRMS (ESI) calcd for C 23 H 23 N5S [M+H] + , 402.1747; found, 402.1748.

[0178] Example 34

[0179] The structure and preparation method of the s-triazine compound in this example are as follows:

[0180] The s-triazine compound 34 conforms to the general formula I, wherein X = NH, R1 = , R2 = , R3 = .

[0181] The preparation method of the s-triazine compound 34 is basically the same as that of Example 1, except that: replace phenylboronic acid in step 2) with 1-methyl-1H-pyrazole-5-boronic acid, and replace 4-methyl-1-piperazineethylamine in step 3) with N,N-diethyl-p-phenylenediamine to obtain compound 34 with a yield of 66.3%. The structure characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.49(d,J=7.3Hz,2H),7.58-7.49(m,5H),7.43(s,1H),7.20(s,2H),6.73(s,2H),4.42(d,J=37.1Hz,3H),3.38(q,J=7.0Hz,4H),1.19(t,J=7.0Hz,6H). 13 C NMR(100MHz,CDCl3)δ137.97,132.21,128.50,123.57,122.79,112.19,44.58,41.02,12.58.HRMS(ESI)calcdfor C 23 H 25 N7[M+H] + ,400.2244;found,400.2250.

[0182] Example 35

[0183] The structure and preparation method of the s-triazine compound in this example are as follows:

[0184] The s-triazine compound 35 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0185] The preparation method of the s-triazine compound 35 is basically the same as that of Example 1, except that: replace phenylboronic acid in step 2) with 1-methyl-1H-pyrazole-4-boronic acid, and replace 4-methyl-1-piperazineethylamine in step 3) with N,N-diethyl-p-phenylenediamine to obtain compound 35 with a yield of 38.5%. The structure characterization is as follows: 11H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 7.0 Hz, 2H), 8.27 (s, 1H), 8.19 (s, 1H), 7.55 - 7.47 (m, 5H), 7.18 (s, 1H), 6.73 (d, J = 8.9 Hz, 2H), 3.97 (s, 3H), 3.37 (q, J = 7.0 Hz, 4H), 1.18 (t, J = 7.0 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ 164.51, 144.94, 140.60, 136.57, 128.60, 126.89, 122.63, 112.45, 44.63, 39.30, 12.61. HRMS (ESI) calcd for C 23 H 25 N7 [M + H] + , 400.2244; found, 400.2247.

[0186] Example 36

[0187] The structure and preparation method of the s-triazine compound in this example are as follows:

[0188] The s-triazine compound 36 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0189] The preparation method of the s-triazine compound 36 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with 2-methoxy-5-pyridineboronic acid, and the 4-methyl-1-piperazineethylamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine to prepare the compound 36 with a yield of 65.1%. The structure characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 9.40 (s, 1H), 8.69 (s, 1H), 8.55 (d, J = 6.2 Hz, 2H), 7.57 - 7.49 (m, 5H), 7.20 (s, 1H), 6.85 (d, J = 8.7 Hz, 1H), 6.75 (d, J = 8.9 Hz, 2H), 4.04 (s, 3H), 3.38 (q, J = 7.0 Hz, 4H), 1.19 (t, J = 7.0 Hz, 6H). 13CNMR(100MHz,CDCl3)δ166.54,164.60,149.03,145.05,136.50,131.99,128.42,126.68,125.88,122.65,112.41,110.52,53.87,44.61,12.63.HRMS(ESI)calcd forC 25 H 26 N6O[M+H] + ,427.2241;found,427.2244.

[0190] Example 37

[0191] The structure and preparation method of the s-triazine compound in this example are as follows:

[0192] The s-triazine compound 37 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0193] The preparation method of the s-triazine compound 37 is basically the same as that in Example 1, except that: the phenylboronic acid in step 2) is replaced by 2-naphthaleneboronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced by N,N-diethyl-p-phenylenediamine, to obtain compound 37 with a yield of 39.6%. The structure characterization is as follows: 1 H NMR(400MHz,CDCl3)δ9.15(s,1H),8.64(d,J = 7.5Hz,3H),8.04(d,J = 7.1Hz,1H),7.96(d,J = 8.6Hz,1H),7.90(d,J = 7.2Hz,1H),7.60 - 7.52(m,7H),7.26(s,1H),6.77(d,J = 8.8Hz,2H),3.39(q,J = 7.0Hz,4H),1.20(t,J = 7.0Hz,6H). 13 C NMR(100MHz,CDCl3)δ164.84,145.01,136.70,135.43,134.00,133.05,131.95,129.46,128.43,128.04,127.77,127.51,126.82,126.24,122.67,112.42,44.62,12.62.HRMS(ESI)calcd for C 29 H 27 N5[M+H] + ,446.2339;found,446.2341.

[0194] Example 38

[0195] The structure and preparation method of the s-triazine compound in this example are as follows:

[0196] The s-triazine compound 38 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0197] The preparation method of the s-triazine compound 38 is basically the same as that in Example 1, except that: replace the phenylboronic acid in step 2) with benzo-1,4-dioxane-6-boronic acid, and replace the 4-methyl-1-piperazineethanamine in step 3) with N,N-diethyl-p-phenylenediamine to prepare the compound 38, and the yield is 34.3%. The structure characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.56(d,J = 6.6Hz,2H),8.12(d,J = 13.4Hz,2H),7.55 - 7.47(m,5H),6.97(d,J = 8.5Hz,1H),6.74(d,J = 9.0Hz,2H),4.31(dd,J = 8.0,4.9Hz,4H),3.36(q,J = 7.0Hz,4H),1.17(t,J = 7.0Hz,6H). 13 C NMR(100MHz,CDCl3)δ164.75,147.14,144.92,143.39,136.74,131.82,130.22,128.71,128.36,127.09,122.52,118.02,117.18,112.56,64.70,64.22,44.63,12.64.HRMS(ESI)calcd for C 27 H 27 N5O2[M + H] + ,454.2238; found,454.2244.

[0198] Example 39

[0199] The structure and preparation method of the s-triazine compound in this example are as follows:

[0200] The s-triazine compound 39 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0201] The preparation method of the s-triazine compound 39 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with N-methylindole-5-boronic acid, and the 4-methyl-1-piperazineethylamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine, and the compound 39 is prepared with a yield of 59.0%. The structural characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.96(s,1H),8.62(d,J=6.1Hz,2H),8.51(d,J=8.5Hz,1H),7.60(d,J=8.7Hz,2H),7.53(q,J=5.3Hz,3H),7.41(d,J=8.7Hz,1H),7.19(s,1H),7.10(d,J=3.1Hz,1H),6.78(d,J=8.7Hz,2H),6.64(d,J=3.0Hz,1H),3.84(s,3H),3.39(q,J=7.0Hz,4H),1.20(t,J=7.1Hz,6H). 13 CNMR(100MHz,CDCl3)δ164.79,139.21,137.06,131.71,129.84,128.73,128.50,128.37,122.50,112.66,108.98,102.71,44.72,12.63.HRMS(ESI)calcd for C 28 H 28 N6[M+H] + ,449.2448;found,449.2449.

[0202] Example 40

[0203] The structure and preparation method of the s-triazine compound in this example are as follows:

[0204] The s-triazine compound 40 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0205] The preparation method of the s-triazine compound 40 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with benzothiophene-2-boronic acid, and the 4-methyl-1-piperazineethylamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine, and the compound 40 is prepared with a yield of 35.3%. The structural characterization is as follows: 11H NMR (400 MHz, CDCl3) δ 8.56 (s, 2H), 8.47 (s, 1H), 7.91 (d, J = 7.5 Hz, 2H), 7.57 - 7.50 (m, 5H), 7.44 - 7.38 (m, 2H), 7.23 (s, 1H), 6.77 (d, J = 8.2 Hz, 2H), 3.39 (q, J = 7.0 Hz, 4H), 1.20 (t, J = 7.0 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ 164.37, 147.71, 147.64, 147.11, 145.05, 142.22, 139.83, 138.57, 138.48, 136.23, 132.12, 128.89, 128.62, 128.45, 127.60, 126.65, 126.19, 125.15, 124.64, 124.49, 124.01, 122.77, 122.64, 122.48, 119.12, 112.41, 44.63, 12.64. HRMS (ESI) calcd for C 27 H 25 N5S [M + H] + , 452.1904; found, 452.1903.

[0206] Example 41

[0207] The structure and preparation method of the s-triazine compound in this example are as follows:

[0208] The s-triazine compound 41 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0209] The preparation method of the s-triazine compound 41 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with 1-ethylpyrazole-4-boronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine to prepare the compound 41, and the yield is 35.3%. The structure characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 7.1 Hz, 2H), 8.28 (s, 1H), 8.23 (s, 1H), 7.53 - 7.47 (m, 5H), 7.16 (s, 1H), 6.74 (d, J = 9.0 Hz, 2H), 4.25 (q, J = 7.3 Hz, 2H), 3.37 (q, J = 7.1 Hz, 4H), 1.55 (t, J = 7.3 Hz, 3H), 1.18 (t, J = 7.0 Hz, 6H).13 13C NMR (100 MHz, CDCl3) δ 164.52, 144.93, 140.43, 136.59, 131.82, 130.72, 128.61, 128.35, 126.89, 122.61, 112.43, 47.45, 44.62, 15.41, 12.60. HRMS (ESI) calcd for C 24 H 27 N7[M + H] + , 414.2401; found, 414.2400.

[0210] Example 42

[0211] The structure and preparation method of the s-triazine compound in this example are as follows:

[0212] The s-triazine compound 42 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0213] The preparation method of the s-triazine compound 42 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with 1-n-propyl-1H-pyrazole-4-boronic acid, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine to obtain compound 42 with a yield of 48.0%. The structure characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 7.0 Hz, 2H), 8.28 (s, 1H), 8.21 (s, 1H), 7.56 - 7.47 (m, 5H), 7.14 (s, 1H), 6.74 (d, J = 8.9 Hz, 2H), 4.15 (t, J = 7.0 Hz, 2H), 3.37 (q, J = 7.0 Hz, 4H), 2.00 - 1.91 (m, 2H), 1.18 (t, J = 7.0 Hz, 6H), 0.96 (t, J = 7.4 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 164.52, 144.94, 140.44, 136.59, 131.82, 131.44, 128.62, 128.35, 126.89, 122.61, 112.43, 54.29, 44.62, 23.59, 12.60, 11.12. HRMS (ESI) calcd for C 25 H 29 N7[M + H] + , 428.2558; found, 428.2560.

[0214] Example 43

[0215] The structure and preparation method of the s-triazine compound in this example are as follows:

[0216] The s-triazine compound 43 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0217] The preparation method of the s-triazine compound 43 is basically the same as that of Example 1, except that: the phenylboronic acid in step 2) is replaced with 1-cyclopropylpyrazole-4-boronic acid pinacol ester, and the 4-methyl-1-piperazineethanamine in step 3) is replaced with N,N-diethyl-p-phenylenediamine, and the compound 43 is prepared with a yield of 48.0%. The structural characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.50(d,J = 7.1Hz,2H),8.26(d,J = 7.7Hz,2H),7.54 - 7.47(m,5H),7.14(s,1H),6.74(d,J = 8.9Hz,2H),3.71 - 3.65(m,1H),3.37(q,J = 7.0Hz,4H),1.20 - 1.11(m,8H),1.08(q,J = 7.4Hz,2H). 13 C NMR(100MHz,CDCl3)δ164.50,144.95,140.51,136.55,131.84,128.63,128.36,126.84,122.61,112.42,44.62,33.17,12.60,6.65.HRMS(ESI)calcd for C 25 H 27 N7[M + H] + ,426.2401; found,426.2401.

[0218] Example 44

[0219] The structure and preparation method of the s-triazine compound in this example are as follows:

[0220] The s-triazine compound 44 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0221] The preparation method of the s-triazine compound 44 is basically the same as that of Example 1, except that: replacing the phenylboronic acid in step 2) with 1-(1-ethoxyethyl)-4-pyrazoleboronic acid pinacol ester, and replacing the 4-methyl-1-piperazineethanamine in step 3) with N,N-diethyl-p-phenylenediamine, the compound 44 is prepared with a yield of 48.0%. The structural characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.52(d,J=7.0Hz,2H),8.42(s,1H),8.29(s,1H),7.54-7.49(m,5H),7.13(s,1H),6.74(d,J=9.0Hz,2H),5.58(q,J=6.0Hz,1H),3.56-3.48(m,1H),3.46-3.35(m,5H),1.74(d,J=6.0Hz,3H),1.19(t,J=7.0Hz,9H). 13 C NMR(100MHz,CDCl3)δ164.53,144.99,136.49,131.91,128.57,128.39,126.77,122.63,112.42,88.02,64.41,58.46,44.62,22.22,14.86.HRMS(ESI)calcd for C 26 H 31 N7O[M+H] + ,458.2663;found,458.2670.

[0222] Example 45

[0223] The structure and preparation method of the s-triazine compound in this example are as follows:

[0224] The s-triazine compound 45 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0225] The preparation method of the s-triazine compound 45 is basically the same as that of Example 1, except that: replacing the phenylboronic acid in step 2) with 1-benzyl-4-pyrazoleboronic acid pinacol ester, and replacing the 4-methyl-1-piperazineethanamine in step 3) with N,N-diethyl-p-phenylenediamine, the compound 45 is prepared with a yield of 48.0%. The structural characterization is as follows: 11H NMR (400 MHz, CDCl3) δ 8.49 (d, J = 7.2 Hz, 2H), 8.33 (s, 1H), 8.21 (s, 1H), 7.54 - 7.46 (m, 5H), 7.38 - 7.32 (m, 3H), 7.27 (d, J = 6.9 Hz, 2H), 7.15 (s, 1H), 6.72 (d, J = 8.5 Hz, 2H), 5.37 (s, 2H), 3.36 (q, J = 7.0 Hz, 4H), 1.18 (t, J = 7.0 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ 164.47, 144.93, 140.82, 136.51, 135.86, 131.84, 131.70, 128.93, 128.59, 128.35, 128.29, 127.83, 126.81, 122.60, 112.40, 56.46, 44.61, 12.60. HRMS (ESI) calcd for C 29 H 29 N7 [M + H] + , 476.2558; found, 476.2558.

[0226] Example 46

[0227] The structure and preparation method of the s - triazine compound of this example are as follows:

[0228] The s - triazine compound 46 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0229] The preparation method of the s - triazine compound 46 comprises the following steps:

[0230] 1) Dissolve compound II (2 g, 10.85 mmol) and 4 - methylphenylmagnesium bromide (0.5 M in THF) (24 mL, 10.85 mmol) in anhydrous tetrahydrofuran (25 mL), react at 0 °C under nitrogen protection, and monitor the reaction progress by TLC. After the reaction is completed, pour the mixture into cold 10% hydrochloric acid aqueous solution. Distill off the solvent under reduced pressure, add ethyl acetate (25 mL) to the obtained reaction system, wash the organic phase with saturated brine (3 × 25 mL), dry over anhydrous magnesium sulfate, and purify by column chromatography to obtain the intermediate compound V.

[0231] 2) Dissolve compound V (300 mg, 1.17 mmol) and sodium bicarbonate (98 mg, 1.17 mmol) in anhydrous tetrahydrofuran (10 mL). Slowly add N,N - diethyl - p - phenylenediamine (192 mg, 1.17 mmol) dropwise at 0 °C, and react at room temperature while monitoring the reaction progress by TLC. After the reaction is completed, remove the solvent by distillation under reduced pressure. Add ethyl acetate (10 mL) to the resulting reaction system, wash the organic phase with saturated brine (3 × 10 mL), dry over anhydrous magnesium sulfate, and purify by column chromatography to obtain intermediate compound VI.

[0232] 3) Dissolve intermediate compound VI (121 mg, 0.32 mmol) and 1 - methylpyrazole - 4 - boronic acid (48 mg, 0.32 mmol) in an aqueous solution of 1,4 - dioxane (V 1,4-二氧六环 :V 水 = 4:1, 10 mL), then successively add potassium carbonate anhydrous (52 mg, 0.38 mmol) and bis(triphenylphosphine)palladium(II) dichloride (15 mg, 0.0214 mmol), and react at 90 °C under nitrogen protection while monitoring the reaction progress by TLC. After the reaction is completed, remove the solvent by distillation under reduced pressure. Add ethyl acetate (10 mL) to the resulting reaction system, wash the organic phase with saturated brine (3 × 10 mL), dry over anhydrous magnesium sulfate, and purify by column chromatography to obtain the s - triazine compound 46. The yield is 28.0%. The structure characterization is as follows: 1 H NMR (400 MHz, CDCl3) δ8.39 (d, J = 8.2 Hz, 2H), 8.25 (s, 1H), 8.18 (s, 1H), 7.54 - 7.48 (m, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.11 (s, 1H), 6.80 - 6.67 (m, 2H), 3.97 (s, 3H), 3.37 (q, J = 7.0 Hz, 4H), 2.43 (s, 3H), 1.18 (t, J = 7.1 Hz, 6H). 13 C NMR (100 MHz, CDCl3) δ167.74, 164.51, 144.92, 142.26, 140.59, 133.87, 132.34, 129.15, 128.60, 127.07, 122.53, 112.54, 44.64, 39.22, 21.59, 12.59. HRMS (ESI) calcd for C 24 H 27 N7[M + H] + , 414.2401; found, 414.2404.

[0233] Example 47

[0234] The structure and preparation method of the s-triazine compound in this embodiment are as follows:

[0235] The s-triazine compound 47 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0236] The preparation method of the s-triazine compound 47 is basically the same as that of Example 46, except that: 4-methylphenylmagnesium bromide in step 1) is replaced with 4-methoxyphenylmagnesium bromide to obtain compound 47 with a yield of 25.0%. The structure characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.49-8.44(m,2H),8.25(s,1H),8.17(s,1H),7.54-7.46(m,2H),7.11(s,1H),7.02-6.94(m,2H),6.77-6.68(m,2H),3.97(s,3H),3.88(s,3H),3.36(q,J = 7.1Hz,4H),1.18(t,J = 7.1Hz,6H). 13 C NMR(100MHz,CDCl3)δ170.88,167.64,164.45,162.81,144.90,140.56,132.28,130.43,129.13,127.12,122.54,113.71,112.54,55.44,44.64,39.32,12.63.HRMS(ESI)calcd for C 24 H 27 N7O[M+H] + ,430.2350; found,430.2352.

[0237] Example 48

[0238] The structure and preparation method of the s-triazine compound in this embodiment are as follows:

[0239] The s-triazine compound 48 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0240] The preparation method of the s-triazine compound 48 is basically the same as that of Example 46, except that: 4-methylphenylmagnesium bromide in step 1) is replaced with 4-chlorophenylmagnesium bromide to obtain compound 48 with a yield of 32.0%. The structure characterization is as follows: 11H NMR (400 MHz, CDCl3) δ 8.47 - 8.40 (m, 2H), 8.24 (s, 1H), 8.16 (s, 1H), 7.48 (m, 2H), 7.46 - 7.41 (m, 2H), 7.15 (s, 1H), 6.79 - 6.67 (m, 2H), 3.97 (s, 3H), 3.37 (q, J = 7.1 Hz, 4H), 1.18 (t, J = 7.1 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ 164.49, 145.07, 140.62, 138.00, 135.11, 132.39, 129.95, 128.56, 126.69, 122.70, 122.18, 112.37, 44.61, 39.25, 12.63. HRMS (ESI) calcd for C 23 H 24 ClN7 [M + H]+, 434.1855; found, 434.1849.

[0241] Example 49

[0242] The structure and preparation method of the s - triazine compound in this example are as follows:

[0243] The s - triazine compound 49 conforms to the general formula I, where X = NH, R1 = R2 = R3 =

[0244] The preparation method of the s - triazine compound 49 is basically the same as that of Example 46, except that: 4 - methylphenylmagnesium bromide in step 1) is replaced by 4 - fluorophenylmagnesium bromide to prepare compound 49, and the yield is 35.0%. The structure characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.54 - 8.48 (m, 2H), 8.25 (s, 1H), 8.16 (s, 1H), 7.52 - 7.46 (m, 2H), 7.18 - 7.11 (m, 3H), 6.73 (d, J = 4.3 Hz, 2H), 3.97 (s, 3H), 3.37 (q, J = 7.1 Hz, 4H), 1.18 (t, J = 7.1 Hz, 6H). 1313C NMR (100 MHz, CDCl3) δ 170.35, 166.64, 164.49, 164.13, 145.05, 140.62, 132.75, 132.35, 130.85, 126.77, 122.72, 122.22, 115.39, 112.42, 44.61, 39.34, 12.63. HRMS (ESI) calcd for C 23 H 24 FN7[M + H]+, 418.2150; found, 418.2155.

[0245] Example 50

[0246] The structure and preparation method of the s-triazine compound in this example are as follows:

[0247] The s-triazine compound 50 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0248] The preparation method of the s-triazine compound 50 is basically the same as that of Example 46, except that: 4-methylphenylmagnesium bromide in step 1) is replaced with 3-fluorophenylmagnesium bromide to prepare compound 50, and the yield is 30.0%. The structure characterization is as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 7.9 Hz, 1H), 8.25 (s, 1H), 8.19 (m, 2H), 7.52 - 7.47 (m, 1H), 7.46 - 7.40 (m, 1H), 7.21 (m, 1H), 7.16 (s, 1H), 6.77 - 6.70 (m, 2H), 3.97 (s, 3H), 3.37 (q, J = 7.0 Hz, 4H), 1.18 (t, J = 7.1 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ 168.10, 164.53, 164.19, 161.76, 145.09, 140.62, 139.15, 132.44, 129.76, 126.65, 124.21, 122.73, 118.50, 115.26, 112.39, 44.61, 39.35, 12.59. HRMS (ESI) calcd for C 23 H 24 FN7[M + H] + , 418.2150; found, 418.2147.

[0249] Example 51

[0250] The structure and preparation method of the s-triazine compound in this embodiment are as follows:

[0251] The s-triazine compound 51 conforms to the general formula I, wherein X = NH, R1 = R2 = R3 =

[0252] The preparation method of the s-triazine compound 51 is basically the same as that in Example 46, except that: 4-methylphenylmagnesium bromide in step 1) is replaced with cyclohexylmagnesium bromide to prepare the compound 51, and the yield is 33.0%. The structure characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.16(s,1H),8.08(s,1H),7.41(d,J = 8.2Hz,2H),6.68(d,J = 8.9Hz,2H),5.03(s,1H),3.93(s,3H),3.35(q,J = 7.0Hz,4H),2.07(s,2H),1.84(dd,J = 9.3,4.0Hz,2H),1.71(s,1H),1.61(dd,J = 11.7,3.6Hz,2H),1.41(t,J = 12.1Hz,2H),1.36 - 1.23(m,2H),1.16(t,J = 7.1Hz,6H). 13 C NMR(100MHz,CDCl3)δ165.62,145.01,140.58,132.33,126.76,122.74,122.69,121.82,112.40,44.61,39.29,39.19,31.73,25.50,24.14,12.54.

[0253] Test example

[0254] LSD1 inhibitory activity assay: The samples are the s-triazine compounds prepared in Examples 1 to 51 after purification. The preparation process of the sample stock solution is as follows: Weigh 1 - 2 mg of the sample respectively, and prepare a solution with a concentration of 20 mM in DMSO, and store it for use at 4°C. Dilute it to the required concentration with DMSO during the test. After incubating the sample to be tested with LSD1 protein at room temperature, add the LSD1 substrate H3K4me2 and incubate, and finally add the fluorescent dye Amplex and horseradish peroxidase HRP and incubate at room temperature. Detect the fluorescence value on an enzyme-labeled instrument at an excitation wavelength of 530 nm and an emission wavelength of 590 nm. The inhibition rate calculation formula is as follows.

[0255] The test results are calculated using SPSS software for the IC 50 value, and the results are shown in Table 1.

[0256]

[0257] Table 1 LSD1 inhibitory activities of the s-triazine compounds in Examples 1 to 51 of the present invention

[0258]

[0259]

[0260]

[0261]

[0262] As can be seen from Table 1, the s-triazine compounds provided by the present invention have inhibitory activities on the LSD1 target protein to varying degrees. Among them, when the compound concentration is 10 μM, the s-triazine compounds 12 - 14, 17 - 18, 21 - 26, 28, 30 - 39, 41 - 42, 44 have relatively high inhibitory activities on LSD1, and the inhibition rates all reach more than 50%. Further, the s-triazine compounds 17, 25 - 26, 30, 35, 41 - 42, 51 have better inhibitory activities, and the inhibition rates on LSD1 can reach more than 80%. In addition, when the s-triazine compounds 18, 25 - 26, 30, 35, 37 - 38, 41, 51 exert their effects, the IC 50 values are relatively low, all lower than 1 μM, indicating that the above s-triazine compounds exert effective inhibitory activities at relatively low concentrations. In particular, for the s-triazine compounds 25, 30, 35, 41, 51, the inhibition rates on LSD1 can reach more than 90%, and the IC 50 values are only 0.1 - 0.8 μM, all lower than 1 μM. This group of compounds exert effective inhibitory activities at relatively low concentrations, have stronger targeting effects, and are comparable to the inhibitory activities of existing commercially available LSD1 inhibitors, and are very suitable for development and application as new LSD1 inhibitor drugs.

[0263] In summary, the s-triazine compounds provided by the present invention have good inhibitory activities on LSD1, show good development potential, can provide new design directions and skeleton selections for the research and development of new inhibitors based on the LSD1 target, and are also of great significance for the research and treatment of related diseases based on the LSD1 target.

[0264] The above embodiments are only the preferred embodiments of the present invention and cannot be used to limit the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention fall within the scope of protection required by the present invention.

Claims

1. A sym-triazine compound, characterized in that, A compound of formula I or a pharmaceutically acceptable salt thereof: In formula I, X, R1, R2, and R3 are selected from the following group of groups: After X, R1, R2, and R3 are selected from the above group of groups, the resulting s-triazine compounds are sequentially denoted as Compound 12, Compound 13, Compound 14, Compound 17, Compound 18, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 28, Compound 30, Compound 31, Compound 32, Compound 33, Compound 34, Compound 35, Compound 36, Compound 37, Compound 38, Compound 39, Compound 41, Compound 42, Compound 44, Compound 47, Compound 48, Compound 49, Compound 50, Compound 51.

2. A method for preparing the s-triazine compound as described in claim 1, characterized in that, It is prepared by using the following Synthetic Route ① or Synthetic Route ②; Synthetic Route ① includes the following steps: Reacting Compound II, phenylboronic acid, basic substance A, and a catalyst in organic solvent A to obtain Compound III; Reacting Compound III, R2B(OH)2, basic substance A, and a catalyst in organic solvent B to obtain Compound IV; Reacting Compound IV, R1XH, and basic substance B in organic solvent C to obtain the s-triazine compound shown in formula I; Synthetic Route ② includes the following steps: Reacting Compound II and a Grignard reagent in organic solvent D to obtain Compound V; Reacting Compound V, N,N-diethyl-p-phenylenediamine, and basic substance C in organic solvent E to obtain Compound VI; Reacting Compound VI, 1-methylpyrazole-4-boronic acid, basic substance D, and a catalyst in organic solvent F to obtain the s-triazine compound shown in formula I; The basic substances A, B, C, and D are each independently selected from one or more of potassium carbonate, cesium carbonate, sodium bicarbonate, sodium tert-butoxide, triethylamine, pyridine, sodium hydroxide, and potassium hydroxide; The catalyst is one or more of tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride, and bis(dibenzylideneacetone)palladium.

3. The preparation method of the s-triazine compound according to claim 2, characterized in that, The organic solvents A, B, C, D, E, and F are each independently selected from one or more of N,N-dimethylformamide, N-methylpyrrolidone, tetrahydrofuran, acetonitrile, dioxane, methanol, ethanol, a dioxane-water mixed solution with a volume ratio of 4:1, and toluene.

4. The preparation method of the s-triazine compound according to claim 2, characterized in that, In Synthetic Route ①, the reaction temperature between Compound II and phenylboronic acid is 50 - 150 °C; the reaction temperature between Compound III and R2B(OH)2 is 50 - 150 °C; the reaction temperature between Compound IV and R1XH is 20 - 80 °C.

5. The preparation method of the s-triazine compound according to claim 2, wherein In Synthetic Route ②, the reaction temperature between Compound II and the Grignard reagent is -10 - 30 °C; the reaction temperature between Compound V and N,N-diethyl-p-phenylenediamine is 0 - 50 °C; the reaction temperature between Compound VI and 1-methylpyrazole-4-boronic acid is 60 - 120 °C.

6. Use of a s-triazine compound as described in claim 1, characterized in that, Use of the s-triazine compound as an active ingredient in the preparation of an inhibitor against the LSD1 target.

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