6-phenyl-purine derivative as well as preparation method and medical application thereof

Abstract

The invention belongs to the technical field of medicine preparation, and particularly relates to 6-phenyl-purine derivatives as well as a preparation method and medical application thereof. The structural formula of the 6-phenyl-purine derivative is shown in the specification. The preparation method of the 6-phenyl-purine derivative comprises the following steps: S1, carrying out substitution reaction on R1-CH2NH2 and a compound 1 under the catalysis of organic base to obtain a compound 2; s2, carrying out Dieckmann condensation reaction on the compound 2 and excessive CDI to obtain a compound 3; s3, the compound 3 and phenylboronic acid are subjected to a Suzuki coupling reaction under catalysis of sodium carbonate, Pd (OAc) 2 and TPPTS, and the 6-phenyl-purine derivative with the structure shown in the general formula I is obtained. The 6-phenyl-purine derivative has antineoplastic activity and can be applied to preparation of antineoplastic drugs.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a class of 6-phenyl-purine derivatives, their preparation methods, and pharmaceutical uses. Background Technology

[0002] In the field of oncology treatment, the contradiction between clinical needs and drug supply is becoming increasingly prominent. Although chemotherapy, targeted drugs, and immunotherapy have formed a multi-dimensional treatment system, the adaptive evolution of tumor cells (such as drug resistance mutations and phenotypic transformation) still leads to treatment failure in approximately 60% of patients. Therefore, developing novel drugs that combine high anti-tumor activity, low toxicity and side effects, and strong targeting has become an urgent need for the pharmaceutical industry.

[0003] Purines are fundamental building blocks of DNA and RNA synthesis, and also the core structure of many key coenzymes (such as ATP and NAD+) and signaling molecules (such as cAMP). Cell proliferation, especially the rapid and unlimited proliferation of tumor cells, is highly dependent on the synthesis and utilization of purine nucleotides. Purine-like compounds, due to their unique chemical structure and biological activity, have shown significant advantages in cancer treatment. These compounds, by mimicking purine analogs, can integrate into DNA or RNA, interfering with DNA synthesis and repair in cancer cells, thereby inhibiting cancer cell proliferation. Simultaneously, by modifying the purine backbone structure to possess ATP-mimicking structural properties, they can competitively inhibit protein kinases that play a crucial role in tumorigenesis, blocking their catalytic activity of transferring phosphate groups to substrate proteins, thereby interrupting signaling pathways driving tumor growth, survival, and metastasis (such as the BCR-ABL, PI3K / Akt / mTOR, and JAK / STAT pathways). Summary of the Invention

[0004] The purpose of this invention is to provide a 6-phenyl-purine derivative, its preparation method, and its pharmaceutical uses.

[0005] In a first aspect, the present invention provides a 6-phenyl-purine derivative having the structure of the following general formula I:

[0006]

[0007] Wherein, R1 is selected from phenyl, pyridyl, methoxy-substituted phenyl, amino-substituted phenyl, fluorine-substituted phenyl, trimethoxy-substituted phenyl, tert-butyl-substituted phenyl, difluoromethoxy-substituted phenyl, trifluoromethyl-substituted phenyl, dimethoxy-substituted phenyl, isopropoxy-substituted phenyl, dimethyl-substituted phenyl, cyano-substituted phenyl, methyl-substituted phenyl, biphenyl, methylamino-substituted phenyl, methoxyfluoro-disubstituted phenyl, methoxy-substituted pyridyl, etc. One of them; R2 is selected from H, amino, hydrogen, cyclopropyl, isopropyl and methyl.

[0008] Furthermore, R1 is selected from phenyl, 3-pyridyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-aminophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4,5-trimethoxyphenyl, 4-tert-butylphenyl, 4-difluoromethoxyphenyl, 4-trifluoromethylphenyl, 3,4-dimethoxyphenyl, 4-isopropoxyphenyl, 3,4-dimethylphenyl, 4-cyanophenyl, 3-methoxyphenyl, 4-methylphenyl, 4-methylaminophenyl, 3-fluoro-4-methoxyphenyl, 2,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2-methoxy-5-pyridyl, One of them; R2 is selected from H, amino, cyclopropyl, isopropyl and methyl.

[0009] The preferred compound designations and corresponding structures of the above general formula I are shown in Table 1:

[0010] Table 1. Compound codes and corresponding structures for some compounds of general formula I.

[0011]

[0012]

[0013] Secondly, the present invention provides a method for preparing the above-mentioned 6-phenyl-purine derivative, the synthetic route of which is as follows:

[0014]

[0015] The preparation method includes the following steps:

[0016] S1.R1-CH2NH2 undergoes a substitution reaction with compound 1 under organic base catalysis to give compound 2;

[0017] S2. Compound 2 reacts with excess carbonyl diimidazole (CDI) via a Dieckmann condensation reaction to give compound 3;

[0018] S3. Compound 3 and phenylboronic acid were coupled via a Suzuki coupling reaction catalyzed by sodium carbonate, Pd(OAc)2 and sodium triphenylphosphine trimethylsulfonate (TPPTS) to obtain a 6-phenyl-purine derivative with the structure shown in general formula I.

[0019] Furthermore, the organic base is triethylamine (TEA) or N,N-diisopropylethylamine (DIPEA).

[0020] Furthermore, in step S1, the organic base is triethylamine or N,N-diisopropylethylamine, and the molar ratio of R1-CH2NH2 to compound 1 is 3.3:3.

[0021] Furthermore, in step S1, the reaction conditions for the substitution reaction are: using n-butanol as a solvent, reacting at 120°C for 2 days.

[0022] Furthermore, in step S2, the molar ratio of compound 2 to CDI is 2.59:12.97, and the Dieckmann condensation reaction is carried out under nitrogen protection at a reaction temperature of 30°C for 12 hours.

[0023] Furthermore, in step S3, the molar ratio of compound 3 to phenylboronic acid is 1:1.2, and the Suzuki coupling reaction is carried out under nitrogen protection at a reaction temperature of 100°C for 3 hours.

[0024] Thirdly, the present invention provides the use of the above-mentioned 6-phenyl-purine derivative or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a medicament for treating and / or preventing malignant tumors, wherein the malignant tumor refers to one of lung cancer, breast cancer, prostate cancer, colon cancer and liver cancer.

[0025] Fourthly, the present invention provides an antitumor drug, wherein the active ingredient of the antitumor drug is the above-mentioned 6-phenyl-purine derivative or a medically acceptable salt thereof, and the antitumor drug is used to treat and / or prevent malignant tumors, wherein the malignant tumor refers to one of lung cancer, breast cancer, prostate cancer, colon cancer and liver cancer.

[0026] Compared with existing technologies, this invention designs and synthesizes novel 6-phenyl-purine derivatives based on a purine skeleton, and no such compounds have been reported to date. The compounds of this invention use an 8-carbonylpurine structure as the parent nucleus, and introduce different substituents onto the parent nucleus. When the substituent is methyl at the 2-position and methoxyphenyl, biphenyl, 3-fluoro-4-methoxyphenyl, or 3-fluorophenyl at the 9-position, its anti-tumor cell activity is significantly enhanced. Activity tests on various types of cancer cells have shown that these compounds selectively and strongly inhibit the proliferation of various tumor cells (including lung cancer, breast cancer, prostate cancer, colon cancer, and liver cancer), with some compounds even exhibiting nanomolar activity. Therefore, the compounds of this invention have significant potential for pharmaceutical applications. Detailed Implementation

[0027] To further illustrate the present invention, a series of embodiments are given below. These embodiments are purely illustrative and are only used to specifically describe the present invention, and should not be construed as limiting the present invention. It should be understood that, within the scope of the present invention, the above-described technical features of the present invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to constitute preferred technical solutions.

[0028] Example 1: Preparation of 9-benzyl-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I1)

[0029] Compound 1 (534 mg, 3 mmol), benzylamine (354 mg, 3.3 mmol), TEA (1.1 ml, 9 mmol), and n-butanol (6 ml) were added sequentially to a Schlenk tube. The tube was protected with N2 and reacted at 120 °C for 2 days. After the reaction was completed by TLC monitoring, the reaction mixture was evaporated to dryness. Dichloromethane / methanol (100:1, v / v) was used as the eluent for column chromatography to purify the mixture and give a white solid 2a with a yield of 86%. 1 HNMR (400MHz, DMSO-d6) δ7.33(d,J=4.4Hz,4H,ArH),7.29-7.23(m,1H,ArH),7.20(m,1H,NH),4.82(s,2H,NH2),4.61(d,J=5.6Hz,2H,CH2),2.23(s,3H,CH3).

[0030] Compound 2a (645 mg, 2.59 mmol) was dissolved in anhydrous tetrahydrofuran (13 ml) under N2 protection. CDI (2 g, 12.97 mmol) was added to the solution, and the reaction was carried out at 30 °C for 12 h. After the reaction was completed by TLC monitoring, water was slowly added to the reaction solution to quench excess CDI, and then an appropriate amount of water was added and stirred. After a large amount of solid precipitated, the mixture was filtered and the filter cake was dried to obtain white solid 3a with a yield of 67%. 1 H NMR (400MHz, DMSO-d6) δ12.03(s,1H,CONH),7.43-7.21(m,5H,ArH),4.99(s,2H,CH2),2.52(s,3H,CH3).

[0031] Compound 3a (77 mg, 0.28 mmol), phenylboronic acid (41.5 mg, 0.34 mmol), sodium carbonate (59.4 mg, 0.56 mmol), palladium acetate (3.2 mg, 0.014 mmol), and trisodium triphenylphosphine tris(m-sulfonate) (20 mg, 0.035 mmol) were added to a Schlenk tube under N2 protection. Water:acetonitrile (2:1, 6 mL) was added to the Schlenk tube as solvent, and the reaction was carried out at 100 °C for about 3 h. After the reaction was completed by TLC monitoring, the reaction solution was extracted with ethyl acetate and water. The ethyl acetate layer was evaporated to dryness, and dichloromethane / methanol (100:1, v / v) was used as the eluent for column chromatography. After purification, a white solid I1 was obtained with a yield of 80%. 1H NMR (400MHz, DMSO-d6) δ11.68(s,1H,CONH),8.05-7.97(m,2H,ArH),7.58-7.50(m,3H,ArH),7.40-7.23(m,5H,ArH),5.04(s,2H,CH2),2.60(s,3H,CH3).

[0032] 13 C NMR(101MHz,DMSO-d6)δ159.57,154.23,151.80,141.39,137.07,135.42,132.12 ,130.34,129.16,129.08,128.60,127.97,127.85,116.42,53.09,42.97,26.01.

[0033] Example 2: Preparation of 9-(4-methoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I2).

[0034] Following the preparation method of 2a in Example 1, compound 4-methoxybenzylamine was used to replace benzylamine in the method, and after purification, a white solid 2b was obtained with a yield of 81%. 1 H NMR(400MHz,DMSO-d6)δ7.32-7.22(m,2H,ArH),7.11(m,1H,ArH),6.93-6.82(m,2H,Ar H),4.80(s,2H,NH2),4.52(d,J=5.5Hz,2H,CH2),3.73(s,3H,OCH3),2.23(s,3H,CH3).

[0035] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2b to obtain white solid 3b with a yield of 91%. 1 H NMR (400MHz, DMSO-d6) δ11.99(s,1H,CONH),7.27(d,J=8.7Hz,2H,ArH),6.89(d,J=8.7Hz,2H,ArH),4.91(s,2H,CH2),3.71(s,3H,OCH3),2.53(s,3H,CH3).

[0036] Referring to the preparation method of I1 in Example 1, compound 3b was substituted for 3a in the method, and after purification, a white solid compound I2 was obtained with a yield of 87%. 1H NMR(400MHz,DMSO-d6)δ11.64(s,1H,CONH),8.02-7.95(m,2H,ArH),7.59-7.45(m,3H,ArH),7.35 -7.26(m,2H,ArH),6.94-6.85(m,2H,ArH),4.96(s,2H,CH2),3.72(s,3H,OCH3),2.61(s,3H,CH3).

[0037] 13 C NMR(101MHz,DMSO-d6)δ158.44,158.08,153.13,150.68,140.24,134.37,12 9.24,128.41,128.08,128.02,127.51,115.33,113.36,54.47,41.41,24.97.

[0038] Example 3: Preparation of 9-(2-methoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I3).

[0039] Following the preparation method of 2a in Example 1, o-methoxybenzylamine was substituted for benzylamine in the method, and after purification, a white solid 2c was obtained with a yield of 78%. ¹H NMR (400 MHz, DMSO-d6) δ 7.32–7.22 (m, 2H, ArH), 7.11 (m, 1H, ArH), 6.93–6.82 (m, 2H, ArH), 4.80 (s, 2H, NH₂), 4.52 (d, J = 5.5 Hz, 2H, CH₂), 3.73 (s, 3H, OCH₃), 2.23 (s, 3H, CH₃).

[0040] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2c to obtain white solid 3c with a yield of 91%. 1 H NMR (400MHz, DMSO-d6) δ11.99(s,1H,CONH),7.27(d,J=8.7Hz,2H,ArH),6.89(d,J=8.7Hz,2H,ArH),4.91(s,2H,CH2),3.71(s,3H,OCH3),2.53(s,3H,CH3).

[0041] Referring to the preparation method of I1 in Example 1, compound 3c was substituted for 3a in the method, and after purification, a white solid compound I3 was obtained with a yield of 82%. 1HNMR(400MHz,DMSO)δ11.69(s,H,NH),8.01-6.86(m,9H,ArH),4.98(s,2H,CH2),3.86(s,3H,CH3),2.54(s,3H,CH3).13C NMR (101MHz, DMSO) δ159.58,156.82,154.30,152.01,141.36,135.43,130.35,129. 19,128.97,128.60,126.68,124.27,120.77,116.54,111.16,55.35,40.48,25.91.

[0042] Example 4: 9-(4-aminobenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purin-8-one (I4) and tert-butyl(4-((2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purin-9-yl)methyl)phenyl)carbamate (I4) 30 Preparation of ).

[0043] Following the preparation method of 2a in Example 1, compound 4-(Boc-amino)benzylamine was used to replace benzylamine in the method, and after purification, a white solid 2c was obtained with a yield of 78%. 1 HNMR (400MHz, DMSO-d6) δ9.30 (s, 1H, NH), 7.39 (d, J = 8.2Hz, 2H, ArH), 7.25-7.18 (m, 2H, ArH), 7. 13(s,1H,NH),4.82(s,2H,NH2),4.51(d,J=5.4Hz,2H,CH2),2.23(s,3H,CH3),1.46(s,9H,CH3).

[0044] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2c to obtain white solid 3c with a yield of 91%. 1 H NMR (400MHz, DMSO-d6) δ12.00(s,1H,NH),9.35(s,1H,NH),7.38(d,J=8.2Hz,2H,ArH ),7.20(d,J=8.5Hz,2H,ArH),4.90(s,2H,CH2),2.52(s,3H,CH3),1.45(s,9H,CH3).

[0045] Referring to the preparation method of I1 in Example 1, compound 3c was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 30The yield was 82%. 1 H NMR(400MHz,DMSO-d6)δ11.64(s,1H,CONH),9.35(s,1H,CONH),8.03-7.97(m,2H,ArH),7.57-7.49(m,3H,Ar H),7.39(d,J=8.3Hz,2H,ArH),7.29-7.21(m,2H,ArH),4.95(s,2H,CH2),2.60(s,3H,CH3),1.45(s,9H,CH3).

[0046] Compound I 30 (180 mg, 0.42 mmol) was mixed with methanol solvent (5 ml), and 4 M hydrochloric acid methanol solution (10 ml) was added. The reaction was carried out for about 12 hours. After the reaction was completed by TLC monitoring, the reaction solution was evaporated to dryness to give compound I4, with a yield of 95%. ¹H NMR (400 MHz, DMSO-d6) δ 11.94 (s, 1H, CONH), 8.00–7.93 (m, 2H, ArH), 7.57 (m, 3H, ArH), 7.49–7.44 (m, 2H, ArH), 7.38–7.32 (m, 2H, ArH), 5.09 (s, 3H), 3.17 (s, 2H, CH2), 2.65 (s, 3H, CH3).

[0047] Example 5: Preparation of 9-(3-fluorobenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I5).

[0048] Following the preparation method of 2a in Example 1, 3-fluorobenzylamine was used to replace benzylamine in the method, and after purification, a white solid 2d was obtained with a yield of 75%. 1 H NMR(400MHz,DMSO-d6)δ7.37(m,1H,ArH),7.27(s,1H,NH),7.20-7.11(m,2H,ArH) ,7.08(m,1H,ArH),4.84(s,2H,NH2),4.63(d,J=5.6Hz,2H,CH2),2.22(s,3H,CH3).

[0049] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2d to obtain white solid 3d with a yield of 96%. 1 H NMR (400MHz, DMSO-d6) δ12.09(s,1H,CONH),7.39(m,1H,ArH),7.22-7.05(m,3H,ArH),5.01(s,2H,CH2),2.52(s,3H,CH3).

[0050] Following the preparation method of I1 in Example 1, compound 3d was substituted for 3a in the method, and after purification, a white solid compound I5 was obtained with a yield of 60%. ¹H NMR (400MHz, DMSO-d6) δ 11.71 (s, ¹H, CONH), 8.01 (d, J = 1.8Hz, ¹H, ArH), 7.99 (d, J = 1.5Hz, ¹H, ArH), 7.54 (d, J = 7.7Hz, ³H, ArH), 7.43–7.38 (m, ¹H, ArH), 7.20–7.13 (m, ³H, ArH), 5.06 (s, ²H, CH₂), 2.59 (s, ³H, CH₃). ¹³C NMR(101MHz,DMSO)δ163.87,161.44,159.56,154.19,151.72,141.48,135.40,1 30.36,129.17,128.61,123.77,116.54,114.94,114.74,114.52,42.46,25.98.

[0051] Example 6: Preparation of 9-(4-fluorobenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I6).

[0052] Referring to the preparation method of 2a in Example 1, 4-fluorobenzylamine was used to replace benzylamine in the method, and after purification, a white solid 2e was obtained with a yield of 90%. 1 HNMR (400MHz, DMSO-d6) δ7.41-7.34(m,2H,ArH),7.22(s,1H,NH),7.19-7.11(m,2H,ArH),4.83(s,2H,NH2),4.58(d,J=5.6Hz,2H,CH2),2.23(s,3H,CH3).

[0053] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2e to obtain white solid 3e with a yield of 71%. 1 HNMR(400MHz,DMSO-d6)δ12.04(s,1H,CONH),7.42-7.33(m,2H,ArH),7.21-7.12(m,2H,ArH),4.97(s,2H,CH2),2.52(s,3H,CH3).

[0054] Referring to the preparation method of I1 in Example 1, 3e was substituted for 3a in the method, and after purification, white solid compound I6 was obtained with a yield of 74%. 1H NMR(400MHz,DMSO-d6)δ11.70(s,1H,CONH),8.03-7.95(m,2H,ArH),7.57-7.50(m,3H,A rH),7.44-7.38(m,2H,ArH),7.22-7.15(m,2H,ArH),5.03(s,2H,CH2),2.60(s,3H,CH3).

[0055] 13C NMR(101MHz,DMSO-d6)δ163.21,160.79,159.56,154.17,151.69,141.43,135.39,133.31,13 3.28,130.35,130.14,130.06,129.17,128.59,116.45,115.98,115.77,42.29,40.41,26.01.

[0056] Example 7: Preparation of 2-methyl-6-phenyl-9-(3,4,5-trimethoxybenzyl)-7,9-dihydro-8H-purine-8-one (I7).

[0057] Following the preparation method of 2a in Example 1, (3,4,5-trimethoxyphenyl)methylamine was used instead of benzylamine in the method, and after purification, a white solid 2f was obtained, with a yield of 77%. 1 H NMR(400MHz,DMSO-d6)δ7.11(s,1H,NH),6.70(s,2H,ArH),4.85(s,2H,NH2),4.5 2(d,J=5.4Hz,2H,CH2),3.75(s,6H,OCH3),3.63(s,3H,OCH3),2.25(s,3H,CH3).

[0058] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2f to obtain white solid 3f with a yield of 86%. 1 H NMR (400MHz, DMSO-d6) δ12.01(s,1H,CONH),6.68(s,2H,ArH),4.91(s,2H,CH2),3.72(s,6H,OCH3),3.62(s,3H,OCH3),2.54(s,3H,CH3).

[0059] Following the preparation method of I1 in Example 1, compound 3f was substituted for 3a in the method, and after purification, a white solid compound I7 was obtained with a yield of 64%. ¹H NMR (400 MHz, DMSO-d6) δ 11.67 (s, ¹H, CONH), 7.99 (m, 2H, ArH), 7.56-7.50 (m, 3H, ArH), 6.74 (s, 2H, ArH), 4.96 (s, 2H, CH2), 3.73 (s, 6H, OCH3), 3.62 (s, 3H, OCH3), 2.62 (s, 3H, CH3). 13 C NMR (101MHz, DMSO-d6) δ159.47,154.23,153.35,151.83,141.35,137.35,135.43,132. 71,130.33,129.16,128.59,116.47,105.63,60.43,56.27,55.39,43.33,40.41,26.00.

[0060] Example 8: Preparation of 9-(4-tert-butylbenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I8).

[0061] Following the preparation method of 2a in Example 1, 4-tert-butylbenzylamine was used to replace benzylamine in the method, and after purification, 2g of white solid was obtained, with a yield of 92%. 1 H NMR(400MHz,DMSO-d6)δ7.35(d,J=8.3Hz,2H,ArH),7.26(d,J=8.3Hz,2H,ArH),7.13(s,1 H,NH),4.83(s,2H,NH2),4.56(d,J=5.4Hz,2H,CH2),2.24(s,3H,CH3),1.26(s,9H,CH3).

[0062] Referring to the preparation method of 3a in Example 1, 2g of compound was substituted for 2a in the method to obtain 3g of white solid with a yield of 93%. 1 H NMR (400MHz, DMSO-d6) δ12.04(s,1H,CONH),7.35(d,J=8.4Hz,2H,ArH),7.24(d,J=8.4Hz,2H,ArH),4.95(s,2H,CH2),2.52(s,3H,CH3),1.24(s,9H,CH3).

[0063] Following the preparation method of I1 in Example 1, 3g of compound was used to replace 3a in the method, and after purification, a white solid compound I8 was obtained with a yield of 71%. 1H NMR (400MHz, DMSO-d6) δ11.68(s,1H,CONH),7.99(m,2H,ArH),7.53(d,J=7.2Hz,3H,ArH),7.37(d,J =8.3Hz,2H,ArH),7.28(d,J=8.2Hz,2H,ArH),5.00(s,2H,CH2),2.60(s,3H,CH3),1.25(s,9H,CH3). 13 C NMR(101MHz,DMSO-d6)δ159.56,154.21,151.78,150.39,141.37,135.42,134.13,13 0.33,129.16,128.59,127.70,127.62,125.83,116.39,42.62,34.67,31.53,26.03.

[0064] Example 9: Preparation of 9-(4-difluoromethoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I9).

[0065] Referring to the preparation method of 2a in Example 1, compound 4-(difluoromethoxy)benzylamine was used to replace benzylamine in the method, and after purification, a white solid was obtained for 2 hours, with a yield of 55%. 1 H NMR(400MHz,DMSO-d6)δ7.41-7.36(m,2H,ArH),7.23(s,1H,NH),7.19(t,J=74.3Hz,1H,CH) ,7.14(d,J=8.5Hz,2H,ArH),4.83(s,2H,NH2),4.59(d,J=5.6Hz,2H,CH2),2.23(s,3H,CH3).

[0066] Referring to the preparation method of 3a in Example 1, 2h was substituted for 2a in the method to obtain white solid 3h with a yield of 94%. 1 H NMR(400MHz,DMSO-d6)δ12.06(s,1H,CONH),7.37(d,J=8.7Hz,2H,ArH),7.21(t,J =74.0Hz,1H,CH),7.14(d,J=8.7Hz,2H,ArH),4.98(s,2H,CH2),2.52(s,3H,CH3).

[0067] Referring to the preparation method of I1 in Example 1, compound 3h was substituted for 3a in the method, and after purification, a white solid compound I9 was obtained with a yield of 68%. 1H NMR (400MHz, DMSO-d6) δ11.70(s,1H,CONH),7.98(dd,J=7.5,2.1Hz,2H,ArH),7.53(d,J=6.9Hz,3H,ArH),7.42( d,J=8.3Hz,2H,ArH),7.12(d,J=74.0Hz,1H,CH),7.16(d,J=8.3Hz,2H,ArH),5.03(s,2H,CH2),2.60(s,3H,CH3). 13 C NMR(101MHz,DMSO-d6)δ159.57,154.17,151.70,150.73,141.44,135.39,134 .05,130.36,129.69,129.17,128.59,119.46,116.79,116.45,42.32,26.01.

[0068] Example 10: 2-Methyl-6-phenyl-9-(4-trifluoromethylbenzyl)-7,9-dihydro-8H-purine-8-one (I 10 Preparation of )

[0069] Following the preparation method of 2a in Example 1, the compound (4-(trifluoromethyl)phenyl)methylamine was substituted for benzylamine in the method, and after purification, a white solid 2i was obtained with a yield of 65%. 1 H NMR(400MHz,DMSO-d6)δ7.70(d,J=8.0Hz,2H,ArH),7.53(d,J=8.0Hz,2H,ArH), 7.36(s,1H,NH),4.87(s,2H,NH2),4.70(d,J=5.7Hz,2H,CH2),2.20(s,3H,CH3).

[0070] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2i to obtain white solid 3i with a yield of 91%. 1 H NMR (400MHz, DMSO-d6) δ12.10(s,1H,CONH),7.71(d,J=8.4Hz,2H,ArH),7.52(d,J=8.1Hz,2H,ArH),5.09(s,2H,CH2),2.51(s,3H,CH3).

[0071] Referring to the preparation method of I1 in Example 1, compound 3i was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 10 Yield: 60%. 1H NMR (400MHz, DMSO-d6) δ11.76(s,1H,CONH),8.00(m,2H,ArH),7.73(d,J=8.1Hz,2H,ArH),7.60-7.50(m,5H,ArH),5.15(s,2H,CH2),2.59(s,3H,CH3). 13 CNMR(101MHz,DMSO-d6)δ159.61,154.18,151.71,141.73,141.54,135.36,130.39 ,129.18,128.60,128.53,128.48,126.03,125.99,123.30,116.53,42.57,25.96.

[0072] Example 11: 9-(3,4-dimethoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I) 11 Preparation of )

[0073] Following the preparation method of 2a in Example 1, compound 3,4-dimethoxybenzylamine was used to replace benzylamine in the method, and after purification, a white solid 2j was obtained with a yield of 91%. 1 H NMR(400MHz,DMSO-d6)δ7.11(m,1H,NH),6.99(d,J=2.0Hz,1H,ArH),6.92-6.81(m,2H,ArH),4.8 4(s,2H,NH2),4.51(d,J=5.5Hz,2H,CH2),3.73(s,3H,CH3),3.72(s,3H,CH3),2.24(s,3H,CH3).

[0074] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2j to obtain white solid 3j with a yield of 90%. 1 H NMR(400MHz,DMSO-d6)δ12.02(s,1H,CONH),7.03(d,J=2.0Hz,1H,ArH),6.88(d,J=8.2Hz, 1H, ArH), 6.79 (m, 1H, ArH), 4.90 (s, 2H, CH2), 3.71 (d, J = 5.3Hz, 6H, CH3), 2.53 (s, 3H, CH3).

[0075] Referring to the preparation method of I1 in Example 1, compound 3j was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 11 Yield: 61%. 1H NMR (400MHz, DMSO-d6) δ11.64(s,1H,CONH),7.98(m,2H,ArH),7.52(d,J=7.0Hz,3H,ArH),7.10(d,J=2.0Hz,1H,ArH), 6.89(d,J=8.3Hz,1H,ArH),6.83(m,1H,ArH),4.96(s,2H,CH2),3.74(s,3H,CH3),3.37(s,3H,CH3),2.61(s,3H,CH3). 13 C NMR(101MHz,DMSO-d6)δ159.49,154.20,151.78,149.07,148.72,141.31,135.43,134.54,130.3 3,129.42,129.16,128.58,127.82,120.18,116.38,112.17,55.93,55.82,42.84,40.41,26.02.

[0076] Example 12: 9-(4-isopropoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I) 12 Preparation of )

[0077] Following the preparation method of 2a in Example 1, compound 4-isopropoxybenzylamine was used to replace benzylamine in the method, and after purification, a white solid 2k was obtained with a yield of 70%. 1 H NMR(400MHz,DMSO-d6)δ7.26-7.20(m,2H,ArH),7.12(m,1H,NH),6.90-6.84(m,2H,ArH),4.84(s,2 H,NH2),4.57(m,1H,CH),4.51(d,J=5.4Hz,2H,CH2),2.24(s,3H,CH3),1.24(d,J=6.0Hz,6H,CH3).

[0078] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2k to obtain white solid 3k with a yield of 90%. 1 H NMR (400MHz, DMSO-d6) δ12.09(s,1H,CONH),7.82(d,J=8.3Hz,2H,ArH),7.49(d,J=8.2Hz,2H,ArH),5.09(s,2H,CH2),2.51(s,10H,CH3,CH).

[0079] Referring to the preparation method of I1 in Example 1, compound 3k was substituted for 3a in the method, and after purification, a white solid compound I was obtained.12 Yield: 57%. 1 HNMR(400MHz,DMSO-d6)δ11.65(s,1H,CONH),7.98(dd,J=7.8,1.9Hz,2H,Arh),7.59-7.48(m,3H,ArH),7.28(d,J=8.7Hz,2H,ArH ),6.87(d,J=8.6Hz,2H,ArH),4.95(s,2H,CH2),4.56(p,J=6.0Hz,1H,CH),2.61(s,3H,CH3),1.24(s,3H,CH3),1.22(s,3H,CH3). 13 C NMR(101MHz,DMSO-d6)δ159.54,157.34,154.18,151.72,141.32,135.41,130.3 1,129.53,129.14,128.79,128.57,116.34,115.99,69.50,42.47,26.03,22.23.

[0080] Example 13: 9-(3,4-dimethylbenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I 13 Preparation of )

[0081] Following the preparation method of 2a in Example 1, 3,4-dimethylbenzylamine was used to replace benzylamine in the method, and after purification, a white solid 2l was obtained with a yield of 88%. 1 HNMR (400MHz, DMSO-d6) δ7.15-7.01(m,4H,ArH,NH),4.84(s,2H,NH2),4.52(d,J=5.5Hz,2H,CH2),2.23(s,3H,CH3),2.20(s,3H,CH3),2.19(s,3H,CH3).

[0082] Referring to the preparation method of 3a in Example 1, 2a was replaced with compound 2l to obtain white solid 3l with a yield of 90%. 1 H NMR (400MHz, DMSO-d6) δ12.02(s,1H,CONH),7.08(m,ArH),7.00(m,1H,ArH),4.90(s,2H,CH2),2.52(s,3H,CH3),2.17(s,6H,CH3).

[0083] Referring to the preparation method of I1 in Example 1, compound 3l was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 13 Yield: 58%.1 H NMR(400MHz,DMSO-d6)δ11.64(s,1H,CONH),8.00(m,2H,ArH),7.57-7.50(m,3H,ArH),7.13(s,1 H,ArH),7.11-7.03(m,2H,ArH),4.96(s,2H,CH2),2.60(s,3H,CH3),2.18(d,J=4.0Hz,6H,CH3).

[0084] Example 14: 4-((2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purine-9-yl)methyl)benzonitrile (I) 14 Preparation of )

[0085] Referring to the preparation method of 2a in Example 1, 4-cyanobenzylamine was used to replace benzylamine in the method, and after purification, a white solid 2m was obtained with a yield of 67%. 1 HNMR(400MHz,DMSO-d6)δ7.80(d,J=8.3Hz,2H,ArH),7.50(d,J=8.1Hz,2H,ArH), 7.38(m,1H,NH),4.87(s,2H,NH2),4.69(d,J=5.7Hz,2H,CH2),2.19(s,3H,CH3).

[0086] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2m to obtain white solid 3m with a yield of 89%. 1 H NMR (400MHz, DMSO-d6) δ12.10(s,1H,CONH),7.85-7.79(m,2H,ArH),7.49(d,J=8.1Hz,2H,ArH),5.09(s,2H,CH2),2.50(s,3H,CH3).

[0087] Referring to the preparation method of I1 in Example 1, compound 3m was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 14 Yield: 53%. 1 H NMR (400MHz, DMSO-d6) δ11.74(s,1H,CONH),8.02-7.97(m,2H,ArH),7.86-7.81(m,2H,ArH),7.56-7.50(m,5H,ArH),5.14(s,2H,CH2),2.58(s,3H,CH3). 13CNMR(101MHz,DMSO-d6)δ159.59,154.16,151.70,142.63,141.56,135.36 ,133.08,130.40,129.19,128.61,119.17,116.58,110.78,42.67,25.97.

[0088] Example 15: 9-(3-methoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I 15 Preparation of )

[0089] Following the preparation method of 2a in Example 1, 3-methoxybenzylamine was used to replace benzylamine in the method, and after purification, a white solid 2n was obtained with a yield of 85%. ¹H NMR (400 MHz, DMSO-d6) δ 7.24 (m, 1H, ArH), 7.17 (m, 1H, ArH), 6.93-6.87 (m, 2H, ArH), 6.82 (m, 1H, NH), 4.82 (s, 2H, NH₂), 4.58 (d, J = 5.6 Hz, 2H, CH₂), 3.73 (s, 3H, OCH₃), 2.23 (s, 3H, CH₃).

[0090] Following the preparation method of 3a in Example 1, compound 2n was substituted for 2a in the method to obtain white solid 3n with a yield of 92%. ¹H NMR (400 MHz, DMSO-d6) δ 12.01 (s, ¹H, CONH), 7.24 (m, ¹H, ArH), 6.93-6.80 (m, 3H, ArH), 4.95 (s, 2H, CH₂), 3.72 (s, 3H, OCH₃), 2.52 (s, 3H, CH₃).

[0091] Referring to the preparation method of I1 in Example 1, compound 3n was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 15 Yield 62%. ¹H NMR (400MHz, DMSO-d6) δ 11.68 (s, ¹H, CONH), 8.03–7.97 (m, 2H, ArH), 7.58–7.48 (m, 3H, ArH), 7.26 (m, ¹H, ArH), 6.94 (m, 1H, ArH), 6.92–6.82 (m, 2H, ArH), 5.01 (s, 2H, CH₂), 3.73 (s, 3H, OCH₃), 2.60 (s, 3H, CH₃).

[0092] 13C NMR(101MHz,DMSO-d6)δ159.82,159.55,154.22,151.80,141.41,138.60,135.43,13 0.34,130.23,129.16,128.61,119.83,116.44,113.77,113.18,55.47,42.90,26.01.

[0093] Example 16: 2-Methyl-9-(4-methylbenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I 16 Preparation of )

[0094] Following the preparation method of 2a in Example 1, 4-methylbenzylamine was substituted for benzylamine in the method, and after purification, a white solid 2n was obtained with a yield of 85%. ¹H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 8.1 Hz, 2H, ArH), 7.19–7.15 (m, 1H, NH), 7.13 (d, J = 8.1 Hz, 2H, ArH), 4.84 (s, 2H, NH₂), 4.55 (d, J = 5.6 Hz, 2H, CH₂), 2.27 (s, 3H, CH₃), 2.22 (s, 3H, CH₃).

[0095] Following the preparation method of 3a in Example 1, compound 2n was substituted for 2a in the method to obtain white solid 3n with a yield of 92%. ¹H NMR (400 MHz, DMSO-d6) δ 12.03 (s, ¹H, CONH), 7.20 (d, J = 7.9 Hz, 2H, ArH), 7.14 (d, J = 7.9 Hz, 2H, ArH), 4.94 (s, 2H, CH₂), 2.52 (s, 3H, CH₃), 2.26 (s, 3H, CH₃).

[0096] Referring to the preparation method of I1 in Example 1, compound 3n was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 15, yield 62%. 1H NMR(400MHz,DMSO-d6)δ11.67(s,1H,CONH),8.02-7.96(m,2H,ArH),7.58-7.48(m,3H,ArH),7.24(d,J =7.9Hz,2H,ArH),7.15(d,J=7.8Hz,2H,ArH),4.99(s,2H,CH2),2.60(s,3H,CH3),2.26(s,3H,CH3).13C NMR(101MHz,DMSO-d6)δ159.53,154.24,151.78,141.33,137.17,135.43,134.54,134.08 ,130.48,130.34,129.60,129.17,128.59,127.88,127.82,116.43,42.74,26.03,21.14.

[0097] Example 17: 2-Amino-9-benzyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I 17 Preparation of )

[0098] Compound 1 was replaced by amino-substituted compound 2, and the preparation method of 2a in Example 1 was followed. After purification, a white solid 2n was obtained with a yield of 85%. 1 H NMR (400MHz, DMSO-d6) δ7.33(d,J=4.4Hz,4H,ArH),7.29-7.16(m,2H,ArH,NH),4.82(s,2H,NH2),4.61(d,J=5.6Hz,2H,CH2),2.23(s,3H,CH3).

[0099] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2n to obtain white solid 3n with a yield of 92%. 1 H NMR (400MHz, DMSO-d6) δ12.03(s,1H,CONH),7.43-7.21(m,5H,ArH),4.99(s,2H,CH2),2.52(s,3H,CH3).

[0100] Referring to the preparation method of I1 in Example 1, compound 3n was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 15 Yield: 62%. 1H NMR(400MHz,DMSO-d6)δ11.14(s,1H,NH),8.05(d,1H,ArH),7.96–7.90(m,2H,ArH),7.81–7.77 (m,3H,ArH),7.52–7.46(m,3H),7.35(d,J=1.1Hz,1H,ArH),6.31(s,2H,NH2),4.95(s,2H,CH2).

[0101] Example 18: 9-([1,1'-biphenyl]-4-ylmethyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I 18 Preparation of )

[0102] Following the preparation method of 2a in Example 1, 4-bromobenzylamine was substituted for benzylamine in the method, and after purification, a white solid 2o was obtained with a yield of 64%. ¹H NMR (400 MHz, DMSO-d⁶) δ 7.56–7.47 (m, 2H, ArH), 7.33–7.20 (m, 3H, ArH), 4.81 (s, 2H, NH₂), 4.57 (d, J = 5.6 Hz, 2H, CH₂), 2.21 (s, 3H, CH₃).

[0103] Following the preparation method of 3a in Example 1, compound 2o was substituted for 2a in the method to obtain white solid 3o, with a yield of 84%. ¹H NMR (400 MHz, DMSO-d6) δ 12.03 (s, ¹H, CONH), 7.58–7.49 (m, ²H, ArH), 7.33–7.21 (m, ²H, ArH), 4.96 (s, ²H, CH₂), 2.49 (s, ³H, CH₃).

[0104] Referring to the preparation method of I1 in Example 1, compound 3o was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 19 , yield 80%. 1H NMR(400MHz,DMSO-d6)δ11.70(s,1H,CONH),8.04-7.97(m,2H,ArH),7.68-7.60(m,4H,ArH),7.58-7 .51(m,3H,ArH),7.48-7.41(m,4H,ArH),7.39-7.33(m,1H,ArH),5.09(s,2H,CH2),2.61(s,3H,CH3).

[0105] 13C NMR(101MHz,DMSO-d6)δ159.58,154.27,151.80,141.42,140.21,139.93,136.27,135.43,13 0.35,129.39,129.18,128.61,128.49,127.94,127.42,127.10,116.48,42.70,39.80,26.04.

[0106] Example 19: 9-([1,1'-biphenyl]-3-ylmethyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I 19 Preparation of )

[0107] Following the preparation method of 2a in Example 1, 3-bromobenzylamine was used instead of benzylamine in the method, and after purification, a white solid 2o was obtained with a yield of 64%. ¹H NMR (400 MHz, DMSO-d6) δ 7.54 (m, ¹H, ArH), 7.45 (m, ¹H, NH), 7.38–7.20 (m, ³H, ArH), 4.94–4.71 (m, ²H, NH₂), 4.61 (d, J = 5.7 Hz, ²H, CH₂), 2.23 (s, ³H, CH₃).

[0108] Following the preparation method of 3a in Example 1, compound 2o was substituted for 2a in the method to obtain white solid 3o, with a yield of 84%. ¹H NMR (400 MHz, DMSO-d6) δ 12.04 (s, ¹H, CONH), 7.60–7.44 (m, 2H, ArH), 7.30 (m, 2H, ArH), 4.99 (s, 2H, CH₂), 2.52 (s, 3H, CH₃).

[0109] Referring to the preparation method of I1 in Example 1, compound 3o was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 19 Yield 80%. ¹H NMR (400MHz, DMSO-d6) δ 11.69 (s, ¹H, CONH), 8.04–7.96 (m, 2H, ArH), 7.71 (m, ¹H, ArH), 7.66–7.31 (m, ¹¹H, ArH), 5.12 (s, 2H, CH₂), 2.61 (s, 3H, CH₃).

[0110] 13C NMR(101MHz,DMSO-d6)δ159.53,154.29,151.83,141.42,140.95,140.34,137.79,135.44,130.34,12 9.78,129.46,129.16,128.61,128.08,127.16,126.87,126.57,126.42,116.51,43.06,40.43,26.03.

[0111] Example 20: 2-Methyl-6-phenyl-9-(pyridin-3-ylmethyl)-7,9-dihydro-8H-purine-8-one (I 20 Preparation of ).

[0112] Following the preparation method of 2a in Example 1, 3-pyridinemethylamine was used to replace benzylamine in the method, and after purification, a white solid 2r was obtained with a yield of 64%. 1 H NMR(400MHz,DMSO-d6)δ8.57(m,1H,ArH),8.46(m,1H,ArH),7.74(m,1H,ArH),7.35(m,1 H, ArH), 7.27 (m, 1H, NH), 4.81 (s, 2H, NH2), 4.61 (d, J = 5.5Hz, 2H, CH2), 2.23 (s, 3H, CH3).

[0113] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2r to obtain white solid 3r with a yield of 84%. 1 H NMR(400MHz,DMSO-d6)δ12.05(s,1H,CONH),8.59(d,J=2.3Hz,1H,ArH),8.50(m, 1H,ArH),7.72(m,1H,ArH),7.36(m,1H,ArH),5.03(s,2H,CH2),2.52(s,3H,CH3).

[0114] Referring to the preparation method of I1 in Example 1, compound 3r was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 20 Yield: 80%. 1H NMR(400MHz,DMSO-d6)δ11.70(s,1H,CONH),8.63(d,J=2.2Hz,1H,ArH),8.51(m,1H,ArH),8.03-7.96(m,2H ,ArH),7.76(m,1H,ArH),7.58-7.50(m,3H,ArH),7.38(m,1H,ArH),5.09(s,2H,CH2),2.61(s,3H,CH3).13C NMR (101MHz, DMSO) δ159.56,154.13,151.64,149.37,149.30,141.50,135. 88,135.37,132.71,130.35,129.15,128.59,124.22,116.51,53.09,25.98.

[0115] Example 21: tert-butyl(4-((2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purine-9-yl)methyl)phenyl)carbamate (I) 21 Preparation of ).

[0116] Following the preparation method of 2a in Example 1, compound 4-(Boc-amino)benzylamine was used to replace benzylamine in the method, and after purification, a white solid 2s was obtained with a yield of 64%. 1 H NMR (400MHz, DMSO-d6) δ9.30 (s, 1H, NH), 7.39 (d, J = 8.2Hz, 2H, ArH), 7.25-7.18 (m, 2H, ArH), 7. 13(s,1H,NH),4.82(s,2H,NH2),4.51(d,J=5.4Hz,2H,CH2),2.23(s,3H,CH3),1.46(s,9H,CH3).

[0117] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2s to obtain white solid 3s with a yield of 84%. 1 H NMR (400MHz, DMSO-d6) δ12.00(s,1H,NH),9.35(s,1H,NH),7.38(d,J=8.2Hz,2H,ArH ),7.20(d,J=8.5Hz,2H,ArH),4.90(s,2H,CH2),2.52(s,3H,CH3),1.45(s,9H,CH3).

[0118] Referring to the preparation method of I1 in Example 1, compound 3s was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 21 Yield: 80%. 1H NMR(400MHz,DMSO-d6)δ11.64(s,1H,CONH),9.35(s,1H,CONH),8.03-7.97(m,2H,ArH),7.57-7.49(m,3H,Ar H),7.39(d,J=8.3Hz,2H,ArH),7.29-7.21(m,2H,ArH),4.95(s,2H,CH2),2.60(s,3H,CH3),1.45(s,9H,CH3).

[0119] ESI-MS(m / z):calcd for C24H27N5O3[M+H] + :432.2031,found 432.2030.

[0120] Example 22: 9-((6-methoxypyridin-3-yl)methyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I) 22 Preparation of ).

[0121] Following the preparation method of 2a in Example 1, 2-methoxy-5-(aminomethyl)pyridine was used to replace benzylamine in the method, and after purification, 2t of white solid was obtained with a yield of 64%. 1 H NMR (400MHz, DMSO-d6) δ8.16 (d, J=2.4Hz, 1H, ArH), 7.69 (m, 1H, ArH), 7.18 (m, 1H, NH), 6.80 (d, J= 8.5Hz,1H,ArH),4.82(s,2H,NH2),4.51(d,J=5.4Hz,2H,CH2),3.82(s,3H,CH3),2.25(s,3H,CH3).

[0122] Referring to the preparation method of 3a in Example 1, 2a was replaced with compound 2t to obtain white solid 3t with a yield of 84%. 1 H NMR(400MHz,DMSO-d6)δ12.02(s,1H,CONH),8.19(d,J=2.5Hz,1H,ArH),7.68(m,1H,A rH), 6.79 (d, J = 8.5Hz, 1H, ArH), 4.94 (s, 2H, CH2), 3.82 (s, 3H, CH3), 2.54 (s, 3H, CH3).

[0123] Referring to the preparation method of I1 in Example 1, compound 3t was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 22Yield 80%. ¹H NMR (400MHz, DMSO) δ 11.65 (s, ¹H, NH), 8.23–8.22 (m, 2H, ArH), 7.97–6.79 (m, 6H, ArH), 4.98 (s, 2H, CH₂), 3.81 (s, 3H, CH₂), 2.61 (s, 3H, CH₂). 13 C NMR(101MHz,DMSO-d6)δ163.58,159.54,154.10,151.60,146.78,141.42,139 .54,135.39,130.34,129.16,128.59,125.85,116.44,111.05,53.66,26.02.

[0124] Example 23: 9-(3-fluoro-4-methoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I) 23 Preparation of ).

[0125] Referring to the preparation method of 2a in Example 1, the compound (3-fluoro-4-methoxyphenyl)methylamine was substituted for benzylamine in the method, and after purification, a white solid 2u was obtained with a yield of 64%. 1 H NMR (400MHz, DMSO-d6) δ7.21-7.15(m,2H,ArH),7.13-7.10(m,2H,ArH),4.85(s,2H,NH2),4.53(d,J=5.5Hz,2H,CH2),3.81(s,3H,OCH3),2.23(s,3H,CH3).

[0126] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2u to obtain white solid 3u with a yield of 84%. 1 H NMR (400MHz, DMSO-d6) δ12.01(s,1H,CONH), δ7.67-6.96(m,4H)4.92(s,2H,CH2),3.80(s,3H,CH3),2.52(s,3H,CH3).

[0127] Referring to the preparation method of I1 in Example 1, compound 3u was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 23 Yield: 80%. 1H NMR(400MHz,DMSO-d6)δ11.67(s,1H,CONH),7.99(m,2H,ArH),7.53(d,J=7.0Hz,3H,ArH),7.26-7 .20(m,1H,ArH),7.16-7.11(m,2H,ArH),4.97(s,2H,CH2),3.81(s,3H,CH3),2.61(s,3H,CH3).13C NMR (101MHz, DMSO) δ159.47,154.25,153.54,151.72,145.65,141.38,135.44,130. 34,129.91,129.17,128.60,124.36,115.81,115.62,114.39,56.45,42.13,26.02.

[0128] Example 24: 9-(2,4-dimethoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I 24 Preparation of ).

[0129] Following the preparation method of 2a in Example 1, compound 2,4-dimethoxybenzylamine was used to replace benzylamine in the method. After purification, a white solid 2v was obtained with a yield of 64%. ¹H NMR (400 MHz, DMSO-d6) δ 7.11 (m, 1H, NH), 6.99 (d, J = 2.0 Hz, 1H, ArH), 6.92-6.81 (m, 2H, ArH), 4.84 (s, 2H, NH₂), 4.51 (d, J = 5.5 Hz, 2H, CH₂), 3.73 (s, 3H, CH₃), 3.72 (s, 3H, CH₃), 2.24 (s, 3H, CH₃).

[0130] Following the preparation method of 3a in Example 1, compound 2v was substituted for 2a in the method to obtain white solid 3v, with a yield of 84%. ¹H NMR (400 MHz, DMSO-d⁶) δ 12.02 (s, ¹H, CONH), 7.03 (d, J = 2.0 Hz, ¹H, ArH), 6.88 (d, J = 8.2 Hz, ¹H, ArH), 6.79 (m, ¹H, ArH), 4.90 (s, 2H, CH₂), 3.71 (d, J = 5.3 Hz, 6H, CH₃), 2.53 (s, 3H, CH₃).

[0131] Referring to the preparation method of I1 in Example 1, compound 3v was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 24Yield 80%. ¹H NMR (400MHz, DMSO) δ 11.64 (s, H, NH), 8.00–7.50 (m, 5H, ArH), 7.49–6.77 (m, 2H, ArH), 6.42 (s, 1H, ArH), 4.91 (s, 2H, CH₂), 3.82 (s, 3H, CH₃), 3.72 (s, 3H, CH₃), 2.55 (s, 3H, CH₃). ¹³C NMR (101MHz, DMSO) δ160.41,159.56,157.89,154.30,138.66,137.54,134.36,132.21 ,130.36,129.21,128.59,128.00,116.52,104.99,98.84,56.03,55.68,40.48,25.94.

[0132] Example 25: 9-(3,5-dimethoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one (I 25 Preparation of ).

[0133] Following the preparation method described in Example 1, 2a, compound 3,5-dimethoxybenzylamine was used to replace benzylamine in the method. After purification, a white solid 2w was obtained, with a yield of 64%. ¹H NMR (400 MHz, DMSO-d6) δ 7.11 (m, 1H, NH), 6.99 (d, J = 2.0 Hz, 1H, ArH), 6.92-6.81 (m, 2H, ArH), 4.84 (s, 2H, NH₂), 4.51 (d, J = 5.5 Hz, 2H, CH₂), 3.73 (s, 3H, CH₃), 3.72 (s, 3H, CH₃), 2.24 (s, 3H, CH₃).

[0134] Following the preparation method of 3a in Example 1, compound 2w was substituted for 2a in the method to obtain white solid 3w with a yield of 84%. ¹H NMR (400 MHz, DMSO-d⁶) δ 12.02 (s, ¹H, CONH), 7.03 (d, J = 2.0 Hz, ¹H, ArH), 6.88 (d, J = 8.2 Hz, ¹H, ArH), 6.79 (m, ¹H, ArH), 4.90 (s, 2H, CH₂), 3.71 (d, J = 5.3 Hz, 6H, CH₃), 2.53 (s, 3H, CH₃).

[0135] Referring to the preparation method of I1 in Example 1, compound 3w was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 25Yield: 80%. 1H NMR(400MHz,DMSO)δ11.64,(s,1H,NH),7.98-7.54(m,2H,ArH),7.54-6.48(m,3H,Ar H),6.48-6.40(m,3H,ArH),4.94(s,2H,CH2),3.69(s,6H,CH3),2.58(s,3H,CH3).13C NMR (101MHz, DMSO) δ161.06,159.58,154.21,151.75,141.48,139.30,135 .37,130.35,129.16,128.59,116.41,105.95,99.24,55.59,42.97,25.95.

[0136] Example 26: tert-butyl(4-((2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purine-9-yl)methyl)benzyl)carbamate (I) 26 Preparation of ).

[0137] Referring to the preparation method of 2a in Example 1, compound 1-(N-Boc-aminomethyl)-4-(aminomethyl)benzene was used to replace benzylamine in the method, and after purification, a white solid 2x was obtained with a yield of 64%. 1 H NMR (400MHz, DMSO-d6) δ7.38(s,1H,NH),7.26(d,J=8.0Hz,2H,ArH),7.18(d,J=7.6Hz,3H,ArH),4.83( s,2H,NH2),4.57(d,J=5.5Hz,2H,CH2),4.09(d,J=6.2Hz,2H,CH2),2.22(s,3H,CH3),1.38(s,9H,CH3).

[0138] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2x to obtain white solid 3x with a yield of 84%. 1 H NMR (400MHz, DMSO-d6) δ12.02(s,1H,NH),7.38(s,1H,NH),7.24(d,J=8.1Hz,2H,ArH),7. 18(d,J=8.0Hz,2H,ArH),4.96(s,2H,CH2),4.07(d,J=6.2Hz,2H,CH2),1.37(s,9H,CH3).

[0139] Referring to the preparation method of I1 in Example 1, compound 3x was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 26 Yield: 80%. 1HNMR(400MHz,DMSO-d6)δ11.67(s,1H,NH),8.01(d,J=7.2Hz,2H,ArH),7.58-7.48(m,3H,ArH),7.38(s,1H,NH),7.28(d,J=7 .9Hz,2H,ArH),7.19(d,J=7.9Hz,2H,ArH),5.01(s,2H,CH2),4.08(d,J=6.2Hz,2H,CH2),2.59(s,3H,CH3),1.37(s,9H,CH3).

[0140] Example 27: 9-(4-methoxybenzyl)-6-phenyl-7,9-dihydro-8H-purine-8-one (I 27 Preparation of ).

[0141] Compound 1 was replaced with unsubstituted compound 3, and the preparation method of 2a in Example 1 was followed. After purification, a white solid 2y was obtained with a yield of 64%. 1 H NMR (400MHz, DMSO-d6) δ7.73 (s, 1H, ArH), 7.25 (d, J=8.5Hz, 3H, ArH), 6.89 (d, J= 8.6Hz, 2H, ArH), 5.09 (s, 2H, NH2), 4.54 (d, J = 5.5Hz, 2H, CH2), 3.72 (s, 3H, CH3).

[0142] Referring to the preparation method of 3a in Example 1, compound 2y was substituted for 2a in the method to obtain white solid 3y with a yield of 84%. 1 H NMR (400MHz, DMSO-d6) 8.45 (s, 1H, ArH), 7.30 (d, J = 8.6Hz, 2H, ArH), 6.89 (d, J = 8.7Hz, 2H, ArH), 4.95 (s, 2H, CH2), 3.72 (s, 3H, CH3).

[0143] Referring to the preparation method of I1 in Example 1, compound 3y was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 27 Yield: 80%. 1 H NMR (400MHz, DMSO-d6) δ11.79(s,1H,CONH),8.67(s,1H,ArH),8.00(d,J=7.0Hz,2H,ArH),7.54(d,J=7.0 Hz,3H,ArH),7.34(d,J=8.1Hz,2H,ArH),6.90(d,J=8.2Hz,2H,ArH),4.99(s,2H,CH2),3.72(s,3H,CH3).13 C NMR (101MHz, DMSO-d6) δ159.20,154.05,151.17,150.98,141.40,135.26,130.47,129.68,129.24,128.98,128.61,118.60,114.43,55.53,42.63.

[0144] Example 28: N-(4-((2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purine-9-yl)methyl)benzyl)neopentamide (I) 28 Preparation of ).

[0145] Following the preparation method of 2a in Example 1, compound 1-(N-Boc-aminomethyl)-4-(aminomethyl)benzene was used to replace benzylamine in the method, and after purification, a white solid 2z was obtained with a yield of 64%. 1 H NMR (400MHz, DMSO-d6) δ7.38(s,1H,NH),7.26(d,J=8.0Hz,2H,ArH),7.18(d,J=7.6Hz,3H,ArH),4.83( s,2H,NH2),4.57(d,J=5.5Hz,2H,CH2),4.09(d,J=6.2Hz,2H,CH2),2.22(s,3H,CH3),1.38(s,9H,CH3).

[0146] Following the preparation method of 3a in Example 1, compound 2z was substituted for 2a in the method to obtain white solid 3z with a yield of 84%. ¹H NMR (400MHz, DMSO-d6) δ 12.02 (s, 1H, NH), 7.38 (s, 1H, NH), 7.24 (d, J = 8.1Hz, 2H, ArH), 7.18 (d, J = 8.0Hz, 2H, ArH), 4.96 (s, 2H, CH2), 4.07 (d, J = 6.2Hz, 2H, CH2), 1.37 (s, 9H, CH3).

[0147] Referring to the preparation method of I1 in Example 1, compound 3z was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 28 Yield: 80%. 1H NMR (400MHz, DMSO-d6) δ11.67(s,1H,NH),8.73(s,1H,NH),8.03-7.95(m,2H,ArH),7.59-7.48(m,3H,ArH),7.31(d,J=8.0Hz,2H,Ar H),7.24(d,J=8.0Hz,2H,ArH),5.02(s,2H,CH2),4.27(d,J=5.9Hz,2H,CH2),4.10(s,3H,CH3),3.83(s,2H,CH2),2.60(s,3H,CH3).

[0148] Example 29: 2-Chloro-N-(4-[(2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purine-9-yl)methyl]benzyl)acetamide (I) 29 Preparation of ).

[0149] Following the preparation method of 2a in Example 1, compound 1-(N-Boc-aminomethyl)-4-(aminomethyl)benzene was used to replace benzylamine in the method, and after purification, a white solid 2a1 was obtained with a yield of 64%. 1 H NMR (400MHz, DMSO-d6) δ7.38(s,1H,NH),7.26(d,J=8.0Hz,2H,ArH),7.18(d,J=7.6Hz,3H,ArH),4.83( s,2H,NH2),4.57(d,J=5.5Hz,2H,CH2),4.09(d,J=6.2Hz,2H,CH2),2.22(s,3H,CH3),1.38(s,9H,CH3).

[0150] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2a1 to obtain white solid 3a1 with a yield of 84%. 1 H NMR (400MHz, DMSO-d6) δ12.02(s,1H,NH),7.38(s,1H,NH),7.24(d,J=8.1Hz,2H,ArH),7. 18(d,J=8.0Hz,2H,ArH),4.96(s,2H,CH2),4.07(d,J=6.2Hz,2H,CH2),1.37(s,9H,CH3).

[0151] Referring to the preparation method of I1 in Example 1, compound 3a was substituted for compound 3a in the method, and after purification, a white solid compound I was obtained. 29 Yield: 80%. 1H NMR(400MHz,DMSO-d6)δ11.66(s,1H,NH),8.08-7.96(m,3H,ArH,),7.57-7.49(m,3H,ArH),7.27(d,J=8.0Hz,2H,Ar H),7.17(d,J=8.0Hz,2H,ArH),5.01(s,2H,CH2),4.22(d,J=6.0Hz,2H,CH2),2.59(s,3H,CH3),1.11(s,9H,CH3).13C NMR (101MHz, DMSO) δ177.86,167.85,159.57,154.21,151.76,141.37,139.99,13 5.42,130.33,129.16,128.60,127.73,116.41,53.10,42.71,38.49,27.90,26.01

[0152] Example 30: 2-Cyclopropyl-9-(4-Methoxybenzyl)-6-phenyl-7,9-dihydro-8H-purine-8-one (I) 31 Preparation of ).

[0153] Compound 1 was replaced with cyclopropyl compound 4, and the preparation method of 2a in Example 1 was followed. After purification, a white solid 2c1 was obtained. 1 H NMR (400MHz, DMSO-d6) δ7.26-7.22(m,2H,ArH),7.20(m,J=6.2Hz,1H,NH),6.91-6.86(m,2H,ArH),4.73(s,2H,NH2),4. 47(d,J=5.5Hz,2H,CH2),3.72(s,3H,CH3),1.78(m,J=7.1,5.6Hz,1H,CH),0.77(d,J=3.3Hz,2H,CH2),0.75(s,2H,CH2).

[0154] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2c1 to obtain white solid 3c1 with a yield of 84%. 1 H NMR(400MHz,DMSO-d6)δ11.90(s,1H,CONH),7.28(d,J=8.6Hz,2H,ArH),6.93-6.86(m,2H,ArH),4.88(s,2H,CH2),3. 72(s,3H,CH3),2.10(m,J=11.2,8.2,4.8Hz,1H,CH),1.00(m,J=8.0,2.9Hz,2H,CH2),0.95(m,J=5.1,2.8Hz,2H,CH2).

[0155] Referring to the preparation method of I1 in Example 1, compound 3c1 was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 31 , yield 80%. HNMR(400MHz,DMSO-d6)δ11.57(s,1H,CONH),7.97(m,J=7.6,2.1Hz,2H,ArH),7.56-7.47(m,3H,ArH),7.33(d,J=8.3Hz,2H,ArH),6. 95-6.88(m,2H,ArH),4.94(s,2H,CH2),3.72(s,3H,CH3),2.18(m,J=12.8,8.1,4.8Hz,1H,CH),1.01(m,J=10.9,4.7,2.8Hz,4H,CH2). 13 C NMR(101MHz,DMSO-d6)δ163.40,159.18,154.12,151.70,141.21,135.52,130.31,1 29.80,129.15,129.10,128.54,116.28,114.39,55.53,42.51,40.42,18.16,10.25.

[0156] Example 31: 2-Isopropyl-9-(4-methoxybenzyl)-6-phenyl-7,9-dihydro-8H-purine-8-one (I 32 Preparation of ).

[0157] Compound 1 was replaced with isopropyl compound 5, and the preparation method of 2a in Example 1 was followed. After purification, a white solid 2d1 was obtained. 1 H NMR(400MHz,DMSO-d6)δ7.31-7.25(m,2H,ArH),7.18(s,1H,NH),6.90-6.85(m,2H,ArH),4.80(s,2H,N H),4.53(d,J=5.5Hz,2H,CH2),3.72(s,3H,CH3),2.74(m,1H,CH),1.14(s,3H,CH3),1.13(s,3H,CH3).

[0158] Referring to the preparation method of 3a in Example 1, 2a was replaced by compound 2c1 to obtain white solid 3d1 with a yield of 84%. 1H NMR(400MHz,DMSO-d6)δ11.90(s,1H,CONH),7.28(d,J=8.6Hz,2H,ArH),6.93-6.86(m,2H,ArH),4.88(s,2H ,CH2),3.72(s,3H,CH3),2.10(m,1H,CH),1.00(m,J=8.0,2.9Hz,2H,CH2),0.95(m,J=5.1,2.8Hz,2H,CH2).

[0159] Referring to the preparation method of I1 in Example 1, compound 3d1 was substituted for 3a in the method, and after purification, a white solid compound I was obtained. 32 Yield: 80%. 1 HNMR(400MHz,DMSO)δ11.61(s,1H,CONH),8.06-7.96(m,4H,ArH),7.58-7.46(m,3H,ArH),7.43-7.30(m,1H,ArH),6.94 -6.82(m,3H,ArH),4.96(s,2H,CH2),3.71(d,J=1.5Hz,4H,CH2),1.32(d,J=6.9Hz,6H,CH3),1.13(d,J=6.9Hz,2H,CH2). 13 CNMR(101MHz,DMSO-d6)δ166.74,159.21,154.19,151.69,141.04,135.63,134.55,130.48,130.30,129.95, 129.59,129.17,129.13,128.57,127.82,116.46,114.37,114.05,55.53,55.50,42.57,37.04,22.39,22.17.

[0160] Example 32 In vitro antitumor activity experiment

[0161] A549 (human lung cancer cell line), PC3 (human prostate cancer cells), HT29 (human colon cancer cells), MCF7 (human breast cancer cells), and HepG2 (human liver cancer cells) were selected, and the inhibitory rate of some target compounds I on the test cells was measured. SKPin C1 was used as a positive control. Detailed test results are shown in Table 2.

[0162] Table 2. Results of inhibitory activity test of the compounds of the present invention on human tumor cells

[0163]

[0164]

[0165] ND: Not detected.

[0166] As shown in Table 2, the in vitro anti-proliferation experiment results indicate that the compounds of this invention have significant inhibitory activity against lung cancer cells A549, with most compounds showing IC50 levels. 50 Values ​​are in the single digits, especially I. 19 The inhibitory activity was at the nanomolar level, significantly superior to the positive control drug. Simultaneously, at a concentration of 20 μM, the compounds of this invention also exhibited varying degrees of tumor cell proliferation inhibitory activity against prostate cancer cells PC-3, colon cancer cells HT29, breast cancer cells MCF-7, and liver cancer cells HepG2.

[0167] While some embodiments of the present general inventive concept have been shown and described, those skilled in the art will understand that changes may be made to these embodiments without departing from the principles and spirit of the present general inventive concept, the scope of which is defined by the claims and their equivalents.

Claims

1. A 6-phenyl-purine derivative, characterized in that, The 6-phenyl-purine derivative has the structure shown in general formula I: Wherein, R1 is selected from phenyl, pyridyl, methoxy-substituted phenyl, amino-substituted phenyl, fluorine-substituted phenyl, trimethoxy-substituted phenyl, tert-butyl-substituted phenyl, difluoromethoxy-substituted phenyl, trifluoromethyl-substituted phenyl, dimethoxy-substituted phenyl, isopropoxy-substituted phenyl, dimethyl-substituted phenyl, cyano-substituted phenyl, methyl-substituted phenyl, biphenyl, methylamino-substituted phenyl, methoxyfluoro-disubstituted phenyl, methoxy-substituted pyridyl, etc. One of them; R2 is selected from H, amino, cyclopropyl, isopropyl and methyl.

2. The 6-phenyl-purine derivative according to claim 1, characterized in that, R1 is selected from phenyl, 3-pyridyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-aminophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4,5-trimethoxyphenyl, 4-tert-butylphenyl, 4-difluoromethoxyphenyl, 4-trifluoromethylphenyl, 3,4-dimethoxyphenyl, 4-isopropoxyphenyl, 3,4-dimethylphenyl, 4-cyanophenyl, 3-methoxyphenyl, 4-methylphenyl, 4-methylaminophenyl, 3-fluoro-4-methoxyphenyl, 2,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2-methoxy-5-pyridyl. One of them; R2 is selected from H, amino, cyclopropyl, isopropyl and methyl.

3. The 6-phenyl-purine derivative according to claim 1, characterized in that, The 6-phenyl-purine derivative is any one of the following compounds: 9-Benzyl-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(4-Methoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(2-Methoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(4-aminobenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(3-Fluorobenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(4-Fluorobenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 2-Methyl-6-phenyl-9-(3,4,5-trimethoxybenzyl)-7,9-dihydro-8H-purine-8-one; 9-(4-tert-butylbenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(4-Difluoromethoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 2-Methyl-6-phenyl-9-(4-trifluoromethylbenzyl)-7,9-dihydro-8H-purine-8-one; 9-(3,4-Dimethoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(4-Isopropoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(3,4-Dimethylbenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 4-((2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purine-9-yl)methyl)benzonitrile; 9-(3-Methoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 2-Methyl-9-(4-methylbenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 2-Amino-9-benzyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-([1,1'-biphenyl]-4-ylmethyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-([1,1'-biphenyl]-3-ylmethyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 2-Methyl-6-phenyl-9-(pyridin-3-ylmethyl)-7,9-dihydro-8H-purine-8-one; 9-((6-methoxypyridin-3-yl)methyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(3-fluoro-4-methoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(2,4-Dimethoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; 9-(3,5-Dimethoxybenzyl)-2-methyl-6-phenyl-7,9-dihydro-8H-purine-8-one; tert-butyl(4-((2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purin-9-yl)methyl)benzyl)carbamate; 9-(4-Methoxybenzyl)-6-phenyl-7,9-dihydro-8H-purine-8-one; N-(4-((2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purin-9-yl)methyl)benzyl)neopentamide; 2-Chloro-N-(4-[(2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purine-9-yl)methyl]benzyl)acetamide; tert-butyl(4-((2-methyl-8-oxo-6-phenyl-7,8-dihydro-9H-purine-9-yl)methyl)phenyl)carbamate; 2-Cyclopropyl-9-(4-Methoxybenzyl)-6-phenyl-7,9-dihydro-8H-purine-8-one; 2-Isopropyl-9-(4-Methoxybenzyl)-6-phenyl-7,9-dihydro-8H-purine-8-one.

4. A method for preparing the 6-phenyl-purine derivative as described in claim 1, characterized in that, The synthetic route of the preparation method is as follows: The preparation method includes the following steps: S1.R1-CH2NH2 undergoes a substitution reaction with compound 1 under organic base catalysis to give compound 2; S2. Compound 2 reacts with excess carbonyl diimidazole via a Dieckmann condensation reaction to give compound 3; S3. Compound 3 and phenylboronic acid were coupled via a Suzuki coupling reaction catalyzed by sodium carbonate, Pd(OAc)2 and sodium triphenylphosphine tris(m-sulfonate) to obtain a 6-phenyl-purine derivative with the structure shown in general formula I.

5. The preparation method according to claim 4, characterized in that, In step S1, the organic base is triethylamine or N,N-diisopropylethylamine, and the molar ratio of R1-CH2NH2 to compound 1 is 3.3:

3.

6. The preparation method according to claim 4, characterized in that, In step S1, the reaction conditions for the substitution reaction are: using n-butanol as a solvent, reacting at 120°C for 2 days.

7. The preparation method according to claim 4, characterized in that, In step S2, the molar ratio of compound 2 to CDI is 2.59:12.

97. The Dieckmann condensation reaction is carried out under nitrogen protection at a temperature of 30°C for 12 hours.

8. The preparation method according to claim 4, characterized in that, In step S3, the molar ratio of compound 3 to phenylboronic acid is 1:1.

2. The Suzuki coupling reaction is carried out under nitrogen protection at a reaction temperature of 100°C for 3 hours.

9. The use of the 6-phenyl-purine derivative or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a medicament for the treatment and / or prevention of malignant tumors, wherein the malignant tumor refers to one of lung cancer, breast cancer, prostate cancer, colon cancer, and liver cancer.

10. An antitumor drug, characterized in that, The active ingredient of the antitumor drug is the 6-phenyl-purine derivative of claim 1 or a medically acceptable salt thereof. The antitumor drug is used to treat and / or prevent malignant tumors, wherein the malignant tumor refers to one of lung cancer, breast cancer, prostate cancer, colon cancer, and liver cancer.

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