A vilazodone derivative V02, its synthesis method, and its application in the preparation of anti-tumor drugs

Abstract

The present invention relates to a new vilazodone derivative (3-(4-(4-(2-chloro-6-methoxyphenyl)piperazine-1-yl)butyl)-cyano-indole) and a synthesis method and application thereof. The vilazodone derivative is 3-(4-(4-(2-chloro-6-methoxyphenyl)piperazine-1-yl)butyl)-cyano-indole, and its chemical structure is as follows: The compound has a significant growth inhibitory effect on a variety of human tumor cells and has excellent inhibitory activity on tumors such as leukemia, lymphoma, breast cancer, melanoma, ovarian cancer, colorectal cancer, cervical cancer, lung cancer, prostate cancer, esophageal cancer, glioma, kidney cancer, pancreatic cancer, nasopharyngeal cancer, liver cancer, and gastric cancer. The IC50 effective concentration of the compound on tumor cells such as breast cancer, colorectal cancer, lung cancer, glioma, pancreatic cancer, and nasopharyngeal cancer is lower than that of cisplatin. Experiments show that the vilazodone derivative has a broad-spectrum anti-tumor activity and is expected to become a new anti-tumor drug.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a vilazodone derivative (3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole, codenamed V02) and a synthesis method thereof, as well as use thereof in the preparation of anti-tumor drugs. Background Art

[0002] Tumor is a serious disease that endangers people's life and health.

[0003] With the continued rise in cancer incidence, the research and development of anti-tumor drugs has become a highly challenging and significant area in the life sciences today. With the continuous development and deepening of molecular oncology, the mechanisms of malignant tumor occurrence and progression are being gradually elucidated, and many new targets are being continuously developed and put into use. The research and development concept of anti-tumor drugs has also undergone a major shift, with the focus of anti-tumor drug research and development shifting from traditional anti-tumor drugs to targeted anti-tumor drugs. Using molecules or genes closely related to tumor occurrence, growth, metastasis, and apoptosis as drug screening targets, and discovering new anti-cancer drugs that are highly effective, low-toxic, and highly specific and selectively act on specific targets has become an important direction in the research and development of anti-tumor drugs today.

[0004] Our previous research has revealed that the depression-related gene HTR1A has tumor suppressor functions. Its specific mechanism of action is that HTR1A significantly inhibits both the canonical TGF-β / TβRII / Smad signaling pathway and the non-canonical TGF-β / TβRII / MEK / ERK / c-Myc signaling pathway. Further studies have confirmed that HTR1A interacts with the E3 ubiquitin ligase TRIM21 and the proteasome subunit PSMD7 to promote TβRII degradation via the ubiquitin-proteasome pathway, thereby inhibiting TGF-β signaling and suppressing the metastasis of triple-negative breast cancer. Studies have also shown that the methylation status of the HTR1A promoter is closely correlated with HTR1A expression levels. Treatment of triple-negative breast cancer cells with the demethylating agent 5-aza-2'-deoxycytidine significantly upregulates HTR1A expression. Furthermore, treatment with the HTR1A agonist vilazodone significantly inhibits triple-negative breast cancer tumor growth in mice. The experimental results suggest that HTR1A is a new target for tumor therapy, and the HTR1A-targeting agonist vilazodone may provide a new approach for the treatment of triple-negative breast cancer. Related work was published in Advanced Science (2022, 2:e2105672).

[0005] Patent application 202111193803X discloses the use of vilazodone and its derivatives in the preparation of anti-tumor drugs, and discloses the anti-tumor effect of vilazodone and the general structure of its derivatives, but the specification of the patent does not disclose the specific structure of vilazodone derivatives, let alone the preparation method of vilazodone derivatives. In the prior art, the synthesis route of vilazodone is long and the reaction conditions are relatively severe, which is not suitable for industrial preparation. Moreover, the existing synthesis method of vilazodone is not suitable for the synthesis of vilazodone derivatives, especially (3-(4-(4-(2-chloro-6-methoxyphenyl)piperazine-1-yl)butyl)-cyano-indole, code-named V02) is a compound with a completely new structure. There are no reports on the structure and anti-tumor effect of this new compound at home and abroad. Summary of the Invention

[0006] The purpose of the present invention is to overcome the defects of the above-mentioned prior art and to provide a highly effective and low-toxic vilazodone derivative and a synthesis method thereof and use thereof in the preparation of anti-tumor drugs.

[0007] The objectives of the present invention can be achieved by the following technical solution: The present invention provides a new vilazodone derivative (3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole, codenamed V02), the chemical structure of which is reported for the first time. The structural formula of vilazodone derivative V02 is as follows:

[0008]

[0009] The present invention discloses a novel vilazodone derivative (3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole). Currently, there are no reports on the synthesis of the vilazodone derivative (3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole), nor on the anti-tumor activity of the compound. The present invention utilizes medicinal chemistry techniques to synthesize this novel vilazodone derivative, which has the Chinese chemical name: 3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole, the English chemical name: 3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-1H-indole-5-carbonitrile, a molecular weight of 459.42, and a molecular formula of C24H27ClN4O. Through cell experiments, it was found that this compound has good anti-tumor activity and is expected to be further developed into a new type of anti-tumor drug with high efficiency and low toxicity.

[0010] The synthetic route is as follows:

[0011]

[0012] The synthesis method specifically comprises the following steps:

[0013] (1) 2-Chloro-6-methoxy-aniline (500 mg, 3.17 mmol) and 2-chloro-N-(2-chloroethyl)ethylamine (1.13 g, 6.35 mmol, hydrochloride) were placed in a 100 mL three-necked flask containing xylene (10 mL). Tetrabutylammonium bromide (204.55 mg, 634.53 μmol) and potassium carbonate (526.17 mg, 3.81 mmol) were added in sequence. The mixture was heated to 140°C and stirred for 12 hours. LC-MS / MS showed that the reactants were completely consumed and the desired molecular weight was detected. The mixture was diluted with methanol (20 mL*3) and filtered to obtain a filtrate, which was then concentrated under reduced pressure to obtain the crude product. The crude product was purified by high performance liquid chromatography (column model: Watersxbridge 150*25mm*10um; mobile phase: [water (ammonium bicarbonate)-acetonitrile]; B%: 14%-44%, 8 minutes) to give 1-(2-chloro-6-methoxyphenyl)piperazine.

[0014] (2) 1-(2-chloro-6-methoxy-phenyl)piperazine (80 mg, 352.89 umol) and 3-(4-chlorobutyl)-cyano-indole (82.12 mg, 352.89 umol) were placed in a 50 mL three-necked flask containing acetonitrile (6 mL), and diisopropylethylamine (182.43 mg, 1.41 mmol, 245.87 uL) and potassium iodide (11.72 mg, 70.58 umol) were added in sequence. The mixture was stirred at 95 ° C for 24 hours. LC-MS showed that the reactants were completely consumed and the desired molecular weight was detected. The reaction solution was directly concentrated under reduced pressure to obtain a crude product. The crude product was purified by high performance liquid chromatography (column model: Welch Xtimate C 18 150*25mm*5um; mobile phase: [water (hydrochloric acid)-acetonitrile]; B%: 22%-52%, 8min) to obtain 3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole.

[0015] The present invention provides a use of a vilazodone derivative V02 or a pharmaceutical composition comprising V02 in preparing a drug for preventing and / or treating tumors.

[0016] The vilazodone derivative V02 includes but is not limited to its tautomers, mesomers, racemates, enantiomers, diastereomers, or derivatives generated based on its structure, or mixtures thereof.

[0017] Furthermore, the vilazodone derivative V02 or its pharmaceutical composition includes but is not limited to pharmaceutically acceptable salts, ethers, esters, prodrugs, metabolites, solvates or crystals thereof.

[0018] Furthermore, the vilazodone derivative V02 or its pharmaceutical composition includes a pharmaceutically acceptable salt thereof; preferably, the pharmaceutically acceptable salt includes but is not limited to hydrochloride, bromate, fumarate, acetate, citrate, sulfate or methanesulfonate.

[0019] Furthermore, the vilazodone derivative V02 or its pharmaceutical composition includes but is not limited to tablets, injections, capsules, oral solutions, pills, granules, powders, aerosols, patches, ointments, paints or suppositories.

[0020] Furthermore, the vilazodone derivative V02 or its pharmaceutical composition further comprises conventional anti-tumor drugs; preferably, including but not limited to chemotherapeutic drugs, biological targeted therapeutic drugs, metabolic therapeutic drugs or immunotherapeutic drugs.

[0021] Furthermore, the vilazodone derivative V02 or its pharmaceutical composition is used for treatments including but not limited to surgical resection, chemotherapy or radiotherapy.

[0022] Furthermore, the effects of the vilazodone derivative V02 or its pharmaceutical composition include but are not limited to inhibiting tumor growth and / or metastasis.

[0023] Furthermore, the vilazodone derivative V02 or its pharmaceutical composition is used for the prevention and / or treatment of diseases including but not limited to leukemia, lymphoma, breast cancer, melanoma, ovarian cancer, colon cancer, cervical cancer, lung cancer, prostate cancer, esophageal cancer, glioma, kidney cancer, pancreatic cancer, nasopharyngeal cancer, liver cancer, and gastric cancer.

[0024] Furthermore, the preventive and / or therapeutic effects on leukemia include but are not limited to preventive and / or therapeutic effects on leukemia cells HL60.

[0025] Furthermore, the preventive and / or therapeutic effects on lymphoma include but are not limited to preventive and / or therapeutic effects on lymphoma cell line MINO.

[0026] Furthermore, the preventive and / or therapeutic effects on breast cancer include but are not limited to preventive and / or therapeutic effects on breast cancer cells MDA-MB-468, MDA-MB-231, MDA-MB-231LM2, Hs578T, HCC1954, JIMT1, T47D, and ZR-75-1.

[0027] Furthermore, the preventive and / or therapeutic effects on melanoma include but are not limited to preventive and / or therapeutic effects on melanoma cells A375.

[0028] Furthermore, the preventive and / or therapeutic effects on ovarian cancer include but are not limited to preventive and / or therapeutic effects on ovarian cancer cell A2780.

[0029] Furthermore, the preventive and / or therapeutic effects on intestinal cancer include but are not limited to preventive and / or therapeutic effects on intestinal cancer cells HCT116.

[0030] Furthermore, the preventive and / or therapeutic effects on cervical cancer include but are not limited to preventive and / or therapeutic effects on cervical cancer cell SiHa.

[0031] Furthermore, the preventive and / or therapeutic effects on lung cancer include but are not limited to preventive and / or therapeutic effects on lung cancer cells A549.

[0032] Furthermore, the preventive and / or therapeutic effects on prostate cancer include but are not limited to preventive and / or therapeutic effects on prostate cancer cells PC-3.

[0033] Furthermore, the preventive and / or therapeutic effects on esophageal cancer include but are not limited to preventive and / or therapeutic effects on esophageal cancer cells EC109.

[0034] Furthermore, the preventive and / or therapeutic effects on glioma include but are not limited to preventive and / or therapeutic effects on glioma cells U251.

[0035] Furthermore, the preventive and / or therapeutic effects on renal clear cell adenocarcinoma include but are not limited to preventive and / or therapeutic effects on renal clear cell adenocarcinoma cell line 786-O.

[0036] Furthermore, the preventive and / or therapeutic effects on pancreatic cancer include but are not limited to preventive and / or therapeutic effects on pancreatic cancer cells Panc-1.

[0037] Furthermore, the preventive and / or therapeutic effects on nasopharyngeal carcinoma include but are not limited to preventive and / or therapeutic effects on nasopharyngeal carcinoma cells 5-8F.

[0038] Furthermore, the preventive and / or therapeutic effects on liver cancer include but are not limited to preventive and / or therapeutic effects on liver cancer cells SMMC-7721.

[0039] Furthermore, the preventive and / or therapeutic effects on gastric cancer include but are not limited to preventive and / or therapeutic effects on gastric cancer cell SGC-7901.

[0040] Compared with the prior art, the present invention has the following beneficial effects:

[0041] 1. Vilazodone derivative V02 is a compound with a completely new structure that has not been reported domestically or internationally. It has the potential to be applied for as a new class of anti-tumor drugs.

[0042] 2. The present invention relates to the anti-tumor activity of the vilazodone derivative V02 and its novel use in the preparation of drugs for treating and / or preventing cancer. The vilazodone derivative V02 has significant and broad-spectrum anti-tumor activity and has inhibitory effects on a variety of human tumor cells cultured in vitro, such as leukemia, lymphoma, breast cancer, melanoma, ovarian cancer, colon cancer, cervical cancer, lung cancer, prostate cancer, esophageal cancer, glioma, kidney cancer, pancreatic cancer, nasopharyngeal cancer, liver cancer, and gastric cancer. The IC50 effective concentration of this compound for tumor cells such as breast cancer, colorectal cancer, lung cancer, glioma, pancreatic cancer, and nasopharyngeal cancer is lower than that of cisplatin. The vilazodone derivative V02 involved in the present invention can be used to prepare anti-tumor drugs and prevent the occurrence and metastasis of tumors.

[0043] 3. The synthesis method of the present invention is simple, low in cost, and the obtained product has high yield and high purity, and is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 It shows the growth inhibition curve of leukemia cells HL60 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h;

[0045] Figure 2 It shows the growth inhibition curve of lymphoma cells MINO treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h;

[0046] Figure 3 The growth inhibition curves of breast cancer cells MDA-MB-231LM2 treated with different concentrations of cisplatin and vilazodone derivative V02 for 248 h are shown;

[0047] Figure 4 represents the growth inhibition curve of melanoma A375 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h;

[0048] Figure 5 The growth inhibition curves of ovarian cancer cells A2780 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h are shown;

[0049] Figure 6 It shows the growth inhibition curve of colorectal cancer cell HCT116 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 hours;

[0050] Figure 7represents the growth inhibition curve of cervical cancer cell SiHa treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h;

[0051] Figure 8 The growth inhibition curves of lung cancer cells A549 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h are shown;

[0052] Figure 9 It shows the growth inhibition curve of prostate cancer cell PC-3 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h;

[0053] Figure 10 It shows the growth inhibition curve of esophageal cancer cell EC109 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h;

[0054] Figure 11 The growth inhibition curves of glioma cells U251 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h are shown;

[0055] Figure 12 The figure shows the growth inhibition curve of renal clear cell adenocarcinoma cell line 786-0 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 hours;

[0056] Figure 13 It shows the growth inhibition curve of pancreatic cancer cells Panc-1 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 hours;

[0057] Figure 14 The figure shows the growth inhibition curve of nasopharyngeal carcinoma cell line 5-8F treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h;

[0058] Figure 15 The growth inhibition curves of liver cancer cells SMMC-7721 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h are shown;

[0059] Figure 16 The growth inhibition curves of gastric cancer cells SGC-7901 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h are shown;

[0060] Figure 17 The growth inhibition curves of triple-negative breast cancer cells MDA-MB-468 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h are shown;

[0061] Figure 18 The growth inhibition curves of triple-negative breast cancer cells MDA-MB-231 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h are shown;

[0062] Figure 19 The growth inhibition curves of triple-negative breast cancer cells HS578T treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 hours are shown;

[0063] Figure 20 The growth inhibition curves of HER2-overexpressing breast cancer cells HCC1954 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h.

[0064] Figure 21 The growth inhibition curves of HER2-overexpressing breast cancer cells JIMT1 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 h.

[0065] Figure 22 The growth inhibition curves of Luminal breast cancer cells T47D treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 hours are shown;

[0066] Figure 23 The growth inhibition curves of Luminal breast cancer cells ZR-75-1 treated with different concentrations of cisplatin and vilazodone derivative V02 for 48 hours. DETAILED DESCRIPTION

[0067] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0068] Example 1: Synthesis of a vilazodone derivative (3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole, code V02):

[0069] 2-Chloro-6-methoxy-aniline (500 mg, 3.17 mmol) and 2-chloro-N-(2-chloroethyl)ethanamine (1.13 g, 6.35 mmol, hydrochloride) were placed in a 100 mL three-necked flask containing xylene (10 mL). Tetrabutylammonium bromide (204.55 mg, 634.53 μmol) and potassium carbonate (526.17 mg, 3.81 mmol) were added sequentially. The mixture was heated to 140°C and stirred for 12 hours. LC / MS / MS indicated complete consumption of the reactants and the desired molecular weight was detected. The mixture was diluted with methanol (20 mL x 3) and filtered to obtain a filtrate, which was then concentrated under reduced pressure to yield the crude product. The crude product was purified by high performance liquid chromatography (column model: Watersxbridge 150*25mm*10μm; mobile phase: [water (ammonium bicarbonate)-acetonitrile]; B%: 14%-44%, 8 minutes) to give 1-(2-chloro-6-methoxyphenyl)piperazine (514 mg, 2.27 mmol, 71.46% yield) as a white solid.

[0070] 1-(2-chloro-6-methoxy-phenyl)piperazine (80 mg, 352.89 μmol) and 3-(4-chlorobutyl)-cyano-indole (82.12 mg, 352.89 μmol) were placed in a 50 mL three-necked flask containing acetonitrile (6 mL), and diisopropylethylamine (182.43 mg, 1.41 mmol, 245.87 uL) and potassium iodide (11.72 mg, 70.58 μmol) were added in sequence. The mixture was stirred at 95 ° C for 24 hours. Liquid chromatography-mass spectrometry showed that the reactants had been completely consumed and the desired molecular weight was detected. The reaction solution was directly concentrated under reduced pressure to obtain a crude product. The crude product was purified by high performance liquid chromatography (column model: Welch Xtimate C 18 150*25mm*5μm; mobile phase: [water (hydrochloric acid)-acetonitrile]; B%: 22%-52%, 8min) to give 3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole (51.81 mg, 111.44μmol, 31.58% yield, 98.82% purity, hydrochloride) as a white solid.

[0071] Example 2: Effects of Cisplatin and Vilazodone Derivative V02 on the Growth Inhibition of Various Tumor Cells

[0072] The CCK8 colorimetric assay was used to compare the cytotoxicity of cisplatin and vilazodone derivative V02 (hydrochloride form) against human leukemia cell line HL60, lymphoma cell line MINO, breast cancer cell line MDA-MB-231LM2, melanoma cell line A375, human ovarian cancer cell line A2780, human colon cancer cell line HCT116, cervical cancer cell line SiHa, lung adenocarcinoma cell line A549, prostate cancer cell line PC-3, esophageal cancer cell line EC109, glioma cell line U251, renal clear cell adenocarcinoma cell line 786-O, pancreatic cancer cell line Panc-1, nasopharyngeal carcinoma cell line 5-8F, hepatoma cell line SMMC-7721, and gastric adenocarcinoma cell line SGC-7901.

[0073] Various cells were seeded in 96-well plates at a density of 8000 cells / well. 24 hours after inoculation, cisplatin was used as a control drug. The vilazodone derivative prepared in Example 1 and the control drug cisplatin were diluted to 0, 0.01, 0.1, 0.5, 1, 10, 20, 40, 80, and 160 μM, respectively. The culture medium in the original wells was discarded, and 100 μL per well was added to the corresponding wells, with 4 replicates per group. At 48 hours of treatment, 10 μL of CCK8 was added to each well and incubated for 3 hours. The OD value at A450 was measured using a multifunctional microplate reader and the inhibition rate was calculated.

[0074] like Figure 1-16As shown, different concentrations of cisplatin (CDDP in the figure) and vilazodone derivatives (VO2 in the figure) inhibit the growth curves of different tumor cells. It can be seen that the vilazodone derivative V02 has an inhibitory effect on a variety of tumor cells (see Figure 1-16 The IC50 values ​​of the vilazodone derivative V02 ranged from 7.832 to 32 μM in various cell types. Compared to the IC50 values ​​of cisplatin, the IC50 values ​​of the vilazodone derivative V02 were significantly lower than those of cisplatin in breast cancer MDA-MB-231LM2 cells, colon cancer HCT116 cells, lung adenocarcinoma cells A549, glioma cells U251, pancreatic cancer cells Panc-1, and nasopharyngeal carcinoma cells 5-8F, demonstrating a more pronounced inhibitory effect on these cells (see Table 1 for details).

[0075] Table 1 IC50 of different tumor cell lines treated with CDDP and V02 for 48 h

[0076] Tumor type cell lines CDDP IC50(μM) V02 IC50 (μM) leukemia HL60 0.8032 16.48 Lymphoma MINO 1.428 18.09 Breast cancer MDA-MB-231LM2 20.32 7.832 Melanoma A375 4.133 12.66 Ovarian cancer A2780 10.24 16.05 colon cancer HCT116 42.10 13.50 Cervical cancer Siha 14.63 24.42 lung cancer A549 44.21 21.46 Prostate cancer PC-3 6.172 16.98 Esophageal cancer EC109 17.25 20.10 glioma U251 41.83 16.66 Kidney cancer 786-O 12.32 18.64 pancreatic cancer Panc-1 57.75 15.72 Nasopharyngeal carcinoma 5-8F 68.64 17.61 Liver cancer SMMC-7721 6.850 23.62 Gastric cancer SGC-7901 6.359 31.90

[0077] Example 3: Effects of Cisplatin and Vilazodone Derivative V02 on the Growth Inhibition of Various Breast Tumor Cells

[0078] The CCK8 colorimetric assay was used to compare the cytotoxicity of cisplatin and the vilazodone derivative V02 (hydrochloride salt form) against triple-negative breast cancer (TNBC) cell lines (MDA-MB-468, MDA-MB-231, HS578T), HER2-type breast cancer cell lines (HCC1954, JIMT1), and luminal breast cancer cell lines (T47D, ZR-75-1). The experimental procedures were the same as in Example 1.

[0079] like Figure 17-23 As shown in the figure, different concentrations of cisplatin (CDDP) and vilazodone derivatives (VO2) inhibit the growth curves of different breast cancer cell lines. The results show that vilazodone derivatives V02 have inhibitory effects on the above 7 types of breast tumor cells (see Figure 17-23 In most breast cancer cells, the IC50 of vilazodone derivative V02 was significantly lower than that of cisplatin, and its inhibitory effect on these cells was more significant (Table 2).

[0080] Table 2 IC50 of CDDP and V02 in treating different breast cancer cell lines for 48h

[0081]

[0082] It should be noted that the above descriptions are merely embodiments of the present invention and are not intended to limit the scope of the present invention. Any direct or indirect application of the present invention's description and accompanying drawings to other related technical fields is also encompassed within the scope of the present invention. Therefore, any technical solution that can be derived by a person skilled in the art through logical analysis, reasoning, or limited experimentation based on the concept of the present invention and the prior art should fall within the scope of protection defined by the claims.

Claims

1. A vilazodone derivative, characterized in that The vilazodone derivative is 3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole, and its chemical structure is shown in (I): ； （Ⅰ）。 2. A method for synthesizing the vilazodone derivative according to claim 1, characterized in that: The specific steps include: (1) 2-chloro-6-methoxy-aniline and 2-chloro-N-(2-chloroethyl)ethylamine are reacted to produce 1-(2-chloro-6-methoxyphenyl)piperazine; (2) 1-(2-chloro-6-methoxyphenyl)piperazine and 3-(4-chlorobutyl)-cyano-indole are reacted to form 3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole.

3. The method for synthesizing the vilazodone derivative according to claim 2, wherein: Step (1) is specifically as follows: 2-chloro-6-methoxy-aniline and 2-chloro-N-(2-chloroethyl)ethylamine are placed in a three-necked flask containing xylene, tetrabutylammonium bromide and potassium carbonate are added in sequence, the mixture is heated to 140° C. and stirred for 12 hours, the mixture is diluted with methanol, filtered to obtain a filtrate, the filtrate is concentrated under reduced pressure to obtain a crude product, and the crude product is purified by high performance liquid chromatography to obtain 1-(2-chloro-6-methoxyphenyl)piperazine.

4. The method for synthesizing the vilazodone derivative according to claim 2, wherein: Step (2) is specifically as follows: 1-(2-chloro-6-methoxy-phenyl)piperazine and 3-(4-chlorobutyl)-cyano-indole are placed in a three-necked flask containing acetonitrile, diisopropylethylamine and potassium iodide are added in sequence, the mixture is stirred at 95° C. for 24 hours, and the reaction solution is directly concentrated under reduced pressure to obtain a crude product, which is purified by high performance liquid chromatography to obtain 3-(4-(4-(2-chloro-6-methoxyphenyl)piperazin-1-yl)butyl)-cyano-indole.

5. A use of the vilazodone derivative according to claim 1, characterized in that: Use of the vilazodone derivative or the pharmaceutical composition comprising the vilazodone derivative in preparing a drug for preventing and / or treating tumors.

6. The use according to claim 5, characterized in that The vilazodone derivative is a pharmaceutically acceptable salt thereof; The pharmaceutically acceptable salts include hydrochloride, bromate, fumarate, acetate, citrate, sulfate or methanesulfonate.

7. The use according to claim 5, characterized in that The drug is in the form of tablets, injections, capsules, oral solutions, pills, granules, powders, aerosols, patches, ointments, paints or suppositories; The drugs are conventional anti-tumor drugs, including chemotherapy drugs, biological targeted therapy drugs, metabolic therapy drugs or immunotherapy drugs.

8. The use according to claim 5, characterized in that The effects of the drug include inhibiting tumor growth and / or metastasis; The vilazodone derivative or its composition is used as a drug for preventing and / or treating leukemia, lymphoma, breast cancer, melanoma, ovarian cancer, colon cancer, cervical cancer, lung cancer, prostate cancer, esophageal cancer, glioma, kidney cancer, pancreatic cancer, nasopharyngeal cancer, liver cancer, and gastric cancer.

9. The use according to claim 8, characterized in that The preventive and / or therapeutic effects on leukemia include preventive and / or therapeutic effects on leukemia cells HL60; The preventive and / or therapeutic effects on lymphoma include preventive and / or therapeutic effects on lymphoma cell MINO; The preventive and / or therapeutic effects on breast cancer include preventive and / or therapeutic effects on breast cancer cells MDA-MB-468, MDA-MB-231, MDA-MB-231 LM2, Hs578T, HCC1954, JIMT1, T47D, and ZR-75-1; The preventive and / or therapeutic effects on melanoma include preventive and / or therapeutic effects on melanoma cells A375; The preventive and / or therapeutic effects on ovarian cancer include preventive and / or therapeutic effects on ovarian cancer cell A2780; The preventive and / or therapeutic effects on colorectal cancer include preventive and / or therapeutic effects on colorectal cancer cells HCT116; The preventive and / or therapeutic effects on cervical cancer include preventive and / or therapeutic effects on cervical cancer cell SiHa; The preventive and / or therapeutic effects on lung cancer include preventive and / or therapeutic effects on lung cancer cells A549; The preventive and / or therapeutic effects on prostate cancer include preventive and / or therapeutic effects on prostate cancer cells PC-3; The preventive and / or therapeutic effects on esophageal cancer include preventive and / or therapeutic effects on esophageal cancer cell EC109; The preventive and / or therapeutic effects on gliomas include preventive and / or therapeutic effects on glioma cells U251; The preventive and / or therapeutic effect on renal clear cell adenocarcinoma includes the preventive and / or therapeutic effect on renal clear cell adenocarcinoma cell line 786-O; The preventive and / or therapeutic effects on pancreatic cancer include preventive and / or therapeutic effects on pancreatic cancer cells Panc-1; The preventive and / or therapeutic effects on nasopharyngeal carcinoma include preventive and / or therapeutic effects on nasopharyngeal carcinoma cells 5-8F; The preventive and / or therapeutic effects on liver cancer include preventive and / or therapeutic effects on liver cancer cells SMMC-7721; The preventive and / or therapeutic effect on gastric cancer includes the preventive and / or therapeutic effect on gastric cancer cell SGC-7901.

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