A compound with anti-tumor activity and its preparation method and application

Abstract

The present invention discloses a compound with anti-tumor activity and its preparation method and application, belonging to the field of biomedicine technology. The new compound prepared by the present invention is a light yellow amorphous powder, soluble in methanol, with a maximum absorption peak of 280nm in the ultraviolet spectrum, and a molecular formula of C 30 H 37 N7O5, after one-dimensional H NMR spectroscopy ( 1 HNMR), one-dimensional carbon nuclear magnetic resonance spectroscopy ( 13 C-NMR), two-dimensional nuclear magnetic resonance spectrum (HMBC), high-resolution mass spectrometry (HRMS), and the molecular structure was determined as follows: #imgabs0# The purity of the new compound with anti-tumor activity obtained by the method of the present invention is more than 97%. The MTT method was used to test the in vitro anti-tumor activity of the new compound. The experimental results showed that this new compound not only has an inhibitory effect on human lung cancer cells A549, but also has an inhibitory effect on human breast cancer cells MDA-MB-231, human liver cancer cells HepaRG, human pancreatic cancer cells PANC-1, and human gastric cancer cells MKN-1.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a compound with anti-tumor activity and a preparation method and application thereof. Background Art

[0002] The main methods of cancer treatment include surgery, radiotherapy and drug therapy. At present, there are more and more options for tumor drug treatment, including traditional chemotherapy drugs, endocrine therapy drugs, small molecule targeted therapy drugs, and immunotherapy drugs. In today's rapid development of anti-tumor treatment, especially in the era of emphasizing precision tumor treatment, in addition to the research of tumor targets, the research and exploration of new anti-tumor drugs are equally important. The discovery of new drugs includes random discovery, obtaining from the active ingredients of natural compounds, taking existing breakthrough drugs as the lead, discovering from drug metabolites / synthetic intermediates, and designing based on biological macromolecule structures.

[0003] Therefore, it is of great significance to explore a wide range of compounds with anti-tumor activity. Summary of the invention

[0004] The purpose of the present invention is to provide a compound with anti-tumor activity and a preparation method and application thereof, so as to solve the problems existing in the above-mentioned prior art.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] The present invention provides a compound having anti-tumor activity and a pharmaceutically acceptable salt, stereoisomer, tautomer, homologue, solvate, prodrug or polymorph thereof. The compound has a molecular formula of C 30 H 37 N7O5, its structural formula is:

[0007]

[0008] The present invention also provides a method for preparing the compound with anti-tumor activity, which comprises dissolving mobotinib in an organic solvent, performing a degradation reaction under alkaline conditions, and purifying the compound to obtain the compound with anti-tumor activity.

[0009] Preferably, the pH of the alkaline condition is 13.

[0010] Preferably, the degradation reaction temperature is 80° C. and the time is 16 h.

[0011] Preferably, after the degradation reaction, the method further comprises a step of adjusting the pH to neutral.

[0012] Preferably, the purification comprises purification using semi-preparative liquid chromatography.

[0013] Preferably, the chromatographic conditions are:

[0014] Chromatographic column: X Select CSH C 18 XP Column (30×150mm, 5μm); flow rate: 60mL / min; detection wavelength: 280nm; mobile phase A: water, mobile phase B: acetonitrile;

[0015] The gradient elution program was as follows: 0-7 min, 45% B→55% B; 7 min-8.5 min, 55% B→95% B; 8.5 min-10 min, 95% B→95% B; 10 min-11 min, 95% B→45% B; 11 min-14 min, 45% B→45% B;

[0016] The sample solution was collected for 7.8 min.

[0017] Preferably, the purification further comprises removing the organic solvent by a rotary evaporator.

[0018] The present invention also provides a pharmaceutical composition, comprising the compound having anti-tumor activity and pharmaceutically acceptable salts, stereoisomers, tautomers, homologues, solvates, prodrugs or polymorphs thereof.

[0019] The present invention also provides a preparation, characterized in that it comprises the compound having anti-tumor activity and its pharmaceutically acceptable salt, stereoisomer, tautomer, homologue, solvate, prodrug or polymorph; or the pharmaceutical composition; and a pharmaceutically acceptable carrier

[0020] The present invention also provides the compound having anti-tumor activity and its pharmaceutically acceptable salts, stereoisomers, tautomers, homologues, solvates, prodrugs or polymorphs; or the use of the pharmaceutical composition as or in the preparation of a preparation having anti-tumor cell activity.

[0021] Preferably, the tumor cells include human lung cancer cells, human breast cancer cells, human liver cancer cells, human pancreatic cancer cells or human gastric cancer cells.

[0022] Based on the above technical solution, the present invention has the following technical effects:

[0023] The new compound prepared by the present invention is a light yellow amorphous powder, soluble in methanol, with a maximum absorption peak of 280nm in the ultraviolet spectrum, a molecular weight of 575, and a molecular formula of C 30 H 37 N7O5, after 1 H-NMR spectrum, 13 C-NMR spectrum, HMBC spectrum, HRMS spectrum, and molecular structure are determined as follows:

[0024]

[0025] The purity of the new compound with anti-tumor activity obtained by the method of the present invention is more than 97%. The in vitro anti-tumor activity test of the new compound was carried out using the MTT method. The experimental results showed that the new compound not only has an inhibitory effect on human lung cancer cells A549, but also has an inhibitory effect on human breast cancer cells MDA-MB-231, human liver cancer cells HepaRG, human pancreatic cancer cells PANC-1, and human gastric cancer cells MKN-1. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0027] Figure 1 is a chromatogram of the compound of the present invention;

[0028] Figure 2 is a high-resolution mass spectrum of the compound of the present invention;

[0029] Figure 3 is a one-dimensional hydrogen nuclear magnetic resonance spectrum of the compound of the present invention;

[0030] Figure 4 is a one-dimensional carbon nuclear magnetic resonance spectrum of the compound of the present invention;

[0031] Figure 5 is a two-dimensional nuclear magnetic resonance spectrum of the compound of the present invention;

[0032] Figure 6 The inhibitory effects of different concentrations of the compounds of the present invention on A549 cells;

[0033] Figure 7 The inhibitory effects of different concentrations of the compounds of the present invention on MDA-MB-231 cells;

[0034] Figure 8 The inhibitory effects of different concentrations of the compounds of the present invention on HepaRG cells;

[0035] Fig. 9 The inhibitory effects of different concentrations of the compounds of the present invention on PANC-1 cells;

[0036] Fig.10 The figure shows the inhibitory effect of different concentrations of the compound of the present invention on MKN-1 cells. DETAILED DESCRIPTION

[0037] The present invention provides a compound having anti-tumor activity, the molecular formula of which is C 30 H 37 N7O5, its structural formula is:

[0038]

[0039] It should be noted that the above-mentioned compound with anti-tumor activity is a light yellow amorphous powder, soluble in methanol, with a maximum absorption peak of 280nm in the ultraviolet spectrum and a molecular weight of 575. The compound is a new compound produced by the degradation of mobotinib, the structure of which has not been reported before, and has an inhibitory effect on human lung cancer cells A549, human breast cancer cells MDA-MB-231, human liver cancer cells HepaRG, human pancreatic cancer cells PANC-1, and human gastric cancer cells MKN-1, and is a candidate drug with great potential value.

[0040] It should be noted that the above-mentioned compounds with anti-tumor activity and their pharmaceutically acceptable salts, stereoisomers, tautomers, homologues, solvates, prodrugs or polymorphs have the ability to kill cancer cells. In addition, stereoisomers, tautomers, homologues, solvates, prodrugs or polymorphs are conventional technical terms in the art and have no other specific meanings.

[0041] Another aspect of the present invention provides a method for preparing the above-mentioned compound having anti-tumor activity, wherein mobotinib is dissolved in an organic solvent, subjected to degradation reaction under alkaline conditions, and purified to obtain the above-mentioned compound having anti-tumor activity.

[0042] In some specific embodiments, the organic solvent may be methanol.

[0043] In some specific embodiments, the pH of the alkaline condition is preferably 13, preferably the pH is adjusted by a NaOH solution, and more preferably the pH is adjusted by a 1 M NaOH solution.

[0044] In some specific embodiments, the temperature of the above degradation reaction is preferably 70-90°C, and more preferably 80°C.

[0045] In some specific embodiments, the degradation reaction time is preferably 14-18 hours, and more preferably 16 hours.

[0046] In some specific embodiments, after the above-mentioned degradation reaction, a step of adjusting the pH to neutral is further included, preferably using a hydrochloric acid solution to neutralize the reaction solution to neutral, and more preferably using a 1M hydrochloric acid solution to neutralize the reaction solution to neutral.

[0047] In some specific embodiments, the above purification includes purification using a semi-preparative liquid chromatography, and the chromatographic conditions are: the chromatographic column is: X Select CSH C 18 XP Column (30×150mm, 5μm); flow rate: 60mL / min; detection wavelength: 280nm; mobile phase A: water, mobile phase B: acetonitrile; the gradient elution program is: 0-7min, 45%B→55%B; 7min-8.5min, 55%B→95%B; 8.5min-10min, 95%B→95%B; 10min-11min, 95%B→45%B; 11min-14min, 45%B→45%B;

[0048] The sample solution was collected for 7.8 min.

[0049] It should be noted that the chromatographic purity obtained by the above-mentioned purification method of the compound having anti-tumor activity can reach more than 97%.

[0050] It should be noted that the purification also includes removing the organic solvent by a rotary evaporator.

[0051] In another aspect, the present invention provides the use of the above-mentioned compound having anti-tumor activity in the preparation of a drug for treating anti-tumor.

[0052] It should be noted that the above-mentioned drug includes the above-mentioned compound with anti-tumor activity and a pharmaceutically acceptable carrier.

[0053] It should be noted that the above-mentioned compounds with anti-tumor activity and their pharmaceutically acceptable salts, stereoisomers, tautomers, homologues, solvates, prodrugs or polymorphs can be used in combination with other active drugs to enhance the killing ability of cancer cells or supplement other therapeutic effects to achieve a synergistic effect.

[0054] In another aspect, the present invention provides a preparation comprising the above-mentioned compound having anti-tumor activity and its pharmaceutically acceptable salts, stereoisomers, tautomers, homologues, solvates, prodrugs or polymorphs; and a pharmaceutically acceptable carrier.

[0055] It should be noted that in the above preparations, pharmaceutically acceptable carriers include but are not limited to: ion exchange materials, alumina, aluminum stearate, lecithin, self-emulsifying drug delivery systems (SEDDS) such as d-vitamin E polyethylene glycol 1000 succinate, Tween or other similar polymer media, surfactants for pharmaceutical preparations, serum proteins such as human serum albumin, buffer substances such as phosphates, aminoacetic acid, sorbic acid, potassium sorbate, a mixture of partial glycerides of saturated vegetable fatty acids, water, salts, electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, silica gel, magnesium silicate, etc. Polyvinyl pyrrolidone, cellulosic materials, polyvinyl alcohol, sodium carboxymethyl cellulose, polyacrylates, ethylene-polyoxyethylene-block polymers and lanolin, cyclodextrins such as α-, β-, γ-cyclodextrin or their chemically modified derivatives such as 2- and 3-hydroxypropyl-β-cyclodextrin and other hydroxyalkyl cyclodextrins or other soluble derivatives can all be used to promote the drug delivery of the above-mentioned compounds with anti-tumor activity and their pharmaceutically acceptable salts, stereoisomers, tautomers, homologs, solvates, prodrugs or polymorphs.

[0056] It should also be noted that in the above-mentioned preparations, pharmaceutically acceptable carriers also include pharmaceutically acceptable excipients, such as fillers (such as anhydrous lactose, starch, lactose beads and glucose), binders (such as microcrystalline cellulose), disintegrants (such as cross-linked carboxymethyl starch sodium, cross-linked carboxymethyl cellulose sodium, low-substituted hydroxypropyl cellulose and cross-linked PVP), lubricants (such as magnesium stearate), absorption promoters, flavoring agents, sweeteners, diluents, excipients, wetting agents, solvents, solubilizers and colorants, etc., which can also be used as pharmaceutically acceptable carriers for preparing the above-mentioned compounds and their pharmaceutically acceptable salts, stereoisomers, tautomers, homologs, solvates, prodrugs or polymorphs into preparations.

[0057] In some embodiments, the pharmaceutically acceptable carrier is suitable for liquid dosage forms, solid dosage forms or paste dosage forms.

[0058] It should be noted that pharmaceutically acceptable carriers suitable for different dosage forms can be selected according to the administration method of the above-mentioned compounds with anti-tumor activity and their pharmaceutically acceptable salts, stereoisomers, tautomers, homologues, solvates, prodrugs or polymorphs. It should also be noted that liquid dosage forms, solid dosage forms, paste dosage forms or emulsion dosage forms are known in the art, such as liquid dosage forms including but not limited to: injections, sprays or oral liquids; solid dosage forms including but not limited to: tablets, powders, granules or capsules; paste dosage forms including but not limited to: creams or ointments. In some specific implementations, the above-mentioned compounds with anti-tumor activity and pharmaceutically acceptable salts, stereoisomers, tautomers, homologues, solvates, prodrugs or polymorphs thereof can be administered by enteral or parenteral routes; parenteral preparations include injections, creams, ointments, patches, sprays, etc.; routes of administration include subcutaneous, intradermal, intraarterial, intravenous, intramuscular, intraarticular, intrasynovial, intrasternal, intrathecal, intralesional, intracranial injection or infusion, or oral, topical, rectal, nasal, buccal, vaginal, sublingual, intradermal, mucosal, tracheal, urethral administration, or administration by inhalation of aerosol or implantation of accumulation or acupuncture.

[0059] In another aspect, the present invention provides the use of the above-mentioned compound with anti-tumor activity and its pharmaceutically acceptable salts, stereoisomers, tautomers, homologues, solvates, prodrugs or polymorphs as or in the preparation of preparations with anti-tumor cell activity.

[0060] In some specific embodiments, the tumor cells include human lung cancer cells A549, human breast cancer cells MDA-MB-231, human liver cancer cells HepaRG, human pancreatic cancer cells PANC-1, or human gastric cancer cells MKN-1.

[0061] In some specific embodiments, in the above application, the tumor cells are cancer cells known in the art, preferably human lung cancer cells, human breast cancer cells, human liver cancer cells, human pancreatic cancer cells or gastric cancer cells, etc., more preferably human lung cancer cells. In some specific embodiments, the IC of the above compounds with anti-tumor activity against A549 cells (human lung cancer cells), MDA-MB-231 cells (human breast cancer cells), HepaRG cells (human liver cancer cells), PANC-1 cells (human pancreatic cancer cells), MKN-1 cells (human gastric cancer cells) is 1.17kcal / cm3, and ... 50 They were 24.1μg / mL, 90.4μg / mL, 77.2μg / mL, 33.2μg / mL and 47.0μg / mL respectively.

[0062] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0063] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0064] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0065] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present application description and examples are exemplary only.

[0066] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0067] The technical solutions described in the present invention, unless otherwise specified, are all conventional solutions in the art, and the reagents or raw materials used, unless otherwise specified, are purchased from commercial channels or are publicly available.

[0068] Mobotinib succinate used in the present invention was purchased from Jinan Shenlikang Chemical Technology Co., Ltd.; methanol and acetonitrile were purchased from Merck (chromatographic grade); hydrochloric acid, phosphoric acid, sodium hydroxide, and triethylamine were purchased from Sinopharm Chemical Reagent Co., Ltd. (analytical grade); MTT was purchased from Beyotime, DMEM, RPMI-1640, and fetal bovine serum were purchased from Gibco.

[0069] Example 1 Preparation of compounds with anti-tumor activity

[0070] Preparation of crude product: Take 300 mg of mobotinib raw material, add 150 mL of methanol to dissolve, then add 75 mL of 1 M NaOH solution, and place at 80° C. to react for 16 hours; then add 1 M hydrochloric acid solution to neutralize the reaction solution to neutrality; then remove the methanol in the solution by rotary evaporator; collect the solution after rotary evaporation and freeze-dry it to obtain a crude product of the compound with anti-tumor activity.

[0071] Purification of crude product: 300 mg of crude new compound was dissolved in 6 mL of 50% methanol water and purified by semi-preparative liquid chromatography. The chromatographic conditions were: X Select CSH C 18 XP Column (30×150mm, 5μm); flow rate is 60mL / min; detection wavelength: 280nm; mobile phase A: water, mobile phase B: acetonitrile; the gradient elution program is: 0-7min, 45% B→55% B; 7min-8.5min, 55% B→95% B; 8.5min-10min, 95% B→95% B; 10min-11min, 95% B→45% B; 11min-14min, 45% B→45% B; collect the sample solution for 7.8min. Remove the salt from the crude product; collect the purified solution, remove the methanol in the solution again by rotary evaporator, and collect the remaining solution; obtain the pure compound with anti-tumor activity by freeze drying, with a yield of 58.9%; finally, the chromatographic purity of the new compound was detected by high performance liquid chromatography, and the purity was 97.8%;

[0072] Example 2 Structural Characterization of New Antitumor Compounds

[0073] Liquid chromatography: High performance liquid chromatography was used to detect new compounds with anti-tumor activity, using Phenomenon Gemini C 18 The column was 4.6 mm × 250 mm, 5 μm, with a flow rate of 1.0 mL / min and a detection wavelength of 280 nm. 2 m mol / L potassium dihydrogen phosphate solution (containing 0.4% triethylamine, adjusted to pH 2.5 with phosphoric acid)-acetonitrile (90:10) was used as mobile phase A, and acetonitrile was used as mobile phase B. The gradient elution procedure was as follows: 0-2 min, 10% B→10% B; 2 min-8 min, 10% B→30% B; 8 min-25 min, 30% B→40% B; 25 min-40 min, 40% B→90% B; 40 min-45 min, 90% B→90% B; 45 min-46 min, 90% B→10% B; 46 min-55 min, 10% B→10% B. The chromatogram of the anti-tumor active compound obtained by the detection is shown in FIG. Figure 1 shown.

[0074] Mass spectrometry detection: Take 5 mg of the new compound with anti-tumor activity, dissolve it in 50% methanol water to a concentration of 1 mg / mL, then gradually dilute it to 100 ng / mL, and detect it by mass spectrometer to determine the molecular weight. Figure 2 shown.

[0075] Nuclear magnetic resonance spectrum detection: 10 mg and 30 mg of the new compound with anti-tumor activity were taken respectively, dissolved in deuterated DMSO and then tested on the machine. The one-dimensional nuclear magnetic resonance hydrogen spectrum is shown in Figure 3 As shown, the one-dimensional carbon NMR spectrum is as follows Figure 4 As shown, the two-dimensional NMR spectrum is Figure 5 shown.

[0076] Example 3 Study on the antitumor activity of new compounds in vitro

[0077] New antitumor active compounds were selected for in vitro antitumor activity experiments. A549 (human lung cancer cells), MDA-MB-231 (human breast cancer cells), HepaRG (human liver cancer cells), PANC-1 (human pancreatic cancer cells), and MKN-1 (human gastric cancer cells) cell lines were selected, and the MTT (3-(4,5-dimethylthiazole-2)-2,5-diphenyltetrazolium bromide) method was used to study the inhibitory activity of the new antitumor active compounds on five human cancer cell lines, and the drug concentration when the inhibition rate reached 50%, i.e., IC 50 The specific steps are as follows:

[0078] (1) Cell culture: A549, MDA-MB-231, HepaRG, PANC-1, and MKN-1 cells were cultured in a 37°C, 5% CO2 incubator. The culture medium for A549, MDA-MB-231, PANC-1, and MKN-1 cells was DMEM, and the culture medium for HepaRG cells was RPMI-1640. 10% fetal bovine serum, 100 U / mL penicillin, and 100 μg / mL streptomycin were added to the culture medium.

[0079] (2) MTT test: Five tumor cells in the logarithmic growth phase were digested with trypsin and the culture medium was prepared to 1×10 5 / mL cell suspension, then inoculate the cell suspension in a 96-well plate, add different concentrations (120, 60, 30, 15, 7.5μg / mL) of new anti-tumor active compounds after 24 hours, set 8 replicates for each concentration, discard the supernatant after 48 hours, wash twice with PBS, add 100μL of freshly prepared MTT solution (1mg / mL) to each well. Place in an incubator and continue incubation for 4 hours, then carefully discard the supernatant in the 96-well plate, add 150μL DMSO to each well and react at 37°C in the dark for 30 minutes. After the crystals are completely dissolved, use an enzyme reader to detect the optical density (OD) of each well at 490nm;

[0080] (3) Calculation of inhibition rate: Growth inhibition rate = (1-OD value of experimental group / OD value of control group) × 100%;

[0081] (4) Calculate IC based on concentration and growth inhibition rate 50 .

[0082] The results are as follows Figure 6-10 The results show that the new anti-tumor active compound has different degrees of growth inhibition on the above tumor cells, and the inhibitory effect on A549 cells is more obvious. The IC of this new anti-tumor active compound on A549 cells, MDA-MB-231 cells, HepaRG cells, PANC-1 cells, MKN-1 cells 50 They were 24.1μg / mL, 90.4μg / mL, 77.2μg / mL, 33.2μg / mL and 47.0μg / mL respectively.

[0083] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A compound having anti-tumor activity and a pharmaceutically acceptable salt thereof, wherein the compound has a molecular formula of C 30 H 37 N7O5, its structural formula is:

2. The method for preparing the compound having anti-tumor activity according to claim 1, characterized in that: Mobotinib is dissolved in methanol, subjected to degradation reaction under alkaline conditions, and purified to obtain the compound with anti-tumor activity.

3. The preparation method according to claim 2, characterized in that: After the degradation reaction, the method further comprises a step of adjusting the pH to neutral.

4. The preparation method according to any one of claims 2 to 3, characterized in that: The purification includes purification using semi-preparative liquid chromatography.

5. The preparation method according to claim 4, characterized in that: The chromatographic conditions are: Chromatographic column: X Select CSH C 18 XP Column (30×150mm, 5μm); flow rate: 60mL / min; detection wavelength: 280nm; mobile phase A: water, mobile phase B: acetonitrile; The gradient elution program was as follows: 0-7 min, 45% B→55% B; 7 min-8.5 min, 55% B→95% B; 8.5 min-10 min, 95% B→95% B; 10 min-11 min, 95% B→45% B; 11 min-14 min, 45% B→45% B; The sample solution was collected for 7.8 min.

6. The preparation method according to claim 5, characterized in that: The purification further comprises removing the organic solvent by rotary evaporation.

7. A pharmaceutical composition, characterized in that The invention comprises the compound with anti-tumor activity as claimed in claim 1 and a pharmaceutically acceptable salt thereof.

8. A preparation, characterized in that It comprises the compound with anti-tumor activity as claimed in claim 1 and its pharmaceutically acceptable salt or the pharmaceutical composition as claimed in claim 7 and a pharmaceutically acceptable carrier.

9. Use of the compound having anti-tumor activity as claimed in claim 1 and its pharmaceutically acceptable salt or the pharmaceutical composition as claimed in claim 7 in the preparation of a preparation having anti-tumor cell activity.

10. The use according to claim 9, characterized in that: The tumor cells include human lung cancer cells, human breast cancer cells, human liver cancer cells, human pancreatic cancer cells or human gastric cancer cells.

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