Small-molecule inhibitor, synthesis method and application

Abstract

The invention relates to the technical field of pharmacy, in particular to a small-molecule inhibitor, a synthesis method and application. The small-molecule inhibitor is a chemical structural formula shown in a formula (I) or a pharmaceutically acceptable salt of the chemical structural formula shown in the formula (I). The small-molecule inhibitor disclosed by the invention has biological activity, can effectively inhibit cell mitosis, and has important significance for preventing abnormal cell proliferation and cancer. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and more particularly to a small molecule inhibitor, a synthesis method and an application thereof. Background Art

[0002] The cell cycle refers to the orderly series of physiological and biochemical processes that a cell undergoes from the end of one division to the end of the next. The cell cycle can be divided into two main phases: interphase and mitosis. Mitosis is a key process in the cell cycle, responsible for equally distributing the genetic material of a parent cell into its two daughter cells. This process is crucial for maintaining normal tissue growth and repair. Mitosis involves multiple complex steps, including chromosome condensation, spindle formation, chromosome segregation, and cytoplasmic division. Precise regulation of these steps is crucial for preventing abnormal cell proliferation and the occurrence of cancer.

[0003] Under normal circumstances, the various phases of the cell cycle are strictly regulated, ensuring that cells divide and proliferate at the appropriate times. However, in cancer, this regulatory mechanism is often disrupted, leading to uncontrolled cell cycle growth and continuous cell division and proliferation. Many types of cancer exhibit abnormal cell cycle regulation, resulting in uncontrolled cell proliferation. Inhibiting mitosis can prevent the division and spread of cancer cells, thereby achieving therapeutic goals and is an important strategy for treating various diseases, especially cancer. Therefore, there is a need to develop small molecule inhibitors that can inhibit cell mitosis. Summary of the Invention

[0004] To solve the above problems, the present invention provides a small molecule inhibitor, a synthesis method and an application.

[0005] The present invention is achieved through the following technical solutions:

[0006] A small molecule inhibitor, wherein the small molecule inhibitor is a chemical formula represented by formula (I) or a pharmaceutically acceptable salt including the chemical formula represented by formula (I);

[0007]

[0008] wherein R1 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, trifluoromethyl or trifluoromethoxy.

[0009] R2 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, trifluoromethyl or trifluoromethoxy.

[0010] R3 is methyl, ethyl or allyl.

[0011] R4 is methoxy or ethoxy.

[0012] R5 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, trifluoromethoxy or trifluoromethyl.

[0013] The synthesis method of the small molecule inhibitor specifically comprises the following steps:

[0014] (1) Compound 1 is subjected to an alkylation reaction with an alkyl iodide in the presence of a basic catalyst to prepare compound 2.

[0015] (2) In the first step, compound 2 is subjected to a condensation reaction with acetaldehyde under the action of an alkaline catalyst to obtain a reaction product; in the second step, the reaction product is subjected to a dehydration reaction under acidic conditions to prepare compound 3.

[0016] (3) Compound 3 is reacted with compound 4, methanol, 2,6-bis[(4S)-4-phenyl-2-oxazolinyl]pyridine and (5aS,10bR)-2-mesityl-4,5a,6,10b-tetrahydro-2H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-11-ium tetrafluoroborate in the presence of a copper catalyst to undergo an asymmetric conjugate addition reaction to prepare the small molecule inhibitor.

[0017]

[0018] In step 1, the molar ratio of compound 1, alkyl iodide and alkaline catalyst is 1:1.1-1.3:2.5-3.5.

[0019] In step 2, the molar ratio of compound 2, acetaldehyde and alkaline catalyst is 1:4-6:0.1-0.12.

[0020] In step 3, the molar ratio of compound 3 to compound 4, methanol, 2,6-bis[(4S)-4-phenyl-2-oxazolinyl]pyridine and (5aS,10bR)-2-mesityl-4,5a,6,10b-tetrahydro-2H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-11-ium tetrafluoroborate and copper catalyst is 1.4-1.6:1:4-6:0.09-0.11:0.04-0.06:0.04-0.06.

[0021] Preferably, the solvent for the reaction in step 1 is acetonitrile or N,N-dimethylformamide; the alkaline catalyst in step 1 is sodium carbonate, potassium carbonate, cesium carbonate or rubidium carbonate; the reaction temperature in step 1 is 80° C. to 100° C., and the reaction time is 10 h to 15 h.

[0022] Preferably, the solvent for the reaction in step 2 is tetrahydrofuran; the alkaline catalyst in step 2 is DBU; the reaction temperature of the first step of step 2 is -30°C to -20°C, and the reaction time is 14h to 18h; the reaction temperature of the second step is 90°C to 110°C, and the reaction time is 20min to 40min.

[0023] Preferably, the solvent for the reaction in step 3 is tetrahydrofuran, toluene or dichloromethane; the copper catalyst in step 3 is copper tetraacetonitrile hexafluorophosphate; the reaction temperature in step 3 is 10° C. to 30° C., and the reaction time is 10 h to 15 h.

[0024] Preferably, the alkyl iodide is methyl iodide, ethyl iodide or allyl iodide.

[0025] Preferably, the acidic condition in step 2 is achieved by adding a mixed solution of sulfuric acid, acetic acid and water to the reaction product.

[0026] Preferably, the volume ratio of sulfuric acid, acetic acid and water is 1:15:5.

[0027] The small molecule inhibitor is used in the preparation of reagents for inhibiting cell mitosis or anti-tumor drugs.

[0028] Preferably, the anti-tumor tumor cells are HeLa cells.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] The present invention provides a small molecule inhibitor. The small molecule inhibitor has biological activity, can effectively inhibit cell mitosis, and exhibits high efficiency, specificity, low toxicity and wide applicability. Experimental results show that the inhibitor can effectively interfere with the mitotic process, leading to metaphase arrest and exit failure of tumor cells, thereby inhibiting their proliferation. Compared with the prior art, the small molecule inhibitor of the present invention has higher anti-tumor activity and lower toxicity to normal cells. At the same time, the preparation process is simple and low-cost, and it is suitable for large-scale industrial production. In addition, its good biocompatibility and environmental advantages further enhance its potential in clinical applications. The present invention provides a new, efficient and safe strategy for tumor treatment, which has important scientific significance and broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. 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 any creative work.

[0032] Figure 1 This is a schematic diagram of the experimental operation flow for testing the effects of small molecules on cells in the present invention.

[0033] Figure 2 This is a schematic diagram of the effects of the small molecule inhibitors of the present invention on cells.

[0034] Figure 3 This is a statistical graph showing the mitotic phenotype of cells after treatment with the small molecule inhibitor of the present invention.

[0035] Figure 4 This is the NMR spectrum verification result diagram of A5 of the present invention.

[0036] Figure 5 This is the verification result of the B5 nuclear magnetic spectrum of the present invention.

[0037] Figure 6 This is the C5 NMR spectrum verification result diagram of the present invention.

[0038] Figure 7 This is the D5 NMR spectrum verification result diagram of the present invention. DETAILED DESCRIPTION

[0039] To facilitate understanding of the present invention, the present invention will be described more fully below, along with preferred embodiments thereof. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a more thorough and comprehensive understanding of the disclosure of the present invention.

[0040] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in this specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0041] The technical solution of the present invention will be further described below with reference to specific embodiments.

[0042] The present invention has discovered for the first time that a small molecule inhibitor having the chemical structure described in formula (I) can significantly inhibit tumor cell division;

[0043]

[0044] wherein R1 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, trifluoromethyl or trifluoromethoxy.

[0045] R2 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, trifluoromethyl or trifluoromethoxy.

[0046] R3 is methyl, ethyl or allyl.

[0047] R4 is methoxy or ethoxy.

[0048] R5 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, trifluoromethoxy or trifluoromethyl.

[0049] The synthesis method of the small molecule inhibitor is as follows:

[0050] (1) Compound 1 is subjected to an alkylation reaction with an alkyl iodide in the presence of a basic catalyst to prepare compound 2.

[0051] (2) In the first step, compound 2 is subjected to a condensation reaction with acetaldehyde under the action of an alkaline catalyst to obtain a reaction product; in the second step, the reaction product is subjected to a dehydration reaction under acidic conditions to prepare compound 3.

[0052] (3) Compound 3 was reacted with compound 4, methanol, 2,6-bis[(4S)-4-phenyl-2-oxazolinyl]pyridine and (5aS,10bR)-2-mesityl-4,5a,6,10b-tetrahydro-2H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-11-ium tetrafluoroborate in the presence of a copper catalyst to produce a small molecule inhibitor.

[0053]

[0054] In step 1, the molar ratio of compound 1, alkyl iodide and alkaline catalyst is 1:1.1-1.3:2.5-3.5.

[0055] In step 2, the molar ratio of compound 2, acetaldehyde and alkaline catalyst is 1:4-6:0.1-0.12.

[0056] In step 3, the molar ratio of compound 3 to compound 4, methanol, 2,6-bis[(4S)-4-phenyl-2-oxazolinyl]pyridine and (5aS,10bR)-2-mesityl-4,5a,6,10b-tetrahydro-2H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-11-ium tetrafluoroborate and copper catalyst is 1.4-1.6:1:4-6:0.09-0.11:0.04-0.06:0.04-0.06.

[0057] In a specific embodiment, the solvent for the reaction in step 1 is acetonitrile or N,N-dimethylformamide.

[0058] The alkaline catalyst in step 1 is sodium carbonate, potassium carbonate, cesium carbonate or rubidium carbonate.

[0059] The reaction temperature of step 1 is 80° C. to 100° C., and the reaction time is 10 h to 15 h.

[0060] In a specific embodiment, the solvent for the reaction in step 2 is tetrahydrofuran.

[0061] The basic catalyst in step 2 is DBU.

[0062] The first step of step 2 has a reaction temperature of -30°C to -20°C and a reaction time of 14 to 18 hours, and the second step has a reaction temperature of 90 to 110°C and a reaction time of 20 to 40 minutes.

[0063] In a specific embodiment, the solvent for the reaction in step 3 is tetrahydrofuran, toluene or dichloromethane.

[0064] The copper catalyst in step 3 is tetraacetonitrile copper hexafluorophosphate.

[0065] The reaction temperature of step 3 is 10° C. to 30° C., and the reaction time is 10 h to 15 h.

[0066] In a specific embodiment, the alkyl iodide is methyl iodide, ethyl iodide or allyl iodide.

[0067] In a specific embodiment, the acidic condition in step 2 is achieved by adding a mixed solution of sulfuric acid, acetic acid and water to the reaction product.

[0068] Example 1: A method for synthesizing a small molecule inhibitor

[0069] For small molecule inhibitors The chemical structure was carried out and synthesized.

[0070] (1) 1.0 equivalent of A1, 1.1 equivalent of iodomethane, and 2.5 equivalents of sodium carbonate were stirred at 80°C for 10 h in acetonitrile as solvent for alkylation reaction, and A2 was separated by chromatography.

[0071]

[0072] (2) In the first step, 1.0 equivalent of A2, 4.0 equivalents of acetaldehyde, and 0.1 equivalent of DBU were stirred at -20°C for 14 hours in tetrahydrofuran as solvent to carry out a condensation reaction to obtain a reaction product; the solvent was dried and the second step was carried out, a mixture of sulfuric acid, acetic acid, and water was added to the reaction product, the volume ratio of sulfuric acid, acetic acid, and water being 1:15:5, and a dehydration reaction was carried out at 90°C for 20 minutes. A3 was separated by chromatography to obtain A3.

[0073]

[0074] (3) 1.4 equivalents of A3, 1.0 equivalent of 4, 4.0 equivalents of methanol, 0.04 equivalent of copper tetraacetonitrile hexafluorophosphate, 0.09 equivalent of 2,6-bis[(4S)-4-phenyl-2-oxazolinyl]pyridine, and 0.04 equivalent of (5aS,10bR)-2-mesityl-4,5a,6,10b-tetrahydro-2H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-11-ium tetrafluoroborate were reacted in tetrahydrofuran as solvent at 10°C for 10 h, and compound A5 was obtained by chromatography.

[0075]

[0076] The compound A5 was verified by NMR spectrum, and the results were as follows Figure 4 As shown, it is shown that the chemical structure is synthesized

[0077] Example 2: A method for synthesizing a small molecule inhibitor

[0078] For small molecule inhibitors The chemical structure was carried out and synthesized.

[0079] (1) 1.0 equivalent of B1, 1.2 equivalents of iodomethane, and 3.0 equivalents of sodium carbonate were stirred at 90°C for 12 hours in acetonitrile as solvent for alkylation reaction, and B2 was separated by chromatography.

[0080]

[0081] (2) In the first step, 1.0 equivalent of B2, 5.0 equivalents of acetaldehyde, and 0.11 equivalents of DBU were stirred at -25°C for 15 hours in tetrahydrofuran as a solvent to carry out a condensation reaction to obtain a reaction product; the solvent was dried and the second step was carried out, a mixture of sulfuric acid, acetic acid, and water was added to the reaction product, the volume ratio of sulfuric acid, acetic acid, and water being 1:15:5, and a dehydration reaction was carried out at 100°C for 30 minutes. B3 was separated by chromatography.

[0082]

[0083] (3) 1.5 equivalents of B3, 1.0 equivalent of 4, 5.0 equivalents of methanol, 0.05 equivalent of copper tetraacetonitrile hexafluorophosphate, 0.1 equivalent of 2,6-bis[(4S)-4-phenyl-2-oxazolinyl]pyridine, and 0.05 equivalent of (5aS,10bR)-2-mesityl-4,5a,6,10b-tetrahydro-2H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-11-ium tetrafluoroborate were reacted in tetrahydrofuran as solvent at 20°C for 13 hours, and compound B5 was obtained by chromatography.

[0084]

[0085] The compound B5 was verified by NMR spectrum, and the results were as follows Figure 5 As shown, it is shown that the chemical structure is synthesized

[0086] Example 3: A method for synthesizing a small molecule inhibitor

[0087] For small molecule inhibitors The chemical structure was carried out and synthesized.

[0088] (1) 1.0 equivalent of A1, 1.3 equivalents of iodoethane, and 3.5 equivalents of sodium carbonate were stirred at 100°C for 15 h in acetonitrile as solvent for alkylation reaction, and C2 was separated by chromatography.

[0089]

[0090] (2) In the first step, 1.0 equivalent of C2, 6.0 equivalents of acetaldehyde, and 0.12 equivalents of DBU were stirred at -30°C for 18 hours in tetrahydrofuran as a solvent to carry out a condensation reaction to obtain a reaction product; the solvent was dried and the second step was carried out, a mixture of sulfuric acid, acetic acid, and water was added to the reaction product, the volume ratio of sulfuric acid, acetic acid, and water being 1:15:5, and a dehydration reaction was carried out at 110°C for 40 minutes, and C3 was separated by chromatography.

[0091]

[0092] (3) 1.6 equivalents of C3, 1.0 equivalent of 4, 6.0 equivalents of methanol, 0.06 equivalent of copper tetraacetonitrile hexafluorophosphate, 0.11 equivalent of 2,6-bis[(4S)-4-phenyl-2-oxazolinyl]pyridine, and 0.06 equivalent of (5aS,10bR)-2-mesityl-4,5a,6,10b-tetrahydro-2H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-11-ium tetrafluoroborate were reacted in tetrahydrofuran as solvent at 30°C for 15 hours, and compound C5 was obtained by chromatography.

[0093]

[0094] The compound C5 was verified by NMR spectrum, and the results were as follows Figure 6 As shown, it is shown that the chemical structure is synthesized

[0095] Example 4: A method for synthesizing a small molecule inhibitor

[0096] For small molecule inhibitors The chemical structure was carried out and synthesized.

[0097] (1) 1.0 equivalent of A1, 1.3 equivalents of iodomethane, and 3.5 equivalents of sodium carbonate were stirred at 100°C for 15 hours in acetonitrile as solvent for alkylation reaction, and A2 was separated by chromatography.

[0098]

[0099] (2) In the first step, 1.0 equivalent of A2, 6.0 equivalents of acetaldehyde, and 0.12 equivalents of DBU were stirred at -30°C for 18 hours in tetrahydrofuran as a solvent to carry out a condensation reaction to obtain a reaction product; the solvent was dried by rotary evaporation to carry out the second step, and a mixture of sulfuric acid, acetic acid, and water was added to the reaction product in a volume ratio of sulfuric acid, acetic acid, and water of 1:15:5. The mixture was dehydrated at 110°C for 40 minutes, and A3 was separated by chromatography.

[0100]

[0101] (3) 1.6 equivalents of A3, 1.0 equivalent of 4, 6.0 equivalents of ethanol, 0.06 equivalent of copper tetraacetonitrile hexafluorophosphate, 0.11 equivalent of 2,6-bis[(4S)-4-phenyl-2-oxazolinyl]pyridine, and 0.06 equivalent of (5aS,10bR)-2-mesityl-4,5a,6,10b-tetrahydro-2H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-11-ium tetrafluoroborate were reacted in tetrahydrofuran as solvent at 30°C for 15 hours, and compound D5 was obtained by chromatography.

[0102]

[0103] The compound D5 was verified by NMR spectrum, and the results were as follows Figure 7 As shown, it is shown that the chemical structure is synthesized

[0104] It should be noted that in all embodiments, the solvent for the reaction in step 1 is acetonitrile or N,N-dimethylformamide; the alkaline catalyst in step 1 is sodium carbonate, potassium carbonate, cesium carbonate or rubidium carbonate; and the solvent for the reaction in step 3 is tetrahydrofuran, toluene or dichloromethane, all of which can be used to synthesize the small molecule inhibitor.

[0105] Experimental Example 1: Effects of small molecule inhibitors on cell mitosis

[0106] Experimental steps, such as Figure 1 As shown:

[0107] 1. Seed HeLa cells on a 12 mm diameter glass coverslip.

[0108] 2. Add thymidine to a final concentration of 2 mM to synchronize HeLa cells to the G1 / S phase.

[0109] 3. After 16 hours of Thymidine treatment, the cells were released and washed three times with preheated PBS, each time for 5 minutes.

[0110] 4. Release for 9 hours to allow cells to enter the G2 phase.

[0111] 5. Dilute the small molecule in Opti-MEM medium, pipette to mix well, and then treat HeLa cells with the medium containing the small molecule for 1 hour.

[0112] 6. After the small molecule treatment, HeLa cells were fixed with preheated PBS buffer containing a final concentration of 3.7% formaldehyde for 10 minutes.

[0113] 7. The fixed HeLa cells were perforated with PBS buffer containing 0.1% Triton X-100 for 3 minutes.

[0114] 8. Wash once with PBS and then block with BSA solution with a final concentration of 1% for 30 minutes.

[0115] 9. After blocking, use DM1A-FITC antibody to label the microtubules in the cells. The antibody incubation time is 30 minutes.

[0116] 10. Use DAPI to label DNA in cells to characterize the cell's chromatin (DNA staining during the interphase of the cell cycle) and chromosomes (DNA staining during mitosis).

[0117] The experimental results are as follows Figure 2 As shown, the left side of the figure shows DMSO as the negative control group and the small molecule inhibitor treatment group in Examples 1 to 4, respectively. The DV microscope randomly takes pictures, and the figure shows three fields of view, field of view 1, field of view 2, and field of view 3. It can be seen that after DMSO treatment, HeLa cells can enter and exit mitosis normally, the chromosome queues in the metaphase of mitosis are normal (blue), and the spindle composed of microtubules is normal (green). After small molecule treatment, different degrees of abnormal metaphase of mitosis are manifested, and mitosis exit fails. 50 mitotic cells were counted in each group, and the statistical data are shown as follows. Figure 3 As shown in the figure, green represents the percentage of cells in normal anaphase, indicating normal exit from mitosis; red represents the percentage of cells in erroneous metaphase alignment, indicating mitotic arrest; and blue represents the percentage of cells in normal metaphase. A percentage of blue below 50% is considered abnormal mitosis. Therefore, the small molecule inhibitors of the present invention can significantly inhibit tumor cell mitosis.

[0118] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0119] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. A small molecule inhibitor, characterized in that The small molecule inhibitor is a pharmaceutically acceptable salt of the chemical structure of formula (I) or a pharmaceutically acceptable salt thereof; wherein R1 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, trifluoromethyl or trifluoromethoxy; R2 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, trifluoromethyl or trifluoromethoxy; R3 is methyl, ethyl or allyl; R4 is methoxy or ethoxy; R5 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, trifluoromethoxy or trifluoromethyl.

2. The method for synthesizing a small molecule inhibitor according to claim 1, wherein: The specific steps include: (1) alkylating compound 1 with an alkyl iodide in the presence of a basic catalyst to prepare compound 2; (2) In the first step, compound 2 is reacted with acetaldehyde in the presence of a basic catalyst to obtain a reaction product; In the second step, the reaction product is dehydrated under acidic conditions to prepare compound 3; (3) Compound 3 is subjected to an asymmetric conjugate addition reaction with compound 4, methanol, 2,6-bis[(4S)-4-phenyl-2-oxazolinyl]pyridine and (5aS,10bR)-2-mesityl-4,5a,6,10b-tetrahydro-2H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-11-ium tetrafluoroborate in the presence of a copper catalyst to prepare the small molecule inhibitor; In step 1, the molar ratio of compound 1, alkyl iodide, and alkaline catalyst is 1:1.1-1.3:2.5-3.5; In step 2, the molar ratio of compound 2, acetaldehyde, and alkaline catalyst is 1:4-6:0.1-0.12; In step 3, the molar ratio of compound 3 to compound 4, methanol, 2,6-bis[(4S)-4-phenyl-2-oxazolinyl]pyridine and (5aS,10bR)-2-mesityl-4,5a,6,10b-tetrahydro-2H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazin-11-ium tetrafluoroborate and copper catalyst is 1.4-1.6:1:4-6:0.09-0.11:0.04-0.06:0.04-0.

06.

3. The method for synthesizing a small molecule inhibitor according to claim 2, wherein: The solvent for the reaction in step 1 is acetonitrile or N,N-dimethylformamide; The alkaline catalyst in step 1 is sodium carbonate, potassium carbonate, cesium carbonate or rubidium carbonate; The reaction temperature of step 1 is 80° C. to 100° C., and the reaction time is 10 h to 15 h.

4. The method for synthesizing a small molecule inhibitor according to claim 2, wherein: The solvent for the reaction in step 2 is tetrahydrofuran; The basic catalyst in step 2 is DBU; The first step of step 2 has a reaction temperature of -30°C to -20°C and a reaction time of 14 to 18 hours, and the second step has a reaction temperature of 90 to 110°C and a reaction time of 20 to 40 minutes.

5. The method for synthesizing a small molecule inhibitor according to claim 2, wherein: The solvent for the reaction in step 3 is tetrahydrofuran, toluene or dichloromethane; The copper catalyst in step 3 is tetraacetonitrile copper hexafluorophosphate; The reaction temperature of step 3 is 10° C. to 30° C., and the reaction time is 10 h to 15 h.

6. The method for synthesizing a small molecule inhibitor according to claim 2, wherein: The alkyl iodide is methyl iodide, ethyl iodide or allyl iodide.

7. The method for synthesizing a small molecule inhibitor according to claim 2, wherein: The acidic condition in step 2 is achieved by adding a mixed solution of sulfuric acid, acetic acid and water to the reaction product.

8. The method for synthesizing a small molecule inhibitor according to claim 7, wherein: The volume ratio of the sulfuric acid, acetic acid and water is 1:15:

5.

9. Use of the small molecule inhibitor according to claim 1 in the preparation of an agent for inhibiting cell mitosis or an anti-tumor drug.

10. The use according to claim 9, characterized in that The anti-tumor tumor cells are HeLa cells.

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