Phthalimide derivative containing N-1, 2, 4-triazole unit as well as preparation method and application of phthalimide derivative

Abstract

The invention belongs to the field of medicines, and discloses a compound with a structure as shown in a formula I. A preparation method of the compound comprises the following steps: heating phthalic anhydride molecules and 3-amino-1, 2, 4-triazole in a glacial acetic acid solution under reflux to carry out acylation reaction, so as to obtain a phthalimide derivative I containing an N-1, 2, 4-triazole unit; the phthalimide derivative containing the N-1, 2, 4-triazole unit is a novel compound, has an obvious inhibition effect on human pancreatic cancer cells, human gastric cancer cells, human brain astroblastoma cells and human liver cancer cells, particularly has a more prominent inhibition effect on the human pancreatic cancer cells, and can be used for preparing a novel compound. The compound can be used as a potential novel anti-tumor candidate drug molecule. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of medicine, and particularly relates to a phthalimide derivative containing an N-1,2,4-triazole unit, a preparation method thereof, and an application thereof. Background Art

[0002] Tumors, especially malignant tumors (cancers), have become one of the major diseases seriously threatening human health globally. According to statistics, the number of death cases caused by malignant tumors reaches millions every year, and with the influence of factors such as population aging, environmental pollution, and bad lifestyle, the incidence rate of cancer is still continuously rising. Common malignant tumors include lung cancer, breast cancer, gastric cancer, liver cancer, and colorectal cancer, etc. These diseases not only endanger the lives of patients but also bring a heavy economic burden to families and society. At present, the treatment of tumors mainly includes various means such as surgical resection, radiotherapy, and chemotherapy. However, these treatment methods all have certain limitations. For example, surgical treatment is only applicable to early-stage tumor patients and has a recurrence risk; radiotherapy is likely to cause damage to normal tissues, resulting in serious side effects; although chemotherapy is one of the most widely used treatment methods in clinical practice, its anti-tumor drugs generally have problems such as strong drug resistance and large toxic side effects, which limit its long-term efficacy. Therefore, the research and development of new, highly efficient, and low-toxic-side-effect anti-tumor drugs have important practical significance for improving the survival rate and quality of life of cancer patients. Summary of the Invention

[0003] Object of the Invention: The first object of the present invention is to provide a phthalimide derivative containing an N-1,2,4-triazole unit with anti-tumor activity. The second object of the present invention is to provide a preparation method of the phthalimide derivative containing an N-1,2,4-triazole unit. The third object of the present invention is to provide an application of the phthalimide derivative containing an N-1,2,4-triazole unit in anti-tumor.

[0004] Technical Solution: The phthalimide derivative containing an N-1,2,4-triazole unit of the present invention has a structural formula as shown in Formula I:

[0005]

[0006] Wherein, R is selected from 3,4,5,6-tetrahydro, 3-nitro, 3-hydroxy, 3-fluoro, 4-fluoro, 4-tert-butyl, 4-nitro, 3,4,5,6-tetrabromo, 3,4,5,6-tetrachloro, 3,4,5,6-tetrafluoro.

[0007] The preparation method of the phthalimide derivative containing N-1,2,4-triazole unit of the present invention comprises heating phthalic anhydride molecules and 3-amino-1,2,4-triazole in glacial acetic acid solution under reflux to produce an acylation reaction to obtain the phthalimide derivative containing N-1,2,4-triazole unit. The synthesis route is as follows:

[0008]

[0009] The present invention discloses an application of a phthalimide derivative containing an N-1,2,4-triazole unit in anti-tumor cell therapy. The tumor cells include human pancreatic cancer cells (PANC-1), human gastric cancer cells (SGC-7901), human astrocytic glioblastoma cells (U-87MG), and human hepatocellular carcinoma cells (HepG2).

[0010] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: (1) The phthalimide derivative containing N-1,2,4-triazole units described in the present invention is a new type of compound; (2) The preparation method of the phthalimide derivative containing N-1,2,4-triazole units described in the present invention has a novel and efficient reaction, simple operation, and readily available raw materials; (3) The phthalimide derivative containing N-1,2,4-triazole units described in the present invention can effectively inhibit the proliferation of tumor cells and can be used as a potential new anti-tumor candidate drug molecule. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 Example 1 Final product 1 H-NMR spectrum; Figure 2 Example 1 Final product 13 C-NMR spectrum;

[0012] Figure 3 Example 2 Final product 1 H-NMR spectrum; Figure 4 Example 2 Final product 13 C-NMR spectrum;

[0013] Figure 5 Example 3 Final product 1 H-NMR spectrum; Figure 6 Example 3 Final product 13 C-NMR spectrum;

[0014] Figure 7 Example 4 Final product 1 H-NMR spectrum; Figure 8 Example 4 Final product 13 C-NMR spectrum;

[0015] Figure 9 1H-NMR spectrum of the final product of Example 5 1 ; Figure 10 13C-NMR spectrum of the final product of Example 5 13 ;

[0016] Figure 11 1H-NMR spectrum of the final product of Example 6 1 ; Figure 12 13C-NMR spectrum of the final product of Example 6 13 ;

[0017] Figure 13 1H-NMR spectrum of the final product of Example 7 1 ; Figure 14 13C-NMR spectrum of the final product of Example 7 13 ;

[0018] Figure 15 1H-NMR spectrum of the final product of Example 8 1 ; Figure 16 13C-NMR spectrum of the final product of Example 8 13 ;

[0019] Figure 17 1H-NMR spectrum of the final product of Example 9 1 ; Figure 18 13C-NMR spectrum of the final product of Example 9 13 ;

[0020] Figure 19 [[ID=5!]]1H-NMR spectrum of the final product of Example 10 1 ; Figure 20 13C-NMR spectrum of the final product of Example 10 13 ;

[0021] Figure 21 1H-NMR spectrum of the final product of Example 11 1 ; Figure 22 13C-NMR spectrum of the final product of Example 11 13 . Detailed implementation manners

[0022] The technical solutions in the specific embodiments of the present invention will be described below.

[0023] Example 1

[0024] The phthalimide derivative containing an N-1,2,4-triazole unit. The chemical name is 2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione, and the English name is 2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione. The structural formula is as follows;

[0025]

[0026] Synthesis of 2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione:

[0027]

[0028] Phthalic anhydride (130 mg) and 3-amino-1,2,4-triazole (84 mg) were added to glacial acetic acid (5 mL). After mixing evenly, the mixture was heated under reflux at 120 °C for 4 hours. The reaction process was monitored by TLC. After the reaction was completed, heating was stopped, and 70 mL of purified water was slowly added to quench the reaction, and stirring was continued for 1 hour. After the reaction was completed, the solid crude product was recovered by suction filtration and separated by silica gel column chromatography. The eluent was petroleum ether:ethyl acetate = 4:1, and the white solid target product DY1 was finally obtained.

[0029] The target compound DY1 was a white needle-like crystal with a yield of 55.86%; 1 H NMR (600 MHz, DMSO-d6) δ 14.53 (s, 1H), 8.77 (s, 1H), 8.01 (dt, 2H), 7.95 (dd, 2H). 13 C NMR (151 MHz, DMSO-d6) δ 166.67, 150.58, 145.73, 135.81, 131.55, 124.47.

[0030] Example 2

[0031] The phthalimide derivative containing an N-1,2,4-triazole unit, R = 3,4,5,6-tetrahydro. The chemical name is 2-(1H-1,2,4-triazol-3-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione, and the English name is 2-(1H-1,2,4-triazol-3-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione. The structural formula is as follows;

[0032]

[0033] Synthesis of 2-(1H-1,2,4-triazol-3-yl)-4,5,6,7-tetrahydro-1H-isoindoline-1,3(2H)-dione

[0034]

[0035] Add 3,4,5,6-tetrahydrophthalic anhydride (152 mg) and 3-amino-1,2,4-triazole (84 mg) into glacial acetic acid (5 mL). After mixing evenly, heat under reflux at 120 °C for 4 hours. Monitor the reaction process by TLC. After the reaction is completed, stop heating, slowly add 70 mL of purified water to quench the reaction, and continue stirring for 1 hour. After the reaction is over, recover the solid crude product by suction filtration and separate it by silica gel column chromatography. The eluent is petroleum ether:ethyl acetate = 4:1, and finally obtain the white solid target product DY2.

[0036] The target compound DY2 is a white needle-like crystal with a yield of 51.28%; 1 H NMR (600 MHz, DMSO-d6) δ 14.39 (s, 1H), 8.68 (s, 1H), 2.34 (p, 4H), 1.73 (p, 4H). 13 C NMR (151 MHz, DMSO-d6) δ 169.31, 150.66, 145.51, 142.57, 21.18, 20.20.

[0037] Example 3

[0038] The phthalimide derivative containing N-1,2,4-triazole unit, R = 3-nitro. The chemical name is 4-nitro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione, and the English name is 4-nitro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione. The structural formula is as follows;

[0039]

[0040] Synthesis of 4-nitro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione

[0041]

[0042] 3-Nitrophthalic anhydride (193 mg) and 3-amino-1,2,4-triazole (84 mg) were added to glacial acetic acid (5 mL). After mixing evenly, the mixture was heated under reflux at 120 °C for 4 hours. The reaction process was monitored by TLC. After the reaction was completed, heating was stopped, and 70 mL of purified water was slowly added to quench the reaction, and stirring was continued for 1 hour. After the reaction was completed, the solid crude product was recovered by suction filtration and separated by silica gel column chromatography. The eluent was petroleum ether:ethyl acetate = 4:1, and the white solid target product DY3 was finally obtained.

[0043] The target compound DY3 was a white needle-like crystal with a yield of 61.53%; 1 H NMR (600 MHz, DMSO-d6) δ 14.57 (s, \alpha H), 8.78 (s, \alpha H), 8.39 (d, \alpha H), 8.29 (d, \alpha H), 8.15 (t, \alpha H). 13 C NMR (151 MHz, DMSO-d6) δ 164.71, 162.07, 150.15, 145.80, 145.18, 137.33, 133.58, 129.60, 128.19, 123.29.

[0044] Example 4

[0045] The phthalimide derivative containing an N-1,2,4-triazole unit, R = - 3-hydroxy. The chemical name is 4-hydroxy-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione, and the English name is 4-hydroxy

[0046]

[0047] Synthesis of 4-hydroxy-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione

[0048]

[0049] 3-Hydroxyphthalic anhydride (164 mg) and 3-amino-1,2,4-triazole (84 mg) were added to glacial acetic acid (5 mL). After mixing evenly, the mixture was heated under reflux at 120 °C for 4 hours. The reaction process was monitored by TLC. After the reaction was completed, heating was stopped, and 70 mL of purified water was slowly added to quench the reaction, and stirring was continued for 1 hour. After the reaction was completed, the solid crude product was recovered by suction filtration and separated by silica gel column chromatography. The eluent was petroleum ether:ethyl acetate = 4:1, and the white solid target product DY4 was finally obtained. It should be noted that in the original text, there is an unclear "\alpha H" in the H NMR data. It is recommended to check and correct it according to the actual situation. Also, in the translation of chemical terms, it is best to refer to the standard chemical nomenclature for more accurate expression. Here, it is translated according to the general method.

[0050] The target compound DY4 is a white needle-like crystal with a yield of 55.43%; 1 H NMR (600 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.72 (dd, 1H), 7.41 (d, 1H), 7.32 (d, 1H). 13 C NMR (151 MHz, DMSO-d6) δ 166.60, 165.22, 156.53, 150.73, 145.63, 137.34, 133.33, 124.41, 115.29, 114.64.

[0051] Example 5

[0052] The phthalimide derivative containing an N-1,2,4-triazole unit, R = 3-fluoro. The chemical name is 4-fluoro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione, and the English name is 4-fluoro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione. The structural formula is as follows;

[0053]

[0054] Synthesis of 4-fluoro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione

[0055]

[0056] 3-Fluorophthalic anhydride (166 mg) and 3-amino-1,2,4-triazole (84 mg) were added to glacial acetic acid (5 mL). After mixing evenly, the mixture was heated under reflux at 120 °C for 4 hours. The reaction process was monitored by TLC. After the reaction was completed, heating was stopped, and 70 mL of purified water was slowly added to quench the reaction, and stirring was continued for 1 hour. After the reaction was completed, the solid crude product was recovered by suction filtration and separated by silica gel column chromatography. The eluent was petroleum ether:ethyl acetate = 4:1, and the white solid target product DY5 was finally obtained.

[0057] The target compound DY5 is a white needle-like crystal with a yield of 50.30%; 1 H NMR (600 MHz, DMSO-d6) δ 14.55 (s, 1H), 8.77 (s, 1H), 7.99 (td, 1H), 7.85 (d, 1H), 7.78 (t, 1H). 1313C NMR (151 MHz, DMSO-d6) δ 165.64, 163.38, 158.49, 156.75, 150.26, 145.75, 138.78, 138.73, 133.76, 123.77, 123.64, 120.97, 120.95, 117.70, 117.62.

[0058] Example 6

[0059] The phthalimide derivative containing an N-1,2,4-triazole unit, where R = 4-fluoro. The chemical name is 5-fluoro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione, and the English name is 5-fluoro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione. The structural formula is as follows;

[0060]

[0061] Synthesis of 5-fluoro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione

[0062]

[0063] 4-Fluorophthalic anhydride (166 mg) and 3-amino-1,2,4-triazole (84 mg) were added to glacial acetic acid (5 mL). After mixing evenly, the mixture was heated under reflux at 120 °C for 4 hours. The reaction process was monitored by TLC. After the reaction was completed, heating was stopped, and 70 mL of purified water was slowly added to quench the reaction, and stirring was continued for 1 hour. After the reaction was completed, the solid crude product was recovered by suction filtration and separated by silica gel column chromatography. The eluent was petroleum ether:ethyl acetate = 4:1, and the white solid target product DY6 was finally obtained.

[0064] The target compound DY6 was a white needle-like crystal with a yield of 47.41%; 1 1H NMR (600 MHz, DMSO-d6) δ 14.55 (s, 1H), 8.77 (s, 1H), 8.09 (dd, 1H), 7.92 (dd, 1H), 7.78 (ddd, 1H). 13 13C NMR (151 MHz, DMSO-d6) δ 167.49, 165.80, 165.68, 165.44, 150.43, 145.75, 134.65, 134.58, 127.82, 127.38, 127.31, 122.81, 122.65, 112.40, 112.24.

[0065] Example 7

[0066] The phthalimide derivative containing an N-1,2,4-triazole unit, where R = 4-tert-butyl. The chemical name is 5-(tert-butyl)-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione, and the English name is 5-(tert-butyl)-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione. The structural formula is as follows;

[0067]

[0068] Synthesis of 5-(tert-butyl)-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione

[0069]

[0070] 4-(tert-Butyl)phthalic anhydride (204 mg) and 3-amino-1,2,4-triazole (84 mg) were added to glacial acetic acid (5 mL). After mixing evenly, the mixture was heated under reflux at 120 °C for 4 hours. The reaction process was monitored by TLC. After the reaction was completed, heating was stopped, and 70 mL of purified water was slowly added to quench the reaction, and stirring was continued for 1 hour. After the reaction was completed, the solid crude product was recovered by suction filtration and separated by silica gel column chromatography. The eluent was petroleum ether:ethyl acetate = 4:1, and finally the white solid target product DY7 was obtained.

[0071] The target compound DY7 was a white needle-like crystal with a yield of 54.46%; 1 H NMR (600 MHz, DMSO-d6) δ 14.49 (s, 1H), 8.75 (s, 1H), 8.00 (d, 2H), 7.95 (d, 1H), 1.38 (s, 9H). 13 C NMR (151 MHz, DMSO-d6) δ 166.84, 166.47, 159.63, 150.64, 145.66, 132.80, 131.82, 129.03, 124.40, 121.22, 36.10, 31.21, 31.14.

[0072] Example 8

[0073] The phthalimide derivative containing an N-1,2,4-triazole unit, where R = 4-nitro. The chemical name is 5-nitro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione, and the English name is 5-nitro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione. The structural formula is as follows;

[0074]

[0075] Synthesis of 5-Nitro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione

[0076]

[0077] 4-Nitrophthalic anhydride (193 mg) and 3-amino-1,2,4-triazole (84 mg) were added to glacial acetic acid (5 mL). After mixing evenly, the mixture was heated under reflux at 120 °C for 4 hours. The reaction process was monitored by TLC. After the reaction was completed, heating was stopped, and 70 mL of purified water was slowly added to quench the reaction, and stirring was continued for 1 hour. After the reaction was completed, the solid crude product was recovered by suction filtration and separated by silica gel column chromatography. The eluent was petroleum ether:ethyl acetate = 4:1, and the white solid target product DY8 was finally obtained.

[0078] The target compound DY8 was a white needle-like crystal with a yield of 64.76%; 1 H NMR (600 MHz, DMSO-d6) δ 14.59 (s, 1H), 8.79 (s, 1H), 8.71 (dd, 1H), 8.62 (d, 1H), 8.25 (d, 1H). 13 C NMR (151 MHz, DMSO-d6) δ 165.05, 164.80, 152.28, 150.23, 145.81, 136.28, 133.11, 130.65, 125.97, 119.27.

[0079] Example 9

[0080] For the phthalimide derivative containing N-1,2,4-triazole unit, R = 3, 4, 5, 6-tetrabromo. The chemical name is 4,5,6,7-tetrabromo-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione, and the English name is 4,5,6,7-tetrabromo-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione. The structural formula is as follows;

[0081]

[0082] Synthesis of 4,5,6,7-Tetrabromo-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione

[0083]

[0084] 3,4,5,6 - Tetrabromophthalic anhydride (464 mg) and 3 - amino - 1,2,4 - triazole (84 mg) were added to glacial acetic acid (5 mL). After mixing evenly, the mixture was heated under reflux at 120 °C for 4 hours. The reaction process was monitored by TLC. After the reaction was completed, heating was stopped, and 70 mL of purified water was slowly added to quench the reaction, and stirring was continued for 1 hour. After the reaction was completed, the solid crude product was recovered by suction filtration and separated by silica gel column chromatography. The eluent was petroleum ether:ethyl acetate = 4:1, and the white solid target product DY9 was finally obtained.

[0085] The target compound DY9 was a white needle - like crystal with a yield of 89.24%; 1 H NMR (600 MHz, DMSO - d6) δ 14.57 (s, 1H), 8.78 (s, 1H). 13 C NMR (151 MHz, DMSO - d6) δ 162.58, 150.19, 145.80, 137.55, 131.28, 121.72, 4058.

[0086] Example 10

[0087] The phthalimide derivative containing N - 1,2,4 - triazole unit, R = 3,4,5,6 - tetrachloro. The chemical name is 4,5,6,7 - tetrachloro - 2 - (1H - 1,2,4 - triazol - 3 - yl) - isoindoline - 1,3 - dione, and the English name is 4,5,6,7 - tetrachloro - 2 - (1H - 1,2,4 - triazol - 3 - yl)isoindoline - 1,3 - dione. The structural formula is as follows;

[0088]

[0089] Synthesis of 4,5,6,7 - tetrachloro - 2 - (1H - 1,2,4 - triazol - 3 - yl) - isoindoline - 1,3 - dione

[0090]

[0091] 3,4,5,6 - Tetrachlorophthalic anhydride (286 mg) and 3 - amino - 1,2,4 - triazole (84 mg) were added to glacial acetic acid (5 mL). After mixing evenly, the mixture was heated under reflux at 120 °C for 4 hours. The reaction process was monitored by TLC. After the reaction was completed, heating was stopped, and 70 mL of purified water was slowly added to quench the reaction, and stirring was continued for 1 hour. After the reaction was completed, the solid crude product was recovered by suction filtration and separated by silica gel column chromatography. The eluent was petroleum ether:ethyl acetate = 4:1, and the white solid target product DY10 was finally obtained.

[0092] The target compound DY10 is a white needle-like crystal with a yield of 90.38%; 1 H NMR (600 MHz, DMSO-d6) δ 14.61 (s, 1H), 8.80 (s, 1H). 13 C NMR (151 MHz, DMSO-d6) δ 162.21, 149.93, 145.88, 139.20, 129.27, 128.62.

[0093] Example 11

[0094] The phthalimide derivative containing an N-1,2,4-triazole unit, where R = 3,4,5,6-tetrafluoro. The chemical name is 4,5,6,7-tetrafluoro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione, and the English name is 4,5,6,7-tetrafluoro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione. The structural formula is as follows;

[0095]

[0096] Synthesis of 4,5,6,7-tetrafluoro-2-(1H-1,2,4-triazol-3-yl)isoindoline-1,3-dione

[0097]

[0098] Add 3,4,5,6-tetrafluorophthalic anhydride (220 mg) and 3-amino-1,2,4-triazole (84 mg) to glacial acetic acid (5 mL). After mixing evenly, heat under reflux at 120 °C for 4 hours. Monitor the reaction process by TLC. After the reaction is completed, stop heating and slowly add 70 mL of purified water to quench the reaction, and continue stirring for 1 hour. After the reaction is over, recover the solid crude product by suction filtration and separate it by silica gel column chromatography. The eluent is petroleum ether:ethyl acetate = 4:1, and finally obtain the white solid target product DY11.

[0099] The target compound DY11 is a pale yellow needle-like crystal with a yield of 47.79%; 1 H NMR (600 MHz, DMSO-d6) δ 14.63 (s, 1H), 8.80 (s, 1H). 13 C NMR (151 MHz, DMSO-d6) δ 161.29, 149.61, 145.95, 144.31, 144.03, 142.57.11438.

[0100] Application performance test

[0101] In vitro anti-tumor activity test method:

[0102] The inhibitory effects of the synthesized target compounds on human pancreatic cancer cells (PANC-1), human gastric cancer cells (SGC-7901), human brain astrocytoma cells (U-87MG), and human liver cancer cells (HepG2) were determined by the CCK 8 method at a concentration of 100 μmol / L. Cells were seeded in 96-well plates at a density of 6000 cells per well, and 100 μL of complete medium was added to each well. The edges of the 96-well plates were filled with PBS and incubated in a 37 °C incubator with 90% humidity and 5% CO2 for 24 h until the cells covered the bottom of the 96-well plates. The drugs synthesized in this patent were diluted to 100 μmol / L with DMEM medium containing 10% serum. Using 5-fluorouracil as a positive control, three replicate wells were set up, and 100 μL of the dilution was added to each well and incubated for 48 h. The medium was replaced with 100 μL of DMEM containing 10 μL of CCK 8 dye and incubated for 2 h. The absorbance at 450 nm was measured using a microplate reader. The cell inhibition rate was calculated based on the measured absorbance. The formula for calculating the inhibition rate is: (OD of negative control group - OD of drug administration group) / (OD of negative control group - OD of blank group) * 100%. The test results are shown in Table 1.

[0103] Table 1 Inhibitory effects of compounds DY1 - DY11 on tumor cells at a concentration of 100 μmol / L

[0104] Compound Number PANC-1 (%) SGC-7901 (%) U-87MG (%) HepG2 (%) DY1 22.50％±1.73 9.88％±0.49 7.82％±1.10 17.26％±0.39 DY2 42.42％±2.10 4.96％±2.51 7.70％±1.07 11.48％±2.04 DY3 36.42％±1.66 32.20％±1.31 39.92％±2.01 42.42％±2.47 DY4 60.86％±0.89 16.26％±0.99 23.82％±1.90 56.58％±3.01 DY5 83.84％±3.03 29.02％±1.12 76.06％±2.88 49.36％±2.87 DY6 32.34％±2.77 23.74％±1.82 14.80％±1.01 8.32％±0.91 DY7 95.72％±1.93 70.32％±3.59 45.34％±2.33 28.52％±1.03 DY8 73.68％±2.84 34.52％±2.01 36.18％±2.90 30.98％±2.07 DY9 69.94％±2.90 60.16％±2.71 9.10％±0.37 19.40％±0.99 DY10 61.72％±1.87 49.24％±1.91 47.22％±2.31 39.22％±1.40 DY11 34.42％±2.01 46.12％±2.36 37.20％±2.19 20.54％±2.06 5-Fluorouracil 82.50％±1.97 79.88％±1.03 87.82％±2.08 91.26％±0.89

[0105] As can be seen from Table 1, the inhibitory effect of the target molecule on human pancreatic cancer cells (PANC-1) at a concentration of 100 μmol / L is generally better than its inhibitory effect on human gastric cancer cells (SGC-7901), human brain astrocytoma cells (U-87MG), and human liver cancer cells (HepG2). Among them, the inhibition rates of the target molecules DY5 and DY6 on human pancreatic cancer cells (PANC-1) reached 83.84% and 95.72% respectively, and the inhibitory effect was better than that of the control drug fluorouracil (82.50%). Compounds DY7 and DY9 showed strong inhibitory activities against human gastric cancer cells (SGC-7901), and the inhibitory effects reached 70.32% and 60.16% respectively. Compound DY5 showed strong inhibitory activity against human brain astrocytoma cells (U-87MG), and its inhibitory effect reached 76.06%. At the same time, compound DY4 showed strong inhibitory activity against human liver cancer cells (HepG2), and its inhibitory effect reached 56.58%. The above activity data fully demonstrate that phthalimide derivatives containing the N-1,2,4-triazole unit have significant inhibitory activities against human pancreatic cancer cells (PANC-1), human gastric cancer cells (SGC-7901), human brain astrocytoma cells (U-87MG), and human liver cancer cells (HepG2), and can be developed as candidate molecules for new anti-tumor drugs.

[0106] As can be seen from Table 1, the inhibitory effect of the target molecule on human pancreatic cancer cells (PANC-1) at a concentration of 100 μmol / L is significantly better than its inhibitory effect on human gastric cancer cells (SGC-7901), human brain astrocytoma cells (U-87MG), and human liver cancer cells (HepG2). Among them, the inhibition rates of compounds DY5 and DY6 on human pancreatic cancer cells (PANC-1) reached 83.84% and 95.72% respectively, and the inhibitory effect was better than that of the control drug fluorouracil (82.50%). Compounds DY7 and DY9 showed strong inhibitory activities against human gastric cancer cells (SGC-7901), and the inhibition rates were 70.32% and 60.16% respectively. Compound DY5 showed excellent performance in inhibiting human brain astrocytoma cells (U-87MG), and the inhibition rate was 76.06%. In addition, compound DY4 also showed significant inhibitory activity against human liver cancer cells (HepG2), and the inhibition rate was 56.58%. The above data fully prove that phthalimide derivatives containing the N-1,2,4-triazole unit have significant inhibitory effects on a variety of tumor cells, and have good anti-tumor potential, and are worthy of further development as candidate molecules for new anti-tumor drugs.

Claims

1. A phthalimide derivative containing an N-1,2,4-triazole unit, characterized in that, The structural formula is as shown in Formula I: Wherein, R is selected from 3,4,5,6-tetrahydro, 3-nitro, 3-hydroxy, 3-fluoro, 4-fluoro, 4-tert-butyl, 4-nitro, 3,4,5,6-tetrabromo, 3,4,5,6-tetrachloro, 3,4,5,6-tetrafluoro.

2. The method for preparing the phthalimide derivative containing an N-1,2,4-triazole unit as claimed in claim 1, characterized in that, The phthalic anhydride molecule and 3-amino-1,2,4-triazole are subjected to an acylation reaction by heating under reflux in an acetic acid solution to obtain the phthalimide derivative I containing an N-1,2,4-triazole unit. The synthetic route is as follows:

3. Use of the phthalimide derivative containing an N-1,2,4-triazole unit according to claim 1 in anti-tumor cells.

4. The application according to claim 3, wherein The tumor cells are human pancreatic cancer cells, human gastric cancer cells, human brain astroglioblastoma cells or human liver cancer cells.

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