A divalent palladium complex containing phthalic acid, a method of preparation and use

Abstract

The present application relates to a kind of bivalent palladium complex containing phthalic acid, and its preparation method and use.The bivalent palladium complex containing phthalic acid of the present application is as shown in formula 1, the complex utilizes the complex of phthalic acid derivative because of unique stability, redox and with DNA excellent effect, bivalent palladium high efficiency antitumor activity, solve the drug resistance of bivalent platinum class, play excellent synergistic antitumor effect.The synthesis route of the bivalent palladium complex of phthalic acid provided in the present application is simple, and synthesis raw material is easy to obtain, synthesis method is easy to realize and cost is cheap.

Description

Technical Field

[0001] This invention relates to a class of divalent palladium complexes containing phthalic acid, and their preparation methods and uses. Background Technology

[0002] The high incidence and mortality rates of malignant tumors bring profound suffering and enormous economic burdens to families. Traditional anti-tumor treatments have limited effectiveness in inhibiting tumor progression; even after surgical removal of the tumor, many patients experience local recurrence or distant metastasis. Treatment for solid tumors primarily involves surgery, but surgery easily leads to micrometastasis, increasing the risk of metastasis. Chemotherapy can kill cancer cells that have metastasized through various pathways, thus preventing metastasis. Platinum-based anti-tumor drugs are widely used clinically for the treatment of malignant tumors. The US FDA has approved three platinum-based drugs for marketing, including cisplatin, carboplatin, and oxaliplatin. Platinum-based anti-tumor drugs are the most widely used chemotherapy drugs for cancer patients in my country, but long-term use easily leads to drug resistance and has side effects such as nephrotoxicity, gastrointestinal adverse reactions, and hematologic toxicity. Oxidizing divalent platinum-based drugs to tetravalent platinum and further introducing other anti-tumor pharmacodynamic groups into the structure is a hot research area for novel platinum-based anti-tumor drugs in recent years. To design anti-tumor drugs with pharmacological indicators exceeding those of cisplatin, it is necessary to overcome the limitations of cisplatin-based drugs and find a new class of anti-tumor drugs. Summary of the Invention

[0003] This invention provides a divalent palladium complex containing phthalic acid, along with a method for preparing and using this complex.

[0004] The complex of the present invention is a divalent palladium complex containing phthalic acid as shown in Formula 1, wherein R1 to R4 are...

[0005] The groups are H, halogen, nitro, carboxyl, ester, amino, and C1-C. 20 Straight-chain or branched alkyl groups, or C3-C4 alkyl groups. 20 cycloalkyl groups, or C6-C6 groups 20 Any of the aryl groups, and R1 to R8 may be the same or different.

[0006] Preferably, in the divalent palladium complex of phthalic acid described in this invention, the substituents R1 to R4 are H, halogen, nitro, carboxyl, ester, amino, C1 to C4, respectively. 10 Straight-chain or branched alkyl groups, or C3-C4 alkyl groups. 10 cycloalkyl groups, or C6-C6 groups 10 Any of the aryl groups.

[0007] More preferably, the divalent palladium complex of phthalic acid of the present invention is a divalent palladium complex of phthalic acid as shown in Formula 2.

[0008] Palladium complexes, wherein R1 to R4 are all H.

[0009] More preferably, the phthalic acid-containing divalent palladium complex of the present invention is 3-methyl-o-phthalic acid as shown in Formula 3.

[0010] Palladium phthalate, wherein R1 is methyl and all other substituents are H.

[0011] More preferably, the phthalic acid-containing divalent palladium complex of the present invention is 4-nitro-ophthalic acid as shown in Formula 4.

[0012] Palladium phthalate, wherein R2 is a nitro group and all other substituents are H.

[0013] More preferably, the phthalic acid-containing divalent palladium complex of the present invention is 3,6-dimethyl phthalate as shown in Formula 5.

[0014] α-Palmium phthalate, wherein R1 and R4 are methyl groups and all other substituents are H groups.

[0015] More preferably, the divalent palladium complex containing phthalic acid in this invention is 3-ethyl-5- (as shown in Formula 6).

[0016] Chloro-palladium phthalate, wherein R1 is ethyl, R3 is chlorine, and all other substituents are H.

[0017] More preferably, the divalent palladium complex containing phthalic acid in this invention is 3-methyl-4-amino as shown in Formula 7.

[0018] α-Palmium phthalate, wherein R1 is methyl, R2 is amino, and all other substituents are H.

[0019] More preferably, the divalent palladium complex containing phthalic acid in this invention is 4,5-dichloro- as shown in Formula 8.

[0020] Palladium phthalate, wherein R2 and R3 are chlorine, and all other substituents are H.

[0021] More preferably, the present invention contains a divalent palladium complex of phthalic acid, such as 3-ethyl-5-ethyl ester as shown in Formula 9.

[0022] α-phthalic acid, wherein R1 is ethyl, R3 is ethyl ester, and all other substituents are H.

[0023] More preferably, the divalent palladium complex containing phthalic acid of the present invention is 3-amino-6- as shown in Formula 10.

[0024] Palladium bromophthalate, wherein R1 is an amino group, R4 is bromine, and all other substituents are H.

[0025] The method for preparing a class of divalent palladium complexes containing phthalic acid described in this invention is shown in Formula 11:

[0026] The specific reaction is as follows: (1) Add 10-100 molar equivalents of organic alcohol to 1 molar equivalent of phthalic acid (II), and heat and stir at 50-80°C for 1-6 hours to obtain a dissolved phthalic acid organic alcohol solution.

[0027] (2) Add 2 molar equivalents of NaOH to the above phthalic acid organic alcohol solution and stir at room temperature for 1 to 12 h to obtain an organic alcohol solution of compound III.

[0028] (3) Add 1 molar equivalent of PdCl2 to 5-20 molar equivalents of organic alcohol, and heat and stir at 50-80 °C for 1-6 h to obtain a dissolved PdCl2 organic alcohol solution.

[0029] (4) The above PdCl2 organic alcohol solution was slowly added to the organic alcohol solution of compound III. After the addition was completed, the mixture was stirred at room temperature for 1 to 6 h to obtain a solid precipitate of complex 1. The precipitate was filtered and dried to obtain complex 1.

[0030] The organic alcohol is any one of methanol, ethanol, propanol, butanol, ethylene glycol, and glycerol, with ethanol and ethylene glycol being preferred.

[0031] This invention relates to divalent palladium complexes containing phthalic acid, which can be used in the preparation of antitumor drugs, particularly in the preparation of drugs for treating pancreatic cancer.

[0032] This invention uses palladium complexes and phthalic acid with a large rigid aromatic ring. The complexes derived from these compounds have good anti-cancer potential due to their unique stability, redox properties, and excellent interaction with DNA.

[0033] By adopting the above technical solution, the present invention has the following advantages and beneficial effects: To address the problems of significant side effects and low activity of current divalent platinum-based antitumor drugs in antitumor treatment, this invention provides a class of divalent palladium complexes containing phthalic acid. This complex utilizes the unique stability, redox properties, and excellent interaction with DNA of phthalic acid derivatives, as well as the highly efficient antitumor activity of divalent palladium, to overcome the drug resistance of divalent platinum-based drugs and exert excellent synergistic antitumor effects.

[0034] This invention provides a class of divalent palladium complexes containing phthalic acid, which exhibit significant inhibitory effects on the proliferation of pancreatic cancer PANC-1 / GEM. Some complexes show significantly superior antitumor activity compared to cisplatin, making them potential candidates for further research. For example, complex 6 demonstrates the best antitumor activity, with an IC50 (half-maximal inhibitory concentration) against pancreatic cancer PANC-1 / GEM. 50 The minimum molecular weight is 1.08 µM. The complex provided by this invention has a novel skeletal structure and exhibits excellent antitumor activity, making it suitable for the development of pancreatic cancer drugs.

[0035] The synthetic route for the divalent palladium complex of phthalic acid provided by this invention is simple, the raw materials are readily available, the synthetic method is easy to implement, and the cost is low. Detailed Implementation

[0036] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments, further clarifies the invention. Those skilled in the art should understand that the specific descriptions below are illustrative rather than restrictive, and should not be construed as limiting the scope of protection of the present invention.

[0037] Preparation of coordination compounds Example

[0038] For the synthesis of complex 1, see Formula 11:

[0039] (1) 3.32 g (0.02 mol) of phthalic acid (II) was added to 50 mL of ethanol and stirred at 60 °C for 2 h until a clear solution was completely dissolved. 1.6 g (0.04 mol) of sodium hydroxide (NaOH) was added to the above solution and stirred at 50 °C for 1 h until the reaction was complete. The mixture was distilled at atmospheric pressure to obtain solid compound III, dried, and weighed. The yield was 96%. The NMR and high-resolution mass spectrometry data of compound III are as follows. 1 ¹H NMR (DMSO-d6): 7.81 (2H), 8.34 (2H). HRMS: m / z molecular ion peak: 209.99.

[0040] (2) 2.10 g (0.01 mol) of compound III was dissolved in 50 mL of ethanol, and 1.78 g (0.01 mol) of palladium chloride (PdCl2) was dissolved in 30 mL of ethanol. The above PdCl2 ethanol solution was slowly added to the ethanol solution of compound III. After the addition was complete, the mixture was stirred at room temperature for 3 h to obtain a solid precipitate of product complex 1. The precipitate was filtered and dried to obtain complex 1 with a yield of 95%. The NMR and high-resolution mass spectrometry data of complex 1 are as follows. 1 ¹H NMR (DMSO-d6): 7.81 (2H), 8.34 (2H). HRMS: m / z molecular ion peak: 269.91. Example

[0041] Synthesis of Complex 3

[0042] (1) 3.60 g (0.02 mol) of 3-methyl-phthalic acid (IV) was added to 50 mL of ethanol and stirred at 60 °C for 2 h until a clear solution was completely dissolved. 1.6 g (0.04 mol) of sodium hydroxide (NaOH) was added to the above solution and stirred at 50 °C for 1 h until the reaction was complete. The mixture was distilled at atmospheric pressure to obtain solid compound V, dried, and weighed. The yield was 98%. The NMR and high-resolution mass spectrometry data of compound V are as follows. 1 ¹H NMR (DMSO-d6): 2.35 (3H), 7.61 (1H), 7.68 (1H), 8.15 (1H). HRMS: m / z molecular ion peak: 224.01.

[0043] (2) 2.24 g (0.01 mol) of compound V was dissolved in 50 mL of ethanol, and 1.78 g (0.01 mol) of palladium chloride (PdCl2) was dissolved in 30 mL of ethanol. The above PdCl2 ethanol solution was slowly added to the ethanol solution of compound V. After the addition was complete, the mixture was stirred at room temperature for 3 h to obtain a solid precipitate of product complex 2. The precipitate was filtered and dried to obtain complex 2 with a yield of 96%. The NMR and high-resolution mass spectrometry data of complex 2 are as follows. 1 ¹H NMR (DMSO-d6): 2.35 (3H), 7.61 (1H), 7.68 (1H), 8.15 (1H). HRMS: m / z molecular ion peak: 283.93. Example

[0044] Synthesis of Complex 4

[0045] (1) 4.22 g (0.02 mol) of 4-nitro-phthalic acid (VI) was added to 60 mL of ethanol and stirred at 50 °C for 2 h until a clear solution was completely dissolved. 1.6 g (0.04 mol) of sodium hydroxide (NaOH) was added to the above solution and stirred at 50 °C for 1 h until the reaction was complete. The mixture was distilled at atmospheric pressure to obtain solid compound VII, dried, and weighed. The yield was 98%. The NMR and high-resolution mass spectrometry data of compound VII are as follows. 1 ¹H NMR (DMSO-d6): 8.60 (2H), 8.74 (1H), 9.27 (1H). HRMS: m / z molecular ion peak: 254.98.

[0046] (2) 2.55 g (0.01 mol) of compound VII was dissolved in 50 mL of ethanol, and 1.78 g (0.01 mol) of palladium chloride (PdCl2) was dissolved in 30 mL of ethanol. The above PdCl2 ethanol solution was slowly added to the ethanol solution of compound VII. After the addition was complete, the mixture was stirred at room temperature for 3 h to obtain a solid precipitate of product complex 3. The precipitate was filtered and dried to obtain complex 3 with a yield of 97%. The NMR and high-resolution mass spectrometry data of complex 3 are as follows. 1 ¹H NMR (DMSO-d6): 8.60 (2H), 8.74 (1H), 9.27 (1H). HRMS: m / z molecular ion peak: 314.90. Example

[0047] Synthesis of Complex 5

[0048] (1) 3.89 g (0.02 mol) of 3,6-dimethyl-phthalic acid (VIII) was added to 60 mL of ethanol and stirred at 60 °C for 2 h until a clear solution was completely dissolved. 1.6 g (0.04 mol) of sodium hydroxide (NaOH) was added to the above solution and stirred at 50 °C for 1 h until the reaction was complete. The mixture was distilled at atmospheric pressure to obtain solid compound IX, dried, and weighed. The yield was 97%. The NMR and high-resolution mass spectrometry data of compound IX are as follows. 1 ¹H NMR (DMSO-d6): 2.36 (6H), 7.49 (2H). HRMS: m / z molecular ion peak: 238.02.

[0049] (2) 2.38 g (0.01 mol) of compound IX was dissolved in 50 mL of ethanol, and 1.78 g (0.01 mol) of palladium chloride (PdCl2) was dissolved in 30 mL of ethanol. The above PdCl2 ethanol solution was slowly added to the ethanol solution of compound IX. After the addition was complete, the mixture was stirred at room temperature for 3 h to obtain a solid precipitate of product complex 4. The precipitate was filtered and dried to obtain complex 4 with a yield of 96%. The NMR and high-resolution mass spectrometry data of complex 4 are as follows. 1 ¹H NMR (DMSO-d6): 2.36 (6H), 7.49 (2H). HRMS: m / z molecular ion peak: 297.95. Example

[0050] Synthesis of Complex 6

[0051] (1) 4.58 g (0.02 mol) of 3-ethyl-5-chloro-phthalic acid (X) was added to 60 mL of ethanol and stirred at 60 °C for 2 h until a clear solution was completely dissolved. 1.6 g (0.04 mol) of sodium hydroxide (NaOH) was added to the above solution and stirred at 50 °C for 1 h until the reaction was complete. The mixture was distilled at atmospheric pressure to obtain solid compound XI, dried, and weighed. The yield was 96%. The NMR and high-resolution mass spectrometry data of compound XI are as follows. 1 ¹H NMR (DMSO-d6): 1.24 (3H), 2.59 (2H), 7.68 (1H), 8.17 (1H). HRMS: m / z molecular ion peak: 271.98.

[0052] (2) 2.72 g (0.01 mol) of compound XI was dissolved in 50 mL of ethanol, and 1.78 g (0.01 mol) of palladium chloride (PdCl2) was dissolved in 30 mL of ethanol. The above PdCl2 ethanol solution was slowly added to the ethanol solution of compound XI. After the addition was complete, the mixture was stirred at room temperature for 3 h to obtain a solid precipitate of product complex 5. The precipitate was filtered and dried to obtain complex 5 with a yield of 95%. The NMR and high-resolution mass spectrometry data of complex 5 are as follows. 1 ¹H NMR (DMSO-d6): 1.24 (3H), 2.59 (2H), 7.68 (1H), 8.17 (1H). HRMS: m / z molecular ion peak: 331.91. Example

[0053] Synthesis of Complex 7

[0054] (1) 3.91 g (0.02 mol) of 3-methyl-4-amino-phthalic acid (XII) was added to 60 mL of ethanol and stirred at 60 °C for 2 h until a clear solution was completely dissolved. 1.6 g (0.04 mol) of sodium hydroxide (NaOH) was added to the above solution and stirred at 50 °C for 1 h until the reaction was complete. The mixture was distilled at atmospheric pressure to obtain solid compound XIII, dried, and weighed. The yield was 96%. The NMR and high-resolution mass spectrometry data of compound XIII are as follows. 1 ¹H NMR (DMSO-d6): 2.35 (3H), 4.00 (2H), 6.89 (1H), 7.90 (1H). HRMS: m / z molecular ion peak: 239.02.

[0055] (2) 2.39 g (0.01 mol) of compound XIII was dissolved in 50 mL of ethanol, and 1.78 g (0.01 mol) of palladium chloride (PdCl2) was dissolved in 30 mL of ethanol. The above PdCl2 ethanol solution was slowly added to the ethanol solution of compound XIII. After the addition was complete, the mixture was stirred at room temperature for 3 h to obtain a solid precipitate of product complex 6. The precipitate was filtered and dried to obtain complex 6 with a yield of 95%. The NMR and high-resolution mass spectrometry data of complex 6 are as follows. 1 ¹H NMR (DMSO-d6): 2.35 (3H), 4.00 (2H), 6.89 (1H), 7.90 (1H). HRMS: m / z molecular ion peak: 298.94. Example

[0056] Synthesis of Complex 8

[0057] (1) 4.70 g (0.02 mol) of 4,5-dichloro-phthalic acid (XIV) was added to 60 mL of ethanol and stirred at 60 °C for 2 h until a clear solution was completely dissolved. 1.6 g (0.04 mol) of sodium hydroxide (NaOH) was added to the above solution and stirred at 50 °C for 1 h until the reaction was complete. The solid compound XV was obtained by atmospheric distillation, dried, and weighed, with a yield of 97%. The NMR and high-resolution mass spectrometry data of compound XV are as follows. 1 ¹H NMR (DMSO-d6): 8.29 (2H). HRMS: m / z molecular ion peak: 277.91.

[0058] (2) 2.78 g (0.01 mol) of compound XV was dissolved in 50 mL of ethanol, and 1.78 g (0.01 mol) of palladium chloride (PdCl2) was dissolved in 30 mL of ethanol. The above PdCl2 ethanol solution was slowly added to the ethanol solution of compound XV. After the addition was complete, the mixture was stirred at room temperature for 3 h to obtain a solid precipitate of product complex 7. The precipitate was filtered and dried to obtain complex 7 with a yield of 96%. The NMR and high-resolution mass spectrometry data of complex 7 are as follows. 1 ¹H NMR (DMSO-d6): 8.29 (2H). HRMS: m / z molecular ion peak: 337.84. Example

[0059] Synthesis of Complex 9

[0060] (1) 5.32 g (0.02 mol) of 3-ethyl-5-ethyl phthalic acid (XVI) was added to 60 mL of ethanol and stirred at 60 °C for 2 h until a clear solution was completely dissolved. 1.6 g (0.04 mol) of sodium hydroxide (NaOH) was added to the above solution, and the mixture was stirred at 50 °C for 1 h until the reaction was complete. The mixture was distilled at atmospheric pressure to obtain solid compound XVII, dried, and weighed. The yield was 95%. The NMR and high-resolution mass spectrometry data of compound XVII are as follows. 1 ¹H NMR (DMSO-d6): 1.24 (3H), 1.30 (3H), 2.59 (2H), 4.29 (2H), 8.38 (1H), 8.87 (2H). HRMS: m / z molecular ion peak: 310.04.

[0061] (2) 2.76 g (0.01 mol) of compound XVII was dissolved in 50 mL of ethanol, and 1.78 g (0.01 mol) of palladium chloride (PdCl2) was dissolved in 30 mL of ethanol. The above PdCl2 ethanol solution was slowly added to the ethanol solution of compound XVII. After the addition was complete, the mixture was stirred at room temperature for 3 h to obtain a solid precipitate of product complex 8. The precipitate was filtered and dried to obtain complex 8 with a yield of 95%. The NMR and high-resolution mass spectrometry data of complex 8 are as follows. 1 ¹H NMR (DMSO-d6): 1.24 (3H), 1.30 (3H), 2.59 (2H), 4.29 (2H), 8.38 (1H), 8.87 (2H). HRMS: m / z molecular ion peak: 369.97. Example

[0062] Synthesis of Complex 10

[0063] (1) 5.18 g (0.02 mol) of 3-amino-6-bromo-phthalic acid (XVIII) was added to 60 mL of ethanol and stirred at 60 °C for 2 h until a clear solution was completely dissolved. 1.6 g (0.04 mol) of sodium hydroxide (NaOH) was added to the above solution and stirred at 30 °C for 1 h until the reaction was complete. The mixture was distilled at atmospheric pressure to obtain solid compound XIX, dried, and weighed. The yield was 97%. The nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HMS) data of compound XIX are as follows. 1 ¹H NMR (DMSO-d6): 4.00 (2H), 6.90 (1H), 7.73 (1H). HRMS: m / z molecular ion peak: 302.91.

[0064] (2) 2.67 g (0.01 mol) of compound XIX was dissolved in 50 mL of ethanol, and 1.78 g (0.01 mol) of palladium chloride (PdCl2) was dissolved in 30 mL of ethanol. The above PdCl2 ethanol solution was slowly added to the ethanol solution of compound XIX. After the addition was complete, the mixture was stirred at room temperature for 3 h to obtain a solid precipitate of product complex 9. The precipitate was filtered and dried to obtain complex 9 with a yield of 95%. The NMR and high-resolution mass spectrometry data of complex 9 are as follows. 1 ¹H NMR (DMSO-d6): 4.00 (2H), 6.90 (1H), 7.73 (1H). HRMS: m / z molecular ion peak: 362.84. Example

[0065] Antitumor activity test of the complexes of the present invention The tumor cell proliferation inhibition assay was performed on the complex of the present invention using the conventional CKK-8 assay. The cell line used was pancreatic cancer PANC-1 / GEM. The culture medium was DMEM + 10% NBS + penicillin antibiotics.

[0066] Sample solution preparation: The test complexes were dissolved in DMSO to prepare stock solutions with a concentration of 10 mM. The stock solutions were diluted with culture medium to prepare final drug concentrations of 50 µM, 25 µM, 10 µM, 5 µM, 1 µM, 0.5 µM, 0.25 µM and 0.125 µM.

[0067] The concentration added to each well of the 96-well plate is 6 × 10⁻⁶. 4100 μL of cell suspension (60,000 cells / well) was added to each well and incubated at 37 °C in a 5% CO2 incubator. After 24 hours, the supernatant was aspirated, and 100 μL of culture medium containing the sample and control solution was added to each well. The well was incubated at 37 °C for 72 hours. 10 μL of CKK-8 was added to each well and the well was incubated for 1 hour. The OD value at 570 nm was measured using an MK-2 automated microplate reader, and the half-maximal inhibitory concentration (IC50) was calculated. 50 The antitumor activity of the complexes is detailed in Table 1. Cisplatin was used as a control sample in the antitumor activity test.

[0068]

[0069] The results in Table 1 show that the complexes of this application generally exhibit excellent pancreatic cancer activity, such as the half-maximal inhibitory concentration (IC50) of complex 6 against pancreatic cancer PANC-1 / GEM. 50 The IC50 value is close to 1 µM, significantly higher than that of the control sample cisplatin. 50 =19.32 µM. Therefore, the complex provided by this invention has a novel skeletal structure and excellent antitumor activity, and can be used for the development of antitumor drugs.

[0070] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make modifications or alterations to the above-described technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A divalent palladium complex containing phthalic acid as shown in Formula 1, wherein R1 to R4 are H, halogen, nitro, carboxyl, ester, amino, C1 to C4, respectively. 20 Straight-chain or branched alkyl groups, or C3-C4 alkyl groups. 20 cycloalkyl groups, or C6-C6 groups 20 Any of the aryl groups, and R1 to R8 are the same or different. 。 2. The divalent palladium complex of phthalic acid according to claim 1, characterized in that... Substituents R1 to R4 are H, halogen, nitro, carboxyl, ester, amino, C1 to C4, respectively. 10 Straight-chain or branched alkyl groups, or C3-C4 alkyl groups. 10 cycloalkyl groups, or C6-C6 groups 10 Any of the aryl groups.

3. The phthalic acid divalent palladium complex according to claim 2 is a phthalic acid divalent palladium complex as shown in Formula 2, wherein R1 to R4 are all H 。 4. The divalent palladium complex containing phthalic acid according to claim 2 is 3-methyl-palladium phthalate as shown in Formula 3, wherein R1 is methyl and all other substituents are H. 。 5. The divalent palladium complex containing phthalic acid according to claim 2 is 4-nitro-palladium phthalate as shown in Formula 4, wherein R2 is a nitro group and the other substituents are all H groups. 。 6. The divalent palladium complex containing phthalic acid according to claim 2 is 3,6-dimethyl-palladium phthalate as shown in Formula 5, wherein R1 and R4 are methyl groups, and the other substituents are all H groups. 。 7. The divalent palladium complex containing phthalic acid according to claim 2 is 3-ethyl-5-chloro-palladium phthalate as shown in Formula 6, wherein R1 is ethyl, R3 is chlorine, and all other substituents are H. 。 8. The divalent palladium complex containing phthalic acid according to claim 2 is 3-methyl-4-amino-phthalic acid palladium as shown in Formula 7, wherein R1 is methyl, R2 is amino, and all other substituents are H. 。 9. The divalent palladium complex containing phthalic acid according to claim 2 is 4,5-dichloro-palladium phthalate as shown in Formula 8, wherein R2 and R3 are chlorine, and the other substituents are all H. 。 10. The divalent palladium complex containing phthalic acid according to claim 2, as shown in Formula 9, is 3-ethyl-5-ethyl phthalic acid, wherein R1 is ethyl, R3 is ethyl ester, and the other substituents are all H. 。 11. The divalent palladium complex containing phthalic acid according to claim 2 is 3-amino-6-bromo-phthalic acid palladium as shown in Formula 10, wherein R1 is amino, R4 is bromine, and the other substituents are all H. 。 12. The method for preparing the divalent palladium complex containing phthalic acid according to claim 1, characterized in that... The synthetic route is shown in Equation 11: The specific reactions are as follows: (1) Add 10-100 molar equivalents of organic alcohol to 1 molar equivalent of phthalic acid (II), and heat and stir at 50-80 °C for 1-6 h to obtain a dissolved phthalic acid organic alcohol solution. (2) Add 2 molar equivalents of NaOH to the above phthalic acid organic alcohol solution, stir at room temperature for 1-12 h to obtain an organic alcohol solution of compound III: (3) Add 1 molar equivalent of PdCl2 to 5-20 molar equivalents of organic alcohol, and heat and stir at 50-80 °C for 1-6 h to obtain a dissolved PdCl2 organic alcohol solution: (4) The above PdCl2 organic alcohol solution was slowly added to the organic alcohol solution of compound III. After the addition was completed, the mixture was stirred at room temperature for 1-6 h to obtain a solid precipitate of complex 1. The precipitate was then filtered and dried to obtain complex 1. The organic alcohol is any one of methanol, ethanol, propanol, butanol, ethylene glycol, and glycerol, preferably ethanol and ethylene glycol. 。 13. The use of any of the divalent palladium complexes containing phthalic acid as described in claims 1 to 11 in the preparation of antitumor drugs.

14. Use of any of the divalent palladium complexes containing phthalic acid as described in claims 1 to 11 in the preparation of a medicament for treating pancreatic cancer.

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