A heterocyclofulvene-1-ketone compound, a preparation method and application thereof

Abstract

This invention discloses an isochoric 1-ketone compound, its preparation method, and its applications. The isochoric 1-ketone compound has the structural formula shown in Formula (I), wherein R1 to R4 are selected from C1-C6 alkyl, hydrogen, halogen, or methoxy groups, respectively; R5 is selected from C1-C6 alkyl, C3-C6 cycloalkyl, phenyl, or substituted phenyl groups. This invention directly constructs isochoric ketone compounds with a quaternary carbon center at the 3-position via addition reaction using 3-substituted isocoumarin compounds as substrates. The synthetic method has the advantages of simplicity, efficiency, readily available raw materials, and high yield. The prepared compound can significantly inhibit the growth of pancreatic cancer cells.

Description

Technical Field

[0001] This invention relates to an isochromatic 1-one compound, its preparation method and application, belonging to the field of medicinal chemistry technology. Background Technology

[0002] Pancreatic cancer (PC) is a common malignant tumor of the digestive tract. Approximately 90% of cases originate from ductal adenocarcinomas of the glandular epithelium, and its incidence and mortality rates are on the rise. Due to its poor prognosis, the mortality rate of pancreatic cancer is almost equal to its incidence rate, making it the seventh leading cause of cancer death worldwide. According to a study of 28 European countries, pancreatic cancer is projected to surpass breast cancer as the third leading cause of cancer death by 2025. According to statistics from the National Cancer Center of China in 2021, pancreatic cancer ranks 7th in incidence among male malignant tumors and 11th among female malignant tumors in my country, ranking 6th in cancer-related mortality.

[0003] The exact causes of pancreatic cancer are not fully understood, but several factors are associated with its development. Smoking is one of the most significant risk factors; smokers are more than twice as likely to develop pancreatic cancer as non-smokers. Other possible risk factors include obesity, high blood sugar, pancreatitis, family history, and certain gene mutations. However, most pancreatic cancer patients do not exhibit obvious symptoms, making prevention and early diagnosis more challenging.

[0004] Currently, drug treatments for pancreatic cancer mainly include targeted therapy and immunotherapy. Targeted therapies work by interfering with the growth and spread of cancer cells, such as inhibiting signaling pathways like EGFR and VEGF. Immunotherapy drugs enhance the body's immune system's ability to attack cancer cells, such as anti-PD-1 antibodies. However, these treatments have some drawbacks, including poor efficacy, significant side effects, high costs, and the inability to completely cure pancreatic cancer, leading to a high recurrence rate. Therefore, developing new drugs for treating pancreatic cancer is urgent and necessary, especially those with low toxicity, high selectivity, and low risk of developing drug resistance.

[0005] The benzohexa-lactone ring structure of isochoroids is an important active component of many natural products. Currently, there are many methods for synthesizing isochoroids, but most of these methods involve multi-step synthesis of raw materials, harsh high-temperature and high-pressure environments, low yields, or the use of complex metal catalysts and ligands. Therefore, developing new methods to obtain isochoroids is a top priority. Summary of the Invention

[0006] Objectives of the Invention: The first objective of this invention is to provide an isochromic 1-one compound having a benzo[6]-membered ring lactone structure. The second objective of this invention is to provide a method for preparing the above-mentioned compound. The third objective of this invention is to provide the application of the above-mentioned compound in its anti-pancreatic cancer activity.

[0007] Technical solution: The structural formula of the heterochromatic 1-one compound of the present invention is shown in formula (Ⅰ):

[0008] (I) R1 to R4 are selected from C1-C6 alkyl, hydrogen, halogen or methoxy groups, respectively; R5 is selected from C1-C6 alkyl, C3-C6 cycloalkyl, phenyl, or substituted phenyl.

[0009] R1 is selected from H or F; R2 is selected from H, Cl, or methyl; R3 is selected from H, F, methyl, or methoxy; R4 is selected from H or methyl; R5 is selected from methyl, ethyl, cyclopropyl, n-hexyl, phenyl, p-fluorophenyl, p-methylphenyl, p-methoxyphenyl, or o-methylphenyl.

[0010] The structural formula of the compound is selected from the following compounds: .

[0011] The method for preparing the isochromic 1-keto compound of the present invention is characterized by comprising the following steps: dissolving 3-substituted isocoumarin in dichloromethane, adding tetrabutylammonium bromide, a halogenating agent and acetic acid, mixing evenly, and after the reaction is completed, separating the solvent, extracting and purifying to obtain the isochromic 1-keto compound.

[0012] The molar ratio of isocoumarin, tetrabutylammonium bromide, halogenating agent and acetic acid is 1: 2-2.5: 2-2.5: 2-2.5.

[0013] The halogenating agent is iodophenyl diacetic acid (PIDA).

[0014] The reaction conditions after uniform mixing are room temperature and the reaction time is 2-12 hours.

[0015] The preparation method of the present invention firstly involves activating PIDA with bromide ions in TBAB in a dichloromethane solution. Subsequently, the double bond at the 3,4-position of isocoumarin attacks the bromine atom to obtain a relatively stable bromium ion. At the same time, acetic acid nucleophilically attacks the bromium ion intermediate, removing a hydrogen proton to obtain the final product, namely, a 4-bromo-3-methoxy-3-phenylisochroman-1-one derivative.

[0016] The application of the isochromic 1-one compounds described in this invention in the preparation of drugs for treating pancreatic cancer.

[0017] The heterochromatic 1-one compounds can inhibit the growth of pancreatic cancer cells.

[0018] The drug contains a pharmaceutically acceptable carrier. Beneficial effects: Compared with the prior art, the present invention has the following outstanding advantages: The present invention discloses an isochoric 1-one compound, which is constructed directly by addition reaction of 3-substituted isocoumarin compounds as substrates. The synthesis method has the advantages of being simple and efficient, with readily available raw materials and high yield. The prepared compound can significantly inhibit the growth of pancreatic cancer cells. Attached Figure Description

[0019] Figure 1 This is the 1H NMR spectrum of compound 2 of the present invention; Figure 2 This is the carbon NMR spectrum of compound 2 of the present invention; Figure 3 The 1H NMR spectrum of compound 5 of this invention; Figure 4 This is the carbon NMR spectrum of compound 5 of the present invention. Detailed Implementation

[0020] The technical solution of the present invention will be further described below with reference to the accompanying drawings.

[0021] Example 1: Preparation of heterochromatic 1-one compounds:

[0022] 3-substituted isocoumarin (1 eq) was dissolved in dichloromethane (DCM), and then tetrabutylammonium bromide (TBAB) (2.2 eq), iodophenyl diacetic acid (PIDA) (2.2 eq) and acetic acid (AcOH) (2.2 eq) were added and mixed thoroughly to obtain a mixture. The mixture was reacted at room temperature for 2.0-12.0 h, and then the solvent dichloromethane was removed by rotary evaporation, the product was extracted three times with ethyl acetate, and the pure product was obtained by column chromatography. In this embodiment, a total of 18 compounds were prepared. The substituents of different isocoumarins are shown in Table 1 (the substituents of the raw material 3-substituted isocoumarin correspond to the compounds prepared). The carbon and hydrogen spectrum data are as follows: 3-substituted isocoumarin (1 eq) was dissolved in dichloromethane (DCM), and then tetrabutylammonium bromide (TBAB) (2.2 eq), iodophenyl diacetic acid (PIDA) (2.2 eq) and acetic acid (AcOH) (2.2 eq) were added to it and mixed evenly to obtain a mixture. After reacting the mixture at room temperature for 2.0-12.0 h, the solvent dichloromethane was removed by rotary evaporation, the mixture was extracted three times with ethyl acetate, and the pure product was obtained by column chromatography. In this embodiment, a total of 18 compounds were prepared. The substituents of the different isocoumarins are shown in Table 1 (the substituents of the 3-substituted isocoumarin used correspond to the compounds prepared). The carbon and hydrogen spectral data are as follows: 3-substituted isocoumarin (1 eq) was dissolved in dichloromethane (DCM), and then tetrabutylammonium bromide (TBAB) (2.2 eq), iodophenyl diacetic acid (PIDA) (2.2 eq), and acetic acid (AcOH) (2.2 eq) were added and mixed thoroughly to obtain a mixture. After reacting the mixture at room temperature for 2.0-12.0 h, the solvent dichloromethane was removed by rotary evaporation, the mixture was extracted three times with ethyl acetate, and the pure product was obtained by column chromatography. In this embodiment, a total of 18 compounds were prepared. The substituents of the different isocoumarins are shown in Table 1 (the substituents of the 3-substituted isocoumarin used correspond to the compounds prepared). The carbon and hydrogen spectral data are as follows: Compound 1 (denoted as C1): white solid, yield 85%. 1 H NMR (500 MHz, CDCl3) δ = 8.21 (d, J = 7.6 Hz, 1H), 7.74 (d, J = 7.0 Hz, 2H), 7.71 – 7.67 (m, 1H), 7.55 (t, J =8.2 Hz, 1H), 7.47 (td, J = 14.3, 13.5, 7.6 Hz, 4H), 5.67 (s, 1H), 1.80 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ166.93, 160.85, 149.09, 136.06, 132.78, 132.52,132.26, 132.00, 127.65, 127.37, 126.11, 125.00, 122.83, 120.67, 77.41, 77.16,76.91, 69.47, 22.05. ESI-MS, m / Z [M+Na] + Theoretical value: 382.9898; Test value: 382.9895.

[0023] Compound 2 (denoted as C2): white solid, yield 84%. 1 H NMR (500 MHz, CDCl3) δ = 8.18 (d, J = 2.2 Hz, 1H), 7.71 (dt, J = 6.1, 1.5 Hz, 2H), 7.66 (dd, J = 8.1, 2.2 Hz,1H), 7.50 – 7.42 (m, 4H), 5.63 (s, 1H), 1.83 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 166.69, 159.99, 137.11, 136.51, 136.14, 134.98, 130.79, 129.84, 129.35, 128.58, 125.85, 124.73, 104.09, 46.50, 21.65. ESI-MS, m / Z [M+H] + Theoretical value: 416.9507; Test value: 416.9505.

[0024] Compound 3 (denoted as C3): white solid, yield 72%. 1 H NMR (500 MHz, CDCl3) δ = 7.75 –7.69 (m, 2H), 7.67 (ddd, J = 8.4, 7.6, 4.9 Hz, 1H), 7.52 – 7.40 (m, 3H), 7.31(dd, J = 7.7, 1.1 Hz, 1H), 7.28 – 7.22 (m, 1H), 5.66 (d,J = 1.6 Hz, 1H), 1.82 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 166.76 , 161.72 , 140.78 ,136.51 , 136.43 , 136.40 , 129.74 , 128.48 , 125.86 , 123.75 , 123.72 ,118.56 , 118.39 , 103.69, 46.86, 46.84, 21.61. ESI-MS, m / Z [M+Na] + Theoretical value: 400.9792; Test value: 400.9801.

[0025] Compound 4 (denoted as C4): white solid, 94% yield. 1 H NMR (500 MHz, Chloroform- d ) δ8.26 (dd, J = 8.6, 5.4 Hz, 1H), 7.75 – 7.70 (m, 2H), 7.53 – 7.43 (m, 3H),7.26 (d, J = 2.5 Hz, 1H), 7.22 (dd, J = 8.0, 2.5 Hz, 1H), 5.59 (s, 1H), 1.86 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 166.56 , 159.97 , 136.44 , 133.91 ,133.83 , 129.69 , 128.45 , 125.71 , 117.50 , 117.33 , 115.01 , 114.82 ,103.90 , 77.23, 46.44, 21.53. ESI-MS, m / Z [M+H] + Theoretical value: 400.9793; Test value: 400.9801.

[0026] Compound 5 (denoted as C5): white solid, yield 88%. 1 H NMR (500 MHz, CDCl3) δ = 8.01 (d, J= 1.9 Hz, 1H), 7.77 – 7.66 (m, 2H), 7.51 – 7.34 (m, 5H), 5.65 (s, 1H), 2.46 (s, 3H), 1.80 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 167.08 , 161.49 ,140.60 , 137.25 , 136.07 , 135.95 , 131.42 , 129.85 , 128.68 , 128.11 ,126.14 , 123.17 , 104.31 , 47.72, 21.89, 21.67. ESI-MS, m / Z [M+H] + Theoretical value: 397.0048; Test value: 397.0051.

[0027] Compound 6 (denoted as C6): white solid, yield 81%. 1 H NMR (500 MHz, CDCl3) δ = 8.09 (d, J = 7.9 Hz, 1H), 7.76 – 7.69 (m, 2H), 7.53 – 7.40 (m, 3H), 7.34 (dd, J = 7.8,1.4 Hz, 1H), 7.30 – 7.28 (m, 1H), 5.61 (s, 1H), 2.48 (s, 3H), 1.81 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 167.08 , 161.49 , 140.60 , 137.25 , 136.07 ,135.95 , 131.42 , 129.85 , 128.68 , 128.11 , 126.14 , 123.17 , 104.31 , 47.72, 21.89, 21.67. ESI-MS, m / Z [M+H] + Theoretical value: 397.0049; Test value: 397.0051.

[0028] Compound 7 (denoted as C7): white solid, yield 39%. 1H NMR (500 MHz, Chloroform- d ) δ 8.07 (dd, J = 7.7, 1.2 Hz, 1H), 7.80 – 7.73 (m, 2H), 7.53 (d, J = 7.6 Hz,1H), 7.50 – 7.40 (m, 4H), 5.77 (s, 1H), 2.49 (s, 3H), 1.79 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 167.12, 161.50, 136.92, 136.67, 136.58, 136.14, 129.71, 129.51, 128.74, 128.48, 125.99, 123.37, 104.04, 44.87,21.69,18.05. ESI-MS, m / Z [M+H] + Theoretical value: 397.0057; Test value: 397.0051.

[0029] Compound 8 (denoted as C8): white solid, yield 70%. 1 H NMR (500 MHz, CDCl3) δ = 8.14 (d, J = 8.7 Hz, 1H), 7.72 (d, J = 9.2 Hz, 2H), 7.51 – 7.37 (m, 3H), 7.02 (dd, J =8.7, 2.5 Hz, 1H), 6.95 (d, J = 2.4 Hz, 1H), 5.58 (s, 1H), 3.93 (s, 3H), 1.82(s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ166.85 , 164.54 , 160.82 , 140.86 ,137.00 , 133.20 , 129.56 , 128.41 , 125.86 , 115.65 , 115.38 , 112.83 ,103.93 , 55.93, 47.52, 21.65. ESI-MS, m / Z [M+ Na] + Theoretical value: 412.9991; Test value: 413.0001.

[0030] Compound 9 (denoted as C9): white solid, yield 94%. 1 H NMR (500 MHz, Chloroform- d ) δ8.12 (dd, J = 7.7, 1.2 Hz, 1H), 7.62 (td, J = 7.6, 1.3 Hz, 1H), 7.50 (td, J =7.7, 1.2 Hz, 1H), 7.37 (d, J = 7.4 Hz, 1H), 5.93 (s, 1H), 2.16 (s, 3H), 1.80 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 168.87, 161.48, 137.96, 134.79, 130.63, 130.02, 127.97, 123.05, 106.45, 43.94, 23.77, 21.50. ESI-MS, m / Z [M+H] + Theoretical value: 320.9746; Test value: 320.9738.

[0031] Compound 10 (denoted as C10): white solid, 95% yield. 1 H NMR (500 MHz, CDCl3) δ = 8.13 (d, J = 7.7 Hz, 1H), 7.62 (t, J = 7.5 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.37 (d, J= 7.6 Hz, 1H), 5.89 (s, 1H), 2.62 (ddq, J = 69.0, 14.8, 7.4 Hz, 2H), 1.83(s, 3H), 1.05 (t, J = 7.4 Hz, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 168.57,161.62, 138.18, 134.74, 130.63, 129.96, 127.92, 123.33, 107.90, 43.96, 28.24, 6.54. ESI-MS, m / Z [M+H] + Theoretical value: 334.9897; Test value: 334.9895.

[0032] Compound 11 (denoted as C11): white solid, 91% yield. 1 H NMR (500 MHz, CDCl3) δ = 8.11(dd, J = 7.8, 1.4 Hz, 1H), 7.61 (td, J = 7.6, 1.4 Hz, 1H), 7.49 (td, J = 7.6, 1.2 Hz, 1H), 7.36 (dd, J = 7.6, 1.2 Hz, 1H), 5.87 (s, 1H), 2.64 – 2.45 (m,2H), 1.77 – 1.64 (m, 1H), 1.50 – 1.09 (m, 8H), 0.94 – 0.82 (m, 3H). 13 C NMR (126 MHz, Chloroform-d) δ 168.55, 161.57, 138.13, 134.69, 130.56, 129.91, 127.89, 123.28, 107.64, 44.12, 34.91, 31.69, 28.92, 22.61, 22.07, 21.27, 14.13. ESI-MS, m / Z [M+H] + Theoretical value: 391.0502; Test value: 391.0521.

[0033] Compound 12 (denoted as C12): white solid, yield 85%. 1 H NMR (500 MHz, Chloroform- d ) δ 8.12 – 8.07 (m, 1H), 7.62 (td, J = 7.6, 1.4 Hz, 1H), 7.51 – 7.46 (m, 1H), 7.39 (dd, J = 7.7, 1.1 Hz, 1H), 6.17 (s, 1H), 1.82 (s, 3H), 1.33 – 1.05 (m, 2H), 0.90 – 0.84 (m, 2H), 0.67 – 0.48 (m, 1H). 13 C NMR (126 MHz, Chloroform- d ) δ 169.21, 161.22, 138.22, 134.83, 130.59, 129.90, 127.89, 123.24, 106.87, 44.34, 21.57, 16.98, 6.67. ESI-MS, m / Z [M+H] + Theoretical value: 346.9886; Test value: 346.9895.

[0034] Compound 13 (denoted as C13): white solid, yield 87%. 1 H NMR (500 MHz, Chloroform- d ) δ 8.23 (dd, J = 8.7, 5.4 Hz, 1H), 7.26 (td, J = 8.5, 2.5 Hz, 1H), 7.15 (dd, J =8.0, 2.5 Hz, 1H), 5.95 (s, 1H), 2.22 (s, 3H), 1.92 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ168.87 , 167.10 , 165.05 , 160.54 , 140.92 , 140.84 , 133.81 , 133.73 , 119.43 , 119.40 , 117.67 , 117.49 , 115.21 , 115.02, 106.39, 43.14, 43.13, 23.70, 21.55. ESI-MS, m / Z [M+H] + Theoretical value: 338.9644; Test value: 338.9644.

[0035] Compound 14 (denoted as C14): white solid, 90% yield. 1 H NMR (500 MHz, CDCl3) δ = 7.86 –7.80 (m, 1H), 7.75 – 7.68 (m, 2H), 7.61 (dt, J = 7.6, 4.1 Hz, 1H), 7.42 –7.35 (m, 2H), 6.95 (t, J = 8.6 Hz, 2H), 5.67 (s, 1H), 1.99 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 166.91 , 160.82 , 138.51 , 134.98 , 132.82 , 130.92, 130.06 , 128.15 , 128.08 , 127.93 , 123.08 , 115.65 , 115.47 , 103.78, 47.08, 21.61. ESI-MS, m / Z [M+H] + Theoretical value: 400.9794; Test value: 400.9801.

[0036] Compound 15 (denoted as C15): white solid, yield 82%. 1 H NMR (500 MHz, Chloroform-d) δ8.20 (dd, J = 7.7, 1.3 Hz, 1H), 7.93 – 7.86 (m, 1H), 7.69 (td, J = 7.6, 1.4Hz, 1H), 7.55 (td, J = 7.7, 1.2 Hz, 1H), 7.52 – 7.48 (m, 1H), 7.31 (dd, J =5.8, 3.4 Hz, 2H), 7.22 (dd, J = 5.6, 3.5 Hz, 1H), 5.75 (s, 1H), 2.59 (s, 3H), 1.83 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ 166.28 , 160.91 , 138.65 ,134.84 , 134.32 , 132.50 , 130.71 , 129.92 , 129.55 , 127.95 , 125.84 ,123.24 , 104.65 , 46.22, 21.23. ESI-MS, m / Z [M+Na] + Theoretical value: 375.0021; Test value: 397.0051375.0231.

[0037] Compound 16 (denoted as C16): white solid, yield 91%. 1 H NMR (500 MHz, Chloroform- d ) δ8.20 (dd, J = 7.7, 1.3 Hz, 1H), 7.69 (td, J = 7.5, 1.4 Hz, 1H), 7.64 – 7.59(m, 2H), 7.54 (td, J = 7.6, 1.2 Hz, 1H), 7.49 (dd, J = 7.6, 1.1 Hz, 1H), 7.31– 7.22 (m, 2H), 5.69 (s, 1H), 2.40 (s, 3H), 1.78 (s, 3H). 13 C NMR (126 MHz, Chloroform- d) δ 166.93, 161.12, 139.67, 138.76, 134.83, 133.88, 130.83, 129.91, 129.19, 127.89, 125.86, 123.26, 104.29 , 47.30, 21.67, 21.43. ESI-MS, m / Z [M+H] + Theoretical value: 397.0055; Test value: 397.0051.

[0038] Compound 17 (denoted as C17): white solid, yield 69%. 1 H NMR (500 MHz, CDCl3) δ = 8.08 (d, J = 7.9 Hz, 1H), 7.60 (s, 2H), 7.34 (d, J = 7.9 Hz, 1H), 7.30 – 7.26 (m, 3H), 5.63 (s, 1H), 2.48 (s, 3H), 2.39 (s, 3H), 1.79 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 167.27 , 146.37 , 139.88 , 138.97 , 134.27 , 131.16 , 131.09, 129.43 , 128.65 , 126.13 , 104.55 , 77.62 , 47.74 , 22.29, 21.98, 21.70. ESI-MS, m / Z [M+H] + Theoretical value: 411.0199; Test value: 411.0208.

[0039] Compound 18 (denoted as C18): white solid, yield 65%. 1 H NMR (500 MHz, CDCl3) δ = 8.17 (d, J = 2.1 Hz, 1H), 7.85 (d, J = 2.3 Hz, 1H), 7.67 (ddd, J = 10.2, 8.4, 2.3 Hz,2H), 7.44 (d, J= 8.2 Hz, 1H), 6.96 (d, J = 8.7 Hz, 1H), 5.64 (s, 1H), 3.94 (s, 3H), 1.83 (s, 3H). 13 C NMR (126 MHz, Chloroform- d ) δ 160.03 , 157.49 ,150.59 , 135.90 , 135.46 , 135.25 , 134.68 , 130.50 , 129.32 , 128.57 ,125.95 , 121.71 , 111.45 , 111.17, 56.57. ESI-MS, m / Z [M+H] + Theoretical value: 446.9601; Test value: 446.9611.

[0040] Table 1 Substituent Summary Table

[0041]

[0042] Example 2: Anti-pancreatic cancer activity test of heterochromatic 1-one compounds Using 5-FU (5-fluorouracil), a commonly used anticancer drug in clinical practice, as a positive control, the in vitro antitumor activity of compounds C1-C18 against pancreatic cancer cells was tested using the CCK-8 assay. Human pancreatic cancer PNAC-1 cells were cultured in DMEM / 10% fetal bovine serum medium at 37°C with 5% CO2. Cells in the logarithmic growth phase were collected and seeded in 96-well plates at a density of 5 × 10⁶ cells / well. 3 Cells were incubated at 100 µL / well for 24 hours, then the solvent (DMSO, 1:2000 dilution, as a blank group) was replaced with different compounds and 5-FU (stock solution concentration 100 mM / L, working solution concentration 50 µM / L) and incubated for another 48 hours. Then, 10 µL of CCK-8 solution was added to each well and incubated for 2 hours. Each group was repeated in triplicate. Finally, absorbance was measured at 450 nm using a microplate reader. Cell inhibition rate was calculated based on absorbance, and survival rate was calculated as: (OD of drug-treated group - OD of blank group) / (OD of positive control group (i.e., 5-FU-treated group) - OD of blank group) * 100%. Specific results are shown in Table 2.

[0043] Table 2. Cell viability test at 100 μM concentration

[0044] Cell viability assay at 100 μM concentration: At a concentration of 100 μM, compared with the positive control, compounds C1 / C2 / C3 / C4 / C5 / C8 / C10 / C11 / C12 / C14 / C16 / C17 showed significantly stronger inhibitory activity against pancreatic cancer cells than 5-FU. Compounds C2 / C5 / C11 / C12 exhibited even more pronounced activity, reducing the survival rate of pancreatic cancer cells to below 10%. Compounds C1 / C3 / C4 / C8 / C10 / C14 / C16 / C17 also showed high inhibitory activity against cancer cell proliferation, showing a significant difference compared to the positive control group. This fully demonstrates that the compounds of this invention have a good ability to inhibit cancer cell proliferation and can be developed as a potential anti-pancreatic cancer drug.

Claims

1. A compound of isochroman-1-one, characterized in that, The structural formula of the compound is selected from the following compounds: 。 2. The use of the isochromic 1-one compound of claim 1 in the preparation of a drug for treating pancreatic cancer.

3. The application according to claim 2, characterized in that, The heterochromatic 1-one compounds can inhibit the growth of pancreatic cancer cells.

4. The application according to claim 2, characterized in that, The drug contains a pharmaceutically acceptable carrier.

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