Selenium-containing isoquinoline N-oxide compound as well as preparation method and medical application thereof
By synthesizing selenium-containing isoquinoline N-oxides through the visible light reaction of 2-alkynylbenzaldehyde oxime and diselen ether in an organic solvent, the limitations of existing synthesis methods are solved, achieving a balance between structural diversity and economy, and demonstrating significant neuroprotective activity.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-18
- Publication Date
- 2026-04-07
AI Technical Summary
In the existing technology, the synthesis methods of selenium-containing isoquinoline N-oxides are limited, making it difficult to balance structural diversity and step economy. The research on bioactivity is not in-depth, and there is a lack of development of neuroprotective active compounds.
In an organic solvent, using 2-alkynylbenzaldehyde oxime and diselenoether as reactants, a stir-dried reaction under visible light irradiation was carried out to synthesize selenium-containing isoquinoline N-oxides, which were then purified by column chromatography, avoiding the use of metal catalysts and oxidants.
The synthesis process is mild and environmentally friendly, and the product exhibits significant neuroprotective activity, effectively preventing or treating neurodegenerative diseases caused by oxidative stress and neuroinflammation. It also has low cytotoxicity and shows promising development potential.
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Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of organic synthetic chemistry, and particularly relates to a selenium-containing isoquinoline N-oxide compound and a preparation method and medical use thereof. BACKGROUND
[0002] Aza-heterocycles are a class of structural backbones widely existing in nature, and have occupied an important position in the pharmaceutical industry due to their excellent biological activity, high stability and significant action efficiency in the biological body. Among them, N-oxidized heterocycles, especially isoquinoline as a representative mother nucleus structure, not only exhibit a broad application prospect in the field of material science as an advantage structural unit, but also have various important pharmacological activities including antibacterial, antiviral, antifungal and anticancer. Therefore, developing a synthetic strategy for efficiently constructing this kind of skeleton has long been widely concerned by organic chemists and medicinal chemists.
[0003] On the other hand, selenium, as an essential trace element for human body, has been proved to have significant pharmacological activity, especially plays a key role in the antioxidant defense system, such as participating in the active center of glutathione peroxidase. In recent years, the pharmacological research of selenium-containing compounds has been increasingly valued, and experimental data show that such compounds not only exhibit good potential in anti-tumor (such as prostate cancer, breast cancer and lung cancer) and anti-virus, but also show application prospect in the field of neuroprotection, which can effectively resist the nerve damage caused by oxidative stress. In the field of chemical synthesis, organoselenium compounds are not only important synthetic intermediates and catalysts, but also widely used in the construction and development of organic molecules such as drugs, dyes and pesticides.
[0004] In view of the unique biological activity and physicochemical properties of N-oxidized heterocycles and selenium units, developing a simple and efficient synthetic strategy to construct novel selenium-containing N-oxidized heterocycles has become an important target for synthetic chemists, for example, research shows that selenium-modified isoquinoline derivatives have good antitumor effect. However, the current reported synthesis methods for selenium-containing isoquinoline N-oxide system are still very limited, especially the practical routes that can balance structural diversity and step economy still need to be developed. More importantly, the biological activity research of selenium-containing isoquinoline N-oxide is still blank, and its structure-activity relationship and mechanism of action need to be further explored. SUMMARY
[0005] One of the purposes of the present application is to provide a class of selenium-containing isoquinoline N-oxide compounds with neuroprotective activity; the second purpose of the present application is to provide a method for preparing and purifying the above-mentioned selenium-containing isoquinoline N-oxide compounds; the third purpose of the present application is to use the above-mentioned selenium-containing isoquinoline N-oxide compounds for preparing clinical neuroprotective drugs.
[0006] The above-mentioned objective of this invention is achieved through the following technical solution: Using 2-alkynylbenzaldehyde oxime with the structure shown in formula (I) and diselen ether with the structure shown in formula (II) as reactants in an organic solvent, the reaction is carried out under visible light irradiation and with open stirring at room temperature. After the reaction is completed, the solvent is removed from the reaction solution under reduced pressure to obtain a crude product. The crude product is purified by column chromatography to obtain a selenium-containing isoquinoline N-oxide compound with the structure shown in formula (III). The reaction equation is shown below:
[0007] Among them, compound (I) is 2-alkynylbenzaldehyde oxime, with substituent R 1 For C1-C 10 Alkyl, phenyl, or phenyl substituted with one or more substituents, wherein the substituents are alkoxy, alkyl, or halogen; the compound of formula (II) is a diaryl diselenide or a dialkyl diselenide, wherein the substituent R 2 It is aryl or alkyl.
[0008] The molar ratio of 2-alkynylbenzaldehyde oxime with the structure shown in formula (I) to diselenoether with the structure shown in formula (II) is 1:0.5-1:1, preferably 1:1.
[0009] The organic solvent is selected from acetonitrile, methanol, DMF, ethanol, tert-butanol or 1,2-dichloroethane, preferably acetonitrile.
[0010] The light source for the reaction is one of sunlight, white fluorescent lamp, blue LED, or purple LED, with blue LED being preferred; the reaction time at room temperature with open stirring is 24 to 36 hours; preferably, the reaction is carried out at room temperature for 30 hours.
[0011] After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the concentrate was separated by column chromatography using a mixture of dichloromethane and methanol as the eluent, wherein the volume ratio of dichloromethane to methanol was (1-50):1. The eluent was collected, and the solvent was evaporated by rotary evaporation to obtain the selenoyl isoquinoline-N-oxide compound shown in formula (III).
[0012] The selenium-containing isoquinoline-N-oxide compounds of this invention possess significant neuroprotective activity and can be used to prepare drugs for the prevention or treatment of neurodegenerative diseases. They exhibit clear intervention and protective potential against neurodegenerative lesions caused by factors such as oxidative stress and neuroinflammation.
[0013] The beneficial effects of this invention are as follows: (1) Excellent synthesis process: mild reaction conditions, no need for harsh reaction conditions, low energy consumption, reduced energy consumption and equipment requirements, and good compatibility with a variety of functional groups.
[0014] (2) Environmentally friendly: The whole process does not rely on metal catalysts and photocatalysts, which fundamentally avoids product pollution caused by metal residues. At the same time, it avoids the use of oxidants, reduces the generation of reaction waste, and conforms to the sustainable development concept of green chemistry.
[0015] (3) Significant biological activity: In vitro experiments have confirmed that the selenium-containing isoquinoline-N-oxide derivative provided by this invention has a significant protective effect in the H2O2-induced SH-SY5Y neuroinflammation model, which can improve cell survival rate and show low cytotoxicity to normal cells, indicating that it has excellent neuroprotective activity and good development prospects. Detailed Implementation
[0016] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0017] The present invention provides the following technical solution: In an organic solvent, 2-alkynylbenzaldehyde oxime with the structure shown in formula (I) and diselenide with the structure shown in formula (II) are used as reaction raw materials. The reaction is carried out under open stirring under visible light irradiation. After the reaction is completed, the solvent is removed from the reaction solution under reduced pressure to obtain a crude product. The crude product is purified by column chromatography to obtain a selenyl isoquinoline-N-oxide compound with the structure shown in formula (III). The reaction equation is shown below:
[0018] Among them, compound (I) is 2-alkynylbenzaldehyde oxime, with substituent R 1 For C1-C 10 Alkyl, phenyl, or phenyl substituted with one or more substituents, wherein the substituent is alkoxy, alkyl, or halogen; the compound of formula (II) is a diaryl diselenide or a dialkyl diselenide, wherein the substituent R 2 It is aryl or alkyl.
[0019] Compound (I) is prepared by the following route: 2'-Iodobenzaldehyde (1 mmol), arylacetylene (1.1 mmol), tetrakis(triphenylphosphine)palladium (0.01 mmol), cuprous iodide (0.02 mmol), and triethylamine (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer and stirred in an oil bath at 50 °C for 12 hours. After the reaction was completed, the mixture was quenched with saturated ammonium chloride solution and extracted with dichloromethane. The organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography to obtain 2-(arylacetylenyl)benzaldehyde oxime.
[0020] 1 mmol of 2-(arylethynyl)benzaldehyde oxime was added to a 20 mL test tube equipped with a magnetic stirrer and dissolved in 2 mL of anhydrous ethanol. Then, pyridine (2 mmol) and hydroxylamine hydrochloride (1.5 mmol) were added sequentially to the solution, and the mixture was stirred at room temperature for 12 hours. After the reaction was complete, the organic phase was extracted with dichloromethane. The organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography to obtain compound (I) 2-ynylbenzaldehyde oxime.
[0021] Example 1: The reaction equation is shown below:
[0022] 0.25 mmol of 2-(2-phenylethynyl)benzaldehyde oxime, 0.25 mmol of diphenyldiselenoether, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel mesh 200-300 mesh, eluent: dichloromethane / methanol = 10 / 1) to obtain the target compound 1a in 90% yield. 1 H NMR (CDCl3, 400 MHz) δ 8.94 (s, 1H), 8.37 (d, J = 8.1Hz, 1H), 7.72 (d, J = 7.8 Hz, 1H), 7.65-7.52 (m, 2H), 7.43-7.39 (m, 3H),7.31-7.28 (m, 2H), 7.13-7.06 (m, 3H), 7.05-7.01 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 154.3, 139.2, 132.3, 130.9, 130.6, 129.8, 129.5, 129.3, 129.2, 129.1, 129.04, 128.51, 128.3, 127.5, 127.1, 124.5.
[0023] Example 2: The reaction equation is shown below:
[0024] 0.25 mmol of 2-(2-phenylethynyl)benzaldehyde oxime, 0.25 mmol of diphenyldiselenoether, and 1 mL of methanol were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 10 / 1) to obtain the target compound 1a in 82% yield.
[0025] Example 3: The reaction equation is shown below: 0.25 mmol of 2-(2-phenylethynyl)benzaldehyde oxime, 0.25 mmol of diphenyldiselenoether, and 1 mL of DMF were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 10 / 1) to obtain the target compound 1a in 77% yield.
[0026] Example 4: The reaction equation is shown below:
[0027] 0.25 mmol of 2-(2-phenylethynyl)benzaldehyde oxime, 0.14 mmol of diphenyldiselenoether, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel mesh 200-300 mesh, eluent: dichloromethane / methanol = 10 / 1) to obtain the target compound 1a in 71% yield.
[0028] Example 5: The reaction equation is shown below:
[0029] 0.25 mmol of 2-(2-phenylethynyl)benzaldehyde oxime, 0.2 mmol of diphenyldiselenoether, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel mesh 200-300 mesh, eluent: dichloromethane / methanol = 10 / 1) to obtain the target compound 1a in 83% yield.
[0030] Example 6: The reaction equation is shown below:
[0031] 0.25 mmol of 2-[2-(4-methylphenyl)ethynyl]benzaldehyde oxime, 0.25 mmol of diphenyldiselenoether, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 4 / 1) to obtain the target compound 1b in 81% yield. 1 H NMR (CDCl3, 400 MHz) δ 8.94 (s, 1H); 8.34 (d,J = 7.6 Hz, 1H), 7.72-7.68 (m, 1H), 7.58-7.52 (m, 2H), 7.23-7.19 (m, 5H),7.12-7.07 (m, 2H), 7.08-7.03 (m, 2H) 2.41 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ153.4, 140.5, 137.6, 134.2, 132.7, 131.6, 130.2, 129.9, 129.6, 129.4, 129.2,129.0, 128.7, 127.4, 127.0, 125.2, 23.2.
[0032] Example 7: The reaction equation is shown below:
[0033] 0.25 mmol of 2-[2-(4-chlorophenyl)ethynyl]benzaldehyde oxime, 0.25 mmol of diphenyldiselenoether, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel mesh 200-300 mesh, eluent: dichloromethane / methanol = 4 / 1) to give the target compound 1c in 82% yield. 1 H NMR (CDCl3, 400 MHz) δ 8.95 (s, 1H), 8.33 (d, J =8.0 Hz, 1H); 7.82 (d, J = 7.4 Hz, 1H); 7.62-7.54 (m, 2H); 7.45-7.41 (m, 3H);7.27-7.24 (m, 2H); 7.09 (d, J = 8.4 Hz, 2H); 6.92 (d, J = 8.4 Hz, 2H). 13 C NMR(100 MHz, CDCl3) δ 154.3, 139.3, 135.9, 134.4, 133.7, 132.8, 131.6, 130.3,129.7,129.6, 129.4, 129.3, 129.0, 128.7, 128.2, 127.1, 124.2.
[0034] Example 8: The reaction equation is shown below:
[0035] 0.25 mmol of 2-(1-hexyn-1-yl)benzaldehyde oxime, 0.25 mmol of diphenyldiselenes, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel mesh 200-300 mesh, eluent: dichloromethane / methanol = 4 / 1) to obtain the target compound 1d, with a yield of 68%. 1H NMR (CDCl3, 400 MHz) δ 8.90 (s, 1H), 8.35-8.27 (m, 1H), 7.66-7.60 (m, 1H), 7.56-7.45 (m, 2H), 7.15-7.12 (m, 5H), 3.54-3.50 (m, 2H), 1.65-1.59 (m, 2H), 1.45-1.39 (m, 2H), 0.91 (t, J = 7.2 Hz, 3H). 13 C NMR (100MHz, CDCl3) δ 156.5, 139.7, 135.4, 133.8, 131.6, 129.94, 129.56, 129.2,128.5, 127.8, 126.5, 125.3, 124.6, 32.7, 29.3, 24.2, 14.5.
[0036] Example 9: The reaction equation is shown below:
[0037] 0.25 mmol of 2-ethynylbenzaldehyde oxime, 0.25 mmol of diphenyldiselenoether, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel mesh 200-300 mesh, eluent: dichloromethane / methanol = 4 / 1) to obtain the target compound 1e in 51% yield. 1 H NMR (CDCl3, 400 MHz) δ 8.65 (s, 1H), 8.20-8.06 (m, 1H), 7.96 (d,J = 1.6 Hz, 1H), 7.79-7.65 (m, 1H), 7.64-7.60 (m, 2H), 7.57 (dd, J = 7.8, 1.5Hz, 2H), 7.45-7.34 (m, 3H). 13 C NMR (100 MHz, CDCl3) δ 139.6, 136.8, 135.5,132.9, 131.4, 130.7, 129.9, 129.4, 129.2, 129.0, 127.4, 126.2, 124.3.
[0038] Example 10: The reaction equation is shown below:
[0039] 0.25 mmol of 2-(2-phenylethynyl)benzaldehyde oxime, 0.25 mmol of di(4-methylphenyl)diselenoether, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 4 / 1) to obtain the target compound 1f in 83% yield. 1 H NMR (CDCl3, 400 MHz) δ 8.92 (s, 1H), 8.38 (d, J =8.2 Hz, 1H), 7.69 (d, J = 7.4 Hz, 1H), 7.57-7.51 (m, 2H), 7.44-7.39 (m, 3H),7.32-7.25 (m, 2H), 6.92-6.87 (m, 4H), 2.21 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ151.6, 139.4, 138.1, 135.8, 133.2, 131.8, 130.3, 129.9, 129.6, 129.4, 129.1,128.9, 128.3, 128.0, 127.6, 125.1, 21.3.
[0040] Example 11: The reaction equation is shown below:
[0041] 0.25 mmol of 2-(2-phenylethynyl)benzaldehyde oxime, 0.25 mmol of di(4-fluorophenyl)diselenoether, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel mesh 200-300 mesh, eluent: dichloromethane / methanol = 4 / 1) to obtain 1 g of the target compound, with a yield of 87%. 1H NMR (CDCl3, 400 MHz) δ 8.95 (s, 1H), 8.42-8.31 (m,1H), 7.74-7.66 (m, 1H), 7.61-7.56 (m, 2H), 7.44-7.38 (m, 3H), 7.26-7.23 (m,2H), 7.01-6.95 (m, 2H), 6.83-6.76 (m, 2H). 13 C NMR (100 MHz, CDCl3) δ 163.4(d, 1 J C-F = 246.1 Hz), 152.4, 139.2, 135.1, 133.7 (d, 3 J C-F = 7.9 Hz), 131.8,130.1, 129.8, 129.6, 129.3, 128.6, 128.4, 128.3, 125.4 (d, 4 J C- F = 3.3 Hz), 125.1, 115.2 (d, 2 J C-F = 21.7 Hz).
[0042] Example 12: The reaction equation is shown below:
[0043] 0.25 mmol of 2-(2-phenylethynyl)benzaldehyde oxime, 0.25 mmol of di-2-naphthyldiselenoether, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 5 / 1) to obtain the target compound in 1 h, with a yield of 75%. 1H NMR (CDCl3, 400 MHz) δ 8.94 (s, 1H), 8.32 (d, J = 8.4Hz, 1H), 7.87 (d, J = 8.3 Hz, 1H), 7.81-7.63 (m, 3H), 7.59-7.34 (m, 4H),7.31-7.26 (m, 3H), 7.23 (dd, J = 7.3, 2.3 Hz, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.97 (dd, J = 7.3, 0.9 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 173.4, 151.5,135.3, 134.9, 133.5, 132.4, 131.9, 130.4, 130.0, 129.8, 129.4, 129.1, 128.7,128.4, 128.1, 128.0, 127.4, 127.2, 126.5, 126.1, 125.8, 125.2.
[0044] Example 13: The reaction equation is shown below:
[0045] 0.25 mmol of 2-(2-phenylethynyl)benzaldehyde oxime, 0.25 mmol of dibenzyl diselenide, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 4 / 1) to obtain the target compound 1i in 54% yield. 1 H NMR (CDCl3, 400 MHz) δ 8.92 (s, 1H), 8.50-8.29 (m, 1H), 7.73-7.65 (m, 1H), 7.62-7.51 (m, 2H), 7.42-7.39 (m, 4H), 7.15-7.10 (m, 6H),6.72 (d, J = 7.7 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 151.9, 136.2, 133.7,132.1, 130.8, 129.9, 129.6, 129.2, 128.7, 128.6, 128.4, 128.3, 128.21, 126.9,124.2, 33.6.
[0046] Example 14: The reaction equation is shown below:
[0047] 0.25 mmol of 2-(2-phenylethynyl)benzaldehyde oxime, 0.25 mmol of dimethyl diselenyl ether, and 1 mL of acetonitrile were added to a 20 mL test tube equipped with a magnetic stirrer. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 4 / 1) to obtain the target compound 1j in 62% yield. 1 H NMR (CDCl3, 400 MHz) δ 9.16 (s, 1H), 8.37 – 8.21 (m, 1H), 8.04 – 7.96 (m, 2H), 7.69 – 7.46 (m, 6H), 2.53 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 145.9, 144.8, 139.5, 136.2, 133.6, 131.2, 130.9, 129.8, 128.6 (d, J= 14.6 Hz), 127.4, 127.1, 124.1, 11.97.
[0048] Example 15: Investigation of the anti-neuroinflammatory activity of the compound.
[0049] The MTT assay was used to detect the in vitro proliferation inhibitory activity of the target compound 1a-1j on SH-SY5Y cultured cells. The specific procedures were as follows: SH-SY5Y cells were cultured in triplicate. H2O2 model group: After routine culture and passage, cells were suspended in serum-containing DMEM and seeded into 96-well plates. Cells were incubated statically at 37 ℃ and 5% CO2 for 12 h until cell adhesion. The drug-treated groups were pretreated with 12.5, 25, and 50 μM of the drug for 1 h, followed by incubation with 200 μM H2O2 for 4 h. Then, 200 mL of MTT was added to each well, and after incubation for 4 h, the absorbance was measured at 490 nm using a microplate reader. Survival rate (%) = [A490 (drug-treated group) - A490 (blank control)] / [A490 (negative control) - A490 (blank control)] × 100%. The specific experimental results are shown in the table below.
[0050] The test results showed that most of the compounds of this invention exhibited significant protective effects in the H2O2-induced SH-SY5Y neuroinflammation model, improving cell survival. Some compounds showed better efficacy than the control drug vitamin E at a concentration of 50 μM. In particular, compounds 1e and 1i achieved cell survival rates of 75.80% and 74.48%, respectively, at a concentration of 50 μM, demonstrating strong anti-neuroinflammation potential.
[0051] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.
Claims
1. A selenium-containing isoquinoline N-oxide compound, characterized in that: The structural formula of the selenium-containing isoquinoline N-oxide compound is: ; where the substituent R 1 For C1-C 10 Alkyl, phenyl, or phenyl substituted with one or more substituents, wherein the substituents are alkoxy, alkyl, or halogen, R 2 It is aryl or alkyl.
2. A method for preparing a selenium-containing isoquinoline N-oxide compound according to claim 1, characterized in that, The preparation method is as follows: 2-Alynylbenzaldehyde oxime and diselenoether are reacted in an organic solvent under visible light irradiation and at room temperature with open stirring to obtain selenium-containing isoquinoline-N-oxide compounds.
3. The method for preparing selenium-containing isoquinoline N-oxide compounds according to claim 2, characterized in that, The structural formula of 2-alkynylbenzaldehyde oxime is: The structural formula of diselenoether is ; Among them, substituent R 1 For C1-C 10 Alkyl, phenyl, or phenyl substituted with one or more substituents, wherein the substituents are alkoxy, alkyl, or halogen, R 2 It is aryl or alkyl.
4. The method for preparing selenium-containing isoquinoline N-oxide compounds according to claim 2, characterized in that, The molar ratio of 2-alkynylbenzaldehyde oxime to diselenoether is 1:0.5 to 1.
5. The method for preparing selenium-containing isoquinoline N-oxide compounds according to claim 2, characterized in that, The organic solvent is selected from acetonitrile, methanol, N,N-dimethylformamide, ethanol, tert-butanol, or 1,2-dichloroethane.
6. The method for preparing selenium-containing isoquinoline N-oxide compounds according to claim 2, characterized in that, The light source for the visible light reaction is one of sunlight, white fluorescent lamp, blue LED, or purple LED; the open-top stirred reaction time at room temperature is 24 to 36 hours.
7. The method for preparing selenium-containing isoquinoline N-oxide compounds according to claim 2, characterized in that, After stirring and reaction, the mixture was concentrated under reduced pressure and separated by column chromatography. A dichloromethane / methanol mixture was used as the eluent, wherein the volume ratio of dichloromethane to methanol was 1–50:
1.
8. An application of the selenium-containing isoquinoline N-oxide compound according to claim 1, characterized in that: Selenium-containing isoquinoline N-oxide compounds are used to prepare drugs for the prevention and / or treatment of neuroinflammatory diseases.
9. The application of the selenium-containing isoquinoline N-oxide compound according to claim 8, characterized in that, The neuroinflammatory-related diseases are neurological diseases caused by or related to the pathological process of neuroinflammatory inflammation.