2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1, 2-a] pyrimidin-4-one

Abstract

The invention belongs to the field of pharmacy, and particularly relates to a 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1, 2-a] pyrimidine-4-ketone compound and application thereof. The compound is prepared through electrochemical driving under the conditions of no metal and no oxidizing agent, is a yellow solid, and gives a quasi-molecular ion peak [M + H] +: 397.0250 through a high-resolution mass spectrum. The invention relates to application of 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1, 2-a] pyrimidine-4-ketone in preparation of drugs for resisting the Alzheimer's disease and the Parkinson's disease, the 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1, 2-a] pyrimidine-4-ketone has a good effect on resisting the Alzheimer's disease and the Parkinson's disease, and the 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1, 2-a] pyrimidine-4-ketone can be used for preparing drugs for resisting the Alzheimer's disease and the Parkinson's disease. A novel medicine is provided for resisting the Alzheimer's disease and the Parkinson's disease.

Description

Technical Field

[0001] The present invention belongs to the field of pharmacy, and specifically relates to a 2-(3-fluorophenyl)-3-(phenylselenoyl)-4H-pyridine-[1,2-a]pyrimidin-4-one compound and application thereof. Background Art

[0002] This invention is based on the results of previous studies and conducts in-depth research on the biological activity of 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one compounds. The previous study was published in Molecules in 2023 and is titled Electro-Oxidative C3-Selenylation of Pyrido[1,2-a]pyrimidin-4-ones. In this study, the C3 selenization reaction of pyrido[1,2-a]pyrimidin-4-one was successfully achieved under electrochemical drive, demonstrating the application potential of this type of chemical structure in the field of synthesis. Based on this, the present invention further studies the structure and function of 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one compounds, focusing on exploring their potential application prospects in the field of biological activity. Summary of the invention

[0003] The object of the present invention is to provide a 2-(3-fluorophenyl)-3-(phenylselenoyl)-4H-pyridine-[1,2-a]pyrimidin-4-one compound and application thereof.

[0004] The technical solution to solve the above technical problems is as follows:

[0005] The method for preparing 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridin-[1,2-a]pyrimidin-4-one under metal-free and oxidant-free conditions is as follows:

[0006] Taking 2-(3-fluorophenyl)-4H-pyrido[1,2-a]pyrimidin-4-one as the starting material, 2-(3-fluorophenyl)-4H-pyrido[1,2-a]pyrimidin-4-one 1e (0.2 mmol), diphenyl diselenide 2a (1.2 equiv, 0.24 mmol), nBu4NPF6 (0.2mmol) and MeCN (10mL) were added, and the reaction flask was equipped with two Pt electrodes (1cm×1cm), which were the cathode and the anode. The electrolysis was carried out in an air atmosphere at 60°C, using a constant voltage of 5V until the starting material was completely consumed (TLC monitoring, about 5h). After the reaction was completed, the mixture was quenched with NaHCO3 (sat.aq. 15mL) and extracted with CH2Cl2 (3×5mL), and the organic solvent was concentrated under reduced pressure to obtain an extract. The dichloromethane layer extract was purified by silica gel column chromatography using a mixed solvent of ethyl acetate and petroleum ether as the eluent (the volume ratio of petroleum ether to ethyl acetate was 5:1) to obtain the product 2-(3-fluorophenyl)-3-(phenylselenoyl)-4H-pyridine-[1,2-a]pyrimidin-4-one (3m).

[0007]

[0008] The use of 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one compound in the preparation of anti-Alzheimer's disease drugs, the structural formula of which is shown in Formula 3m:

[0009]

[0010] The present invention provides the use of a 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one compound in the preparation of a drug for preventing and treating Alzheimer's disease. 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one can be used alone or in combination with other drugs to prevent and treat Alzheimer's disease. It is particularly effective in the ICR mouse model.

[0011] The present invention provides the use of 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one in the preparation of a drug for improving learning and memory disorders. 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one can be used alone or in combination with other drugs to improve learning and memory disorders. It is particularly effective when applied to an ICR mouse model.

[0012] The present invention provides the use of 2-(3-fluorophenyl)-3-(phenylselenoyl)-4H-pyridine-[1,2-a]pyrimidin-4-one in the preparation of a drug for improving impaired exploratory ability.

[0013] The present invention provides the use of 2-(3-fluorophenyl)-3-(phenylselenoyl)-4H-pyridine-[1,2-a]pyrimidin-4-one in the preparation of a drug for alleviating the inactivation of hippocampal acetylcholine neurotransmitters.

[0014] The present invention provides the use of 2-(3-fluorophenyl)-3-(phenylselenoyl)-4H-pyridine-[1,2-a]pyrimidin-4-one in the preparation of a drug for reducing hippocampal ROS and lipid peroxidation levels.

[0015] The use of 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one compound in the preparation of anti-Parkinson's drugs, the structural formula of which is shown in Formula 3m:

[0016]

[0017] The present invention provides the use of a 2-(3-fluorophenyl)-3-(phenylselenoyl)-4H-pyridine-[1,2-a]pyrimidin-4-one compound in the preparation of a drug for improving the reduced content of GSH and SOD caused by Parkinson's disease.

[0018] The present invention provides the use of a 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one compound in the preparation of a drug for resisting Parkinson's disease and improving the anti-oxidative stress level of brain tissue and reducing the content of inflammatory factors.

[0019] Beneficial effects of the present invention: 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one synthesized by the electrochemical driving method of the present invention can significantly improve the cognitive function of Alzheimer's disease model mice, reduce the level of oxidative stress, and improve the antioxidant capacity, showing a good anti-Alzheimer's disease effect. In addition, 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one also showed significant therapeutic effects in the Parkinson's disease rat model, improved the anti-oxidative stress level of brain tissue, and effectively reduced the content of inflammatory factors. 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one can be developed as an anti-Alzheimer's disease and anti-Parkinson's disease drug, and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 For compound 3m 1 H NMR spectrum;

[0021] Figure 2 For compound 3m 13 C NMR spectrum;

[0022] Figure 3 For compound 3m 19 F NMR spectrum;

[0023] Figure 4 is the high-resolution mass spectrum of compound 3m;

[0024] Figure 5 The escape latency of mice was tested in Morris water maze;

[0025] Figure 6 Morris water maze test: the number of times mice cross the target platform

[0026] Figure 7 The swimming speed of mice was tested in Morris water maze;

[0027] Figure 8 The index of movement distance and novel object recognition in the central area of ​​the open field;

[0028] Fig. 9 The effect of compound 3m on the levels of ChAT and AChE in the hippocampus of AD mice;

[0029] Fig.10 The effect of compound 3m on Ach level in the hippocampus of AD mice;

[0030] Fig.11 The effect of compound 3m on the levels of ROS, CAT, and MDA in the hippocampus of AD mice;

[0031] Fig.12 The effect of compound 3m on ROS level in the hippocampus of AD mice;

[0032] Fig.13 The effect of compound 3m on the number of circles of Parkinson's disease rats;

[0033] Fig.14 The effect of compound 3m on the total head turning time of Parkinson's disease rats;

[0034] Fig.15 The effect of compound 3m on the total climbing time of Parkinson's disease rats;

[0035] Fig.16 The effect of compound 3m on the oxidative stress level in the brain tissue of Parkinson's disease rats;

[0036] Fig.17 This is the effect of compound 3m on the levels of inflammatory factors in the brain tissue of Parkinson's disease rats. DETAILED DESCRIPTION

[0037] The present invention is further described in detail below in conjunction with embodiments so that those skilled in the art can implement the invention with reference to the description.

[0038] Example 1

[0039] In this embodiment, the method for preparing 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one under metal-free and oxidant-free conditions is as follows:

[0040] Taking 2-(3-fluorophenyl)-4H-pyrido[1,2-a]pyrimidin-4-one as the starting material, 2-(3-fluorophenyl)-4H-pyrido[1,2-a]pyrimidin-4-one 1e (0.2 mmol), diphenyl diselenide 2a (1.2 equiv, 0.24 mmol), n Bu4NPF6 (0.2mmol) and MeCN (10mL), the reaction flask was equipped with two Pt electrodes (1cm×1cm), the cathode and the anode. The electrolysis was carried out in an air atmosphere at 60°C, using a constant voltage of 5V until the starting material was completely consumed (TLC monitoring, about 5h). After the reaction was completed, the mixture was quenched with NaHCO3 (sat.aq.15mL) and extracted with CH2Cl2 (3×5mL), and the organic solvent was concentrated under reduced pressure to obtain an extract. The dichloromethane layer extract was purified by silica gel column chromatography using a mixed solvent of ethyl acetate and petroleum ether as the eluent (the volume ratio of petroleum ether to ethyl acetate was 5:1) to obtain the product 3m with a yield of 96%.

[0041]

[0042] According to compound 3m 1 H NMR, 13 C NMR and 19 The structure of the compound was determined by F NMR spectroscopy ( Figure 1 , Figure 2 and Figure 3 ), specifically: Compound 3m was purified by silica gel column chromatography (petroleum ether:ethyl acetate=5:1, Rf=0.11), yellow solid (54.75 mg, 96%): mp: 133-134°C. 1 H NMR(500MHz, CDCl3)δ9.08(d,J=7.1Hz,1H),7.83-7.76(m,1H),7.72(d,J=8.8Hz,1H),7.3 5(t,J=5.4Hz,2H),7.30(dd,J=8.6,5.5Hz,3H),7.19(t,J=6.9Hz,1H),7.16-7.06(m,4H). 13C NMR (126MHz, CDCl3) δ166.44,163.46,161.01,157.76,150.27,142.23,142.15,137.12,1 31.53,131.33,129.49,129.06,128.00,126.75,124.77,116.30,116.08,115.89,105.97. 19 F NMR (471MHz, CDCl3) δ-113.07. High-resolution mass spectrometry gave a quasi-molecular ion peak C 20 H 14 FN2OSe[M+H] + :397.0244 (calcd for 397.0250), the molecular formula is C 20 H 13 FN2OSe( Figure 4 ).

[0043] Example 2

[0044] The following is an introduction through specific examples. The experimental methods used in each example are conventional experimental methods in the art unless otherwise specified. The materials, reagents, and instruments used are conventional materials, reagents, and instruments in the art unless otherwise specified, and can be obtained through commercial channels or prepared by conventional methods.

[0045] 1 Experimental methods

[0046] 1.1 Experimental animal grouping, modeling and drug administration

[0047] Randomly select 40 8-10 week old, clean grade, male healthy ICR mice, weighing 18-24g, and randomly divide them into 4 groups, namely blank group, model group, compound group and positive drug group, with 10 mice in each group. According to relevant literature research, the scopolamine method was used to construct the AD mouse model, and the behavioral test was used to verify whether the scopolamine modeling was successful. After 1 week of adaptive feeding, the mice in the compound group were gavaged with 50mg·kg of the compound saline suspension. -1 ·d -1 , mice in the positive drug group were gavaged with 3 mg·kg of donepezil in normal saline -1 ·d -1 , once a day for 21 consecutive days. Two hours after administration on days 22 to 28, each mouse in the model group, compound group, and positive drug group was treated with 0.01 mL·g -1 (body weight) intraperitoneal injection of scopolamine saline solution 3 mg kg -1 ·d -1The blank group was intraperitoneally injected with the same volume of saline. Behavioral tests were performed 30 minutes after the last intraperitoneal injection of scopolamine.

[0048] 1.2 Morris water maze test

[0049] The Morris water maze test lasted for 7 days and was conducted in a quiet environment. The first day was the training adaptation stage, during which the mice practiced standing on the platform; from the second to the fifth day, the swimming time from the mouse entering the water to finding the platform was used as an observation indicator, which was called the escape latency. If the mouse did not find the platform within 90 seconds, it was recorded as 90 seconds; on the morning of the sixth day, the platform was removed, and the time the mouse stayed in the fourth quadrant where the original platform was located, as well as the swimming path and swimming speed, were measured. At the same time, the number of times the mouse crossed the original platform position was recorded.

[0050] 1.3 Open field test

[0051] The experiment was conducted in a quiet environment, with a central area set up in a 50cm×50cm×40cm behavioral test box with a white interior. After the adaptation test, the mouse was placed in the test box from the designated corner to explore freely and start the analysis. The analysis was stopped after 5 minutes of observation, and the data of the overall movement path of the mouse and the range covered were recorded. After the recording was completed, the animal was replaced and the experiment continued. Before the test, each animal was cleaned with 75% ethanol to remove the excrement and odor of the previous mouse and eliminate interference with the test results of the next mouse.

[0052] 1.4 New object recognition test

[0053] Adaptation period: mice move freely in the box for 3 minutes to adapt to the box environment; learning period: two identical objects a and b are placed in the test box, and then the mouse is placed in the box from a fixed corner, explored for 5 minutes, and the time the mouse explores objects a and b is recorded; test period: replace b with a new object c and keep the position unchanged, and put the mouse into the box from the other corner, observe for 5 minutes, and record the total time the mouse explores the new and old objects as N and F respectively. The new object recognition index is used as an indicator to judge the mouse's situational memory ability, and the new object recognition index = N / (N+F). Before each mouse is tested, the inner wall of the box is wiped with 75% ethanol to eliminate the interference of excrement and odor on the test results.

[0054] 1.5 Determination of ROS, CAT, MDA, Ach, AChE, and ChAT contents in hippocampal tissue

[0055] Mouse hippocampal tissue was obtained, and tissue homogenization, lysis, and reaction detection were performed according to the instructions of the ROS (chemiluminescence method), CAT (ammonium molybdate method), MDA (TBA method), Ach (microplate method), AChE (colorimetric method), and ChAT (ultraviolet colorimetric method) kits. The fluorescence values ​​or absorbance values ​​(OD values) were recorded using a microplate reader at wavelengths of 525, 450, 405, 550, 412, and 324 nm, respectively, and the changes in the levels of ROS, CAT, MDA, Ach, AChE, and ChAT were calculated.

[0056] SPSS 26.0 software was used for statistical analysis, and the measurement data were expressed as mean ± standard deviation. Multiple groups were compared using one-way analysis of variance or two-way analysis of variance; P < 0.05 was considered statistically significant.

[0057] 2 Experimental results

[0058] 2.1 Morris water maze test results

[0059] The results are shown in Tables 1-3 and Figure 5-7 , compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01. Compared with the blank group, the escape latency of the model group mice on the 1st to 4th day of the Morris water maze test was prolonged, but the difference was not statistically significant (P>0.05); compared with the model group, the escape latency of the compound group was shortened, and the difference was statistically significant on the 5th day (P<0.05). In the water maze test on the last day: compared with the blank group, the escape latency of the model group mice was prolonged (P<0.05), and the number of crossing the target platform was significantly reduced (P<0.001); compared with the model group, the escape latency and the number of crossing the target platform of the compound group mice increased (P<0.05). There was no statistically significant difference in the swimming speed of mice in each group (P>0.05). It shows that the mice in each group may be affected by factors such as motor ability or fear in the Morris water maze test. The above results indicate that the learning and memory abilities of scopolamine-induced AD mice are impaired, and compound 3m has the effect of improving the learning and memory abilities of AD model mice.

[0060] Table 1 Morris water maze test mouse escape latency (unit: s)

[0061]

[0062] Note: Compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01 Table 2 Morris water maze test mice crossed the target platform times (unit: times)

[0063]

[0064] Note: Compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01 Table 3 Morris water maze test mouse swimming speed (unit: mm / s)

[0065]

[0066] Note: Compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01

[0067] 2.2 Open field and novel object test results

[0068] The results are shown in Table 4 and Figure 8 Compared with the blank group, the movement distance of the model group mice in the central area of ​​the open field was significantly shortened (P < 0.01); compared with the model group, the movement distance of the compound group mice in the central area of ​​the open field was significantly prolonged (P < 0.01). This shows that the exploration ability of AD model mice is impaired, and compound 3m can improve the exploration ability of AD model mice. In the novel object recognition test, the novel object recognition index of the model group mice was lower than that of the blank group (P < 0.05); compared with the model group, the novel object recognition index of the compound group mice increased (P < 0.05). This shows that compound 3m can improve the novel object recognition ability of AD model mice.

[0069] Table 4 Movement distance and novel object recognition index in the central area of ​​the open field

[0070]

[0071] Note: Compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01

[0072] 2.3 Effects of compound 3m on ChAT, Ach, and AChE levels in the hippocampus of AD mice

[0073] The results are shown in Table 5 and Figure 9-10 Compared with the blank group, the levels of ChAT and Ach in the model group were significantly decreased (P < 0.01), and the level of AChE was significantly increased (P < 0.01); compared with the model group, the levels of ChAT and Ach in the compound group were significantly increased (P < 0.05), and the level of AChE was significantly decreased (P < 0.05). This indicates that the acetylcholine neurotransmitter in the hippocampus of AD mice is inactivated, and compound 3m can alleviate this phenomenon.

[0074] Table 5 Effects of compound 3m on ChAT, Ach and AChE levels in the hippocampus of AD mice

[0075]

[0076] Note: Compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01

[0077] 2.4 Effects of compound 3m on ROS, CAT, and MDA levels in the hippocampus of AD mice

[0078] The results are shown in Table 6 and Figure 11-12 Compared with the blank group, the CAT level in the model group was significantly decreased (P < 0.01), and the ROS and MDA levels were significantly increased (P < 0.01); compared with the model group, the CAT level in the compound group was significantly increased (P < 0.01), and the ROS and MDA levels in the compound group were significantly decreased (P < 0.05). This indicates that the levels of ROS and lipid peroxidation in the hippocampus of AD mice are increased, and compound 3m can reduce the levels of ROS and lipid peroxidation in the hippocampus of AD mice.

[0079] Table 6 Effects of compound 3m on ROS, CAT and MDA levels in the hippocampus of AD mice

[0080]

[0081] Note: Compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01

[0082] The results showed that compound 3m can significantly improve the cognitive function of Alzheimer's disease model mice, including learning and memory ability and exploratory behavior, and alleviate the inactivation of acetylcholine neurotransmitters in the hippocampus. In addition, it can significantly reduce the level of oxidative stress and improve antioxidant capacity, which overall shows its potential application value in the treatment of Alzheimer's disease.

[0083] Example 3

[0084] 1 Experimental methods

[0085] 1.1 Grouping and dosing

[0086] 8-10 weeks old, clean grade, healthy male Wistar rats, weighing 200-240g, were randomly selected and divided into 4 groups, 10 rats in each group, namely blank group, model group, positive group, and compound group, and 50 mg kg -1 ·d -1 The compound, model group and control group were given an equal amount of saline, and the positive group was given 1.67 mg·kg -1·d -1 Levodopa was administered continuously for 28 days after the model was established.

[0087] 1.2 Modeling

[0088] After 7 days of adaptive feeding, rats in the model group, positive group, and compound group were anesthetized by intraperitoneal injection of sodium pentobarbital (30 mg / kg), fixed and cut the skin of the skull, located the striatum, determined 1.0 mm in front of the anterior fontanelle and 3.0 mm to the right of the midline as the first injection point, determined 0.2 mm behind the anterior fontanelle, 2.7 mm to the right of the midline, and 5.0 mm below the dura as the second injection point, and injected 5 μL of 6-OHDA containing 0.2 wt% ascorbic acid at the above two injection points, sutured the wound after surgery, and prevented wound infection. After 7 days of feeding, 0.5 mg / kg apomorphine was intravenously injected, and the rats' rotation behavior was observed. When the rats rotated to the left more than 210 times within 30 minutes, it means that the Parkinson's disease rats were successfully modeled.

[0089] 1.3 Behavioral testing

[0090] 1.3.1 Spinning in circles

[0091] The number of rotations of rats in each group within 30 minutes was counted before and after the intervention. Each rat was measured 3 times and the average value was taken as the final result.

[0092] 1.3.2 Pole climbing experiment

[0093] Prepare several bamboo poles of equal length and guide each group of rats to climb the poles. Record the time it takes for each group of rats to turn around and the time it takes to complete the climb. Test each rat three times and take the average value as the final result.

[0094] 1.4ELISA detection of oxidative stress and inflammatory factors in brain tissue

[0095] The brain tissues of rats in each group were obtained, homogenized and centrifuged, and the supernatant was used to detect the contents of TNF-α, NO, GSH and SOD in the brain tissues according to the instructions of the ELISA kit.

[0096] SPSS 26.0 software was used for statistical analysis, and the measurement data were expressed as mean ± standard deviation. Indicates that multiple groups of data were analyzed using one-way analysis of variance or two-way analysis of variance; P < 0.05 was considered statistically significant.

[0097] 2 Test results

[0098] 2.1 Effect of compound 3m on the number of circles in Parkinson's disease rats

[0099] The results are shown in Table 7 and Fig.13Compared with the blank group, the number of circles of the rats in the model group increased, and compound 3m could significantly reduce the number of circles of the rats with Parkinson's disease.

[0100] Table 7 Effect of compound 3m on the number of circles of Parkinson's disease rats (unit: circle)

[0101]

[0102]

[0103] Note: Compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01

[0104] 2.2 Effects of compound 3m on the total time of head turning and pole climbing in Parkinson's disease rats

[0105] The results are shown in Table 8 and Figure 14-15 Compared with the blank group, the total time of head turning and pole climbing in the model group was significantly prolonged. Compound 3m could significantly reduce the total time of head turning and pole climbing in Parkinson's disease rats.

[0106] Table 8 Effect of compound 3m on the total time of head turning and pole climbing in Parkinson's disease rats (unit: s)

[0107]

[0108] Note: Compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01

[0109] 2.3 Effect of compound 3m on oxidative stress levels in brain tissue of Parkinson's disease rats

[0110] The results are shown in Table 9 and Fig.16 Compared with the blank group, the levels of GSH and SOD in the model group were significantly reduced. Compound 3m could significantly increase the levels of GSH and SOD in Parkinson's disease rats.

[0111] Table 9 Effect of compound 3m on oxidative stress level in brain tissue of Parkinson's disease rats (unit: U / mg)

[0112]

[0113] Note: Compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01

[0114] 2.4 Effects of compound 3m on the levels of inflammatory factors in the brain tissue of Parkinson's disease rats

[0115] The results are shown in Table 10 and Fig.17Compared with the blank group, the TNF-α and NO levels in the model group were significantly increased. Therefore, compound 3m can significantly reduce the TNF-α and NO levels in Parkinson's disease rats.

[0116] Table 10 Effect of compound 3m on the level of inflammatory factors in brain tissue of Parkinson's disease rats (unit: U / mg)

[0117]

[0118]

[0119] Note: Compared with the blank group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01

[0120] This study showed that compound 3m exhibited significant therapeutic effects in the Parkinson's disease rat model, including reducing the number of rotations, shortening the time of turning the head and climbing the pole, and improving the level of antioxidant stress in brain tissue and reducing the content of inflammatory factors. This indicates that compound 3m has good potential therapeutic effects on movement disorders and neuroprotection in Parkinson's disease.

[0121] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. Use of a 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one compound in the preparation of an anti-Parkinson's drug, the structural formula of the compound is shown in Formula 3m:

2. Application of 2-(3-fluorophenyl)-3-(phenylseleno)-4H-pyridine-[1,2-a]pyrimidin-4-one compound in the preparation of drugs for improving the reduced GSH and SOD content caused by Parkinson's disease.

3. Application of 2-(3-fluorophenyl)-3-(phenylselenyl)-4H-pyridine-[1,2-a]pyrimidine-4-one compound in the preparation of drugs for anti-Parkinson's disease and improving the antioxidant stress level of brain tissue and reducing the content of inflammatory factors.

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