A compound containing polybrominated diphenyl ether structure and its preparation method and application

Abstract

The present invention provides a compound containing a polybrominated diphenyl ether structure, and the structure of the compound containing a polybrominated diphenyl ether structure is shown below: The present invention also provides a method for preparing the above-mentioned compound containing a polybrominated diphenyl ether structure, which is simple to prepare and easy to operate; the present invention also provides the use of the above-mentioned compound containing a polybrominated diphenyl ether structure in the preparation of NMDA receptor agonist or antagonist drugs and in the preparation of drugs for treating or preventing central nervous system diseases and / or mental disorders.

Description

Technical Field

[0001] The invention patent relates to the technical field of organic synthesis and medicinal chemistry, and in particular refers to a compound containing a polybrominated diphenyl ether structure and its preparation method and application. Background Art

[0002] N-methyl-D-aspartate receptors (NMDARs) are an important class of receptors in the brain and are part of the ionotropic glutamate receptors. They play key roles in the nervous system, especially in the transmission of neurotransmitters, neuroplasticity, and the formation of learning and memory. NMDARs are unique in that their activation requires the simultaneous binding of two co-agonists, glycine and glutamate, as well as the removal of magnesium ions upon depolarization of the cell membrane. These receptors are composed of seven different genetically encoded subunits forming different heterogeneous complexes, which makes them highly diverse in function.

[0003] NMDARs play a crucial role in maintaining brain function and health. These receptors are particularly highly permeable to calcium ions and are a key component of long-term synaptic plasticity. They are essential for the formation of memories, cognitive functions, and adaptive adjustments of neural networks. In addition, NMDARs are involved in regulating neuronal excitability and signal transduction. Dysfunction of NMDARs has been widely associated with a variety of neurological diseases. For example, their overactivation is considered a factor in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. On the other hand, their insufficient function is related to psychiatric diseases such as depression and schizophrenia. These findings emphasize the importance of NMDARs as targets for drug development, especially in the treatment of neurological and psychiatric diseases.

[0004] Currently, there are certain limitations in the treatment of NMDARs-related diseases. For example, although some drugs on the market such as memantine and ketamine have shown effectiveness in treating certain diseases, their side effects and treatment limitations indicate the need for more precise and selective treatment options. In addition, most of these existing drugs are channel blockers, rather than agonists or inhibitors targeting specific subtypes. NMDARs agonists may help treat diseases associated with their decreased function, such as certain types of cognitive dysfunction and psychiatric disorders. Conversely, NMDARs inhibitors may help alleviate pathological conditions caused by their overactivation, such as certain neurodegenerative diseases and neural damage.

[0005] Therefore, given the complexity of NMDARs and their roles in disease, the development of agonists and inhibitors targeting these receptors is of great importance. Summary of the invention

[0006] The present invention aims to solve one of the technical problems existing in the prior art to at least a certain extent. Therefore, in a first aspect of the present invention, the present invention provides a compound containing a polybrominated diphenyl ether structure, and the structure of the compound containing a polybrominated diphenyl ether structure is shown as follows:

[0007]

[0008] wherein R1 is selected from C1-3 alkyloxy, propynyl, ethoxy, cyclopropane ester, furanyl, thiazolyl, benzoate, benzenesulfonate, hydroxyl, hydroxymethyl, amino, protected amino, nitro, propynyl, carboxyl, and aldehyde;

[0009] R2 is selected from C1-3 alkoxy, C2-6 alkynyloxy, C1-3 ester, C3-6 cycloalkyl ester, furanyl ester, thiazolyl ester, benzoate, benzene sulfonate, substituted benzoate, substituted benzene sulfonate, hydroxy, hydroxy C1-3 alkyl, amino, protected amino, nitro, carboxyl, aldehyde, R4 is selected from fluorine, chlorine, bromine, iodine;

[0010] R3 is selected from hydrogen, fluorine, chlorine, bromine, and iodine.

[0011] In one or more embodiments of the present invention, R1 is selected from C1-3 alkyloxy, hydroxyl; R2 is selected from C1-3 alkoxy, propynyloxy, ethoxy, cyclopropane ester, furanyl ester, thiazolyl ester, halogen-substituted methyl substituted benzoate, halogen-substituted methyl substituted benzenesulfonate, hydroxyl, hydroxymethyl, amino, nitro, carboxyl, aldehyde,

[0012]

[0013] In one or more embodiments of the present invention, the compound containing a polybrominated diphenyl ether structure is selected from the following structures:

[0014]

[0015] In one or more embodiments of the present invention, the compound containing a polybrominated diphenyl ether structure is selected from the following structures:

[0016]

[0017]

[0018] In the second aspect of the present invention, the present invention provides a method for preparing the above-mentioned compound containing a polybrominated diphenyl ether structure. When the compound containing a polybrominated diphenyl ether structure is compound I-1, I-10, II-5, II-6, II-7, II-8, II-9, II-10, or II-11, the reaction formula for preparing the compound containing a polybrominated diphenyl ether structure is as follows:

[0019]

[0020] The preparation of the compound containing polybrominated diphenyl ether structure comprises the following steps:

[0021] (a) Compound 1 is brominated to obtain Compound 2;

[0022] (b) etherification of compound 2 with 4-bromo-2-fluorobenzaldehyde to obtain compound II-5;

[0023] (c) Compound II-5 is hydrolyzed by Baeyer-Villiger reaction to obtain compound II-8, and compound II-5 is oxidized by Jones reagent to obtain compound II-6;

[0024] (d) Compound II-5 is reduced with sodium borohydride to obtain compound II-10;

[0025] (e) Compounds II-10, II-8, and I-1 are demethylated to obtain compounds II-11, II-7, and I-10;

[0026] (f) Compound II-8 is methylated to obtain compound II-9;

[0027] (g) Compound II-8 is brominated to obtain compound I-1.

[0028] In one or more embodiments of the present invention, when the compound containing a polybrominated diphenyl ether structure is compound I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, the reaction formula for preparing the compound containing a polybrominated diphenyl ether structure is as follows:

[0029]

[0030] X is selected from methyl, propynyl, formyl, cyclopropanecarboxyl, furanoyl, thiazolecarboxyl,

[0031] Preparing compounds I-2, I-3, I-4, I-5, I-6, I-7, I-8, and I-9 includes the following steps:

[0032] (h) Compound I-1 is reacted with iodomethane, propyne bromide, formyl chloride, cyclopropanecarbonyl chloride, furancarbonyl chloride, thiazolecarbonyl chloride, The reaction yields I-2, I-3, I-4, I-5, I-6, I-7, I-8, and I-9.

[0033] In one or more embodiments of the present invention, when the compound containing a polybrominated diphenyl ether structure is compound II-1, II-2, II-3, or II-4, the reaction formula for preparing the compound containing a polybrominated diphenyl ether structure is as follows:

[0034]

[0035] The preparation of the compound containing polybrominated diphenyl ether structure comprises the following steps:

[0036] (i) etherification of compound 2 to obtain compound II-4;

[0037] (j) hydrogenation reduction of compound II-4 to obtain compound II-2;

[0038] (k) demethylation of compound II-2 to compound II-3;

[0039] (l) Compound II-4 is demethylated to obtain compound II-1.

[0040] In one or more embodiments of the present invention, when the compound containing a polybrominated diphenyl ether structure is compound III-1, III-2, III-3, III-4, III-5, or III-6, the reaction formula for preparing the compound containing a polybrominated diphenyl ether structure is as follows:

[0041]

[0042] R is selected from

[0043] (m) Compound II-6 and The reaction yields compounds III-1, III-2, III-3, III-4, and III-5;

[0044] (n) Compound III-1 is demethylated to obtain compound III-6.

[0045] In the third aspect of the present invention, the present invention provides a pharmaceutical composition comprising the above-mentioned compound containing a polybrominated diphenyl ether structure.

[0046] The pharmaceutical composition also includes a pharmaceutically acceptable carrier, which includes at least one of sugar, starch, cellulose and its derivatives, gelatin, talc, solid lubricants, vegetable oils, polyols, emulsifiers, wetting agents, colorants, flavoring agents, stabilizers, antioxidants, preservatives and pyrogen-free water.

[0047] In the fourth aspect of the present invention, the present invention provides a use of the above-mentioned compound containing a polybrominated diphenyl ether structure and / or the above-mentioned pharmaceutical composition in the preparation of NMDA receptor agonist or antagonist drugs.

[0048] In the fifth aspect of the present invention, the present invention provides a use of the above-mentioned compound containing a polybrominated diphenyl ether structure and / or the above-mentioned pharmaceutical composition in the preparation of drugs for treating or preventing central nervous system diseases and / or mental disorders.

[0049] Central nervous system diseases and / or psychiatric disorders include Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy, depression, bipolar disorder (bipolar disorder), generalized anxiety disorder, panic disorder, schizophrenia, and mania.

[0050] The beneficial effects of the present invention are:

[0051] 1. The present invention provides a compound containing a polybrominated diphenyl ether structure, which has NMDA receptor agonist or inhibitory activity;

[0052] 2. The present invention provides a method for preparing the above-mentioned compound containing a polybrominated diphenyl ether structure, which is simple to prepare and easy to operate;

[0053] 3. The present invention provides an application of the above-mentioned compound containing a polybrominated diphenyl ether structure in the preparation of NMDA receptor agonist or antagonist drugs;

[0054] 4. The present invention provides an application of the above-mentioned compound containing a polybrominated diphenyl ether structure in the preparation of drugs for treating or preventing central nervous system diseases and / or mental disorders. BRIEF DESCRIPTION OF THE DRAWINGS

[0055] Figure 1 This is a graph showing the inhibitory effect of compound II-7 on NMDA receptors;

[0056] in, Figure 1 A is a representative current trace of compound II-7 on GluN1-2C receptors under 0.2 μM glycine and 100 μM glutamate; Figure 1 B is a representative current trace of compound II-7 on GluN1-2C receptors under 100 μM glycine and 0.4 μM glutamate; Figure 1C is the dose-response curve of compound II-7 on GluN1-2C receptor under unsaturated agonist (n≥3).

[0057] Figure 2 The graph is the result of the inhibitory effect of compound II-11 on NMDA receptors at a concentration of 10 μM;

[0058] in, Figure 2 A is a representative current trace of compound II-11 on GluN1-2C and GluN1-2A receptors at 100 μM glycine and 100 μM glutamate; Figure 2 B is the inhibitory level of compound II-11 on GluN1-2C and GluN1-2A receptors.

[0059] Figure 3 The graph is a result of the inhibitory effect of compound III-2 on NMDA receptor and chimera at a concentration of 10 μM;

[0060] in, Figure 3 A is to verify the inhibitory effect of compound III-2 on NMDA chimera, white represents GluN2D, and blue represents GluN2A; Figure 3 B is the inhibitory level of compound III-2 on GluN1-N2Dwt, GluN1-N2Awt, GluN1-N2D (2AS1) and GluN1-N2D (2AS2) receptors (n ≥ 3, paired t-test); Figure 3 C is the current-voltage curve of GluN1-N2D receptor under compound III-2 (10 μM) and control (Ctrl, without small molecules) conditions. DETAILED DESCRIPTION

[0061] The present invention will be further described below in conjunction with specific examples, but the following examples are only used to illustrate the present invention and should not be considered to limit the scope of the present invention. In the following examples, if specific conditions are not specified, they are carried out according to normal conditions or conditions recommended by the manufacturer. The methods used are conventional methods known in the art unless otherwise specified, and the consumables and reagents used are commercially available unless otherwise specified. Unless otherwise specified, the professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any method or material similar or equivalent to the recorded content may also be applied to the present invention.

[0062] In the embodiment, 1H NMR was recorded by Avance III-400 or Avance III-600 nuclear magnetic resonance instrument, and chemical shift was expressed in δ (ppm); mass spectra were recorded by MS mass spectrometry-LCQ-DECA ion trap mass spectrometer (ESI / LR) and MS mass spectrometry-Q-TOF quadrupole time-of-flight mass spectrometer (ESI-HR); the thin layer chromatography silica gel plate (HSGF254) used in the reaction detection was from Sinopharm Chemical Reagent Co., Ltd.; 200-300 mesh silica gel from Sinopharm Chemical Reagent Co., Ltd. was used for compound separation.

[0063] Example 1-3 is a method for preparing compounds I-1, I-10, II-5, II-7, II-8, II-9, II-10, and II-11

[0064] The reaction formulas for preparing compounds I-1, I-10, II-5, II-7, II-8, II-9, II-10, and II-11 are as follows:

[0065]

[0066] The preparation of the compound containing polybrominated diphenyl ether structure comprises the following steps:

[0067] (a) Compound 1 is brominated to obtain Compound 2;

[0068] (b) etherification of compound 2 with 4-bromo-2-fluorobenzaldehyde to obtain compound II-5;

[0069] (c) Compound II-5 is hydrolyzed by Baeyer-Villiger reaction to obtain compound II-8;

[0070] (d) Compound II-5 is reduced with sodium borohydride to obtain compound II-10;

[0071] (e) Compounds II-10, II-8, and I-1 are demethylated to obtain compounds II-11, II-7, and I-10;

[0072] (f) Compound II-8 is methylated to obtain compound II-9;

[0073] (g) brominating compound II-8 to obtain compound I-1;

[0074] Example 1 Preparation of Compounds I-1, I-10, II-5, II-7, II-8, and II-11

[0075] (1) o-Methoxyphenol (Compound 1) (200 mg, 1.6 mmol) was dissolved in 25 ml of dichloromethane, and then 10 ml of methanol was added to form a mixed solvent. Benzyltrimethylammonium tribromide (1.4 g, 2.2 mmol) was slowly added while the solution was stirred, and the mixture was reacted at room temperature for 2 hours. After the reaction was completed by TLC monitoring, the reaction solution was concentrated, 10 mL of water was added to the residual solution, and the mixture was extracted with dichloromethane (20 mL×3). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. 2,4-dibromo-6-methoxyphenol (Compound 2) was separated by silica gel column chromatography (petroleum ether: dichloromethane = 3:1) to obtain 406 mg of white solid, yield 90%;

[0076] (2) 2,4-dibromo-6-methoxyphenol (Compound 2) (1.0 g, 3.6 mmol), potassium carbonate (1.1 g, 3.0 mmol), and 18-crown-6 (74 mg, 0.3 mmol) were dissolved in 10 ml DMSO, and 4-bromo-2-fluorobenzaldehyde (730 mg, 3.6 mmol) was added. After the raw materials were dissolved, the reaction bottle was placed in an oil bath under nitrogen protection, heated to 120°C and reacted for 12 hours. After the reaction, the reaction solution was cooled to room temperature, 20 ml of water was added, and extracted with ethyl acetate (3×15 ml) until the organic phase was clear. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Compound II-5 (white solid 900 mg, yield 55%) was isolated by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1).

[0077] (3) Add 10 ml of dichloromethane solution to a 25 ml round-bottom flask, place it in an ice bath and cool it to 0°C. Add 30% hydrogen peroxide solution (362 mg, 3.2 mmol) to the flask under ice bath conditions, take trifluoroacetic anhydride (3.3 g, 16.0 mmol) in a dropping funnel, and add it dropwise within 5 min. The solution continues to react in an ice bath for 1 hour to generate trifluoroperacetic acid, which is kept in an ice bath for later use. Take another 50 ml reaction bottle and add compound II-5 (465 mg, 1 mmol). Add 5 ml of dichloromethane to dissolve it. Slowly add the prepared trifluoroperacetic acid solution in dichloromethane to the reaction bottle at 0°C and place it at room temperature for reaction for 1 hour. After the reaction is complete as monitored by TLC, slowly add a saturated sodium thiosulfate solution until the reaction is completely quenched. Extract with dichloromethane (3×5 ml), combine the organic phases, and concentrate directly without removing water. After drying, dissolve the product in 10 ml of methanol, place it in a 25 ml round-bottom flask, add 3-4 drops of concentrated hydrochloric acid, and react at room temperature for 4 hours. After the reaction is complete as monitored by TLC, concentrate the reaction solution and separate it through silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain compound II-8 (350 mg of white solid, 77% yield).

[0078] (4) Compound II-8 (45 mg, 0.1 mmol) was placed in a 25 ml round-bottom flask, 10 ml of methanol was added, and the mixture was stirred to dissolve. N-bromosuccinimide (17.8 mg, 0.1 mmol) and p-toluenesulfonic acid (2 mg, 0.01 mmol) were added thereto, and the mixture was stirred at room temperature for one hour. After the reaction was completed as monitored by TLC, the reaction solution was concentrated to one-third of the volume, 3 ml of water was added, and a light yellow solid precipitated. The solid was filtered with filter paper and washed with clean water for 3-4 times. The solid was collected and dried to obtain compound I-1 (45 mg of white solid, yield 84%).

[0079] (5) Demethylation of compound I-1 to obtain compound I-10: Compound I-1 (53 mg, 0.1 mmol) was placed in a 25 ml round-bottom flask, 10 ml of anhydrous dichloromethane was added, the solution was placed in an ice bath, and 1 mol / L boron tribromide solution (5 ml) was slowly added under nitrogen protection. After the addition was complete, the mixture was allowed to react overnight at room temperature. After the reaction was completed as monitored by TLC, methanol was slowly added dropwise until the reaction was completely quenched. The concentrated reaction solution was separated by silica gel column chromatography (dichloromethane: methanol = 40: 1) to obtain compound I-10 (40 mg of white solid, yield 77%).

[0080] (6) Compound II-8 and Compound II-10 are demethylated to obtain Compound II-7 and Compound II-11, respectively. The demethylation method is the same as step (5).

[0081] Example 2 Preparation of Compound II-10

[0082] Compound II-5 (465 mg, 1 mmol) was placed in a 25 ml round-bottom flask, 15 ml of methanol was added, sodium borohydride (38 mg, 1 mmol) was slowly added to the suspension while stirring in an ice bath, and the reaction was continued at 0°C for 2 hours. After the reaction was completed as monitored by TLC, dilute hydrochloric acid was added dropwise until the pH was acidic. The reaction solution was spin-dried and separated by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain compound II-10 (360 mg white solid, 78% yield).

[0083] Example 3 Preparation of Compound II-9

[0084] Compound II-8 (45 mg, 0.1 mmol) was placed in a 25 ml round-bottom flask, 10 ml of acetone was added, the reaction solution was stirred at room temperature and iodomethane (22 mg, 0.15 mmol) was added dropwise, and the reaction was continued for 2 hours. After the reaction was completed by TLC monitoring, the reaction solution was spin-dried and separated by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain compound II-9 (360 mg white solid, yield 78%).

[0085] Example 4 Preparation of Compounds I-2, I-3, I-4, I-5, I-6, I-7, I-8 and I-9

[0086] Compound I-1 (53 mg, 0.1 mmol) was placed in a 25 ml round-bottom flask, 10 ml of acetone was added, anhydrous potassium carbonate (28 mg, 0.2 mmol) was added, and iodomethane (25 mg, 0.15 mmol) was added dropwise. After completion, the mixture was allowed to react at room temperature for 4 hours. After the reaction was completed as monitored by TLC, the reaction solution was dried and separated by silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1) to obtain compound I-2 (44 mg white solid, yield 79%).

[0087] Among them, when iodomethane is replaced by bromopropyne, compound I-3 is obtained, when iodomethane is replaced by formyl chloride, compound I-4 is obtained, when iodomethane is replaced by cyclopropanecarbonyl chloride, I-5 is obtained, when iodomethane is replaced by furancarbonyl chloride, I-6 is obtained, when iodomethane is replaced by thiazolecarbonyl chloride, I-7 is obtained, when iodomethane is replaced by When I-8 is obtained and methyl iodide is replaced by Get an I-9 when you apply.

[0088] Example 5-7 is a method for preparing compounds II-1, II-2, II-3, and II-4

[0089] Example 5 Preparation of Compound II-4

[0090] Take 2,4-dibromo-6-methoxyphenol (compound 2) (281 mg, 1 mmol) and place it in a 25 ml round-bottom flask, add 15 ml acetone and anhydrous potassium carbonate (280 mg, 2 mmol), add 4-bromo-2-fluoronitrobenzene (220 mg, 1.0 mmol) under stirring, and place the flask in an oil bath at 60 ° C for 6 hours. After the reaction is complete, the reaction solution is spin-dried and separated by silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) to obtain compound II-4 (372 mg white solid, yield 77%).

[0091] Example 6 Preparation of Compound II-2

[0092] Compound II-4 (480 mg, 1 mmol) was placed in a 25 ml round-bottom flask, 15 ml of methanol and solid ammonium chloride (196 mg, 4 mmol) were added, water was added dropwise until the ammonium chloride was just dissolved, zinc powder (220 mg, 1.0 mmol) was added under stirring, and the mixture was reacted at room temperature for 6 hours. After the reaction was completed as monitored by TLC, the reaction solution was spin-dried and separated by silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1) to obtain compound II-2 (405 mg white solid, 90% yield).

[0093] Example 7 Preparation of Compounds II-1 and II-3

[0094] Compound II-4 is demethylated to obtain compound II-1, and compound II-2 is demethylated to obtain compound II-3. The demethylation method is the same as step (5) in the example.

[0095] Example 8 Preparation of Compound II-6

[0096] Compound II-6 was obtained by oxidation of compound II-5 with Jones reagent. Compound II-5 (50 mg, 0.11 mmol) was dissolved in 5 ml of acetone and placed at 0°C. Jones reagent was slowly added dropwise and the reaction was allowed to proceed for 4-6 hours. After TLC monitoring, the reaction solution was concentrated and extracted with ether (5 ml x 3). After drying over anhydrous magnesium sulfate, it was concentrated and separated by silica gel column chromatography (petroleum ether: ethyl acetate = 1:3) to obtain compound II-6 (light yellow solid, yield 70%).

[0097] Example 9 Preparation of Compound III Series

[0098] Compound II-6 (1 eq) was placed in a 25 ml round-bottom flask, and 10 ml of dichloromethane, DMAP (1.5 eq) and EDCI (1.2 eq) were added. The mixture was stirred at room temperature for 15 minutes. (1.1 eq) was placed at room temperature to react for 6 hours. After the reaction was completed as monitored by TLC, the reaction solution was spin-dried and separated by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain compounds III-1, III-2, III-3, III-4, and III-5. III-1 was demethylated to obtain compound III-6. The demethylation method was the same as step (5) in Example 1.

[0099] The numbering, structure and characterization of the compound I obtained in the above example are as follows:

[0100]

[0101] Compound I-1: white solid, yield 84%; 1 H NMR (600MHz, Chloroform-d) δ7.41(d,J=2.1Hz,1H),7.34(d,J=2.1Hz,1H),7.09(d,J=2.1Hz,1H),6.56(d,J=2.2Hz,1H),6.11(s,1H),3.79(s,3H); 13C NMR (151MHz, CDCl3) δ153.55,145.28,142.94,140.11,129.29,127.58,119.97,118.72,116.63,115.76,111.66,110.06,56.71.HR-ESI-MS:[MH] + calcdfor C 13 H7Br4O3526.7134,found:526.7167.

[0102] Compound I-2: white solid, yield 78%; 1 H NMR (600MHz, Chloroform-d) δ7.41(d,J=2.1Hz,1H),7.36(d,J=2.3Hz,1H),7.09(d,J=2.2Hz,1H),6.46(d,J=2.2Hz,1H),4.00(s,3H),3.76(s,3H); 13 C NMR (151MHz, CDCl3) δ153.59,151.48,145.64,139.41,128.92,127.57,119.63,119.05,118.82,116.55,115.78,61.14,56.63.HR-ESI-MS:[MH] + calcdfor C 14 H9Br4O3541.5380,found:541.5381.

[0103] Compound I-3: white solid, yield 78%; 1 H NMR(600MHz,Chloroform-d)δ7.40(d,J=2.1Hz,1H),7.38(d,J=2.1Hz,1H),7.09(d,J =2.2Hz,1H),6.46(d,J=2.2Hz,1H),4.94(d,J=2.5Hz,2H),3.77(s,3H),2.53(t,1H); 13 C NMR (151MHz, CDCl3) δ153.51,151.41,143.27,139.28,129.04,127.58,119.82,119 .79,118.84,117.24,116.51,115.80,78.68,76.16,60.52,56.67.HR-ESI-MS:[M+H] + Calculate for C 16H9Br4O3565.5659,found:565.556658.

[0104] Compound I-4: white solid, yield 78%; 1 H NMR (600MHz, Chloroform-d) δ7.42(d,J=2.1Hz,1H),7.40(d,J=2.1Hz,1H),7.08(d,J=2.1Hz,1H),6.56(d,J=2.1Hz,1H),3.77(s,3H),2.37(s,3H); 13 C NMR (151MHz, CDCl3) δ167.41,153.59,150.33,139.39,137.33,128.87,127.57,119. 81,119.39,118.92,118.75,116.90,115.79,56.70,29.84,20.59.HR-ESI-MS:[M+H] + Calculate for C 15 H 11 Br4O4570.7378,found:570.7385.

[0105] Compound I-5: white solid, yield 78%; 1 H NMR(600MHz,Chloroform-d)δ7.42(d,J=2.1Hz,1H),7.40(d,J=2.1Hz,1H),7.08(d,J= 2.1Hz,1H),6.57(d,J=2.1Hz,1H),3.76(s,3H),1.91(m,1H),1.04(m,2H),0.87(m,2H); 13 C NMR (151MHz, CDCl3) δ171.14,153.62,150.41,139.61,137.35,128.88,127.56,119.67 ,119.17,119.06,118.73,117.11,115.80,56.69,29.85,12.99,9.55.HR-ESI-MS:[M+H] + Calculate for C 17 H 13 Br4O4596.7537,found:596.7542.

[0106] Compound I-6: white solid, yield 78%; 1H NMR (600MHz, Chloroform-d) δ7.69 (s, 1H), 7.46 (s, 2H), 7.35 (t, J = 1.6Hz, 1H), 7.04 (s, 1H), 6.65-6.57 (m, 2H), 3.76 (s, 3H); 13 C NMR (151MHz, CDCl3) δ154.74,153.57,150.59,147.71,143.21,139.55,136.69,129.00,127.4 8,120.48,119.75,119.70,119.09,118.70,117.33,115.77,112.41,56.69.HR-ESI-MS:[M+H] + Calculate for C 18 H 11 Br4O5622.7329,found:622.7334.

[0107] Compound I-7: white solid, yield 78%; 1 H NMR(600MHz,Chloroform-d)δ8.03(dd,J=3.8,1.3Hz,1H),7.68(dd,J=4.9,1.3Hz,1H),7.46(d,J=2.1 Hz,1H),7.33(d,J=2.2Hz,1H),7.18(m,1H),7.03(d,J=2.2Hz,1H),6.66(d,J=2.1Hz,1H),3.76(s,3H); 13 C NMR (151MHz, CDCl3) δ158.45,153.59,150.62,139.75,137.21,135.53,134.14,131.67,1 29.00,128.20,127.50,119.61,119.19,118.68,117.57,115.81,56.71.HR-ESI-MS:[M+H] + Calculate for C 18 H 11 Br4O4S638.7106,found:638.7106.

[0108] Compound I-8: white solid, yield 78%; 1H NMR(600MHz,Chloroform-d)δ8.20(d,J=8.2Hz,2H),7.73(d,J=8.2Hz,2H),7.44(d,J=2.2 Hz,1H),7.34(d,J=2.1Hz,1H),7.03(d,J=2.2Hz,1H),6.49(d,J=2.2Hz,1H),3.74(s,3H); 13 C NMR (151MHz, CDCl3) δ153.03,150.93,141.16,138.64,136.58,135.92,135.70,135.48,135.26,129.59,129.17,127.65,1 26.01,125.98,125.96,125.94,124.05,122.24,120.89,120.08,119.95,118.23,117.24,115.79,56.61.HR-ESI-MS:[M+H] + Calculate for C 21 H 12 Br4F3O4704.2119,found:704.2122.

[0109] Compound I-9: white solid, yield 78%; 1 H NMR(600MHz,Chloroform-d)δ8.36(d,J=7.9Hz,2H),7.79(d,J=8.2Hz,2H),7.48(d,J=2.2 Hz,1H),7.33(d,J=2.2Hz,1H),7.04(d,J=2.2Hz,1H),6.67(d,J=2.2Hz,1H),3.77(s,3H); 13 C NMR (151MHz, CDCl3) δ162.08,153.53,150.37,139.52,137.25,135.75,135.54,135.32,135.10,131.94,131.07,129.05,127.5 4,125.84,125.81,125.79,125.76,124.57,122.76,119.82,119.78,118.86,118.64,117.49,115.78,56.69.HR-ESI-MS:[M+H] + Calculate for C 18 H 11 Br4O3590.7411,found:590.7436.

[0110] Compound I-10: white solid, yield 78%; 1 H NMR(400MHz,Chloroform-d)δ1H 7.40(d,J=2.1Hz,1H),7.35(d,J=2.3Hz,1H),7.21(d,J=2.3Hz,1H),6.65(d,J=2.2Hz,1H).13CNMR(125MHz,Chloroform-d): 13 C NMR(150MHz,Chloroform-d)δ150.30,144.45,142.54,138.50,129.74,127.80,120.09,119.90,117.27,117.14,112.14,110.79.HR-ESI-MS:[M+H] + Calculate for C 18 H 11 Br4O3590.7411,found:590.7436.

[0111] The numbering, structure and characterization of the compound II obtained in the above example are as follows:

[0112]

[0113] Compound II-1: white solid, yield 78%; 1 H NMR(600MHz,Chloroform-d)δ7.80(d,J=8.6Hz,1H),7.37(s,2H),7.23(s,1H),7.01(s,1H).HR-ESI-MS:[M+H] + Calculate for C 12 H6Br3NO4 464.7847,found:464.7845.

[0114] Compound II-2: white solid, yield 78%; 1 H NMR(600MHz,Chloroform-d)δ7.40(d,J=2.1Hz,1H),7.08(d,J=2.2Hz,1H),6.96( dd,J=8.4,2.1Hz,1H),6.68(d,J=8.3Hz,1H),6.42(d,J=2.1Hz,1H),3.78(s,3H); 13C NMR(151MHz,Chloroform-d)δ153.85,145.21,140.40,135.23,127.40,125.77,116.97,116.18,115.57,109.32,56.54.HR-ESI-MS:HR-ESI-MS:[M+H] + Calculate for C 13 H 11 Br3NO2 488.8262,found:488.8265.

[0115] Compound II-3: white solid, yield 78%; 1 H NMR (600MHz, Chloroform-d) δ7.32(d,J=2.3Hz,1H),7.13(d,J=2.3Hz,1H),6.99(dd,J=8.5,2.3Hz,1H),6.81(d,J=8.5Hz,1H),6.45(d,J=2.3Hz,1H); 13 C NMR(151MHz,Chloroform-d)δ153.69,147.12,140.72,127.11,126.67,120.72,119.75,119.40,118.91,117.87,111.37.HR-ESI-MS:[M+H] + Calculate for C 12 H9Br3NO2434.8105,found:434.8102.

[0116] Compound II-4: white solid, yield 78%; 1 H NMR(600MHz,Chloroform-d)δ7.88(d,J=8.7Hz,1H),7.42(d,J=2.1Hz,1H),7.28( dd,J=8.7,2.0Hz,1H),7.11(d,J=2.1Hz,1H),6.76(d,J=1.9Hz,1H),3.78(s,3H); 13 C NMR(151MHz,Chloroform-d)δ153.40,151.04,139.21,138.39,128.53,127.73,127 .27,125.84,120.24,119.34,118.51,115.95,56.82.HR-ESI-MS:HR-ESI-MS:[M+H] + Calculate for C 13H9Br3NO4 478.8003,found:478.8001.

[0117] Compound II-5: white solid, yield 78%; 1 H NMR(600MHz,Chloroform-d)δ10.63(d,J=0.8Hz,1H),7.79(d,J=8.3Hz,1H),7.43(d,J=2 .2Hz,1H),7.28-7.26(m,1H),7.12(d,J=2.1Hz,1H),6.67(d,J=1.7Hz,1H),3.79(s,3H); 13 C NMR (151MHz, Chloroform-d) δ188.50,159.78,153.79,139.57,130.23,129.69,127.71,126.45,124.05,119.98,118.86,117.74,115.83,56.70.

[0118] Compound II-6: white solid, yield 78%; 1 H NMR (600MHz, DMSO-d6) δ13.07(s,1H),7.76(d,J=8.3Hz,1H),7.60(d,J=2.2Hz,1H),7.47( d,J=2.1Hz,1H),7.34(dd,J=8.3,1.8Hz,1H),6.60(d,J=1.8Hz,1H),3.79(d,J=1.1Hz,3H); 13 C NMR(151MHz,DMSO-d6)δ165.69,156.21,153.47,138.85,133.32,126.73,125 .95,125.25,120.14,119.22,117.76,116.59,116.5,56.87.HR-ESI-MS:[M+H] + Calculate for C 14 H 10 Br3O4 478.8124,found:478.8130.

[0119] Compound II-7: white solid, yield 78%; 1 H NMR (400MHz, Methanol-d4) δ7.32(d,J=2.2Hz,1H),7.13(d,J=2.3Hz,1H),6.99(dd,J=8.5,2.3Hz,1H),6.81(d,J=8.5Hz,1H),6.45(d,J=2.2Hz,1H);13 C NMR(151MHz,Methanol-d4)δ153.59,147.12,140.72,127.11,126.67,120.72,119.77,119.41,118.91,117.87,111.38.HR-ESI-MS:[MH] - Calculate for C 12 H6Br3O3 434.7873,found:434.7862..

[0120] Compound II-8: white solid, yield 78%; 1 H NMR (600MHz, Chloroform-d) δ7.41(d,J=2.1Hz,1H),7.07(dd,J=7.7,2.2Hz,2H),6.90(d,J=8.6Hz,1H),6.61(d,J=2.3Hz,1H),5.82(s,1H),3.79(s,3H); 13 C NMR(151MHz,Chloroform-d)δ153.70,145.29,145.02,140.58,127.55,126.75,119.62,118.82,117.53,117.30,115.70,111.53,56.67.HR-ESI-MS:[M+Na] + Calculate for C 13 H9Br3NaO3472.7992,found:472.7994.

[0121] Compound II-9: white solid, yield 78%; 1 H NMR(600MHz,Chloroform-d)δ7.39(d,J=2.2Hz,1H),7.10(dd,J=8.6,2.3Hz,1H),7.07( d,J=2.2Hz,1H),6.84(d,J=8.6Hz,1H),6.48(d,J=2.3Hz,1H),3.94(s,3H),3.76(s,3H); 13 C NMR(151MHz,Chloroform-d)δ153.86,148.25,147.25,140.20,127.55,125.49,119.14,118.95,116.82,115.70,114.07,112.56,56.66.HR-ESI-MS:[M+Na] + Calculate for C 14 H11 Br3NaO3 486.8151,found:486.8146

[0122] Compound II-10: white solid, yield 78%; 1 H NMR(600MHz,Chloroform-d)δ7.41(d,J=2.2Hz,1H),7.28(d,J=8.0Hz,1H),7.16(dd,J= 8.0,1.8Hz,1H),7.09(d,J=2.2Hz,1H),6.52(d,J=1.8Hz,1H),4.82(s,2H),3.76(s,3H); 13 C NMR(151MHz,Chloroform-d)δ155.50,153.68,139.94,130.56,128.53,127.59,1 25.86,121.89,119.46,119.08,116.19,115.73,61.15,56.64.HR-ESI-MS:[M+Cl - ]calcd for C 14 H 11 Br3ClO3 498.7952found 498.7948.

[0123] Compound II-11: white solid, yield 78%; 1 H NMR (600MHz, Methanol-d4) δ7.39(d,J=8.0Hz,1H),7.33(d,J=2.3Hz,1H),7.20( dd,J=8.1,1.9Hz,1H),7.14(d,J=2.3Hz,1H),6.50(d,J=1.8Hz,1H),4.82(s,2H); 13 C NMR(151MHz,Methanol-d4)δ156.21,153.63,140.45,130.90,130.36,127.10,126.47,122.10,120.94,120.07,119.37,116.93,60.01.HR-ESI-MS:[MH] - Calculate for C 13 H8Br3O3 447.1547,found:447.1540.

[0124] The numbering, structure and characterization of the compound III obtained in the above example are as follows:

[0125]

[0126] Compound III-1: white solid, yield 65%; 1 H NMR(600MHz,Chloroform-d)δ10.10(s,1H),8.01(d,J=8.6Hz,2H),7.86(d,J=8.4Hz,1H),7.70(d,J=8.6Hz,2H) ,7.48(d,J=2.1Hz,1H),7.29(dd,J=8.5,1.8Hz,1H),7.17(d,J=2.1Hz,1H),6.69(d,J=1.7Hz,1H),3.85(s,3H); 13 CNMR(151MHz,Chloroform-d)δ161.91,155.30,153.24,138.84,137.81,133.74,132.39,130.37,1 29.47,129.07,127.84,127.31,121.03,119.26,119.03,117.94,115.95,56.89.HR-ESI-MS:[M+H] + Calculate for C 20 H 14 Br4NO5S 695.7315,found:695.7321.

[0127] Compound III-2: white solid, yield 72%; 1 H NMR(600MHz,Chloroform-d)δ10.37(s,1H),8.44(dd,J=7.9,1.8Hz,1H),7.85(d,J=8.4Hz,1H),7.72(dd,J=7.9,1.2Hz,1H),7.57(t d,J=7.7,1.3Hz,1H),7.48(d,J=2.1Hz,2H),7.28(dd,J=8.5,1.8Hz,1H),7.17(d,J=2.1Hz,1H),6.69(d,J=1.7Hz,1H),3.85(s,3H); 13 C NMR (151MHz, CDCl3) δ161.78,155.49,153.20,141.36,138.52,137.93,135.32,135.12,134.94,133.89,1 30.07,128.07,127.94,127.81,127.15,120.98,120.42,119.74,117.55,115.96,56.91.HR-ESI-MS:[M+H] + Calculate for C20 H 14 Br4NO5S 695.7315,found:695.7321.

[0128] Compound III-3: white solid, yield 67%; 1 H NMR(600MHz,Chloroform-d)δ10.12(s,1H),8.25(s,1H),8.11(d,J=7.9Hz,1H),7.88(d,J=8.4Hz,1H),7. 77(d,J=8.0Hz,1H),7.49(s,1H),7.44(t,J=8.0Hz,1H),7.30(d,J=8.2Hz,1H),6.71(s,1H),3.85(s,3H); 13 CNMR (151MHz, CDCl3) δ161.88,155.32,153.24,140.63,138.86,137.15,133.76,131.44,130.54,129. 10,127.86,127.56,127.33,122.91,121.05,119.26,119.07,117.99,115.95,56.92.HR-ESI-MS:[M+H] + Calculate for C 20 H 14 Br4NO5S 695.7315,found:695.7321.

[0129] Compound III-4: white solid, yield 71%; 1 H NMR (600MHz, Methanol-d4) δ7.39(d,J=8.0Hz,1H),7.33(d,J=2.3Hz,1H),7.20( dd,J=8.1,1.9Hz,1H),7.14(d,J=2.3Hz,1H),6.50(d,J=1.8Hz,1H),4.82(s,2H); 13 C NMR(151MHz,Methanol-d4)δ156.21,153.63,140.45,130.90,130.36,127.10,126.47,122.10,120.94,120.07,119.37,116.93,60.01.HR-ESI-MS:[M+H] + Calculate for C 20 H 14 Br3FNO5S 634.8049,found:634.8051.

[0130] Compound III-5: white solid, yield 74%; 1 H NMR(600MHz,Chloroform-d)δ10.11(s,1H),8.09(d,J=8.6Hz,2H),7.86(d,J=8.5Hz,1H),7.53(d,J=8.6Hz,2H) ,7.48(d,J=2.1Hz,1H),7.29(dd,J=8.5,1.8Hz,1H),7.17(d,J=2.1Hz,1H),6.69(d,J=1.7Hz,1H),3.85(s,3H); 13 CNMR(151MHz,Chloroform-d)δ161.91,155.30,153.24,138.84,137.81,133.74,132.39,129.37,1 29.47,129.07,127.84,127.31,121.03,119.26,119.03,117.94,115.95,56.89.HR-ESI-MS:[M+H] + Calculate for C 20 H 14 Br3ClNO5S 650.7753,found:650.7755.

[0131] Compound III-6: white solid, yield 60%; 1 H NMR(600MHz,Methanol-d4)δ7.96(d,J=8.7Hz,1H),7.74(d,J=8.7Hz,1H),7.57(d,J=8.3Hz,1H), 7.38(d,J=2.2Hz,1H),7.33(dd,J=8.3,1.7Hz,1H),7.18(d,J=2.3Hz,1H),6.71(d,J=1.7Hz,1H); 13 C NMR(151MHz,Methanol-d4)δ165.29,156.42,152.96,139.85,139.71,133.38,132.91,131.13 ,129.93,128.37,127.61,127.46,123.04,121.00,120.92,119.24,118.94.HR-ESI-MS:[M+H] + calcdfor C 19 H 11 Br4NO5S 365.1860,found:365.1858.

[0132] NMDA receptor activity test of compounds I-1 to I-9, II-1 to II-11, III-1 to III-6

[0133] 1) Oocyte acquisition: The African clawed frog is buried in ice for 60 minutes, and after it has no reflex response to stimulation, it is moved to ice for surgery. During the surgery, the whole body of the clawed frog is wrapped in ice, and only the abdomen on the surgical side is exposed. Sterilize the surgical instruments, cut the abdomen about one centimeter with surgical scissors, and use forceps to remove the egg sac from the opening and place it in a culture dish containing OR2. Suture the wound with absorbable sutures, place it in a bucket with an appropriate amount of breeding water, observe for a week, and return it to the breeding tank after the wound heals. Tear the removed egg sac into about 10 pieces in a group in OR2 solution. Prepare collagenase digestion, weigh 40mg collagenase, dissolve it in 20ml OR2 solution, and put the fragmented egg sac into it. Place the centrifuge tube on a shaker and shake it slowly for 60 minutes. Observe that the oocytes in the tube are basically dispersed and fall off from the outer egg sac and then remove it. Take an appropriate amount and observe it under a microscope. If the digestion is complete, wash it twice with OR2 solution, and then wash it 3-5 times with Barth solution until the solution is clear. Transfer the oocytes to a Barth solution culture dish, select the oocytes with clear black and white, round and large, and no spots on the surface under a microscope, and transfer them to Barth solution with Pen Strep. Label them and store them in a 16°C incubator.

[0134] 2) DNA / RNA plasmid injection: Take the oocytes, arrange them neatly and adhere them to the lid of a 6cm culture dish filled with Barth's solution. Use tweezers to gently move the egg surface so that the black side faces the direction of the injection needle. Dilute the commercially available NMDAR plasmid to 30ng / ul, mix it at a ratio of 1:1 and take 3ul to inhale the injection needle. Use a microsyringe to inject the plasmid into the center of the black side, and inject 46.6nl into each oocyte. After the injection, transfer the oocytes to Barth's solution with 100μM D-AP5 (D-AP5 can inhibit NMDARs expressed in oocytes, prevent over-activation of receptors from causing cytotoxicity and damaging oocytes), and place them in a 16°C incubator for expression.

[0135] 3) Electrode pulling: Sutter needle puller P-97, parameters are Heat 554, Pull 6, Vel 30, Time 254. Put in the capillary and pull it into a glass electrode with a tip of 2μm. Fill it with 3M KCl solution, install it on the electrophysiological instrument and measure the resistance. The value is 2~30MΩ.

[0136] 4) Two-electrode voltage clamp recording (TEVC): After injection, the expression is left to stand for about 16 to 48 hours before recording (different subtypes of receptors have different expression times). After the glass electrode is assembled on the electrophysiological equipment, the two electrodes are inserted into the black side of the oocyte, Clampex10.6 is opened, the program is set, and the voltage is stabilized at -60mV before recording can begin. The oocyte was recorded in Ringer solution throughout the process, and NMDARs were activated with 100μM glutamate and 100μM glycine to generate current, which was taken as the current of the receptor at a saturating agonist concentration, Igg. After the drug was added and perfused, the current was stabilized and recorded as I. The relative current (Relative Currents) is the ratio of the current after the drug is added (concentration is 10μM) to the current under the saturated agonist, that is, I / Igg. The relevant test results are shown in Table 1.

[0137] Table 1

[0138]

[0139]

[0140] Figure 1 The figure is the result of the inhibitory effect of compound II-7 on NMDA receptors; wherein, Figure 1 A is a representative current trace of compound II-7 on GluN1-2C receptors under 0.2 μM glycine and 100 μM glutamate. Figure 1 B is a representative current trace of compound II-7 on GluN1-2C receptors in the presence of 100 μM glycine and 0.4 μM glutamate. Figure 1 C is the dose-response curve of compound II-7 on GluN1-2C receptor under unsaturated agonist (n≥3).

[0141] Figure 2 The graph is a result of the inhibitory effect of compound II-11 on NMDA receptors at a concentration of 10 μM; wherein, Figure 2 A is a representative current trace of compound II-11 at GluN1-2C and GluN1-2A receptors under 100 μM glycine and 100 μM glutamate. Figure 2 B is the inhibitory level of compound II-11 on two subtypes of receptors.

[0142] Figure 3 The graph is a result of the inhibitory effect of compound III-2 on NMDA receptors and chimeras at a concentration of 10 μM; wherein, Figure 3 A is a test to verify the inhibitory effect of III-2 on NMDA chimera, GluN2D (white) and GluN2A (blue). Figure 2B is the inhibitory level of compound III-2 on GluN1-N2Dwt, GluN1-N2Awt, GluN1-N2D (2AS1) and GluN1-N2D (2AS2) receptors (n ≥ 3, paired t-test). (C) Current-voltage curves of GluN1-N2D receptors under III-2 and control (Ctrl, without small molecules).

[0143] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention, which shall all be included in the scope of protection of the present invention.

Claims

1. A compound containing a polybrominated diphenyl ether structure, characterized in that: The structure of the compound containing polybrominated diphenyl ether structure is shown below: wherein R1 is selected from C1-3 alkyloxy, propynyl, ethoxy, cyclopropane ester, furanyl, thiazolyl, benzoate, benzenesulfonate, hydroxyl, hydroxymethyl, amino, protected amino, nitro, propynyl, carboxyl, and aldehyde; R2 is selected from C1-3 alkoxy, C2-6 alkynyloxy, C1-3 ester, C3-6 cycloalkyl ester, furanyl ester, thiazolyl ester, benzoate, benzene sulfonate, substituted benzoate, substituted benzene sulfonate, hydroxy, hydroxy C1-3 alkyl, amino, protected amino, nitro, carboxyl, aldehyde, R4 is selected from fluorine, chlorine, bromine, iodine; R3 is selected from hydrogen, fluorine, chlorine, bromine, and iodine.

2. The compound containing a polybrominated diphenyl ether structure according to claim 1, characterized in that: R1 is selected from C1-3 alkyloxy, hydroxyl; R2 is selected from C1-3 alkoxy, propynyloxy, ethoxy, cyclopropane ester, furanyl ester, thiazolyl ester, halogen-substituted methyl substituted benzoate, halogen-substituted methyl substituted benzenesulfonate, hydroxyl, hydroxymethyl, amino, nitro, carboxyl, aldehyde, 3. The compound containing a polybrominated diphenyl ether structure according to claim 1, characterized in that: The compound containing a polybrominated diphenyl ether structure is selected from the following structures:

4. The compound containing a polybrominated diphenyl ether structure according to claim 1, characterized in that: The compound containing a polybrominated diphenyl ether structure is selected from the following structures:

5. A method for preparing a compound containing a polybrominated diphenyl ether structure according to claim 4, characterized in that: When the compound containing a polybrominated diphenyl ether structure is compound I-1, I-10, II-5, II-6, II-7, II-8, II-9, II-10, or II-11, the reaction formula for preparing the compound containing a polybrominated diphenyl ether structure is as follows: The preparation of the compound containing polybrominated diphenyl ether structure comprises the following steps: (a) Compound 1 is brominated to obtain Compound 2; (b) etherification of compound 2 with 4-bromo-2-fluorobenzaldehyde to obtain compound II-5; (c) Compound II-5 is hydrolyzed by Baeyer-Villiger reaction to obtain compound II-8, and compound II-5 is oxidized by Jones reagent to obtain compound II-6; (d) Compound II-5 is reduced with sodium borohydride to obtain compound II-10; (e) Compounds II-10, II-8, and I-1 are demethylated to obtain compounds II-11, II-7, and I-10; (f) Compound II-8 is methylated to obtain compound II-9; (g) brominating compound II-8 to obtain compound I-1; When the compound containing a polybrominated diphenyl ether structure is compound I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, the reaction formula for preparing the compound containing a polybrominated diphenyl ether structure is as follows: X is selected from methyl, propynyl, formyl, cyclopropanecarboxyl, furanoyl, thiazolecarboxyl, Preparing compounds I-2, I-3, I-4, I-5, I-6, I-7, I-8, and I-9 includes the following steps: (h) Compound I-1 is reacted with iodomethane, propyne bromide, formyl chloride, cyclopropanecarbonyl chloride, furancarbonyl chloride, thiazolecarbonyl chloride, The reaction yields I-2, I-3, I-4, I-5, I-6, I-7, I-8, and I-9.

6. A method for preparing a compound containing a polybrominated diphenyl ether structure according to claim 4, characterized in that: When the compound containing a polybrominated diphenyl ether structure is compound II-1, II-2, II-3, or II-4, the reaction formula for preparing the compound containing a polybrominated diphenyl ether structure is as follows: The preparation of the compound containing polybrominated diphenyl ether structure comprises the following steps: (i) etherification of compound 2 to obtain compound II-4; (j) hydrogenation reduction of compound II-4 to obtain compound II-2; (k) demethylation of compound II-2 to compound II-3; (l) Compound II-4 is demethylated to obtain compound II-1.

7. A method for preparing a compound containing a polybrominated diphenyl ether structure according to claim 4, characterized in that: When the compound containing a polybrominated diphenyl ether structure is compound III-1, III-2, III-3, III-4, III-5, or III-6, the reaction formula for preparing the compound containing a polybrominated diphenyl ether structure is as follows: R is selected from (m) Compound II-6 and The reaction yields compounds III-1, III-2, III-3, III-4, and III-5; (n) Compound III-1 is demethylated to obtain compound III-6.

8. A pharmaceutical composition, characterized in that The invention comprises a compound containing a polybrominated diphenyl ether structure as described in any one of claims 1 to 4.

9. Use of the compound containing a polybrominated diphenyl ether structure as described in any one of 1 to 4 and / or the pharmaceutical composition as described in claim 8 in the preparation of NMDA receptor agonist or antagonist drugs.

10. Use of the compound containing a polybrominated diphenyl ether structure as described in any one of 1 to 4 and / or the pharmaceutical composition as described in claim 8 in the preparation of drugs for treating or preventing central nervous system diseases and / or mental disorders.

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