Piperazinyl-heterocyclic compounds and uses thereof

Abstract

The application belongs to the field of medicine, and particularly relates to a piperazinyl-heterocyclic compound and application thereof. The application provides a compound which has certain affinity to D3 and 5-HT6, and is presumed to have the effect of improving cognition in clinic.

Description

Technical Field

[0001] This invention belongs to the pharmaceutical field, specifically relating to a piperazine-based heterocyclic compound and its uses. Background Technology

[0002] The study found that D1, D2, D3, and 5-HT 2A Five receptors, including 5-HT6 and H1, play crucial roles in schizophrenia. D1 receptors are primarily located in the cortex; antagonism of D1 receptors helps improve positive symptoms. D2 receptors are mainly located in the striatum, limbic system, and tuberous infundibulum; antagonism of D2 receptors also helps improve positive symptoms. D3 receptors are mainly located in the nucleus accumbens in the midbrain limbic system, with smaller amounts also found in the caudate nucleus and putamen. Antagonism of D3 receptors improves cognition, reduces extrapyramidal side effects, and has a sedative effect. The serotonin system plays a vital role in regulating the functions of the prefrontal cortex, including emotional control, cognitive behavior, and working memory. Pyramidal neurons and GABA interneurons in the prefrontal cortex contain serotonin receptors (5-HT6, 5-HT6, and 5-HT6). 1A and 5-HT 2A 5-HT 1A In association with atypical antipsychotic medications, it can improve negative symptoms and cognitive impairment. 5-HT 2A Receptors are involved in various aspects of perception, emotion regulation, and motor control; blocking 5-HT... 2A Receptors can normalize the release of dopamine, thus playing an antipsychotic role.

[0003] Dopaminergic neurons in the brain exhibit two types of electrical activity: low-frequency activity, which is the neuron's inherent basic electrical activity, and high-frequency activity, generated by nerve impulses and termed "burst firing," which is related to the occurrence and maintenance of reward behavior in animals. The 5-HT neural pathway in the prefrontal cortex regulates burst firing. In animals with low prefrontal cortex function (lower prefrontal cortex temperature), burst firing of domino neurons in the limbic system is inhibited (but basic electrical activity remains unaffected), and 5-HT... 2A Antagonists can restore the firing ignition of DA neurons, 5-HT 2A This regulatory effect of antagonists on dopamine (DA) may be a mechanism for treating negative symptoms.

[0004] Pharmacological tests revealed that 5-HT 2A Antagonists can cause a slight increase in dopamine (DA) release from the nigrostriatal system. Risperidone, by both blocking D2 receptors and DA release, can also cause a slight increase (through blocking 5-HT). 2A The receptor (which relieves the inhibition of DA by 5-HT) and the receptor compete with each other. The slight increase in DA offsets part of the antagonistic effect of DA, thus reducing EPS (extrapyramidal side effects).

[0005] 5-HT 2A The characteristic of mixed action of 5-HT and D2 receptors has been used as a hallmark of atypical antipsychotics. 2A Only drugs with antagonistic effects greater than D2 are classified as atypical antipsychotics. For example, 5-HT... 2A Atypical antipsychotics such as risperidone, which are D2 balance antagonists, belong to the 5-HT group. 2A / D2 receptor mixed antagonists are characterized by relatively weak D2 receptor antagonism that improves positive symptoms and has limited effect on EPS, and strong 5-HT 2A Receptor antagonism can improve negative symptoms and affective symptoms, and partially counteract EPS caused by D2 antagonism.

[0006] 5-HT6 receptor antagonists have been shown to improve cognitive function in patients with schizophrenia. Firstly, blocking 5-HT6 receptors increases glutamate and cholinergic neurotransmission in multiple brain regions and promotes the release of dopamine (DA) and norepinephrine in the prefrontal cortex. Furthermore, the 5-HT6 receptor antagonist SB-399885 exhibits a synergistic effect with anti-schizophrenia drugs in promoting DA release. Additionally, the therapeutic effect of 5-HT6 receptor antagonists is also related to their inhibition of the mammalian target of rapamycin (mTOR) pathway. Studies have shown that 5-HT6 receptor activation enhances the mTOR signaling pathway in the rat prefrontal cortex, and in a PCP (phenylcycline)-induced chronic schizophrenia model, mTOR activity in the prefrontal cortex is significantly enhanced. The mTOR receptor antagonist rapamycin can also improve cognitive deficits in model animals.

[0007] Among the targets associated with antipsychotic drugs, the H1 receptor is a target associated with side effects. Antagonism of the H1 receptor can lead to drowsiness, weight gain, and low blood pressure.

[0008] Therefore, there is an urgent need to find new compounds that can treat the positive symptoms of schizophrenia, improve the negative symptoms and cognitive impairment, and reduce the side effect of weight gain. Summary of the Invention

[0009] To address the aforementioned technical problems, this invention provides relevant solutions.

[0010] This invention provides a compound of formula I or a pharmaceutically acceptable salt thereof:

[0011]

[0012] Where n is an integer between 2 and 6, and W is either O or S.

[0013] The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof, wherein n is 2 and W is S.

[0014] On the other hand, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

[0015] On the other hand, the present invention provides the use of a compound of formula I or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating neuropsychiatric disorders, further wherein the neuropsychiatric disorders are schizophrenia, depression, and psychosis. depression .

[0016] Pharmaceutically acceptable salts of the compounds of Formula I of the present invention include, but are not limited to, salts selected from the group consisting of: oxalates, hydrochlorides, hydrobroms, hydroiodates, nitrates, sulfates, hydrogen sulfates, phosphates, acid phosphates, acetates, lactates, citrates, tartrates, maleates, fumarates, methanesulfonates, gluconates, glycosides, benzoates, ethanesulfonates, benzenesulfonates, or p-toluenesulfonates.

[0017] On the other hand, the present invention provides a method for preparing a compound of formula I or a pharmaceutically acceptable salt thereof, characterized in that it comprises condensing compounds of formula II and formula III in the presence of a base to prepare compound I:

[0018] Wherein, X is a halogen, preferably chlorine or bromine;

[0019] W represents O or S;

[0020] n is an integer between 2 and 6.

[0021] In the preparation method of Formula I, the solvent used is selected from at least one of water, alcohol, nitrile, ketone, ether, unsubstituted aromatic hydrocarbon, monoalkyl or polyalkyl substituted aromatic hydrocarbon, monohalogenated and polyhalogenated aromatic hydrocarbon, sulfoxide, and amide solvent, preferably water, methanol, ethanol, isopropanol, n-butanol, acetonitrile, methyl isobutyl ketone, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, toluene, xylene, chlorobenzene, dimethyl sulfoxide, and N,N-dimethylformamide, more preferably water.

[0022] In the preparation method of Formula I, the alkali is selected from at least one of inorganic alkalis and organic alkalis (such as amines), preferably one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, triethylamine, pyridine, and 4-dimethylaminopyridine, and more preferably sodium carbonate.

[0023] In the preparation method of Formula I, the reaction is carried out under reflux conditions.

[0024] In the preparation method of Formula I, the molar ratio of the compounds of Formula II and III to the base is 1.0:(1.0~1.2):(2.0~3.0).

[0025] On the other hand, the present invention provides a method for preparing Formula II, wherein the compound of Formula II is further prepared from the compound of Formula IV in the presence of a reducing agent:

[0026] ;

[0027] Wherein, X is a halogen, preferably chlorine or bromine;

[0028] W represents O or S;

[0029] n is an integer between 2 and 6.

[0030] In the preparation method of compound II, the reducing agent is selected from one of sodium borohydride / zinc chloride, sodium borohydride / aluminum chloride, and trifluoroacetic acid / triethylsilane, preferably trifluoroacetic acid / triethylsilane.

[0031] In the preparation method of compound II, no solvent is used in the reaction.

[0032] In the preparation method of compound II, the reaction temperature is -5 to 60℃, preferably 0 to 45℃.

[0033] On the other hand, the present invention provides a method for preparing a compound of formula IV, wherein the compound of formula IV is prepared by an acylation reaction of a compound of formula V in the presence of an acid:

[0034] ;

[0035] Wherein, X is a halogen, preferably chlorine or bromine;

[0036] W represents O or S;

[0037] n is an integer between 2 and 6.

[0038] In the preparation method of compound IV, the acid is selected from at least one Lewis acid, preferably one or more of aluminum trichloride, zinc chloride, ferric chloride, boron tribromide, trifluoromethanesulfonic acid, phosphotungstic acid, and phosphomolybdic acid, and more preferably aluminum trichloride.

[0039] In the preparation method of compound IV, the solvent used for the acylation reaction is selected from at least one of haloalkanes, unsubstituted aromatic hydrocarbons, monoalkyl or polyalkyl substituted aromatic hydrocarbons, monohalogenated or polyhalogenated aromatic hydrocarbons, nitro-substituted aromatic hydrocarbons, and nitriles, preferably one or more of dichloromethane, 1,2-dichloroethane, carbon dichloride, chloroform, carbon tetrachloride, chlorobenzene, nitrobenzene, and acetonitrile, more preferably dichloromethane.

[0040] The solvent used is selected from at least one of haloalkanes, unsubstituted aromatic hydrocarbons, monoalkyl or polyalkyl substituted aromatic hydrocarbons, monohalogenated or polyhalogenated aromatic hydrocarbons, nitro-substituted aromatic hydrocarbons, and nitriles, preferably one or more of dichloromethane, 1,2-dichloroethane, carbon dichloride, chloroform, carbon tetrachloride, chlorobenzene, nitrobenzene, and acetonitrile, more preferably dichloromethane.

[0041] In the preparation method of compound IV, the acylation reagent used in the reaction is a haloacyl chloride, more preferably chloroacetyl chloride, 3-chloropropionyl chloride, 4-chlorobutyryl chloride, 5-chlorovaleryl chloride, 6-chlorohexanoyl chloride, bromoacetyl chloride, 3-bromopropionyl chloride, 4-bromobutyryl chloride, 5-bromovaleryl chloride, or 6-bromohexanoyl chloride.

[0042] In the preparation method of compound IV, the reaction is carried out under reflux conditions.

[0043] In the preparation method of compound IV, the molar ratio of compound V, acylation reagent and acid is 1.0:(1.0~2.0):(2.5~4.0).

[0044] Terminology Explanation:

[0045] The "schizophrenia and depression" described in this invention mainly refers to schizoaffective disorder, depressive type, in psychiatry; the patient has both symptoms of schizophrenia and typical symptoms of depression, and the symptoms of the two diseases are equally prominent and coexist.

[0046] The halogenated acyl chlorides of this invention refer to chloroacetyl chloride, 3-chloropropionyl chloride, 4-chlorobutyryl chloride, 5-chlorovaleryl chloride, 6-chlorohexanoyl chloride, bromoacetyl chloride, 3-bromopropionyl chloride, 4-bromobutyryl chloride, 5-bromovaleryl chloride, and 6-bromohexanoyl chloride.

[0047] In this invention, "n" refers to an integer from 1 to 6, an integer from 2 to 4, an integer from 2 to 5, and an integer from 2 to 6, specifically 2, 3, 4, 5, and 6.

[0048] Beneficial technical effects of the present invention:

[0049] 5-[2-[4-(1,2-benzisothiazol-3-yl)piperazinyl-1-]ethyl]-6-bromo-1,3-dihydro-2H-indole-2-one (bromoziprasidone) for 5-HT 2AThe affinity for the D2 receptor is significantly stronger than that for the D2 receptor, a characteristic similar to ziprasidone, both belonging to atypical antipsychotic drugs. Bromoziprasidone exhibits higher affinity for SERT, NET, and DAT than ziprasidone, indicating a significant potential benefit for schizophrenia patients with depression. Bromoziprasidone also has a high affinity for the 5-HT6 receptor, which can improve cognition. Its affinity for the D3 receptor is significantly stronger than that of ziprasidone; antagonizing the D3 receptor improves cognition, reduces extrapyramidal side effects, and provides sedation. It has no effect on H1 receptors and poses no risk of weight gain or hypotension. Detailed Implementation

[0050] General synthetic preparation methods:

[0051] .

[0052] Ziprasidone was prepared according to reference CN1242987; chloroacetyl chloride, 4-chloroacetyl chloride and 6-bromoindole-2-one were purchased from Aladdin Reagent Co., Ltd.; 3-(1-piperazinyl)-1,2-benzisothiazole was purchased from Jiangxi Kaiyuan Biomedical Technology Co., Ltd.

[0053] Example 1: Preparation method

[0054]

[0055] 1. Preparation of 5-(2-chloroacetyl)-6-bromo-1,3-dihydro-indole-2-(2H)-one

[0056] Anhydrous aluminum trichloride (266.6 g, 2.0 mol) and chloroacetyl chloride (84.7 g, 0.75 mol) were added to 530 mL of dichloromethane and stirred for 0.5 h. Then, 6-bromoindol-2-one (106.0 g, 0.5 mol) was added, and the mixture was refluxed for 48 h. The reaction solution was quenched in ice water, filtered, and the crude product was obtained. The crude product was recrystallized from 2100 mL of glacial acetic acid, filtered, washed with water, and dried to obtain 101.0 g of a pink solid, yield 70.0%, HPLC purity 99.2%.

[0057] MS:( [MH] - ): 285.85, 287.80

[0058] 1 HNMR(400MHz,DMSO-d6)δ:10.82(s,1H,NH);7.70(s,1H,ArH);7.10(s,1H,ArH);

[0059] 4.99(s,2H,CH2);3.53(s,2H,CH2).

[0060] 2. Preparation of 5-(2-chloroethyl)-6-bromo-1,3-dihydro-indole-2-(2H)-one

[0061] 101.0 g (0.35 mol) of 5-(2-chloroacetyl)-6-bromo-1,3-dihydro-indole-2-(2H)-one was added to 500 mL of trifluoroacetic acid. The mixture was cooled to 0 °C, and then 122.1 g (1.05 mol) of triethylsilane was added. The mixture was heated to 45 °C and reacted for 3 hours. The mixture was then cooled to 0 °C, stirred for 1 hour, filtered, and dried to give 84.5 g of a pink solid, with a yield of 88.0% and an HPLC purity of 99.0%.

[0062] MS:( [MH] - ): 271.90, 273.90

[0063] 1 HNMR(500MHz,DMSO-d6)δ:10.42(s,1H,NH);7.25(s,1H,ArH);6.98(s,1H,ArH);

[0064] 3.75~3.78(t,2H,CH2);3.44(s,2H,CH2);3.07~3.10(t,2H,CH2).

[0065] 3. Preparation of 5-[2-[4-(1,2-benzisothiazol-3-yl)piperazinyl-1-]ethyl]-6-bromo-1,3-dihydro-2H-indole-2-(2H)-one

[0066] 84.5 g (0.3 mol) of 5-(2-chloroethyl)-6-bromo-1,3-dihydro-indole-2-(2H)-one, 3-(1-piperazinyl)-1,2-benzisothiazole (65.8 g (0.3 mol)) and anhydrous sodium carbonate (79.4 g (0.75 mol)) were added to 1700 mL of water, and the mixture was refluxed for 20 hours. After cooling to room temperature, the mixture was filtered, washed with water, and the crude product was obtained. 850 mL of tetrahydrofuran was added, and the mixture was refluxed and stirred for 1 hour. After cooling to room temperature, the mixture was filtered, dried, and 107.0 g of a pale yellow solid was obtained, with a yield of 78.0% and an HPLC purity of 99.0%.

[0067] MS:( [M+H] + ): 456.95, 459.00

[0068] 1 HNMR(400MHz,DMSO-d6)δ:10.41(s,1H,NH);8.05~8.07(d, J= 7.48,2H,ArH);

[0069] 7.56(s,1H,ArH);7.43(s,1H,ArH);7.24(s,1H,ArH);6.96(s,1H,ArH);3.33~3.46(m,6H,CH2);2.86(s,2H,CH2);2.70(s,4H, CH2);2.50~2.54(m,2H,CH2).

[0070] Example 2: Pharmacological Example

[0071] 1. In vitro receptor binding assay method

[0072] 1.1 Preparation of Buffer and Compound

[0073] A: (used to prepare α) 2B α 2C (Receptor membrane): Weigh 146 mg of EDTA and add it to a 50 mM Tris-HCl buffer solution to a total volume of 1000 mL. Adjust the pH to 7.7 to achieve a final concentration of 0.5 mM EDTA.

[0074] B: (used in the preparation of 5-HT) 1A 5-HT 2A (5-HT6 receptor membrane): Weigh 11.7 mg EDTA and 380.84 mg MgCl2, add 50 mM Tris-HCl buffer to a total volume of 400 mL, and adjust the pH to 7.4. This will give you final concentrations of 0.1 mM EDTA and 10 mM MgCl2.

[0075] C: (for preparing D1, D2, and D3 receptor membranes): Dopamine Binding Buffer: 50 mM NaCl, 50 mM HEPES-HCl, 5 mM MgCl2, 0.5 mM EDTA, pH 7.4.

[0076] D: (used for preparing SERT, NET, and DAT receptor membranes): 50 mM Tris HCl, 150 mM NaCl, 5 mM KCl, pH 7.4.

[0077] E: (used for preparing Sigma-1 and Sigma-2 receptor membranes): 

[0078] 1) 10 mM Tris-HCl buffer containing 320 mM sucrose solution, pH 7.4.

[0079] 2) 10 mM Tris-HCl buffer, pH 7.4.

[0080] F (used for preparing H1 receptor membrane): 50 mM Tris HCl, 0.5 mM EDTA, pH 7.4.

[0081] G: (for preparing M1 receptor membrane): 50mM Tris-HCl Buffer: pH 7.4.

[0082] H: (used for preparing NMDA receptor membrane): 50 mM Tris HCl, 1 mM EDTA, pH 7.4.

[0083] 1.2 Preparation of receptor membrane

[0084] 1.2.1 Preparation of cell receptor membrane

[0085] CHO-α 2B ,CHO-α 2C CHO-5-HT 1A CHO-5-HT 2A Cells of various types, including CHO-5-HT6, CHO-D1, CHO-D2, CHO-D3, 293-NET, 293-SERT, 293-DAT, CHO-M1, and 293-H1, were removed from a -80°C freezer and thawed naturally. They were then centrifuged at 2000g at 4°C for 10 min, the supernatant was discarded, and the pellet was collected. Buffer was added to the pellet, and homogenization was performed for 20-30 s. The pellet was then centrifuged at 48000g at 4°C for 25 min, the supernatant was discarded, and the pellet was again homogenized by adding buffer and homogenizing for 20-30 s. It was then centrifuged at 48000g at 4°C for 25 min, the supernatant was discarded, and the pellet was stored at -80°C.

[0086] 1.3 Receptor competition binding assay

[0087] 1.3.1 Conditions for Radioactive Binding Tests

[0088] Table 1. Conditions for Radioactive Binding Tests

[0089]

[0090] In the table above 3 H is marked with 3H, for example 3 H-Methylspiperone is 3H-labeled methylspiroperone; Paroxetine refers to paroxetine, Pyrilamine refers to pyramine, Quinuclidiny benzilate is a quinine cycloester, Nisoxetine refers to nisoxetine, Methylspiperone is methylspiroperone, and Ketanserin refers to sertraline. 3H-WIN35428 (code name WIN35428 is a dopamine reuptake inhibitor) 3 H-SCH 23390 (code name SCH 23390 is a dopamine D1 receptor antagonist). 3 H-8-OH-DPAT (code name 8-OH-DPAT is a selective 5-HT1A agonist).

[0091] 1.3.2 Receptor Binding Assay Procedure

[0092] 1.3.2.1 Cell Receptor Affinity Assay

[0093] Step 1: Add 50 μL of solvent (1% DMSO) to the total bound well (TB) and 50 μL of non-specific bound well (NB) with a final concentration of 1.0 × 10⁻⁶. -5 M), add 50 μL of the test compound to each well (CB).

[0094] Step 2: Add 100 μL of buffer solution to each reaction well.

[0095] Step 3: First, prepare the membrane into a suspension of the appropriate concentration using a homogenizing solution for later use.

[0096] Step 4: Add 50 μL of radioactive ligand to each reaction well.

[0097] Step 5: Add 50 μL of membrane suspension to each reaction well.

[0098] Step 6: Incubate each reaction well at 25℃ for 90 min. After the reaction is complete, the bound ligands are rapidly filtered under reduced pressure. The UniFilter-96 GF / C plate is soaked in 0.5% PEI for more than 1 hour beforehand. After filtration, the filter membrane is dried in an oven at 60℃. After attaching the base film, add 40 µL of scintillation solution, seal the membrane, and let it stand.

[0099] Step 7: Place the filter plate into the liquid scintillation counter for counting.

[0100] 1.3.2.2 Tissue receptor affinity assay

[0101] Step 1: Add 50 μL of solvent (1% DMSO) to the total binding tube (TB), and add 50 μL of non-specific binding agent (final concentration 1.0 × 10⁻⁶) to the non-specific binding tube (NB). -5 M), 50 μL of the test compound was added to each test compound tube (CB).

[0102] Step 2: Add 100 μL of buffer solution to each reaction tube.

[0103] Step 3: First, prepare the membrane into a membrane suspension of the appropriate concentration using a homogenizing solution for later use.

[0104] Step 4: Add 50 μL of the corresponding radioactive ligand to each reaction tube.

[0105] Step 5: Add 50 μL of membrane solution to each reaction tube.

[0106] Step 6: Incubate each reaction tube according to the incubation conditions. After the reaction is complete, the bound ligands are rapidly filtered under reduced pressure. The Whatman test strip GF / C is saturated with 0.5% PEI solution 1 hour in advance, and thoroughly washed with ice-cold Tris-HCl buffer. The filter is then removed and placed in a 4 mL scintillation cup, dried at 60°C for 30 min, and 1 mL of toluene scintillation solution is added and mixed well.

[0107] Step 7: Place the scintillation cup into the liquid scintillation counter for counting.

[0108] 2. Data Analysis

[0109] Based on the effect values ​​at different concentration test points of the compound sample, the GraphPad Prism software was used to fit the curve of the compound sample's interaction with the receptor, and the Ki value was calculated.

[0110] 3. Experimental Results

[0111] The results of in vitro receptor assays are shown in the table below.

[0112] Table 2. In vitro receptor binding assay data of ziprasidone and 5-[2-[4-(1,2-benzisothiazol-3-yl)piperazinyl-1-]ethyl]-6-bromo-1,3-dihydro-2H-indole-2-one (bromoziprasidone)

[0113]

[0114] brominated ziprasidone for 5-HT 2A Its affinity for the D2 receptor is significantly stronger than that for the D2 receptor, a characteristic similar to ziprasidone; both belong to the class of atypical antipsychotic drugs. It also has an affinity for 5-HT. 2A Antagonistic effects can improve negative symptoms and reduce EPS (extrapyramidal side effects) caused by D2 receptor antagonism. In addition, bromoziprasidone and ziprasidone have a high affinity for dopamine D1 receptors, and D1 receptor antagonism helps improve positive symptoms.

[0115] Bromoziprasidone has a higher affinity for SERT, NET, and DAT than ziprasidone, indicating that bromoziprasidone has a significant advantage in treating schizophrenia patients with depression.

[0116] Bromoziprasidone exhibits a high affinity for 5-HT6 receptors, suggesting it may play a role in improving cognition. However, no significant affinity for ziprasidone was observed for 5-HT6 receptors. Studies have shown that 5-HT6 receptor antagonists regulate the levels of neurotransmitters such as ACh, Glu, DA, and GABA, and that antagonism of 5-HT6 receptors can improve cognition. Furthermore, bromoziprasidone shows a significantly stronger affinity for D3 receptors than ziprasidone. D3 receptors are primarily located in the nucleus accumbens in the mesolimbic region, with smaller amounts also found in the caudate nucleus and putamen. Antagonism of D3 receptors can improve cognition, reduce extrapyramidal side effects, and provide sedation.

[0117] Ziprasidone has a moderate affinity for the H1 receptor, while bromoziprasidone has virtually no affinity for this receptor and carries no risk of drowsiness, weight gain, or hypotension.

Claims

1. A compound of Formula I or a pharmaceutically acceptable salt thereof: in, n is 2, W is S.

2. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.

3. The use of the compound of claim 1 or the pharmaceutical composition of claim 2 in the preparation of a drug for treating neuropsychiatric disorders, wherein the neuropsychiatric disorders are schizophrenia and depression.

4. The method for preparing the compound according to claim 1, characterized in that, Compound I was prepared by condensation of compound II and compound III in the presence of a base. ， Where X is a halogen, n is 2, and W is S.

5. The preparation method according to claim 4, characterized in that, The solvent used in the condensation reaction is selected from at least one of water, methanol, ethanol, isopropanol, n-butanol, acetonitrile, methyl isobutyl ketone, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, toluene, xylene, chlorobenzene, dimethyl sulfoxide, and N,N-dimethylformamide. The base is selected from one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, triethylamine, pyridine, and 4-dimethylaminopyridine. The reaction is carried out under reflux conditions, and the molar ratio of compound II and compound III to the base is 1.0:(1.0-1.2):(2.0-3.0).

6. The preparation method according to claim 5, characterized in that, The solvent used in the condensation reaction is water, and the base is sodium carbonate.

7. The preparation method according to claim 4, characterized in that, The method further includes a method for preparing compound II, specifically, preparing compound II from compound IV in the presence of a reducing agent: ， Where X is a halogen and n is 2.

8. The preparation method according to claim 7, characterized in that, In the preparation method of compound II, the reducing agent is selected from one of sodium borohydride / zinc chloride, sodium borohydride / aluminum chloride, and trifluoroacetic acid / triethylsilane, and the reaction temperature is -5 to 60°C.

9. The preparation method according to claim 8, characterized in that, In the preparation method of compound II, the reducing agent is trifluoroacetic acid / triethylsilane, and the reaction temperature is 0-45℃.

10. The preparation method according to claim 7, characterized in that, The method further includes a method for preparing compound IV, specifically, preparing compound IV by acylation of compound V in the presence of an acid: ， Where X is a halogen and n is 2.

11. The preparation method according to claim 10, characterized in that, In the preparation method of compound IV, the acid is selected from one or more of aluminum trichloride, zinc chloride, ferric chloride, boron tribromide, trifluoromethanesulfonic acid, phosphotungstic acid, and phosphomolybdic acid; the solvent used in the acylation reaction is selected from one or more of dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, chlorobenzene, nitrobenzene, and acetonitrile; the acylation reagent used in the reaction is chloroacetyl chloride or bromoacetyl chloride; the reaction is carried out under reflux conditions; and the molar ratio of compound V, acylation reagent, and acid is 1.0:(1.0-2.0):(2.5-4.0).

12. The preparation method according to claim 11, characterized in that, In the preparation method of compound IV, the acid is aluminum trichloride, and the solvent used in the acylation reaction is dichloromethane.

13. The preparation method according to any one of claims 4-10, characterized in that, X is chlorine or bromine.

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