A compound and its application

Abstract

This invention belongs to the field of medicinal chemistry and discloses a compound and its use. The compound, represented by Formula I, or its stereoisomers, provided herein can effectively alleviate behavioral disturbances exhibited in a rat model of autism induced by valproic acid, providing a potential candidate for the development of novel autism treatments.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicinal chemistry, and in particular relates to a compound and application thereof. Background Art

[0002] Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by social interaction impairments, delayed language development, and repetitive behaviors. In recent years, the prevalence of ASD has steadily increased, making it a global public health concern. Although the etiology of ASD remains unclear, studies have shown that it is closely linked to multiple mechanisms, including genetic factors, abnormalities in the neurotransmitter system, and immune dysfunction.

[0003] Currently, clinically available medications for the treatment of core symptoms of autism are limited, primarily focusing on controlling comorbid symptoms (such as aggressive behavior, anxiety, and irritability). Risperidone and aripiprazole are currently FDA-approved medications for the treatment of irritability associated with autism. However, their use is limited by adverse effects (such as weight gain, metabolic disturbances, and extrapyramidal reactions) and their limited effectiveness in improving core ASD symptoms. Therefore, developing new, safer, and more effective medications to address clinical needs has become an important research direction in this field.

[0004] Topiramate is an anti-epileptic drug with a multi-target mechanism of action, acting through multiple mechanisms, including modulation of glutamatergic and gamma-aminobutyric acid (GABA) neurotransmitter systems, inhibition of sodium channels, and enhancement of GABA activity. This application explores a dosing regimen based on topiramate that can improve core symptoms of ASD, with the goal of providing a novel, more potent compound. Summary of the Invention

[0005] The purpose of the present invention is to provide a compound or a stereoisomer thereof that can effectively alleviate the core symptoms of autism, such as repetitive stereotyped behaviors and emotional disorders.

[0006] In a first aspect, the present invention provides a compound represented by formula (I) or a stereoisomer thereof:

[0007]

[0008] in,

[0009] X=(CH-OR6) n , n=0,1,2;

[0010] Y is selected from O or N. When Y is O, there is no R1 substituent. When Y is N, R1 is a straight or branched alkyl group;

[0011] R2, R3, and R6 are each independently selected from hydroxyl and alkoxy;

[0012] R4 is selected from hydrogen, hydroxy or alkoxy;

[0013] R5 is selected from 、 or ,in Selected from hydrogen, or substituted or unsubstituted alkyl, Cycloalkyl, 5-10 membered aryl or heteroaryl;

[0014] R7 is selected from hydrogen, hydroxymethyl or C 1-4 Alkoxy.

[0015] Furthermore, the above Optionally substituted with 1-3 substituents independently selected from halogen, hydroxy or C1-4 alkyl.

[0016] Preferably, the above R5 is selected from: -SO2CCl3, -C(O)CCl3, -C(OH)CCl3, 、 、 or , For the connection site.

[0017] Furthermore, in the compound represented by the above formula (I), X=(CH-OR6) n , n=0;

[0018] R2 and R3 are each independently selected from hydroxyl; R7 is selected from hydrogen or hydroxymethyl; R5 is selected from -C(O)CCl3, -C(OH)CCl3 or -SO2CCl3.

[0019] Furthermore, in the compound represented by the above formula (I), X=(CH-OR6) n , n=1 or 2;

[0020] R2 and R6, R2 and R3, R3 and R4 or two R6, any two adjacent groups together form a methylenedioxy structure of the following formula:

[0021]

[0022] wherein R8 and R9 are independently selected from hydrogen or alkyl.

[0023] Preferably, in the compound represented by the above formula (I):

[0024] Y is selected from O or N. When Y is O, there is no R1 substituent. When Y is N, R1 is a straight or branched alkyl group;

[0025] R2, R3, R6 are each independently selected from hydroxyl or alkoxy;

[0026] R4 and R7 are selected from hydrogen;

[0027] R5 is selected from 、 or ,in is selected from hydrogen or haloalkyl.

[0028] Furthermore, the above compound or its stereoisomer is selected from the following compounds:

[0029]

[0030]

[0031] Furthermore, the hydrogen in the above compound structure may be replaced by one or more deuteriums.

[0032] In a second aspect, the present invention provides a pharmaceutical composition comprising any one of the above-mentioned topiramate skeleton derivatives and a pharmaceutically acceptable carrier.

[0033] In a third aspect, the present invention provides a use of the above-mentioned topiramate skeleton derivative or the above-mentioned pharmaceutical composition in the preparation of a drug for treating autism spectrum disorders.

[0034] Furthermore, the above-mentioned autism spectrum disorders are induced by valproic acid during pregnancy.

[0035] In a fourth aspect, the present invention provides a use of the above-mentioned compound or its stereoisomer in drug quality testing or the use of the above-mentioned compound or its stereoisomer as a standard or reference substance.

[0036] The present invention has the following beneficial effects:

[0037] The present invention provides a compound represented by formula (I), which has a good therapeutic effect in a valproic acid-induced autism model in rats, can effectively improve autism-related behavioral disorders, and has the potential to become a new drug for the treatment of autism. DETAILED DESCRIPTION

[0038] The present invention is explained below with reference to the examples. The examples are only used to explain the present invention and are not intended to limit the scope of the present invention. Where specific conditions are not specified in the examples, the methods were carried out according to conventional conditions or the conditions recommended by the manufacturer. Where the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially.

[0039] Example 1: Preparation of [2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydro-3aH-di[1,3]dioxolato[4,5-d:4',5'-b]pyran-3a-yl]methyl 2-methylpropane-2-sulfonate (Compound 1)

[0040]

[0041] Step 1: Preparation of intermediate 1-1

[0042] Add 450 ml of acetone to the reaction flask, then slowly add 20 ml of concentrated sulfuric acid dropwise under an ice bath, maintaining the temperature at 3-5°C. After the addition is complete, compound 1-0 (47.6 g, 0.26 mol) is added. The reaction is allowed to react at room temperature for 4 hours, then stopped. After cooling to 0°C, a 60 ml aqueous NaOH solution (6.58 mol / L) is slowly added dropwise. Continue stirring thoroughly, then add 40 ml of triethylamine. After concentration under reduced pressure, dissolve the concentrate in 400 ml of water and 200 ml of dichloromethane. The layers are separated, and the lower organic phase is collected. The upper aqueous phase is extracted twice with dichloromethane (2 x 200 ml). The combined organic phases are washed with water (300 ml) and saturated brine (300 ml), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to yield 49.8 g of intermediate 1-1, with a yield of 72.4% and a purity of 97.2%.

[0043] MS-ESI(+):m / z=261.2(M+H) + .

[0044] Step 2: Preparation of compound 1

[0045] To a reaction flask, add 100 ml of dichloromethane, followed by intermediate 1-1 (10.0 g, 38.4 mmol) and triethylamine (7.8 g, 77.0 mmol). After stirring to dissolve, the reaction solution was cooled to 0-5°C and a 20 ml dichloromethane solution containing tert-butylsulfonyl chloride (7.2 g, 46.0 mmol) was added dropwise under temperature control. After 2 h of reaction, the reaction solution was quenched by adding 50 ml of water. The layers were separated, and the organic phase was collected and extracted twice with dichloromethane (2 x 100 ml). The organic phases were combined, washed with water (100 ml), then with saturated brine (100 ml), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to obtain 12.1 g of compound 1, with a yield of 82.8% and a purity of 98.4%.

[0046] Structural confirmation of compound 1: MS-ESI(+), m / z: 381.2 (M+H + ), 1 H NMR (400 MHz, DMSO-d6 )δ 4.50 – 4.47 (m, 1H), 4.41 – 4.29 (m, 4H), 3.88 – 3.84 (m, 2H), 1.39 – 1.34(m, 12H), 1.24 (s, 9H).

[0047] Example 2: Preparation of [2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydro-3aH-di[1,3]dioxolato[4,5-d:4',5'-b]pyran-3a-yl]methylcyclobutanesulfonate (Compound 2)

[0048]

[0049] According to the preparation method in Example 1, compound 2 with a purity of 98.5% was prepared by replacing tert-butylsulfonyl chloride in step 2 with an equal molar amount of cyclobutanesulfonyl chloride.

[0050] Structural confirmation of compound 2: MS-ESI(+), m / z: 379.2 (M+H) + , 1 H NMR: (400 MHz, DMSO- d6 ) δ4.48 – 4.45 (m, 1H), 4.41 – 4.29 (m, 4H), 3.87 – 3.83 (m, 2H), 3.56 – 3.50 (m, 1H), 2.23 – 2.15 m, 2H), 1.97 –1.89 (m, 2H), 1.83 – 1.66 (m, 2H), 1.39 –1.34 (m, 12H).

[0051] Example 3: Preparation of [2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydro-3aH-di[1,3]dioxolato[4,5-d:4',5'-b]pyran-3a-yl]methyl 2,5-dimethylfuran-3-sulfonate (Compound 3)

[0052]

[0053] According to the preparation method in Example 1, compound 3 with a purity of 98.4% was prepared by replacing tert-butylsulfonyl chloride with an equal molar amount of 2,5-dimethyl-3-furansulfonyl chloride.

[0054] Structural confirmation of compound 3: MS-ESI(+), m / z: 419.1 (M+H) + , 1 H NMR: (400 MHz, DMSO- d6) δ6.65 (s, 1H), 4.55 – 4.53 (m, 1H), 4.41 – 4.33 (m, 4H), 3.88 – 3.84 (m, 2H), 2.57 (s, 3H), 2.32 (s, 3H), 1.39 – 1.34 (m, 12H).

[0055] Example 4: Preparation of [2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydro-3aH-di[1,3]dioxolato[4,5-d:4',5'-b]pyran-3a-yl]methyl 2-methylpropane-1-sulfonate (Compound 4)

[0056]

[0057] According to the preparation method in Example 1, compound 4 with a purity of 97.8% was prepared by replacing tert-butylsulfonyl chloride with an equal molar amount of 2-methylpropanesulfonyl chloride.

[0058] Structural confirmation of compound 4: MS-ESI(+), m / z: 381.2 (M+H) + , 1 H NMR: (400 MHz, DMSO- d6 ) δ4.48 – 4.45 (m, 1H), 4.41 – 4.28 (m, 4H), 3.88 – 3.84 (m, 2H), 2.99 – 2.86(m, 2H), 2.27 – 2.14 (m, 1H), 1.39 – 1.34 (m, 12H), 1.03 (d, 3H), 0.98 (d, 3H).

[0059] Example 5: Preparation of [2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydro-3aH-di[1,3]dioxolato[4,5-d:4',5'-b]pyran-3a-yl]methyl trichloromethanesulfonate (Compound 5)

[0060]

[0061] According to the preparation method in Example 1, compound 5 with a purity of 96.7% was prepared by replacing tert-butylsulfonyl chloride with an equal molar amount of trichloromethanesulfonyl chloride.

[0062] Structural confirmation of compound 5: MS-ESI(+), m / z: 441.1 (M+H) + , 1 H NMR: (400 MHz, DMSO- d6) δ4.67 – 4.64 (m, 1H), 4.41 – 4.33 (m, 3H), 4.12 – 4.09 (m, 1H), 3.90 – 3.84(m, 2H), 1.39 – 1.34 (m, 12H).

[0063] Example 6: Preparation of [2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydro-3aH-di[1,3]dioxolato[4,5-d:4',5'-b]pyran-3a-yl]methyl 2,2,2-trichloroacetate (Compound 6)

[0064]

[0065] According to the preparation method in Example 1, compound 6 with a purity of 96.4% was prepared by replacing tert-butylsulfonyl chloride with an equal molar amount of trichloroacetyl chloride.

[0066] Structural confirmation of compound 6: MS-ESI(+), m / z: 405.1 (M+H) + , 1 H NMR: (400 MHz, DMSO- d6 ) δ 4.68– 4.61 (m, 2H), 4.39 – 4.30 (m, 3H), 3.90 – 3.80 (m, 2H), 1.39 – 1.34(m, 12H).

[0067] Example 7: Preparation of 1-({[2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydro-3aH-di[1,3]dioxolato[4,5-d:4',5'-b]pyran-3a-yl]methyl}oxy)-2,2,2-trichloroethane-1-ol (Compound 7)

[0068]

[0069] Under argon, compound 6 (5.0 g, 12.3 mmol) was dissolved in 25 mL of tetrahydrofuran. The reaction mixture was cooled to below -70°C, and a toluene solution of diisobutylaluminum hydride (DIBAL-H, 24.6 mmol) was added dropwise over approximately 30 minutes. The reaction mixture was stirred at low temperature for 2–3 hours. The reaction was quenched by addition of saturated aqueous potassium sodium tartrate. The mixture was extracted three times with 100 mL of tert-butyl methyl ether, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by reverse-phase column chromatography to obtain 1.2 g of compound 7 in a yield of 23.9% and a purity of 97.8%.

[0070] Structural confirmation of compound 7: MS-ESI(+), m / z: 407.1 (M+H) + , 1 H NMR: (400 MHz, DMSO- d6 ) δ 5.89 (s, 1H), 5.59 (s, 1H), 4.40 – 4.32 (m, 3H), 4.07 – 3.98 (m, 2H), 3.91 – 3.81 (m, 2H), 1.39 – 1.34 (m, 12H).

[0071] Example 8: Preparation of [(3aS,6R,7S,8aR,8S)-7,8-dihydroxy-2,2-dimethyl-3a,4,6,7,8,8a-hexahydro[1,3]dioxol-[4,5-c]oxep-6-yl]methyl trichloromethanesulfonate (Compound 8)

[0072]

[0073] Step 1: Preparation of intermediate 8-2

[0074] According to the preparation method of step 1 in Example 1, compound 1-0 was replaced with an equal molar amount of compound 8-1 (obtained by referring to the synthesis method of compound 8A in Chinese patent CN 116041308A) to obtain intermediate 8-2 with a purity of 97.7%.

[0075] MS-ESI(+):m / z=505.2(M+H) + .

[0076] Step 2: Preparation of intermediate 8-3

[0077] In a hydrogenation reaction flask, compound 8-2 (22 mg, 0.047 mmol) was dissolved in methanol (3 mL) and 10% palladium-carbon catalyst (10 mg) was added. The reaction mixture was stirred at room temperature under hydrogen for 4 h. After the reaction was completed, the filtrate was filtered, collected, and concentrated under reduced pressure to obtain intermediate 8-3.

[0078] Step 3: Preparation of compound 8

[0079] According to the preparation method of step 2 in Example 1, intermediate 1-1 was replaced with an equal molar amount of compound 8-3, and tert-butylsulfonyl chloride was replaced with trichloromethanesulfonyl chloride to obtain compound 8 with a purity of 97.5%.

[0080] Structural confirmation of compound 8: MS-ESI(+), m / z: 414.9 (M+H) + ,1 H NMR: (400 MHz, DMSO- d6 ) δ4.81 (d, 1H), 4.37 – 4.35 (m, 1H), 4.31 – 4.25 (m, 2H), 4.15 – 4.12 (m, 1H), 4.01 – 3.96 (m, 1H), 3.92 – 3.77 (m, 4H), 3.64 – 3.59 (m, 1H), 1.37 (s, 6H).

[0081] Example 9: Preparation of [(3aS,6R,7S,8aR,8S)-7,8-dihydroxy-2,2-dimethyl-3a,4,6,7,8,8a-hexahydro[1,3]dioxol[4,5-c]oxepin-6-yl]methyl 2,2,2-trichloroacetate (Compound 9)

[0082]

[0083] According to the preparation method in Example 8, compound 9 with a purity of 97.3% was prepared by replacing trichloromethanesulfonyl chloride with an equal molar amount of trichloroacetyl chloride.

[0084] Structural confirmation of compound 9: MS-ESI(+), m / z: 379.0 (M+H) + , 1 H NMR: (400 MHz, DMSO- d6 ) δ4.49 (d, 1H), 4.42 – 4.30 (m, 3H), 4.15 –4.12 (m, 1H), 4.02 – 3.91 (m, 3H), 3.90 – 3.79 (m, 2H), 3.65 – 3.57 (m, 1H), 1.37 (s, 6H).

[0085] Example 10: Preparation of [(2R,3S,4R,5S,6S)-3,4,5,6-tetrahydroxyoxepan-2-yl]methyl 2,2,2-trichloroacetate (Compound 10)

[0086]

[0087] According to the preparation method of step 2 in Example 1, intermediate 1-1 was replaced with an equimolar amount of compound 10-1 (obtained with reference to the synthesis method of compound 9A in Chinese patent CN 116041308A), tert-butylsulfonyl chloride was replaced with an equimolar amount of trichloroacetyl chloride, and the reaction solvent was replaced with N,N-dimethylformamide. After post-treatment and quenching, the mixture was directly purified by reverse phase column chromatography to obtain compound 10 with a purity of 96.8%.

[0088] Structural confirmation of compound 10: MS-ESI(+), m / z: 338.9 (M+H) + , 1 H NMR: (400 MHz, D2O) δ4.43 – 4.34 (m, 2H), 3.95 – 3.91 (m, 1H), 3.81 – 3.68 (m, 4H), 3.65 – 3.60(m, 1H), 3.49 – 3.45(m, 1H).

[0089] Example 11: Preparation of [2,3,4-trihydroxy-5-(hydroxymethyl)tetrahydro-2-furyl]methyl 2,2,2-trichloroacetate (Compound 11)

[0090]

[0091] According to the preparation method in Example 10, compound 11 can be prepared by replacing compound 10-1 with an equal mole of compound 11-1 with a purity of 97.7%.

[0092] Structural confirmation of compound 11: MS-ESI(+), m / z: 325.0 (M+H) + , 1 H NMR: (400 MHz, D2O) δ4.39 (s, 2H), 4.11 – 4.03 (m, 2H), 3.87 – 3.79 (m, 2H), 3.78 – 3.70 (m, 1H).

[0093] Example 12: Preparation of 5-(hydroxymethyl)-2-{[(2,2,2-trichloro-1-hydroxyethyl)oxy]methyl}tetrahydrofuran-2,3,4-triol (Compound 12)

[0094]

[0095] According to the preparation method in Example 7, compound 12 was prepared by replacing compound 6 with an equal molar amount of compound 11 with a purity of 97.5%.

[0096] Structural confirmation of compound 12: MS-ESI(+), m / z: 327.0 (M+H) + , 1 H NMR: (400 MHz, DMSO- d6 )δ 5.81 (brs, 1H), 5.58 (s, 1H), 4.35 (d, 1H), 4.13 (brd, 1H), 3.99 (d, 1H), 3.82 – 3.80(m, 1H), 3.74 – 3.72(m, 1H), 3.59 – 3.56(m, 1H), 3.46 – 3.42(m, 1H).

[0097] Example 13: Preparation of [1-butyl-3,4,5-trihydroxyhexahydropyridin-2-yl]methyl trichloromethanesulfonate (Compound 13)

[0098]

[0099] According to the preparation method of Example 10, compound 13 with a purity of 96.8% was obtained by replacing compound 10-1 with an equal mole of compound migroot (CAS No.: 72599-27-0) and replacing trichloroacetyl chloride with an equal mole of trichloromethylsulfonyl chloride.

[0100] Structural confirmation of compound 13: MS-ESI(+), m / z: 400.0 (M+H + ), 1 H NMR: (400 MHz, D2O) δ4.46 –4.26 (m, 2H), 3.80 – 3.68 (m, 2H), 3.67 – 3.59 (m, 1H), 3.01 – 2.98 (m,1H), 2.84 – 2.80 (m, 1H), 2.63 – 2.53 (m, 3H), 1.49 – 1.40 (m, 2H), 1.39 –1.29 (m, 2H), 0.93 (t, 3H).

[0101] Example 14: Preparation of [2,3,4-trihydroxy-5-(hydroxymethyl)tetrahydro-2-furyl]methyl trichloromethanesulfonate (Compound 14)

[0102]

[0103] According to the preparation method of Example 11, except that trichloroacetyl chloride was replaced with an equal mole of trichloromethanesulfonyl chloride, compound 14 was prepared with a purity of 98.1%.

[0104] Structural confirmation of compound 14: MS-ESI(+), m / z: 361.1 (M+H) + , 1 H NMR: (400 MHz, D2O) δ4.21 (s, 2H), 4.14 – 4.11 (m, 1H), 4.07 – 4.03 (m, 1H), 3.86 – 3.74 (m, 3H).

[0105] Comparative Example 1: Topiramate

[0106]

[0107] Comparative Example 2:

[0108]

[0109] Test example

[0110] This test example discloses a drug efficacy test on the compound of the present application in improving valproic acid (VPA)-induced autism in rats.

[0111] 1. ASD model establishment

[0112] Wistar rats were induced with valproic acid (VPA) at 12.5 days of gestation to induce autism. Pregnant females were intraperitoneally injected with either VPA (500 mg / kg) or saline (10 mL / kg) and then returned to their original cages. Offspring of both sexes born to VPA-treated dams with one of four tail abnormalities (short tail, mid-curved tail, short curved tail, or double curved tail) were enrolled in the ASD model. Offspring born to VPA- or saline-treated dams were weaned and housed separately by sex at 21 days of age. The offspring were randomly divided into a blank control group (pregnant rats not treated with VPA), a model group (ASD model), control groups 1-2 (ASD model), and compound groups 1-14 (ASD model), with 6 rats per group (3 females and 3 males), for a total of 18 groups.

[0113] 2. Dosage regimen

[0114] Rats in the blank control group and model group were orally gavaged with 10 mL / kg of normal saline. Rats in the comparative example 1 group were orally gavaged with 3 mg / kg of topiramate. Rats in the comparative example 2 group and compound 1-14 groups were orally gavaged with equimolar amounts (dosage calculated based on 3 mg / kg of topiramate) of the compound in comparative example 2 and compounds 1-14, respectively. Dosing was performed once daily from day 21 to day 50 (a total of 29 days).

[0115] 3. Test results

[0116] 3.1 Behavioral testing: open field test

[0117] The day after treatment, an open field test was conducted. Rats were randomly placed in an opaque acrylic square open field (100 × 100 × 45 cm). The bottom of the box was divided into a central and peripheral compartment. Before the test, the rats were allowed to explore the environment for 1 minute. Afterward, the rats were placed in the center of the field and their spontaneous activity was measured for 1 hour. The time spent in the center and peripheral compartments, as well as the number of times the rats groomed, was recorded. The rats' spontaneous locomotor activity was tested to assess their emotions. The time spent in the center and peripheral compartments was used to assess fear and anxiety, while excessive and abnormal grooming behavior was used to assess repetitive and aggressive behavior.

[0118] Table 1 Open field test results

[0119]

[0120] According to the results of the open field test, the compounds of the present invention can significantly improve the behavioral abnormalities of VPA-induced autism model rats. The central residence time and combing times of the compound 5-14 group were restored to levels close to those of the blank control group, and the effects were significantly better than those of the comparative example 1 and comparative example 2 groups.

[0121] 3.2 Biochemical tests: detection of SOD and AChE in hippocampal tissue

[0122] After the behavioral experiment, the anesthetized rats were perfused with the heart. The hippocampal tissue was quickly isolated and frozen in liquid nitrogen. The collected tissue was homogenized and the supernatant was used to determine the levels of superoxide dismutase (SOD) and acetylcholinesterase (AChE).

[0123] Table 2 Results of superoxide dismutase (SOD) and acetylcholinesterase (AChE) in hippocampus

[0124]

[0125] As can be seen from the above table, the SOD activity and AChE levels of the compound 1-14 group of the present invention were significantly different from those of the model group (P < 0.001). Among them, the SOD activity and AChE levels of the compound 5-14 group returned to the normal range, and the improvement effect was significantly better than that of the comparative example 1 group and the comparative example 2 group (P < 0.05), showing excellent neuroprotective effects and providing important candidate molecules for the development of new autism treatment drugs.

[0126] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A compound or a stereoisomer thereof, characterized in that: The compound or its stereoisomer is selected from: 、 、 、 、 、 、 、 、 、 、 、 、 or .

2. A pharmaceutical composition comprising the compound according to claim 1 or a stereoisomer thereof, and a pharmaceutically acceptable carrier.

3. Use of the compound or stereoisomer thereof according to claim 1 or the pharmaceutical composition according to claim 2 in the preparation of a medicament for treating autism spectrum disorder.

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