A derivative containing an arylpiperazine structure, a composition thereof and applications thereof

Abstract

The present invention discloses a derivative containing an arylpiperazine structure, a composition and its application. The derivative is a compound having the structure as shown in general formula (I) or a pharmaceutically acceptable salt thereof; the composition includes a derivative containing an arylpiperazine structure or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers. The present invention also provides the application of a derivative containing an arylpiperazine structure or a pharmaceutically acceptable salt thereof in the preparation of an antidepressant drug. The derivative can not only have a high affinity for 5-HT 1A receptor and 5-HT 2A receptor, but also have a good affinity for 5-HT transporter (SERT) and norepinephrine transporter (NET); when it is applied to the treatment of depression, it can have the characteristics of high response rate, short onset time, and small side effects, so as to meet the needs of clinical medication.

Description

Technical Field

[0001] The present invention belongs to the field of organic chemical synthesis, and particularly relates to a derivative containing an arylpiperazine structure, a composition and their applications. Background Art

[0002] Depression is a common mental disorder, mainly manifested as symptoms such as low mood, reduced interest, and anhedonia. Some severely affected patients may also exhibit behaviors such as anxiety, self-blame, and attempted suicide. Research has found that the gene polymorphism of SERT is closely related to the occurrence of depression. The deletion of SERT in the dorsal raphe nucleus can reduce the activity of 5-hydroxytryptamine (5-HT or serotonin) neurons, and low levels of 5-HT in the brain can lead to depression. Serotonin transporter or 5-HT transporter (SERT or 5-hydroxytryptamine, 5-HTT) is a Na + / Cl - +-dependent high-affinity transmembrane transporter protein with 12 transmembrane domains, and both the N-terminus and C-terminus are located in the cytoplasm. It has a high affinity for 5-HT and is a key modulator of 5-HT signaling. 5-HTT can reuptake 5-HT in the synaptic cleft, thereby regulating the transduction of nerve signals. Inhibiting the serotonin transporter can significantly increase the concentration of 5-HT in the synaptic cleft and the selectivity of drug action, thereby improving the patient's depressive mood and the adverse reactions of the drug.

[0003] Selective Serotonin Reuptake Inhibitors (SSRIs) are currently the most widely used class of antidepressants in clinical practice. Compared with other antidepressants such as norepinephrine reuptake inhibitors (such as tricyclic antidepressants and monoamine oxidase inhibitors), this class of drugs has high selectivity, good safety, and significantly lower side effects than tricyclics. However, the activity of this class of drugs is comparable to that of tricyclics, and it is the first choice for patients with cardiovascular complications and depression. Fluoxetine, Fluvoxamine, Paroxetine, Citalopram, and Sertraline are vividly called the "five golden flowers" in the Chinese psychiatric community. Selective serotonin transporter inhibitors are an important subgroup of SSRIs. Although SSRIs are widely used in clinical practice, due to low response rates, long onset times, and potential side effects of some drugs, there are still quite a number of patients who are ineffective after various treatments, and some still need to resort to electroconvulsive therapy. Therefore, the development of antidepressants remains a hot topic in new drug research. Summary of the Invention

[0004] One object of the present invention is to provide a derivative and a composition containing an arylpiperazine structure. This derivative not only has high affinity for 5-HT 1A receptors and 5-HT 2A receptors, but also has good affinity for 5-HT transporter (SERT) and norepinephrine transporter (NET); when applied in the treatment of depression, it can have characteristics such as high response rate, short onset time, and small side effects, so as to meet the needs of clinical medication.

[0005] Another object of the present invention is to provide the use of a derivative containing an arylpiperazine structure or a pharmaceutically acceptable salt thereof in the preparation of drugs for treating depressive diseases.

[0006] To achieve the above object, the technical solution adopted by the present invention is: a derivative containing an arylpiperazine structure, which is characterized in that it is a compound having the general structural formula (I) or a pharmaceutically acceptable salt thereof:

[0007]

[0008] Wherein, Z is -(CH 2 ) i - or substituted -(CH 2 ) i -, i is an integer from 1 to 6, and the substituent in the substituted -(CH 2 ) i - is a hydroxyl group or a methyl group; Q is N or CH; n and m are respectively 0, 1 or 2;

[0009] R 1 is selected from one of hydrogen, halogen, C 1-5 alkoxy, C 1-5 alkyl, substituted C 1-5 alkyl, R 2 is selected from one of hydrogen, C 1-5 alkoxy, C 1-5 alkyl, substituted C 1-5 alkyl, C 3-7 cycloalkyl, substituted C 3-7 cycloalkyl, aryl, substituted aryl, and the substituent is selected from one of alkyl, cyano, hydroxyl, halogen.

[0010] Preferably, R 1 is selected from one of methyl, ethyl, N,N-dimethylamino.

[0011] Preferably, the salt is a pharmaceutically acceptable anion salt, selected from hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, hydrogen phosphate, acetate, lactate, citrate, tartrate, maleate, fumarate, mesylate, gluconate, saccharate, benzoate, esylate, benzenesulfonate, p-toluenesulfonate.

[0012] Preferably, the derivative containing an arylpiperazine structure is:

[0013] 1-(5-(1-Hydroxy-3-(4-phenylpiperazin-1-yl)propyl)indolin-1-yl)ethan-1-one,

[0014] 1-(5-(1-Hydroxy-3-(4-(pyridin-2-yl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one,

[0015] 1-(5-(1-Hydroxy-3-(4-(pyrimidin-2-yl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one,

[0016] 1-(5-(1-Hydroxy-3-(4-(o-tolyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one,

[0017] 1-(5-(1-Hydroxy-3-(4-(m-tolyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one,

[0018] 1-(5-(3-(4-(2,3-Dimethylphenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one,

[0019] 1-(5-(3-(4-(2,3-Dimethylphenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)propan-1-one,

[0020] 5-(3-(4-(2,3-Dimethylphenyl)piperazin-1-yl)-1-hydroxypropyl)-N,N-dimethylindoline-1-carboxamide,

[0021] 1-(5-(1-Hydroxy-3-(4-(4-methoxyphenyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one,

[0022] 1-(5-(1-Hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one,

[0023] 1-(5-(1-Hydroxy-3-(4-(3-methoxyphenyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one,

[0024] 1-(5-(3-(4-(4-Fluorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one,

[0025] 1-(5-(3-(4-(2-Fluorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one,

[0026] 1-(5-(3-(3-Chlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one,

[0027] 1-(5-(3-(4-Chlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one,

[0028] 1-(5-(3-(4-(2,3-Dichlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one,

[0029] 1-(5-(3-(4-(2,3-Dichlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)propan-1-one,

[0030] 5-(3-(4-(2,3-Dichlorophenyl)piperazin-1-yl)-1-hydroxypropyl)-N,N-dimethylindoline-1-carboxamide,

[0031] 1-(5-(3-(4-Cyclohexylpiperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one.

[0032] On the other hand, the present invention also provides a pharmaceutical composition, which comprises a therapeutically effective amount of the derivative containing an arylpiperazine structure or a pharmaceutically acceptable salt thereof as described in any one of claims 1-5, and one or more pharmaceutically acceptable carriers and / or excipients. This pharmaceutical composition is a compound containing a sufficient amount to produce pain and neuralgia analgesic activity.

[0033] The present invention further provides the use of the derivative containing an arylpiperazine structure or a pharmaceutically acceptable salt thereof of the present invention in the preparation of drugs for treating depressive diseases.

[0034] The general synthetic method of the derivatives of the present invention is to first synthesize an acylated indoline or tetrahydro(iso)quinoline, then react it with a straight-chain chloroacyl chloride, and then react it with arylpiperazines (piperidines) with different substituents, and then reduce it with sodium borohydride to obtain the target compound. For example:

[0035]

[0036] The effective dose of the compounds of the present invention can be administered orally together with an inert diluent or a carrier. It can be enclosed in gelatin capsules or compressed into tablets. For oral therapeutic purposes, the compounds of the present invention can be used with excipients and used in the form of tablets, lozenges, capsules, suspensions, syrups, etc. These preparations should contain at least 0.5 wt% of the active compound of the present invention, but can vary according to the specific dosage form, and it is convenient to account for 4% to about 70% of the unit weight. The amount of the active compound in such a composition should reach an appropriate dose. The oral unit dose of the preferred compositions and preparations of the present invention contains 1.0 - 300 mg of the active compound of the present invention.

[0037] The compounds provided by the present invention and their pharmaceutically acceptable salts, solvates and hydrates can be combined with pharmaceutically acceptable carriers or diluents to form pharmaceutical preparations. Suitable pharmaceutically acceptable carriers include inert solid fillers or diluents and sterile aqueous or organic solutions.

[0038] The dosage of the compounds of the present invention depends on the type and severity of the disease or disorder, and also depends on the characteristics of the subject, such as general health, age, gender, weight and drug tolerance. Those skilled in the art can determine the appropriate dose based on these or other factors. The effective doses of commonly used central nervous system drugs are well known to those skilled in the art. The total daily dose is usually between about 0.05 mg and 2000 mg.

[0039] The present invention relates to pharmaceutical compositions, and each unit dose can provide about 0.01 - 1000 mg of the active ingredient. The compositions can be administered by any suitable route, such as orally in the form of capsules, parenterally in the form of injection solutions, topically in the form of ointments or lotions, rectally in the form of suppositories, and transdermally in the form of a patch delivery system.

[0040] The compounds provided by the present invention can be combined with suitable solid or liquid carriers or diluents to form capsules, tablets, pills, powders, syrups, solutions, etc. Tablets, pills, capsules, etc. contain about 0.01 to about 99 weight percentages of the active ingredient and binders such as gelatin, corn starch, gum arabic; excipients such as calcium hydrogen phosphate; disintegrants such as corn starch, potato starch or alginic acid; lubricants such as magnesium stearate; and sweeteners such as sucrose, lactose. When the preparation form is a capsule, in addition to the above types of raw materials, it can also contain a liquid carrier such as an oil.

[0041] For parenteral administration, the compounds provided by the present invention can be combined with sterile water or an organic medium to form injectable solutions or suspensions.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] The derivatives provided by the present invention not only act on 5-HT1A Receptor and 5-HT 2A The receptor has a high affinity for 5-HT, and also has a good affinity for the 5-HT transporter (SERT) and the norepinephrine transporter (NET); when it is applied to the treatment of depression, it has the characteristics of high response rate, short onset time, and small side effects, meeting the requirements of clinical medication. Specific implementation manners

[0044] The present invention will be further described in detail below in conjunction with embodiments.

[0045] Embodiment 1

[0046] Preparation of 1-(5-(1-hydroxy-3-(4-phenylpiperazin-1-yl)propyl)indolin-1-yl)ethan-1-one, and the reaction formula is as follows:

[0047]

[0048] The specific preparation process is as follows:

[0049] (1) Take 5.0 g of indoline, add 50 ml of acetone, and then slowly add 3.3 g of acetyl chloride, stir until reflux, and the reaction is completed after 4 h; cool to room temperature, concentrate the reaction solution, dissolve it with ethyl acetate, and then successively carry out water washing, drying with anhydrous magnesium sulfate, suction filtration, concentration, and pulping to obtain 6.3 g of white solid, and the yield is 93.2%;

[0050] (2) Take 5.0 g of the product obtained in step (1), add 4.9 g of 3-chloropropionyl chloride and 25 mL of 1,2-dichloroethane, cool the temperature to about 0 °C in an ice-water bath, add 11.8 g of anhydrous aluminum trichloride in batches, control the internal temperature at about 0 °C, keep warm for 0.5 h after adding, remove the ice-water bath, and react at room temperature for 2 h; add ice water to quench the system, and successively carry out filtration, extraction with ethyl acetate, water washing, drying with anhydrous magnesium sulfate, suction filtration, concentration, and column chromatography (PE:EA = 6:1) to obtain 6.8 g of solid, and the yield is 87.3%;

[0051] (3) Take 0.5 g of the product obtained in step (2), add 0.35 g of 1-phenylpiperazine, 1 g of anhydrous potassium carbonate, 0.01 g of potassium iodide and 25 ml of DMF, react at 80 °C for 7 h, cool to room temperature, add 100 ml of tap water, add an appropriate amount of dichloromethane, wash with water, separate the water layer, dry the organic layer with anhydrous magnesium sulfate, evaporate the solvent to obtain a light yellow oil, and column chromatography to obtain 0.53 g of white solid;

[0052] (4) Take 0.5 g of the product obtained in step (3), add 50 ml of methanol, slowly add 0.098 g of sodium borohydride under an ice-water bath, slowly warm up to room temperature, then react at room temperature for 1 h, add 100 ml of tap water, add an appropriate amount of dichloromethane, wash with water, separate the aqueous layer, dry the organic layer with anhydrous magnesium sulfate, evaporate the solvent to obtain a light yellow oil, and obtain 0.45 g of a colorless oil by column chromatography.

[0053] 1 H NMR(400MHz,Chloroform-d)δ8.27(d,J=8.4Hz,1H),7.95–7.79(m,2H),7.35–7.20(m,2H),6.96(d,J=8.2Hz,2H),6.88(t,J=7.3Hz,1H),4.96(dd,J=7.7,3.9Hz,1H),4.10(t,J=8.4Hz,2H),3.23(t,J=8.4Hz,2H),3.02(t,J=4.7Hz,6H),2.82(ddd,J=13.1,8.7,4.6Hz,3H),2.68(dt,J=12.9,4.6Hz,2H),2.26(s,3H),1.90(dq,J=9.2,4.2Hz,2H).MS(ESI)m / z 380.2([M+H] + ).

[0054] Example 2

[0055] Preparation of 1-(5-(1-hydroxy-3-(4-(pyridin-2-yl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one

[0056] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(pyridin-2-yl)piperazine", and prepare the target compound by the method of Example 1 for other processes.

[0057] 11H NMR (400 MHz, Chloroform-d) δ 8.28–8.12 (m, 2H), 7.51 (ddd, J = 8.7, 7.2, 2.0 Hz, 1H), 7.28 (d, J = 3.2 Hz, 1H), 7.18 (d, J = 8.5 Hz, 1H), 6.66 (t, J = 7.1 Hz, 2H), 4.94 (dd, J = 7.9, 3.6 Hz, 1H), 4.08 (t, J = 8.4 Hz, 2H), 3.62 (t, J = 5.0 Hz, 5H), 3.22 (t, J = 8.4 Hz, 2H), 2.77 (dt, J = 11.9, 5.0 Hz, 3H), 2.63 (dp, J = 11.1, 4.9 Hz, 3H), 2.24 (s, 3H), 1.94–1.88 (m, 2H). MS (ESI) m / z 381.2 ([M+H] + ).

[0058] Example 3

[0059] Preparation of 1-(5-(1-Hydroxy-3-(4-(pyrimidin-2-yl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one

[0060] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(pyrimidin-2-yl)piperazine", and prepare the target compound by the method of Example 1 for other processes.

[0061] 1H NMR (400 MHz, Chloroform-d) δ 8.27–8.12 (m, 2H), 7.53–7.48 (m, 1H), 7.27 (d, J = 3.2 Hz, 1H), 7.17 (d, J = 8.5 Hz, 1H), 6.56 (t, J = 7.1 Hz, 1H), 4.95 (dd, J = 7.9, 3.6 Hz, 1H), 4.10 (t, J = 8.4 Hz, 2H), 3.63 (t, J = 5.0 Hz, 5H), 3.24 (t, J = 8.4 Hz, 2H), 2.81–2.75 (m, 3H), 2.66–2.60 (m, 3H), 2.24 (s, 3H), 1.92–1.89 (m, 2H). MS (ESI) m / z 382.2 ([M+H]+).

[0062] Example 4

[0063] Preparation of 1-(5-(1-Hydroxy-3-(4-(o-tolyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one

[0064] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(2-methylphenyl)piperazine hydrochloride", and prepare the target compound according to the method of Example 1 for other processes.

[0065] 1HNMR(400MHz,Chloroform-d)δ8.18(d,J=8.3Hz,1H),7.29(d,J=3.2Hz,1H),7.20(t,J=6.8Hz,3H),7.07–6.97(m,2H),4.95(dd,J=7.7,3.9Hz,1H),4.09(t,J=8.4Hz,2H),3.22(t,J=8.4Hz,2H),3.01(t,J=4.7Hz,6H),2.80(ddd,J=13.1,8.7,4.6Hz,3H),2.68(dt,J=12.9,4.6Hz,2H),2.32(s,3H),2.25(s,3H),1.90(dq,J=9.2,4.2Hz,2H).MS(ESI)m / z 394.2([M+H]+).

[0066] Example 5

[0067] Preparation of 1-(5-(1-hydroxy-3-(4-(m-tolyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one

[0068] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(3-methylphenyl)piperazine hydrochloride", and prepare the target compound according to the method of Example 1 for other processes.

[0069] 1 H NMR(400MHz,Chloroform-d)δ8.18(d,J=8.3Hz,1H),7.22–7.15(m,2H),6.81–6.70(m,4H),4.94(dd,J=7.8,3.8Hz,1H),4.08(t,J=8.5Hz,2H),3.30–3.19(m,6H),2.81(td,J=10.3,9.5,4.5Hz,4H),2.66(dt,J=9.2,5.2Hz,3H),2.35(s,3H),2.25(s,3H),1.90(dq,J=9.8,4.3Hz,2H).MS(ESI)m / z 394.2([M+H] + ).

[0070] Example 6

[0071] Preparation of 1-(5-(3-(4-(2,3-dimethylphenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one

[0072] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(2,3-dimethylphenyl)piperazine hydrochloride", and prepare the target compound by the method of Example 1 for other processes.

[0073] 1 H NMR(400MHz,Chloroform-d)δ8.18(d,J=8.3Hz,1H),7.29(s,1H),7.19(d,J=8.5Hz,1H),7.11(t,J=7.7Hz,1H),6.94(d,J=7.7Hz,2H),4.95(dd,J=7.6,3.9Hz,1H),4.09(t,J=8.4Hz,2H),3.22(t,J=8.4Hz,2H),2.98(t,J=4.7Hz,4H),2.80(ddd,J=13.1,8.6,4.5Hz,2H),2.68(dt,J=12.8,4.5Hz,2H),2.29(s,3H),2.24(d,J=2.0Hz,6H),1.89(p,J=4.5Hz,2H),1.63(s,3H).MS(ESI)m / z 408.3([M+H] + ).

[0074] Example 7

[0075] Preparation of 1-(5-(3-(4-(2,3-dimethylphenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)propan-1-one

[0076] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(2,3-dimethylphenyl)piperazine hydrochloride", and replace "acetyl chloride" in step (1) of Example 1 with "propionyl chloride", and prepare the target compound by the method of Example 1 for other processes.

[0077] 11H NMR (400 MHz, Chloroform-d) δ 8.18 (d, J = 8.3 Hz, 1H), 7.25 (s, 1H), 7.16 (d, J = 8.3 Hz, 1H), 7.07 (t, J = 7.7 Hz, 1H), 6.90 (d, J = 7.7 Hz, 2H), 4.91 (dd, J = 7.8, 3.7 Hz, 1H), 4.03 (t, J = 8.5 Hz, 2H), 3.18 (t, J = 8.4 Hz, 2H), 2.94 (t, J = 4.6 Hz, 7H), 2.82–2.72 (m, 2H), 2.66 (dd, J = 11.0, 6.3 Hz, 2H), 2.43 (q, J = 7.3 Hz, 2H), 2.26 (s, 3H), 2.20 (s, 3H), 1.93–1.81 (m, 2H), 1.22 (q, J = 7.3, 5.9 Hz, 3H). MS (ESI) m / z 422.3 ([M+H] + ).

[0078] Example 8

[0079] Preparation of 5-(3-(4-(2,3-dimethylphenyl)piperazin-1-yl)-1-hydroxypropyl)-N,N-dimethylindoline-1-carboxamide

[0080] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(2,3-dimethylphenyl)piperazine hydrochloride", and replace "acetyl chloride" in step (1) of Example 1 with "N,N-dimethylformyl chloride", and prepare the target compound by the method of Example 1 for other processes.

[0081] 1 1H NMR (400 MHz, Chloroform-d) δ 7.22 (s, 1H), 7.15–7.04 (m, 2H), 6.90 (dd, J = 8.0, 2.9 Hz, 3H), 4.88 (d, J = 8.1 Hz, 1H), 3.90 (t, J = 8.2 Hz, 2H), 3.01 (t, J = 8.2 Hz, 2H), 2.93 (d, J = 9.6 Hz, 11H), 2.83–2.71 (m, 2H), 2.66 (d, J = 13.0 Hz, 2H), 2.26 (s, 3H), 2.20 (s, 3H), 1.95–1.77 (m, 2H), 1.25 (s, 2H). MS (ESI) m / z 437.3 ([M+H] + ).

[0082] Example 9

[0083] Preparation of 1-(5-(1-Hydroxy-3-(4-(4-methoxyphenyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one

[0084] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(4-methoxyphenyl)piperazine hydrochloride", and prepare the target compound by the method of Example 1 for other processes.

[0085] 1 H NMR(400MHz,Chloroform-d)δ8.18(d,J=8.3Hz,1H),7.28(d,J=5.0Hz,1H),7.18(d,J=8.5Hz,1H),6.93(d,J=9.1Hz,2H),6.86(d,J=9.1Hz,2H),4.93(dd,J=7.8,3.8Hz,1H),4.08(t,J=8.4Hz,2H),3.79(s,3H),3.27–3.11(m,6H),2.80(ddt,J=21.5,8.6,4.7Hz,4H),2.66(dq,J=12.5,4.8Hz,3H),2.24(s,3H),1.89(dq,J=9.6,4.7,4.2Hz,2H).MS(ESI)m / z 410.2([M+H] + ).

[0086] Example 10

[0087] Preparation of 1-(5-(1-Hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one

[0088] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(2-methoxyphenyl)piperazine hydrochloride", and prepare the target compound by the method of Example 1 for other processes.

[0089] 11H NMR (400 MHz, Chloroform-d) δ 8.18 (d, J = 8.2 Hz, 1H), 7.28 (s, 1H), 7.19 (d, J = 8.5 Hz, 1H), 7.04 (ddd, J = 8.3, 5.7, 3.2 Hz, 1H), 6.96 (d, J = 3.2 Hz, 2H), 6.89 (d, J = 7.9 Hz, 1H), 4.95 (dd, J = 7.9, 3.6 Hz, 1H), 4.08 (t, J = 8.4 Hz, 2H), 3.89 (s, 3H), 3.28–3.07 (m, 6H), 2.96–2.76 (m, 4H), 2.75–2.63 (m, 3H), 2.25 (s, 3H), 1.97–1.82 (m, 2H). MS (ESI) m / z 410.2 ([M+H] + ).

[0090] Example 11

[0091] Preparation of 1-(5-(1-Hydroxy-3-(4-(3-methoxyphenyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one

[0092] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(3-methoxyphenyl)piperazine hydrochloride", and prepare the target compound by the method of Example 1 for other processes.

[0093] 1 1H NMR (400 MHz, Chloroform-d) δ 8.17 (d, J = 8.3 Hz, 1H), 7.28 (d, J = 5.1 Hz, 1H), 7.24–7.15 (m, 2H), 6.57 (dd, J = 8.2, 2.2 Hz, 1H), 6.51–6.44 (m, 2H), 4.93 (dd, J = 7.8, 3.7 Hz, 1H), 4.08 (t, J = 8.4 Hz, 2H), 3.81 (s, 3H), 3.24 (dt, J = 16.7, 6.7 Hz, 6H), 2.80 (td, J = 9.7, 8.5, 4.3 Hz, 4H), 2.65 (dt, J = 9.7, 4.9 Hz, 3H), 2.24 (s, 3H), 1.90 (dq, J = 9.8, 4.8, 4.2 Hz, 2H). MS (ESI) m / z 410.2 ([M+H] + ).

[0094] Example 12

[0095] Preparation of 1-(5-(3-(4-(4-Fluorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one

[0096] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(4-fluorophenyl)piperazine", and prepare the target compound according to the method of Example 1 for other processes.

[0097] 1 H NMR(400MHz,Chloroform-d)δ8.18(d,J=8.3Hz,1H),7.28(d,J=6.3Hz,1H),7.18(d,J=8.5Hz,1H),6.99(t,J=8.6Hz,2H),6.90(dd,J=9.1,4.5Hz,2H),4.93(dd,J=7.6,4.0Hz,1H),4.08(t,J=8.4Hz,2H),3.28–3.13(m,6H),2.82(td,J=11.6,11.2,5.6Hz,4H),2.69–2.64(m,3H),2.24(s,3H),1.89(q,J=4.3Hz,2H).MS(ESI)m / z 398.2([M+H] + ).

[0098] Example 13

[0099] Preparation of 1-(5-(3-(4-(2-fluorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one

[0100] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(2-fluorophenyl)piperazine", and prepare the target compound according to the method of Example 1 for other processes.

[0101] 1 H NMR(400MHz,Chloroform-d)δ8.18(d,J=8.3Hz,1H),7.28(s,1H),7.19(d,J=8.4Hz,1H),7.07(ddd,J=12.4,7.0,4.3Hz,2H),7.01–6.92(m,2H),4.94(dd,J=7.8,3.8Hz,1H),4.08(t,J=8.4Hz,2H),3.28–3.14(m,6H),2.81(ddd,J=26.2,10.5,5.8Hz,4H),2.69(dq,J=8.6,5.2,4.7Hz,3H),2.24(s,3H),1.90(dq,J=9.7,4.7,4.3Hz,2H).MS(ESI)m / z 398.2([M+H] + ).

[0102] Example 14

[0103] Preparation of 1-(5-(3-(3-chlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one

[0104] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(3-chlorophenyl)piperazine", and prepare the target compound according to the method of Example 1 for other processes.

[0105] 1 H NMR(400MHz,Chloroform-d)δ8.18(d,J=8.3Hz,1H),7.28(d,J=5.3Hz,1H),7.19(t,J=8.1Hz,2H),6.90(d,J=2.3Hz,1H),6.87–6.79(m,2H),4.94(dd,J=7.6,4.0Hz,1H),4.08(t,J=8.4Hz,2H),3.24(dt,J=16.8,6.7Hz,6H),2.80(dq,J=13.3,8.4,6.7Hz,4H),2.65(dt,J=11.5,5.0Hz,3H),2.25(s,3H),1.90(p,J=4.5Hz,2H).MS(ESI)m / z 414.2([M+H] + ).

[0106] Example 15

[0107] Preparation of 1-(5-(3-(4-chlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one

[0108] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(4-chlorophenyl)piperazine", and prepare the target compound according to the method of Example 1 for other processes.

[0109] 1 H NMR(400MHz,Chloroform-d)δ8.18(d,J=8.3Hz,1H),7.28–7.15(m,4H),6.86(d,J=8.6Hz,2H),4.93(dd,J=7.5,4.1Hz,1H),4.08(t,J=8.4Hz,2H),3.22(q,J=8.0,6.4Hz,6H),2.79(ddt,J=16.2,8.2,5.0Hz,4H),2.65(dt,J=9.6,4.9Hz,3H),2.25(s,3H),1.90(dq,J=9.1,4.2Hz,2H).MS(ESI)m / z 414.2([M+H] + ).

[0110] Example 16

[0111] Preparation of 1-(5-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one

[0112] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(2,3-dichlorophenyl)piperazine hydrochloride", and prepare the target compound by the method of Example 1 for other processes.

[0113] 1 H NMR(400MHz,Chloroform-d)δ8.12(d,J=8.3Hz,1H),7.21(s,1H),7.14(ddt,J=6.9,5.4,1.9Hz,3H),6.92(ddd,J=6.6,2.8,1.0Hz,1H),4.89(dd,J=7.8,3.9Hz,1H),4.01(td,J=8.6,2.0Hz,2H),3.15(t,J=8.4Hz,2H),3.08(s,4H),2.88–2.53(m,6H),2.18(s,3H),1.88–1.79(m,2H).MS(ESI)m / z 448.2([M+H] + ).

[0114] Example 17

[0115] Preparation of 1-(5-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)propan-1-one

[0116] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(2,3-dichlorophenyl)piperazine hydrochloride", and replace "acetyl chloride" in step (1) of Example 1 with "propionyl chloride", and prepare the target compound by the method of Example 1 for other processes.

[0117] 11H NMR (400 MHz, Chloroform-d) δ 8.17 (d, J = 8.3 Hz, 1H), 7.18–7.08 (m, 4H), 6.93 (dd, J = 6.9, 2.7 Hz, 1H), 4.89 (dd, J = 7.9, 3.7 Hz, 1H), 4.01 (t, J = 8.4 Hz, 2H), 3.16 (t, J = 8.4 Hz, 2H), 3.09 (s, 5H), 2.82–2.63 (m, 6H), 2.41 (q, J = 7.3 Hz, 2H), 1.94–1.78 (m, 2H), 1.20 (t, J = 7.3 Hz, 3H). MS (ESI) m / z 462.2 ([M+H] + ).

[0118] Example 18

[0119] Preparation of 5-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)-1-hydroxypropyl)-N,N-dimethylindoline-1-carboxamide

[0120] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-(2,3-dichlorophenyl)piperazine hydrochloride", and replace "acetyl chloride" in step (1) of Example 1 with "N,N-dimethylcarbonyl chloride", and prepare the target compound by the method of Example 1 for other processes.

[0121] 1 1H NMR (400 MHz, Chloroform-d) δ 7.20 (s, 1H), 7.19–7.13 (m, 2H), 7.16–7.08 (m, 2H), 6.98–6.87 (m, 1H), 4.88 (d, J = 7.5 Hz, 1H), 3.89 (t, J = 8.2 Hz, 2H), 3.10 (s, 3H), 3.05–2.93 (m, 4H), 2.91 (s, 8H), 2.78 (m, 2H), 2.69 (s, 2H), 1.94–1.80 (m, 2H). MS (ESI) m / z 477.2 ([M+H] + ).

[0122] Example 19

[0123] Preparation of 1-(5-(3-(4-cyclohexylpiperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one

[0124] Replace "1-phenylpiperazine" in step (3) of Example 1 with "1-cyclohexylpiperazine", and prepare the target compound by the method of Example 1 for other processes.

[0125] 11H NMR (400 MHz, Chloroform-d) δ 8.17 (d, J = 8.3 Hz, 1H), 7.26 (s, 1H), 7.17 (d, J = 8.4 Hz, 1H), 4.91 (dd, J = 7.5, 4.0 Hz, 1H), 4.08 (t, J = 8.4 Hz, 2H), 3.21 (t, J = 8.4 Hz, 2H), 2.83–2.50 (m, 7H), 2.24 (s, 3H), 1.94–1.78 (m, 6H), 1.65 (d, J = 13.0 Hz, 5H), 1.19 (dq, J = 35.5, 12.4 Hz, 6H). MS (ESI) m / z 386.3 ([M+H] + ).

[0126] The structural formulas of the compounds prepared in the above examples are shown in Table 1 below:

[0127] Table 1 Structural formulas of the compounds prepared in Examples 1-19

[0128]

[0129]

[0130] Example 20 Preparation of receptor membrane and determination of ligand affinity (inhibition rate)

[0131] Receptor binding experimental materials:

[0132] Isotope ligand 3 3H]-Ketanserin, 3 3H-8-OH-DPAT, 3 3H]-paroxetine, 3 3H]-Nisoxetine was purchased from PerkinElmer; Methysergide was purchased from RBI; GF / C glass fiber filter paper was purchased from Whatman; Tris was imported and repackaged; PPO and POPOP were purchased from Shanghai Reagent Factory; Lipid-soluble scintillation fluid. Wallace 1450 MicroBeta TriLux scintillation counter, product of Perkin Elmer. CHO-5-HT 1A cells, ThermoFisher.

[0133] (1) 5HT 1A Preparation of receptor membrane and determination of ligand affinity (inhibition rate)

[0134] CHO-5-HT 1AThe cells were taken out of the -80°C refrigerator and thawed naturally. Then, 1000 g of the cells were centrifuged at 4°C for 10 min. The supernatant was discarded, and the precipitate was taken. Homogenate (50 mM Tris-HCl buffer containing 1 mM EDTA, 0.1% ascorbic acid, 20 μM pargyline, and 10 mM MgSO 4 , pH = 7.4) was added to the precipitate and mixed for 20 - 30 s. Then, it was centrifuged at 50000 g at 4°C for 15 min. The upper layer was carefully discarded, and homogenate (50 mM Tris-HCl buffer containing 1 mM EDTA, 0.1% ascorbic acid, 20 μM pargyline, and 10 mM MgSO 4 , pH = 7.4) was added again and mixed. It was centrifuged at 50000 g at 4°C for 15 min, and the centrifugation was repeated three times. After centrifugation, the supernatant was discarded, and the precipitate was stored at -80°C for later use.

[0135] Experimental method:

[0136] (1 - 1) Appropriate amount of homogenate (0.05 M Tris-HCl buffer containing 0.1% ascorbic acid, 10 μM pargyline, and 4 mM CaCl 1A ) was added to the prepared 5HT 2 receptor membrane, and it was dispersed evenly with a homogenizer to prepare a suspension of 8 mg / mL membrane for later use.

[0137] (1 - 2) 100 μL of the membrane suspension was added to each reaction tube, and 100 μL of homogenate (0.05 M Tris-HCl buffer containing 0.1% ascorbic acid, 10 μM pargyline, and 4 mM CaCl 2 ) was added.

[0138] (1 - 3) 100 μL of homogenate (0.05 M Tris-HCl buffer containing 0.1% ascorbic acid, 10 μM pargyline, and 4 mM CaCl 2 ) was added to the total binding tube (TB), 100 μL of 5-HT (final concentration 10 -5 M) was added to the non-specific binding tube (NB), and 100 μL of the test compound (final concentration 10 -5 M) was added to each specific binding tube (SB) of the test compound.

[0139] (1 - 4) 10 μL of radioactive ligand 3 ³H-8-OH-DPAT was added to each reaction tube (two parallel tubes were set for each reaction tube, and each tube was placed on ice during sample addition).

[0140] (1-5) Incubate each reaction tube at 37 °C for 10 min. After the reaction is completed, the bound ligand is rapidly filtered under reduced pressure and washed thoroughly with ice-cold assay buffer (0.05 M Tris-HCl). Remove the filter disc and place it in a 3 ml scintillation vial. Add 2 ml of toluene scintillation fluid and mix well;

[0141] (1-6) Place the scintillation vial in a liquid scintillation counter for counting.

[0142] For each compound, two replicate tubes are used for each experiment, and two separate experiments are conducted.

[0143] (2) 5HT 2A Preparation of 5HT receptor membrane and determination of ligand affinity (inhibition rate)

[0144] 5HT 2A Preparation of receptor membrane: Decapitate the rats and operate on ice. Quickly remove the striatum. Combine 2 striata in a centrifuge tube. Add 3 ml of buffer (0.05 M Tris-HCl buffer) and homogenize at speed 4 for 3 - 4 s, homogenize 4 times. Then add 5 ml of buffer (0.05 M Tris-HCl buffer) and incubate at 37 °C for 10 min. After incubation, adjust the weight of the tube with a balance. Centrifuge at 12000 r, 4 °C for 20 min. Discard the supernatant. Add 3 ml of homogenate (0.05 M Tris-HCl buffer), mix well with a vortex mixer. Then add 5 ml of buffer (0.05 M Tris-HCl buffer), centrifuge, and discard the supernatant. Store the precipitate at -80 °C for later use.

[0145] Experimental method:

[0146] (2-1) Add an appropriate amount of homogenate (0.05 M Tris-HCl buffer) to the prepared 5HT 2A membrane and disperse it evenly with a homogenizer to prepare a suspension of 210 mg / mL membrane for later use;

[0147] (2-2) Add 100 μL of the membrane suspension and 100 μL of homogenate (0.05 M Tris-HCl buffer) to each reaction tube respectively;

[0148] (2-3) Add 100 μL of homogenate (0.05 M Tris-HCl buffer) to the total binding tube (TB), add 100 μL of Methysergide (final concentration 10 -5 M) to the non-specific binding tube (NB), and add 100 μL of the test compound (final concentration 10 -5 M) to each specific binding tube (SB) of the test compounds;

[0149] (2-4) Add radioactive ligand to each reaction tube respectively 3H-Ketanserin 10 μL (two parallel tubes were set in each reaction tube, and each tube was placed on ice during sample addition);

[0150] (2 - 5) Incubate each reaction tube at 37 °C for 15 min. After the reaction is completed, the bound ligand is rapidly filtered under reduced pressure, washed thoroughly with ice-cold 0.05 M Tris-HCl buffer, take out the filter and place it in a 3 ml scintillation vial, add 2 ml of toluene scintillation fluid and mix well;

[0151] (2 - 6) Place the scintillation vial into a liquid scintillation counter for counting.

[0152] For each experiment of the compound, two duplicate tubes were made and two separate experiments were carried out.

[0153] (3) Preparation of SERT and NET (tissue) receptor membranes

[0154] Take the cerebral cortex of rats, add homogenate (50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, pH = 7.4) for homogenization, centrifuge at 50000 g and 4 °C for 10 min, discard the supernatant, add homogenate (50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, pH = 7.4) for homogenization and incubate at 37 °C for 10 min, take the precipitate after centrifugation, then add 50 mM Tris-HCl buffer (pH = 7.4) for washing, repeat centrifugation three times, after centrifugation, discard the supernatant, and store the precipitate at -80 °C for standby.

[0155] SERT receptor competitive binding assay

[0156] First, disperse the prepared membrane evenly with an appropriate amount of homogenate (50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, pH = 7.4) using a homogenizer to prepare a membrane suspension of 210 mg / mL for standby; add 100 μl of the membrane suspension to each reaction tube; add 100 μl of homogenate (50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, pH = 7.4) to the total binding tube (TB), add 100 μl of paroxetine (final concentration 1.0*10 -5 M) to the non-specific binding tube (NSB), and add 100 μl of the test compound (final concentration 1.0*10 -5 M) to each test compound binding tube (CB); add radioactive ligand to each reaction tube 3The final concentration of [H]-paroxetine was 0.5 nM; each reaction tube was incubated at 23 °C for 60 min. After the reaction was completed, the bound ligand was rapidly filtered under reduced pressure. Whatman paper GF / C was saturated with 0.5% PEI solution 1 h in advance and washed thoroughly with ice-cold assay buffer (50 mM Tris-HCl buffer, pH = 7.4).

[0157] The filter was taken out and placed in a 2 ml scintillation vial, 1 ml of toluene scintillation fluid was added and mixed well; the scintillation vial was placed in a liquid scintillation counter for counting.

[0158] NET receptor competitive binding assay

[0159] First, the prepared membrane was dispersed evenly with an appropriate amount of homogenate (50 mM Tris-HCl, pH = 7.4) using a homogenizer to prepare a suspension of 210 mg / mL membrane for standby; 100 μl of the membrane suspension was added to each reaction tube; 100 μl of homogenate (50 mM Tris-HCl, pH = 7.4) was added to the total binding tube (TB), 100 μl of desipramine (final concentration 1.0×10 -5 M) was added to the non-specific binding tube (NSB), and 100 μl of the test compound (final concentration 1.0×10 -5 M) was added to each test compound binding tube (CB); 0.5 nM of the radioactive ligand [3H]-Nisoxetine was added to each reaction tube; each reaction tube was incubated at 25 °C for 30 min. After the reaction was completed, the bound ligand was rapidly filtered under reduced pressure. Whatman paper GF / C was saturated with 0.5% PEI solution 1 h in advance and washed thoroughly with ice-cold assay buffer (50 mM Tris-HCl, pH = 7.4). The filter was taken out and placed in a 2 ml scintillation vial, 1 ml of toluene scintillation fluid was added and mixed well; the scintillation vial was placed in a liquid scintillation counter for counting.

[0160] Calculate the inhibition rate percentage of each compound's binding to the isotope ligand according to the following formula:

[0161] Inhibition rate (I%) = (TB - SB) / (TB - NB) × 100%

[0162] TB: Total binding and constant; NB: Non-specific binding constant; SB: Binding constant of the compound.

[0163] The experimental results are shown in Table 2. The in vitro experimental results show that: compared with duloxetine, the compounds prepared in Examples 3-6, Examples 10-11, and Examples 13-14 have 5HT 1AThe receptor affinity is comparable; the compounds prepared in Example 5 and Example 6 respectively have comparable affinity for SERT; the compound prepared in Example 14 has comparable affinity for NET; the compounds prepared in Example 1, Example 3 - 6, Example 10, Example 12, and Example 14 respectively have comparable affinity for 5HT 2A receptor; among them, the compounds prepared in Example 5 and Example 6 respectively have relatively high affinity for 5HT 1A , 5HT 2A and SERT, and the compound prepared in Example 14 has relatively high affinity for 5HT 1A , 5HT 2A and NET, and also has good affinity for SERT, showing potential therapeutic effects on depression.

[0164] Table 2 Affinity results of compounds for various receptors (inhibition rate (%))

[0165]

[0166]

[0167] Study on the antidepressant activity of the preferred compound of Example 21 in animals

[0168] The forced swimming "immobility" test in mice was used, with duloxetine as the positive control drug, to conduct a preliminary study on the antidepressant effect of the preferred compound in vivo.

[0169] One day before the experiment, mice with qualified body weights were screened and randomly divided into groups of 8 each, with a vehicle control group and a positive control group established. Each group was administered by gavage (ig), and the drug was administered 1 h before each experiment. The mice were placed in a transparent glass cylinder (water depth 15 cm, water temperature 23 - 25 °C) for 6 min, and video recorded for 6 min. Then, the immobility time of the mice in the last 4 min during the 6 - min swimming period was analyzed by software or manually.

[0170] Table 3 Effects of the compounds prepared in Example 5, Example 6, and Example 14 respectively on the swimming immobility time of mice after gavage administration

[0171]

[0172] *P < 0.05, **P < 0.01 compared with the blank control group.

[0173] As can be seen from the table, in the forced swimming test of mice, the compounds prepared in Preferred Example 5, Example 6, and Example 14 can significantly shorten the time of immobility due to despair. The shorter the immobility time, the stronger the antidepressant effect. At the same dose, the antidepressant effect of the compounds prepared in the present invention is significantly stronger than that of duloxetine.

Claims

1. A derivative containing an arylpiperazine structure, characterized in that, the derivative is: 1-(5-(1-Hydroxy-3-(4-phenylpiperazin-1-yl)propyl)indolin-1-yl)ethan-1-one, 1-(5-(1-Hydroxy-3-(4-(pyridin-2-yl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one, 1-(5-(1-Hydroxy-3-(4-(pyrimidin-2-yl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one, 1-(5-(1-Hydroxy-3-(4-(o-tolyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one, 1-(5-(1-Hydroxy-3-(4-(m-tolyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one, 1-(5-(3-(4-(2,3-Dimethylphenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one, 1-(5-(3-(4-(2,3-Dimethylphenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)propan-1-one, 5-(3-(4-(2,3-Dimethylphenyl)piperazin-1-yl)-1-hydroxypropyl)-N,N-dimethylindoline-1-carboxamide, 1-(5-(1-Hydroxy-3-(4-(4-methoxyphenyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one, 1-(5-(1-Hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one, 1-(5-(1-Hydroxy-3-(4-(3-methoxyphenyl)piperazin-1-yl)propyl)indolin-1-yl)ethan-1-one, 1-(5-(3-(4-(4-Fluorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one, 1-(5-(3-(4-(2-Fluorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one, 1-(5-(3-(3-Chlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one, 1-(5-(3-(4-Chlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one, 1-(5-(3-(4-(2,3-Dichlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one, 1-(5-(3-(4-(2,3-Dichlorophenyl)piperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)propan-1-one, 5-(3-(4-(2,3-Dichlorophenyl)piperazin-1-yl)-1-hydroxypropyl)-N,N-dimethylindoline-1-carboxamide, 1-(5-(3-(4-Cyclohexylpiperazin-1-yl)-1-hydroxypropyl)indolin-1-yl)ethan-1-one.

2. A pharmaceutical composition, characterized in that, The pharmaceutical composition comprises a therapeutically effective amount of the derivative containing an arylpiperazine structure as claimed in claim 1, and one or more pharmaceutically acceptable carriers.

3. Use of the derivative containing an arylpiperazine structure as claimed in claim 1 in the preparation of a medicament for treating depressive disorders.

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