N-substituted quinolinone compounds, their preparation and use

Abstract

The present invention belongs to the field of medicinal chemistry, specifically relates to N-substituted quinolinone compounds, their preparation methods and their medical uses. The structure of the compound of the present invention is shown in formula (I), which has excellent oil solubility and is capable of 5-HT 2A Receptor, dopamine D 2 / 3 Receptor, 5-HT 1A It has a multi-targeting effect on the receptor and 5-HT transporter, which is useful for regulating the balance of neurotransmitters in the brain. It has relatively good therapeutic effects on various central nervous system diseases, and has low toxicity and side effects, high safety and tolerance, good comprehensive drug discovery potential, and good prospects for clinical application. JPEG2025511343000219.jpg42110

Description

[Technical field]

[0001] This application claims priority to a Chinese patent application filed on March 30, 2022, with application number 202210333341.5 and title "N-substituted quinolinone compounds, their preparation and use," the entire contents of which are incorporated herein by reference.

[0002] The present invention belongs to the field of medicinal chemistry, specifically to N-substituted quinolinone compounds, their preparation methods and their medicinal uses. [Background technology]

[0003] With the rapid development of society, people's life rhythm and stress are increasing day by day, and psychiatric disorders have become diseases that seriously affect people's health, bringing serious consequences to patients and their families. Due to factors such as susceptibility to suicide, lack of medical care, and relatively high risk of complications, the average life expectancy of patients with psychiatric disorders is significantly shortened. Many studies have shown that psychiatric disorders are related to the abnormal functioning of various neurotransmitters and receptors in the central nervous system, for example, the brain monoamine transmitters, especially the dopamine (DA) system and the 5-hydroxytryptamine (5-HT) system, are closely related to the normal mental activity of the human body. When the DA and 5-HT systems are dysfunctional, various neuropsychiatric disorders such as schizophrenia, depression, neuropathic pain, mania, anxiety disorder, and Parkinson's disease are more likely to occur.

[0004] Neuropsychiatric disorders often cause comorbidity with each other, for example, schizophrenia patients often have depression and anxiety comorbidity, and schizophrenia patients with depression or anxiety symptoms have a worse outcome. 5-HT transporter is an important target of antidepressants and anxiolytics, and conventional SSRIs (selective 5-HT reuptake inhibitors) drugs can selectively inhibit 5-HT transporter and increase the concentration of 5-HT in the synaptic cleft, thereby exerting their medicinal effects. Clinically, antipsychotics are often used in combination with SSRIs to treat depression and anxiety symptoms of schizophrenia. Therefore, antipsychotics with 5-HT transporter inhibitory effect can theoretically improve depression and anxiety comorbidity of schizophrenia better.

[0005] Therefore, drugs with multi-target effects, including those on the 5-HT transporter, can better regulate the balance of various receptors in the brain and regulate the DA / 5-HT system, which is advantageous for better treating diseases in the field of the central nervous system.

[0006] Patent WO2015131856 reports heterocyclic compounds with broad therapeutic activity against central nervous system disorders (e.g., schizophrenia, etc.), the general formula of which is as follows: [ka]

[0007] The above compounds, particularly the compound of Example 85 (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-3,4-dihydroquinolin-2(1H)-one, named "Compound 1-a" in the present invention), are antipsychotic drugs that have a broader therapeutic range, fewer side effects, and excellent safety and tolerability compared to conventional typical and atypical antipsychotic drugs.

[0008] However, these compounds are poorly soluble in oily media (eg, sesame oil and benzyl benzoate), limiting their application in oily injections.

[0009] The present invention has been made in view of these issues. Summary of the Invention [Problem to be solved by the invention]

[0010] The present invention aims to provide a novel N-substituted quinolinone compound having improved and more excellent solubility in oily media (e.g., sesame oil and benzyl benzoate), and its preparation method and medical use, and at the same time, the prototype or in vivo metabolite of the compound is 5-HT 2A It has antagonistic effects on the dopamine D3 receptor and 5-HT transporter. 1A It has an agonistic effect on the receptor and is relatively safe and well tolerated. [Means for solving the problem]

[0011] In a first aspect, the present invention provides N-substituted quinolinone compounds having the general formula (I) or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled or prodrug thereof: [ka] Among them, R6, R7, R8 and R9 are each independently selected from hydrogen, deuterium, a halogen, a methyl group, an ethyl group, a hydroxyl group, an amino group or an acetamide group; [ka] represents a single bond or a double bond, and when it is a double bond, one of R6 and R7 is absent, and one of R8 and R9 is absent, preferably [ka] represents a single bond, R1 is -Y1-OC(=O)-R2, -Y1-OC(=O)-O-R3, -Y1-O-R4 or -C(=O)-R5; Y1 is each independently a C1 to C6 alkylene group, preferably a C1 to C4 alkylene group, more preferably a methylene group, an ethylene group, or a propylene group; R2 is a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a C2-C30 alkenyl group, an amino C1-C30 alkyl group, an amino group substituted with a C1-C30 alkyl group, an amino group substituted with a C2-C30 alkenyl group, an amino group substituted with a halogenated C1-C30 alkyl group, an amino group substituted with a phenyl C1-C30 alkyl group, an amino group substituted with a hydroxy C1-C30 alkyl group, an amino group substituted with a C3-C10 cycloalkyl group, an amino group substituted with a C3-C10 cycloalkyl C1-C6 alkyl group, R2 is a C3-C10 cycloalkyl group, a 5-10 membered heterocyclyl group, a C6-C12 aryl group, a C6-C12 aryl C1-C30 alkyl group, a C1-C30 alkoxycarbonyl C1-C30 alkyl group, a C1-C30 alkoxy C1-C30 alkyl group, a C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkyl group or a C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkyl group, and preferably R2 is a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a C2-C30 alkoxy ... nyl group, amino C1-C16 alkyl group, amino group substituted with C1-C16 alkyl group, amino group substituted with C2-C16 alkenyl group, amino group substituted with halogenated C1-C16 alkyl group, amino group substituted with phenyl C1-C16 alkyl group, amino group substituted with hydroxy C1-C16 alkyl group, amino group substituted with C3-C10 cycloalkyl group, amino group substituted with C3-C10 cycloalkyl C1-C6 alkyl group, C3-C10 cycloalkyl group, 5-10 membered heterocyclyl group, C6-C12 aryl group, C R2 is preferably a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a C2-C30 alkenyl group, an amino C1-C12 alkyl group, an amino group substituted with a C1-C12 alkyl group,an amino group substituted with a C2-C12 alkenyl group, an amino group substituted with a halogenated C2-C12 alkyl group, an amino group substituted with a phenyl C1-C12 alkyl group, an amino group substituted with a hydroxy C1-C12 alkyl group, an amino group substituted with a C3-C7 cycloalkyl group, an amino group substituted with a C3-C7 cycloalkyl C1-C4 alkyl group, a C3-C7 cycloalkyl group, a 5-10 membered heterocyclyl group, a C6-C12 aryl group, a C6-C12 aryl C1-C12 alkyl group, a C1-C12 alkoxycarbonyl C1-C12 alkyl group, R2 is preferably a C1-C12 alkoxy C1-C12 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, and more preferably a C1-C30 alkyl group (e.g., a C1-C30 linear alkyl group, an isopropyl group, a tert-butyl group, a 1-methylpropyl group, a 3-methylbutyl group, a 1-methylbutyl group, a 1,1-dimethylpentyl group, a 1-methylpentyl group, a 1-methylhexyl group, a 1-pentylhexyl group, etc.), a halo halogenated C1-C30 alkyl groups (for example, halogenated C1-C16 alkyl groups, for example, halogenated C1-C12 alkyl groups or halogenated C1-C6 alkyl groups, further for example, 3,3,3-trifluoropropyl group), C2-C30 alkenyl groups (for example, C2-C20 alkenyl groups), amino C1-C6 alkyl groups (for example, NH2-methyl group), amino groups substituted with C1-C12 alkyl groups (for example, decyl-NH-, heptyl-NH-), amino groups substituted with C2-C6 alkenyl groups (for example, allyl-NH-), halogenated C1-C6 alkyl groups. (e.g., 3,3,3-trifluoropropyl-NH-), an amino group substituted with a phenyl C1-C6 alkyl group (e.g., benzyl-NH-), an amino group substituted with a hydroxy C1-C6 alkyl group (e.g., hydroxyethyl-NH-), an amino group substituted with a C3-C7 cycloalkyl group (e.g., cycloalkyl-NH-), an amino group substituted with a C3-C7 cycloalkyl C1-C6 alkyl group (e.g., C3-C7 cycloalkylmethyl-NH-), a C3-C7 cycloalkyl group, a 5-10 membered heterocyclyl group (e.g.,pyridyl group, piperidinyl group, 4-tetrahydropyranyl group, morpholinyl group, furyl group, thienyl group, pyrimidine group, quinolyl group, etc.), phenyl group, naphthyl group, phenyl C1-C6 alkyl group (for example, benzyl group), C1-C6 alkoxycarbonyl C1-C6 alkyl group (for example, tert-butoxycarbonylmethyl group), C1-C6 alkoxy C1-C6 alkyl group (for example, methoxymethyl group), C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (for example, methoxyethoxymethyl group, butoxyethoxymethyl group) or C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (for example, methoxyethoxyethoxymethyl group), For example, R2 is a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a C2-C16 alkenyl group, an amino C1-C16 alkyl group, an amino group substituted with a C1-C16 alkyl group, an amino group substituted with a C2-C16 alkenyl group, an amino group substituted with a halogenated C1-C16 alkyl group, an amino group substituted with a phenyl C1-C16 alkyl group, an amino group substituted with a hydroxy C1-C16 alkyl group, an amino group substituted with a C3-C10 cycloalkyl group, an amino group substituted with a C3-C10 cycloalkyl C1-C6 alkyl group, a C3-C10 cycloalkyl group, a 5-10 membered heterocyclyl group, a C6-C12 aryl group, a C6-C12 aryl C1-C16 alkyl group, a C1-C16 alkoxycarbonyl C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkyl group, a C1-C16 aryl ... R2 is, for example, a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a 5-10 membered heterocyclyl group, a C6-C12 aryl group, a C6-C12 aryl C1-C16 alkyl group, or a C1-C16 alkoxy C1-C16 alkyl group; R2 is, for example, a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl group, a naphthyl group, a phenyl C1-C16 alkyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a furyl group, a thienyl group, a pyrimidine group, or a quinolyl group; and most particularly, R2 is a C1-C16 alkyl group or a phenyl group; R3 is a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a phenyl group, a phenyl C1-C30 alkyl group or a C3-C10 cycloalkyl group, preferably R3 is a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl group, a phenyl C1-C16 alkyl group or a C3-C10 cycloalkyl group, preferably R3 is a C1-C16 alkyl group, a halogenated C1-C12 alkyl group, a phenyl group, a phenyl C1-C12 alkyl group or a C3-C7 cycloalkyl group (e.g., a cyclohexyl group), more preferably R3 is a C1-C16 alkyl group, a halogenated C1-C6 alkyl group (e.g., a 2,2,2-trifluoroethyl), a phenyl group, a phenyl C1-C6 alkyl group (e.g., a benzyl group) or a C3-C7 cycloalkyl group (e.g., a cyclohexyl group); For example, R3 is a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl group, a phenyl C1-C16 alkyl group, or a C3-C10 cycloalkyl group; for example, R3 is a C1-C16 alkyl group or a halogenated C1-C16 alkyl group; and for example, R3 is a C1-C12 alkyl group; R4 is hydrogen, a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a phenyl C1-C30 alkyl group or a phenyl C1-C30 alkoxy C1-C30 alkyl group, preferably R4 is hydrogen, a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl C1-C16 alkyl group or a phenyl C1-C16 alkoxy C1-C16 alkyl group, preferably R4 is hydrogen, a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a phenyl C1-C12 alkyl group or a phenyl C1-C12 alkoxy C1-C12 alkyl group, more preferably R4 is hydrogen, a C1-C6 alkyl group (e.g., an isopropyl group), a halogenated C1-C6 alkyl group (e.g., a 2,2,2-trifluoroethyl group), a phenyl C1-C6 alkyl group (e.g., a benzyl group) or a phenyl C1-C6 alkoxy C1-C6 alkyl group (e.g., a benzyloxymethyl group); Preferably, R4 is hydrogen, a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl C1-C16 alkyl group or a phenyl C1-C16 alkoxy C1-C16 alkyl group; R5 is a C1-C30 alkyl group, a C2-C30 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C30 alkyl group, a hydroxy C1-C30 alkyl group, a C3-C10 cycloalkyl group, a C1-C30 alkoxy group, a phenyloxy group, a phenyl C1-C30 alkoxy group, a C1-C30 alkoxy C1-C30 alkoxy group, an amino C1-C30 alkyl group, an amino group substituted with a C1-C30 alkyl group, an amino group substituted with a hydroxy C1-C30 alkyl group, an amino group substituted with a phenyl C1-C30 alkyl group, a C3- R5 is a C10 cycloalkoxy group, a C1-C30 alkanoyloxy C1-C6 alkoxy group, a C1-C30 alkoxy C1-C30 alkyl group, a C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkyl group, or a C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkyl group, and preferably R5 is a C1-C16 alkyl group, a C2-C16 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C16 alkyl group, a hydroxy C1-C16 alkyl group, a C3-C10 cycloalkyl group, a C1-C1 6 alkoxy group, phenyloxy group, phenyl C1-C16 alkoxy group, C1-C16 alkoxy C1-C16 alkoxy group, amino C1-C16 alkyl group, amino group substituted with C1-C16 alkyl group, amino group substituted with hydroxy C1-C16 alkyl group, amino group substituted with phenyl C1-C16 alkyl group, C3-C10 cycloalkoxy group, C1-C16 alkanoyloxy C1-C6 alkoxy group, C1-C16 alkoxy C1-C16 alkyl group, C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group or is a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, and preferably, R5 is a C1-C12 alkyl group, a C2-C12 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C12 alkyl group, a hydroxy C1-C12 alkyl group, a C3-C10 cycloalkyl group, a C1-C12 alkoxy group, a phenyloxy group, a phenyl C1-C12 alkoxy group, a C1-C12 alkyloxy C1-C12 alkoxy group, an amino C1-C12 alkyl group, or an amino group substituted with a C1-C12 alkyl group,an amino group substituted with a hydroxy C1-C12 alkyl group, an amino group substituted with a phenyl C1-C12 alkyl group, a C3-C10 cycloalkoxy group, a C1-C12 alkanoyloxy C1-C6 alkoxy group, a C1-C12 alkoxy C1-C12 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, preferably More preferably, R5 is a C1-C6 alkyl group (e.g., a methyl group, an ethyl group, a propyl group, etc.), a C2-C16 alkenyl group (e.g., a decenyl group), a morpholinyl group, a phenyl group, a phenyl C1-C6 alkyl group, a hydroxy C1-C6 alkyl group, a C3-C10 cycloalkyl group (e.g., a cyclopentyl group, a cyclohexyl group), a C1-C6 alkoxy group (e.g., a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, etc.), a phenoxy group, A phenyl C1-C6 alkoxy group, a C1-C6 alkoxy C1-C6 alkoxy group (for example, a methoxyethoxy group), an amino C1-C6 alkyl group (NH2-methyl group), an amino group substituted with a C1-C6 alkyl group (for example, a propylamino group), an amino group substituted with a hydroxy C1-C6 alkyl group (for example, a hydroxyethyl-NH-), an amino group substituted with a phenyl C1-C6 alkyl group (for example, a benzyl-NH-), a C1-C16 alkanoyloxy C1-C6 alkoxy group (decanoyloxymethyloxy group), a C1-C6 alkoxy C1-C6 alkyl group (for example, a methoxymethyl group), a C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (for example, a methoxyethoxymethyl group, a methoxyethoxymethyl group), or a C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (for example, a methoxyethoxyethoxymethyl group). For example, R5 is a C1-C16 alkyl group, a C2-C16 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C16 alkyl group, a hydroxy C1-C16 alkyl group, a C3-C10 cycloalkyl group, a C1-C16 alkoxy group, a phenyl C1-C16 alkoxy group, a C1-C16 alkoxy C1-C16 alkoxy group, an amino C1-C16 alkyl group, a C1-C16 R5 is, for example, a C1-C16 alkyl group, a phenyl C1-C16 alkyl group, an amino group substituted with a hydroxy C1-C16 alkyl group, a phenyl C1-C16 alkyl group, a C3-C10 cycloalkoxy group, a C1-C16 alkoxy C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, or a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group. R5 is, for example, a C1-C6 alkyl group (e.g., a methyl group, an ethyl group, a propyl group, etc.), a phenyl C1-C6 alkyl group, a C1-C6 alkoxy group (e.g., a methoxy group, an ethoxy group, a propoxy group, etc.), a phenyl C1-C6 alkoxy group, a C1-C6 alkoxy C1-C6 alkoxy group, or a C1-C6 alkoxy C1-C6 alkyl group.

[0012] In some embodiments, the N-substituted quinolinone compound, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product, or prodrug thereof, is represented by the following general formula (I-1) or (I-2): [ka] Among them, R1, R6, R7, R8 and R9 have the definitions described in the above general formula (I).

[0013] In some preferred embodiments, R1 is -Y1-OC(=O)-R2, -Y1-OC(=O)-O-R3, -Y1-O-R4 or -C(=O)-R5, preferably -Y1-OC(=O)-R2; Y1 is each independently a C1 to C4 alkylene group, preferably -CH2- or -CH(CH3)-; R2 is a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a C2-C30 alkenyl group, an amino C1-C16 alkyl group, an amino group substituted with a C1-C16 alkyl group, an amino group substituted with a C2-C16 alkenyl group, an amino group substituted with a halogenated C1-C16 alkyl group, an amino group substituted with a phenyl C1-C16 alkyl group, an amino group substituted with a hydroxy C1-C16 alkyl group, an amino group substituted with a C3-C10 cycloalkyl group, or an amino group substituted with a C3-C10 cycloalkyl C1-C6 alkyl group; R2 is a C3-C10 cycloalkyl group, a 5-10 membered heterocyclyl group, a C6-C12 aryl group, a C6-C12 aryl C1-C16 alkyl group, a C1-C16 alkoxycarbonyl C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group or a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, and preferably R2 is a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a C2-C30 alkoxy group, nyl group, amino C1-C12 alkyl group, amino group substituted with C1-C12 alkyl group, amino group substituted with C2-C12 alkenyl group, amino group substituted with halogenated C1-C12 alkyl group, amino group substituted with phenyl C1-C12 alkyl group, amino group substituted with hydroxy C1-C12 alkyl group, amino group substituted with C3-C7 cycloalkyl group, amino group substituted with C3-C7 cycloalkyl C1-C4 alkyl group, C3-C7 cycloalkyl group, 5-10 membered heterocyclyl group, C6-C12 aryl group, C6-C R2 is preferably a C1-C30 alkyl group (e.g., a C1-C30 linear alkyl group, an isopropyl group, a tert-butyl group, a 1-methylpropyl group, a 3-methylbutyl group, a 1-methylbutyl group, a 1,2-dimethylphenyl group, a 1-methylbutyl ...1-dimethylpentyl group, 1-methylpentyl group, 1-methylhexyl group, 1-pentylhexyl group, etc.), halogenated C1 to C30 alkyl group (for example, halogenated C1 to C16 alkyl group, halogenated C1 to C12 alkyl group, halogenated C1 to C6 alkyl group, further, for example, 3,3,3-trifluoropropyl group), C2 to C30 alkenyl group (for example, C2 to C20 alkenyl group), amino C1 to C6 alkyl group (for example, NH2-methyl group), C1 to C12 alkyl group (e.g., decyl-NH-, heptyl-NH-), amino groups substituted with C2-C6 alkenyl groups (e.g., 2-allyl-NH-), amino groups substituted with halogenated C1-C6 alkyl groups (e.g., 3,3,3-trifluoropropyl-NH-), amino groups substituted with phenyl C1-C6 alkyl groups (e.g., benzyl-NH-), amino groups substituted with hydroxy C1-C6 alkyl groups (e.g., hydroxyethyl-NH-), C3-C77 cycloaliphatic alkenyl groups (e.g., cycloaliphatic alkenyl groups) ... an amino group substituted with a C3-C7 cycloalkyl C1-C6 alkyl group (for example, a C3-C7 cycloalkylmethyl-NH-), a C3-C7 cycloalkyl group, a 5-10 membered heterocyclyl group (for example, a pyridyl group, a piperidinyl group, a morpholinyl group, a furyl group, a thienyl group, a pyrimidine group, a quinolyl group, etc.), a phenyl group, a naphthyl group, a phenyl C1-C6 alkyl group (for example, a benzyl group), C1-C6 alkoxycarbonyl C1-C6 alkyl group (for example, a tert-butoxycarbonylmethyl group), C1-C6 alkoxy C1-C6 alkyl group (for example, a methoxymethyl group), C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (for example, a methoxyethoxymethyl group, a butoxyethoxymethyl group) or C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (for example, a methoxyethoxyethoxymethyl group), R3 is a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl group, a phenyl 1-C16 alkyl group or a C3-C10 cycloalkyl group, preferably R3 is a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a phenyl group, a phenyl C1-C12 alkyl group or a C3-C7 cycloalkyl group (e.g., a cyclohexyl group), more preferably R3 is a C1-C6 alkyl group, a halogenated C1-C6 alkyl group (e.g., a 2,2,2-trifluoroethyl group), a phenyl group, a phenyl C1-C6 alkyl group (e.g., a benzyl group) or a C3-C7 cycloalkyl group (e.g., a cyclohexyl group); R4 is hydrogen, a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl C1-C16 alkyl group or a phenyl C1-C16 alkoxy C16-C16 alkyl group, preferably R4 is hydrogen, a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a phenyl C1-C12 alkyl group or a phenyl C1-C12 alkoxy C1-C12 alkyl group, more preferably R4 is hydrogen, a C1-C6 alkyl group (e.g., an isopropyl group), a halogenated C1-C6 alkyl group (e.g., a 2,2,2-trifluoroethyl group), a phenyl C1-C6 alkyl group (e.g., a benzyl group) or a phenyl C1-C6 alkoxy C1-C6 alkyl group (e.g., a benzyloxymethyl group); R5 is a C1-C16 alkyl group, a C2-C16 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C16 alkyl group, a hydroxy C1-C16 alkyl group, a C3-C10 cycloalkyl group, a C1-C16 alkoxy group, a phenyloxy group, a phenyl C1-C16 alkoxy group, a C1-C16 alkoxy C1-C16 alkoxy group, an amino C1-C16 alkyl group, an amino group substituted with a C1-C16 alkyl group, an amino group substituted with a hydroxy C1-C16 alkyl group, an amino group substituted with a phenyl C1-C16 alkyl group, a C3-C10 R5 is a cycloalkoxy group, a C1-C16 alkanoyloxy C1-C6 alkoxy group, a C1-C16 alkoxy C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, or a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, and preferably R5 is a C1-C12 alkyl group, a C2-C12 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C12 alkyl group, a hydroxy C1-C12 alkyl group, a C3-C10 cycloalkyl group, a C1-C12 alkoxy a phenyloxy group, a phenyl C1-C12 alkoxy group, a C1-C12 alkyloxy C1-C12 alkoxy group, an amino C1-C12 alkyl group, an amino group substituted with a C1-C12 alkyl group, an amino group substituted with a hydroxy C1-C12 alkyl group, an amino group substituted with a phenyl C1-C12 alkyl group, a C3-C10 cycloalkoxy group, a C1-C12 alkanoyloxy C1-C6 alkoxy group, a C1-C12 alkoxy C1-C12 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group or a C1-C R5 is preferably a C1-C6 alkyl group (e.g., a methyl group, an ethyl group, a propyl group, etc.), a C2-C16 alkenyl group (e.g., a decenyl group), a morpholinyl group, a phenyl group, a phenyl C1-C6 alkyl group, a hydroxy C1-C6 alkyl group, a C3-C10 cycloalkyl group (e.g., a cyclopentyl group, a cyclohexyl group), a C1-C6 alkoxy group (e.g., a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, etc.), a phenoxy group,a phenyl C1-C6 alkoxy group, a C1-C6 alkoxy C1-C6 alkoxy group (for example, a methoxyethoxy group), an amino C1-C6 alkyl group (NH2-methyl group), an amino group substituted with a C1-C6 alkyl group (for example, a propylamino group), an amino group substituted with a hydroxy C1-C6 alkyl group (for example, a hydroxyethyl-NH-), an amino group substituted with a phenyl C1-C6 alkyl group (for example, benzyl-NH-), a C1-C16 alkanoyloxy C1-C6 alkoxy group (decanoyloxymethoxy group), a C1-C6 alkoxy C1-C6 alkyl group (for example, a methoxymethyl group), a C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (for example, a methoxyethoxymethyl group, a methoxyethoxymethyl group), or a C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (for example, a methoxyethoxyethoxymethyl group); The remaining groups are as defined above.

[0014] In some preferred embodiments, R1 is -Y1-OC(=O)-R2 or -Y1-OC(=O)-O-R3, preferably -Y1-OC(=O)-R2; Y1 is each independently a C1 to C4 alkylene group, preferably -CH2- or -CH(CH3)-; R2 is a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a C2-C12 alkenyl group, an amino C1-C12 alkyl group, an amino group substituted with a C1-C12 alkyl group, an amino group substituted with a C2-C12 alkenyl group, an amino group substituted with a halogenated C1-C12 alkyl group, an amino group substituted with a phenyl C1-C12 alkyl group, an amino group substituted with a hydroxy C1-C12 alkyl group, an amino group substituted with a C3-C6 cycloalkyl group, an amino group substituted with a C3-C6 cycloalkyl C1-C4 alkyl group, a C3-C6 cycloalkyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a furyl group, a thienyl group, a pyrimidine group, a quinolyl group, a phenyl group, a phenyl C1-C12 alkyl group, a C1-C12 alkoxycarbonyl C1-C12 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, preferably a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a C3-C6 cycloalkyl group, a phenyl group, a phenyl C1-C12 alkyl group, a C1-C12 alkoxycarbonyl C1-C12 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group; R3 is a C1 to C12 alkyl group, a halogenated C1 to C12 alkyl group, a phenyl group, a phenyl C1 to C12 alkyl group or a C3 to C6 cycloalkyl group, preferably a C1 to C12 alkyl group, a halogenated C1 to C12 alkyl group, a phenyl group or a C3 to C6 cycloalkyl group.

[0015] In some preferred embodiments, R1 is -Y1-OC(=O)-R2; Y1 is a C1-C4 alkylene group, preferably -CH2- or -CH(CH3)-; R2 is a C3-C16 alkyl group, a halogenated C3-C16 alkyl group, a C3-C16 alkenyl group, an amino C3-C16 alkyl group, an amino group substituted with a C3-C16 alkyl group, an amino group substituted with a C3-C16 alkenyl group, an amino group substituted with a halogenated C3-C16 alkyl group, an amino group substituted with a phenyl C3-C16 alkyl group, an amino group substituted with a hydroxy C3-C16 alkyl group, an amino group substituted with a C3-C6 cycloalkyl group, an amino group substituted with a C3-C6 cycloalkyl C3-C16 alkyl group, a C3-C6 cycloalkyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a furyl group, a thienyl group, a pyrimidine group, a quinolyl group, or a phenyl group. , a phenyl C3-C16 alkyl group, a C1-C12 alkoxycarbonyl C3-C16 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C3-C16 alkyl group or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C3-C16 alkyl group, and preferably a C3-C16 alkyl group, a halogenated C3-C16 alkyl group, a C3-C6 cycloalkyl group, a phenyl group, a phenyl C3-C16 alkyl group, a C1-C12 alkoxycarbonyl C3-C16 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C3-C16 alkyl group or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C3-C16 alkyl group.

[0016] In some preferred embodiments, R1 is -Y1-O-R4; R4 is hydrogen, a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a phenyl C1-C12 alkyl group, or a phenyl C1-C12 alkoxy C1-C12 alkyl group, and is preferably hydrogen, a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, or a phenyl C1-C12 alkyl group.

[0017] In some preferred embodiments, R1 is -C(=O)-R5; R5 is a C1-C12 alkyl group, a C2-C12 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C12 alkyl group, a hydroxy C1-C12 alkyl group, a C3-C6 cycloalkyl group, a C1-C12 alkoxy group, a phenyl C1-C12 alkoxy group, an amino C1-C12 alkyl group, an amino group substituted with a C1-C12 alkyl group, an amino group substituted with a hydroxy C1-C12 alkyl group, an amino group substituted with a phenyl C1-C12 alkyl group, a C3-C6 cycloalkoxy group, a C1-C12 alkoxy C1-C12 alkoxy group, and preferably a C1-C12 alkyl group, a phenyl group, a phenyl C1-C12 alkyl group, a C3-C6 cycloalkyl group, a C1-C12 alkoxy group, a phenyl C1-C12 alkoxy group, a C3-C6 cycloalkoxy group, a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group.

[0018] In some preferred embodiments, in the above general formula (I-1) or (I-2), R6, R7, R8, and R9 are each independently hydrogen; R1 is -Y1-OC(=O)-R2, -Y1-OC(=O)-O-R3, -Y1-O-R4 or -C(=O)-R5; Y1 is each independently a C1 to C4 alkylene group, preferably -CH2- or -CH(CH3)-; R2 is a C1 to C16 alkyl group or a phenyl group; R3 is a C1-C12 alkyl group; R4 is hydrogen; R5 is a C1 to C6 alkyl group or a C1 to C6 alkoxy group.

[0019] In some preferred embodiments, R6, R7, R8 and R9 are each independently hydrogen; R1 is -Y1-OC(=O)-R2, Y1 is a C1-C4 alkylene group, preferably -CH2- or -CH(CH3)-; R2 is a C1 to C30 alkyl group.

[0020] In a second aspect, the present invention provides the following N-substituted quinolinone compounds, or pharma- ceutically acceptable salts, solvates, stereoisomers, geometric isomers, isotopically labeled or prodrugs thereof: (1) 7-(2-(4-(6-fluorobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-1-(hydroxymethyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (2) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl isopropyl carbonate, [ka] (3) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)dodecanoic acid methyl ester, [ka] (4) isopropyl 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate, [ka] (5) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl acetate, [ka] (6) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)pentanoic acid methyl ester, [ka] (7) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)decanoic acid methyl ester, [ka] (8) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl palmitate, [ka] (9) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-quinolin-1(2H)-yl)methyl palmitate, [ka] (10) (7-(2-(4-(6-fluorophenylthiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-quinolin-1(2H)-yl)decanoic acid methyl ester, [ka] (11) 1-acetyl-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (12) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)benzoate methyl [ka] (13) 1-(7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)dodecanoate ethyl. [ka] (14) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylundecyl carbonate, [ka] (15) 1-(7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl palmitate, [ka] (16) ethyl 1-(7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)isobutyrate, [ka] (17) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl pivalate, [ka] (18) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)hexanoate methyl [ka] (19) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl carbonate, [ka] (20) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)methyl carbonate, [ka] (21) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl ethyl carbonate, [ka] (22) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl propyl carbonate, [ka] (23) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl butyl carbonate, [ka] (24) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylhexyl carbonate, [ka] (25) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylheptyl carbonate, [ka] (26) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl octyl carbonate, [ka] (27) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl nonyl carbonate, [ka] (28) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl decyl carbonate, [ka] (29) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl dodecyl carbonate, [ka] (30) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl tetradecyl carbonate, [ka] (31) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl hexadecyl carbonate, [ka] (32) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl phenyl carbonate, [ka] (33) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)methyl phenyl carbonate, [ka] (34) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl benzyl carbonate, [ka] (35) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl(2,2,2-trifluoroethyl)carbonate, [ka] (36) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylcyclohexyl carbonate, [ka] (37) (4-fluoro-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)hexanoate methyl [ka] (38) (4-fluoro-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)dodecanoic acid methyl ester, [ka] (39) (4-chloro-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)hexanoate methyl [ka] (40) (4-amino-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)hexanoate methyl ester, [ka] (41) (4-acetamido-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)hexanoate methyl ester, [ka] (42) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-4,4-dimethyl-2-oxo-3,4-dihydroquinolin-1(2H)-yl)hexanoate methyl ester, [ka] (43) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-4,4-dimethyl-2-oxo-3,4-dihydroquinolin-1(2H)-yl)dodecanoate methyl ester, [ka] (44) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-4-methyl-2-oxoquinolin-1(2H)-yl)hexanoate methyl ester, [ka] (45) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-3-methyl-2-oxoquinolin-1(2H)-yl)hexanoate methyl [ka] (46) (3-ethyl-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)hexanoate methyl ester, [ka] (47) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-3-hydroxy-2-oxoquinolin-1(2H)-yl)hexanoate methyl ester, [ka] (48) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-4-hydroxy-2-oxoquinolin-1(2H)-yl)hexanoate methyl ester, [ka] (49) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-4-hydroxy-2-oxoquinolin-1(2H)-yl)dodecanoic acid methyl ester, [ka] (50) methyl 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl-4-deutero)hexanoate; [ka] (51) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl-4-deutero)dodecanoate methyl ester, [ka] (52) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-(isopropoxymethyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (53) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-(isopropoxymethyl)quinolin-2(1H)-one, [ka] (54) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-((2,2,2-trifluoroethoxy)methyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (55) 1-((benzyloxy)methyl)-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (56) 1-((benzyloxy)methoxy)methyl)-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (57) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl propionate, [ka] (58) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)butyric acid methyl ester, [ka] (59) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2-methoxyacetate methyl [ka] (60) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)heptanoate methyl [ka] (61) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)octylate methyl ester, [ka] (62) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)nonanoic acid methyl ester, [ka] (63) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)undecanoic acid methyl ester, [ka] (64) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)tridecanoate methyl ester, [ka] (65) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)tetradecanoate methyl ester, [ka] (66) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)pentadecanoate methyl ester, [ka] (67) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)heptadecanoic acid methyl ester, [ka] (68) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl stearate, [ka] (69) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)eicosanoic acid methyl ester, [ka] (70) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl allylcarbamate, [ka] (71) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyldecylcarbamate, [ka] (72) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)undecenoic acid methyl ester, [ka] (73) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)oleic acid methyl ester, [ka] (74) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)docosanoic acid methyl ester, [ka] (75) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)tetracosanoate methyl ester, [ka] (76) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)heptadecanoate methyl ester, [ka] (77) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)methyl oleate, [ka] (78) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylcyclobutanecarboxylate, [ka] (79) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl cyclopentanecarboxylate, [ka] (80) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)cyclohexanecarboxylate, [ka] (81) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylpiperidine-1-carboxylate, [ka] (82) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)cycloheptanecarboxylate, [ka] (83) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylcyclohexylcarbamate, [ka] (84) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl(3,3,3-trifluoropropyl)carbamate, [ka] (85) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl(cyclohexylmethyl)carbamate, [ka] (86) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)furan-2-formate methyl ester, [ka] (87) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)furan-3-formate methyl ester, [ka] (88) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)furan-2-formate methyl ester, [ka] (89) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)thiophene-2-formate methyl ester, [ka] (90) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl tetrahydro-2H-pyran-4-carboxylic acid ester, [ka] (91) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)picolinate methyl ester, [ka] (92) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl nicotinate. [ka] (93) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylpyrimidine-5-carboxylic acid ester, [ka] (94) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylquinoline-6-carboxylate, [ka] (95) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)benzoate methyl [ka] (96) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2-phenylacetate methyl [ka] (97) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-4,4,4-trifluorobutyrate ethyl. [ka] (98) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl benzyl carbamate, [ka] (99) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl(2-hydroxyethyl)carbamate, [ka] (100) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methylheptylcarbamate, [ka] (101) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2-(2-methoxyethoxy)acetate methyl [ka] (102) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2-(2-(2-methoxyethoxy)ethoxyacetate methyl ester, [ka] (103) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2-(2-butoxyethoxy)acetate methyl [ka] (104) ((7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl)tert-butyl malonate, [ka] (105) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2-methylbutyrate methyl ester, [ka] (106) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-4-methylpentanoate methyl ester. [ka] (107) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2-methylpentanoate methyl ester, [ka] (108) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2,2-dimethylhexanoate methyl ester, [ka] (109) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2-methylhexanoate methyl ester. [ka] (110) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2-methylheptanoate methyl ester, [ka] (111) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)methyl pivalate. [ka] (112) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-2-pentylheptanoate methyl ester, [ka] (113) (7-(2-(4-(6-fluorophenylthiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)-2-pentylheptanoate methyl ester, [ka] (114) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)glycinate methyl ester. [ka] (115) 1-benzoyl-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (116) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-(2-phenylacetyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (117) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinoline-1(2H)-phenylcarboxylic acid ester, [ka] (118) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate benzyl [ka] (119) 1-(cyclopentanecarbonyl)-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (120) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-(2-hydroxyacetyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (121) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-glycine-3,4-dihydroquinolin-2(1H)-one, [ka] (122) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-N-(2-hydroxyethyl)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxamide, [ka] (123) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-N-propyl-3,4-dihydroquinoline-1(2H)-carboxamide, [ka] (124) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-(2-(2-methoxyethoxy)acetyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (125) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-(2-(2-methoxyethoxy)acetyl)quinolin-2(1H)-one, [ka] (126) 7-(2-(4-(6-fluorobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-1-(2-(2-(2-methoxyethoxy)ethoxyethyl)acetyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (127) N-benzyl-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxamide, [ka] (128) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-(morpholine-4-carbonyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (129) 1-(cyclohexanecarbonyl)-7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (130) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-(2-methoxyacetyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (131) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylic acid-2-methoxyethyl ester, [ka] (132) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-1-(undec-10-enoyl)-3,4-dihydroquinolin-2(1H)-one, [ka] (133) (Decanoyloxy) 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate methyl. [ka] (134) (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxoquinolin-1(2H)-yl)dodecanoic acid methyl ester, [ka]

[0021] In a third aspect, the present invention provides a method for producing the above-mentioned N-substituted quinolinone compound, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product, or prodrug thereof, the method being any one of Methods 1 to 4.

[0022] Method 1: subjecting a compound represented by formula (II) or a salt thereof to an N-alkylation reaction with a compound represented by formula (III) or a salt thereof; [ka] Among them, [ka] , R1, R6, R7, R8 and R9 are as defined above; X represents a leaving group and is a halogen, a C1-C6 alkylsulfonyloxy group, a benzenesulfonyloxy group, or a naphthalenesulfonyloxy group, and the C1-C6 alkylsulfonyloxy group, the benzenesulfonyloxy group, or the naphthalenesulfonyloxy group is optionally substituted with one or more groups selected from a halogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, a nitro group, a hydroxy group, an amino group, and a C1-C6 alkanoyl group, and preferably, X represents a halogen, a C1-C4 alkylsulfonyloxy group, a benzenesulfonyloxy group, or a naphthalenesulfonyloxy group, and the C1-C4 alkylsulfonyloxy group, the benzenesulfonyloxy group, or the naphthalenesulfonyloxy group is optionally substituted with one or more groups selected from a halogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, a nitro group, a hydroxy group, an amino group, and a C1-C6 alkanoyl group. The sulfonyloxy or naphthalenesulfonyloxy group is optionally substituted with one or more groups selected from halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a nitro group, a hydroxy group, an amino group, and a C1-C4 alkanoyl group, and more preferably, X is chlorine, bromine, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, a benzenesulfonyloxy group, a naphthalenesulfonyloxy group, a methylbenzenesulfonyloxy group, a nitrobenzenesulfonyloxy group, an aminobenzenesulfonyloxy group, a chlorobenzenesulfonyloxy group, a bromobenzenesulfonyloxy group, or a methoxybenzenesulfonyloxy group.

[0023] The above reaction is carried out in the presence or absence of a solvent, and is preferably carried out in a solvent in the presence or absence of a base.

[0024] The solvent includes ethers such as water, dioxane, tetrahydrofuran, diethyl ether, methyl tert-butyl ether, diisopropyl ether, diethylene glycol dimethyl ether, ethylene glycol dimethyl ether, etc., aromatic hydrocarbons such as benzene, toluene, xylene, nitrobenzene, chlorobenzene, etc., alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, ethylene glycol, etc., ketones such as acetone, methyl ethyl ketone, 4-methyl-2-pentanone, etc., amides such as N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, etc., halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, carbon tetrachloride, etc., esters such as ethyl acetate, ethyl formate, methyl acetate, isopropyl acetate, etc., others such as dimethyl sulfoxide, acetonitrile, etc., or mixtures of the above solvents.

[0025] The base is selected from inorganic bases or organic bases, inorganic bases include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, cesium hydroxide, lithium hydroxide, alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, alkali metal bicarbonates such as sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, alkali metals such as potassium, sodium, sodium amide, potassium amide, sodium hydride, potassium hydride, etc., and organic bases include sodium methoxide, sodium ethoxide, potassium methoxide, etc. , potassium ethoxide, sodium acetate, triethylamine, pyridine, diisopropylamine, diisopropylethylamine, tripropylamine, diethylamine, pyrimidine, quinoline, piperidine, piperazine, imidazole, dimethylaminopyridine, trimethylamine, N-ethyldiisopropylamine, N-methylmorpholine, dimethylaniline, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO). These bases may be used alone or in combination of two or more.

[0026] Preferably, the reaction is carried out in the presence of alkali metal iodides, including potassium iodide and sodium iodide, as reaction promoters.

[0027] Preferably, the reaction temperature is from room temperature to 200° C., preferably from room temperature to 150° C., and the reaction time is from 1 to 120 hours, preferably from 5 to 80 hours.

[0028] Method 2: by subjecting a compound represented by formula (IV) or a salt thereof to a coupling reaction with a compound represented by formula (V) or a salt thereof; [ka] Among them, [ka] , R1, R6, R7, R8 and R9 are as defined above; X1 is a halogen atom or a trifluoromethanesulfonyloxy group, preferably a bromine atom, an iodine atom, a chlorine atom or a trifluoromethanesulfonyloxy group; Preferably, the coupling reaction is carried out in the presence of a palladium catalyst and a base.

[0029] The above palladium catalysts include palladium acetate (Pd(OAc)2), bis(triphenylphosphine)palladium(II) dichloride ((Ph3P)2PdCl2), bis(benzonitrile)palladium(II) chloride ((PhCN)2PdCl2), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), bis(triphenylphosphinepalladium) acetate ((Ph3P)2Pd(OAc)2), [1,2-bis(diphenylphosphino)ethane]dichloropalladium(II) (PdCl2(dppe)2 ), bis[1,2-bis(diphenylphosphino)ethane]palladium(0) (Pd(dppe)2), bis(dibenzylideneacetone)palladium(0) (Pd(dba)2), tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3), dichloro[1,3-bis(diphenylphosphino)propane]palladium(II) (PdCl2(dippp)), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2).

[0030] The base is one or more of sodium bis(trimethylsilyl)amide, potassium tert-butoxide, sodium tert-butoxide, cesium carbonate, potassium phosphate, sodium phosphate, sodium methoxide, sodium ethoxide, potassium hydroxide, sodium hydroxide, potassium fluoride, sodium fluoride, tetrabutylammonium fluoride (TBAF), sodium acetate, potassium acetate, cesium carbonate, potassium carbonate, and sodium carbonate.

[0031] The reaction solvent for the above reaction is not particularly limited as long as it does not inhibit the reaction, and includes water, ethers such as dioxane and tetrahydrofuran, aromatic hydrocarbons such as toluene and xylene, alcohols such as tert-butanol, ketones such as acetone, amides such as N,N-dimethylformamide, others such as dimethylsulfoxide and acetonitrile, or a mixture of the above solvents.

[0032] Preferably, the reaction is carried out in the presence of a ligand, which is one or more of 2,2'-diphenylphosphino-1,1'-binaphthyl (BINAP), tri-tert-butylphosphine (P(t-Bu)3), 1,1'-di-(diphenylphosphino)ferrocene (dppf), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (x-phos), 4,5-bisdiphenylphosphine-9,9-dimethylxanthone (Xantphos), tri-tert-butylphosphine tetrafluoroborate, and tris(2-methylphenyl)phosphine (P(o-tolyl)3) as a reaction promoter.

[0033] Preferably, the reaction temperature is from room temperature to 200° C., preferably from room temperature to 150° C., and the reaction time is from 1 to 30 hours, preferably from 5 to 20 hours.

[0034] Method 3: A compound represented by formula (Ia) or a salt thereof is subjected to a substitution reaction with a compound represented by R1X, [ka] Among them, [ka] , R1, R6, R7, R8 and R9 are as defined above; X is as defined in Method 1 above, The reaction conditions in Method 3 are the same as those in Method 1 above.

[0035] Method 4: A substitution reaction is carried out between a compound represented by formula (Ib) or a salt thereof and a compound represented by XC(=O)-R2, XOC(=O)-O-R3 or X-R4, [ka] wherein R1 is -Y1-OC(=O)-R2, -Y1-OC(=O)-O-R3 or -Y1-O-R4; [ka] , R6, R7, R8, R9, Y1, R2, R3 and R4 are as defined above; X is a halogen, preferably bromine, iodine or chlorine; The reaction conditions in Method 4 are the same as those in Method 1 above.

[0036] Each target compound obtained in each reaction scheme is separated and purified from the reaction mixture by cooling the reaction mixture, isolating the crude product by methods such as filtration, extraction or concentration, and then purifying it by conventional methods such as column chromatography, slurrying or recrystallization.

[0037] In a fourth aspect, the present invention provides a pharmaceutical composition comprising the above-mentioned N-substituted quinolinone compound, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product, or prodrug thereof, and at least one pharma- ceutically acceptable vector.

[0038] In a fifth aspect, the present invention provides a method for preparing a pharmaceutical composition, comprising mixing the above-mentioned N-substituted quinolinone compound, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product, or prodrug thereof, with a pharma- ceutically acceptable vector.

[0039] The pharmaceutical composition of the present invention may be in a variety of pharmaceutical formulation forms selected according to the purpose of treatment, including, but not limited to, tablets, pills, capsules, granules, suspensions, solutions, creams, ointments, powders, suppositories, aerosols, and injections (e.g., fat-soluble or oil-soluble injections).

[0040] In a sixth aspect, the present invention provides the use of an N-substituted quinolinone compound as defined above, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled or prodrug thereof, or a pharmaceutical composition as defined above, in the manufacture of a medicament for the prophylaxis and / or treatment of a central nervous system disease, condition or disorder.

[0041] In a seventh aspect, the present invention provides a method for treating and / or preventing a disease, condition or disorder of the central nervous system comprising administering to a human or animal an effective amount of an N-substituted quinolinone compound as defined above, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled or prodrug thereof, or a pharmaceutical composition as defined above.

[0042] In an eighth aspect, the N-substituted quinolinone compound provided by the present invention, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product or prodrug thereof, or the pharmaceutical composition is an N-substituted quinolinone compound or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product or prodrug thereof, for inhibiting 5-HT 1A Receptor agonist / 5-HT 2A It can be used as a receptor antagonist / D2 receptor antagonist / D3 receptor agonist / 5-HT transporter inhibitor.

[0043] The central nervous system disease, condition or disorder is selected from schizophrenia (preferably uncontrolled, unmanageable or chronic schizophrenia), affective disorder, mental disorder, mood disorder, bipolar I disorder, bipolar II disorder, depression (preferably endogenous, severe or uncontrollable depression), dysthymic disorder, cyclothymic disorder, panic attack, panic disorder, social anxiety disorder, obsessive-compulsive disorder, impulsive disorder, post-traumatic stress disorder, anxiety disorder, acute stress disorder, hysteria, anorexia nervosa, sleep disorder, adjustment disorder, cognitive disorder, autism, neurotic headache, mania, Parkinson's disease, Huntington's disease, Alzheimer's disease, dementia, memory disorder, hyperactivity disorder, attention-deficit / hyperactivity disorder and tic disorder. Effect of the Invention

[0044] In order to solve the problem of low solubility of compounds in oily media in the prior art, the inventors conducted various studies and found that the fat-solubility of the compound can be significantly improved by introducing a substituent into a specific position of quinolinone. Based on this finding, the present invention has been completed. The beneficial effects of the present invention are as follows:

[0045] 1) Excellent oil solubility The compound of the present invention has a remarkably excellent solubility in oil (sesame oil, benzyl benzoate, etc.), and can be applied to oil-based injections. Compared with aqueous suspensions, oil-based injections are more advantageous in terms of sustained blood concentration delivery (diffusion control at administration site by oil base), shortening the preparation time of drug solution (no need for mixing or shaking), ensuring sterilization by filtration (oil base can be filtered), avoiding physical irritation at administration site (stability of oil base), and improving accuracy of syringe filling (container filled with oil base).

[0046] 2) Multi-targeting: High therapeutic effect and minimal side effects The compounds of the present invention or their in vivo metabolites are 2A Receptor, dopamine D 2 / 3 Receptor, 5-HT 1A It has a multi-targeting effect on the 5-HT receptor and the 5-HT transporter.2A It has antagonistic effects on D3 receptors and 5-HT transporters. 1A It has partial agonist effect on the receptor and has IC 50 or EC 50 reaches 0.1-10 nM levels, and the antagonistic / agonistic effects are significant.

[0047] This multi-targeting property can regulate the DA / 5-HT system, which is helpful in regulating the balance of neurotransmitters in the brain, and has a good therapeutic effect on various central nervous system diseases. At the same time, this multi-targeting property is more effective than a single D2 receptor antagonist or D2 / 5-HT 2A Side effects caused by receptor antagonists, such as extrapyramidal symptoms (EPS) and hyperprolactinemia, can be reduced or avoided.

[0048] The compounds of the present invention have multi-target effects and are more suitable for drug discovery than the compounds in Patent WO2015131856. They can be used to treat various central nervous system diseases, particularly depression, major depressive disorder (MDD), bipolar disorder, schizophrenia, negative symptoms of schizophrenia, anxiety disorder, phobia, autism, Alzheimer's disease, bipolar disorder, cognitive dysfunction, Parkinson's disease, hysteria, obsessive-compulsive disorder, hyperactivity disorder, and the like.

[0049] The compound of the present invention or its in vivo metabolites have a good inhibitory effect on the 5-HT transporter, and can improve comorbidities such as anxiety and depression associated with schizophrenia and other central nervous system diseases.

[0050] The compounds of the present invention or their in vivo metabolites are 5-HT 1A It has a good regulatory effect on 5-HT receptors, which can improve the negative symptoms and cognitive deficits of schizophrenia. 1A It does not cause central or peripheral side effects due to complete agonization of the receptor.

[0051] 3) Better safety and tolerability The compounds of the present invention are expected to have lower hERG inhibitory activity than the compounds in patent WO2015131856, and to have higher clinical safety.

[0052] The compound of the present invention can gradually release active metabolites in vivo, with small fluctuations in blood concentration, improving the safety and tolerance of the drug. The compound of the present invention can be converted into active metabolites with multi-targeting effects in blood, and is also excellent in maintaining the blood concentration of active metabolites with desired therapeutic effects for a long period of time, so the compound of the present invention shows excellent metabolic stability and sustained blood concentration, making it more suitable for the production of long-acting preparations.

[0053] The compounds of the present invention are orally effective, and may be prepared into oral formulations or oily injections. They have the characteristics of long-lasting action, low effective dose, and low toxicity and side effects, thereby improving patient compliance.

[0054] 4) Easy to crystallize and has excellent stability The compound of the present invention is easily crystallized, easy to handle, and has excellent chemical stability.

[0055] 5) High efficacy when administered in combination The compound of the present invention, when administered in combination with at least one clinically used drug selected from (1) mood stabilizers, (2) serotonin reuptake inhibitors, (3) norepinephrine reuptake inhibitors, (4) serotonin and norepinephrine reuptake inhibitors, and (5) antidepressants, can exhibit effects that cannot be achieved by conventional treatments, such as reduced dosage, amelioration of side effects, and improved therapeutic effects.

[0056] In summary, compared with conventional antipsychotic drugs, the compounds of the present invention have advantages such as excellent oil solubility, multi-target action, lower effective dose, less toxicity and side effects, higher safety and tolerance, etc., and have high comprehensive druggability and good prospects for clinical application. [Brief description of the drawings]

[0057] [Figure 1] 1 is a graph showing time-active metabolite concentration after intramuscular injection of compounds 3, 5, and 7 in SD rats. [Diagram 2] 1 is a graph showing time-active metabolite concentration after intramuscular injection of compounds 2, 6, and 8 in SD rats. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0058] The definitions of each group in the present invention are as follows: Halogen means fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine or bromine, more preferably fluorine or chlorine; In the present invention, Cn to Cm indicate that the group contains n to m carbon atoms, and the following carbon numbers are exemplified.

[0059] The alkyl group refers to a linear or branched saturated hydrocarbon group, and the C1-C30 alkyl group refers to a linear or branched saturated hydrocarbon group containing 1 to 30 carbon atoms, such as a C1-C16 alkyl group, a C1-C12 alkyl group, or a C1-C6 alkyl group, such as a C1-C30 linear alkyl group or a C1-C26 linear alkyl group, and examples thereof include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, an n-hexyl group, an undecyl group, a pentadecyl group, a nonadecyl group, and a tricosyl group, and examples thereof include a C1-C30 branched alkyl group, a C1-C a 12-branched alkyl group, examples of which include an isopropyl group, an isobutyl group, a tert-butyl group, a sec-butyl group, a 1-methylpropyl group, a 1-ethylpropyl group, an isopentyl group, a neopentyl group, a 1-methylbutyl group, a 3-methylbutyl group, an isohexyl group, a 1-methylpentyl group, a 3-methylpentyl group, a 1,1-dimethylpentyl group, a n-hexyl group, a 1-methylhexyl group, a 1-pentylhexyl group, and the like, and preferably a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, or a n-hexadecyl group; A C1-C6 alkylene group means a divalent alkyl group containing 1 to 6 carbon atoms, such as -CH2-, -CH(CH3)-, -C(CH3)2-, -CH2CH2-, -CH2CH(CH3)-, -CH2C(CH3)2-, -CH2CH2CH2- or -(CH2)6-; The halogenated C1-C30 alkyl group refers to a linear or branched saturated hydrocarbon group containing 1 to 30 carbon atoms, such as a halogenated C1-C16 alkyl group, a halogenated C1-C12 alkyl group, or a halogenated C1-C6 alkyl group, in which a hydrogen atom is substituted with one or more identical or different halogen atoms. Examples of the halogenated C1-C30 alkyl group include a trifluoromethyl group, a fluoromethyl group, a difluoromethyl group, a chloromethyl group, a bromomethyl group, a dichlorofluoromethyl group, a chloroethyl group, a bromopropyl group, a 2-chlorobutyl group, a pentafluoroethyl group, or a -(CH2) 15 CF3, etc. The C1-C30 alkoxy group refers to a straight-chain or branched-chain alkoxy group containing 1 to 30 carbon atoms, such as a C1-C16 alkoxy group, a C1-C12 alkoxy group, or a C1-C6 alkoxy group. Examples include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a tert-butoxy group, a sec-butoxy group, an n-pentyloxy group, an isopentyloxy group, a neopentyloxy group, an isohexyloxy group, a 3-methylpentyloxy group, or an n-hexyloxy group, and preferably a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, or an n-hexadecyloxy group. The halogenated C1-C30 alkoxy group refers to a linear or branched alkoxy group containing 1 to 30 carbon atoms, such as a halogenated C1-C16 alkoxy group, a halogenated C1-C12 alkoxy group, or a halogenated C1-C6 alkoxy group, in which the hydrogen atom is substituted with one or more identical or different halogen atoms. Examples include -OCF3, -OCH2CH2Cl, -OCHBrCH2Cl, -OCF2CF3, or -O(CH2) 15 CF3, etc. A C2-C30 alkenyl group means a straight-chain or branched-chain unsaturated hydrocarbon group containing 1, 2 or 3 double bonds and 2 to 16 carbon atoms, including both cis and trans configurations, such as a C2-C16 alkenyl group, a C2-C12 alkenyl group, or a C2-C6 alkenyl group, examples of which are a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-methyl-1-propenyl group, a 2 ... methyl-2-propenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1,3-butadienyl group, 1,3-pentadienyl group, 1-hexenyl group, 2-hexenyl group, 3-hexenyl group, 4-hexenyl group, 5-hexenyl group, 3,3-dimethyl-1-propenyl group, 2-ethyl-1-propenyl group, and the like. The phenyl C1-C30 alkyl group means a group in which one carbon atom of a linear or branched saturated hydrocarbon group containing 1 to 30 carbon atoms is linked to a carbon atom of a phenyl group, such as a phenyl C1-C16 alkyl group, a phenyl C1-C12 alkyl group, or a phenyl C1-C6 alkyl group, and examples thereof include a benzyl group, a phenethyl group, or a phenylpropyl group, and the like. A phenyl C1-C30 alkoxy group refers to a group in which one carbon atom of a linear or branched alkoxy group containing 1 to 30 carbon atoms is linked to a carbon atom of a phenyl group, such as a phenyl C1-C16 alkoxy group, a phenyl C1-C12 alkoxy group, or a phenyl C1-C6 alkoxy group, and examples thereof include a benzyloxy group, -OCH(CH3)Ph, a phenylethoxy group, or a phenylpropoxy group, etc.; The amino group substituted with a C1 to C30 alkyl group is -NHMe, -NHEt, -N(Me)Et, -NEt2 or -NH(CH2) 15 It means a group in which a hydrogen atom on an amino group, such as CH3, is substituted with one or two identical or different C1 to C30 alkyl groups.

[0060] The amino group substituted with a C2 to C30 alkenyl group is -NHCH=CH2, -NHCH=CHCH3, -NHCH=CHCH2CH3 or -NHCH=CH(CH2) 13CH3, etc., a group in which a hydrogen atom on an amino group is substituted with one or two identical or different C2 to C30 alkenyl groups, The amino group substituted with a halogenated C1-C30 alkyl group is -NHCH2CF3, -NHCF2CF3, -N(CH2CF3)2 or -NH(CH2) 15 CF3, etc., a group in which a hydrogen atom on an amino group is substituted with one or two identical or different halogenated C1-C30 alkyl groups, An amino group substituted with a phenyl C1-C30 alkyl group is -NHCH2Ph, -N(CH2Ph)2 or -NH(CH2) 15 Ph, etc., in which a hydrogen atom on an amino group is substituted with one or two identical or different phenyl C1-C30 alkyl groups, An amino group substituted with a hydroxy C1-C30 alkyl group is -NHCH2CH2OH, -N(CH2CH2OH)2 or -NH(CH2) 16 OH, a hydrogen atom on an amino group is substituted with one or two identical or different hydroxy C1-C30 alkyl groups, The amino group substituted with a C3 to C10 cycloalkyl group means a group in which one or two hydrogen atoms on the amino group are substituted with the same or different C3 to C10 cycloalkyl groups, such as -NHCH(CH2)2 or -NHCH(CH2)4, The amino group substituted with a C3-C10 cycloalkyl C1-C6 alkyl group means a group in which one or two hydrogen atoms on the amino group are substituted with identical or different C3-C10 cycloalkyl C1-C6 alkyl groups, such as -NHCH2CH(CH2)2, -NHCH2CH2CH(CH2)2 or -NHCH2CH(CH2)4, The C1-C30 alkoxycarbonyl C1-C30 alkyl group is -CH2(CO)OCH2CH3, -CH2CH2(CO)OCH2CH3 or -CH2(CO)O(CH2) 15 CH3, etc., means a group in which the carbonyl carbon atom of a C1-C30 alkoxycarbonyl group is linked to a C1-C30 alkyl group, A C3-C10 cycloalkyl group means a saturated cyclic hydrocarbon group containing 3 to 10 carbon atoms, such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, or a cyclooctyl group; The C3-C10 cycloalkoxy group means a group in which a hydrogen atom on a hydroxy group is substituted with a C3-C10 cycloalkyl group, such as -OCH(CH2)2, -OCH(CH2)3 or -OCH(CH2)4, The C1-C30 alkoxy C1-C30 alkyl group is -CH2OCH2CH3, -CH2CH2OCH2CH3 or -CH2O(CH2) 15 CH3, etc., means a group in which a C1-C30 alkoxy group or a C1-C30 alkyl group is linked by a single bond, The C1-C30 alkoxy C1-C30 alkoxy group is -OCH2OCH2CH3, -OCH2CH2OCH2CH3 or -OCH2O(CH2) 15 CH3, or a group in which C1-C30 alkoxy groups are linked by a single bond; The phenyl C1-C30 alkoxy C1-C30 alkyl group is -CH2OCH2CH2Ph, -CH2CH2OCH2CH2Ph ​​or -CH2O(CH2) 16 Ph, etc., means a group in which a phenyl group, a C1-C30 alkoxy group, and a C1-C30 alkyl group are linked in sequence by a single bond, The C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkyl group is -CH2OCH2CH2OCH2CH3, -CH2CH2OCH2CH2OCH2CH3 or -CH2OCH2CH2O(CH2) 15 CH3, etc., means a group in which a C1-C30 alkoxy group, a C1-C30 alkoxy group, and a C1-C30 alkyl group are linked in sequence by a single bond, The C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkyl group is -CH2OCH2CH2OCH2CH2OCH2CH3, -CH2CH2OCH2CH2OCH2CH2OCH2CH3 or -CH2OCH2CH2OCH2CH2O(CH2) 15CH3, etc., a group in which a C1-C30 alkoxy group, a C1-C30 alkoxy group, a C1-C30 alkoxy group, and a C1-C30 alkyl group are linked in sequence by a single bond, Hydroxy C1-C30 alkyl group is -CH2OH, -CH2CH2OH, -CH(OH)CH3, -CH2CH2CH2OH, -CH2CH2CH2CH2OH, -CH2CH(CH3)CH2OH or -(CH2) 15 means a group in which one carbon atom of a linear or branched alkyl group containing 1 to 30 carbon atoms is linked to a hydroxy group, such as CHOH; The amino C1-C30 alkyl group is -CH2NH2, -CH2CH2NH2, -CH(NH2)CH3, -CH2CH2CH2NH2 or -(CH2) 15 means a group in which one carbon atom of a linear or branched alkyl group containing 1 to 30 carbon atoms is linked to an amino group, such as CH2NH2, The C6-C12 aryl group refers to a monocyclic or polycyclic aromatic ring group containing 6 to 12 ring atoms but not containing heteroatoms among the ring atoms, such as a phenyl group or a naphthyl group; C6-C12 aryl C1-C30 alkyl group means a group in which one carbon atom of a linear or branched saturated hydrocarbon group containing 1 to 30 carbon atoms is linked to a carbon atom of a C6-C12 aryl group, such as a benzyl group, a naphthylmethyl group, or a naphthylethyl group; Heterocyclyl groups include "heterocycloalkyl groups" and "heteroaryl groups" and refer to monocyclic or polycyclic groups containing at least one heteroatom selected from nitrogen, oxygen and sulfur as a ring member, and may be aromatic or non-aromatic. A 5- to 10-membered heterocyclyl group refers to a heterocyclyl group containing 5 to 10 ring atoms, such as a pyridyl group, a piperidinyl group, a morpholinyl group, a furyl group, a thienyl group, a thiazolyl group, an imidazolyl group, a pyrrolyl group, a pyrazinyl group, a pyridazinyl group or a pyrimidine group.

[0061] The term "pharmaceutically acceptable salts" refers to salts of the compounds of the present invention, e.g., pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts, which are, within the scope of reasonable medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit / risk ratio, and which, where possible, are effective for the intended use.

[0062] The term "solvate" refers to a complex of variable stoichiometry formed by a solute (e.g., a compound of the present invention) and a solvent (e.g., water, ethanol, or acetic acid). This physical association may involve different degrees of ionic and covalent bonding, including hydrogen bonding. In some cases, the solvate may be isolated (e.g., when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid). In general, such solvents selected according to the present invention do not interfere with the biological activity of the solute. Representative solvates include hydrates, ethanolates, methanolates, and the like. The term "hydrate" refers to a solvate in which the solvent is water.

[0063] The term "stereoisomer" or "optical isomer" refers to a stable isomer that has at least one chiral element, e.g., a chiral atom or has a perpendicular plane of asymmetry as a result of restricted rotation (e.g., some biphenyls, propadiene and spiro compounds) and is capable of rotating plane-polarized light. The compounds of the invention (and derivatized forms thereof, such as salts, solvates or prodrugs) contain asymmetric carbon atoms and can therefore exist as single stereoisomers, racemates, and mixtures of enantiomers and diastereomers.

[0064] The term "geometric isomer" or "cis-trans isomer" refers to stable isomers resulting from restricted rotational freedom about a double bond (e.g., cis-2-butene and trans-2-butene) or ring structure (e.g., cis-1,3-dichlorocyclobutane and trans-1,3-dichlorocyclobutane). The specific configuration of the isomer is represented by using the cis / trans convention or by using the E or Z system, where the term "E" or "E-form" refers to the higher order substituent on the opposite side of the double bond and the term "Z" or "Z-form" refers to the higher order substituent on the same side of the double bond. The determination of E and Z isomers can be performed by X-ray crystallography, 1 H-NMR and 13 This can be done by analytical methods such as C-NMR.

[0065] The term "isotopically labeled" refers to a derivative compound formed by replacing a particular atom in the compound of the present invention with its isotope atom. The compounds of the present invention, unless otherwise indicated, may contain various isotopes of H, C, N, O, F, P, S, Cl, e.g. 2 H(D), 3 H(T), 13 C. 14 C. 15 N, 17 O. 18 O. 18 F, 31 P, 32 P, 35 S, 36 S and 37 Contains Cl.

[0066] The term "prodrug" or "prodrug derivative" refers to a covalent derivative or vector of a parent compound or active drug substance, which undergoes at least some biotransformation before exhibiting its one or more pharmacological actions. Generally, such prodrugs have a metabolically cleavable group and are rapidly converted in vivo to generate the parent compound. Prodrugs are usually formulated for the purpose of improving chemical stability, improving individual acceptance and compliance, improving bioavailability, prolonging the duration of action, improving organ selectivity, improving formulation (e.g., increasing water solubility), and / or reducing side effects (e.g., toxicity). Generally, prodrugs have weak or no biological activity themselves, are stable under normal conditions, and can be easily prepared from the parent compound using methods known in the art.

[0067] The compounds of formula (II), formula (III), formula (IV), formula (V) and formula (Ia) in the present invention are either commercially available compounds or are prepared according to art-known methods or methods for the synthesis of similar compounds.

[0068] The starting compounds used in each reaction scheme of the present invention may be in the form of a pharma- ceutically acceptable salt thereof, and the pharma-ceutically acceptable salts include alkali metal salts and alkaline earth metal salts such as sodium salt, potassium salt, calcium salt, magnesium salt, etc., organic base salts such as pyridine salt, triethylamine salt, etc., inorganic acid salts such as hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, phosphate, etc., and organic acid salts such as formate, acetate, propionate, glycolate, oxalate, malonate, succinate, fumarate, maleate, lactate, malate, citrate, tartrate, picrate, glutamate, methanesulfonate, benzenesulfonate, etc.

[0069] Furthermore, the starting compounds used in each reaction scheme of the present invention may be in the form of a solvate such as a hydrate or an alcoholate.

[0070] The N-substituted quinolinone compound of the present invention represented by the general formula (I) and its stereoisomers may be in the form of a solvate such as a hydrate or an alcoholate, and the above solvates are included in the scope of the present invention.

[0071] The pharma- ceutically acceptable salts of the N-substituted quinolinone compound of the present invention represented by general formula (I) and its stereoisomers refer to the N-substituted quinolinone compound of the present invention represented by general formula (I) or its stereoisomers, which are treated with an appropriate acid to convert into a non-toxic addition salt form having therapeutic activity.The above salts include hydrochloride, hydrobromide, hydroiodide, sulfate, hydrogen sulfate, nitrate, phosphate, acid phosphate, perchlorate, formate, acetate, trifluoroacetate, propionate, pyruvate, glycolate, oxalate, malonate, succinate, glutarate, maleate, fumarate, lactate, malate, citrate, tartrate, picrate, glutamate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, salicylate, ascorbate, camphorate or camphorsulfonate. Conversely, the salt form can be converted into the free base form by treatment with a base.

[0072] The term "pharmaceutically acceptable salt" as used above may be a solvate thereof, and the solvate is included within the scope of the present invention. Examples of solvates are hydrates, alcoholates, etc.

[0073] In the present invention, "room temperature" means 10 to 30°C.

[0074] The abbreviations and definitions in the present invention are as shown in the following table: [Table 1] EXAMPLES

[0075] The following examples and experimental examples further explain the present invention, but are not intended to limit the scope of the present invention. Unless otherwise specified, the raw materials, reagents, methods, etc. used in the examples and experimental examples are all raw materials, reagents, and methods commonly used in the relevant fields, and the raw materials and reagents used are all commercially available.

[0076] <Production Example> Example 1 Preparation of 7-(2-(4-(6-fluorobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-1-(hydroxymethyl)-3,4-dihydroquinolin-2(1H)-one [ka] Compound 1-a (4.8 g, 1 eq), 37% aqueous formaldehyde solution (15 mL), triethylamine (593 mg, 0.5 eq) and DMF (15 mL) were added to a 100 mL one-neck flask, and the mixture was reacted at 85 ° C for 3 h, and the progress of the reaction was monitored by TLC. Work-up: The reaction solution was diluted with 100 mL of DCM, washed with water (100 mL × 4), and concentrated under reduced pressure to obtain a crude product. Acetonitrile (10 mL) was added to the crude product, slurried at room temperature, and filtered to obtain 3.6 g of wet product. DCM (6 mL) was added to the wet product, slurried at 0-10 ° C, and filtered to obtain 2.3 g of wet product. DCM (4.6 mL) was continued to be used to slurried at 0-10 ° C, filtered, and dried to obtain 2 g of the target compound (white solid, HPLC purity 98%). 1HNMR (400MHz, DMSO-d6): δ ppm 7.66(d, J=5.5 Hz, 1H), 7.49(dd, J=8.6, 1.7 Hz, 1H), 7.37(d, J=5.5 Hz, 1H), 7.19(s, 1H), 7.11(d, J=7.6 Hz, 1H), 6.90(d, J=7.4 Hz, 1H), 6.75(dd, J=11.5, 2.0 Hz, 1H), 6.15(t, J=6.8 Hz, 1H), 5.23(d, J=6.8 Hz, 2H), 3.10(br, 4H), 2.78(m, 4H), 2.69(br, 4H), 2.62(m, 2H), 2.51(m, 2H). ESI-MS (m / z): 440.28 [M+H] + .

[0077] Example 2 Preparation of (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl isopropyl carbonate [ka] Compound 1-a (400 mg, 1 eq) was taken, dissolved in DMF (10 mL), protected with nitrogen gas, and the temperature was controlled at about 20 ° C., sodium hydrogen (4 eq) was added, and the mixture was reacted at room temperature for 30 min, isopropyl chloromethyl carbonate (4 eq) was added dropwise, and the reaction was heated to 60-65 ° C. and continued to react for 2 h, and the reaction was monitored by TLC to confirm that a small amount of raw material remained. The reaction was stopped, and the reaction liquid was poured into ethyl acetate and ice water (30 mL each), stirred, allowed to stand, and separated. The organic phase was washed with water and saturated saline (30 mL each), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain 440 mg of an oily product. 1HNMR (400MHz, CDCl3): δ ppm 7.33(m, 2H), 7.21(dd, J=8.2, 1.9 Hz, 1H), 7.11(d, J=7.6 Hz, 1H), 6.98(s, 1H), 6.94(d, J=7.6 Hz, 1H), 6.66(dd, J=11.1, 2.1 Hz, 1H), 5.96(s, 2H), 4.94(m, 1H), 3.20(br, 4H), 2.89(m, 2H), 2.85(m, 2H), 2.77(br, 4H), 2.70(m, 4H), 1.31(d, J=6.3 Hz, 6H). ESI-MS (m / z): 526.50 [M+H] + .

[0078] Example 3 Preparation of methyl (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)dodecanoate [ka] Compound 1-a (500 mg, 1 eq) was taken, dissolved in DMF (10 mL), protected with nitrogen gas, and the temperature was controlled at about 20 ° C., sodium hydrogen (4 eq) was added, and the reaction was allowed to proceed at room temperature for 30 min. Chloromethyl dodecanoic acid (4 eq) was added dropwise, and the reaction was allowed to proceed at 60-65 ° C. for 2 h. The reaction was monitored by TLC to confirm that a small amount of raw material remained. The reaction was stopped, and the reaction liquid was poured into ethyl acetate and ice water (30 mL each), stirred, allowed to stand, and separated. The organic phase was washed with water and saturated saline (30 mL each), dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 670 mg of an oily product. The product was clarified by adding isopropyl ether (6.7 mL), freeze-crystallized (-40 ° C.), filtered, and dried to obtain 500 mg of a white solid. 1HNMR (400MHz, CDCl3): δ ppm 7.33(m, 2H), 7.21(dd, J=8.2, 1.9 Hz, 1H), 7.11(d, J=7.6 Hz, 1H), 6.94(d, J=7.6 Hz, 1H), 6.90(s, 1H), 6.66(dd, J=11.1, 2.1 Hz, 1H), 5.94(s, 2H), 3.20(br, 4H), 2.90(m, 2H), 2.85(m, 2H), 2.77(br, 4H), 2.70(m, 4H), 2.36(t, J=7.6 Hz, 2H), 1.64(m, 2H), 1.35-1.17(m, 16H), 0.86(t, J=6.9Hz, 3H). ESI-MS (m / z): 622.52 [M+H] + .

[0079] Example 4 Preparation of isopropyl 7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate [ka] Compound 1-a (400 mg, 1 eq) was taken, dissolved in DMF (10 mL), protected with nitrogen gas, and the temperature was controlled at about 20 ° C., sodium hydrogen (4 eq) was added, and the reaction was allowed to proceed at room temperature for 30 min. Isopropyl chloroformate (4 eq) was added dropwise, and the reaction was allowed to proceed at 60-65 ° C. for 2 h. The reaction was monitored by TLC to confirm that a small amount of raw material remained. The reaction was stopped, and the reaction liquid was poured into ethyl acetate and ice water (30 mL each), stirred, allowed to stand, and separated. The organic phase was washed with water and saturated saline (30 mL each), dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 440 mg of an oily product. 1HNMR (400MHz, CDCl3): δ ppm 7.33(m, 2H), 7.21(dd, J=8.2, 2.0 Hz, 1H), 7.11(d, J=7.6 Hz, 1H), 6.95(dd, J=7.6, 1.1 Hz, 1H), 6.84(s, 1H), 6.66(dd, J=11.1, 2.1 Hz, 1H), 5.24(m, 1H), 3.20(br, 4H), 2.93(m, 2H), 2.82(m, 2H), 2.77(br, 4H), 2.67(m, 4H), 1.41(d, J=6.3 Hz, 6H). ESI-MS (m / z): 496.25 [M+H] + .

[0080] Example 5 Preparation of methyl (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetate [ka] Compound 1-a (200 mg, 1 eq) and DMF (4 mL) were added to a 25 mL reaction flask, protected with nitrogen gas, and the temperature was controlled to <30 ° C. 60% sodium hydrogen (78 mg, 4 eq) was added, stirred at room temperature for 30 min, chloromethyl acetate (212 mg, 4 eq) and sodium iodide (73 mg, 1 eq) were added in sequence, and reacted at room temperature for 2 to 3 h. Water (1 mL) was added to quench and stop the reaction, ethyl acetate was added to dilute (8 mL), and the mixture was washed with water three times (8 mL × 3), and the organic phase was concentrated and purified by column chromatography to obtain an oily product, which was added with isopropyl ether and stirred at room temperature to crystallize, obtaining 115 mg of a white solid with a yield of 49%. 1HNMR (400MHz, CDCl3): δ ppm 7.33(m, 2H), 7.21(dd, J=8.2, 1.8 Hz, 1H), 7.12(m, 1H), 6.95(d, J=7.6 Hz, 1H), 6.91(s, 1H), 6.66(dd, J=11.1, 2.1 Hz, 1H), 5.93(s, 2H), 3.21(br, 4H), 2.93-2.82(m, 4H), 2.78(br, 4H), 2.70(m, 4H), 2.12(s, 3H). ESI-MS (m / z): 482.29 [M+H] + .

[0081] Example 6 Preparation of methyl (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)pentanoate [ka] Compound 1-a (200 mg, 1 eq) and DMF (4 mL) were added to a 25 mL reaction flask, protected with nitrogen gas, and the temperature was controlled to <30 ° C. 60% sodium hydrogen (78 mg, 4 eq) was added, stirred at room temperature for 30 min, n-chloromethyl valerate (294 mg, 4 eq) and sodium iodide (73 mg, 1 eq) were added in sequence, and reacted at room temperature for 2 to 3 h. Water (1 mL) was added to quench and stop the reaction, ethyl acetate was added to dilute (8 mL), and the mixture was washed with water three times (8 mL × 3), and the organic phase was concentrated and purified by column chromatography to obtain an oily product, which was added with isopropyl ether and crystallized by stirring at low temperature to obtain a white solid of 100 mg, 39% yield. 1HNMR (400MHz, CDCl3): δ ppm 7.33(m, 2H), 7.21(dd, J=8.2, 1.9 Hz, 1H), 7.12(m, 1H), 6.95(d, J=7.6 Hz, 1H), 6.89(s, 1H), 6.66(dd, J=11.1, 2.1 Hz, 1H), 5.94(s, 2H), 3.21(br, 4H), 2.94-2.81(m, 4H), 2.77(br, 4H), 2.69(m, 4H), 2.37(t, J=7.5 Hz, 2H), 1.63(m, 2H), 1.35(m, 2H), 0.90(t, J=7.3 Hz, 3H). ESI-MS (m / z): 524.31 [M+H] + .

[0082] Example 7 Preparation of methyl (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)dodecanoate [ka] Step 1: The preparation of compound 3-a can be referred to patent WO2015131856. The raw material 3-a (250 mg, 1 eq) and DMF (5 mL, 20 V) were added to a 25 mL reaction flask, protected with nitrogen gas, and the temperature was controlled to <30 ° C., 60% sodium hydrogen (56 mg, 1.5 eq) was added, and the mixture was stirred at room temperature for 30 min, and chloromethyl dodecanoate (347 mg, 1.5 eq) and sodium iodide (140 mg, 1 eq) were added in sequence, and the mixture was reacted at room temperature for 2 to 3 h. The reaction was quenched by adding water (1 mL) to stop the reaction, and the reaction solution was diluted with ethyl acetate (10 mL), washed with water three times (10 mL × 3), and the organic phase was concentrated and purified by column chromatography (PE / EA = 30 / 1 ~ 20 / 1), and 300 mg of oil (intermediate 3-b) was obtained in a yield of 67%. Step 2: 3-c (161 mg, 1 eq), 3-b (300 mg, 1.2 eq), sodium bicarbonate (218 mg, 5 eq), sodium iodide (78 mg, 1 eq) and DMF (3.2 mL, 20 V) were added to a 25 mL reaction flask, protected with nitrogen gas, and reacted at 85 ° C for 2 h. The reaction solution was diluted with dichloromethane (6.4 mL), washed with water (6.4 mL × 4), concentrated, and purified by column chromatography (PE / EA = 5 / 1 ~ 2 / 1) to obtain the title compound (white solid 200 mg, yield 62%).

[0083] Example 8 Preparation of methyl (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)decanoate [ka] With reference to the above Examples, the title compound (yield 52%, white solid) was produced using compound 1-a and chloromethyl decacarboxylate as raw materials. 1 HNMR (400MHz, CDCl3): δ ppm 7.33(m, 2H), 7.21(dd, J=8.2, 1.8 Hz, 1H), 7.11(d, J=7.6 Hz,1H), 6.94(d, J=7.6 Hz, 1H), 6.90(s, 1H), 6.66(dd, J=11.1, 2.0 Hz, 1H), 5.94(s, 2H), 3.21(br, 4H), 2.91(m, 2H), 2.85(m, 2H), 2.77(br, 4H), 2.69(m, 4H), 2.35(t, J=7.6 Hz, 2H), 1.64(m, 2H), 1.25(br, 12H), 0.85(t, J=6.8 Hz, 3H). ESI-MS (m / z): 594.43 [M+H] + .

[0084] Example 9 Preparation of methyl (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)palmitate [ka] With reference to the above Examples, the title compound (yield 38%, white solid) was produced using compound 1-a and chloromethyl hexadecanoate as raw materials. 1 HNMR (400MHz, CDCl3): δ ppm 7.33(m, 2H), 7.21(dd, J=8.2, 1.9 Hz, 1H), 7.12(m, 1H), 6.95(d, J=7.6 Hz, 1H), 6.89(s, 1H), 6.66(dd, J=11.1, 2.1 Hz, 1H), 5.94(s, 2H), 3.21(br, 4H), 2.90(m, 2H), 2.85(m, 2H), 2.77(br, 4H), 2.69(m, 4H), 2.36(t, J=7.5 Hz, 2H), 1.63(m, 2H), 1.25(br, 24H), 0.87(t, J=7.3 Hz, 3H). ESI-MS (m / z): 678.51 [M+H] + .

[0085] Example 10 Preparation of methyl (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)docosanoate [ka] Docosanoic acid (1.0 g, 1.5 eq) was taken, thionyl chloride (10 mL) was added, a small amount of DMF was added to catalyze, and the mixture was refluxed for 3 hours, after which the reaction was completed as detected by TLC, and the mixture was concentrated under reduced pressure to give docosanoic acid chloride. Separate the reaction flask, add compound 1 (220 mg, 1.0 eq), add dichloromethane (5 mL), triethylamine (150 mg, 3 eq), then add the newly prepared docosanoic acid chloride to the reaction system and react with stirring for 15 min. Add water to quench the reaction, separate the liquid, and keep the organic phase, concentrate under reduced pressure, and purify by chromatography to obtain 127 mg of off-white solid compound 74. 1 HNMR (400MHz, CDCl3): δ ppm 7.67(m, 1H), 7.50(m,1H), 7.36(m, 1H), 7.16(d, J=8.0 Hz, 1H), 7.10-6.97(m, 2H), 6.75(m, 1H), 5.86(s, 2H), 3.10(m, 4H), 2.86-2.60(m, 12H), 2.32(t, J=8.0 Hz, 2H), 1.51(m, 2H), 1.22-1.17(m, 36H), 0.84(t, t, J=8.0 Hz, 3H). ESI-MS (m / z): 763.41 [M+H] + .

[0086] Example 11 Preparation of methyl (7-(2-(4-(6-fluorobenzothiophen-4-yl)piperazin-1-yl)ethyl)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)heptadecanoate [ka] Heptacosanoic acid (0.3 g, 1.5 eq) was taken, thionyl chloride (3 mL) was added, a small amount of DMF was added to catalyze the reaction, refluxed for 2 hours, the reaction was completed as detected by TLC, and concentrated under reduced pressure to give heptacosanoyl chloride. Compound 1 (150 mg, 1.0 eq) was added to the reaction flask, followed by dichloromethane (3 mL) and triethylamine (100 mg, 3 eq). The newly prepared heptacosanoyl chloride was then added to the reaction system and stirred for 15 min to react. Water was added to quench the reaction, and the liquids were separated. The organic phase was retained, concentrated under reduced pressure, and purified by chromatography to obtain 167 mg of compound 76, an off-white solid. 1 HNMR (400MHz, CDCl3): δ ppm 7.35-7.32(m, 2H), 7.24-7.21(m,1H), 7.12(d, J=8.0 Hz, 1H), 6.95(d, J=8.0 Hz, 1H), 6.90(s,1H), 6.69-6.65(m, 1H), 5.95(s, 2H), 3.20(m, 4H), 2.92-2.70(m, 12H), 2.36(t, J=16 Hz, 2H), 1.66-1.61(m, 2H), 1.28-1.22(m, 48H), 0.88(t, t, J=12.0 Hz, 3H). ESI-MS (m / z): 833.21 [M+H] + .

[0087] The compounds shown in the following table were prepared using methods similar to those in the above examples, except for using starting materials and intermediates corresponding to the final products. [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6]

Table 2-7

Table 2-8

Table 2-9

Table 2-10

Table 2-11

Table 2-12

Table 2-13

Table 2-14

Table 2-15

Table 2-16

Table 2-17

Table 2-18

Table 2-19

Table 2-20

Table 2-21

Table 2-22

Table 2-23

[0088] 1) 5-HT 1A Measurement of receptor agonist activity Human Recombinant 5-HT 1A 5-HT receptor expressing HEK293 cells 1A The agonist effect of a compound on the receptor was measured using the LANCE TM cAMP 384 Kit (PerkinElmer, USA) was used to measure the inhibitory effect of the compound on cAMP production in HEK293 cells. 1A The receptor agonist effect was evaluated. The cAMP concentration was measured according to the method in the kit's instruction manual, and the compound concentrations were 0.0128 nM to 1000 nM. 8-OH-DPAT was used as a positive control. The specific procedure is as follows: a) Compounds were added to assay plates (384-well plates) using an Echo 550, the final concentration of DMSO was <1%, and cells were harvested using Stimulation Buffer (HBSS + 5 mM HEPES + 0.5 mM IBMX + 0.1% BSA). b) Transfer 10 μL of the prepared cell solution to the assay plate containing the compounds. c) Centrifuge at 600 rpm for 3 minutes and incubate at room temperature for 1 hour; d) 5 μL of 4X Eu-cAMP tracer solution and 5 μL of 4X ULight TM -Anti-cAMP solution was added, centrifuged at 600 rpm for 3 minutes, and incubated at room temperature for 1 hour. e) Data were read using EnVision and analyzed using Graphpad Prism software. 50 was calculated and the results are shown in Table 1.

[0089] 2) D 2L Measurement of receptor antagonist activity Human recombinant D 2L D expressing receptor CHO cells 2L The antagonistic effect of the compound on the receptor was measured using LANCE® Ultra cAMP Kit (a product of PerkinElmer, USA). The antagonistic effect of the compound on the D2 receptor was evaluated by measuring the inhibitory effect of the compound on the dopamine antagonistic production of cAMP in CHO cells. The cAMP concentration was measured according to the method in the kit's instruction manual, the starting concentration of the compound was 1000 nM, and it was diluted 5 times. Amisulpride was used as a positive control. The specific procedure is as follows: a) Prepare 1× Stimulation Buffer according to the kit instructions and prepare for use. b) The positive compounds and compounds to be measured were diluted in DMSO to 10 concentrations, and then the positive compounds and DMSO were diluted to 10x with 1x Stimulation Buffer. c)D 2L -CHO cells were trypsinized, the medium was removed after centrifugation, the cells were resuspended in 1×Stimulation Buffer, and after cell counting, the cells were inoculated into 384-well plates, the inoculation density was 3000 cells / well / 5 μL; d) Add 1 μL of the compound diluted in step b) to the corresponding experimental wells (compounds are 10x, 10 concentrations, 2 replicates), among which, add 1 μL of the positive compound at 10x initial concentration to the PC wells, add 1 μL of 10x DMSO buffer (2%) to the VC wells, and incubate at 37°C for 20 min after centrifugation; e) Take 4 μL of 10 μM Forskolin & 25 nM Dopamine solution and dilute it. 2L The receptor inhibitor was added to the experimental wells, centrifuged, and incubated at 37°C for 30 min to induce cAMP production. f) Dilute Eu-cAMP to the working concentration with Detection buffer, and add 5 μL / well to the corresponding experimental wells. g) ULight TM - Anti-cAMP was diluted to the working concentration with Detection buffer, and 5 μL / well was added to the corresponding experimental wells. After centrifugation, the mixture was incubated at room temperature for 1 h. h) After the incubation was completed, the readings at 665 nm and 620 nm were detected. The inhibition rate of the compounds at different concentrations was calculated and the IC 50 was calculated by Graphpad Prism software and the results are shown in Table 1.

[0090] 3) 5-HT 2A Measurement of receptor antagonist activity Human Recombinant 5-HT 2A 5-HT receptor expressing CHO cells 2A The antagonistic effect of the compound on the receptor was measured using IP-One-Gq kit (a product of Cisbio). The measurement was performed according to the method in the kit's instruction manual, the starting concentration of the compound was 5000 nM, and it was diluted 5 times, and risperidone was used as a positive control. The measurement method is as follows: a) 5-HT 2A -CHO cells were trypsinized, the medium was removed after centrifugation, the cells were resuspended in F12 + 10% Dialyzed FBS medium, the cells were inoculated into 384-well plates after cell counting, the inoculation density was 7000 cells / well / 25 μL, and the wells were placed in an incubator after centrifugation and incubated for about 18 to 20 hours. b) Prepare 1× Stimulation Buffer according to the kit instructions and prepare for use. c) The positive compounds and compounds to be measured were diluted in DMSO to a concentration of 10, and then the compounds were diluted to 10x with 1x Stimulation Buffer, and mixed uniformly by shaking to prepare for use. d) Remove the cell plate, invert and centrifuge to discard the medium, then add 9.1 μL of 1× Stimulation Buffer to each experimental well; e) 1.4 μL of the 10× compound diluted in step c) was taken and added to the corresponding experimental wells (compounds were 10×, 10 concentrations, 2 replicates), among which 1.4 μL of the positive compound at 10× initial concentration was added to the PC wells, and 1.4 μL of 10× DMSO buffer (1%) was added to the VC wells, and after centrifugation, incubated at 37°C for 10 min; f) Prepare 160 nM Serotonin solution using 1 × Stimulation Buffer, add 3.5 μL to each experimental well, centrifuge, and incubate at 37 ° C for 60 min. g) Dilute d2-IP1 and Anti-IP1-Cryptate to working concentrations using Lysis & Detection Buffer. h) After incubation is complete, add 3 μL of d2-IP1 to all experimental wells; i) Next, 3 μL of Anti-IP1-Cryptate was added to all experimental wells, centrifuged, and then allowed to stand at room temperature for 1 h. j) After the incubation was completed, readings were taken at 665 nm and 620 nm.

[0091] Calculate the inhibition rate of the compound at different concentrations and calculate the IC 50 was calculated by Graphpad Prism software and the results are shown in Table 1. [Table 3]

[0092] 4) Measurement of 5-HT transporter (SERT) inhibitory activity The transporter inhibitory effect of the compound on HEK-293 cells expressing human SERT was evaluated using a Neurotransmitter Transporter Uptake Assay Kit (Molecular Devices). The measurement was performed according to the method in the kit's instruction manual, and citalopram was used as a positive control. The specific procedure is as follows: a) HEK-hSERT cells were seeded at 20,000 cells / well in a 384-well plate, then transferred to an incubator and incubated at 37°C overnight. b) The next day, citalopram was transferred to a 384-well plate using 0.1% BSA solution, and the final concentrations of citalopram were 2 μM, 0.5 μM, 0.125 μM, 30 nM, 10 nM, 3 nM, 1 nM, 0.3 nM, 0.1 nM, and 0.03 nM. The starting concentration of the compounds to be measured was 10 μM, diluted 3×, and each concentration was repeated twice. c) remove the 384-well plate from the incubator, aspirate the medium from the wells, add 25 μL / well of compound solution to be measured, incubate at 37° C. for 30 min, add 25 μL of fluorescent dye detection solution per well, and incubate at 37° C. for 30 min; d) Fluorescence values ​​were read on a Flexstation3 and the data was analyzed using Graphpad Prism software, the results of which are shown in Table 2. [Table 4]

[0093] 5) Dopamine D3 receptor agonist effect The D3 receptor agonist activity of the compounds was evaluated on CHO cells expressing human D3 receptors by measuring the effect of the compounds on cAMP regulation using HTRF detection method.

[0094] Experimental protocol: Cells were suspended in HBSS buffer containing 20 mM Hepes / NaOH (pH 7.4), 70 mM NaCl, 5.33 mM KCl, 1.25 mM CaCl2, 0.5 mM MgCl2, 0.41 mM MgSO4, 0.441 mM KH2PO4, 0.3 mM Na2HPO4, 0.1% glucose, 0.1% BSA and 500 μM IBMX. Cells were then incubated with HBSS (basal control), 300 nM dopamine (stimulated control) or different concentrations of dopamine (EC 50 In the presence of either the compound to be measured or the compound to be measured, 4The cells were distributed in a microplate at a density of 1000 cells / well. The adenylate cyclase activator NKH477 was then added at a final concentration of 1.5 μM. After 30 min of incubation at 37°C, the cells were lysed and the fluorescent acceptor (D2-labelled cAMP) and fluorescent donor (Europium-labelled anti-cAMP antibody) were added. After 60 min of incubation at room temperature, the fluorescence transfer was measured at em=337 nm and em=620 and 665 nm using a microplate reader (Envision, Perkin Elmer). The cAMP concentration was determined by dividing the signal measured at em=665 nm by the signal measured at em=620 nm (ratio). The data was analysed using Graphpad Prism software and the results are shown in Table 3. [Table 5]

[0095] 6) Measurement of hERG potassium channel activity hERG potassium channel blockade experiments were performed using a fully automated patch clamp technique (QPatch HTX The assay was completed using a 50-mL PBS (Sophion, Stockholm, Sweden). The cell line was CHO cells stably expressing the hERG potassium channel. The highest measured concentration of the compounds was 20 μM and was diluted 3-fold (n=3). The DMSO content in the final measured concentrations did not exceed 0.2%. The data was analyzed using Graphpad Prism software and the results are shown in Table 4. [Table 6]

[0096] As can be seen from the results in Tables 1 to 4 above, Compound 1-a and Compound 1 have the D2 receptor antagonism / 5-HT 1A Receptor agonist / 5-HT 2ACompound 1 has similar receptor antagonist activity and inhibits the 5-HT transporter, and is expected to improve comorbidities such as anxiety and depression in schizophrenia relatively well. Compound 1 has dopamine D3 receptor agonist activity and is expected to have better therapeutic effects on psychiatric and neurological disorders and lower extrapyramidal side effects than compound 1-a. Compound 1 has lower hERG inhibitory activity than compound 1-a, and is expected to reduce the risk of hERG-related cardiotoxicity and have higher clinical safety.

[0097] 7) Human liver microsome experiments Preparation of magnesium potassium buffer: 100 mM potassium buffer was preheated with 5 mM MgCl2 to form magnesium potassium buffer with pH=7.41. Preparation of 0.5 mM working solution: 10 mM compound stock solution was added to 95 μL acetonitrile. Preparation of 1.5 μM microsome (0.75 mg / mL) containing working solution: 1.5 μL of the above 0.5 mM working solution was taken and added to 479.75 μL of magnesium potassium buffer along with 18.75 μL of 20 mg / mL human liver microsome solution. Preparation of NADPH stock solution (6 mM, 5 mg / mL): NADPH was dissolved in potassium magnesium buffer. 30 μL of 1.5 μM working solution containing 0.75 mg / mL human liver microsome was added to a 96-well plate in order and pre-incubated at 37 °C for 5 min. For the 0 min sample, 150 μL of acetonitrile solution containing the internal standard was added, followed by 15 μL of NADPH stock solution (6 mM) to start the reaction. For the other samples, 15 μL of NADPH stock solution was added directly to start the reaction (6 mM). Final content of each component: compound (1 μM), human liver microsomes (0.5 mg / mL), NADPH (2 mM). At 5 min, 15 min, 30 min, and 45 min, 150 μL of stop solution containing the internal standard was added to stop the sample reaction, centrifuged at 600 rpm for 10 min and 6000 rpm for 15 min, and the supernatant was taken for LC-MS / MS analysis.

[0098] Using Excel software, incubation time was plotted against the ln fraction of drug remaining in the incubation system, and linear regression was performed to obtain the slope k, and the half-life T 1 / 2 (min) and intrinsic clearance CL int (mL / min / kg) values ​​were calculated according to the following formula:

number

number

[0099] The experimental results are shown in Table 5 below: [Table 7]

[0100] The above data indicate that Compound 3, Compound 7 and Compound 8 have good metabolic stability in human liver microsomes.

[0101] 8) Oil solubility experiment The solubility was measured by quantitative analysis using the external standard method of high performance liquid chromatography.

[0102] Equipment information: [Table 8]

[0103] Chromatography conditions: [Table 9]

[0104] Preparation of solutions: Control solution: 10 mg of the control was weighed and placed in a 20 mL measuring flask, diluted to the mark with 80% acetonitrile, and shaken to obtain a uniform solution.

[0105] Test solution: An appropriate amount of sample was taken and dissolved in benzyl benzoate to form a saturated solution. It was placed in a shaker and shaken at 25°C and 800 rpm for 2 hours. The sample was filtered, and 100 μL of the filtrate was taken and placed in a 10 mL measuring flask, diluted to the mark with 80% acetonitrile, and shaken to obtain a homogeneous solution.

[0106] The solubility measurements are shown in Table 6: [Table 10]

[0107] As can be seen from the above table, the compounds of the examples of the present invention have better solubility in the oily medium benzyl benzoate than compound 1-a, and their good lipid solubility makes them more suitable for the preparation of long-acting formulations.

[0108] 9) Pharmacokinetics in rats Pharmacokinetic experiments were conducted in rats for compounds 2, 3, 5, 6, 7, and 8 (non-fasted SD male rats, intramuscular administration, dose 43.3 mmol / kg, n=3). The solvent was benzyl benzoate, the injection site was the hind leg thigh muscle, and approximately 0.3 mL of blood samples were collected from the rat jugular vein at blood collection points day 0.25, day 2, day 4, day 6, day 8, day 15, day 22, day 29, and day 36. The collected blood was stored under ice-cooled conditions, and the plasma was quickly separated by centrifugation, a precipitant was added, and the concentration of compound 1 (active metabolite) was quantitatively detected by LCMS. The time-active metabolite concentration graphs after administration of each compound are shown in Figures 1 and 2.

[0109] As can be seen from the experimental results, the compounds of the examples of the present invention (except compound 1) can gradually release the active metabolite (compound 1) in rats after intramuscular administration, reducing the fluctuation of blood concentration and improving the safety and tolerance of the drug. In particular, the fluctuation of the blood concentration of the active metabolite after administration of compound 3 and compound 8 was minimal.

Claims

1. An N-substituted quinolinone compound represented by general formula (I) or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotope-labeled product or prodrug thereof, 【Chemistry 1】 Among them, R ６ , R ７ , R ８ and R ９ are each independently hydrogen, deuterium, a halogen, a methyl group, an ethyl group, a hydroxyl group, an amino group, or an acetamide group; 【Chemistry 2】 represents a single bond or a double bond, 【Chemistry 3】 is a double bond, R ６ and R ７ does not exist and R ８ and R ９ One of them does not exist, R １ is -Y １ -OC(=O)-R ２ , -Y １ -OC(=O)-OR ３ , -Y １ -O-R ４ Or -C(=O)-R ５ and Y １ are each independently a C1 to C6 alkylene group, R ２ is a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a C2-C30 alkenyl group, an amino C1-C30 alkyl group, an amino group substituted with a C1-C30 alkyl group, an amino group substituted with a C2-C30 alkenyl group, an amino group substituted with a halogenated C1-C30 alkyl group, an amino group substituted with a phenyl C1-C30 alkyl group, an amino group substituted with a hydroxy C1-C30 alkyl group, an amino group substituted with a C3-C10 cycloalkyl group, a C3-C10 cycloalkenyl group, an amino group substituted with a C1-C6 alkyl group, a C3-C10 cycloalkyl group, a 5-10 membered heterocyclyl group, a C6-C12 aryl group, a C6-C12 aryl C1-C30 alkyl group, a C1-C30 alkoxycarbonyl C1-C30 alkyl group, a C1-C30 alkoxy C1-C30 alkyl group, a C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkyl group, or a C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkyl group; R ３ is a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a phenyl group, a phenyl C1-C30 alkyl group, or a C3-C10 cycloalkyl group, R ４ is hydrogen, a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a phenyl C1-C30 alkyl group, or a phenyl C1-C30 alkoxy C1-C30 alkyl group; R ５ is a C1-C30 alkyl group, a C2-C30 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C30 alkyl group, a hydroxy C1-C30 alkyl group, a C3-C10 cycloalkyl group, a C1-C30 alkoxy group, a phenyloxy group, a phenyl C1-C30 alkoxy group, a C1-C30 alkoxy C1-C30 alkoxy group, an amino C1-C30 alkyl group, an amino group substituted with a C1-C30 alkyl group, an amino group substituted with a hydroxy C1-C30 alkyl group, an amino group substituted with a phenyl C1-C30 alkyl group, a C3-C10 cycloalkoxy group, a C1-C30 alkanoyloxy C1-C6 alkoxy group, a C1-C30 alkoxy C1-C30 alkyl group, a C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkyl group, or a C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkoxy C1-C30 alkyl group; An N-substituted quinolinone compound, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product, or prodrug thereof.

2. In the general formula (I), R １ is -Y １ -OC(=O)-R ２ , -Y １ -OC(=O)-OR ３ , -Y1-O-R ４ Or -C(=O)-R ５ and preferably -Y １ -OC(=O)-R ２ and Y １ are each independently a C1 to C4 alkylene group, preferably -CH ２ - or -CH(CH ３ )- and / or R ２ is a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a C2-C30 alkenyl group, an amino C1-C16 alkyl group, an amino group substituted with a C1-C16 alkyl group, an amino group substituted with a C2-C16 alkenyl group, an amino group substituted with a halogenated C1-C16 alkyl group, an amino group substituted with a phenyl C1-C16 alkyl group, an amino group substituted with a hydroxy C1-C16 alkyl group, an amino group substituted with a C3-C10 cycloalkyl group, a C3-C10 cycloalkyl group, a C3-C10 cycloalkyl group, a C1-C16 ... an amino group substituted with a 1-C6 alkyl group, a C3-C10 cycloalkyl group, a 5-10 membered heterocyclyl group, a C6-C12 aryl group, a C6-C12 aryl C1-C16 alkyl group, a C1-C16 alkoxycarbonyl C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, or a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, preferably R ２ is a C1-C30 alkyl group, a halogenated C1-C30 alkyl group, a C2-C30 alkenyl group, an amino C1-C12 alkyl group, an amino group substituted with a C1-C12 alkyl group, an amino group substituted with a C2-C12 alkenyl group, an amino group substituted with a halogenated C2-C12 alkyl group, an amino group substituted with a phenyl C1-C12 alkyl group, an amino group substituted with a hydroxy C1-C12 alkyl group, an amino group substituted with a C3-C7 cycloalkyl group, a C3-C7 cycloalkyl C1 an amino group substituted with a C1-C4 alkyl group, a C3-C7 cycloalkyl group, a 5- to 10-membered heterocyclyl group, a C6-C12 aryl group, a C6-C12 aryl C1-C12 alkyl group, a C1-C12 alkoxycarbonyl C1-C12 alkyl group, a C1-C12 alkoxy C1-C12 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, preferably R ２ is a C1 to C30 alkyl group (for example, a C1 to C30 straight chain alkyl group, an isopropyl group, a tert-butyl group, a 1-methylpropyl group, a 3-methylbutyl group, a 1-methylbutyl group, a 1,1-dimethylpentyl group, a 1-methylpentyl group, a 1-methylhexyl group, a 1-pentylhexyl group, etc.), a halogenated C1 to C30 alkyl group (for example, a halogenated C1 to C16 alkyl group, a halogenated C1 to C12 alkyl group, a halogenated C1 to C6 alkyl group, or further, for example, a 3,3,3-trifluoropropyl group), a C2 to C30 alkenyl group (for example, a C2 to C20 alkenyl group), an amino C1 to C6 alkyl group (for example, NH ２ -methyl group), an amino group substituted with a C1 to C12 alkyl group (e.g., decyl-NH-, heptyl-NH-), an amino group substituted with a C2 to C6 alkenyl group (e.g., 2-allyl-NH-), an amino group substituted with a halogenated C1 to C6 alkyl group (e.g., 3,3,3-trifluoropropyl-NH-), an amino group substituted with a phenyl C1 to C6 alkyl group (e.g., benzyl-NH-), an amino group substituted with a hydroxy C1 to C6 alkyl group (e.g., hydroxyethyl-NH-), an amino group substituted with a C3 to C7 cycloalkyl group (e.g., C3 to C7 cycloalkyl-NH-), an amino group substituted with a C3 to C7 cycloalkyl C1 to C6 alkyl group (e.g., C3 to C7 cycloalkylmethyl-NH-), a C3 to C7 cycloalkyl group , a 5- to 10-membered heterocyclyl group (e.g., a pyridyl group, a piperidinyl group, a 4-tetrahydropyranyl group, a morpholinyl group, a furyl group, a thienyl group, a pyrimidine group, a quinolyl group, etc.), a phenyl group, a naphthyl group, a phenyl C1-C6 alkyl group (e.g., a benzyl group), a C1-C6 alkoxycarbonyl C1-C6 alkyl group (e.g., a tert-butoxycarbonylmethyl group), a C1-C6 alkoxy C1-C6 alkyl group (e.g., a methoxymethyl group), a C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (e.g., a methoxyethoxymethyl group, a butoxyethoxymethyl group) or a C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (e.g., a methoxyethoxyethoxymethyl group), and / or R ３ is a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl group, a phenyl C1-C16 alkyl group, or a C3-C10 cycloalkyl group, preferably R ３ is a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a phenyl group, a phenyl C1-C12 alkyl group, or a C3-C7 cycloalkyl group (e.g., a cyclohexyl group), more preferably R ３ is a C1-C6 alkyl group, a halogenated C1-C6 alkyl group (e.g., 2,2,2-trifluoroethyl group), a phenyl group, a phenyl C1-C6 alkyl group (e.g., benzyl group) or a C3-C7 cycloalkyl group (e.g., cyclohexyl group), and / or R ４ is hydrogen, a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl C1-C16 alkyl group, or a phenyl C1-C16 alkoxy C1-C16 alkyl group, preferably R ４ is hydrogen, a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a phenyl C1-C12 alkyl group or a phenyl C1-C12 alkoxy C1-C12 alkyl group, more preferably R ４ is hydrogen, a C1-C6 alkyl group (e.g., an isopropyl group), a halogenated C1-C6 alkyl group (e.g., a 2,2,2-trifluoroethyl group), a phenyl C1-C6 alkyl group (e.g., a benzyl group) or a phenyl C1-C6 alkoxy C1-C6 alkyl group (e.g., a benzyloxymethyl group), and / or R ５ is a C1-C16 alkyl group, a C2-C16 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C16 alkyl group, a hydroxy C1-C16 alkyl group, a C3-C10 cycloalkyl group, a C1-C16 alkoxy group, a phenyloxy group, a phenyl C1-C16 alkoxy group, a C1-C16 alkoxy C1-C16 alkoxy group, an amino C1-C16 alkyl group, an amino group substituted with a C1-C16 alkyl group, an amino group substituted with a hydroxy C1-C16 alkyl group, an amino group substituted with a phenyl C1-C16 alkyl group, a C3-C10 cycloalkoxy group, a C1-C16 alkanoyloxy C1-C6 alkoxy group, a C1-C16 alkoxy C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, or a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, preferably R ５ is a C1-C12 alkyl group, a C2-C12 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C12 alkyl group, a hydroxy C1-C12 alkyl group, a C3-C10 cycloalkyl group, a C1-C12 alkoxy group, a phenyloxy group, a phenyl C1-C12 alkoxy group, a C1-C12 alkyloxy C1-C12 alkoxy group, an amino C1-C12 alkyl group, an amino group substituted with a C1-C12 alkyl group, a hydroxy C1-C1 an amino group substituted with a phenyl C1-C12 alkyl group, an amino group substituted with a phenyl C1-C12 alkyl group, a C3-C10 cycloalkoxy group, a C1-C12 alkanoyloxy C1-C6 alkoxy group, a C1-C12 alkoxy C1-C12 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, more preferably R ５ is a C1-C6 alkyl group (e.g., methyl, ethyl, propyl, etc.), a C2-C16 alkenyl group (e.g., decenyl), a morpholinyl group, a phenyl group, a phenyl C1-C6 alkyl group, a hydroxy C1-C6 alkyl group, a C3-C10 cycloalkyl group (e.g., cyclopentyl, cyclohexyl), a C1-C6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, etc.), a phenoxy group, a phenyl C1-C6 alkoxy group, a C1-C6 alkoxy C1-C6 alkoxy group (e.g., methoxyethoxy), an amino C1-C6 alkyl group (NH ２ -methyl group), an amino group substituted with a C1-C6 alkyl group (e.g., a propylamino group), an amino group substituted with a hydroxy C1-C6 alkyl group (e.g., a hydroxyethyl-NH-), an amino group substituted with a phenyl C1-C6 alkyl group (e.g., a benzyl-NH-), a C1-C16 alkanoyloxy C1-C6 alkoxy group (decanoyloxymethoxy group), a C1-C6 alkoxy C1-C6 alkyl group (e.g., a methoxymethyl group), a C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (e.g., a methoxyethoxymethyl group, a methoxyethoxymethyl group), or a C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl group (e.g., a methoxyethoxyethoxymethyl group); 2. The N-substituted quinolinone compound according to claim 1, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotope-labeled product, or prodrug thereof.

3. In the general formula (I), R ６ , R ７ , R ８ and R ９ are each independently hydrogen, deuterium, a halogen, a methyl group, an ethyl group, a hydroxyl group, an amino group, or an acetamide group; 【Chemistry 4】 represents a single bond or a double bond, 【Chemistry 5】 is a double bond, R ６ and R ７ does not exist and R ８ and R ９ One of them does not exist, R １ is -Y １ -OC(=O)-R ２ , -Y １ -OC(=O)-OR ３ , -Y １ -O-R ４ Or -C(=O)-R ５ and Y １ is a C1-C6 alkylene group, R ２ is a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a C2-C16 alkenyl group, an amino C1-C16 alkyl group, an amino group substituted with a C1-C16 alkyl group, an amino group substituted with a C2-C16 alkenyl group, an amino group substituted with a halogenated C1-C16 alkyl group, an amino group substituted with a phenyl C1-C16 alkyl group, an amino group substituted with a hydroxy C1-C16 alkyl group, an amino group substituted with a C3-C10 cycloalkyl group, a C3-C10 cycloalkenyl group, an amino group substituted with alkyl C1-C6 alkyl group, a C3-C10 cycloalkyl group, a 5-10 membered heterocyclyl group, a C6-C12 aryl group, a C6-C12 aryl C1-C16 alkyl group, a C1-C16 alkoxycarbonyl C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, or a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group; R ３ is a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl group, a phenyl C1-C16 alkyl group, or a C3-C10 cycloalkyl group, R ４ is hydrogen, a C1-C16 alkyl group, a halogenated C1-C16 alkyl group, a phenyl C1-C16 alkyl group or a phenyl C1-C16 alkoxy C1-C16 alkyl group, R ５ is a C1-C16 alkyl group, a C2-C16 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C16 alkyl group, a hydroxy C1-C16 alkyl group, a C3-C10 cycloalkyl group, a C1-C16 alkoxy group, a phenyl C1-C16 alkoxy group, a C1-C16 alkoxy C1-C16 alkoxy group, an amino C1-C16 alkyl group, an amino group substituted with a C1-C16 alkyl group, an amino group substituted with a hydroxy C1-C16 alkyl group, an amino group substituted with a phenyl C1-C16 alkyl group, a C3-C10 cycloalkoxy group, a C1-C16 alkoxy C1-C16 alkyl group, a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, or a C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkoxy C1-C16 alkyl group, 2. The N-substituted quinolinone compound according to claim 1, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotope-labeled product, or prodrug thereof.

4. Represented by the following general formula (I-1) or (I-2): 【Chemistry 6】 Among them, R １ , R ６ , R ７ , R ８ and R ９ have the definition given in the respective claim, 4. The N-substituted quinolinone compound according to claim 1, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotope-labeled product, or prodrug thereof.

5. R １ is -Y １ -OC(=O)-R ２ Or -Y １ -OC(=O)-OR ３ and preferably -Y １ -OC(=O)-R ２ and Y １ is a C1 to C4 alkylene group, preferably -CH ２ - or -CH(CH ３ ) - and R ２ is a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a C2-C12 alkenyl group, an amino C1-C12 alkyl group, an amino group substituted with a C1-C12 alkyl group, an amino group substituted with a C2-C12 alkenyl group, an amino group substituted with a halogenated C1-C12 alkyl group, an amino group substituted with a phenyl C1-C12 alkyl group, an amino group substituted with a hydroxy C1-C12 alkyl group, an amino group substituted with a C3-C6 cycloalkyl group, an amino group substituted with a C3-C6 cycloalkyl C1-C4 alkyl group, a C3-C6 cycloalkyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a furyl group, a thienyl group, a pyrimidine group, a quinolyl group, a phenyl group, a furyl group, a quinolyl group, a phenyl group, a cycloalkyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a furyl group, a thienyl group, a pyrimidine ... cycloalkyl group, a pyridyl group, a cycloalkyl group, a pyridyl group, a cycloalkyl group, a pyridyl group, a cycloalkyl group, a pyridyl group, a cycloalkyl group, a pyridyl group, a cycloalkyl group, a pyridyl group, a cycloalkyl group, a cycloalkyl group, a pyridyl group, a cycloalkyl group, a cycloalkyl group, a cycloalkyl group, a cycloalkyl group, a cycloalkyl group, a cycloalkyl group, a cycloalkyl group and preferably a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a C3-C6 cycloalkyl group, a phenyl group, a phenyl C1-C12 alkyl group, a C1-C12 alkoxycarbonyl C1-C12 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, R ３ is a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a phenyl group, a phenyl C1-C12 alkyl group, or a C3-C6 cycloalkyl group, preferably a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a phenyl group, or a C3-C6 cycloalkyl group; 5. The N-substituted quinolinone compound according to claim 1, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotope-labeled product, or prodrug thereof.

6. R １ is -Y １ -OC(=O)-R ２ and Y １ is a C1 to C4 alkylene group, preferably -CH ２ - or -CH(CH ３ ) - and R ２ is a C3-C16 alkyl group, a halogenated C3-C16 alkyl group, a C3-C16 alkenyl group, an amino C3-C16 alkyl group, an amino group substituted with a C3-C16 alkyl group, an amino group substituted with a C3-C16 alkenyl group, an amino group substituted with a halogenated C3-C16 alkyl group, an amino group substituted with a phenyl C3-C16 alkyl group, an amino group substituted with a hydroxy C3-C16 alkyl group, an amino group substituted with a C3-C6 cycloalkyl group, an amino group substituted with a C3-C6 cycloalkyl C3-C16 alkyl group, a C3-C6 cycloalkyl group, a pyridyl group, a piperidinyl group, a morpholinyl group, a furyl group, a thienyl group, a pyrimidine group, a quinolyl group, a phenyl group, a phenyl C3-C16 alkyl group, a C1-C12 alkoxycarbonyl C3-C16 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C3-C16 alkyl group, or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C3-C16 alkyl group, preferably a C3-C16 alkyl group, a halogenated C3-C16 alkyl group, a C3-C6 cycloalkyl group, a phenyl group, a phenyl C3-C16 alkyl group, a C1-C12 alkoxycarbonyl C3-C16 alkyl group, a C1-C12 alkoxy C1-C12 alkoxy C3-C16 alkyl group, or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C3-C16 alkyl group; 5. The N-substituted quinolinone compound according to claim 1, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotope-labeled product, or prodrug thereof.

7. R １ is -Y １ -O-R ４ Or -C(=O)-R ５ and R ４ is hydrogen, a C1-C12 alkyl group, a halogenated C1-C12 alkyl group, a phenyl C1-C12 alkyl group or a phenyl C1-C12 alkoxy C1-C12 alkyl group, preferably hydrogen, a C1-C12 alkyl group, a halogenated C1-C12 alkyl group or a phenyl C1-C12 alkyl group, R ５ is a C1-C12 alkyl group, a C2-C12 alkenyl group, a morpholinyl group, a phenyl group, a phenyl C1-C12 alkyl group, a hydroxy C1-C12 alkyl group, a C3-C6 cycloalkyl group, a C1-C12 alkoxy group, a phenyl C1-C12 alkoxy group, an amino C1-C12 alkyl group, an amino group substituted with a C1-C12 alkyl group, an amino group substituted with a hydroxy C1-C12 alkyl group, an amino group substituted with a phenyl C1-C12 alkyl group, a C3-C6 cycloalkoxy group, a C1-C12 alkoxy C1-C12 alkoxy group, a C1-C12 alkyl group or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group, preferably a C1-C12 alkyl group, a phenyl group, a phenyl C1-C12 alkyl group, a C3-C6 cycloalkyl group, a C1-C12 alkoxy group, a phenyl C1-C12 alkoxy group, a C3-C6 cycloalkoxy group, a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group or a C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkoxy C1-C12 alkyl group; 5. The N-substituted quinolinone compound according to claim 1, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotope-labeled product, or prodrug thereof.

8. R ６ , R ７ , R ８ and R ９ are each independently hydrogen; R １ is -Y １ -OC(=O)-R ２ , -Y １ -OC(=O)-OR ３ , -Y １ -O-R ４ Or -C(=O)-R ５ and Y １ is a C1 to C4 alkylene group, preferably -CH ２ - or -CH(CH ３ ) - and R ２ is a C1 to C16 alkyl group or a phenyl group, R ３ is a C1 to C12 alkyl group, R ４ is hydrogen, R ５ is a C1-C6 alkyl group or a C1-C6 alkoxy group; 5. The N-substituted quinolinone compound according to claim 1, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotope-labeled product, or prodrug thereof.

9. R ６ , R ７ , R ８ and R ９ are each independently hydrogen; R １ is -Y １ -OC(=O)-R ２ and Y １ is a C1 to C4 alkylene group, preferably -CH ２ - or -CH(CH ３ ) - and R ２ is a C1 to C30 alkyl group; 5. The N-substituted quinolinone compound according to claim 1, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotope-labeled product, or prodrug thereof.

10. The following N-substituted quinolinone compound or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product, or prodrug thereof: 【Chemistry 7-1】 【Chemistry 7-2】 【Chemistry 7-3】 【Chemistry 7-4】 【Chemistry 7-5】 【Chemistry 7-6】 【Chemistry 7-7】 【Chemistry 7-8】 That is, An N-substituted quinolinone compound, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product, or prodrug thereof.

11. A method for producing an N-substituted quinolinone compound according to any one of claims 1 to 10, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product, or prodrug thereof, which is any one of methods 1 to 4, comprising the steps of: Method 1: reacting a compound represented by formula (II) or a salt thereof with a compound represented by formula (III) or a salt thereof; 【Chemistry 8】 Among them, 【Chemistry 9】 , R １ , R ６ , R ７ , R ８ and R ９ is as defined in any one of claims 1 to 10, X is a halogen, a C1-C6 alkylsulfonyloxy group, a benzenesulfonyloxy group, or a naphthalenesulfonyloxy group, and the C1-C6 alkylsulfonyloxy group, the benzenesulfonyloxy group, or the naphthalenesulfonyloxy group is optionally substituted with one or more groups selected from a halogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, a nitro group, a hydroxy group, an amino group, and a C1-C6 alkanoyl group; The reaction is carried out in the presence or absence of a solvent, preferably in a solvent in the presence or absence of a base, The reaction temperature is from room temperature to 200° C., and the reaction time is from 1 to 120 hours. Method 2: reacting a compound represented by formula (IV) or a salt thereof with a compound represented by formula (V) or a salt thereof; 【Chemistry 10】 Among them, 【Chemistry 11】 , R １ , R ６ , R ７ , R ８ and R ９ is as defined in any one of claims 1 to 10, X １ is a halogen or a trifluoromethanesulfonyloxy group, Preferably, the reaction is carried out in the presence of a palladium catalyst and a base; The reaction temperature is from room temperature to 200° C., and the reaction time is from 1 to 30 hours. Method 3: Reacting a compound represented by formula (I-a) or a salt thereof with R １ Reacting with X, 【Chemistry 12】 Among them, 【Chemistry 13】 , R １ , R ６ , R ７ , R ８ and R ９ is as defined in any one of claims 1 to 10, X is a halogen, a C1-C6 alkylsulfonyloxy group, a benzenesulfonyloxy group, or a naphthalenesulfonyloxy group, and the C1-C6 alkylsulfonyloxy group, the benzenesulfonyloxy group, or the naphthalenesulfonyloxy group is optionally substituted with one or more groups selected from a halogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, a nitro group, a hydroxy group, an amino group, and a C1-C6 alkanoyl group; The reaction is carried out in the presence or absence of a solvent, preferably in a solvent in the presence or absence of a base, The reaction temperature is from room temperature to 200° C., and the reaction time is from 1 to 120 hours. Method 4: Reacting a compound represented by formula (I-b) or a salt thereof with X-C(=O)-R ２ Or X-O-C(=O)-O-R ３ or X-R ４ and a compound represented by the formula: 【Chemistry 14】 Among them, R １ is -Y １ -OC(=O)-R ２ , -Y １ -OC(=O)-OR ３ Or -Y １ -O-R ４ and 【Chemistry 15】 , R ６ , R ７ , R ８ , R ９ , Y １ , R ２ , R ３ and R ４ is as defined in any one of claims 1 to 10, X is a halogen, preferably bromine, iodine or chlorine; The reaction is carried out in the presence or absence of a solvent, preferably in a solvent in the presence or absence of a base, The reaction temperature is from room temperature to 200°C, and the reaction time is from 1 to 120 hours. method.

12. A pharmaceutical composition comprising an N-substituted quinolinone compound according to any one of claims 1 to 10, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product or prodrug thereof, and at least one pharma- ceutically acceptable vector. Drug compositions.

13. A method for producing the pharmaceutical composition according to claim 12, comprising the step of mixing the N-substituted quinolinone compound according to any one of claims 1 to 10, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product or prodrug thereof, with a pharma- ceutically acceptable vector; method.

14. Use of an N-substituted quinolinone compound according to any one of claims 1 to 10, or a pharma- ceutically acceptable salt, solvate, stereoisomer, geometric isomer, isotopically labeled product or prodrug thereof, or a pharmaceutical composition according to claim 12, in the manufacture of a medicament for preventing and / or treating a central nervous system disease, condition or disorder, comprising: Preferably, said central nervous system disease, condition or disorder is selected from schizophrenia, affective disorder, mental disorder, mood disorder, bipolar I disorder, bipolar II disorder, depression, dysthymic disorder, cyclothymic disorder, panic attack, panic disorder, social anxiety disorder, obsessive-compulsive disorder, impulsive disorder, post-traumatic stress disorder, anxiety disorder, acute stress disorder, hysteria, anorexia nervosa, sleep disorder, adjustment disorder, cognitive disorder, autism, neurotic headache, mania, Parkinson's disease, Huntington's disease, Alzheimer's disease, dementia, memory disorder, hyperactivity disorder, attention-deficit / hyperactivity disorder and tic disorder; More preferably, said schizophrenia is uncontrolled, unmanageable or chronic schizophrenia; More preferably, the depression is endogenous, severe or uncontrolled depression. use.

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