TW201831462A - Dibenzodiazepine derivative - Google Patents

Abstract

The present invention relates to a dibenzodiazepine derivative of formula (1) wherein ring Q1 and ring Q2 are independently selected from optionally-substituted benzene ring and optionally-substituted pyridine ring; R<SP>a</SP> is hydrogen atom, or C1-6 alkyl which may be optionally substituted with the same or different 1 to 3 halogen atoms; n is 0, 1, or 2; m is 1, 2, 3, or 4; and R<SP>b</SP> is, independently when it exists plurally, hydrogen atom, C1-6 alkyl which may be optionally substituted with the same or different 1 to 3 halogen atoms, or a pharmaceutically acceptable salt thereof, which is useful as a medicament for treating and/or preventing a central nervous system disease.

Description

Dibenzodiazepine derivative

The present invention relates to a dibenzodiazepine derivative having dopamine D ₁ receptor antagonism, dopamine D ₂ receptor antagonism and serotonin 5-HT _2A receptor antagonism or a pharmaceutically acceptable salt thereof And a therapeutic agent and/or a preventive agent for a central nervous system disease using the derivative as an active ingredient.

According to reports, the number of patients with schizophrenia in the world is more than 45 million. Schizophrenia is a mental illness with positive symptoms, negative symptoms and cognitive impairment as the main symptoms. At present, as a drug for treating schizophrenia, antagonism with dopamine D ₂ receptor (hereinafter referred to as D ₂ receptor) or serotonin 5-HT _2A receptor (hereinafter referred to as 5-HT _2A receptor) antagonism is used. An antipsychotic drug, but it is known that about 30% of patients with schizophrenia have an effect of using the existing antipsychotic drug, that is, a patient suffering from refractory schizophrenia (Non-Patent Document 1). In this case, clozapine, which is known as an atypical antipsychotic drug, shows high efficacy against schizophrenia patients and is reported to be the only agent that is also effective for patients with refractory schizophrenia (non-patented) Document 1). However, it has been reported that 0.8% of patients taking clozapine have serious side effects called granular ball deficiency, and blood monitoring is required when taking the drug. Further, side effects such as epilepsy, digestive system damage, sedation, weight gain, and salivation have been reported, and such side effects have made it difficult to continue treatment with clozapine (Non-Patent Documents 2 and 3). Therefore, the development of antipsychotic drugs that are safer and effective for refractory schizophrenia patients has become an urgent issue. It is known that clozapine has an antagonistic action on dopamine D ₁ receptor (hereinafter referred to as D ₁ receptor) in addition to dopamine D ₂ receptor antagonism and serotonin 5-HT _2A receptor antagonism. Further, it has been reported that in the PET test for patients with schizophrenia, clozapine occupies both the D ₂ receptor and the D ₁ receptor at the same ratio (Non-Patent Documents 4, 5, and 6). In Patent Document 1, as a substance having an antagonistic action on a D ₁ receptor, a D ₂ receptor, and a 5-HT _2A receptor, a 1-piperidinyl-1,2-dihydroindole derivative is disclosed, but basic The chemical structure of the skeleton and the side chain moiety is different from the dibenzodiazepine derivative of the present invention. Patent Document 2 discloses a dibenzothiazepine derivative which can be used as an antipsychotic drug, but the chemical structure of the basic skeleton is different from that of the dibenzodiazepine derivative of the present invention. [Prior Art Document] [Patent Document 1] Japanese Patent No. 3255416 [Patent Document 2] US Pat. No. 4,221,714 [Non-Patent Document] [Non-Patent Document 1] Pharmgenomics Pers Med. (2016) 9 117-129. [Non-Patent Document 2] Lancet. (2013) 382, 951-962. [Non-Patent Document 3] Neurotheapeutics (2017) 14, 750-761. [Non-Patent Document 4] Journal of Neural Transmission (1998) 105, 181-191. [Non-Patent Document 5] The American Journal of Psychiatry (2004); 161 (9): 1620-1625. [Non-Patent Document 6] The American Journal of Psychiatry (1995) 152, 1444-1449 .

[Problems to be Solved by the Invention] An object of the present invention is to provide a prevention for central nervous system diseases characterized by D ₁ receptor antagonism, D ₂ receptor antagonism, and 5-HT _2A receptor antagonism. A therapeutic compound or a pharmaceutically acceptable salt thereof, a process for producing the same, a composition comprising the same, and the like. [Technical means for solving the problem] The present inventors believe that compounds having antagonistic effects on the D ₁ receptor, the D ₂ receptor, and the 5-HT _2A receptor exhibit a refractory schizophrenia or other mental illness. As a result of the intensive study of the drug, it has been found that the compound represented by the following formula (1) and the pharmaceutically acceptable salt thereof (hereinafter sometimes referred to as "the compound of the present invention" as needed) are for the D ₁ receptor. The D ₂ receptor and the 5-HT _2A receptor have strong antagonistic effects, thereby completing the present invention. That is, the present invention is as follows. [Item 1] A compound or a pharmaceutically acceptable salt thereof, which is represented by the formula (1): [wherein, ring Q ¹ represents a benzene ring which may be substituted or a pyridine ring which may be substituted; ring Q ² represents a benzene ring which may be substituted, or a pyridine ring which may be substituted; R ^a represents a hydrogen atom, or may be a C _1-6 alkyl group substituted with 1 to 3 halogen atoms of the same or different species; n represents 0, 1 or 2; m represents 1, 2, 3 or 4; R ^b is independently in the presence of a plurality of cases The ground represents a hydrogen atom, a halogen atom, or a C _1-6 alkyl group which may be substituted with 1 to 3 halogen atoms of the same or different species. [Claim 2] The compound according to Item 1, or a pharmaceutically acceptable salt thereof, wherein the ring Q ¹ is a benzene ring or a pyridine ring (the benzene ring or the pyridine ring may be selected from a halogen atom, a cyano group, and the same species) Or a C _1-6 alkyl group substituted with 1 to 3 halogen atoms of a heterogeneous group, a C _1-6 alkoxy group which may be substituted with 1 to 3 halogen atoms of the same or different kinds, and 1 to 2 which may be homologous or heterologous a group of 1 to 4 groups of the same or different species in the group consisting of a C _1-6 alkyl-substituted amine group; the ring Q ² is a benzene ring or a pyridine ring (the benzene ring or the pyridine ring may be selected from a halogen group) An atom, a cyano group, a C _1-6 alkyl group which may be substituted with 1 to 3 halogen atoms of the same or different species, a C _1-6 alkoxy group which may be substituted with 1 to 3 halogen atoms of the same or different kinds, and 1 to 4 groups of the same or different species in the group consisting of 1 or 2 C _1-6 alkyl-substituted amine groups of the same or different species). [Item 3] as permitted by the compound or a pharmaceutically described in item 1 or 2, wherein the ring Q ¹ is a benzene ring (which ring may be selected from the group consisting of a halogen atom, a cyano group, may be the same or different species of ~ 1 the 3 halogen atoms substituted C _1-6 alkyl group, and the group may be substituted with the same species or different species of 1 to 3 halogen atoms, C _1-6 alkoxy group consisting of heterogeneous or in the 1 to 4 groups of Substituted); ring Q ² is a benzene ring (the ring may be selected from a C _1-6 alkyl group substituted by a halogen atom, a cyano group, a 1-3 ring halogen atom of the same or different species, and may be homologous or heterologous) One to four bases of the same or different species in the group consisting of 1 to 3 halogen atoms substituted by C _1-6 alkoxy groups). The compound according to any one of items 1 to 3, wherein the n is 1 or a pharmaceutically acceptable salt thereof. The compound according to any one of items 1 to 4, wherein the R ^b is independently a halogen atom or may be homologous or heterogeneous, in the case where a plurality of compounds are present, respectively. One to three halogen atoms are substituted for the C _1-6 alkyl group. [Claim 6] The compound according to Item 1, or a pharmaceutically acceptable salt thereof, which is represented by the formula (1a): Wherein R ^a represents a hydrogen atom or a C _1-6 alkyl group which may be substituted with 1 to 3 halogen atoms of the same or different species; R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ each independently represent a hydrogen atom, a halogen atom, a cyano group, a C _1-6 alkyl group which may be substituted with 1 to 3 halogen atoms of the same or different kinds, and may have 1 to 3 halogens of the same or different species. An atom-substituted C _1-6 alkoxy group, or an amine group which may be substituted with 1 to 2 C _1-6 alkyl groups of the same or different species; R ¹¹ , R ¹² , R ¹³ and R ¹⁴ each independently represent a hydrogen atom a halogen atom or a C _1-6 alkyl group which may be substituted by 1 to 3 halogen atoms of the same or different species. The compound according to Item 6, wherein the compound of any one of R ¹¹ , R ¹² , R ¹³ and R ¹⁴ is a halogen atom or may be the same or a heterogeneous one. ～3 halogen atoms substituted by C _1-6 alkyl. [Claim 8] The compound according to Item 6, or a pharmaceutically acceptable salt thereof, which is represented by the formula (1b): [wherein, R ^a , R ² , R ⁷ , R ¹³ and R ¹⁴ are synonymous with the term 6]. The compound according to any one of items 6 to 8, wherein R ¹³ is a C _1-6 alkyl group, or a pharmaceutically acceptable salt thereof. The compound according to any one of items 6 to 8, wherein R ¹³ is a methyl group, or a pharmaceutically acceptable salt thereof. The compound according to any one of items 6 to 10, wherein R ¹⁴ is a hydrogen atom, or a pharmaceutically acceptable salt thereof. [Claim 12] The compound according to Item 6, or a pharmaceutically acceptable salt thereof, which is represented by the formula (1b-1): [wherein, R ^a , R ² and R ⁷ are synonymous with item 6]. The compound according to any one of items 1 to 12, wherein the R ^{a is a} C _1-6 alkyl group which may be substituted with 1 to 3 halogen atoms of the same or different species, or ^a pharmaceutically acceptable salt thereof. . The compound according to any one of items 1 to 12, wherein R ^a is a methyl group, or a pharmaceutically acceptable salt thereof. [Claim 15] The compound according to any one of items 6 to 14, wherein R ² and R ⁷ are each independently a hydrogen atom, a halogen atom, a cyano group, or the same or a heterogeneous group, or a pharmaceutically acceptable salt thereof. the substituent of from 1 to 3 halogen atoms, C _1-6 alkyl group, a substituted or may be of the same type or different 1 to 3 halogen atoms, C _1-6 alkoxy group. The compound according to any one of items 6 to 14, or a pharmaceutically acceptable salt thereof, wherein any one of R ² and R ⁷ is a halogen atom, a cyano group, or the same or different species the substituent of from 1 to 3 halogen atoms, C _1-6 alkyl group, a substituted or may be of the same type or different 1 to 3 halogen atoms, C _1-6 alkoxy group. The compound according to any one of items 6 to 14, wherein R ² is a hydrogen atom, a fluorine atom, a chlorine atom, a C _1-3 alkyl group or a C _1-3 , or a pharmaceutically acceptable salt thereof. alkoxy, R ⁷ is a hydrogen atom, a fluorine atom, a chlorine atom, a cyano group, the substituents may be 1 to 3 fluorine atoms, C _1-3 alkyl, or may be substituted with 1 to 3 fluorine atoms C _{1- 6} alkoxy. [Claim 18] The compound according to Item 1, or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: 11-[(6S)-1,6-dimethyl-1,2,3 ,6-tetrahydropyridin-4-yl]-8-methyl-2-(trifluoromethyl)-5H-dibenzo[b,e][1,4]diazepine (Example 32), 8-Methyl-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethyl) -5H-dibenzo[b,e][1,4]diazepine (Example 33), 8-chloro-11-[(6S)-1,6-dimethyl-1,2, 3,6-tetrahydropyridin-4-yl]-2-(trifluoromethoxy)-5H-dibenzo[b,e][1,4]diazepine (Example 38), 8-chloro -11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethoxy)- 5H-dibenzo[b,e][1,4]diazepine (Example 39), 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6 -tetrahydropyridin-4-yl]-2-ethyl-5H-dibenzo[b,e][1,4]diazepine (Example 45), 8-chloro-2-ethyl-11- [(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1, 4] diazepine (Example 46), 11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-ethyl-8- Fluoro-5H-dibenzo[b,e][1,4]diazepine (Example 49), 2-ethyl-8- Fluor-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e ][1,4]diazepine (Example 50), 2-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl] -8-fluoro-5H-dibenzo[b,e][1,4]diazepine (Example 57), 2-chloro-8-fluoro-11-[(6S)-6-methyl-1 -( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine (Example 58), 8-Chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-methyl-5H-dibenzo[b,e ][1,4]diazepine (Example 65), 8-chloro-2-methyl-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2, 3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine (Example 66), 8-chloro-11-[(6S)-1, 6-Dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-methoxy-5H-dibenzo[b,e][1,4]diazepine (Example 72), 8-Chloro-2-methoxy-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl ]-5H-dibenzo[b,e][1,4]diazepine (Example 73), 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3 ,6-tetrahydropyridin-4-yl]-2-ethoxy-5H-dibenzo[b,e][1,4]diazepine (Example 88) and 8-chloro-2-ethoxyl Base-11-[(6S)-6-methyl-1-( ² H ₃ Methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine (Example 89). [Claim 19] The compound according to Item 1, or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: 11-[(6S)-1,6-dimethyl-1,2,3 ,6-tetrahydropyridin-4-yl]-8-methyl-2-(trifluoromethyl)-5H-dibenzo[b,e][1,4]diazepine (Example 32), 8-Methyl-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethyl) -5H-dibenzo[b,e][1,4]diazepine (Example 33), 8-chloro-11-[(6S)-1,6-dimethyl-1,2, 3,6-tetrahydropyridin-4-yl]-2-(trifluoromethoxy)-5H-dibenzo[b,e][1,4]diazepine (Example 38), 8-chloro -11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethoxy)- 5H-dibenzo[b,e][1,4]diazepine (Example 39), 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6 -tetrahydropyridin-4-yl]-2-ethyl-5H-dibenzo[b,e][1,4]diazepine (Example 45), 8-chloro-2-ethyl-11- [(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1, 4] diazepine (Example 46), 11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-ethyl-8- Fluoro-5H-dibenzo[b,e][1,4]diazepine (Example 49), 2-ethyl-8- Fluor-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e ][1,4]diazepine (Example 50), 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl] 2-methoxy-5H-dibenzo[b,e][1,4]diazepine (Example 72), 8-chloro-2-methoxy-11-[(6S)-6- Methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine Example 73), 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-ethoxy-5H-diphenyl And [b,e][1,4]diazepine (Example 88) and 8-chloro-2-ethoxy-11-[(6S)-6-methyl-1-( ² H ₃ ) A Base-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine (Example 89). [20] The compound according to Item 1, or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: 11-[(6S)-1,6-dimethyl-1,2,3 ,6-tetrahydropyridin-4-yl]-8-methyl-2-(trifluoromethyl)-5H-dibenzo[b,e][1,4]diazepine (Example 32), 8-Methyl-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethyl) -5H-dibenzo[b,e][1,4]diazepine (Example 33), 8-chloro-11-[(6S)-1,6-dimethyl-1,2, 3,6-tetrahydropyridin-4-yl]-2-(trifluoromethoxy)-5H-dibenzo[b,e][1,4]diazepine (Example 38), 8-chloro -11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethoxy)- 5H-dibenzo[b,e][1,4]diazepine (Example 39), 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6 -tetrahydropyridin-4-yl]-2-ethyl-5H-dibenzo[b,e][1,4]diazepine (Example 45), 8-chloro-2-ethyl-11- [(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1, 4] diazepine (Example 46), 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-ethyl Oxy-5H-dibenzo[b,e][1,4]diazepine (Example 88) and 8-chloro-2- Oxy -11 - [(6S) -6- methyl -1- ⁽² H ₃₎ methyl-1,2,3,6-tetrahydropyridin-4-yl] -5H- dibenzo [b, e] [1,4]diazepine (Example 89). [Claim 21] A pharmaceutical composition containing the compound according to any one of Items 1 to 20 or a pharmaceutically acceptable salt thereof as an active ingredient. [Claim 22] A therapeutic agent for a central nervous system disease, which comprises the compound according to any one of Items 1 to 20 or a pharmaceutically acceptable salt thereof as an active ingredient. [Claim 23] The therapeutic agent according to Item 22, wherein the central nervous system disease is schizophrenia, bipolar disorder, autism, ADHD, depression, anxiety, sleep disorder, behavior and psychological symptoms of dementia (BPSD ( Behavioral and Psychological Symptoms of Dementia)) or psychotic symptoms of neurodegenerative diseases. [Claim 24] A method for treating a central nervous system disease, which comprises administering a therapeutically effective amount of a compound according to any one of items 1 to 20 or a pharmaceutically acceptable compound thereof to a patient in need of treatment. Salt. [Claim 25] The use of a compound according to any one of items 1 to 20, or a pharmaceutically acceptable salt thereof, for the manufacture of a therapeutic agent for diseases of the central nervous system. [Claim 26] The compound according to any one of items 1 to 20, or a pharmaceutically acceptable salt thereof, for use in the treatment of diseases of the central nervous system. [Claim 27] A therapeutic agent for a central nervous system disease, which comprises the compound according to any one of items 1 to 20, or a pharmaceutically acceptable salt thereof, selected from the group consisting of aripiprazole, olanzapine, and quinine. Thiopenic, risperidone, bunnerin, piperpirone, paliperidone, ziprasidone, asenapine, ipidine, sputum, lurasidone and the like At least one agent selected from the group consisting of pharmaceutically acceptable salts is combined. [Claim 28] A therapeutic agent containing the compound according to any one of Items 1 to 20 or a pharmaceutically acceptable salt thereof as an active ingredient, which is selected from the group consisting of aripiprazole, olanzapine, quetiapine Ping, risperidone, bunnerin, piperpirone, paliperidone, ziprasidone, asenapine, ipidine, sputum, lurasidone and the pharmacy of these At least one agent selected from the group consisting of the above-mentioned salts is used in combination to treat diseases of the central nervous system. [Effect of the Invention] The compound of the present invention exhibits an antagonistic action against the D ₁ receptor, the D ₂ receptor, and the 5-HT _2A receptor. In addition, in a preferred aspect, brain transition property is excellent, and further, it is considered to be one of particulate ball deficiencies because the amount of reactive metabolites produced is also low. In a further preferred aspect, the histamine receptor, the muscarinic receptor, and the serotonin 5-HT _2c receptor (hereinafter referred to as 5-HT) are considered to be associated with side effects such as digestive system damage, sedation, and weight gain. The antagonistic effect of _2c receptors and the like is weak. Therefore, the compound of the present invention can be used as a therapeutic and/or preventive agent for a highly safe and excellent central nervous system disease such as schizophrenia.

Hereinafter, the present invention will be described in detail. In the present specification, the amount of carbon in the definition of "substituent" is also referred to as "C"._1-6 "etc. Specifically, "C_1-6 The description of "alkyl" is synonymous with an alkyl group having 1 to 6 carbon atoms. Specific examples of the "halogen atom" include a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. It is preferably a fluorine atom or a chlorine atom. "C_1-6 "Alkyl" means a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms. Preferably "C_1-4 alkyl". As "C_1-6 Specific examples of the alkyl group include, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a second butyl group, a tert-butyl group, a pentyl group, an isopentyl group, and a neopentyl group. Base, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl Wait. "C_1-6 "Alkoxy"_1-6 "Alkyl" part is related to the above "C_1-6 Alkyl is synonymous. Preferably "C_1-4 Alkoxy group". As "C_1-6 Specific examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a second butoxy group, a third butoxy group, and the like. . In the compound represented by the formula (1), R^b If the group is substitutable, it can be substituted with any carbon atom on the nitrogen-containing monocyclic ring. If it is substitutable, it can be the same or different two R groups on the same carbon atom.^b The base is substituted. In the compound represented by the formula (1), in the ring Q¹ And / or ring Q² In the case of a pyridine ring, the four atoms represented by the arrows shared by the rings which are fused are carbon. [Chemical 5]Examples of the substituent in the "substitutable benzene ring" and the "substituted pyridine ring" include (a) a halogen atom, (b) a cyano group, and (c) C._1-6 An alkyl group (the group may be selected from a halogen atom, a hydroxyl group, and C_1-6 (1) to 1 or 3 of the same or different species in the group consisting of alkoxy groups), (d) C_1-6 Alkoxy group (the group may be selected from a halogen atom, a hydroxyl group, and C_1-6 a group of 1 to 3 groups of the same or different species in the group consisting of alkoxy groups), (e) a phenyl group (the group may be selected from a halogen atom, C_1-6 Alkyl and C_1-6 a group of 1 to 4 substituents of the same or different species in the group consisting of alkoxy groups, (f) a heteroaryl group of 5 or 6 members (the group may be selected from a halogen atom, C)_1-6 Alkyl and C_1-6 a group of 1 to 4 groups of the same or different species in the group consisting of alkoxy groups), (g) a phenoxy group (the group may be selected from a halogen atom, C)_1-6 Alkyl and C_1-6 1 to 4 substituents of the same or different species in the group consisting of alkoxy groups), (h) hydroxyl groups, (i) amine groups (the group may be 1 to 2 C of the same or different species)_1-6 Alkyl substituted) and (j) aminocarbonyl (the amine group may be 1 to 2 C of the same or different species)_1-6 Alkyl substitution) and the like. Preferably, it is a halogen atom, a cyano group, and a C which may be substituted by 1 to 3 halogen atoms of the same or different species._1-6 Alkyl, which may be substituted by one or three halogen atoms of the same or different species_1-6 Alkoxy group, and 1 to 2 C which can be homologous or heterologous_1-6 Alkyl substituted amino group. More preferably, it is a halogen atom, which may be substituted by one or three halogen atoms of the same or different species._1-6 Alkyl, and C which may be substituted by 1 to 3 halogen atoms of the same or different species_1-6 Alkoxy. In the compound of the present invention represented by the formula (1a), R^a , R¹ , R² , R³ , R⁴ , R⁵ , R⁶ , R⁷ , R⁸ , R¹¹ , R¹² , R¹³ And R¹⁴ The preferred ones are as follows, but the technical scope of the present invention is not limited to the scope of the compounds listed below. As R^a Preferably, C is substituted by one or three halogen atoms of the same or different species._1-6 alkyl. Better for C_1-3 An alkyl group; further preferably a methyl group. Also, as R^a Another aspect is 氘methyl (CD)₃ ). As R¹ , R³ , R⁴ , R⁵ , R⁶ And R⁸ Preferably, a hydrogen atom and a halogen atom are mentioned. More preferably, it is a hydrogen atom. As R² And R⁷ Preferably, it is a hydrogen atom, a halogen atom, a cyano group, and a C which may be substituted by one or three halogen atoms of the same or different species._1-6 Alkyl, and C which may be substituted by 1 to 3 halogen atoms of the same or different species_1-6 Alkoxy. More preferably, it is a halogen atom, which may be substituted by one or three halogen atoms of the same or different species._1-6 Alkyl, and C which may be substituted by 1 to 3 halogen atoms of the same or different species_1-6 Alkoxy. R¹¹ , R¹² , R¹³ And R¹⁴ Individually substituted by a hydrogen atom, a halogen atom, or a C atom which may be substituted by one or three halogen atoms of the same or different species_1-6 Alkyl group, preferably R¹¹ , R¹² , R¹³ And R¹⁴ Any one of the above is a halogen atom, or may be substituted by one or three halogen atoms of the same or different species._1-6 alkyl. More preferably R¹¹ , R¹² , R¹³ And R¹⁴ Any one of them is C_1-6 alkyl. As R¹¹ , R¹² And R¹⁴ Preferably, a hydrogen atom and C are exemplified_1-6 alkyl. More preferably, it is a hydrogen atom. As R¹³ Preferably, a hydrogen atom and C are exemplified_1-6 alkyl. Better for C_1-4 An alkyl group; further preferably a methyl group. As R¹¹ , R¹² , R¹³ And R¹⁴ Another aspect, R¹¹ And R¹² Is a hydrogen atom; R¹³ For C_1-6 Alkyl; R¹⁴ Is a hydrogen atom or C_1-6 alkyl. As R¹¹ , R¹² , R¹³ And R¹⁴ Another aspect, R¹¹ , R¹² And R¹⁴ Is a hydrogen atom; R¹³ For C_1-4 alkyl. The compound represented by the formula (1) may also exist in the form of a tautomer. Therefore, the compound of the present invention also contains a tautomer of the compound represented by the formula (1). The compound represented by the formula (1) may also have a case of having at least one asymmetric carbon atom. Therefore, the compound of the present invention contains not only the racemates of the compounds represented by the formula (1) but also optically active compounds of the compounds. Further, any one or more of the compounds represented by the formula (1)¹ H is converted to² The hydrazone transformant formed by H(D) is also included in the compound represented by the formula (1). The compound represented by the formula (1) and the pharmaceutically acceptable salt thereof are also present in the form of a hydrate and/or a solvate, and the solvate such as the hydrate or the ethanol solvate is also Included in the compounds of the invention. Further, the compounds of the present invention also encompass all forms of crystal form. In the case where the compound represented by the formula (1) has an acidic group, examples of the pharmaceutically acceptable salt include an alkali metal salt such as a sodium salt or a potassium salt; an alkaline earth metal salt such as a calcium salt or a magnesium salt; and zinc. An inorganic metal salt such as a salt; an organic alkali salt such as triethylamine, triethanolamine, trishydroxymethylaminomethane or amino acid. When the compound represented by the formula (1) has a basic group, for example, inorganic acid salts such as hydrochloride, hydrobromide, sulfate, phosphate, and nitrate; and acetate, propionate; , succinate, lactate, malate, tartrate, citrate, maleate, fumarate, methanesulfonate, p-toluenesulfonate, besylate, An organic acid salt such as ascorbate. Hereinafter, a method for producing the compound represented by the formula (1) in the present invention will be described by way of example, but the present invention is of course not limited thereto. Production Method The compound of the present invention is synthesized by a combination of the production method shown below and a known synthesis method. The compound in the reaction formula also contains a salt, and the salt is the same as the salt of the compound represented by the formula (1). Furthermore, the reactions are merely illustrative, and the compounds of the invention may be suitably prepared by other methods based on the knowledge of an organic synthesizer. In each of the production methods described below, even in the case where the use of the protective group is not specifically indicated, in the case where the functional group to be protected is present, the functional group is optionally protected, after the reaction is completed or a series of After the reaction, deprotection is carried out, whereby the target is obtained. The introduction and detachment of the protecting group can be carried out by a method commonly used in organic synthetic chemistry (for example, TW Greene and PGM Wuts, "Protective Groups in Organic Synthesis", 3rd Ed., John Wiley and Sons, inc., New York (1999). The method described, etc.) or according to the method thereof. Examples of the protective group of the amino group include a third butoxycarbonyl group, a benzyloxycarbonyl group, a p-toluenesulfonyl group, an o-nitrophenylsulfonyl group, and the like. Production Method 1 Among the compounds represented by the formula (1), the compounds represented by the formulae (1c) and (1d) are produced, for example, by the method shown below. [Chemical 6][in the formula, ring Q¹ Ring Q² , R^b , m and n are synonymous with [Item 1] above; R^A1 Represents C which can be substituted by 1 to 3 halogen atoms of the same or different species_1-6 Alkyl; X represents halogen; Pro represents a protecting group of an amine group; A represents a boronic acid or a boronic ester] Step 1-1: Production step of the compound (1-2) The compound (1-2) is obtained by a suitable inert solvent The halogenating agent is produced by allowing the halogenating agent to act on the compound (1-1) in the presence of a base or in the absence of a base. The compound (1-1) can be produced by a commercially available compound or by a known method (for example, International Publication No. 2007/047776). Examples of the halogenating agent include 1-chloro-N,N,2-trimethylpropenylamine, phosphorus oxychloride, phosphorus trichloride, sulfinium chloride, and phosphorus pentachloride. Examples of the base include N,N-dimethylaniline and the like. Examples of the inert solvent include toluene, dichloromethane, and the like. The reaction time is usually from 5 minutes to 72 hours, preferably from 30 minutes to 2 hours. The reaction temperature is usually -78 ° C to 200 ° C, preferably 20 ° C to 100 ° C. Step 1-2: Production step of compound (1d) Compound (1d) is obtained by coupling compound (1-2) with compound (1-3) in the presence of a palladium catalyst in a suitable inert solvent. Manufacturing. This step can be carried out as needed in the presence of a base and/or a phosphorus ligand. The compound (1-3) can be produced by using a commercially available compound or by a known method (for example, International Publication No. 2002/066470). Further, those manufactured by the following production method 4 can be used. As the palladium catalyst, various palladium catalysts used in a conventional method can be used, and tetrakis(triphenylphosphine)palladium (0) is preferable. Examples of the base include potassium carbonate and cesium carbonate. Examples of the phosphorus ligand include triphenylphosphine or bis(diphenylphosphino)methane. Examples of the inert solvent include 1,4-dioxane, tetrahydrofuran, water, and a mixed solvent thereof. The reaction temperature is usually from 0 ° C to 200 ° C, preferably from 20 ° C to 150 ° C, and may be carried out under microwave irradiation as needed. The reaction time varies depending on the reaction temperature, the palladium catalyst to be used, the raw material, and the solvent, and is usually from 5 minutes to 72 hours, preferably from 30 minutes to 24 hours. Step 1-3: Production step of the compound (1-5) The compound (1-5) is produced from the compound (1-2) and the compound (1-4) according to the method described in the step 1-2. The compound (1-4) can be produced by the following Production Method 2. Step 1-4: Production Step of Compound (1c) Compound (1c) is obtained by using a known method (for example, Protective Group in Organic Synthesis, 3rd edition (Theodora W. Green, Peter GM Wuts, issued by John Wiley & Sons Inc, 1999) Manufactured according to the deprotection of the protecting group Pro of the amine group of the compound (1-5). Step 1-5: The production step of the compound (1d) The compound (1d) is also used in a suitable inert solvent in the reducing agent. In the presence of the compound (1c), it is produced by reacting the compound (1c) with various alkyl aldehydes. Examples of the reducing agent include sodium borohydride, sodium triethoxy borohydride, sodium cyanoborohydride, and the like. For example, toluene, THF (tetrahydrofuran, tetrahydrofuran), dichloroethane, methanol, etc. The reaction time is usually 5 minutes to 48 hours, preferably 1 hour to 24 hours. The reaction temperature is usually -78 ° C to 100 ° C. Further, the compound (1d) is also produced by reacting the compound (1c) with various alkyl halides in the presence of a base in a suitable inert solvent. For example, potassium carbonate, Carbonic acid hydride, sodium hydride, lithium diisopropyl guanamine, etc. Examples of the inert solvent include DMF (dimethylformamide, dimethylformamide), dimethyl hydrazine, THF, and 1,4-dioxane. The reaction time is usually from 5 minutes to 48 hours, preferably from 1 hour to 24 hours. The reaction temperature is usually -78 ° C to 100 ° C, preferably 0 ° C to 80 ° C. Manufacturing Method 2 Formula (1-4) The compound represented is produced, for example, by the method shown below.[where, R^b , m and n are synonymous with [Item 1] above; X¹ Represents a halogen or a triflate (trifluoromethanesulfonyloxy); Pro represents a protecting group for an amine group; A represents a boronic acid or a boronic ester] Step 2-1: a compound of the compound (2-2) (2-2) is produced by allowing a trifluoromethanesulfonating agent to act on the compound (2-1) in the presence of a base in a suitable inert solvent. The compound (2-1) can be produced by a commercially available compound or by a known method (for example, International Publication No. 2012/142668). Examples of the base include lithium diisopropylguanamine or sodium bis(trimethyldecyl)decylamine. As the trifluoromethanesulfonating agent, various trifluoromethanesulfonating agents used in the conventional methods can be used, and preferably N-phenylbis(trifluoromethanesulfonimide) is exemplified. Examples of the inert solvent include THF and the like. The reaction time is usually from 5 minutes to 72 hours, preferably from 30 minutes to 8 hours. The reaction temperature is usually -78 ° C to 200 ° C, preferably -78 ° C to 20 ° C. Step 2-2: Production Step of Compound (1-4) Compound (1-4) is obtained by coupling compound (2-2) with a boronating reagent in the presence of a palladium catalyst in a suitable inert solvent. And manufacturing. This step can be carried out as needed in the presence of a base and/or a phosphorus ligand. As a base, potassium acetate is mentioned, for example. Examples of the phosphorus ligand include triphenylphosphine or bis(diphenylphosphino)methane. As the borating agent, various boronating agents used in the conventional method can be used, and preferably, bis(pinacol ester) diborane is exemplified. As the palladium catalyst, various palladium catalysts used in a conventional method can be used, and preferably, 1,1'-bis(diphenylphosphino)ferrocene-palladium (II) dichloride is exemplified. Examples of the inert solvent include 1,4-dioxane, THF, and the like. The reaction temperature is usually from 0 ° C to 200 ° C, preferably from 50 ° C to 120 ° C, and may be carried out under microwave irradiation as needed. The reaction time varies depending on the reaction temperature, the palladium catalyst to be used, the raw material, and the solvent, and is usually from 5 minutes to 72 hours, preferably from 2 hours to 8 hours. Production Method 3 Among the compounds represented by the formula (1), the compound represented by the formula (1e) is produced, for example, by the method shown below. [化8][in the formula, ring Q¹ Ring Q² , R^b And the m system are synonymous with the above [Item 1]; R^A1 Represents C which can be substituted by 1 to 3 halogen atoms of the same or different species_1-6 Alkyl; X represents halogen; A represents boric acid or borate] Step 3-1: Production step of compound (3-2) Compound (3-2) is derived from compound (1-2) and compound (3-1) , manufactured according to the method described in step 1-2. The compound (3-1) can be produced by using a commercially available compound or by a known method (for example, International Publication No. 2011/119518). Step 3-2: Production step of compound (1e) Compound (1e) is obtained by reacting compound (3-2) with compound (3-3) to produce a quaternary ammonium cation by a suitable inert solvent. The reducing agent acts to produce it. Examples of the inert solvent include acetonitrile, THF, and 1,4-dioxane. The reaction time of the alkylation step is usually from 5 minutes to 48 hours, preferably from 1 hour to 24 hours. The reaction temperature of the alkylation step is from 0 ° C to 100 ° C. Examples of the reducing agent used in the subsequent reduction reaction include sodium borohydride, sodium triethoxy borohydride, sodium cyanoborohydride and the like. Examples of the solvent to be used include toluene, THF, dichloroethane, and methanol. The reaction time is usually from 5 minutes to 48 hours, preferably from 1 hour to 24 hours. The reaction temperature is usually -78 ° C to 100 ° C, preferably -78 ° C to 20 ° C. Production Method 4 The compound represented by the formula (1-3) is also produced, for example, by the method shown below. [Chemistry 9][where, R^b , m and n are synonymous with [Item 1] above; R^A1 Represents C which can be substituted by 1 to 3 halogen atoms of the same or different species_1-6 Alkyl; X¹ Represents a halogen or a triflate; Pro represents a protecting group of an amine group; A represents a boric acid or a boric acid ester] Step 4-1: Production Step of Compound (4-1) Compound (4-1) is utilized A known method (for example, Protective Group in Organic Synthesis, 3rd edition (Theodora W. Green, by Peter GM Wuts, issued by John Wiley & Sons Inc, 1999), which is produced by deprotecting the protecting group Pro of the amine group of the compound (2-2) Step 4-2: Production Step of Compound (4-2) Compound (4-2) is also subjected to compound (4-1) and various alkyl aldehydes in the presence of a reducing agent in a suitable inert solvent. The reducing agent may, for example, be sodium borohydride, sodium triethoxy borohydride or sodium cyanoborohydride. Examples of the inert solvent include toluene, THF, dichloroethane and methanol. The reaction time is usually from 5 minutes to 48 hours, preferably from 1 hour to 24 hours. The reaction temperature is usually -78 ° C to 100 ° C, preferably 0 ° C to 80 ° C. Further, the compound (4-2) is also Halogenation of compound (4-1) with various alkyl groups in the presence of a base in a suitable inert solvent The base is, for example, potassium carbonate, cesium carbonate, sodium hydride, lithium diisopropyl guanamine or the like. Examples of the inert solvent include DMF, dimethyl hydrazine, THF, and 1, 4-dioxane, etc. The reaction time is usually 5 minutes to 48 hours, preferably 1 hour to 24 hours. The reaction temperature is usually -78 ° C to 100 ° C, preferably 0 ° C to 80 ° C. Step 4-3 Production Step of Compound (1-3) The compound (1-3) is produced by coupling a compound (4-2) with a boronating reagent in the presence of a palladium catalyst in a suitable inert solvent. The step may be carried out in the presence of a base and/or a phosphorus ligand. The base may, for example, be potassium acetate. Examples of the phosphorus ligand include triphenylphosphine or bis(diphenylphosphino)methane. As the borating agent, various boriding agents used in the conventional method can be used, and preferably, bis(pinacol ester) diborane is used. As the palladium catalyst, various palladium contacts used in the conventional method can be used. The medium is preferably 1,1'-bis(diphenylphosphino)ferrocene-palladium (II) dichloride as an inert solvent. For example, 1,4-dioxane, THF, etc. The reaction temperature is usually 0 ° C to 200 ° C, preferably 50 ° C to 120 ° C, and may be carried out under microwave irradiation as needed. The reaction time is based on the reaction temperature, The conditions of the palladium catalyst, the raw material and the solvent to be used are usually from 5 minutes to 72 hours, preferably from 2 hours to 8 hours. By appropriately combining the above-described production methods, it is possible to obtain at a desired position. The compound of the present invention which is a desired substituent, and the separation and purification of the intermediate and the product in the above production method can be appropriately combined with a method used in usual organic synthesis, for example, filtration, extraction, washing, drying, concentration, and crystallization. And various kinds of chromatography methods and the like. Further, the intermediate may be supplied to the next reaction without special purification. The raw material compound or the intermediate in the above production method may be present in the form of a salt such as a hydrochloride salt depending on the reaction conditions and the like, but may be used as it is or in a free form. When the raw material compound or the intermediate is to be obtained in the form of a salt, and the raw material compound or the intermediate is used in a free form, the solvent may be dissolved or suspended in a suitable solvent, for example, by an aqueous solution of sodium hydrogencarbonate or the like. The base or the like is neutralized, thereby being converted into a free form. In the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof, there may be a tautomer, a positional isomer, a geometric isomer or an optical isomerism such as a keto-enol group. Any of the isomers and the mixture of any of the isomers may be included in the present invention. Further, the optical isomer can be separated by a known separation step such as a method using an optically active column or a fractional crystallization method by an appropriate step of the above production method. Further, an optically active substance can also be used as a starting material. In the case of obtaining a salt of the compound represented by the formula (1), in the case of obtaining a salt of the compound represented by the formula (1), it is only necessary to directly carry out the purification, and further, a formula for obtaining a free form (1) In the case of the compound represented by the formula (1), the compound represented by the formula (1) may be dissolved or suspended in a suitable solvent, and an acid or a base may be added to form a salt. Further, the compound (1) or a pharmaceutically acceptable salt thereof may be present in the form of a solvate with water or various solvents, and such solvates are also included in the present invention. In the present specification, "refractory schizophrenia" refers to schizophrenia in which a sufficient amount of two or more antipsychotic drugs are administered even after a sufficiently long period of time. It is defined in the Japanese schizophrenia drug guidelines as follows: Two or more antipsychotic drugs are administered in an amount of 600 mg/day or more in terms of chlorpromium, and after four weeks or more, the equivalent function is not achieved. The Global Assessment of Functioning (GAF) is 41 or more. It is known that clozapine is effective for refractory schizophrenia except D₂ Receptor antagonism, 5-HT_2A In addition to receptor antagonism, also on D₁ The receptor has an antagonistic action (Non-Patent Documents 4, 5, and 6). It can be expected to be the same as clozapine₁ Receptor, D₂ Receptor and 5-HT_2A The compounds of the invention in which the receptor has an antagonistic effect are effective against refractory schizophrenia. Also, due to the compound of the invention versus D₂ Receptor and 5-HT_2A Receptors show antagonism, so expect to be also schizophrenia, bipolar disorder, autism, ADHD (Attention Deficit Hyperactivity Disorder), depression, anxiety, sleep disorders, dementia behavior・Psychiatric symptoms of BPSD (Behavioral and Psychological Symptoms of Dementia) and neurodegenerative diseases are effective. Although there is currently no common animal model for refractory schizophrenia, it is considered that by performing a hyperalkamine-induced hyperactivity test (test case 5) in a rat model of positive symptoms of schizophrenia, it can be found Schizophrenia treatment drug, by confirming the above D₁ Receptor and D₂ The receptor has an antagonistic effect and can be used to explore agents that are also effective against refractory schizophrenia. When a pharmaceutical compound is introduced into a living body, the chemical structure changes due to metabolism, and a highly reactive intermediate, that is, a reactive metabolite is formed, thereby exhibiting toxicity (granular ball deficiency, hepatotoxicity, allergy). , tissue necrosis, mutagenicity or carcinogenicity, etc.). As one of the tests for easily evaluating the risk of toxicity caused by the reactive metabolite, there is a glutathione capture test using dansylsulfonated glutathione (dGSH). The higher the value of the dGSH covalent bond amount, the more the above-mentioned toxicity risk is increased when exposed to the whole body. Regarding the particulate spherical deficiency seen in clozapine, it has been reported that one of the causes is the formation of a reactive metabolite (refer to The Journal of Pharmacology and Experimental Therapeutics, 1997, 283 (3) 1375-1382, etc.). The compound of the present invention was subjected to a dansyl glutathione (dGSH) capture test, and as a result, it was unexpectedly known that the value of the dGSH covalent bond of the compound of the present invention was extremely low, and the formation of a reactive metabolite was remarkably lowered (Test Example 2). . From this, it is expected that the compound of the present invention has a low risk of causing particulate globus deficiency and the like, and can be safely administered for a long period of time. Regarding side effects such as digestive system damage, sedation, and weight gain seen in clozapine, it has been reported that one of the causes is the histamine receptor, muscarinic receptor, 5-HT._2c Antagonism of receptors and the like (cf. Molecular Psychiatry (2008) 13, 27-35; Prim Care Companion J Clin Psychiatry. 2004, 6 (suppl 2): 3-7; CNS Drugs. 2013 Jun; 27 (6): 423 -34; J Clin Psychiatry 2004, 6 (Suppl 2): 20-23; Clin Psychopharmacol Neurosci. 2012 Aug; 10 (2): 71-77, etc.). The compounds of the present invention were subjected to an antagonist activity evaluation test for these receptors, and as a result, it was unexpectedly known that the compounds of the present invention have a lower antagonistic effect on the receptors when they are in a better aspect (Test Example 8). It is thus expected that the compounds of the present invention have a lower risk of causing digestive system damage, sedation, weight gain, etc., in a more favorable manner, and can be administered safely. Further, in the present invention, "prevention" is an action of administering the active ingredient of the present invention to a normal person who is not afflicted, for example, for the purpose of preventing the onset of the disease. "Treatment" is the act of administering the active ingredient of the present invention to a person (patient) who has been diagnosed by a doctor. The compounds of the present invention can be administered by oral administration or parenteral administration, either directly or by using a suitable dosage form. The dosage form may, for example, be a tablet, a capsule, a powder, a granule, a liquid, a suspension, an injection, a patch, a dressing or the like, but is not limited thereto. The preparation is produced by a known method using a pharmaceutically acceptable additive. The additive may be used according to the purpose, using an excipient, a disintegrating agent, a binder, a plasticizer, a lubricant, a coating agent, a dissolving agent, a dissolution aid, a tackifier, a dispersing agent, a stabilizer, a sweetener, and a fragrance. Wait. Specific examples thereof include lactose, mannitol, crystalline cellulose, low-substituted hydroxypropylcellulose, corn starch, partially gelatinized starch, calcium carboxymethylcellulose, and croscarmellose sodium. Hydroxypropyl cellulose, hypromellose, polyvinyl alcohol, magnesium stearate, sodium stearyl succinate, polyethylene glycol, propylene glycol, titanium oxide, talc, and the like. The administration route is preferably the most effective for use in the treatment, and examples thereof include oral, intravenous, smear, inhalation, and eye drops, and oral administration is preferred. Examples of the administration form include a tablet, an injection, and the like, and a tablet is preferred. The dosage or the number of administrations of the pharmaceutical compositions differs depending on the form of administration, the disease or symptom of the patient, the age or weight of the patient, and the like, and cannot be generally prescribed, but usually, the adult can be administered once a day or The amount of the active ingredient per day is preferably from about 0.0001 to about 5000 mg, preferably from about 0.001 to about 1000 mg, more preferably about 0.1, preferably divided into one to three times a day. It is in the range of about 500 mg, particularly preferably in the range of about 1 to about 300 mg. The compound of the present invention can be used in combination with other drugs for the purpose of enhancing the effect and/or reducing the side effects. For example, it can be combined with aripiprazole, olanzapine, quetiapine, risperidone, bunnerin, piperoprolone, paliperidone, ziprasidone, asenapine, iloperidone, Antipsychotic drugs such as sputum, lurasidone or a pharmaceutically acceptable salt thereof are used in combination. Hereinafter, the drug which can be used in combination with the compound of the present invention is simply referred to as a concomitant drug. The administration time of the compound of the present invention and the concomitant drug is not limited, and it may be administered to the subject at the same time, or may be administered at intervals. Further, a combination of the compound of the present invention and a concomitant agent can also be used. The dosage of the pharmaceutical agent can be appropriately selected based on the amount of the clinical use. Further, the ratio of the compound of the present invention to the concomitant agent can be appropriately selected depending on the administration target, the administration route, the target disease, the symptom, the combination, and the like. For example, when the administration target is a human, it may be used in an amount of 0.01 to 100 parts by weight based on 1 part by weight of the compound of the present invention. Moreover, for the purpose of suppressing the side effects, it can be used in combination with an agent such as an antiemetic agent, a sleep introducing agent, or an anticonvulsant (a combination). [Examples] Hereinafter, the present invention will be specifically described by reference examples, examples, and test examples, but the present invention is not limited thereto. Further, the names of the compounds shown in the following Reference Examples and Examples are not necessarily based on the IUPAC (International Union of Pure and Applied Chemistry) nomenclature. In order to simplify the description of the specification, in the reference examples, examples, and test examples, the following abbreviations are also used. Me: methyl Et: ethyl DMF: N, N-dimethylformamide DMSO: dimethyl hydrazine THF: tetrahydrofuran TFA: trifluoroacetic acid as a mark used in NMR (nuclear magnetic resonance) , s means single peak, d means doublet, dd means doublet of doublet, t means triplet, td means doublet of triplet, q means quadruple, m means multiple Peak, br means wide, brs means wide singlet, brm means wide multiple peak, and J means coupling constant. High-speed liquid chromatography mass spectrometer; LCMS measurement conditions are as follows, with [M+H]⁺ Or [M-H]^- Indicates the value of the observed mass analysis [MS(m/z)], and the retention time is expressed in Rt (minutes). Measurement conditions (1) Testing equipment: ACQUITY (registered trademark) SQ deteceter (Waters) HPLC: ACQUITY UPLC (registered trademark) system Column: Waters ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm, 2.1 mm × 30 mm) Flow rate: 0.75 mL/min Measurement wavelength: 254 nm Moving bed: A solution 0.05% formic acid aqueous solution B solution acetonitrile Time program: Step time (minutes) 1 0.0-1.3 A solution: B solution = 90:10 to 1:99 2 1.3 -1.5 A liquid: B liquid = 1:99 3 1.5-2.0 A liquid: B liquid = 90:10 Measurement conditions (2) Testing equipment: ACQUITY (registered trademark) SQ deteceter (Waters) HPLC: ACQUITY UPLC (registered trademark) System Column: Waters ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm, 2.1 mm × 30 mm) Flow rate: 0.80 mL/min Measurement wavelength: 254 nm Moving bed: A solution 0.05% formic acid aqueous solution B liquid acetonitrile Time program: Step time (minutes) 1 0.0-1.3 A solution: B solution = 90:10 to 5:95 2 1.3-1.5 A solution: B solution = 90:10 Determination conditions (3) MS detector: LCMS-IT-TOF HPLC :Shimadzu Nexera X2 LC 30AD Column: Kinetex 1.7 μ C18 100A New column 50×2.1 mm Flow rate: 1.2 mL/min Measurement wavelength: 2 54 nm moving bed: liquid A; 0.1% formic acid aqueous solution B; acetonitrile time program: step time (minutes) 1 0.01-1.40 A liquid: B liquid = 90:10~5:95 2 1.40-1.60 A liquid: B liquid =5:95 3 1.61-2.00 A liquid: B liquid = 99:1 Measurement conditions (4) Testing machine: LCMS-2020 (Shimadzu Corporation) Column: Phenomenex Kinetex (1.7 μm, C18, 50 mm × 2.10 mm) Flow rate :0.50 mL/min Measurement wavelength: 220, 254 nm Moving bed: A solution 0.05% TFA aqueous solution B solution Acetonitrile column Temperature: 40 ° C Time program: Step time (minutes) 1 0.0 A solution: B solution = 90:10 2 0.0-1.9 A liquid: B liquid = 90:10～1:99 3 1.9-3.0 A liquid: B liquid=90:10 Reference example 1 8-chloro-2-fluoro-5,10-dihydro-11H-two Benzo[b,e][1,4]diazepine-11-one [10]a) Preparation of 2-[(4-chloro-2-nitrophenyl)amino]-5-fluorobenzoic acid (Compound W1) in 4-chloro-1-fluoro-2-nitrobenzene (5.0 g) 2-Amino-5-fluorobenzoic acid (4.4 g) and cesium carbonate (28 g) were added to a solution of DMF (29 mL), and stirred at 120 ° C overnight. Water was added to the reaction mixture at 0 ° C, and the mixture was adjusted to pH 5 with 1 mol/L hydrochloric acid, and then extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the dried organic layer was distilled off under reduced pressure, whereby Compound W1 (8.8 g) was obtained. LC-MS ([M+H]⁺ /Rt(min)): 311/1.18 Measurement conditions (1) b) 2-[(2-Amino-4-chlorophenyl)amino]-5-fluorobenzoic acid (Compound W2) was produced in Compound W1 (8.8 g) of THF/MeOH/H₂ Ammonium chloride (15 g) and iron (16 g) were added to the O(3:2:1) (300 mL) solution, and stirred at 80 ° C for 2 hours. After cooling the reaction liquid, it was filtered through celite, washed with methanol, and then the solvent was distilled off under reduced pressure. After the obtained residue was subjected to liquid separation extraction with ethyl acetate-water, the obtained organic layer was washed with saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure, whereby Compound W2 (8.0 g) was obtained. LC-MS ([M+H]⁺ /Rt(min)): 281/1.06 Determination conditions (1) c) 8-Chloro-2-fluoro-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepine Preparation of -11-ketone (Reference Example 1) Addition of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide to a solution of compound W2 (8.0 g) in DMF (143 mL) Hydrochloride (6.0 g) and 1-hydroxybenzotriazole (4.2 g) were stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer obtained was washed with saturated brine, dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue obtained was washed with chloroform (20 mL) to give the title compound (3 g). LC-MS ([M+H]⁺ /Rt(min)): 263/0.93 Measurement conditions (1) Reference examples 2 to 8 According to the method described in Reference Example 1, the compounds shown in the following table were obtained using the corresponding starting compounds. [Table 1] The LC-MS in the above table was measured using the measurement conditions (1).Reference example 9 6-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1 ( 2H)-carboxylic acid tert-butyl ester and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester [Chemical 11]a) 6-methyl-4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester and 2-methyl- 4-{[(Trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester (Substance A) manufactured in 1-(Third A solution of 1.5 mol/L of lithium diisopropylamide in THF (4.0 mL) was dissolved in THF (10 mL) of oxycarbonyl)-2-methylpiperidin-4-one (1.1 g) at -78 °C. mL). After stirring at -78 ° C for 10 minutes, a solution of N-phenylbis(trifluoromethanesulfonimide) (2.1 g) in THF (5 mL) was evaporated. After stirring at room temperature for 4 hours, a saturated aqueous solution of ammonium chloride was added at 0 ° C and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the dried organic layer was distilled off under reduced pressure, and then subjected to silica gel column chromatography (solvent solvent; chloroform/methanol) and NH.₂ The material was purified by a silica gel column chromatography (solvent solvent; hexane/ethyl acetate), whereby substance A (1.7 g, a mixture of isomers) was obtained.¹ H-NMR (400 MHz, CDCl₃ ) δ: 5.73, 5.69(s, 1H, isomer ratio=1:1), 4.65-4.23(m, 2H), 3.64-2.52(m, 2H), 2.21-2.02(m, 1H), 1.45(s, 9H), 1.23, 1.16 (ds, 3H, J=6.8 Hz, isomer ratio=1:1). b) 6-Methyl-4-(4,4,5,5-tetramethyl-1,3, 2-Dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester and 2-methyl-4-(4,4,5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester (Reference Example 9) Adding bis(pinacol ester) diborane (1.4 g), 1,1'-bis(diphenylphosphino)ferrocene-di, to a solution of material A (1.7 g) in THF (50 mL) Palladium (II) chloride (0.73 g) and potassium acetate (1.5 g). After stirring at 80 ° C for 2 hours, it was cooled to room temperature, and the precipitate was removed by filtration through celite. Water was added to the filtrate, and extraction was performed with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the organic layer after drying was distilled off under reduced pressure, and then purified by silica gel column chromatography (solvent solvent; hexane/ethyl acetate) to obtain the compound of Reference Example 9 (1.2 g, isomer a mixture of substances). LC-MS ([M+H]⁺ /Rt(min)): 324/1.37 Measurement conditions (1)¹ H-NMR (400 MHz, CDCl₃ δ: 5.73, 5.69(s, 1H, isomer ratio=1:1), 4.43-4.16(m, 2H), 3.61-2.37(m, 2H), 2.13-2.01(m, 1H), 1.44(s, 9H), 1.24(s, 12H), 1.16, 1.03 (d, 3H, J=6.8 Hz, isomer ratio=1:1). Reference Examples 10 to 12 According to the method described in Reference Example 9, the corresponding raw material compound was used. The compound (mixture of isomers) shown in the table below was obtained. [Table 2] The LC-MS in the above table was measured using the measurement conditions (1). Reference Examples 13 to 29 According to the method described in Reference Example 1, the compounds shown in the following Table were obtained by using the corresponding starting compounds. [table 3] The LC-MS in the above table was measured using the measurement conditions (2). Reference Example 30 8-Methyl-2-(trifluoromethyl)-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepine-11-one [Chemical 12]a) Preparation of 4-methyl-2-nitrophenyl trifluoromethanesulfonate (compound W3) A solution of 4-methyl-2-nitrophenol (2.0 g) in chloroform (26 mL) was cooled to 0 ° C. Triethylamine (5.4 mL) and trifluoromethanesulfonic anhydride (2.4 mL) were added and stirred at 0 ° C for 1 hour. Sodium hydrogencarbonate water was added to the reaction mixture at 0 ° C, and extracted with chloroform. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent of the organic layer after drying was evaporated under reduced pressure, and purified by silica gel chromatography (solvent solvent: hexane/ethyl acetate) to give the title compound (3.4 g). LC-MS ([M-H]^- /Rt(min)): 283/0.99 Determination conditions (2) b) Methyl 2-[(4-methyl-2-nitrophenyl)amino]-5-(trifluoromethyl)benzoate ( Preparation of Compound W4) In a solution of compound W3 (2.0 g) in toluene (68 mL), methyl 2-amino-5-(trifluoromethyl)benzoate (1.5 g), potassium carbonate (0.95 g), Triphenylphosphine (0.36 g) and tetrakis(triphenylphosphine)palladium(0) (0.79 g) were stirred under reflux for 2 hours. The reaction solution was returned to room temperature, water was added and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent of the organic layer after drying was evaporated under reduced pressure, and purified by silica gel chromatography (solvent solvent: hexane/ethyl acetate) to give the title compound (2.0 g). LC-MS ([M+H]⁺ /Rt(min)): 355/1.21 Determination conditions (2) c) Methyl 2-[(2-amino-4-methylphenyl)amino]-5-(trifluoromethyl)benzoate ( Compound W5) was prepared from compound W4 (2.0 g) in THF / MeOH / H₂ Ammonium chloride (3.6 g) and iron (1.9 g) were added to a solution of O (3:2:1) (30 mL), and the mixture was stirred for 1 hour under reflux. After cooling the reaction mixture, it was filtered through Celite and washed with ethyl acetate. After the obtained filtrate was subjected to liquid separation extraction with ethyl acetate-water, the organic layer was washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated. LC-MS ([M+H]⁺ /Rt(min)): 325/1.17 Determination conditions (2) d) 2-[(2-Amino-4-methylphenyl)amino]-5-(trifluoromethyl)benzoic acid (Compound W6 THF/H manufactured on compound W5 (1.8 g)₂ Lithium hydroxide (1.6 g) was added to a solution of O (1:1) (30 mL), and stirred under heating and reflux for 2 hr. After cooling the reaction mixture, water was added thereto at 0 ° C, and adjusted to pH 5 with 1 mol/L hydrochloric acid, and then extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (1.6 g). LC-MS ([M+H]⁺ /Rt(min)): 311/0.98 Determination conditions (2) e) 8-Methyl-2-(trifluoromethyl)-5,10-dihydro-11H-dibenzo[b,e][1 , 4] Preparation of diazepine-11-one To a solution of compound W6 (1.6 g) in DMF (23 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbazide Amine hydrochloride (1.4 g) and 1-hydroxybenzotriazole (1.0 g) were stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent of the organic layer after drying was evaporated under reduced pressure, and purified by silica gel chromatography (solvent solvent: hexane/ethyl acetate) to give the title compound (0.41 g). LC-MS ([M+H]⁺ /Rt(min)): 293/0.89 Measurement conditions (2)Reference example 31 and 32 According to the method described in Reference Example 30, the corresponding compound was used to obtain the compound shown in the following table. [Table 4] The LC-MS in the above table was measured using the measurement conditions (2). Reference Example 33 8-Chloro-11- pendantoxy-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepine-2-carbonitrile [Chemical 13]a) 2-[(4-Chloro-2-nitrophenyl)amino]-5-cyanobenzoic acid (Compound W7) was prepared from 4-chloro-1-fluoro-2-nitrobenzene (0.50 g Methyl 2-amino-5-cyanobenzoate (0.50 g) and cesium carbonate (2.8 g) were added to a solution of DMF (2.8 mL) and stirred at 120 ° C for 4 hours. After cooling the reaction mixture, water was added thereto at 0 ° C, and adjusted to pH 5 with 1 mol/L hydrochloric acid, and then extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the dried organic layer was evaporated under reduced pressure to give the title compound (0.90 g). LC-MS ([M-H]^- /Rt(min)): 316/0.87 Determination conditions (2) b) 2-[(2-Amino-4-chlorophenyl)amino]-5-cyanobenzoic acid (Compound W8) manufactured in the compound W7 (0.90 g) in THF/MeOH/H₂ Ammonium chloride (1.5 g) and iron (0.73 g) were added to a solution of O (3:2:1) (30 mL), and the mixture was stirred under reflux for 1 hour. After cooling the reaction mixture, it was filtered through Celite and washed with ethyl acetate. After the obtained filtrate was subjected to liquid separation extraction with ethyl acetate-water, the organic layer was washed with saturated brine. The title compound (0.82 g) was obtained as a crude material. LC-MS ([M+H]⁺ /Rt(min)): 288/0.84 Determination conditions (2) c) 8-Chloro-11-sideoxy-10,11-dihydro-5H-dibenzo[b,e][1,4] Preparation of azine-2-carbonitrile In a solution of compound W8 (0.82 g) in DMF (14 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride Salt (0.60 g) and 1-hydroxybenzotriazole (0.42 g) were stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer obtained was washed with saturated brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue obtained was washed with chloroform (5 mL) to give the title compound (0.25 g). LC-MS ([M+H]⁺ /Rt(min)): 270/0.71 Determination conditions (2) Reference Example 34 (6S)-1,6-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2 -Dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine hydrochloride [Chem. 14]a) (6S)-6-Methyl-4-[(trifluoromethanesulfonyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester and (2S)- Manufacture of 2-methyl-4-[(trifluoromethanesulfonyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester (Substance C) in (2S)- 2-methyl-4-oxopiperidine-1-carboxylic acid tert-butyl ester (10 g) in THF (117 mL), 0.1 mol/L of lithium diisopropylamide at 0 ° C -THF solution (56 mL). After stirring at 0 ° C for 10 minutes, N-phenylbis(trifluoromethanesulfonimide) (22 g) was added at -78 °C. After stirring at -78 ° C for 10 minutes, it was further stirred at room temperature for 3 hours. A saturated aqueous ammonium chloride solution was added at room temperature, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the dried organic layer was distilled off under reduced pressure, and then purified by silica gel column chromatography (solvent solvent; hexane/ethyl acetate) to obtain substance C (18 g, mixture of isomers) ).¹ H-NMR (400 MHz, CDCl₃ δ: 5.73, 5.69(s, 1H, isomer ratio=1:1), 4.65-4.24(m, 2H), 3.64-2.52(m, 2H), 2.21-2.02(m, 1H), 1.45(s, 9H), 1.21, 1.16(d, 3H, J=6.8 Hz, isomer ratio=1:1). b)(6S)-6-Methyl-1,2,3,6-tetrahydropyridin-4-yl Preparation of triflate and (2S)-2-methyl-1,2,3,6-tetrahydropyridin-4-yltrifluoromethanesulfonate (Substance D) in substance C (17 g) A 4 mol/L hydrogen chloride-ethyl acetate solution (61 mL) was added to the ethyl acetate solution (98 mL). After stirring at room temperature for 3 hours, the solvent was distilled off under reduced pressure. Saturated sodium hydrogencarbonate water was added to the obtained crude product, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the dried organic layer was distilled off under reduced pressure, whereby substance D (14 g, mixture of isomers) was obtained. LC-MS ([M+H]⁺ /Rt(min)): 246/0.76 Determination conditions (4) c) (6S)-1,6-Dimethyl-1,2,3,6-tetrahydropyridin-4-yltrifluoromethanesulfonate (Compound W11) Manufactured in a solution of material D (12 g) in MeOH (163 mL), EtOAc (EtOAc) After stirring at room temperature for 1 hour, the solvent was distilled off under reduced pressure. Saturated sodium hydrogencarbonate water was added to the obtained crude product, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the dried organic layer was distilled off under reduced pressure, and then subjected to silica gel column chromatography (solvent solvent; chloroform/ethyl acetate) and NH.₂ The compound was purified by a silica gel column chromatography (solvent solvent; chloroform/ethyl acetate), whereby Compound W11 (3.9 g) was obtained.¹ H-NMR (400 MHz, CDCl₃ ) δ: 5.60 (s, 1H), 2.94-2.92 (m, 2H), 2.61-2.53 (m, 2H), 2.32-2.25 (m, 1H), 2.36 (s, 3H), 1.18 (d, 3H, J=6.7 Hz). d)(6S)-1,6-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane- Preparation of 2-yl)-1,2,3,6-tetrahydropyridine hydrochloride (Reference Example 34) in a solution of compound W11 (3.9 g) in THF (51 mL). That is an alcohol ester) diborane (4.3 g), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) chloride (0.62 g) and potassium acetate (4.5 g). After stirring at 80 ° C for 1 hour, it was cooled to room temperature. After the precipitate was removed by filtration through diatomaceous earth, the solvent was distilled off under reduced pressure. Diethyl ether was added to the crude product, and the precipitate was removed by filtration through celite, and the solvent was evaporated under reduced pressure. The obtained crude product (6.5 g) was dissolved in diethyl ether (40 mL), and 4 mol/L hydrogen chloride-ethyl acetate solution (4.0 mL) was added. The precipitated solid was filtered and washed with hexane to obtain Reference Example 34 (3.5 g). LC-MS ([M+H]⁺ /Rt(min)): 238/1.25 Determination conditions (4) Example 1 8-Chloro-2-fluoro-11-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl) -5H-dibenzo[b,e][1,4]diazepine [Chemical 15]a) 8,11-Dichloro-2-fluoro-5H-dibenzo[b,e][1,4]diazepine (Compound W9), which was produced from the compound of Reference Example 1 (1.0 g) of toluene ( 20 mL) solution was added with N,N-dimethylaniline (2.3 g) and phosphorus oxychloride (1.8 g). After stirring at 95 ° C for 2 hours, it was cooled. To the reaction mixture were added THF and aq. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. After the solvent of the dried organic layer was distilled off under reduced pressure, N,N-dimethylaniline was removed by a silica gel column chromatography (solvent solvent; hexane/ethyl acetate) to obtain compound W9 (0.9 g). . b) 8-Chloro-2-fluoro-11-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-dibenzo[b,e][1,4] Preparation of diazepine (Example 1) In a solution of compound W9 (0.9 g) in THF/water (4/1) (50 mL), 1-methyl-4-(4,4,5,5-tetra Methyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (1.0 g), potassium carbonate (1.6 g) and tetrakis (triphenyl) Phenylphosphine) palladium (0) (0.88 g). After stirring at 75 ° C for 1 hour, it was cooled. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the dried organic layer was distilled off under reduced pressure, and then subjected to silica gel column chromatography (solvent solvent; chloroform/methanol) and NH.₂ The title compound (0.70 g) was obtained. LC-MS ([M+H]⁺ /Rt(min)): 342/0.67 Measurement conditions (1)¹ H-NMR (400 MHz, CDCl₃ ) δ: 7.20 (d, 1H, J = 2.4 Hz), 7.00-6.92 (m, 3H), 6.72-6.68 (m, 1H), 6.61 (d, 1H, J = 8.0 Hz), 6.09-6.05 (m , 1H), 4.78(s, 1H), 3.15-3.11(m, 2H), 2.74-2.70(m, 2H), 2.64(t, 2H, J=5.2 Hz), 2.40(s, 3H). 2 to 6 According to the method described in Example 1, the compounds of Examples 2 to 6 were obtained by using the compound of the corresponding Reference Example and the starting compound. [table 5]The LC-MS in the above table was measured using the measurement conditions (1). Example 7 and Example 8 8-chloro-2-fluoro-11-(6-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-dibenzo[b,e] [1,4]diazepine (Example 7) 8-chloro-2-fluoro-11-(2-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-diphenyl And [b,e][1,4]diazepine (Example 8) [Chemical 16]a) 4-(8-chloro-2-fluoro-5H-dibenzo[b,e][1,4]diazepine-11-yl)-6-methyl-3,6-dihydropyridine- 1(2H)-carboxylic acid tert-butyl ester and 4-(8-chloro-2-fluoro-5H-dibenzo[b,e][1,4]diazepine-11-yl)-2-yl Preparation of benzyl-3,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester (substance B) was added to a solution of compound W9 (1.1 g) in THF/water (4/1) (50 mL) Reference compound 9 (mixture of isomers) (1.3 g), potassium carbonate (1.7 g) and tetrakis(triphenylphosphine)palladium(0) (0.92 g). After stirring at 75 ° C for 1 hour, it was cooled, and water was added to the reaction mixture, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the dried organic layer was distilled off under reduced pressure, and then purified by silica gel column chromatography (solvent solvent; hexane/ethyl acetate) to obtain substance B (1.0 g, mixture of isomers) ). LC-MS ([M+H]⁺ /Rt(min)): 442/1.45 Determination conditions (1) b) 8-Chloro-2-fluoro-11-(6-methyl-1,2,3,6-tetrahydropyridin-4-yl)- 5H-dibenzo[b,e][1,4]diazepine (Example 7) and 8-chloro-2-fluoro-11-(2-methyl-1,2,3,6-tetrahydrol Pyridin-4-yl)-5H-dibenzo[b,e][1,4]diazepine (Example 8) was added to a solution of material B (0.17 g) in dichloromethane (4 mL) Trifluoroacetic acid (1 mL) was stirred at room temperature for 1 hour. Saturated sodium hydrogencarbonate water was added to the reaction mixture cooled in ice-bath, and extracted with chloroform. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. After the solvent of the dried organic layer was distilled off under reduced pressure, the obtained residue was subjected to reverse phase refining by ODS (octadecylsilyl, octadecyl decyl) column (0.05% aqueous solution of trifluoroacetic acid: acetonitrile). The TFA salt was freed by a liquid separation operation using chloroform-saturated sodium hydrogencarbonate, whereby the compound of Example 7 (10 mg) and the compound of Example 8 (10 mg) were obtained. 8-chloro-2-fluoro-11-(6-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-dibenzo[b,e][1,4]diazepine呯 (Example 7): LC-MS ([M+H]⁺ /Rt(min)): 342/0.73 Measurement conditions (1)¹ H-NMR (400 MHz, CDCl₃ ) δ: 7.19 (d, 1H, J = 2.3 Hz), 7.00-6.89 (m, 3H), 6.73-6.70 (m, 1H), 6.62 (d, 1H, 8.3 Hz), 5.98 (s, 1H), 4.80(s, 1H), 3.64-3.62(m, 1H), 3.28-3.23(m, 1H), 2.98-2.91(m, 1H), 2.61-2.46(m, 2H), 1.19(d, 3H, J =6.9 Hz). 8-Chloro-2-fluoro-11-(2-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-dibenzo[b,e][1 , 4] diazepine (Example 8): LC-MS ([M+H]⁺ /Rt(min)): 342/0.75 Measurement conditions (1)¹ H-NMR (400 MHz, CDCl₃ ) δ: 7.20 (d, 1H, J = 2.3 Hz), 7.01-6.89 (m, 3H), 6.73-6.69 (m, 1H), 6.61 (d, 1H, J = 8.7 Hz), 6.12 (s, 1H) ), 4.79(s, 1H), 3.65-3.62(m, 2H), 2.98-2.89(m, 1H), 2.84-2.79(m, 1H), 2.16-2.06(m, 1H), 1.25(d, 3H) , J = 6.4 Hz). Examples 9 to 16 According to the methods described in Example 7 and Example 8, the compounds of Examples 9 to 16 were obtained by using the compound of the corresponding Reference Example and the starting compound. [Table 6]The LC-MS in the above table was measured using the measurement conditions (1). Example 17 and Example 18 8-chloro-11-(1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-fluoro-5H-dibenzo[b] , e][1,4]diazepine (Example 17) 8-chloro-11-(1,2-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2- Fluoro-5H-dibenzo[b,e][1,4]diazepine (Example 18) [Chem. 17]To a solution of the mixture of Example 7 and Example 8 (1:1) (1.0 g) in methanol (20 mL) was added 37% formaldehyde solution (0.73 g) and magnesium sulfate (5.0 g), and stirred at 50 ° C hour. The reaction solution was cooled in an ice bath, and sodium borohydride (0.68 g) was slowly added. After stirring at room temperature for 1 hour, the solid matter was removed by filtration through celite. Water was added to the filtrate, and extraction was performed with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. After the solvent of the dried organic layer is distilled off under reduced pressure, by NH₂ The compound of Example 17 (0.20 g) and the compound of Example 18 (0.20 g) were obtained by the purification of the column chromatography (solvent solvent; hexane/ethyl acetate). 8-Chloro-11-(1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-fluoro-5H-dibenzo[b,e][1,4 Diazoxide (Example 17):¹ H-NMR (400 MHz, CDCl₃ ) δ: 7.20 (d, 1H, J = 2.3 Hz), 7.01-6.89 (m, 3H), 6.72-6.69 (m, 1H), 6.61 (d, 1H, J = 8.7 Hz), 5.87 (s, 1H) ), 4.78(s, 1H), 3.01-2.88(m, 2H), 2.73-2.43(m, 3H), 2.41(s, 3H), 1.19(d, 3H, J=6.8 Hz). LC-MS( [M+H]⁺ /Rt(min)): 356/0.71 Determination conditions (1) 8-Chloro-11-(1,2-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-fluoro -5H-dibenzo[b,e][1,4]diazepine (Example 18):¹ H-NMR (400 MHz, CDCl₃ ) δ: 7.20 (d, 1H, J = 2.8 Hz), 7.00-6.92 (m, 3H), 6.72-6.68 (m, 1H), 6.61 (d, 1H, J = 8.7 Hz), 6.05 (s, 1H) ), 4.77(s, 1H), 3.49-3.39(m, 2H), 3.06-2.22(m, 3H), 2.36(s, 3H), 1.18(d, 3H, J=4.8 Hz). LC-MS( [M+H]⁺ /Rt(min)): 356/0.73 Measurement conditions (1) Examples 19 to 21 According to the methods described in Example 17 and Example 18, the compounds of the corresponding reference examples and the starting compounds were used to obtain Examples 19-21. Compound. [Table 7]The LC-MS in the above table was measured using the measurement conditions (1). Example 22 8-Chloro-2-fluoro-11-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-dibenzo[b,e][1,4 Diazoxide [Chemical 18]a) 8-Chloro-2-fluoro-11-(pyridin-4-yl)-5H-dibenzo[b,e][1,4]diazepine (W10) manufactured from compound W9 (107 mg) Pyridine-4-boronic acid (94 mg), potassium carbonate (0.16 g) and tetrakis(triphenylphosphine)palladium(0) (88 mg) were added to a solution of THF/water (4/1) (5 mL). After stirring at 75 ° C for 1 hour, water was added to the reaction mixture cooled in an ice bath, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the dried organic layer was distilled off under reduced pressure, and then subjected to silica gel column chromatography (solvent solvent; chloroform/methanol) and NH.₂ This was purified by a silica gel column chromatography (solvent solvent; hexane/ethyl acetate), whereby Compound W10 (45 mg) was obtained. LC-MS ([M+H]⁺ /Rt(min)): 324/1.03 Determination conditions (1) b) 8-Chloro-2-fluoro-11-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)- 5H-Dibenzo[b,e][1,4]diazepine (Example 22) was added to a solution of compound W10 (15 mg) in acetonitrile (0.42 mL). After stirring at 60 ° C for 1 hour, the reaction solution was concentrated. The residue obtained was dissolved in methanol (0.20 mL), and sodium borohydride (16 mg) was added at 0 °C. After stirring at room temperature for 1 hour, water was added to the reaction mixture and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. The solvent of the dried organic layer was distilled off under reduced pressure, and then subjected to silica gel column chromatography (solvent solvent; chloroform/methanol) and NH.₂ The title compound (10 mg) was obtained by chromatography eluting elution elution LC-MS ([M+H]⁺ /Rt(min)): 342/0.67 Measurement conditions (1)¹ H-NMR (400 MHz, CDCl₃ ) δ: 7.20 (d, 1H, J = 2.4 Hz), 7.00-6.92 (m, 3H), 6.72-6.68 (m, 1H), 6.61 (d, 1H, J = 8.0 Hz), 6.09-6.05 (m , 1H), 4.78(s, 1H), 3.15-3.11(m, 2H), 2.74-2.70(m, 2H), 2.64(t, 2H, J=5.2 Hz), 2.40(s, 3H). 23 to 31 According to the method described in Example 22, the compounds of Examples 23 to 31 were obtained by using the compound of the corresponding Reference Example and the starting compound. [Table 8][Table 9]The LC-MS in the above table was measured using the measurement conditions (1). Examples 32 to 89 According to the methods described in Example 1, Example 7, and Example 8, Example 17 and Example 18, the compounds of Examples 32 to 89 were obtained by using the compound of the corresponding Reference Example and the starting compound. [Table 10][Table 11][Table 12][Table 13][Table 14][Table 15][Table 16][Table 17][Table 18][Table 19]Test Example Hereinafter, the pharmacological test results of the compound of the present invention will be described, and the pharmacological action of the compound will be described. However, the present invention is not limited to the test examples. Test Example 1: For human type D₁ Receptor, human D₂ Receptor, human 5-HT_2A Receptor antagonist activity evaluation test for human type D₁ Receptor, human D₂ Receptor, human 5-HT_2A The antagonist activity of the receptor was measured using intracellular calcium concentration as an index. Temporarily presenting aequorin, Gα16 protein, and each receptor in CHO-K1 cells (Chinese hamster ovary), seeded in 384-well plates, in CO₂ Incubate overnight at 37 ° C in an incubator. After the addition of coelenterazine, FDSS (manufactured by Hamamatsu Photonics) was added, and a DMSO suspension of the compound of the present invention was added, followed by addition of dopamine (final concentration of 100 nmol/L) or serotonin (final concentration of 30 nmol/L) to measure luminescence. The change in quantity. The antagonist activity was calculated by setting the amount of luminescence of the well to which only DMSO was added to 100% inhibition, and the compound of the present invention 1 μmol/L when the amount of luminescence of the well to which only dopamine or serotonin was added was 0% inhibition. The inhibition rate below. Further, the concentration in the following table indicates the inhibition rate at the concentration described (for example, the expression of 58@0.1 μmol/L indicates that the inhibition rate at 0.1 μmol/L is 58%). Further, clozapine was used as a comparative substance as a comparative example. The results are shown in the table below. [Table 20] [Table 21] [Table 22] Test Example 2: Capture analysis of dansyl glutathione (dGSH) The compound of the present invention was metabolized in liver microsomes, and the reaction of the produced metabolite was detected by reaction with dansole glutathione (dGSH). Metabolites are quantified. The metabolic reaction system was performed using a screening robot (manufactured by Tecan Co., Ltd.), and the metabolite-dGSH conjugate concentration was measured using a UPLC (ultra performance liquid chromatography) system (manufactured by Waters Co., Ltd.). (Presolution Preparation) The compound of the present invention was dissolved in DMSO to prepare a 10 mmol/L test substance solution. Further, clozapine was used as a comparative substance as a comparative example. A microsomal solution was prepared by mixing 7.6 mL of potassium phosphate buffer (500 mmol/L, pH 7.4), human liver microsomes (manufactured by Xenotech, 20 mg protein/mL), 1.9 mL, and 1.27 mL of pure water. A microsome (dGSH(-)) solution was prepared by adding 0.67 mL of pure water to 3.78 mL of the microsome solution. A microsome (dGSH(+)) solution was prepared by adding 1.14 mL of dGSH solution (20 mmol/L) to 6.48 mL of the microsome solution. A cofactor solution was prepared by dissolving 80.9 mg of NADPH (nicotinamide adenine dinucleotide phosphate) in 30 mL of pure water. A reaction stop solution was prepared by dissolving 33 mg of tris(2-carboxyethyl)phosphine (TECP, Tris(2-carboxyethyl)phosphin) in 115 mL of methanol. (Reaction) 12 μL of the test substance solution was mixed with 388 μL of pure water, and dispensed to 6 holes per 50 μL in a 96-well plate. The above 6 wells were divided into three groups of two wells, and were designated as "reaction group", "unreacted group", and "dGSH unadded group". A microsome (dGSH(+)) solution was added to 50 μL of the "reaction group" and "unreacted group", and a microsome (dGSH(-)) solution was added to 50 μL of the "dGSH unadded group". Cofactor solution was added to 50 μL of "reaction group" and "dGSH unadded group", and pure water was added to 50 μL of "unreacted group". After incubation at 37 ° C for 60 minutes, the reaction was terminated by adding a reaction stop solution per 450 μL. Add pure water to 50 μL of the "reaction group" and "dGSH unadded group", add a cofactor solution every 50 μL in the "unreacted group", and cool the plate at -20 ° C for 1 hour. , centrifuge (4000 rpm, 10 minutes). The supernatant was recovered in another dish for analysis. (Analysis) Using a fluorescent detection UPLC system (manufactured by Waters Co., Ltd.), "reaction group", "unreacted group", and "dGSH unadded group" were analyzed under the following conditions. Column: Waters ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm, 2.1 mm × 10 mm) Dissolution solvent: A solution 0.2% formic acid / 40% methanol B solution 0.2% formic acid / methanol gradient: B solution, 0% (0 Min)→83.3%(9.33 min)→83.3%(10.63 min)→0%(10.64 min)→0%(13 min) The fluorescence intensity varies depending on the composition of the organic solvent, so it is composed of the organic solvent at the time of dissolution. Make corrections. The metabolite-dGSH conjugate concentration of the "reaction group" was calculated by subtracting the fluorescence peaks detected in the "unreacted group" and "dGSH unadded group" from the fluorescence peak detected in the "reaction group". . By measuring the concentration of the metabolite-dGSH conjugate of the "reaction group", the risk of the reactive metabolite of the test substance can be evaluated. The results of the concentration of the metabolite-dGSH conjugate of the "reaction group" of clozapine and the compound of the present invention are shown in the following table. [Table 23] [Table 24] Further, based on the analysis result of Test Example 2, the fluorescence peak detected in the "unreacted group" was subtracted from the fluorescence peak detected in the "dGSH unadded group", thereby calculating the dGSH binding of the "unreacted group". Concentration of matter. By measuring the concentration of the dGSH conjugate of the "unreacted group", the covalent bonding property of the test substance considered to be related to cytotoxicity or immunotoxicity can be evaluated. The results of the dGSH conjugate concentration of the "unreacted group" of the compound of the present invention are shown in the following table. [Table 25] Test Example 3: Human liver microsome metabolic stability test In this test, the stability of the test substance to human liver microsome metabolism can be evaluated. The human liver microsomal stability (MS) of the compounds of the present invention was evaluated by the following method. The human liver particle system uses the manufacturer of Xenontech. Human liver microsomes, NADPH, and test substances were mixed in a 125 mmol/L phosphate buffer (pH 7.4) to have the following concentrations, and cultured at 37 ° C for 30 minutes.・Human liver microsomes: 0.1 mg/mL ・NAPDH: 3.2 mmol/L ・Substance: 0.1 μmol/L The residual rate of the test substance in the sample after 30 minutes by LC-MS, according to the following formula Calculate the stability of the test substance to human liver microsome metabolism. Stability to human liver microsome metabolism (mL/min/mg protein) = -LN (residual ratio) / 30/0.1 The results are shown in the table below. [Table 26] Test Example 4: Rat brain transition test In this test, the intracerebral mobility of the compound of the present invention can be evaluated. For the SD rats of 7 weeks, the compound of the present invention was administered subcutaneously by a 0.01 mol/L hydrochloric acid aqueous solution, and plasma and brain were collected 1 hour after the administration, and the plasma and brain drug concentrations were measured by LC-MS. Serum and brain protein binding rates of the compounds of the invention were determined using equilibrium dialysis. Kp, uu, brain (brain/plasma unconjugated drug concentration ratio) can be calculated by applying the plasma and intracerebral compound concentration obtained by the above test and the serum and intracerebral protein binding rate to the following formula. . Kp, uu, brain=(concentration of compound in brain × (100-intraceramic protein binding rate (%)) / 100) / (concentration of compound in plasma × (100 - serum protein binding rate (%)) / 100) The results are shown in the table below. [Table 27] Test Example 5: Evaluation of Positive Symptoms by Induction of Hyperactivity of Rat Methamphetamine The exercise hyperactivity caused by administration of methamphetamine to rats was used as schizophrenia. The evaluation system for positive symptoms can evaluate the inhibitory effect when the compound of the present invention is administered. After administration of the compound of the present invention to rats of 6 to 10 weeks, the amount of exercise from 90 minutes after the administration of methamphetamine was measured. SuperMex (Muromachi Machinery Co., Ltd.) was used for the measurement. The inhibition rate when the amount of exercise in which the solvent was administered to the group was set to 100% was calculated. Test Example 6: Evaluation of the effectiveness of patients with schizophrenia In the clinical, as a criterion for evaluating the psychotic symptoms of schizophrenia, PANSS (Positive and Negative Syndrome Scale) and CGI-S (CGI-S) were used. Clinical Global Impression Severity scale, etc. After administration of the compound of the present invention for 6 to 24 weeks, the effectiveness was evaluated using the above evaluation criteria. Test Example 7: Cyano capture assay In this test, a reactive metabolite not captured by sulforaphane glutathione was detected. Metabolizing a compound of the invention in human liver microsomes with radioactive potassium cyanide (K¹⁴ CN) The reaction is carried out, whereby the reactive metabolite is detected and quantified. The human liver microparticle system was subjected to a reaction at 37 ° C for 60 minutes under the following conditions using a manufacturer of Xenontech. Concentration conditions ・Phosphate buffer (pH 7.4): 100 mM ・Human liver microsomes: 1 mg/mL ・K¹⁴ CN: 0.1 mM ・Test substance: 50 μM ・NADPH: 0 mM or 1 mM will be combined with K¹⁴ The reactive metabolite in which the CN is reacted is fractionated by solid phase extraction, and the radioactive concentration is measured using a liquid scintillation counter. The generation gap of the reactive metabolite was calculated by subtracting the measurement value obtained under the condition that NADPH was not added from the measurement value obtained under the condition of adding NADPH. Test Example 8: For human 5-HT_2C Receptor, human histamine H₁ Receptor (hereinafter referred to as H₁ Receptor), human muscarinic M₁ Receptor (hereinafter referred to as M₁ Receptor), human muscarinic M₂ Receptor (hereinafter referred to as M₂ Receptor), human muscarinic M₃ Receptor (hereinafter referred to as M₃ Receptor) and human muscarinic M₄ Receptor (hereinafter referred to as M₄ Receptor) antagonist activity evaluation test for human 5-HT_2C Receptor, human H₁ Receptor, human M₁ Receptor, human M₂ Receptor, human M₃ Receptor and human M₄ The antagonist activity of the receptor was measured using intracellular calcium concentration as an index. Temporarily presenting aequorin, Gα16 protein and each receptor in CHO-K1 cells (Chinese hamster ovary), seeded in 384-well plates, in CO₂ Incubate overnight at 37 ° C in an incubator. After the addition of coelenterazine, a DMSO suspension of the compound of the present invention was added using FDSS (manufactured by Hamamatsu Photonics Co., Ltd.), and then the corresponding ligand shown in the following table was added, and the change in the amount of luminescence was measured. The ligands used in the evaluation of the antagonist activity of each receptor and the concentrations thereof used are shown in the table below. [Table 28] The antagonist activity was such that the amount of luminescence of the well to which only DMSO was added was 100% inhibition, and the amount of luminescence of the well to which only the corresponding ligand was added was set to 0% inhibition, and the concentration of the compound of the present invention was calculated to be 1 μmol/L. Or inhibition rate in the case of 0.1 μmol/L. [Table 29] Test Example 9: For human 5-HT_2A Receptor, human D₁ Receptor, human D₂ Receptor, human 5-HT_2C Receptor, human H₁ Receptor, human M₁ Receptor, human M₂ Receptor, human M₃ Receptor and human M₄ Evaluation of binding activity of the receptor In this test, the compound of the present invention can be assayed for human 5-HT_2A Receptor, human D₁ Receptor, human D₂ Receptor, human 5-HT_2C Receptor, human H₁ Receptor, human M₁ Receptor, human M₂ Receptor, human M₃ Receptor and human M₄ The binding affinity of the receptor. Using a CHO cell membrane component or a CHO-K1 cell membrane component or the like which exhibits such receptors, in a binding evaluation test, a test compound dissolved in DMSO, a sample of various receptor membranes diluted with a buffer, and The receptors are mixed with RI (Radio Isotope) labeled ligands and incubated at room temperature for 30 minutes or 60 minutes, respectively. As an RI-labeled ligand for a receptor, it can be appropriately selected according to test conditions, etc., and can be used for 5-HT._2A The receptor uses [3H] ketanserin (Ketanserin), for D₂ The receptor uses [3H] Spiperone, for D₁ The receptor used [3H]SCH23390. Non-specific binding to receptors based on 5-HT_2A The receptor exists in Mianserin, for D₂ Receptor in the presence of dopamine, for D₁ The receptor is determined by a competitive binding assay such as SCH23390. After measuring the radioactivity bound to the receptor using a liquid scintillation counter, the 50% inhibitory concentration was calculated, and the Ki value was evaluated from the dissociation constant and the substrate concentration calculated from the saturation binding test, and used as the binding affinity. In addition to this, about the human 5-HT_2C Receptor, human H₁ Receptor, human M₁ Receptor, human M₂ Receptor, human M₃ Receptor and human M₄ The binding affinity of the receptor can also be determined according to the above method. As the RI-labeled ligand for the receptors, it can be appropriately selected according to the test conditions and the like, for example, for human 5-HT_2C The receptor uses [3H] Mesulergine for human H₁ The receptor uses [3H] Pyrilamine for human M₁ Receptor, human M₂ Receptor, human M₃ Receptor and human M₄ As the receptor, [3H]N-methylethylpolamine or the like is used. Furthermore, the non-specific binding of these receptors is based on human 5-HT_2C The receptor exists in Mianserin, targeting human H₁ Receptor Pyrilamine for human M₁ Receptor, human M₂ Receptor, human M₃ Receptor and human M₄ The receptor is determined by a competitive binding assay such as Atropine. [Industrial Applicability] The compound of the present invention is due to dopamine D₁ Receptor, dopamine D₂ Receptor and serotonin 5-HT_2A The receptor exhibits antagonism and is therefore useful as a therapeutic and/or prophylactic agent for central nervous system diseases.

Claims (28)

A compound or a pharmaceutically acceptable salt thereof, which is represented by the formula (1): [wherein, ring Q ¹ represents a benzene ring which may be substituted or a pyridine ring which may be substituted; ring Q ² represents a benzene ring which may be substituted, or a pyridine ring which may be substituted; R ^a represents a hydrogen atom, or may be a C _1-6 alkyl group substituted with 1 to 3 halogen atoms of the same or different species; n represents 0, 1 or 2; m represents 1, 2, 3 or 4; R ^b is independently in the presence of a plurality of cases The ground represents a hydrogen atom, a halogen atom, or a C _1-6 alkyl group which may be substituted with 1 to 3 halogen atoms of the same or different species. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the ring Q ¹ is a benzene ring or a pyridine ring (the benzene ring or the pyridine ring may be selected from a halogen atom, a cyano group, the same or a heterogeneous one) a C _1-6 alkyl group substituted with 3 halogen atoms, a C _1-6 alkoxy group which may be substituted with 1 to 3 halogen atoms of the same or different kinds, and 1 to 2 C _{1 which} may be homologous or heterologous _a group of 1 to 4 groups of the same or a heterogeneous group of ₆ alkyl-substituted amine groups; the ring Q ² is a benzene ring or a pyridine ring (the benzene ring or the pyridine ring may be selected from a halogen atom, a cyano group) a C _1-6 alkyl group which may be substituted with 1 to 3 halogen atoms of the same or different species, a C _1-6 alkoxy group which may be substituted by 1 to 3 halogen atoms of the same or different species, and may be homologous or heterogeneous One to four bases of the same or different species in the group consisting of 1 to 2 C _1-6 alkyl-substituted amine groups). The compound of claim 1 or 2, wherein the ring Q ¹ is a benzene ring (the ring may be selected from a halogen atom, a cyano group, a ^1-3 ring halogen atom which may be homologous or heterologous) a substituted C _1-6 alkyl group, and a _1-4 amino group of the same or a heterogeneous group of the C _1-6 alkoxy group which may be substituted with 1 to 3 halogen atoms of the same or different species; Q ² is a benzene ring (the ring may be a C _1-6 alkyl group selected from a halogen atom, a cyano group, a 1-3 ring halogen atom which may be substituted by the same species or a heterogeneous group), and one to three groups which may be homologous or heterologous One to four substituents of the same or different species in the group consisting of a C _1-6 alkoxy group substituted by a halogen atom). The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein n is 1. The compound of any one of claims 1 to 4, wherein the R ^b is independently a halogen atom, or may be homologous or heterologous, 1 to 3, in the case where a plurality of compounds are present. A C _1-6 alkyl group substituted by a halogen atom. The compound of claim 1 or a pharmaceutically acceptable salt thereof, which is represented by the formula (1a): Wherein R ^a represents a hydrogen atom or a C _1-6 alkyl group which may be substituted with 1 to 3 halogen atoms of the same or different species; R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ each independently represent a hydrogen atom, a halogen atom, a cyano group, a C _1-6 alkyl group which may be substituted with 1 to 3 halogen atoms of the same or different kinds, and may have 1 to 3 halogens of the same or different species. An atom-substituted C _1-6 alkoxy group, or an amine group which may be substituted with 1 to 2 C _1-6 alkyl groups of the same or different species; R ¹¹ , R ¹² , R ¹³ and R ¹⁴ each independently represent a hydrogen atom a halogen atom or a C _1-6 alkyl group which may be substituted by 1 to 3 halogen atoms of the same or different species. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein any one of R ¹¹ , R ¹² , R ¹³ and R ¹⁴ is a halogen atom or may be one or three halogens of the same or different species A _C1-6 alkyl group substituted by an atom. The compound of claim 6 or a pharmaceutically acceptable salt thereof, which is represented by the formula (1b): [wherein, R ^a , R ² , R ⁷ , R ¹³ and R ¹⁴ are synonymous with the claim 6]. The compound of any one of claims 6 to 8, or a pharmaceutically acceptable salt thereof, wherein R ¹³ is a C _1-6 alkyl group. The compound of any one of claims 6 to 8, or a pharmaceutically acceptable salt thereof, wherein R ¹³ is methyl. A compound according to any one of claims 6 to 10, wherein R ¹⁴ is a hydrogen atom, or a pharmaceutically acceptable salt thereof. The compound of claim 6 or a pharmaceutically acceptable salt thereof, which is represented by the formula (1b-1): [wherein, R ^a , R ² and R ⁷ are synonymous with claim 6]. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein R ^a is ^a C _1-6 alkyl group which may be substituted with 1 to 3 halogen atoms of the same or different species. The compound of any one of claims 1 to 12, wherein R ^a is a methyl group, or a pharmaceutically acceptable salt thereof. The compound of any one of claims 6 to 14, or a pharmaceutically acceptable salt thereof, wherein R ² and R ⁷ are each independently a hydrogen atom, a halogen atom, a cyano group, and may be homologous or heterologous 1 to 3 the halogen atoms substituted C _1-6 alkyl group, a substituted or may be of the same type or different 1 to 3 halogen atoms, C _1-6 alkoxy group. The compound of any one of claims 6 to 14, or a pharmaceutically acceptable salt thereof, wherein any one of R ² and R ⁷ is a halogen atom, a cyano group, and the same or different species may be 1 to 3 the halogen atoms substituted C _1-6 alkyl group, a substituted or may be of the same type or different 1 to 3 halogen atoms, C _1-6 alkoxy group. The compound of any one of claims 6 to 14, wherein R ² is a hydrogen atom, a fluorine atom, a chlorine atom, a C _1-3 alkyl group or a C _1-3 alkoxy group, or a pharmaceutically acceptable salt thereof. R ⁷ is a hydrogen atom, a fluorine atom, a chlorine atom, a cyano group, a C _1-3 alkyl group which may be substituted by 1 to 3 fluorine atoms, or a C _1-6 alkoxy group which may be substituted by 1 to 3 fluorine atoms. . The compound of claim 1 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: 11-[(6S)-1,6-dimethyl-1,2,3,6-tetra Hydropyridin-4-yl]-8-methyl-2-(trifluoromethyl)-5H-dibenzo[b,e][1,4]diazepine, 8-methyl-11-[( 6S)-6-Methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethyl)-5H-dibenzo[ b,e][1,4]diazepine, 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2 -(trifluoromethoxy)-5H-dibenzo[b,e][1,4]diazepine, 8-chloro-11-[(6S)-6-methyl-1-( ² H ₃ Methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethoxy)-5H-dibenzo[b,e][1,4]diazepine, 8-Chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-ethyl-5H-dibenzo[b,e ][1,4]diazepine, 8-chloro-2-ethyl-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetra Hydropyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine, 11-[(6S)-1,6-dimethyl-1,2,3,6- Tetrahydropyridin-4-yl]-2-ethyl-8-fluoro-5H-dibenzo[b,e][1,4]diazepine, 2-ethyl-8-fluoro-11-[( 6S)-6-Methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1,4] Dinitrogen 2-Chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-8-fluoro-5H-dibenzo[b,e ][1,4]diazepine, 2-chloro-8-fluoro-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydro Pyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine, 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3 ,6-tetrahydropyridin-4-yl]-2-methyl-5H-dibenzo[b,e][1,4]diazepine, 8-chloro-2-methyl-11-[(6S )-6-Methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1,4] Nitrogen, 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-methoxy-5H-dibenzo [b,e][1,4]diazepine, 8-chloro-2-methoxy-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2, 3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine, 8-chloro-11-[(6S)-1,6-dimethyl -1,2,3,6-tetrahydropyridin-4-yl]-2-ethoxy-5H-dibenzo[b,e][1,4]diazepine and 8-chloro-2-ethyl Oxyl-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b, e] [1,4] diazepine. The compound of claim 1 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: 11-[(6S)-1,6-dimethyl-1,2,3,6-tetra Hydropyridin-4-yl]-8-methyl-2-(trifluoromethyl)-5H-dibenzo[b,e][1,4]diazepine, 8-methyl-11-[( 6S)-6-Methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethyl)-5H-dibenzo[ b,e][1,4]diazepine, 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2 -(trifluoromethoxy)-5H-dibenzo[b,e][1,4]diazepine, 8-chloro-11-[(6S)-6-methyl-1-( ² H ₃ Methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethoxy)-5H-dibenzo[b,e][1,4]diazepine, 8-Chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-ethyl-5H-dibenzo[b,e ][1,4]diazepine, 8-chloro-2-ethyl-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetra Hydropyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine, 11-[(6S)-1,6-dimethyl-1,2,3,6- Tetrahydropyridin-4-yl]-2-ethyl-8-fluoro-5H-dibenzo[b,e][1,4]diazepine, 2-ethyl-8-fluoro-11-[( 6S)-6-Methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1,4] Dinitrogen , 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-methoxy-5H-dibenzo[b ,e][1,4]diazepine, 8-chloro-2-methoxy-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3, 6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine, 8-chloro-11-[(6S)-1,6-dimethyl-1 ,2,3,6-tetrahydropyridin-4-yl]-2-ethoxy-5H-dibenzo[b,e][1,4]diazepine and 8-chloro-2-ethoxyl -11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e] [1,4]diazepine. The compound of claim 1 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: 11-[(6S)-1,6-dimethyl-1,2,3,6-tetra Hydropyridin-4-yl]-8-methyl-2-(trifluoromethyl)-5H-dibenzo[b,e][1,4]diazepine, 8-methyl-11-[( 6S)-6-Methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethyl)-5H-dibenzo[ b,e][1,4]diazepine, 8-chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2 -(trifluoromethoxy)-5H-dibenzo[b,e][1,4]diazepine, 8-chloro-11-[(6S)-6-methyl-1-( ² H ₃ Methyl-1,2,3,6-tetrahydropyridin-4-yl]-2-(trifluoromethoxy)-5H-dibenzo[b,e][1,4]diazepine, 8-Chloro-11-[(6S)-1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl]-2-ethyl-5H-dibenzo[b,e ][1,4]diazepine, 8-chloro-2-ethyl-11-[(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetra Hydropyridin-4-yl]-5H-dibenzo[b,e][1,4]diazepine, 8-chloro-11-[(6S)-1,6-dimethyl-1,2, 3,6-tetrahydropyridin-4-yl]-2-ethoxy-5H-dibenzo[b,e][1,4]diazepine and 8-chloro-2-ethoxy-11- [(6S)-6-methyl-1-( ² H ₃ )methyl-1,2,3,6-tetrahydropyridin-4-yl]-5H-dibenzo[b,e][1, 4] two Nitrogen. A medicine comprising the compound according to any one of claims 1 to 20 or a pharmaceutically acceptable salt thereof as an active ingredient. A therapeutic agent for a central nervous system disease, which comprises the compound according to any one of claims 1 to 20 or a pharmaceutically acceptable salt thereof as an active ingredient. The therapeutic agent according to claim 22, wherein the central nervous system disease is schizophrenia, bipolar disorder, autism, ADHD, depression, anxiety disorder, sleep disorder, dementia behavior and psychological symptoms (BPSD (Behavioral and Psychological Symptoms) Of Dementia)) or mental symptoms of neurodegenerative diseases. A method for treating a central nervous system disorder, comprising administering a therapeutically effective amount of a compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, to a patient in need of treatment. A use of a compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, for the manufacture of a therapeutic agent for diseases of the central nervous system. A compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, for use in the treatment of diseases of the central nervous system. A therapeutic agent for a central nervous system disease, which is a compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, selected from the group consisting of aripiprazole, olanzapine, quetiapine, and li Perindyl ketone, bunnerin, piperoprolone, paliperidone, ziprasidone, asenapine, ipidine, sputum, lurasidone and the pharmaceutically acceptable At least one agent selected from the group consisting of salts is combined. A therapeutic agent containing the compound according to any one of claims 1 to 20 or a pharmaceutically acceptable salt thereof as an active ingredient, which is selected from the group consisting of aripiprazole, olanzapine, quetiapine, and risper Ketone, bunner, piperpilone, paliperidone, ziprasidone, asenapine, ipidine, sputum, lurasidone and the pharmaceutically acceptable At least one agent selected from the group consisting of salts is used to treat diseases of the central nervous system.