JP2003146973A - Therapeutic and/or prophylactic agent for depression, melancholic state or anxiety disorder - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a therapeutic and/or prophylactic agent for depression, melancholic state or anxiety disorder. SOLUTION: The therapeutic and/or prophylactic agent for depression, melancholic state or anxiety disorder contains a compound represented by formula (I) (which can bear a variety of substituents), or salts thereof or solvates of any of them.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to therapeutic agents and preventive agents for anxiety disorders such as depression, depressive state and obsessive-compulsive disorder, panic disorder, and social phobia.

[0002]

BACKGROUND OF THE INVENTION Depression is a disease characterized by autonomic neuropathy and suppression of cognitive / behavior, in addition to persistent affective disorder.
It is also known that patients with depression often have anxiety disorders such as obsessive-compulsive disorder, panic disorder, and social phobia at the same time (Kessler RC et al, Br J Psychiatrysuppl,
17-30 (1996), Weissman MM et al, JAMA 276, 293-299
(1996)).

Currently, for depression, there are tricyclic antidepressants and selective serotonin reuptake inhibitors (Selective Serotonin).
Reuptake Inhibitor: SSRI) is used. These antidepressants have also been used for the treatment of anxiety disorders and their effectiveness has been reported (McTavish D et al, Pharmacother.
apy 10, 175-198 (1990), Pigott TA et al, J Clin Psyc
hiatry 60, 4-11 (1999), Sheehan DV, J Clin Psychia
try 60, 16-21 (1999)), saying that antidepressants that are effective in both depression and anxiety improvement are more effective, especially in patients with coexisting depression and anxiety disorders. Hoehn-Saric R et al, J Clin Psychiatry 49, 293-3
01 (1988), Kahn RJ et al, ArchGen Psychiatry 43, 79
-(1986)).

However, although the therapeutic effects of tricyclic antidepressants are relatively strong, they have side effects such as dizziness, lowering of blood pressure, sleepiness, dry mouth, and constipation because they have binding activity to various receptors. It has been reported. Selective serotonin reuptake inhibitors (SSRIs) are effective in patients with mild depression and anxiety disorders, but their therapeutic effect in patients with moderate to severe depression is lower than that of tricyclic antidepressants Headaches, dizziness, sexual dysfunction, etc. have been reported as weak and side effects based on drug efficacy.

[0005]

PROBLEM TO BE SOLVED BY THE INVENTION There is provided a therapeutic and / or prophylactic drug for depression, depressive state or anxiety disorder, which has less side effects and a higher therapeutic effect.

[0006]

Means for Solving the Problems As a result of intensive studies, the inventors have found that the compound represented by the formula (I) is effective for treating anxiety disorders such as depression, depression or obsessive-compulsive disorder, panic disorder, and social phobia. The present invention has been completed by finding that it is effective for treatment and / or prevention.

[0007]

The present invention is of the formula (I)

[0008]

[Chemical 3] (In the formula, Q is an aryl group, a heterocyclic group, a diarylmethyl group, an aralkyl group composed of an aryl group and an alkylene group having 1 to 6 carbon atoms, an alkyl group having 1 to 8 carbon atoms, or A cycloalkyl group having 3 to 8 is represented, where the aryl group, the heterocyclic group, and the aryl group in the diarylmethyl group and the aralkyl group are: 1. an alkyl group having 1 to 6 carbon atoms; To 6 alkoxyl group, 3. trifluoromethyl group and 2,2,2-trifluoroethyl group, 4. trifluoromethoxyl group and 2,2,2-trifluoroethoxy group, 5. carbon number of 1 to 6 Alkylthio group, 6. alkylsulfinyl group having 1 to 6 carbon atoms, 7. alkylsulfonyl group having 1 to 6 carbon atoms, 8. alkyl group having 1 to 6 carbon atoms and carbonyl group An alkanoyl group composed of an alkyl group, 9. an alkanoyloxy group having 2 to 7 carbon atoms, 10. an alkanoylamino group having 2 to 7 carbon atoms, 11. an amino group, 12. an alkyl group having 1 to 6 carbon atoms 13. a monoalkylamino group having, 13. a dialkylamino group each of which is independently an alkyl group having 1 to 6 carbon atoms, 14. a hydroxyl group, 15. a halogen atom, 16. a perfluoroalkyl group having 2 to 6 carbon atoms, 17. Cyano group, 18. Nitro group, 19. Carboxyl group, 20. Alkoxycarbonyl group composed of an alkoxyl group having 1 to 6 carbon atoms and a carbonyl group, 21. Tetrazolyl group, 22. Sulfamoyl group, 23. Methylenedioxy Group, ethylenedioxy group and propylenedioxy group, 24. morpholinosulfonyl group, 25. Piperazino sulfonyl group, 26. 4-alkyl piperazino sulfonyl group having an alkyl group having 1 to 6 carbon atoms, 27. 4- each independently having a dialkylamino group which is an alkyl group having 1 to 6 carbon atoms One or more substituents selected from the group consisting of (dialkylamino) piperidino group, 28. 4- (monoalkylamino) piperidino group having an alkyl group having 1 to 6 carbon atoms, and 29.4-aminopiperidino group. R may have a group.
Is the expression

[0009]

[Chemical 4]

(Wherein G is a phenyl group which may have a substituent, b. A benzoyl group which may have a substituent in the phenyl group portion, and c. A substituent group in the phenyl group portion. A benzylcarbonyl group which may have a d. A benzoylmethyl group which may have a substituent in the phenyl group part, an e. A-hydroxybenzyl group which may have a substituent in the phenyl group part, f. A 5-membered aromatic heterocyclic group containing a nitrogen atom, an oxygen atom or a sulfur atom as a hetero atom and optionally having a substituent (wherein, when the hetero atom is a nitrogen atom, this nitrogen atom is ,
It has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or serves as a bonding portion with the indazole ring. ), G. A 5-membered aromatic heterocyclic group containing a nitrogen atom as a hetero atom and a nitrogen atom, an oxygen atom or a sulfur atom as a second hetero atom and optionally having a substituent (here, When the two different atoms are nitrogen atoms, the nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or serves as a bonding portion with the indazole ring), h. A 5-membered aromatic heterocyclic group which contains two nitrogen atoms as different atoms and a nitrogen atom, an oxygen atom, or a sulfur atom as a third different atom and may have a substituent (here,
When the third hetero atom is a nitrogen atom, this nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or becomes a bonding portion with the indazole ring. ), I. A 6-membered aromatic heterocyclic group containing one or two nitrogen atoms and optionally having a substituent, j. Heterocyclic substitution consisting of a 5-membered aromatic heterocyclic group containing a nitrogen atom, an oxygen atom or a sulfur atom as a hetero atom and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms. An alkyl group (where the heteroatom is a nitrogen atom, the nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms), k. One nitrogen atom as a hetero atom, a nitrogen atom, an oxygen atom or a sulfur atom as a second hetero atom, and a 5-membered aromatic heterocyclic group which may have a substituent, and a carbon number of 1
A heterocyclic-substituted alkyl group composed of an alkylene group of 1 to 3 (wherein the second hetero atom is a nitrogen atom, this nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or It becomes a bonding part with an alkylene group.), L. 5-membered aromatic heterocyclic group, which contains two nitrogen atoms as different atoms and a nitrogen atom, an oxygen atom, or a sulfur atom as a third different atom, and may have a substituent, and a carbon number A heterocyclic-substituted alkyl group composed of 1 to 3 alkylene groups (wherein if the third hetero atom is a nitrogen atom, this nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms) Or a bonding portion with an alkylene group), m. A heterocyclic-substituted alkyl group composed of a 6-membered aromatic heterocyclic group containing 1 or 2 nitrogen atoms and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms, n ． A phenylhydroxyalkyl group composed of an alkylene group having 2 to 3 carbon atoms having one hydroxyl group and a phenyl group which may have a substituent, o. 2-phenylethynyl group (this phenyl group may have a substituent), p. A tetrazolyl group, q. A morpholino group, r. An alkanoylamino group having 2 to 7 carbon atoms, s. A tetrazolylalkyl group composed of a tetrazolyl group and an alkylene group having 1 to 3 carbon atoms (wherein the alkylene group is bonded at the carbon atom or nitrogen atom of the tetrazolyl group), t. A morpholinoalkyl group composed of a morpholino group and an alkylene group having 1 to 3 carbon atoms, u. 4-alkoxycarbonylcyclohexyl group (wherein the alkoxyl group has 1 to 6 carbon atoms), v. An alkoxycarbonyl group (wherein the alkoxyl group has 1 to 6 carbon atoms), w. A 1-alkylindol-2-yl group (wherein the alkyl group has 1 to 6 carbon atoms, and indole may further have a substituent), x. A pyrrolidone-1-yl group, y. A 2-guanidinothiazolyl group, z. A (2-guanidinothiazolyl) -alkyl group composed of a 2-guanidinothiazolyl group and an alkylene group having 1 to 3 carbon atoms, A. An optionally substituted 1,4-dihydropyridyl group, B. A 4-alkylpiperazinoalkyl group composed of a 4-alkylpiperazino group having an alkyl group having 1 to 6 carbon atoms and an alkylene group having 1 to 6 carbon atoms, C.I. A 4- (morpholinosulfonyl) phenylalkyl group composed of a 4- (morpholinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms, D. A 4- (piperazinosulfonyl) phenylalkyl group composed of a 4- (piperazinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms, E. 4- (4-alkylpiperazinosulfonyl) phenylalkyl composed of a 4- (4-alkylpiperazinosulfonyl) phenyl group having an alkyl group having 1 to 6 carbon atoms and an alkylene group having 1 to 6 carbon atoms Group, F. An alkoxycarbonylalkyl group composed of an alkoxycarbonyl group having 2 to 7 carbon atoms and an alkylene group having 1 to 6 carbon atoms, G. A carboxyalkyl group composed of a carboxyl group and an alkylene group having 1 to 6 carbon atoms, H.I. A 4-dialkylaminopiperidino group having a dialkylamino group substituted with two alkyl groups having 1 to 6 carbon atoms at the 4-position of piperidine is bonded to the 4-position of a phenyl group.
A 4- (4-dialkylaminopiperidino) phenyl group and an alkylene group having 1 to 6 carbon atoms [4- (4-dialkylaminopiperidino) phenyl]
An alkyl group, I. A 4-monoalkylaminopiperidino group having a monoalkylamino group substituted with an alkyl group having 1 to 6 carbon atoms at the 4-position of piperidine is bonded to the 4-position of a phenyl group.
It is composed of a 4- (4-monoalkylaminopiperidino) phenyl group and an alkylene group having 1 to 6 carbon atoms.
4- (4-monoalkylaminopiperidino) phenylalkyl group, J. A 4- (4-aminopiperidino) phenyl group having a 4-aminopiperidino group bonded to the 4-position of the phenyl group and an alkylene group having 1 to 6 carbon atoms [4- (4
-Aminopiperidino) phenyl] alkyl groups, K.I. A 4-dialkylaminopiperidino group having a dialkylamino group substituted with two alkyl groups having 1 to 6 carbon atoms at the 4-position of piperidine and an alkylene group having 1 to 6 carbon atoms (4-dialkyl An aminopiperidino) alkyl group, L. It is composed of a 4-monoalkylaminopiperidino group having a monoalkylamino group substituted with an alkyl group having 1 to 6 carbon atoms at the 4-position of piperidine and an alkylene group having 1 to 6 carbon atoms (4-mono An alkylaminopiperidino) alkyl group, M.I. A (4-aminopiperidino) alkyl group composed of a 4-aminopiperidino group and an alkylene group having 1 to 6 carbon atoms; A phenylalkyl group composed of a phenyl group which may have a substituent and an alkylene group having 1 to 6 carbon atoms. And O. Represents a substituent selected from the group consisting of a hydrogen atom, wherein a. To O. With respect to the substituents of the substituent group represented by, it means that it may have a substituent. An alkyl group having 1 to 6 carbon atoms; 2. an alkoxyl group having 1 to 6 carbon atoms, A trifluoromethyl group and a 2,2,2-trifluoroethyl group, 4. 4. Trifluoromethoxyl group and 2,2,2-trifluoroethoxyl group, 5. An alkylthio group having 1 to 6 carbon atoms, 6. An alkylsulfinyl group having 1 to 6 carbon atoms, 7. An alkylsulfonyl group having 1 to 6 carbon atoms, 8. An alkanoyl group composed of an alkyl group having 1 to 6 carbon atoms and a carbonyl group, An alkanoyloxy group having 2 to 7 carbon atoms, 10. 10. Alkanoylamino group having 2 to 7 carbon atoms, 11. An amino group, 12. 13. A monoalkylamino group having an alkyl group having 1 to 6 carbon atoms, 13. Dialkylamino groups each independently having an alkyl group having 1 to 6 carbon atoms, Hydroxyl group, 15. Halogen atom, 16. 17. A perfluoroalkyl group having 2 to 6 carbon atoms, A cyano group, 18. A nitro group, 19. A carboxyl group, 20. 21. An alkoxycarbonyl group composed of an alkoxyl group having 1 to 6 carbon atoms and a carbonyl group, 21. A tetrazolyl group, 22. 23. a sulfamoyl group, 23. Methylenedioxy group, ethylenedioxy group and propylenedioxy group; A morpholinosulfonyl group, 25. 26. a piperazinosulfonyl group, 26. 27. A 4-alkylpiperazinosulfonyl group having an alkyl group having 1 to 6 carbon atoms, 27. 27. A 4- (dialkylamino) piperidino group, each independently having a dialkylamino group which is an alkyl group having 1 to 6 carbon atoms, 29. 4- (monoalkylamino) piperidino group having an alkyl group having 1 to 6 carbon atoms, and 29. 4-aminopiperidino group means having one or more substituents selected from the group consisting of substituents. R ¹
And R ² are each independently an alkyl group having 1 to 6 carbon atoms,
An alkoxyl group having 1 to 6 carbon atoms, a trifluoromethyl group, a 2,2,2-trifluoroethyl group, a trifluoromethoxyl group, a 2,2,2-trifluoroethoxyl group, an alkylthio group having 1 to 6 carbon atoms, 1 to 6 carbon atoms
, An alkylsulfinyl group, an alkylsulfonyl group having 1 to 6 carbon atoms, an alkanoyl group composed of an alkyl group having 1 to 6 carbon atoms and a carbonyl group, and 2 to 7 carbon atoms
Alkanoyloxy group, alkanoylamino group having 2 to 7 carbon atoms, amino group, monoalkylamino group having an alkyl group having 1 to 6 carbon atoms, dialkylamino group each being an alkyl group having 1 to 6 carbon atoms , Hydroxyl group,
Halogen atom, perfluoroalkyl group having 2 to 6 carbon atoms, cyano group, nitro group, carboxyl group, alkoxycarbonyl group composed of alkoxyl group and carbonyl group having 1 to 6 carbon atoms, tetrazolyl group, sulfamoyl group, methylene Dioxy group, ethylenedioxy group, morpholinosulfonyl group, piperazinosulfonyl group, 4-alkylpiperazinosulfonyl group having an alkyl group having 1 to 6 carbon atoms, each independently an alkyl group having 1 to 6 carbon atoms Represents a 4-dialkylaminopiperidino group having a dialkylamino group at the 4-position, a 4-monoalkylaminopiperidino group having an alkyl group having 1 to 6 carbon atoms, or a 4-aminopiperidino group. ), Z
Is an alkylene group having 1 to 3 carbon atoms, an alkenylene group having 2 to 4 carbon atoms, an alkylene group having 1 to 3 carbon atoms having 1 hydroxyl group, a carbonyl atomic group, and a carbonyl atomic group at one end or in the middle of a carbon chain. It represents an alkylene group having 1 to 2 carbon atoms including or an oxalyl group. ), Z is an alkylene group having 1 to 3 carbon atoms, an alkenylene group having 2 to 4 carbon atoms, an alkylene group having 1 to 3 carbon atoms having 1 hydroxyl group, a carbonyl atom group, one end or an intermediate portion of a carbon chain Represents an alkylene group having 1 to 2 carbon atoms containing one carbonyl atom group, or an oxalyl group. The present invention relates to a therapeutic and / or prophylactic drug for depression, depressive state or anxiety disorder, which comprises a compound represented by the formula (4) or a salt thereof, or a solvate of any of them. Also, 3- [2- [4- (3-chloro-2-methylphenyl) -1-piperazinyl] ethyl] -5,6-
The present invention relates to a therapeutic and / or preventive agent for depression, depressive state or anxiety disorder, which comprises dimethoxybenzyl) -1H-indazole or a salt thereof, or a solvate of any of them. Furthermore, 3- [2- [4- (3-chloro-2-methylphenyl) -1-piperazinyl] ethyl] -5,6
-Dimethoxy-1- (4-imidazolylmethyl) -1H
-Indazole or a salt thereof, or a solvate of either thereof, especially 3- [2- [4- (3-chloro-2-methylphenyl) -1-piperazinyl] ethyl] -5,6
-Dimethoxy-1- (4-imidazolylmethyl) -1H
-The present invention relates to a therapeutic and / or preventive agent for depression, depression or anxiety disorder, which comprises indazole dihydrochloride 3.5 hydrate. And it relates to the above-mentioned therapeutic agent and / or preventive agent in which the anxiety disorder is obsessive-compulsive disorder, panic disorder or social phobia.

The compound according to the present invention is disclosed in JP-A-7-973.
It is a compound described in Japanese Patent Laid-Open No. 64. And, as its action, a cerebral nerve cell death inhibitory action by inhibiting calmodulin (JP-A-7-41431)
However, the therapeutic and / or prophylactic action of these compounds on anxiety disorders such as depression, depressive state or obsessive-compulsive disorder, panic disorder and social phobia is unknown. These compounds can be easily produced, for example, by the method described in JP-A-7-97364. The compound represented by formula (I) will be described.

The partial structure Q of the compound according to the present invention has an aryl group, a heterocyclic group, a diarylmethyl group, an aralkyl group composed of an aryl group and an alkylene group having 1 to 6 carbon atoms, and an aralkyl group having 1 to 8 carbon atoms. It is a substituent having a structure selected from an alkyl group or a cycloalkyl group having 3 to 8 carbon atoms.

The aryl group is a substituent derived from an aromatic compound, and is typically a phenyl group or a naphthyl group. Although an aromatic compound is present in the heterocyclic compound, the compound according to the present invention means a substituent derived from an aromatic hydrocarbon compound.

The heterocyclic group is a substituent derived from a heterocyclic compound. Among the heterocyclic compounds, a nitrogen-containing heterocyclic compound is preferable in the compound according to the present invention. Even a nitrogen-containing heterocyclic compound has aromaticity, partial saturation, saturation, etc.,
Of these, aromatic heterocycles are preferable. Examples of the nitrogen-containing aromatic heterocyclic compound include pyrrole, imidazole, pyrazole, pyridine, pyridazine, pyrimidine,
Examples thereof include pyrazine, indole, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, quinoxaline, naphthyridine, pyridopyridines, carbazole, carboline, phenanthridine, acridine, etc. Can have. Among these substituents, a pyridyl group, a pyrimidyl group and an isoquinolyl group are preferable.

In addition to the nitrogen-containing heterocyclic substituent, a heterocyclic substituent containing an oxygen atom or a sulfur atom may be used. Even in this case, it can be saturated, partially saturated or aromatic. For example, it may be thienyl, benzothienyl, furyl, furanyl, benzofuranyl, chromenil and the like. Of these, a benzofuranyl group, a dihydrobenzofuranyl group and the like are preferable.

In addition, substituents having plural kinds of different atoms such as isothiazolyl, isoxazolyl and oxazinyl may be used.

The diarylmethyl group is a substituent having a structure in which two of the hydrogen atoms of the methyl group are replaced with two aryl groups, and the aryl group may be those described above. The most typical diarylmethyl group is the diphenylmethyl group.

An aralkyl group composed of an aryl group and an alkylene group having 1 to 6 carbon atoms is used for the purpose of explaining the structure of the aralkyl group. It is meant to be captured as being composed of one part, and thus not the actual aralkyl group is prepared by the reaction of such a combination of two parts. The same expression is used below for the explanation of the substituents in 1.), and is a substituent having a structure in which one end of the alkylene group is bonded to the aryl group described above.
Typical examples are a benzyl group and a phenethyl group.

The alkyl group may have 1 to 8 carbon atoms, but may be linear or branched.

The cycloalkyl group may have 3 to 8 carbon atoms, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group and a cyclooctyl group.

An aryl group, a heterocyclic group, a diarylmethyl group, an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an aryl group and an alkylene group having 1 to 6 carbon atoms as described above. Each substituent of the aralkyl group composed of may be further substituted with various substituents. In particular, the aryl group, the heterocyclic group, and the aryl group of the diarylmethyl group and the aralkyl group may have a substituent. Such a substituent is selected from the group of substituents shown below.

Alkyl group. The alkyl group has 1 to 6 carbon atoms and may be linear or branched.
Further, when the carbon number is 3 or more, it may be a cyclic alkyl group.

Alkoxyl group. The alkoxyl group has a carbon number of 1 to 6, but may be composed of the above alkyl group and an oxygen atom, that is, the alkyl moiety may be linear, branched or cyclic.

Trifluoromethyl group and 2,2,2-trifluoroethyl group.

Trifluoromethoxyl group and 2,2,2-trifluoroethoxyl group.

Alkylthio group. The alkylthio group is composed of the above-mentioned alkyl group having 1 to 6 carbon atoms and a sulfur atom, that is, the alkyl moiety may be linear, branched or cyclic. It has the following structure.

[0027]

Embedded image An alkyl-S-alkylsulfinyl group. The alkylsulfinyl group is
It is a substituent formed by oxidizing the sulfur atom of the above alkylthio group with one oxygen atom, and has the structure shown below.

[0028]

Embedded image An alkyl-SO-alkylsulfonyl group. The alkylsulfonyl group is a substituent formed by oxidizing the sulfur atom of the above alkylthio group with two oxygen atoms, and has a structure shown below.

[0029]

Embedded image Alkyl-SO ₂ -alkanoyl group. The alkanoyl group is a substituent having a structure formed by removing a hydroxyl group from the carboxylic acid moiety of an aliphatic carboxylic acid. It has the following structure.

[0030]

Embedded image Alkyl-CO-alkanoyloxy groups. The alkanoyloxy group is a substituent having a structure in which an oxygen atom is added to the above alkanoyl group or a structure in which a hydrogen atom is removed from the carboxylic acid moiety of an aliphatic carboxylic acid. It has the following structure.

[0031]

Embedded image Alkyl-CO—O-alkanoylamino group. The alkanoylamino group has a structure in which one of two hydrogen atoms of the amino group is replaced with an alkanoyl group. It has the following structure.

[0032]

Embedded image Alkyl-CO-NH- Amino group.

Monoalkylamino group and dialkylamino group. A monoalkylamino group has a structure in which one of two hydrogen atoms of an amino group becomes an alkyl group, and a dialkylamino group has a structure in which both of the hydrogen atoms of an amino group become an alkyl group. ing.

Hydroxyl group.

Halogen atom.

Perfluoroalkyl group. The perfluoroalkyl group has a structure in which all hydrogen atoms of the alkyl group are replaced with fluorine atoms, and has a linear, branched or cyclic structure.

Cyano group.

Nitro group.

Carboxyl group.

Alkoxylcarbonyl group. The alkoxylcarbonyl group has a structure in which an alkyl group and a carbonyl group are bonded via an oxygen atom, and the alkyl group portion may be linear, branched or cyclic. It has the following structure.

[0041]

Embedded image Alkyl-O—CO— tetrazolyl group. The tetrazolyl group is a 5-membered heterocyclic substituent.

Sulfamoyl group.

Methylenedioxy group. The methylenedioxy group, ethylenedioxy group and propylenedioxy group are

[0044]

Embedded image It has a structure of —O— (CH ₂ ) _q —O—, where q is 1 to 3. The carbon atoms to which the two oxygen atoms are bonded are adjacent carbon atoms.

Morpholinosulfonyl group. The morpholinosulfonyl group has the formula:

[0046]

Embedded image It has a structure represented by morpholino (that is, 4-morphonyl group) —SO ₂ —.

A piperazinosulfonyl group. The piperazinosulfonyl group has the following formula:

[0048]

Embedded image It has a structure represented by (1-piperazinyl) -SO ₂ —.

4-alkylpiperazinosulfonyl group. The 4-alkylpiperazinosulfonyl group has the following formula:

[0050]

Embedded image The structure has the structure represented by (4-alkyl-1-piperazinyl) -SO ₂ —, and the 4-position alkyl group of the piperazinyl group is an alkyl group having 1 to 6 carbon atoms.

4- (dialkylamino) piperidino group. Four-
The (dialkylamino) piperidino group has the formula

[0052]

Embedded image It has a structure represented by 4-dialkylamino-1-piperidinyl, and each dialkylamino group at the 4-position of the piperazinyl group independently has an alkyl group having 1 to 6 carbon atoms.

4- (monoalkylamino) piperidino group.
The 4- (monoalkylamino) piperidino group has the formula

[0054]

Embedded image It has a structure represented by 4-monoalkylamino-1-piperidinyl, and the monoalkylamino group at the 4-position of the piperazinyl group has an alkyl group having 1 to 6 carbon atoms.

4-aminopiperidino group. The 4-aminopiperidino group has an amino group at the 4-position of the piperidinyl group.

The number of substituents selected from the group of substituents composed of the above substituents may be 1 or more, and may be the same or different.

Further, the substituent selected from these substituent groups may be present on the alkyl group and cyclic alkyl group of the substituents contained in Q.

The substituent Q is preferably an aryl group among those described above. A phenyl group is preferred as the aryl group. This phenyl group may have one or more substituents. The substituent on this phenyl group is preferably in the meta position (this meta position is based on the site where the phenyl group binds to piperazine). As the substituent on the phenyl group, a substituent having an electron-withdrawing substituent as the meta-position and an electron-donating substituent in this case as the second substituent are preferable. As the electron-withdrawing substituent at the meta position, a halogen atom, especially a chlorine atom, and a trifluoromethyl group are preferable. When the substituent at the meta position is a halogen atom, this phenyl group may further have an alkyl group as a substituent.
On the other hand, when the electron-withdrawing substituent at the meta position is a trifluoromethyl group, it may further have an alkoxyl group as a substituent.

Particularly preferable partial structure Q is a phenyl group having at least one substituent in the meta position, and a halogen atom is particularly preferable as the substituent.
Of these, a 2-methyl-3-chlorophenyl group is most preferable.

In the nitrogen atom on the other side of the piperazine ring in the compound according to the present invention, an alkylene group having 1 to 3 carbon atoms, an alkenylene group having 2 to 4 carbon atoms, and an alkyl group having 1 to 3 carbon atoms having one hydroxyl group. Alkylene group, carbonyl atom group, carbonyl atom group 1 at one end or in the middle of the carbon chain
R moiety through the Z moiety of an alkylene group having 1 to 2 carbon atoms containing 1 or 2, or an oxalyl group

[0061]

[Chemical 17]

Has been replaced.

The alkylene group of the Z moiety is represented by the following structural formula:

[0064]

Embedded image-(CH ₂ ) _r-- r is 1 to 3 and the alkenylene group is an alkylene group having 2 to 4 carbon atoms, in which one carbon-carbon bond is a double bond. The position of the double bond may be terminal or intermediate.

The alkylene group having 1 to 3 carbon atoms having one hydroxyl group is one in which one carbon atom of the alkylene group having 1 to 3 carbon atoms has a hydroxyl group, but the position of the hydroxyl group is not particularly limited. Instead, it may be at the end or in the middle.

Carbonyl group (or carbonyl group)
Is

[0067]

[Chemical 19] -CO- It has a structure represented by

An alkylene group having 1 or 2 carbon atoms containing one carbonyl atom group at one end or in the middle of the carbon chain is

[0069]

[Chemical Formula 20] -CO-CH _2-

[0070]

[Chemical 21] -CH ₂ -CO-

[0071]

[Chemical Formula 22] -CO- CH ₂ -CH _2-

[0072]

[Of 23] - CH ₂ -CO- CH ₂ - or,

[0073]

Embedded image is any structure of —CH ₂ —CH ₂ —CO—.

The oxalyl group is

[0075]

[Chemical 25] -CO-CO- It has the structure of.

Z, which is the bond between the substituent R and the piperazine
For, an alkylene group is preferred. The alkylene group is preferably one having 2 or 3 carbon atoms, and among these, one having 2 carbon atoms is more preferable.

Examples of the substituent G of the partial structure represented by R include those shown by the following a to z and A to O. a. A phenyl group which may have a substituent. b. A benzoyl group which may have a substituent on the phenyl group portion. c. A benzylcarbonyl group which may have a substituent on the phenyl moiety. d. A benzoylmethyl group which may have a substituent on the phenyl group portion. e. An α-hydroxybenzyl group which may have a substituent in the phenyl group moiety. f. A 5-membered aromatic heterocyclic group containing a nitrogen atom, an oxygen atom or a sulfur atom as a hetero atom and optionally having a substituent (wherein, when the hetero atom is a nitrogen atom, this nitrogen atom is ,
It has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or serves as a bonding portion with the indazole ring. ). For example, a pyrrolyl group, a furyl group or a thienyl group. g. One nitrogen atom as the foreign atom and the second foreign atom,
A 5-membered aromatic heterocyclic group containing a nitrogen atom, an oxygen atom or a sulfur atom and optionally having a substituent (wherein, when the second hetero atom is a nitrogen atom, this nitrogen atom is hydrogen. It has an atom or an alkyl group having 1 to 6 carbon atoms, or becomes a bonding portion with the indazole ring). Examples thereof include a pyrazolyl group, an imidazolyl group, a thiazolyl group, an isothiazolyl group, an oxazolyl group and an isoxazolyl group. h. Two nitrogen atoms as foreign atoms and a third foreign atom,
A 5-membered aromatic heterocyclic group containing a nitrogen atom, an oxygen atom, or a sulfur atom and optionally having a substituent (here,
When the heteroatom of is a nitrogen atom, this nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or becomes a bonding portion with the indazole ring. ). Specifically, 1,
2,3-triazolyl group, 1,2,4-triazolyl group, 1,2,3-thiadiazyl group, 1,2,4-thiadiazyl group, 1,2,5-thiadiazyl group, 1,3,4-thiadiazyl group Group, 1,2,3-oxadiazyl group, 1,2,4-oxadiazyl group, 1,2,5-oxadiazyl group, 1,3,4-oxadiazyl group and the like. i. A 6-membered aromatic heterocyclic group which contains one or two nitrogen atoms and may have a substituent. It is a pyridyl group, a pyridazinyl group, a pyrimidyl group, or a pyrazinyl group. These binding sites for R are all possible sites in these. j. A hetero atom composed of a 5-membered aromatic heterocyclic group containing a nitrogen atom, an oxygen atom or a sulfur atom as a hetero atom and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms. Ring-substituted alkyl group (here, when the hetero atom is a nitrogen atom, the nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms). For example, pyrrolyl-methyl, ethyl or propyl group, thienyl-methyl, ethyl or propyl group, furyl-methyl, ethyl or propyl group. k. One nitrogen atom as a foreign atom, and a second foreign atom,
A heterocyclic-substituted alkyl group containing a 5-membered aromatic heterocyclic group containing a nitrogen atom, an oxygen atom or a sulfur atom and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms ( Here, when the second hetero atom is a nitrogen atom, this nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or becomes a bonding portion with an alkylene group.).
Pyrazolyl-methyl, ethyl or propyl group, imidazolyl-methyl, ethyl or propyl group, thiazolyl-methyl, ethyl or propyl group, oxazolyl-methyl, ethyl or propyl group. l. Two nitrogen atoms as foreign atoms and a third foreign atom,
A heterocyclic-substituted alkyl group containing a 5-membered aromatic heterocyclic group containing a nitrogen atom, an oxygen atom, or a sulfur atom and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms. (Here, when the third hetero atom is a nitrogen atom, the nitrogen atom has a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or serves as a bonding portion with an alkylene group.). 1,2,3-triazolyl-methyl, ethyl or propyl group, 1,2,4-triazolyl-methyl, ethyl or propyl group, 1,2,3-thiadiazyl-methyl, ethyl or propyl group, 1, 2,4-thiadiazyl-methyl, ethyl,
Or propyl group, 1,2,5-thiadiazyl-methyl, ethyl or propyl group, 1,3,4-thiadiazyl-methyl, ethyl or propyl group, 1,2,3-oxadiazyl-methyl, ethyl or propyl group Group, 1,2,4-oxadiazyl-
And a methyl, ethyl, or propyl group, a 1,2,5-oxadiazyl-methyl, ethyl, or propyl group, a 1,3,4-oxadiazyl-methyl, ethyl, or a propyl group. m. A heterocyclic-substituted alkyl group composed of a 6-membered aromatic heterocyclic group containing 1 or 2 nitrogen atoms and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms. . Pyridyl-methyl, ethyl, or propyl group, pyridazinyl-methyl, ethyl, or propyl group, pyrimidyl-methyl, ethyl, or propyl group, or pyrazinyl-methyl, ethyl, or propyl group. n. A phenylhydroxyalkyl group composed of an alkylene group having one hydroxyl group and having 2 to 3 carbon atoms and a phenyl group which may have a substituent. 1-hydroxy-2-phenylethyl, 2-hydroxy-2-phenylethyl, 1-hydroxy-3-phenylpropyl, 2-hydroxy-3-phenylpropyl, 3-hydroxy-3-phenylpropyl and the like. o.2-Phenylethynyl group (this phenyl group may have a substituent). p. tetrazolyl group. q. Morpholino group. r. an alkanoylamino group having 2 to 7 carbon atoms. s. A tetrazolylalkyl group composed of a tetrazolyl group and an alkylene group having 1 to 3 carbon atoms (wherein the alkylene group is bonded at the carbon atom or nitrogen atom of the tetrazolyl group). It is a tetrazolyl-methyl, ethyl or propyl group. t. a morpholino alkyl group composed of a morpholino group and an alkylene group having 1 to 3 carbon atoms. A morpholino-methyl, ethyl, or propyl group. u.4-alkoxycarbonylcyclohexyl group (where
The alkoxyl group has 1 to 6 carbon atoms. ). Here, the steric structure at the bonding portion at the 1-position with the alkoxycarbonyl group may be trans or cis. Further, either an axial bond or an equatorial bond may be used. v. Alkoxycarbonyl group (wherein the alkoxyl group has 1 to 6 carbon atoms). w.1-alkylindol-2-yl group (wherein the alkyl group has 1 to 6 carbon atoms, and the indole may further have a substituent). x. Pyrrolidone-1-yl group. The position of the oxo moiety is 2- or 3-
Is. y.2-guanidinothiazolyl group. z.2-Consisting of a guanidinothiazolyl group and an alkylene group having 1 to 3 carbon atoms (2-guanidinothiazolyl)-
Alkyl group. A. A 1,4-dihydropyridyl group which may have a substituent.
Examples of the substituent include an alkyl group and a carboxyl group. For example, a 2,6-bis (methoxycarbonyl) -3,5-dimethyl-1,4-dihydropyridyl group can be mentioned. B. A 4-alkylpiperazinoalkyl group composed of a 4-alkylpiperazino group having an alkyl group having 1 to 6 carbon atoms and an alkylene group having 1 to 6 carbon atoms. C. 4- (morpholinosulfonyl) phenylalkyl group composed of a 4- (morpholinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms. D. 4- (piperazinosulfonyl) phenylalkyl group composed of 4- (piperazinosulfonyl) phenyl group and alkylene group having 1 to 6 carbon atoms. E. 4- (4-Alkylpiperazinosulfonyl) composed of 4- (4-alkylpiperazinosulfonyl) phenyl group having an alkyl group having 1 to 6 carbon atoms and alkylene group having 1 to 6 carbon atoms Phenylalkyl group. F. Alkoxycarbonyl group having 2 to 7 carbon atoms and 1 carbon atom
To an alkylene group of 6 to 6. G. A carboxyalkyl group composed of a carboxyl group and an alkylene group having 1 to 6 carbon atoms. H. A 4-dialkylaminopiperidino group having a dialkylamino group substituted by two alkyl groups having 1 to 6 carbon atoms at the 4-position of piperidine is bonded to the 4-position of a phenyl group 4- (4-
Dialkylaminopiperidino) phenyl group and carbon number 1
[4- (4-dialkylaminopiperidino) phenyl] alkyl group consisting of the alkylene groups of 1 to 6 above. I. A 4-monoalkylaminopiperidino group having a monoalkylamino group substituted with an alkyl group having 1 to 6 carbon atoms at the 4-position of piperidine is bonded to the 4-position of a phenyl group 4- (4-
A 4- (4-monoalkylaminopiperidino) phenylalkyl group composed of a monoalkylaminopiperidino) phenyl group and an alkylene group having 1 to 6 carbon atoms. J. 4-Aminopiperidino group bonded to 4-position of phenyl group
A [4- (4-aminopiperidino) phenyl] alkyl group composed of a 4- (4-aminopiperidino) phenyl group and an alkylene group having 1 to 6 carbon atoms. K. A 4-dialkylaminopiperidino group having a dialkylamino group substituted with two alkyl groups having 1 to 6 carbon atoms at the 4-position of piperidine and an alkylene group having 1 to 6 carbon atoms (4 -Dialkylaminopiperidino) alkyl groups. L. It is composed of a 4-monoalkylaminopiperidino group having a monoalkylamino group substituted with an alkyl group having 1 to 6 carbon atoms at the 4-position of piperidine and an alkylene group having 1 to 6 carbon atoms (4 -Monoalkylaminopiperidino) alkyl groups. An (4-aminopiperidino) alkyl group composed of a 4-aminopiperidino group and an alkylene group having 1 to 6 carbon atoms. N. A phenylalkyl group composed of a phenyl group which may have a substituent and an alkylene group having 1 to 6 carbon atoms. O. Hydrogen atom.

With respect to the substituents described in these substituent groups, "which may have a substituent" may have a substituent selected from the group of the substituents described below. It means that. The number of substituents selected from the following groups of substituents may be 1 or more, and when 2 or more, they may be the same or different. 1. Alkyl group having 1 to 6 carbon atoms, 2. Alkoxyl group having 1 to 6 carbon atoms, 3. Trifluoromethyl group and 2,2,2-trifluoroethyl group, 4. Trifluoromethoxyl group and 2,2 , 2-trifluoroethoxy group, 5. C1 to C6 alkylthio group, 6. C1 to C6 alkylsulfinyl group, 7. C1 to C6 alkylsulfonyl group, 8. C1 to C6 , An alkanoyl group composed of an alkyl group and a carbonyl group, 9. an alkanoyloxy group having 2 to 7 carbon atoms, 10. an alkanoylamino group having 2 to 7 carbon atoms, 11. an amino group, 12. 1 to 6 carbon atoms A monoalkylamino group having an alkyl group of, 13. a dialkylamino group each independently having an alkyl group having 1 to 6 carbon atoms, 14. a hydroxyl group, 15. a halogen atom, 16. a perfluoroalkyl having 2 to 6 carbon atoms Base, 17. Cyano group, 18. Nitro group, 19. Carboxyl group, 20. Alkoxycarbonyl group composed of an alkoxyl group having 1 to 6 carbon atoms and a carbonyl group, 21. Tetrazolyl group, 22. Sulfamoyl group, 23. Methylene Dioxy group, ethylenedioxy group and propylenedioxy group, 24. morpholinosulfonyl group, 25. piperazinosulfonyl group, 26. 4-alkylpiperazinosulfonyl group having an alkyl group having 1 to 6 carbon atoms, 27. . 4- (dialkylamino) piperidino group having a dialkylamino group each being an alkyl group having 1 to 6 carbon atoms, 28. 4- (monoalkylamino) piperidino group having an alkyl group having 1 to 6 carbon atoms , 29. 4-Aminopiperidino group.

Preferred as the substituent G are those included in the following groups selected from those already defined as the substituent G. -A phenyl group which may have a substituent. -A benzoyl group which may have a substituent on the phenyl group portion, and a benzylcarbonyl group which may have a substituent on the phenyl group portion. -A benzoylmethyl group which may have a substituent in the phenyl group portion. An α-hydroxybenzyl group which may have a substituent on the phenyl group portion. A 6-membered aromatic heterocyclic group which contains 1 or 2 nitrogen atoms and may have a substituent. A heterocycle composed of a 5-membered aromatic heterocyclic group containing a nitrogen atom, a sulfur atom or an oxygen atom as a hetero atom and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms Group-substituted alkyl group. -Including one nitrogen atom, the second hetero atom is a nitrogen atom,
A heterocyclic group-substituted alkyl group comprising a 5-membered aromatic heterocyclic group containing a sulfur atom or an oxygen atom, which may have a substituent, and an alkylene group having 1 to 3 carbon atoms. -Containing two nitrogen atoms, a nitrogen atom as the third foreign atom,
A heterocyclic group-substituted alkyl group comprising a 5-membered aromatic heterocyclic group containing a sulfur atom or an oxygen atom, which may have a substituent, and an alkylene group having 1 to 3 carbon atoms. -Heterocyclic group-substituted alkyl group composed of a 6-membered aromatic heterocyclic group containing 1 or 2 nitrogen atoms and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms . A phenylhydroxyalkyl group composed of an alkylene group having 2 to 3 carbon atoms having one hydroxyl group and a phenyl group which may have a substituent. -A 2-phenylethynyl group having a phenyl group which may have a substituent. -Alkanoylamino group having 2 to 7 carbon atoms. A tetrazolylalkyl group composed of a tetrazolyl group and an alkylene group having 1 to 3 carbon atoms (wherein the alkylene group is bonded at the carbon atom or nitrogen atom of the tetrazolyl group). A morpholinoalkyl group composed of a morpholino group and an alkylene group having 1 to 3 carbon atoms. An alkoxycarbonyl group composed of an alkoxyl group having 1 to 6 carbon atoms and a carbonyl group. 1-alkylindole-2 having an alkyl group having 1 to 6 carbon atoms at the 1-position of an indole which may have a substituent
-Ile group. -A pyrrolidone-1-yl group which may have a substituent. A (2-guanidinothiazolyl) alkyl group composed of a 2-guanidinothiazolyl group and an alkylene group having 1 to 3 carbon atoms. -A 1,4-dihydropyridyl group which may have a substituent. -A 4-alkylpiperazino group having an alkyl group having 1 to 6 carbon atoms at the 4-position of the piperazino group and an alkylene group having 1 to 6 carbon atoms (4-alkylpiperazino)
Alkyl group. .Having a morpholinosulfonyl group at the 4-position of the phenyl group
A [4- (morpholinosulfonyl) phenyl) alkyl group composed of a 4- (morpholinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms. .Having a piperazinosulfonyl group at the 4-position of the phenyl group
A [4- (piperazinosulfonyl) phenyl) alkyl group composed of a 4- (piperazinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms. -A 4-alkylpiperazinosulfonyl group having an alkyl group having 1 to 6 carbon atoms is substituted at the 4-position of the phenyl group 4-
A [4- (4-alkylpiperazinosulfonyl) phenyl] alkyl group composed of a (4-alkylpiperazinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms.・ Alkoxycarbonyl group having 2 to 7 carbon atoms and 1 carbon atom
To an alkylene group of 6 to 6. A carboxyalkyl group composed of a carboxyl group and an alkylene group having 1 to 6 carbon atoms. -A 4-dialkylaminopiperidino group each having a dialkylamino group having an alkyl group having 1 to 6 carbon atoms at the 4-position of piperidine is independently substituted at the 4-position of the phenyl group.
A [4- (4-dialkylaminopiperidino) phenyl] alkyl group composed of a 4- (4-dialkylaminopiperidino) phenyl group and an alkylene group having 1 to 6 carbon atoms. 4- (4-monoalkylaminopiperidi) in which 4-monoalkylaminopiperidino group having a monoalkylamino group having an alkyl group having 1 to 6 carbon atoms at 4-position of piperidine is substituted at 4-position of phenyl group No) Phenyl group and carbon number 1
To a 6-alkylene group, a [4- (4-monoalkylaminopiperidino) phenyl) alkyl group. -A 4-aminopiperidino group having an amino group at the 4-position of piperidine substituted at the 4-position of a phenyl group, and an alkylene group having 1 to 6 carbon atoms [4- (4 -Aminopiperidino) phenyl] alkyl groups. -A 4-dialkylaminopiperidino group each having a dialkylamino group, which is an alkyl group having 1 to 6 carbon atoms, at the 4-position of piperidine, and an alkylene group having 1 to 6 carbon atoms (4- Dialkylaminopiperidino) alkyl group. -A monoalkylamino group having a C1-6 alkyl group at the 4-position of piperidine, a 4-monoalkylaminopiperidino group and an alkylene group having a C1-6 (4-mono) Alkylaminopiperidino) alkyl group. A (4-aminopiperidino) alkyl group composed of a 4-aminopiperidino group having an amino group at the 4-position of piperidine and an alkylene group having 1 to 6 carbon atoms. A phenylalkyl group composed of a phenyl group which may have a substituent and an alkylene group having 1 to 6 carbon atoms. -Hydrogen atom.

Further preferred of these are those included in the following groups. A heterocycle composed of a 5-membered aromatic heterocyclic group containing a nitrogen atom, a sulfur atom or an oxygen atom as a hetero atom and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms Group-substituted alkyl group. -Including one nitrogen atom, the second hetero atom is a nitrogen atom,
A heterocyclic group-substituted alkyl group comprising a 5-membered aromatic heterocyclic group containing a sulfur atom or an oxygen atom, which may have a substituent, and an alkylene group having 1 to 3 carbon atoms. -Containing two nitrogen atoms, a nitrogen atom as the third foreign atom,
A heterocyclic group-substituted alkyl group comprising a 5-membered aromatic heterocyclic group containing a sulfur atom or an oxygen atom, which may have a substituent, and an alkylene group having 1 to 3 carbon atoms. A heterocyclic group-substituted alkyl group composed of a 6-membered aromatic heterocyclic group containing a nitrogen atom 1 or 2 and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms. -Phenylhydroxyalkyl group. -A 2-phenylethenyl group having a phenyl group which may have a substituent. -Tetrazolylalkyl. -A morpholino alkyl group. -(2-guanidinothiazolyl) alkyl group. -A 1,4-dihydropyridyl group which may have a substituent. -[4- (morpholinosulfonyl) phenyl] alkyl group. -[4- (piperazinosulfonyl) phenyl] alkyl group. -[4- (4-Alkylpiperazinosulfonyl) phenyl] alkyl group. -Alkoxycarbonylalkyl group. -Carboxyalkyl group. -[4- (4-Dialkylaminopiperidino) phenyl] alkyl group. -[4- (4-Monoalkylaminopiperidino) phenyl] alkyl group. -[4- (4-aminopiperidino) phenyl] alkyl group. -(4-Dialkylaminopiperidino) alkyl group. -(4-Monoalkylaminopiperidino) alkyl group. -(4-Aminopiperidino) alkyl group. -Phenylalkyl group. -Hydrogen atom.

The substituent G is particularly preferably an aralkyl group composed of an aryl group and an alkylene group having 1 to 6 carbon atoms and a hydrogen atom. The aryl group contained in the aralkyl group includes not only a substituent derived from an aromatic hydrocarbon compound but also a heterocyclic group derived from an aromatic heterocyclic compound. Examples of the aralkyl group mentioned here include the following. -Α-hydroxybenzyl group. -Aromatic heterocyclic group having a 5-membered ring containing a hetero atom selected from a nitrogen atom, a sulfur atom or an oxygen atom and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms Heterocyclic group-substituted alkyl group. -Including one nitrogen atom, the second hetero atom is a nitrogen atom,
Heterocyclic group substitution consisting of a 5-membered aromatic heterocyclic group containing a hetero atom selected from a sulfur atom or an oxygen atom and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms Alkyl group. -Containing two nitrogen atoms, a nitrogen atom as the third foreign atom,
Heterocyclic group substitution consisting of a 5-membered aromatic heterocyclic group containing a hetero atom selected from a sulfur atom or an oxygen atom and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms Alkyl group. A heterocyclic group-substituted alkyl group which may have a substituent and is composed of a 6-membered aromatic heterocyclic group containing a nitrogen atom 1 or 2 and an alkylene group having 1 to 3 carbon atoms. A phenylhydroxyalkyl group composed of a phenyl group which may have a substituent and an alkylene group having 2 to 3 carbon atoms which is substituted with one hydroxyl group. -A 2-phenylethynyl group having a phenyl group which may have a substituent. A tetrazolylalkyl group composed of a tetrazolyl group and an alkylene group having 1 to 3 carbon atoms (wherein the alkylene group is bonded on the carbon atom or nitrogen atom of the tetrazolyl group). A morpholinoalkyl group composed of a morpholino group and an alkylene group having 1 to 3 carbon atoms. -Comprised of a 2-guanidinothiazolyl group and an alkylene group having 1 to 3 carbon atoms (2-guanidinothiazolyl)
Alkyl group. .Having a morpholinosulfonyl group at the 4-position of the phenyl group
A [4- (morpholinosulfonyl) phenyl] alkyl group composed of a 4- (morpholinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms. .Having a piperazinosulfonyl group at the 4-position of the phenyl group
A [4- (piperazinosulfonyl) phenyl] alkyl group composed of a 4- (piperazinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms. -A 4-alkylpiperazinosulfonyl group having an alkyl group having 1 to 6 carbon atoms is substituted at the 4-position of the phenyl group 4-
A [4- (4-alkylpiperazinosulfonyl) phenyl] alkyl group composed of a (4-alkylpiperazinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms. -A 4-dialkylaminopiperidino group, each independently having a dialkylamino group which is an alkyl group having 1 to 6 carbon atoms at the 4-position of piperidine, is substituted at the 4-position of the phenyl group 4-
A [4- (4-dialkylaminopiperidino) phenyl] alkyl group composed of a (4-dialkylaminopiperidino) phenyl group and an alkylene group having 1 to 6 carbon atoms. 4- (4-monoalkylaminopiperidi) in which 4-monoalkylaminopiperidino group having a monoalkylamino group having an alkyl group having 1 to 6 carbon atoms at 4-position of piperidine is substituted at 4-position of phenyl group No) Phenyl group and carbon number 1
To a 6-alkylene group, a [4- (4-monoalkylaminopiperidino) phenyl] alkyl group. -A 4-aminopiperidino group having an amino group at the 4-position of piperidine substituted at the 4-position of a phenyl group, and an alkylene group having 1 to 6 carbon atoms [4- (4 -Aminopiperidino) phenyl] alkyl groups. A phenyl group which may have a substituent,
A phenylalkyl group composed of an alkylene group having 1 to 6 carbon atoms.

Among such aralkyl groups, those having 1 or 2 carbon atoms in the alkylene group are preferable. And, of those having 1 or 2 carbon atoms, those having 1 carbon atom are more preferable. That is, an arylmethyl group is more preferable. As described above, the aryl group includes not only hydrocarbon type but also heterocyclic type.

As the substituent G, a hydrogen atom, a 3,4-dimethoxybenzyl group, a 4-imidazoylmethyl group, a 2-pyridylmethyl group, a 3-pyridylmethyl group or a 4-pyridylmethyl group is most preferable, and among them, Hydrogen atom,
A 4-imidazoylmethyl group is preferred.

Preferred substituents as the substituents R ¹ and R ² include the following groups. -Alkoxyl group having 1 to 6 carbon atoms. -Trifluoromethoxyl group. -2,2,2-trifluoroethoxy group. -Alkylthio group having 1 to 6 carbon atoms. An alkylsulfinyl group having 1 to 6 carbon atoms. -Alkylsulfonyl group having 1 to 6 carbon atoms. An alkanoyl group composed of an alkyl group having 1 to 6 carbon atoms and a carbonyl group. -Alkanoylamino group having 2 to 7 carbon atoms. -A monoalkylamino group having an alkyl group having 1 to 6 carbon atoms. A dialkylamino group, each of which is independently an alkyl group having 1 to 6 carbon atoms. -Hydroxyl group. -Halogen atom. -Carboxyl group. An alkoxycarbonyl group composed of an alkoxyl group having 1 to 6 carbon atoms and a carbonyl group. -A tetrazolyl group. -Sulfamoyl group. -Methylenedioxy group. -Ethylenedioxy group. -A morpholinosulfonyl group. -Piperazinosulfonyl group. -A 4-alkylpiperazinosulfonyl group having an alkyl group having 1 to 6 carbon atoms.・ Each of which is independently an alkyl group having 1 to 6 carbon atoms 4-
(Dialkylamino) piperidino group. -A 4- (monoalkylamino) piperidino group having an alkyl group having 1 to 6 carbon atoms. -A 4-aminopiperidino group.

Of these, more preferred are those of the following groups. -Alkoxyl group having 1 to 6 carbon atoms. -Trifluoromethyl group-2,2,2-trifluoroethoxy group. -Hydroxyl group. A halogen atom, especially a fluorine atom. -A tetrazolyl group. -Sulfamoyl group. -Methylenedioxy group. -Ethylenedioxy group. -A morpholinosulfonyl group. -Piperazinosulfonyl group. -A 4-alkylpiperazinosulfonyl group having an alkyl group having 1 to 6 carbon atoms.・ Each of which is independently an alkyl group having 1 to 6 carbon atoms 4-
(Dialkylamino) piperidino group. -A 4- (monoalkylamino) piperidino group having an alkyl group having 1 to 6 carbon atoms. -A 4-aminopiperidino group.

Among these, more preferred are: an alkoxyl group having 1 to 6 carbon atoms. -Sulfamoyl group. -Methylenedioxy group. -Ethylenedioxy group. Can be mentioned.

Substituent R¹And R^TwoAs R¹And R
^TwoIs a methoxyl group or R¹And R ^TwoTogether
Most preferred is the formation of a tolylenedioxy group.

Among the compounds according to the present invention, preferred compounds include the following.

3- [2- [4- (3-chloro-2-methylphenyl) -1-piperazinyl] ethyl] -5,6-dimethoxy-1- (4-imidazolylmethyl) -1H-indazole or a salt thereof Or a solvate of any of them. 3- [2- [4- (3-chloro-2-methylphenyl) -1
-Piperazinyl] ethyl] -5,6-dimethoxybenzyl] -1H-indazole or a salt thereof, or a solvate of any of them, particularly 3- [2- [4- (3-chloro-2-methylphenyl)- 1-piperazinyl] ethyl]
-5,6-Dimethoxy-1- (4-imidazolylmethyl) -1H-indazole dihydrochloride 3.5 hydrate The compound represented by the formula (I) is a free form compound or a pharmaceutically acceptable compound. Any of the compounds in salt form may be used. A typical pharmaceutically acceptable salt is an acid addition salt, but the acid added to form this salt may be either an inorganic acid or an organic acid. Examples of the inorganic acid include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and the like. The organic acid may be a carboxylic acid or a sulfonic acid, and examples thereof include acetic acid, propionic acid, lactic acid, maleic acid, fumaric acid, and the like, and methanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, and the like. It goes without saying that the compound of the formula (1) can be used as a salt in the human body as long as it is not harmful to the human body among the acids forming the acid addition salt. On the other hand, if the compound according to the present invention contains an acidic partial structure such as a carboxyl group or a sulfonyl group, it goes without saying that it is also possible to form a salt thereof with a base.

Further, the compound according to the present invention and its salt are
A solvate such as its hydrate can also be used. Further, the compound according to the present invention naturally includes tautomers of the compound represented by the formula (I). Since the compound according to the present invention can exert the effect by both oral and parenteral administration, the administration method may be oral or parenteral. The dose of the compound according to the present invention may be appropriately increased or decreased depending on the patient's symptoms, age, body weight, degree of symptoms and the like. In the case of oral administration, the daily dose for an adult is generally in the range of 1 mg to 1000 mg, preferably 10 mg to 500 mg, which is administered once or in several divided doses. In the case of parenteral administration, the daily dose for an adult is 1 mg to 500 mg, preferably 10 mg to 200 mg, and may be intravenous, transdermal or nasal. , Sublingually or rectally or by inhalation.
The compounds according to the invention may be used in dosage forms such as tablets, pills, capsules, powders, granules, sterile parenteral solutions or suspensions, metered aerosol or liquid sprays, solutions, ampoules or suppositories. it can. These can be produced by known formulation techniques together with additives such as ordinary excipients, lubricants and binders.

By using the compound of the present invention represented by the formula (I) in combination with other drugs, additive and synergistic effects can be expected in the prevention and treatment of various diseases. Examples of such agents include tricyclic and tetracyclic antidepressants (imipramine, amitriptyline, mianserin, etc.), SSRIs (fluvoxamine, paroxetine, etc.), monoamine oxidase inhibitors (moclobemide), etc.

[0092]

EXAMPLE As a compound according to the present invention, compound A: 3- [2- [4- (3-chloro-2-methylphenyl) -1-piperazinyl] ethyl] -5,6-dimethoxy-1- (4 -Imidazolylmethyl) -1H-indazole dihydrochloride 3.5 hydrate Compound B: 3- [2- [4- (3-chloro-2-methylphenyl) -1-piperazinyl] ethyl] -5,6-dimethoxy The effect of the present invention was confirmed in the following examples using benzyl] -1H-indazole. Example 1 Evaluation was carried out using a forced swimming test method which is often used as a screening evaluation test for antidepressants. (Method) Male Slc: ddY mice were used in groups of 10.
The day before the administration of each compound, the mouse was placed in a water tank (internal diameter: 11 cm, height: 40 cm) up to a height of about 20 cm, and a swimming trial was performed for 15 minutes. The next day, each compound was administered and
One hour later, the mouse was placed in the water tank, and immediately after that, the immobility time (sec) was measured for 6 minutes. (Results and Summary) Compound A showed a reduction in immobility time in this test at a dose of 1-3 mg / kg. Compound B is 0.
A dose of 1-0.3 mg / kg showed a reduction in immobility time. Since both Compound A and Compound B showed the action of shortening the immobility time in the animal model in this experiment, their usefulness as antidepressants was suggested. Example 2 Evaluation was carried out using the tail suspension test method used as a screening evaluation test for antidepressants. (Method) Male Slc: ddY mice were used in groups of 10.
One hour after the administration of each compound, a wire (diameter 1.1 m) was stretched horizontally about 1 cm from the tip of the tail of the mouse to a height of about 30 cm on the desk.
m) and hooked the mouse down. Immediately after that, the immobility time (sec) in 6 minutes was measured. (Results and Summary) Compound A showed a reduction in immobility time in this test at a dose of 1-3 mg / kg. Compound B is 0.
A dose of 1-0.3 mg / kg showed a reduction in immobility time. Since both Compound A and Compound B showed the action of shortening the immobility time in the animal model in this experiment, their usefulness as antidepressants was suggested.

[Brief description of drawings]

FIG. 1 is a view showing the antidepressant effect of Compound A and Compound B by the forced swimming test method.

FIG. 2 shows the antidepressant effect of Compound A and Compound B by the tail suspension test method.

Continued front page    F-term (reference) 4C063 AA01 BB03 CC25 DD22 EE01                 4C086 AA01 AA02 BC37 BC38 GA07                       GA12 MA01 MA04 NA14 ZA12                       ZA18

Claims (13)

[Claims] 1. Formula (I): (In the formula, Q is an aryl group, a heterocyclic group, a diarylmethyl group, an aralkyl group composed of an aryl group and an alkylene group having 1 to 6 carbon atoms, an alkyl group having 1 to 8 carbon atoms, or A cycloalkyl group having 3 to 8 is represented, where the aryl group, the heterocyclic group, and the aryl group in the diarylmethyl group and the aralkyl group are: 1. an alkyl group having 1 to 6 carbon atoms; To 6 alkoxyl group, 3. trifluoromethyl group and 2,2,2-trifluoroethyl group, 4. trifluoromethoxyl group and 2,2,2-trifluoroethoxy group, 5. carbon number of 1 to 6 Alkylthio group, 6. alkylsulfinyl group having 1 to 6 carbon atoms, 7. alkylsulfonyl group having 1 to 6 carbon atoms, 8. alkyl group having 1 to 6 carbon atoms and carbonyl group An alkanoyl group composed of an alkyl group, 9. an alkanoyloxy group having 2 to 7 carbon atoms, 10. an alkanoylamino group having 2 to 7 carbon atoms, 11. an amino group, 12. an alkyl group having 1 to 6 carbon atoms 13. a monoalkylamino group having, 13. a dialkylamino group each of which is independently an alkyl group having 1 to 6 carbon atoms, 14. a hydroxyl group, 15. a halogen atom, 16. a perfluoroalkyl group having 2 to 6 carbon atoms, 17. Cyano group, 18. Nitro group, 19. Carboxyl group, 20. Alkoxycarbonyl group composed of an alkoxyl group having 1 to 6 carbon atoms and a carbonyl group, 21. Tetrazolyl group, 22. Sulfamoyl group, 23. Methylenedioxy Group, ethylenedioxy group and propylenedioxy group, 24. morpholinosulfonyl group, 25. Piperazino sulfonyl group, 26. 4-alkyl piperazino sulfonyl group having an alkyl group having 1 to 6 carbon atoms, 27. 4- each independently having a dialkylamino group which is an alkyl group having 1 to 6 carbon atoms One or more substituents selected from the group consisting of (dialkylamino) piperidino group, 28. 4- (monoalkylamino) piperidino group having an alkyl group having 1 to 6 carbon atoms, and 29.4-aminopiperidino group. R may have the formula: (In the formula, G is a phenyl group which may have a substituent, b. A benzoyl group which may have a substituent in the phenyl group portion, and c. Which has a substituent group in the phenyl group portion. Optionally a benzylcarbonyl group, d. A benzoylmethyl group optionally having a substituent on the phenyl group moiety, e. An α-hydroxybenzyl group optionally having a substituent on the phenyl group moiety, f. A 5-membered aromatic heterocyclic group which contains a nitrogen atom, an oxygen atom or a sulfur atom as an atom and may have a substituent (wherein, when the hetero atom is a nitrogen atom, this nitrogen atom is
It has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or serves as a bonding portion with the indazole ring. ), G. A 5-membered aromatic heterocyclic group containing a nitrogen atom as a hetero atom and a nitrogen atom, an oxygen atom or a sulfur atom as a second hetero atom and optionally having a substituent (here, When the two different atoms are nitrogen atoms, the nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or serves as a bonding portion with the indazole ring), h. A 5-membered aromatic heterocyclic group which contains two nitrogen atoms as different atoms and a nitrogen atom, an oxygen atom, or a sulfur atom as a third different atom and may have a substituent (here,
When the third hetero atom is a nitrogen atom, this nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or becomes a bonding portion with the indazole ring. ), I. A 6-membered aromatic heterocyclic group containing one or two nitrogen atoms and optionally having a substituent, j. Heterocyclic substitution consisting of a 5-membered aromatic heterocyclic group containing a nitrogen atom, an oxygen atom or a sulfur atom as a hetero atom and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms. An alkyl group (where the heteroatom is a nitrogen atom, the nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms), k. One nitrogen atom as a hetero atom, a nitrogen atom, an oxygen atom or a sulfur atom as a second hetero atom, and a 5-membered aromatic heterocyclic group which may have a substituent, and a carbon number of 1
A heterocyclic-substituted alkyl group composed of an alkylene group of 1 to 3 (wherein the second hetero atom is a nitrogen atom, this nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or It becomes a bonding part with an alkylene group.), L. 5-membered aromatic heterocyclic group, which contains two nitrogen atoms as different atoms and a nitrogen atom, an oxygen atom, or a sulfur atom as a third different atom, and may have a substituent, and a carbon number A heterocyclic-substituted alkyl group composed of 1 to 3 alkylene groups (wherein if the third hetero atom is a nitrogen atom, this nitrogen atom has a hydrogen atom or an alkyl group having 1 to 6 carbon atoms) Or a bonding portion with an alkylene group), m. A heterocyclic-substituted alkyl group composed of a 6-membered aromatic heterocyclic group containing 1 or 2 nitrogen atoms and optionally having a substituent, and an alkylene group having 1 to 3 carbon atoms, n ． A phenylhydroxyalkyl group composed of an alkylene group having 2 to 3 carbon atoms having one hydroxyl group and a phenyl group which may have a substituent, o. 2-phenylethynyl group (this phenyl group may have a substituent), p. A tetrazolyl group, q. A morpholino group, r. An alkanoylamino group having 2 to 7 carbon atoms, s. A tetrazolylalkyl group composed of a tetrazolyl group and an alkylene group having 1 to 3 carbon atoms (wherein the alkylene group is bonded at the carbon atom or nitrogen atom of the tetrazolyl group), t. A morpholinoalkyl group composed of a morpholino group and an alkylene group having 1 to 3 carbon atoms, u. 4-alkoxycarbonylcyclohexyl group (wherein the alkoxyl group has 1 to 6 carbon atoms), v. An alkoxycarbonyl group (wherein the alkoxyl group has 1 to 6 carbon atoms), w. A 1-alkylindol-2-yl group (wherein the alkyl group has 1 to 6 carbon atoms, and indole may further have a substituent), x. A pyrrolidone-1-yl group, y. A 2-guanidinothiazolyl group, z. A (2-guanidinothiazolyl) -alkyl group composed of a 2-guanidinothiazolyl group and an alkylene group having 1 to 3 carbon atoms, A. An optionally substituted 1,4-dihydropyridyl group, B. A 4-alkylpiperazinoalkyl group composed of a 4-alkylpiperazino group having an alkyl group having 1 to 6 carbon atoms and an alkylene group having 1 to 6 carbon atoms, C.I. A 4- (morpholinosulfonyl) phenylalkyl group composed of a 4- (morpholinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms, D. A 4- (piperazinosulfonyl) phenylalkyl group composed of a 4- (piperazinosulfonyl) phenyl group and an alkylene group having 1 to 6 carbon atoms, E. 4- (4-alkylpiperazinosulfonyl) phenylalkyl composed of a 4- (4-alkylpiperazinosulfonyl) phenyl group having an alkyl group having 1 to 6 carbon atoms and an alkylene group having 1 to 6 carbon atoms Group, F. An alkoxycarbonylalkyl group composed of an alkoxycarbonyl group having 2 to 7 carbon atoms and an alkylene group having 1 to 6 carbon atoms, G. A carboxyalkyl group composed of a carboxyl group and an alkylene group having 1 to 6 carbon atoms, H.I. A 4-dialkylaminopiperidino group having a dialkylamino group substituted with two alkyl groups having 1 to 6 carbon atoms at the 4-position of piperidine is bonded to the 4-position of a phenyl group.
A 4- (4-dialkylaminopiperidino) phenyl group and an alkylene group having 1 to 6 carbon atoms [4- (4-dialkylaminopiperidino) phenyl]
An alkyl group, I. A 4-monoalkylaminopiperidino group having a monoalkylamino group substituted with an alkyl group having 1 to 6 carbon atoms at the 4-position of piperidine is bonded to the 4-position of a phenyl group.
It is composed of a 4- (4-monoalkylaminopiperidino) phenyl group and an alkylene group having 1 to 6 carbon atoms.
4- (4-monoalkylaminopiperidino) phenylalkyl group, J. A 4- (4-aminopiperidino) phenyl group having a 4-aminopiperidino group bonded to the 4-position of the phenyl group and an alkylene group having 1 to 6 carbon atoms [4- (4
-Aminopiperidino) phenyl] alkyl group, K. A 4-dialkylaminopiperidino group having a dialkylamino group substituted with two alkyl groups having 1 to 6 carbon atoms at the 4-position of piperidine and an alkylene group having 1 to 6 carbon atoms (4-dialkyl An aminopiperidino) alkyl group, L. It is composed of a 4-monoalkylaminopiperidino group having a monoalkylamino group substituted with an alkyl group having 1 to 6 carbon atoms at the 4-position of piperidine and an alkylene group having 1 to 6 carbon atoms (4-mono An alkylaminopiperidino) alkyl group, M.I. A (4-aminopiperidino) alkyl group composed of a 4-aminopiperidino group and an alkylene group having 1 to 6 carbon atoms; A phenylalkyl group composed of a phenyl group which may have a substituent and an alkylene group having 1 to 6 carbon atoms. And O. Represents a substituent selected from the group consisting of a hydrogen atom, wherein a. To O. With respect to the substituents of the substituent group represented by, it means that it may have a substituent. An alkyl group having 1 to 6 carbon atoms; 2. an alkoxyl group having 1 to 6 carbon atoms, A trifluoromethyl group and a 2,2,2-trifluoroethyl group, 4. 4. Trifluoromethoxyl group and 2,2,2-trifluoroethoxyl group, 5. An alkylthio group having 1 to 6 carbon atoms, 6. An alkylsulfinyl group having 1 to 6 carbon atoms, 7. An alkylsulfonyl group having 1 to 6 carbon atoms, 8. An alkanoyl group composed of an alkyl group having 1 to 6 carbon atoms and a carbonyl group, An alkanoyloxy group having 2 to 7 carbon atoms, 10. 10. Alkanoylamino group having 2 to 7 carbon atoms, 11. An amino group, 12. 13. A monoalkylamino group having an alkyl group having 1 to 6 carbon atoms, 13. Dialkylamino groups each independently having an alkyl group having 1 to 6 carbon atoms, Hydroxyl group, 15. Halogen atom, 16. 17. A perfluoroalkyl group having 2 to 6 carbon atoms, A cyano group, 18. A nitro group, 19. A carboxyl group, 20. 21. An alkoxycarbonyl group composed of an alkoxyl group having 1 to 6 carbon atoms and a carbonyl group, 21. A tetrazolyl group, 22. 23. a sulfamoyl group, 23. Methylenedioxy group, ethylenedioxy group and propylenedioxy group; A morpholinosulfonyl group, 25. 26. a piperazinosulfonyl group, 26. 27. A 4-alkylpiperazinosulfonyl group having an alkyl group having 1 to 6 carbon atoms, 27. 27. A 4- (dialkylamino) piperidino group, each independently having a dialkylamino group which is an alkyl group having 1 to 6 carbon atoms, 29. 4- (monoalkylamino) piperidino group having an alkyl group having 1 to 6 carbon atoms, and 29. 4-aminopiperidino group means having one or more substituents selected from the group consisting of substituents. R ¹
And R ² are each independently an alkyl group having 1 to 6 carbon atoms,
An alkoxyl group having 1 to 6 carbon atoms, a trifluoromethyl group, a 2,2,2-trifluoroethyl group, a trifluoromethoxyl group, a 2,2,2-trifluoroethoxyl group, an alkylthio group having 1 to 6 carbon atoms, 1 to 6 carbon atoms
, An alkylsulfinyl group, an alkylsulfonyl group having 1 to 6 carbon atoms, an alkanoyl group composed of an alkyl group having 1 to 6 carbon atoms and a carbonyl group, and 2 to 7 carbon atoms
Alkanoyloxy group, alkanoylamino group having 2 to 7 carbon atoms, amino group, monoalkylamino group having an alkyl group having 1 to 6 carbon atoms, dialkylamino group each being an alkyl group having 1 to 6 carbon atoms , Hydroxyl group,
Halogen atom, perfluoroalkyl group having 2 to 6 carbon atoms, cyano group, nitro group, carboxyl group, alkoxycarbonyl group composed of alkoxyl group and carbonyl group having 1 to 6 carbon atoms, tetrazolyl group, sulfamoyl group, methylene Dioxy group, ethylenedioxy group, morpholinosulfonyl group, piperazinosulfonyl group, 4-alkylpiperazinosulfonyl group having an alkyl group having 1 to 6 carbon atoms, each independently an alkyl group having 1 to 6 carbon atoms Represents a 4-dialkylaminopiperidino group having a dialkylamino group at the 4-position, a 4-monoalkylaminopiperidino group having an alkyl group having 1 to 6 carbon atoms, or a 4-aminopiperidino group. ), Z
Is an alkylene group having 1 to 3 carbon atoms, an alkenylene group having 2 to 4 carbon atoms, an alkylene group having 1 to 3 carbon atoms having 1 hydroxyl group, a carbonyl atomic group, and a carbonyl atomic group at one end or in the middle of a carbon chain. It represents an alkylene group having 1 to 2 carbon atoms including or an oxalyl group. ) A therapeutic and / or prophylactic drug for depression, depression or anxiety disorder, which comprises a compound represented by the formula 2. The substituent Q in the compound of formula (I) is
Treatment and / or prevention of depression, depressive state or anxiety disorder containing the compound according to claim 1, which is a phenyl group having at least one substituent in the meta position, or a salt thereof, or a solvate thereof. medicine 3. The compound according to claim 2 or a salt thereof, or a salt thereof, wherein when the substituent Q in the compound of formula (I) is a phenyl group, the substituent at the meta position of the phenyl group is a halogen atom. And / or preventive agent for depression, depressive state or anxiety disorder containing solvate of 4. A depression or depressive state containing the compound according to claim 1, wherein the substituent Q in the formula (I) is a 2-methyl-3-chlorophenyl group, or a salt thereof, or a solvate thereof. Or therapeutic and / or preventive agent for anxiety disorder 5. In the compound of formula (I), Z has 2 carbon atoms.
Or the alkylene group of 3 or more, the treatment and / or prevention of depression, depressive state or anxiety disorder containing the compound according to any one of claims 1 to 4, a salt thereof, or a solvate thereof. medicine 6. The treatment and / or prevention of depression, depression or anxiety disorder, which comprises the compound according to claim 5, wherein Z is an alkylene group having 2 carbon atoms, or a salt thereof, or a solvate thereof. medicine 7. The compound according to claim ¹ , wherein the substituents R ¹ and R ² on the substituent R in the compound of formula (I) are methoxy groups, or a salt thereof, or a solvate thereof. For treating and / or preventing depression, depression or anxiety disorder 8. The compound or a salt thereof according to claim 1, wherein the substituents R ¹ and R ² on the substituent R in the compound of formula (I) are taken together to form a methylenedioxy group. Or a therapeutic and / or preventive agent for depression, depressive state or anxiety disorder containing a solvate of any of these 9. The substituent G on the substituent R in the compound of formula (I) is hydrogen atom, 3,4-dimethoxybenzyl group,
4-imidazoylmethyl group, 2-pyridylmethyl group, 3
A therapeutic and / or preventive agent for depression, depression or anxiety disorder, which comprises the compound according to claim 1, which is a -pyridylmethyl group or a 4-pyridylmethyl group, or a salt thereof, or a solvate thereof. 10. 3- [2- [4- (3-chloro-2-
Methylphenyl) -1-piperazinyl] ethyl] -5,
6-Dimethoxybenzyl) -1H-indazole or a salt thereof, or a therapeutic and / or prophylactic agent for depression, depressive state or anxiety disorder containing a solvate thereof 11. 3- [2- [4- (3-chloro-2-
Methylphenyl) -1-piperazinyl] ethyl] -5,
6-dimethoxy-1- (4-imidazolylmethyl) -1
Treatment and / or preventive agent for depression, depressive state or anxiety disorder containing H-indazole or a salt thereof, or a solvate of either of them 12. 3- [2- [4- (3-chloro-2-
Methylphenyl) -1-piperazinyl] ethyl] -5,
6-dimethoxy-1- (4-imidazolylmethyl) -1
Treatment and / or prevention agent for depression, depressive state or anxiety disorder containing H-indazole dihydrochloride 3.5 hydrate 13. The therapeutic and / or prophylactic agent according to claim 1, 10, 11 or 12, wherein the anxiety disorder is obsessive-compulsive disorder, panic disorder or social phobia.