JPH07258252A - Thiazole compound and salt thereof - Google Patents

Abstract

PURPOSE:To obtain a compound or its salt which can provide a therapeutic agent for circulatory disease and psychotropic medicines such as antischizophrenic, antianxiety, or antidepressant. CONSTITUTION:This compound is expressed by formula I [n is 1-4; R<1> is H, -NR<10>R<11> (R<10>, R<11> are H, a lower acyl); R<2> is H, a lower alkyl; W is formula II, formula III; X is H, halogen; Y is O, S; Z is C, N] or its salt, for example, 5-{2-[4-(1,2-benzoisothiazole-3-yl)-1-piperazinyl]ethyl}-4-methylthiaz ole. The compound or its salt is obtained by reaction of a compound of the formula, H-W with a compound of formula IV (R<1> may be protected by an arbitrary protecting group; A is a removable group such as a halogen, p-toluenesulfonyloxy) in the presence of an acid scavenger and, when needed, a small amount of potassium iodide in an inert solvent at 20 to 110 deg.C, preferably at 40 to 80 deg.C, for 2 to 24 hours (usually for 2 to 8 hours) and, when needed, deprotection.

Description

Detailed Description of the Invention

BACKGROUND OF THE INVENTION

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a psychotropic drug containing a compound having a psychotropic action, and at least one compound or a pharmacologically acceptable salt thereof as an active ingredient. The present invention also provides a circulation comprising, as an active ingredient, a compound having the above-mentioned psychotropic action, which further has a circulatory system regulating action, and at least one of the compound or a pharmacologically acceptable salt thereof. The present invention relates to a therapeutic drug for organic diseases.

[0002]

[Outline of Invention]

[0003]

DISCLOSURE OF THE INVENTION The present inventors have now found that certain thiazole compounds have a strong psychotropic action and further have a high affinity for receptors related to the circulatory system. Was completed.

The present invention therefore aims at providing compounds having psychotropic effects.

Another object of the present invention is to provide a compound having a circulatory system regulating effect.

Another object of the present invention is to provide a psychotropic drug and a therapeutic drug for cardiovascular disease, which comprises the above derivative.

[0007]

The compounds according to the invention are
A compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof.

[0008]

[Chemical 3] [In the above formula, n represents an integer of 1 to 4, R ¹ represents a hydrogen atom, or a group —NR ¹⁰ R ¹¹ (wherein R ¹⁰ and R ¹¹
Each independently represents a hydrogen atom; a lower acyl group; an optionally substituted lower alkyl group; or a cycloalkyl group) R ² represents a hydrogen atom or a lower alkyl group, and a group W
Represents any of the groups represented by the following formulas (i) to (iii).

[0009]

[Chemical 4] (In the above groups, X represents a hydrogen atom or a halogen atom, Y represents an oxygen atom or a sulfur atom, and Z represents a carbon atom or a nitrogen atom.)] Represented by the general formula (I). The compounds have a strong psychotropic effect, and some of the compounds have a psychotropic effect and a circulatory system regulating effect. Therefore, according to the present invention, it is possible to provide a psychotropic drug (an anti-schizophrenia drug, an anxiolytic drug, an antidepressant drug, etc.) and a cardiovascular disease therapeutic drug that act effectively on mental functions.

DETAILED DESCRIPTION OF THE INVENTION Compounds of General Formula (I) In the present specification, the term “lower alkyl” as a group or a part of a group means that the group has a straight chain or branched chain carbon number of 1
~ 6, preferably 1-4, alkyl groups are meant. The halogen atom means a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

In the general formula (I), the group represented by R ¹ is -N.
Preferred examples of R ¹⁰ R ¹¹ are amino group; mono- or di-lower acylamino group (preferably mono-C _1-6 acylamino, more preferably mono-C _1-4 acylalkyl group); mono- or di-lower alkyl group; mono- or The C
_3-7 cycloalkylamino group (preferably mono C
_5-6 cycloalkyl groups). Further, the mono- or di-lower alkyl group may be substituted,
Halogen atoms examples of the substituent group, hydroxyl group, an acyloxy group (preferably a _{C 1 to 6} acyloxy, more preferably _{C 1 to 4} acyloxy groups), alkoxy groups (preferably _{C 1 to 6} alkoxy groups, more preferably _{C 1 .About.4} alkoxy groups). Specific examples of mono- or di-lower alkylamino substituted with these substituents include monohalogeno-lower alkyl (eg, trifluoromethylamino, difluoromethylamino), hydroxyethylamino, lower acyloxyethylamino, (alkoxyethyl) methylamino. And so on.

Further, a preferable example of R ² is a hydrogen atom or a methyl group.

As a preferred example of the compound according to the present invention, X in the formula (i) is a fluorine atom or a hydrogen atom,
A compound in which Y is an oxygen atom or a sulfur atom, Z is a carbon atom or a nitrogen atom, a compound of the formula (ii) in which X is a fluorine atom and Y is a sulfur atom, and a compound of the formula (iii) in which X is a fluorine atom or chlorine The compound which is an atom or a hydrogen atom is mentioned.

Further, specific examples of the preferred compound group of the present invention include 5- [2- [4- (1,2-benzisothiazol-3-yl) -1-piperazinyl] ethyl] -4.
-Methylthiazole, 5- [2- [4- (6-Fluoro-1-benzothiophen-3-yl) -1-piperidinyl] ethyl] -4-methylthiazole, 5- [2- [4
-(1H-Benztriazol-1-yl) -1-piperidinyl] ethyl] -4-methylthiazole, 2-acetylamino-5- [2- [4- (1,2-benzisothiazol-3-yl)) -1-Piperazinyl] ethyl]-
4-methylthiazole, and 2-acetylamino-5
-[2- [4- (6-Fluoro-1-benzothiophen-3-yl) -1-piperidinyl] ethyl] -4-methylthiazole and the like can be mentioned.

The compound of the present invention can be a salt thereof. Such salts include medically acceptable non-toxic salts. Examples thereof include hydrohalides such as hydrochlorides, inorganic acid salts such as sulfates, organic acid salts such as succinic acid, citric acid, fumaric acid and maleic acid, and amino acid salts such as glycine and phenylalanine. To be

Preparation of Compounds of General Formula (I) The compounds according to the present invention can be prepared by the following methods.

The compound of the general formula (I) according to the present invention has the following general formula (II): HW (II) (wherein W has the same meaning as defined in the above general formula (I). Represented by the following general formula (II
I):

[0018]

[Chemical 5] (In the above formula, R ¹ and R ² have the same meanings as defined in the above general formula (I), but R ¹ may be protected by a general protecting group in some cases, and A is A halogen atom such as a chlorine atom or a bromine atom, or a compound represented by a leaving group such as a p-toluenesulfonyloxy group or a methanesulfonyloxy group is used as a solvent that does not participate in the reaction (for example, anhydrous acetonitrile). , Dimethylformamide or tetrahydrofuran),
20-110 ° C, preferably 40-80 ° C in the presence of acid scavenger and optionally small amount of potassium iodide
At a reaction temperature of 2 to 24 hours, usually 2 to 8 hours, and optionally deprotected.

Examples of the acid scavenger used in the above reaction include alkali carbonates such as potassium carbonate and sodium bicarbonate, and organic amines such as triethylamine.

Use of Compound / Pharmaceutical Composition The compound represented by the general formula (I) and the pharmaceutically acceptable salt thereof according to the present invention have an anti-methamphetamine action, and further, an important mechanism of antipsychotic action. D considered to be an introduction
₂ receptor, and, 5H which are to be associated with psychiatric and neurological disorders of the central nervous system including depression, anxiety-schizophrenia
High affinity with T receptor. Therefore, the compounds and pharmaceutically acceptable salts according to the present invention can be used as psychotropic drugs. In addition, in this specification, a psychotropic drug shall include an anti-schizophrenia drug, an anxiolytic drug, and an antidepressant drug.

Further, a part of the compound represented by the general formula (I) according to the present invention includes a compound having a high affinity with the 5HT receptor or the adrenergic-α ₁ receptor which regulates the circulatory system. Be done. Therefore, such a compound and a pharmaceutically acceptable salt thereof according to the present invention can also be used as a therapeutic agent for cardiovascular disease involving an adrenergic receptor or a serotonin receptor.

A pharmaceutical composition containing the present invention as an active ingredient can be administered to humans or non-humans by any of oral and parenteral (eg, intravenous, intramuscular, subcutaneous, rectal, transdermal) routes of administration. Can be administered to any animal. Therefore, the pharmaceutical composition containing the compound according to the present invention as an active ingredient is made into a suitable dosage form depending on the administration route.

Specific examples of the oral agent include tablets, capsules, powders, granules and syrups, and parenteral agents include injections such as intravenous injection and intramuscular injection, rectal administration, Examples include oily suppositories and aqueous suppositories.

These various preparations can be produced by a conventional method using commonly used excipients, disintegrating agents, binders, lubricants, coloring agents and the like.

Examples of the excipient include lactose, glucose,
Corn starch, sorbit, crystalline cellulose, etc.
Examples of the disintegrant include starch, sodium alginate, gelatin powder, calcium carbonate, calcium citrate, dextrin, and the like, and examples of the binder include dimethyl cellulose, polyvinyl alcohol, polyvinyl ether, methyl cellulose, ethyl cellulose, gum arabic, gelatin, hydroxypropyl cellulose. , Polyvinylpyrrolidone and the like, and examples of the lubricant include talc, magnesium stearate, polyethylene glycol, hydrogenated vegetable oil and the like.

If necessary, the above injection may be a buffer,
It can be manufactured by adding a pH adjuster, a stabilizer and the like.

The content of the compound according to the present invention in the pharmaceutical composition varies depending on its dosage form, but it is usually 0.
It is about 5 to 50% by weight, preferably about 0.5 to 20% by weight.

The dose is appropriately determined depending on the individual case in consideration of the age, weight, sex, difference in disease, degree of symptoms, etc. of the patient, but usually 1 to 1000 m per adult per day.
g, preferably 1 to 300 mg, which is administered once or several times a day.

[0029]

EXAMPLES The present invention will be described in more detail by the following examples, but the present invention is not limited to these examples. Example 1 5- [2- [4- (1,2-benzisothia
Zol-3-yl) -1-piperazinyl] ethyl] -4
-Methylthiazole 1- (1,2-benzisothiazol-3-yl) piperazine (100 mg, 0.46 mmol), 4-methyl-5- (2-paratoluenesulfonyloxyethyl) thiazole (128 mg, 0.48 mmol) And potassium carbonate (95 mg, 0.69 mmol) were suspended in 3 ml of dimethylformamide, and the mixture was stirred at room temperature for 12 hours. The insoluble matter was filtered, and the solvent was concentrated under reduced pressure. The residue was dissolved in chloroform, washed with water and then the solvent was distilled off to obtain a residue. The residue was purified by silica gel column chromatography to obtain 65 mg (yield 41%) of the title compound as an oil.

¹ H-NMR (CDCl ₃ ) δ 2.43
(3H, s, CH ₃ ), 2.68 (2H, t, J = 7.
_{4Hz, N-CH 2),} 2.77 (4H, t, J = 4.
8 Hz, piperazine CH ₂ ), 2.99 (2H, t, J
= 7.4 Hz, CH ₂ ), 3.60 (4H, t, J =
4.8 Hz, piperazine), 7.36 (1H, dd, J
= 8.2, 6.9 Hz, Ar), 7.48 (1H, d
d, J = 8.2, 6.9 Hz, Ar), 7.82 (1
H, d, J = 8.2 Hz, Ar), 7.91 (1H,
d, J = 8.2 Hz, Ar), 8.57 (1 H, s, thiazole); MW 344.48 (C ₁₇ H ₂₀ N
₄ S ₂ ); Mass spectrum EIMS, m / z 344
(M) ⁺ . Hydrochloride mp 220-223 ° C (dec.). Example 2 5- [2- [4- (6-fluoro-1-ben
Zothiophen-3-yl) -1-piperidinyl] eth
[Lu] -4-methylthiazole 1- (1,2-benzisothiazol-3-yl) piperazine was replaced with 4- (6-fluoro-1-benzothiophen-3-yl) piperidine. Example 1
Was synthesized in the same manner as.

¹ H-NMR (CDCl ₃ ) δ1.86
(2H, ddd, J = 13.0, 12.2, 3.6H
z, piperidine CH ₂ ), 2.06 (2H, m, piperidine), 2.25 (2H, ddd, J = 2.2, 11.
7, 12.2Hz, piperidine), 2.42 (3H,
s, CH ₃ ), 2.65 (2H, t, J = 7.5 Hz,
_{N-CH 2), 2.90 (} 1H, tt, J = 13.0,
2.2 Hz, piperidine), 2.98 (2H, t, J =
7.5 Hz, CH ₂ ), 3.13 (2H, br d, J
= 11.7 Hz, piperidine), 7.10 (1H, d,
J = 0.8 Hz, Ar), 7.13 (1H, dt, J =
8.9, 2.5 Hz, Ar), 7.54 (1H, dd,
J = 8.9, 2.5 Hz, Ar), 7.71 (1H, d
d, J = 8.9, 5.0 Hz, Ar), 8.57 (1
H, s, thiazole); MW 360.50 (C ₁₉ H ₂₁
N ₂ S ₂ F); mass spectrum SIMS, m / z 3
61 (M + 1) ⁺ . Hydrochloride mp 208 ° C (dec.). Example 3 5- [2- [4- (1H-benztriazo
L-1-yl) -1-piperidinyl] ethyl] -4-me
1- (1H-benzotriazole-1-) in place of tilthiazole 1- (1,2-benzisothiazol-3-yl) piperazine
It was synthesized in the same manner as in Example 1 except that yl) piperidine was used.

¹ H-NMR (CDCl ₃ ) δ2.20
(2H, m, piperidine), 2.37 (2H, m, _{piperidine), 2.43 (3H, s,} CH 3), 2.55
(2H, m, piperidine), 2.68 (2H, t, J =
_{7.2Hz, N-CH 2),} 2.98 (2H, t, J =
7.2 Hz, CH ₂ ), 3.18 (2H, br d, J
= 12.2 Hz, piperidine), 4.75 (1H, t
t, J = 4.2, 11.7 Hz, piperidine), 7.3
8 (1H, dd, J = 8.3, 6.9Hz, Ar),
7.49 (1H, dd, J = 8.3, 6.9Hz, A
r), 7.61 (1H, d, J = 8.3 Hz, Ar),
8.08 (1H, d, J = 8.3Hz, Ar), 8.6
0 (1H, s, thiazole); MW 327.44 (C
₁₇ H ₂₁ N ₅ S); mass spectrum FDMS, m / z
327 (M) ⁺ . Hydrochloride mp 222 ° C (dec.). Example 4 2-Acetylamino-5- [2- [4-
(1,2-benzisothiazol-3-yl) -1-pi
Perazinyl] ethyl] -4-methylthiazole 4-methyl-5- (2-paratoluenesulfonyloxyethyl) thiazole instead of 2-acetylamino-4-
Synthesis was performed in the same manner as in Example 1 except that methyl-5- (2-paratoluenesulfonyloxyethyl) thiazole was used.

¹ H-NMR (CDCl ₃ ) δ2.21
(3H, s, CH ₃ ), 2.26 (3H, s, C
H ₃ ), 2.67 (2H, t, J = 7.7 Hz, NC)
H ₂ ), 2.76 (4H, t, J = 4.9Hz, piperazine), 2.91 (2H, t, J = 7.7Hz, C
H ₂ ), 3.61 (4H, t, J = 4.9Hz, piperazine), 7.36 (1H, dd, J = 8.0, 7.2H)
z, Ar), 7.47 (1H, dd, J = 8.0, 7.
2Hz, Ar), 7.81 (1H, d, J = 8.0H
z, Ar), 7.91 (1H, d, J = 8.0 Hz, A
r); MW 401.53 (C ₁₉ H ₂₃ N ₅ OS ₂ ); mass spectrum EIMS, m / z 401 (M) ⁺ ; m
p170-172 ° C. Example 5 2-Acetylamino-5- [2- [4- (6
-Fluoro-1-benzothiophen-3-yl) -1-
Piperidinyl] ethyl] -4-methylthiazole 4-methyl-5- (2-paratoluenesulfonyloxyethyl) thiazole instead of 2-acetylamino-4-
It was synthesized in the same manner as in Example 2 except that methyl-5- (2-paratoluenesulfonyloxyethyl) thiazole was used.

¹ H-NMR (CDCl ₃ ) δ 1.90
(2H, m, piperidine), 2.04 (2H, m, _{piperidine), 2.22 (3H, s,} CH 3), 2.24
(2H, m, piperidine), 2.26 (3H, s, CH
₃ ), 2.63 (2H, t, J = 7.2Hz, N-CH
₂ ), 2.89 (2H, t, J = 7.2Hz, C
H ₂ ), 2.90 (1H, m, piperidine), 3.13
(2H, br d, J = 11.8 Hz, piperidine),
7.09 (1H, s, Ar), 7.13 (1H, dt,
J = 8.8, 2.6 Hz, Ar), 7.53 (1H, d
d, J = 8.7, 2.6 Hz, Ar), 7.71 (1
H, dd, J = 8.7, 5.1 Hz, Ar); MW 4
17.54 (C ₂₁ H ₂₄ N ₃ OS ₂ F); mass spectrum SIMS, m / z 718 (M + 1) ⁺ ; mp 19
3 to 196 ° C.

The structures of the above compounds are shown in the following table.

[0036]

[Table 1] Pharmacological test (1) Antipsychotic effect The antipsychotic effect of the compound according to the present invention was evaluated using the inhibitory effect on methamphetamine-induced hyperlocomotion in mice as an index. 25-35g d
A group of 3 to 6 mice was used using male dY mice. Methamphetamine 2 mg / kg was subcutaneously administered to the mouse, and 15 minutes later, the compound of the present invention was intraperitoneally administered. After 15 minutes, the mouse was used for measuring the amount of exercise (Muromachi Kikai: ANIME X
UTMK-110) was placed in a transparent acrylic box (both vertical and horizontal height: 30 cm), and the momentum was measured for 30 minutes. The effects of haloperidol and chlorpromazine as comparative drugs were similarly evaluated. The results are as shown in Table 2.

[0037] (2) Extrapyramidal action The extrapyramidal action of the compounds according to the present invention was evaluated using the catalepsy inducing action, which is a typical pharmacological evaluation method, as an index. Using male ddY mice weighing 25 to 35 g, 1
The group consisted of 3 to 6 animals. The compound of the present invention is intraperitoneally administered, and 2
The presence or absence of catalepsy was determined after 0, 30 and 40 minutes. The presence or absence of catalepsy was judged to be positive for catalepsy when a mouse whose forelimbs were forcibly hung on a horizontal iron rod having a diameter of 1 mm horizontally placed at a height of 3 cm showed the unnatural state for 30 seconds or longer. The effects of haloperidol and chlorpromazine as comparative drugs were similarly evaluated.
The results are shown in Table 3.

[0038] (3) Binding Affinity with Various Receptors (a) Binding Affinity with Dopamine-D ₂ Receptor The affinity of the compound of the present invention for D ₂ receptor was examined using rat brain striatal P ₂ fraction. did. 10 rat brain striatum
Homogenize in double volume 0.32M sucrose,
The supernatant obtained by centrifugation at 900 xg for 10 minutes was further centrifuged at 11,500 xg for 20 minutes. Incubation buffer (50 mM Tri
s, 120 mM NaCl, 5 mM KCl, 1 mM
MgCl ₂ , 1 mM CaCl ₂ , pH 7.4) was added, and the mixture was further centrifuged at 39,900 × g for 20 minutes, and the obtained precipitate was designated as P ₂ fraction. This was incubated at 37 ° C. for 30 minutes in a 20-fold amount of a buffer containing 0.1 nM of [ ³ H] spiperone and each concentration of the compound of the present invention, and after the reaction, collected by Whatman GF / B glass filter and bound [ ³ The amount of [H] spiperone was measured by a liquid scintillation counter. Nonspecific binding amount is measured in the coexistence 10 ^-5 M sulpiride, [the present compound 10 ^-7 M
The binding inhibition rate of [ ³ H] spiperone to the D ₂ receptor was determined. The results are shown in Table 4.

[0039] (b) to evaluate the affinity of the compound of the present invention 5HT ₂ receptor binding affinity rat brain cortex of serotonin -5HT ₂ receptors as follows. P ₂ fraction was prepared by the same method as in (a). 50 mM containing [ ³ H] ketanserin 1 nM and each concentration of the compound of the present invention
37 ° C in Tris / HCl buffer (pH 7.4),
After incubating for 15 minutes, the amount of bound [ ³ H] ketanserin was measured after the reaction. The amount of non-specific binding was measured in the presence of 10 ^-5 M ketanserin, and the binding inhibition rate of [ ³ H] ketanserin to the 5HT ₂ receptor in the compound of the present invention 10 ^-9 M was determined. The results are as shown in Table 5.

Table 5 Binding affinity with serotonin-5HT ₂ receptors Inhibition rate (%) of compound 10 ⁻⁹ M Example 2 65.1 Chlorpromazine 12.4 (e) Binding Affinity with Adrenergic-α ₁ Receptor The affinity of the compound of the present invention for α ₁ receptor of rat cerebral cortex membrane fraction was evaluated as follows. Rat cerebral cortex 1
Add 0 volume of 0.25M sucrose and add 10 mM
The precipitate obtained by homogenizing in Tris / HCl buffer (pH 7.4) and centrifuging at 40,000 × g for 30 minutes was added with 20 volumes of 50 mM Tris / HCl buffer (pH 7.4). In addition, a membrane fraction sample was obtained. This was incubated in a buffer containing 0.2 nM [ ³ H] prazosin and each compound of the present invention at 25 ° C. for 45 minutes to measure the amount of bound [ ³ H] prazosin. The amount of non-specific binding was measured in the presence of 10 ^-5 M prazosin, and the rate of inhibition of [ ³ H] prazosin binding to the adrenaline-α ₁ receptor at the compound concentration of the present invention of 10 ^-9 M was determined. The results are shown in Table 6.

Table 6 Binding Affinity with Adrenergic-α ₁ Receptor Inhibition rate (%) of compound 10 ⁻⁹ M Example 4 53.8 Chlorpromazine 55.3 As is clear from these results, haloperidol and chlorpromazine evaluated as comparative drugs have anti-methamphetamine action, that is, antipsychotic action, but at the same time, catalepsy-inducing action, that is, extrapyramidal action is also strong. To be understood.

On the other hand, of the compounds of the present invention, for example, Example 1
Has an antipsychotic effect similar to the comparative drug,
It is clear that the extrapyramidal action is very weak. Therefore, the compound of the present invention can be said to be a drug having a wide safety margin as an antipsychotic drug.

In addition, among the compounds of the present invention, in addition to the compound having a high binding affinity with the D ₂ receptor, which is considered to be an important mechanism of antipsychotic action (for example, Example 5), depression / A compound having a high affinity for 5HT receptors (eg, Example 2) which is said to be associated with psychiatric / neurological disorders of the central nervous system including schizophrenia such as anxiety or α ₁ receptor which regulates circulatory system A compound having a high affinity with the body (for example, Example 4) has been found. From this, it is considered that the compound of the present invention can be applied to central nervous system or circulatory system diseases involving D ₂ , 5HT ₂ and α ₁ receptor.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Internal reference number FI Technical display location C07D 417/12 275 (72) Inventor Kenji Murase 760 Mojioka-cho, Kohoku-ku, Yokohama-shi, Kanagawa Made by Meiji (72) Inventor Yoshimasa Fukuda Meiji Seika 760, Shimooka-cho, Kohoku-ku, Yokohama, Kanagawa

Claims (7)

[Claims] 1. A compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof. [Chemical 1] [In the above formula, n represents an integer of 1 to 4, R ¹ represents a hydrogen atom, or a group —NR ¹⁰ R ¹¹ (wherein R 1
¹⁰ and R ¹¹ each independently represent a hydrogen atom; a lower acyl group; an optionally substituted lower alkyl group; or a cycloalkyl group) R ² represents a hydrogen atom or a lower alkyl group, and the group W is Represents any of groups represented by the following formulas (i) to (iii). [Chemical 2] (In the above groups, X represents a hydrogen atom or a halogen atom, Y represents an oxygen atom or a sulfur atom, and Z represents a carbon atom or a nitrogen atom.)] 2. W represents a group (i) (wherein X represents a hydrogen atom or a halogen atom, Y represents an oxygen atom or a sulfur atom, and Z represents a carbon atom or a nitrogen atom). The compound and pharmacologically acceptable salt according to claim 1, which are: 3. The method according to claim 1, wherein W is a group (ii) (wherein X represents a hydrogen atom or a halogen atom, and Y represents an oxygen atom or a sulfur atom). And a pharmacologically acceptable salt thereof. 4. The compound and pharmacologically acceptable salt according to claim 1, wherein W is a group (iii) (wherein X represents a hydrogen atom or a halogen atom). 5. 5- [2- [4- (1,2-Benzisothiazol-3-yl) -1-piperazinyl] ethyl]-
4-methylthiazole, 5- [2- [4- (6-fluoro-1-benzothiophen-3-yl) -1-piperidinyl] ethyl] -4-methylthiazole, 5- [2- [4- (1H -Benztriazol-1-yl) -1-piperidinyl] ethyl] -4-methylthiazole, 2-acetylamino-5- [2- [4- (1,2-benzisothiazol-3-yl) -1- Piperazinyl] ethyl] -4-methylthiazole, and 2-acetylamino-5- [2- [4- (6-fluoro-1-benzothiophen-3-yl) -1-piperidinyl] ethyl]-
A compound according to claim 1 selected from 4-methylthiazole and pharmaceutically acceptable salts thereof. 6. A psychotropic drug comprising at least one compound of the general formula (I) according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof as an active ingredient. . 7. A circulatory system comprising at least one compound of general formula (I) according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof as an active ingredient. Disease remedy.