JPS6183171A - Dibebzo (b,f) (1,5) oxazocin derivative, its preparation and pharmaceutical containing said derivative as active component - Google Patents

Abstract

NEW MATERIAL:The compound of formula I (R1 and R2 are H, halogen, lower alkyl, trihalomethyl, lower alkoxy, or lower acyl; R3 and R4 are lower alkyl, or R3 is H or di-lower alkylamino-lower alkyl and R4 is di-lower alkylamino- lower alkyl, or R3 and R4 bonds with each other at the terminals together with adjacent N atom and optionally interposing a hetero-atom in the chain, form a heterocyclic group which may have substituent group inert to the reaction; m and n are integer of 1-4). EXAMPLE:3-Methyl-12-[2-(dimethylamino)ethylamino]-6H-dibenzo-[b,f]-[1,5 qoxazocine. USE:A psychotropic agent (especially an antidepressant) or an analgesic agent. PREPARATION:The compound of formula I can be prepared by reacting the compound of formula II with a halogenation agent, and condensing the resultant compound of formula III (X is halogen) with the compound of formula IV.

Description

Detailed Description of the Invention Technical Field The present invention relates to a novel dibenzo(b,f)CL5]oxazosine derivative, a method for producing the same, and a psychotropic drug containing the same as an active ingredient, particularly an antidepressant or analgesic. It is related to.

That is, the present invention has the following general formula [I]: (However, R and R2 are each a hydrogen atom.

It is any one of a halogen atom, a lower alkyl group, a trihalomethyl group, a lower alkoxy group, and a lower acyl group; R3 and R4 each represent a lower alkyl group, or R3 is a hydrogen atom or a di-lower alkyl group. In an amino lower alkyl group, R4 represents a di-lower alkylamino lower alkyl group, or R3 and R4 are connected terminally, with or without a heteroatom, to form a heterocyclic group with the adjacent nitrogen atom. represents that the heterocyclic group may have a substituent that does not participate in the reaction; m and n are each an integer of 1 to 4) Novel dibenzo(b,f)CI
, 5) Provides oxazosine derivatives, conductors, and acid addition salts thereof such as inorganic acid salts and organic acid salts.

Background of the Invention By the way, a compound having such a structure in which two benzene nuclei are bonded to an oxazosine ring is disclosed in Japanese Patent Application Laid-open No. 50-12
According to Publication No. 6689, dibenzo (b, g) (1,4)
Oxazocins are known, and it has been clarified that compounds with this structure have antireserpine effects and are expected to be effective as psychotropic agents, such as antidepressants. No specific gaps have been made.

Among such oxazosine derivatives, the present inventors focused on dibenzo(b, fL (L, 5) oxazosine derivatives, introduced various amino groups at the 12th position, synthesized various derivatives corresponding to these, and each As a result of pharmacological tests, as will be shown in the examples below,
It was discovered that it has extremely excellent pharmacological effects. The present invention has been completed based on this knowledge.

Summary of the Invention In short, the present invention aims to provide a novel dibenzo(b,f)(1,5)oxazocine derivative represented by the general formula CI) and an acid addition salt thereof, and such a compound By using it, it was possible to achieve excellent psychotropic effects, especially antidepressant and analgesic effects.

Further, the compounds according to the present invention can be synthesized by the route shown in the following reaction formula.

(However, R+, RZ, R3+ Ra, m and n are
each has the same meaning as above, and X represents a halogen atom), i.e., 6.11-dihydro-12H-dibenzo(b, f
) [1,5) Oxazocin-12-one derivative (If)
is reacted with a halogenating agent to produce 12-halogeno-6H-
Dibenzo(b,f)(1,5]oxazocine derivative (I
II), which is then treated with the corresponding aminating agent (I
By reacting with V), the target compound 12-
Amino-6H-dibenzo(b,f)(1,5)oxazosine derivative (1) can be produced.

The halogen atoms employed as R1 and R2 in the compounds represented by the above general formulas and the general formulas described later can be any of the four halogen atoms, preferably fluorine, chlorine or bromine. and lower alkyl groups include -2 such as methyl, ethyl, and propyl.

Isopropyl, butyl, isobutyl, t-butyl.

Those having 1 to 6 carbon atoms such as amyl are preferably used, and trihalomethyl groups include trifluoromethyl groups and the like. Examples of lower alkoxy groups include methoxy, ethoxy, and propoxy.

Those having 1 to 4 carbon atoms such as isopropoxy and butoxy are preferably used, and lower acyl groups having 1 to 4 carbon atoms such as acetyl, propionyl and butyryl groups are preferably used.
-4 are preferably used.

Further, m and n are each an integer of 1 to 4, and both may be the same number or different numbers.

Then, in the first step of the reaction, the general formula (n
) Examples of the halogenating agent that can be reacted with the compound shown in
Phosphorus tribromide, phosphorus oxychloride, and the like can be suitably used, and the amount used is usually approximately equimolar to 1 to 2 times the molar amount. And also, this halogenation reaction can be used for, for example, benzene, toluene, xylene, etc. 8
It can be carried out in a medium or without a solvent, and in some cases, the rehalodination agent itself is used as a solvent, and the compound (
This is carried out by allowing a halogenating agent to act on n). The reaction at this time is, for example, 3 to 1
The process progresses suitably by heating for 0 hours, and the compound (I
[I) can be obtained in good yield.

The compound (I[[) thus obtained may be separated and purified and then subjected to the reaction in the next step, but there is no problem in using it as a raw material in the next step without being separated and purified.

In addition, as the aminating agent (IV) in the second step, as R1 and R4, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, -butyl, amyl, etc., a lower alkyl group having 1 to 6 carbon atoms, etc. are preferably used, and the two may be the same or different. And further, R1 and R4 may be terminally bonded with or without a heteroatom to form a heterocyclic group with the adjacent nitrogen atom; such a heterocycle may also be There is no problem even if the compound has a substituent that does not participate in the reaction. Such a heterocycle, i.e. -N (R
3) The heterocyclic group represented by (R4) is, for example, piperidino or substituted piperidino.

Pyrrolidino, substituted pyrrolidino, morpholino, substituted morpholino, piperazino, substituted piperazino.

These include hexamethyleneimino, substituted hexamethyleneimino, homopiperazino, substituted homopiperazino, and the like.

Furthermore, R8 is hydrogen or a di-lower alkylamino lower alkyl group, and R4 may be a di-lower alkylamino lower alkyl group, such as dimethylamine ethyl, diethylaminoethyl , dipropylaminoethyl,
Diisopropylaminoethyl, dimethylaminopropyl, diethylaminopropyl, dipropylaminopropyl.

Examples include diisopropylaminopropyl and dimethylaminoisobutyl groups.

This amination reaction can be carried out by using a suitable solvent such as benzene, toluene, or xylene, or by using the amino agent itself as a solvent without using such a solvent. This can be carried out by reacting J with a predetermined aminating agent (IV). Reaction temperature at this time.

Although the reaction time etc. can be selected as appropriate during the implementation, it is preferably carried out by heating at room temperature to 150°C for 2 to 10 hours, whereby the reaction proceeds suitably and the target compound can be obtained.

In addition, in the above reaction, separation and purification of the target compound [■] from the reaction mixture after the reaction can be carried out by means known per se, such as filtration, extraction, and solvent distillation.

This can be carried out by any combination of means such as chromatography and recrystallization.

The compound represented by the general formula (1) as described above can be used in the form of a free base, and it can also be used in the form of a physiologically important acid addition salt. Examples of such acid addition salts include various inorganic salts and organic salt forms, including hydrohalides such as hydrochlorides, hydrobromides, and hydroiodides; salts, sulfates.

Other mineral salts such as nitrates; oxalates, tartrates.

malate, maleate, fumarate, citrate, methanesulfonate, benzenesulfonate, toluenesulfonate, salicylate, benzoate, ascorbate, mandelate, pamoate. Examples include organic acid salts such as

In addition, when producing compound (I) according to the present invention,
The compound of formula (n) that is the raw material is a new compound,
The manufacturing method is explained in detail in Japanese Patent Application No. 58-2094, which was previously filed by the applicant of the present application. be.

(However, R,, R,, m and n each have the same meaning as above.) That is, unsubstituted or R3-substituted methyl salicylate (V) and unsubstituted or R2-substituted 0- A compound represented by the formula [■] was obtained by reacting nitrobenzyl bromide [■] in methanol in the presence of sodium methylate, and this was reduced with stannous chloride and hydrogen chloride in ethyl acetate. , expression [■]
To obtain a compound represented by formula (IX) and to protect the amino group of such compound [■], 2-nitrophenylsulfenyl chloride was reacted with 2-nitrophenylsulfenyl chloride in dichloromethane to form a compound of formula (IX). The compound shown above was obtained, and then the compound (IX) was treated with potassium hydroxide in a water-containing organic solvent (e.g., ethanol, tetrahydrofuran, or dioxane) (at this time, 18-crown ether was used as a catalyst). The carboxylic acid represented by formula (X) is obtained by hydrolysis, and this carboxylic acid (X) is further ring-closed with thionyl chloride and triethylamine in dimethylformamide to obtain the desired raw material compound ( n).

And such compounds provided by the present invention,
That is, dibenzo (b, f) represented by the above general formula (1)
(1,5) As mentioned above, detailed pharmacological tests conducted by the present inventors have shown that oxazocin FA4 and its acid addition salts act on the central nervous system, particularly analgesic, sedative, and central stimulatory effects. Action.

It has been revealed that it has muricide inhibitory and anticataleptic effects, and these actions have shown that it is useful as a psychotropic drug, especially as an antidepressant, and as an analgesic. They are recognized and can be used as their active ingredients.

The compound of the present invention can be used as a drug having the above-mentioned excellent pharmacological effects, and can also be formulated into parenteral preparations, such as injections, as desired. be. In addition, when used as an oral preparation, it is formulated using conventional stabilizers and excipients, and the dosage is generally 25 to 300 μ/person/day, preferably 25 to 1
The dosage will be within the range of 25 μ/person/day. Examples of stabilizers and excipients used in such formulations include known ones such as starch, colloidal silicon dioxide, and magnesium stearate.

EXAMPLES Examples of the present invention are shown below to clarify the present invention more specifically, but it goes without saying that the present invention is not limited in any way by the description of these examples. .

3-Methyl-6,11-dihydro-12H-dibenzo (
b, f) 3.0 of (1,5)oxazocin-12-one
90 ml of toluene and 3.2 g of phosphorus pentachloride were added to the mixture, and the mixture was stirred under heating under reflux for 3 hours. Next, the solvent was distilled off, and 5 Q ml of toluene was added to the remaining 3-methyl-12-chloro-6H-dibenzo(b,f)(1,5)oxazosine to dissolve it, and 2-(dimethylamino ) 1 g of ethylamine was added, and the mixture was stirred under heating under reflux for 3 hours. Then, the solvent was distilled off from this reaction product, and 70 ml of ethyl acetate was added to the residue to dissolve it, washed three times with 5 Qmf of saturated brine, and then dried over anhydrous sodium sulfate. Then, the solvent was distilled off to obtain a yellow oil as a residue. This product was subjected to silica gel column chromatography (developing solvent: chloroform:methanol = 9:1), the third eluate was collected, and the solvent was distilled off to obtain a yellow oil. This was recrystallized from ethyl acetate to produce a colorless prism product, melting point: 98~
3-Methyl-12-(2-(dimethylamino) at 99°C
Ethylaminoco-6H-dihenzo(b,f)(1,5)
1.67 g of oxazosine was obtained.

Σ琶且光扼 (CDC1yu) δ; 2.16 (3H, s) 2.23 (6H, s) 2.54 (2H, t, J=6Hz) 3.98 (2H, t, J=6Hz > 4, 86. 5.34 (2H, AtBzQ+ J=1
2Hz) 6.58~7.30 (7H,m)
1610-1630 (>C=N) Elemental analysis: Theoretical value as C1q HZ 3 N 30 C: 73.36. H Near, 49. N:13.
58 Actual value C: 73.47. H Near, 54. N
:13.509-chloro-6,11-dihydro-12
H-dibenzo(b,f)(1,53oxazosine-12
90 ml of toluene and 2.7 g of phosphorus pentachloride were added to 3.0 g of -one, and the mixture was stirred under heating under reflux for 3 hours.

Next, the solvent was distilled off from this reaction product, and 70 mj of toluene was added to the residue. was added to dissolve it, and then N
- 11.5 g of methylpiperazine was added, and the mixture was stirred under heating under reflux for 3 hours. Next, 100 mff of ethyl acetate was added to the residue obtained by distilling off the solvent of this reaction product to dissolve it, and the mixture was further washed three times with 80 mj+ of saturated brine, and then dried over anhydrous sodium sulfate. Furthermore, the solvent was distilled off from the obtained solution to obtain a yellow oil, which was subjected to silica gel column chromatography (developing solvent...C
HCl3:CH30H=9:1), the third eluate was collected, and the solvent was evaporated to give a yellow oil. This product was recrystallized from methanol to give colorless prismatic crystals of 9-chloro-12-(4-methyl-1-piperazinyl)-6H with a melting point of 113 to 115°C.
3.4 g of -dibenzo(b,B(1,5)oxazosine) was obtained. Furthermore, methanol containing 10% hydrogen chloride was added to this to form a hydrochloride, and the resulting crude crystals were converted into methanol-ether. When recrystallized from 9-chloro-1
3.5 g of 2-(4-methyl-1-piperazinyl)-6H-dibenzo(b,f) (1,5) oxazocine hydrochloride (colorless phosphorus flakes, melting point = 240-243°C) was obtained. .

NMR analysis [free base] (CDC/!,) δ: 2.32 (3
H, s) 2.44 (4H, m) 3.48 (4H, m) 4.86, 5.26 (2H, AzBzq, J=12
Hz) 6.79-7.28 (7H, m) [Hydrochloride) (DMSO-d6) δ: 2.88 (3H, s) 3.38-4.01 (8H, m) 5.22.5 .49 (2H, AzBzql J=1
2Hz) 7.06-7.58 (7H, m> YuJ■shiki [free base) v stomach cs-': 1560-1570
C-N-) [Hydrochloride] ν5 cm": 1610 (>C=N-
) jJ Wataku [free base] CI9H! Theoretical value as 6N30CIl
C: 66.76, H2 5.90. N: 12.2
9 Actual measurement value C: 67.02. H:5.90. N
:12.30 [Hydrochloride] 'CrqHzor'J+
OCIl ・2 HCl ・415H, Theoretical value as O C: 53.1? , H:5.54. N:
9.79 Actual value C: 53.32. H:5.83.
N: 9.43 Example 3 9-chloro-12-(1
-homopiperazinyl)-6H-dibenzo(b, f) (1,5) Synthesis of oxazocine hydrochloride 9-chloro-6,11-dihydro-12H-dibenzo(
b, f) To 3.0 g of (1,5)oxazosin-12-one, 90 ml of toluene and 2 phosphorus pentachloride
．． 7 g was added, and the mixture was stirred under heating and reflux for 3 hours. After cooling the reaction product, the solvent was distilled off, and 7 toluene was added to the resulting residue.
Add 0 mA to dissolve, and add homopiperazine 11 to this.
．． Next, 5 g was added and stirred under heating and reflux for 3 hours.
The solvent of this reaction product was distilled off, and 100 ml of ethyl acetate was added to the residue to dissolve it, followed by 80 ml of saturated brine.
After washing with mf three times, it was dried with anhydrous sodium sulfate.

Next, the solvent was distilled off from this solution to obtain a yellow oil, which was further subjected to silica gel column chromatography (developing solvent: CHCl3:CH30H=9:1), and the third eluate was collected. Further, the solvent was distilled off to obtain a yellow oil. This product was recrystallized from methanol to produce colorless prism crystals, melting point: 144-145°C, 9-chloro-12-(1-homopiperazinyl)-6H-dibenzo(b,f)(1°5)oxazosine 3.5 g Further, this product was dissolved in methanol, saturated with hydrogen chloride gas under water cooling, the solvent was distilled off, and the residue was recrystallized from methanol to obtain colorless fine needle-like crystals.

9-chloro-12- with melting point: 240-248°C (decomposed)
(1-homopiperazinyl)-6H-dibenzo(b,r)
3.64 g of (1,5)oxazosine hydrochloride was obtained.

Ordinary 1 minute Kaji [free base] (CDC1:+) δ; 1.62. 1.98 (2H, m, m) 1.7
5 (IH, s) 2.76-4.35 (8H, m) 4.85, 5.29 (2H, AZB2q, J=12
Hz) 6.7 1-7.26 (7H, m) [Hydrochloride] (D
MSO-d6) δ: 2.08.2.46 (2H, m, m) 3, 19-4
．． 58 (8H, m) 5.24, 5.52 (2H, AzBzq, J word 12H2) 7.09-7.64 (7H, m) 10.14 (IH, S) -Lm previous kaji [free base] cI11-1:3345 (-NH
-).

1555-1570 (>C=N-) [Hydrochloride] C↓cn-': 1605 (C=N-) Former 1E monthly [free base] C19Hz. Theoretical value C as Nx0C1
: 66.76, H:5.90. N: 12.29
Actual measurements: C: 66.76, H: 5.94. N:
12.2B [hydrochloride] CI 9 Hz. N5OCj
!・Theoretical value C as 2HCj2・3/2HtO: 51.65. H:5.70+N:
9.51 Actual value C: 51.54. H:5.55.
N: 9.50 In addition, various compounds having different substituents as shown in Tables 1 and 2 were synthesized by performing the same reaction operation as above. The substituents in Tables 1 and 2 below are represented by the following general formula.

Example 4 The analgesic effects of various dibenzo(b,f)(1,5)oxazocine derivatives obtained in the previous examples were tested by the blood treatment Tiriacetic acid stretching method. ED of the obtained analgesic effect
S values are shown in Table 3 below.

The test was conducted using 5 groups of DD male mice, 4 weeks old and weighing 20 to 25 g, after fasting for about 5 hours, with 5 mice per group. In addition, 15 minutes after oral administration of the sample (compound of the present invention, the same applies hereinafter), 0.7% acetic acid (diluted with physiological saline) O, imf/10 g (body weight) was intraperitoneally administered to suppress stretching symptoms. If the number of times is less than half of that of the control group, the analgesic effect is considered to be positive, and all or no response (all or
Litchfield-Wilcoxon (Litchfield-Wilcoxon)
ED by the field-Wilcoxson method. It was determined by the ratio of values. The specimen should be an aqueous solution or 0.2
% sodium carboxymethyl cellulose solution, and the dose was adjusted to be 0.2 mn/10 g (body weight) for administration. For the control group, water or 0.2%
Carboxymethylcellulose sodium solution was administered.

In addition, R,, R,, R, 3, and R in the table below are substituents represented by the following general formula, and the same applies to the substituents shown in the following examples.

Example 5 Muricide control The bilateral olfactory bulbs of male Wistar rats aged 10 to 11 weeks old and weighing 240 to 250 g were removed by suction, and 7 days after the surgery, the mice were chewed within 5 minutes. Rats to be sacrificed (muricide) were selected, and then five rats were used per group that developed muricide (within 5 minutes) about 30 minutes before administration of the sample.

The specimen was dissolved in distilled water for injection or prepared as Q3i solution with 0.2% sodium carboxymethylcellulose solution, and administered in an applied volume of 0.5 ml/100 g (body weight).

Muricide suppression rate is 20 kg/kg or 40 kg of sample.
Animals that did not develop muricide (within 5 minutes) at 1 hour after intraperitoneal administration of the ■/kg dose were considered to be muricide suppressed based on a complete response.

As a result, most of the compounds of the present invention were found to have muricide inhibitory effects. An example is given in Table 4.

Example 6 Reserpine 2.5 μ/kg was intraperitoneally administered to ddY male mice, 5 weeks old and weighing 20 to 25 g.
After an hour, the specimen was orally administered at a dose of 40 μ/kg or 80 μ/kg, and catalepsy was observed 2 to 3 hours after administration of the specimen.

For catalepsy observation, mice were placed in a cage with a diameter of 21 layers and a height of 4 cm.
When the forelimbs were placed on top of a wire and placed in a certain position, those that remained in that position for 30 seconds or more were considered positive for catalepsy. Those that suppressed catalepsy within 30 seconds were considered anti-catalepsy positive, and the catalepsy suppression rate was determined from the ratio.

Using imibramine, clomipramine, desibramine, and amitributyline, which are currently widely used, as standard products, the anticatalepsy effect was determined when orally administered at the same dose as above, and compared with the compound of the present invention.

The results are shown in Table 5.

Table 5 Example 7 Mouse - Using 1 group of 3 male ddY mice, aged 5 years after neutrality and weighing 20-25 g, the central nervous system was sterilized in an arbitrary manner based on Arvin's method. 34 as an indicator of nervous effects, autonomic nervous effects, acute toxicity, etc.
For the behavior of the item, 100, 200 or 4 samples were collected.
00 ■/dose oral administration, or so, ioo or 2
A dose of 00 μ/kg was administered intraperitoneally, and observations were made over time until 2 hours later.

For oral administration, the sample should be dissolved in purified water or as a 0.2% sodium carboxymethylcellulose suspension, and for intraperitoneal administration, the sample should be dissolved in physiological saline or as a 0.2% sodium carboxymethylcellulose suspension. As a suspension, the applied capacity is 0.2mA/10g
(body weight) and administered.

As a result, as shown in Table 6, sedative effects, central stimulation effects, and sympathostimulatory effects were observed in most of the samples, and in some samples, body temperature lowering effects were also observed.

゛＼、

Claims (6)

[Claims] (1) General formula: ▲Mathematical formula, chemical formula, table, etc.▼ (However, R_1 and R_2 are each a hydrogen atom, a halogen atom, a lower alkyl group, a trihalomethyl group, a lower alkoxy group, or a lower acyl group) R and R_4 each represent a lower alkyl group, or R_3 is a hydrogen atom or a di-lower alkylamino lower alkyl group, and R_4 represents a di-lower alkylamino lower alkyl group, or R_3 and R_4 is attached at the end with or without a heteroatom,
Indicates that a heterocyclic group is formed together with the adjacent nitrogen atom, and that the heterocyclic group may have a substituent that does not participate in the reaction, and m and n are each 1 to 1. (representing an integer of 4) A novel dibenzo[b,f][1,5]oxazocine derivative or an acid addition salt thereof. (2) General formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, R_1 and R_2 are each a hydrogen atom, a halogen atom, a lower alkyl group, a trihalomethyl group, a lower alkoxy group, or a lower acyl group) m and n are integers from 1 to 4, respectively, and X represents a halogen atom). each represents a lower alkyl group, or R_3 is a hydrogen atom or a di-lower alkylamino lower alkyl group, and R_4 represents a di-lower alkylamino lower alkyl group, or R_3 and R_
4 is bonded at the terminal with or without a heteroatom to form a heterocyclic group together with the adjacent nitrogen atom, and the heterocyclic group does not participate in the reaction. Indicates that it may have a group. ) characterized by a condensation reaction with a compound represented by
The following general formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, R_1, R_2, R_3, R_4, m and n each have the same meaning as above) A novel dibenzo [b, f] [ 1,5] Method for producing an oxazosin derivative or an acid addition salt thereof. (3) General formula: ▲Mathematical formula, chemical formula, table, etc.▼ (However, R_1 and R_2 are each a hydrogen atom, a halogen atom, a lower alkyl group, a trihalomethyl group, a lower alkoxy group, or a lower acyl group) (m and n are integers from 1 to 4, respectively) are reacted with a halogenating agent to form the general formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, R_1, R_2 , m and n each have the same meaning as above, and X represents a halogen atom), and then convert this into the following general formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, , R_3 and R_4 each represent a lower alkyl group, or R_3 is a hydrogen atom or a di-lower alkylamino lower alkyl group, and R_4 represents a di-lower alkylamino lower alkyl group, or R_3 and R_
4 is bonded at the terminal with or without a heteroatom to form a heterocyclic group together with the adjacent nitrogen atom, and the heterocyclic group does not participate in the reaction. (indicating that it may have a group) is characterized by a condensation reaction with a compound represented by
The following general formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, R_1, R_2, R_3, R_4, m and n each have the same meaning as above) A novel dibenzo [b, f] [ 1,5] Method for producing an oxazosin derivative or an acid addition salt thereof. (4) General formula; ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, R_1 and R_2 are each a hydrogen atom, a halogen atom, a lower alkyl group, a trihalomethyl group, a lower alkoxy group, a lower acyl group) R_3 and R_4 each represent a lower alkyl group, or R_3 is a hydrogen atom or a di-lower alkylamino lower alkyl group, and R_4 represents a di-lower alkylamino lower alkyl group, or R_3 and R_4 are , indicates that the heterocyclic group is bonded at the terminal with or without a heteroatom to form a heterocyclic group together with the adjacent nitrogen atom, and the heterocyclic group does not contain a substituent that does not participate in the reaction. m and n each represent an integer of 1 to 4) The active ingredient is a dibenzo[b,f][1,5]oxazosine derivative or an acid addition salt thereof. Psychotropic drugs. (5) The medicament according to claim 4, wherein the psychotropic drug is an antidepressant. (6) General formula: ▲Mathematical formula, chemical formula, table, etc.▼ (However, R_1 and R_2 are each a hydrogen atom, a halogen atom, a lower alkyl group, a trihalomethyl group, a lower alkoxy group, or a lower acyl group) R_3 and R_4 each represent a lower alkyl group, or R_3 is a hydrogen atom or a di-lower alkylamino lower alkyl group, and R_4 represents a di-lower alkylamino lower alkyl group, or R_3 and R_4 are , indicates that the heterocyclic group is bonded at the terminal with or without a heteroatom to form a heterocyclic group together with the adjacent nitrogen atom, and the heterocyclic group does not contain a substituent that does not participate in the reaction. The active ingredient is a dibenzo[b,f][1,5]oxazocine derivative or an acid addition salt thereof, represented by (m and n are each an integer of 1 to 4) painkillers.