JPH01203352A - Aromatic compound and medicine - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [two R<1> groups are same and lower alkyl; Y is a-CH=CH-CH=N-b, a-CH=CH-N=CH-b, a-N=CH- N(COR<2>)-b, etc.; a and b are binding position to the benzene ring; R<2> is lower alkyl] and/or salt thereof. EXAMPLE:5,8-Diacetoxyquinoline. USE:A remedy for wounds and delayed type allergy having promoting action on granuloma formation and inhibitory action on auricular edema. PREPARATION:A quinone expressed by formula II is reduced with a reducing agent, such as sodium hydrosulfite, to provide hydroquinone, which is then subjected to acylation reaction to afford the aimed compound expressed by formula I. Combination of an acid anhydride with a basic or acidic catalyst or an acid halide with a base is used as the acylating agent.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a novel aromatic compound and its use as a medicine.

<Prior Art> Certain aromatic compounds having an acyloxy group are known. For example, Journal of Chemical Society (J, Chem, 5oc
) 2759 (1952) contains 6-methyl-1,4
-Diacetoxynaphthalene is added to Helvetica Himica Acta (He1v, Chem.

Acta) Vol. 31, 1691 (1948) further describes 6-medoxy 1,4-diacetoxynaphthalene in the Journal of the Pharmaceutical Society of Japan (J, Pharm, Soc.

Japan) Volume 75, 203-207 (1955)
describes 6-acetyl-1,4-dimethoxynaphthalene. In addition, patent application No. 61-97539
There are compounds described in the specifications of No., No. 97540, and No. 97541.

However, the usefulness of the aromatic compound according to the present invention as a wound therapeutic agent or delayed allergic disease therapeutic agent has not been clarified at all.

<Problems to be Solved by the Invention> The purpose of the present invention is to provide a novel aromatic compound not found in the prior art;
We seek to provide pharmaceutically acceptable salts thereof.

Another object of the present invention is to provide a wound therapeutic agent and a delayed allergy therapeutic agent using the above-mentioned novel substance.

Means for Solving the Problems> That is, the present invention provides a compound having the general formula (I) (wherein, two R1s are the same and represent a lower alkyl group, and Y is a compound of the formula (II) to [■)]. Represents any of the groups shown.

■-CH=CH-CH=N-■ (II)■-
CH=CH-N=CH-■ (Ill)■-N
=CH-N (COR2)-■ (IV)■-〇〇= (: (OR3) CH2CH2-■ (V
)(Vl) ■-CH= C(II:OR') -CH2-CH2-
■ (■) [In the formula, ■ and ■ indicate the bonding positions to the benzene ring of formula (1), R2-R4 are lower alkyl groups that may be the same or different from each other, and X is a halogen atom. . ] The aromatic compound represented by the formula and its pharmacologically acceptable salt are defined as a material invention, and a wound treatment drug and a delayed allergic reaction drug containing the compound and/or its salt as an active ingredient are each defined as a use invention. This is what we provide.

The present invention will be explained in detail below.

The aromatic compound of the present invention is represented by formula (I).

In the present invention, lower refers to straight chain or branched chain with 1 carbon number.
4° to 4° is shown.

The lower alkyl group represented by R1-R4 includes methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, isobutyl group, 5ec-butyl group, tart
Examples include -butyl group, among which methyl group is preferred.

The halogen atom represented by X is preferably a chlorine or bromine atom, with a chlorine atom being particularly preferred.

Preferred compounds of the present invention include those shown in Table 1.

The pharmacologically acceptable salts of the compound of the present invention represented by formula (1) include those in which formula (I) has a nitrogen atom, and include inorganic salts such as hydrochloride, sulfate, and phosphate. Examples include salts with acids, or salts with organic acids such as acetates and propionates.

Preferred compounds of the present invention include those shown in Table 1.

Table 1 Next, production examples of the compounds of the present invention will be described, but the present invention is not limited to these production examples.

[Production method 1] Among the compounds of the present invention, - formula (1-1) (in the formula, two R1s are the same and are lower alkyl groups, and ■ and ■ are formulas (11) to (m ) to the benzene ring of formula (I), Y represents formula (II) or formula (I
II) ■-CH=CH-CH=N-■ [1
1] ■-CH=CH-N=CH-■ (Ill
). The compound represented by ] can be produced according to the following reaction formula.

Step A is a reaction that reduces quinone to hydroquinone.
As the reducing agent, sodium hydrosulfide, zinc, tin, iron powder, etc. can be used, and sodium hydrosulfide is particularly preferred.

As a reaction solvent, a combination of water and an organic solvent is preferably used. Examples of organic solvents include lower alcohols such as methanol, ethanol, and isopropanol, ester necks such as ethyl acetate, methyl acetate, and propyl acetate, or ethyl ether, Examples include ethers such as tetrahydrofuran and dioxane, and aromatic hydrocarbons such as benzene, toluene and xylene.

The amount of reducing agent used for (1-2) is 0.5 to 20
The amount of the solvent is 2 to 100 times, preferably 5 to 50 times by weight, preferably 1 to 10 times by mole. The reaction temperature is 0 to 100°C, preferably 10 to 60°C, and the reaction is carried out for 2 to 60 minutes, preferably 5 to 30 minutes. After the reaction is completed, it is separated and purified by a conventional method to obtain (I-3).

Step B is an acylation reaction of (I-3), which can be carried out under commonly used acylation conditions. As the acylating agent, a combination of an acid anhydride and a base catalyst or an acid catalyst, or a combination of an acid halide and a base can be used. As the acid anhydride, lower fatty acid anhydrides such as acetic anhydride, propionic anhydride, and butyric anhydride can be used.

Examples of the base catalyst include alkali metal salts of lower fatty acids such as sodium acetate, potassium acetate, and sodium propionate, triethylamine, N-methylmorpholine, and N-methylmorpholine.
, tertiary amines such as N-dimethylaniline, or nitrogen-containing heteroaromatic compounds such as pyridine and picoline.

As acid catalysts, mineral acids such as hydrochloric acid, sulfuric acid, perchloric acid,
Phosphoric acid, etc., or organic acids such as methanesulfonic acid, p-toluenesulfonic acid, etc. can be used.

As the acid halide, acid chlorides such as acetyl chloride, propionyl chloride, butyryl chloride, etc., or acid bromides such as acetyl bromide, propionyl bromide, butyryl bromide, etc. can be used as the acid halide.

The reaction may be carried out without a solvent or in the presence of a solvent inert to the reaction. Examples of inert solvents include ethers such as diethyl ether, tetrahydrofuran, dioxane, etc., or aromatic hydrocarbons such as benzene and toluene. , xylene, etc., or aliphatic hydrocarbons such as n-hexane, petroleum ether, etc. can be used.

The amount of acid anhydride or acid halide used in (1-3) is 1 to 50 times, preferably 4 to 20 times, by mole.
2 to 20 times the base, preferably 5 to 10 times the mole, and the same <0 when using an acid catalyst.
．． The amount of the reaction solvent is 1 to 10 times by mole, preferably 0.5 to 5 times by mole, and the reaction solvent is 2 to 50 times by weight, preferably 5 to 20 times by weight.

The reaction temperature is 0 to 150°C, preferably 20 to 1
The reaction is carried out at 00°C for 1 to 10 hours, preferably 2 to 5 hours. After completion of the reaction, separation and purification are performed according to conventional methods to obtain 1-1).

[Production method 2] Among the compounds of the present invention, in formula (u-1)C, three R1s are the same and are lower alkyl groups. ) can be produced according to the following reaction formula.

(n -2) I (n -3) Step C is a reaction to hydrolyze the ether bond in (11-2), and the reaction reagent is sulfuric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, etc. Lewis acids such as protonic acid, boron trichloride, boron tribromide, aluminum chloride, and aluminum bromide, or pyridine hydrochloride can be used.

The reaction can be carried out without a solvent, but in the case of a protonic acid, acetic acid, propionic acid, acetic acid-water, etc. can be used, and in the case of a Lewis acid,
Benzene, toluene, xylene, etc. can be used.

The amount of acid used is 1 to 50 times mole relative to (n-2),
Preferably, the amount of the solvent is 2 to 20 times by mole, and the solvent is also 2 to 50 times by weight, preferably 5 to 20 times by weight.

The reaction temperature is 0 to 200°C, preferably 20 to 150°C, and the reaction is carried out for 30 minutes to 6 hours, preferably 1 to 1.5 hours. After the reaction is completed, it is separated according to a conventional method and used for the reaction in step D.

Step D is an acylation reaction between phenolic -〇H and NH of the imidazole ring.
) can be obtained.

[Production method 3] Among the compounds of the present invention, - formula (m-1) [wherein R1
and R3 is a lower alkyl group. The compound represented by ] can be produced according to the following reaction formula.

(lll-2) (III-3) (nt-
4) Step E is benzoquinone and 2-alkoxy-1,3
-Diels-A of butadiene
lder) reaction, and examples of (nt-3) include methoxybutadiene and ethoxybutadiene. The reaction can be carried out without a solvent or in an inert solvent.

Examples of the solvent include aromatic hydrocarbons such as benzene, toluene, and xylene, and ethers such as dimethoxyethane and dioxane.

The amount of (III-3) to be used is 0.2 to 10 times mole relative to (III-2), preferably 0.4 to 5
The amount of the reaction solvent is 1 to 50 times by mole, preferably 2 to 20 times by weight. The reaction temperature is 10 to 200°C, preferably 50 to 150°C, and the reaction is carried out for 30 minutes to 20 hours, preferably 2 to 10 hours. After the reaction is completed, (m-4) is separated according to a conventional method and used for the reaction in step F.

Step F isomerization of enedione to hydroquinone,
(III-1) can be obtained by isomerizing the double bond and acylating the phenolic -○H in the same manner as in Step B of Production Method 1.

[Manufacturing method 4] Among the compounds of the present invention, - formula (■-1) [wherein, X is a chlorine or bromine atom]. ] The compound represented by
It can be produced according to the reaction formula below.

(Summer V-2) (mV -3) (IV-1) That is, it is an addition reaction of sulfenyl halide to the double bond of (■-2), and can be carried out in an inert solvent. Examples of the solvent include aliphatic halogenated hydrocarbons such as methylene chloride, chloroform, and dichloroethane, ethers such as ethyl ether, tetrahydrofuran, and dioxane, and aromatic hydrocarbons such as benzene, toluene, and xylene. Halogenated hydrocarbons are preferred.

The amount of (IV-3) used relative to (IV-2) is 0.
The amount of the reaction solvent is 5 to 10 times by mole, preferably 0.8 to 5 times by mole, and the reaction solvent is 2 to 100 times by weight, preferably 5 to 50 times by weight. The reaction temperature is from -70°C to 50°C, preferably from -50°C to 20°C, and the reaction is carried out for 30 minutes to 10 hours, preferably for 1 hour to 6 hours. After the reaction is completed, it is separated and purified according to a conventional method to obtain (r
V-1) is obtained.

[Production method 5] Among the compounds of the present invention, - formula (V-1) (in the formula, R1
and R4 is a lower alkyl group. The compound represented by ] can be produced according to the following reaction formula.

(IV-2) (V-2) (V-t) That is, the double bond portion of (rV-23 is reacted with an acid halide or an acid anhydride in the presence of a Lewis acid, and in this case, As the Lewis acid, aluminum chloride, zinc chloride, stannic chloride, titanium tetrachloride, etc. can be used.

As acid halides, acetyl chloride, propionyl chloride, butyryl chloride, isobutyryl chloride, etc., and as acid anhydrides, acylating agents such as acetic anhydride, propionic anhydride, butyric anhydride, etc. can be used.

As the reaction solvent, in addition to the above-mentioned acylating agent itself, a solvent inert to the reaction, such as nitrobenzene, nitromethane, chloroform, methylene chloride, dichloroethane, etc., can be used. The amount of Lewis acid to be used is 0.5 to 20 times the mole relative to (IV-2), preferably 3 to 5 times the mole, and the same amount (V-2) is 0.5 to 50 times the mole, preferably 3 to 5 times the mole. The amount of the solvent is 2 to 50 times by weight, preferably 5 to 20 times by weight.

The reaction temperature is 0 to 100°C, preferably 5 to 50°C.
The reaction is then carried out for 30 minutes to 10 hours, preferably for 1 to 5 hours. After the reaction is complete, separate and purify using conventional methods.
(V-1) is obtained.

Compound (I) of the present invention exhibits excellent wound healing action and anti-delayed allergic action, and is used for the treatment of trauma, frostbite, burns, hemorrhoids, etc., as well as for the treatment of various diseases based on delayed-type allergic diseases. . In addition, for the purpose of making the compound of the present invention have a tissue repair effect or an antiallergic effect,
It may be added to cosmetics.

When administering the compound of the present invention to a patient as a therapeutic agent for the above-mentioned diseases, it is possible to administer it orally, but it is preferable to administer it parenterally, especially in the form of an external preparation. External preparations include ointments, gels, Examples include suspensions. These preparations are
The compound of the present invention and excipients commonly used in pharmaceutical preparations may be mixed and formulated according to the dosage form. Alternatively, the compound of the present invention may be pulverized with other suitable formulations and applied directly to the affected area.

The dosage varies depending on the symptoms, the range of the lesion, and the number of administrations, but when administered as an ointment, an amount equivalent to 10 mg to 5 g of the compound of the present invention may be applied to the affected area once to several times per day.

Examples of drug preparation using the compounds of the present invention are shown below, but the present invention is not limited thereto.

Production Example 1 Ointment Compound of the present invention 1.0 g Light liquid paraffin 10. Og color vaseline
Total amount: 100 g Prepare 1% ointment according to the above recipe according to the usual method.

Production Example 2 External cream (1) Mixture A Compound of the present invention 1.0 g Stearic acid 15.0 g Cetano
5.0 g Nikkor MMS-405゜0
g Liquid paraffin 4.0 g (2) Mixture B Ethylparaben 0.1 g Glycerin 10.0 g Blue ice
Total amount: 100 g Prepare mixture A and mixture B, mix them according to the usual method, and make a total amount of 100 g.
It is made into a 1% external cream.

Production Example 3 Powder for external use Compound of the present invention 1.0g Carbobol 940 5.0g Lactose
A total of 100 g of the above formulation is mixed and ground to prepare a 1% powder for external use.

<Examples> The present invention will be specifically described below with reference to Examples, but the present invention is not limited thereto.

(Example 1) Synthesis of 5.8-diacetoxyquinoline (Compound No. 1, Table 1) 3.05 g (19 mmol) of 5.8-dioxoquinoline, 7 sodium hydrosulfide
．． 20 g (47 mmol) was added to a 300 mfL separatory funnel, and 15 portions of ethyl acetate were added. The ethyl acetate layer was separated, dried over anhydrous sodium sulfate, and the solid was separated.
When ethyl acetate was distilled off, a brown solid was obtained.

This solid and 9.62 g (94 mmol) of acetic anhydride were added to 30 ml of pyridine and stirred at 3° C. for 1 hour. After the reaction, acetic anhydride and lysine were distilled off under reduced pressure to obtain a solid. When this solid was recrystallized from ethyl acetate-methylene chloride, 3.72 g (yield 74%) of a white solid was obtained.

Melting point: 194.4°C 'Fl-NMR spectrum (CDCfl s , I)p
m) 2,48 (3H,s), 2.50 (3H.

s), 7.26 to 7.52 (3H, m), 8, 2
2 (IH, d, 7Hz), 8.40 (IH, d, 2
Hz) (Example 2) 5.8-diacetoxyisoquinoline (
Synthesis of Compound No. 2, Table 1) 5,8-Dioxoisoquinoline 1. OOg (6.28 mmol), sodium hydrosulfide 2.14 g
(12.56 mmol) was added to a 200 mJ2 Erlenmeyer flask, 60 ml of ethyl acetate and 10 mJZ of water were added, and the mixture was stirred at room temperature for 1 hour. After the reaction, a solid will precipitate, so collect it by filtration and add CH3 0H3mJZ, acetone 3m
I! .

When washed with water, a light brown solid was obtained.

This solid and 4.41 g (7 $: 3.2 mmol) of acetic anhydride were added to 10 ml of pyridine and stirred at 3°C for 30 minutes and at room temperature for 1 hour. After the reaction, acetic anhydride and pyridine were distilled off under reduced pressure to obtain a solid. Silica gel chromatography (developing solvent: methylene chloride: ethyl acetate; 20
:1), 0.97 g (yield 64%) of a white solid was obtained.

Melting point: 91.0°C' H-NMR spectrum (CDCl2s, ppm
) 2.48 (3H,S), 2.52 (3H.

s), 7.42 (2H, d, 7Hz), 7.64
(IH, a, 7Hz), 8.60 (IH, d, 7Hz)
, 9.34 (IH, d.

IHz) (Example 3) Synthesis of 1-acetyl-4,7-diacedoxybenzimidazole (Compound No. 3, Table 1) 4.7-Simethoxybenzimidazole (L Wein
Berger et al., J. Org., Che.
It was obtained by the method described in J. M., 24, 1451 (1959). ) was added to 47% hydrobromic acid and stirred at 130° C. for 1 hour.

The mixture was cooled to 5°C, and the precipitated crystals were filtered and dried.

The obtained black-green crystals, 1.24 g (15 mmol) of sodium acetate and 3.06 g of acetic anhydride
g (30 mmol) was stirred at 130° C. for 2 hours. After cooling to room temperature, ethyl acetate was added, insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure. The residue was separated by silica gel column chromatography (developing solvent: ethyl acetate), and then recrystallized from methylene chloride-hexane to obtain 0.50 g of pale pink crystals (yield 25%).

Melting point; 158°C') l-NMR spectrum (CDCII 3,1)p
ln) 2.37 (3H,s), 2.44 (3H.

s), 2.69 (3H, s), 7.07 (IH, d
, J=7Hz), 7.19 (IH.

d, J=7H2), 8.25 (IH, S) (Example 4
) 1,4-diacetoxy-7,8-dihydro-6-
Synthesis of Medoxynaphthalene (Compound No. 4, Table 1) In a 50 m JZ three-loaf flask equipped with a culler, 6.2 g of 6-medoxy 1.4,5,8,9.10-hexahydronaphthalene-1,4-dione, 8.3 g of acetic anhydride and 13.1 g of pyridine were added, and the mixture was heated and stirred at 140° C. for 2.5 hours under a nitrogen atmosphere. 30 ml of cooled condensed water and 50 ml of ethyl acetate were added for extraction.

Next, the ethyl acetate layer was washed with dilute hydrochloric acid, saturated sodium bicarbonate solution, and saturated brine, and then dried over anhydrous magnesium sulfate. After distilling off ethyl acetate under reduced pressure, the residue was subjected to silica gel column chromatography (solvent: chloroform)
to obtain 8.8 g of the target product as pale yellow crystals (yield: 9
8%).

Melting point: 94-95°C' H-NMR spectrum (CDCl23.ppH1)
(a)or(b)2. 30 (3H,5)(
b)or(a)2. 33 (3H,5)(C
) 2. 32-2. 90 (4H,
m) (d) 3. 70 (3H, 5)
(e)5. 47 (IH,S)
(f) or (g) a, 73 (IH, d,
J=8. IHz) (g)or(f)6. 89 (IH, d,
J-8,1Hz) (Example 5) 1,4-diacetoxy-6-chloro-7-
Synthesis of phenylthio-5,6,7,8-tetrahydronaphthalene (Compound No. 5, Table 1) In a 50 ml three-neck flask equipped with a dropping funnel, 1.4-
1.0 g of diacetoxy 5.8-dihydronaphthalene was added and dissolved in 5 mj2 of methylene chloride. The mixture was cooled to −40° C., and 5 ml of a methylene chloride solution containing 1.2 g of sulfenyl chloride was added dropwise thereto, followed by stirring at 0° C. for 4 hours. Water was added and extracted with methylene chloride.

The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The brown powder obtained by distilling off methylene chloride under reduced pressure was washed with n-hexane to obtain 1.4 g of the desired product as a light brown powder.
was obtained (yield 67%).

Melting point; 131-132°C' H-NMR spectrum ((:DCj!s, Pp
II) (a) or (b) 2. 30 (3H,
5)(b)or(a)2. 33 (3H,5
)(c) 2. 60-3. 50 (4
H, m) (d) 3. 88 (IH, q
, J=5. 4Hz) (e) 4. 32 (IH, q, J
=4. 5Hz) (f) 7.00 (2H,S) (g)
7. 20-7. 60 (5H, m) (Example 6) 6-acetyl-1,4-diacetoxy-7,8
-Synthesis of dihydronaphthalene (Compound No. 6, Table 1) 1.4-Diacetoxy-5,8-dihydronaphthalene
(R, Gaertner, J, Org, Chem
, 24.61 (1959). )0
．． 248g (1 mmol), aluminum chloride 0.4
A mixture of 0 g (3 mmol) and 4 mJl of nitrobenzene was ice-cooled, and 0.11 g (1,
4 mmol) was added.

After reacting for 1 hour under water cooling and further for 2 hours at room temperature, the mixture was added to dilute hydrochloric acid and extracted with ethyl acetate.

After drying the oil layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (developing solvent: ethyl acetate/hexane = 172) to obtain the desired product as pale yellow crystals of 0.1
8g was obtained (yield 45%).

Melting point: 146°C'H-NMR spectrum (CDC1s, 1)pm)
2, 33 (3H,s), 2. 38 (3
H.

s), 2. 43 (3H,s), 2. 48~
2, 77 (4H, m), 7. 03 (2H
.

s), 7. 40 (IH, s) Pharmacological Effect> The following is an experiment on the granuloma formation promoting effect that supports the wound treatment effect of the compound (I) of the present invention and the auricular edema suppressing effect that supports the anti-delayed allergic effect. This will be explained in detail by giving an example.

(1) Granuloma formation promoting effect test method A sterile felt sphere weighing 35±1 mg was impregnated with the test compound prepared in the example dissolved in acetone, and the mixture was left at room temperature to evaporate the acetone.

The felt balls prepared as described above were implanted subcutaneously on the shaved backs of male Wistar rats (body weight 150 to taog) under anesthesia, one each on the left and right controls, and the formed granulomas were removed 5 days later. After drying at 60° C. until the weight of the excised granuloma became constant, the weight was measured, and the value obtained by subtracting 35 mg from the dry weight of each granuloma was determined as the weight of the formed granuloma.

Sterile felt balls were implanted in the control group.

The results are shown in Table 2 as the percentage increase in granuloma formation in the test compound administration group relative to the control group.

Table 2 (2) Anti-delayed allergic effect experimental method Jcl: ICR male mouse (weight 20-23 g)
0.1 m2 of an ethanol solution of oxacilone (0.5 w/v%) was applied to the shaved abdominal skin of the mouse to sensitize it. After 58 days of sensitization, acetone solution of oxacilone (0.5w
/v%) was dissolved in the test compound prepared in the example, and 10 μm each of the solution was applied to both sides of the skin of the right auricle using a micropipette (10 uIL).

After 24 hours, the animals were anesthetized with ether, and a portion of the auricle where the drug was applied and the corresponding portion of the left (non-applied) auricle were punched into circles (5.5 mm in diameter), and their weights were measured. The swelling rate of the right auricle was calculated based on the weight of the left auricle piece. In addition, an acetone solution of oxacilone (0.5 w/v%) was applied to the control group.
The results are shown in Table 3 as the inhibition rate of the test compound administration group relative to the control group.

Claims (3)

[Claims] (1) General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [I] [In the formula, the two R^1s are the same and represent a lower alkyl group, and Y is the formula [II] Represents any group represented by [VII]. (a) -CH=CH-CH=N- (b) [II] (a)-
CH=CH-N=CH-(b)[III](a)-N=C
H-N(COR^2)-(b) [IV](a)-CH=C
(OR＾3)-CH_2-CH_2-(b)[V]▲There are mathematical formulas, chemical formulas, tables, etc.▼[VI] (a)-CH=C(COR＾4)-CH_2-CH_2
-(b) [VII] [wherein (a) and (b) are formulas [I
] indicates the bonding position to the benzene ring, R^2 ~ R^4
are lower alkyl groups which may be the same or different, and X is a halogen atom. ] and/or a pharmacologically acceptable salt thereof. (2) General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [I] [In the formula, the two R^1 are the same and represent a lower alkyl group, and Y is the formula [II] Represents any group represented by [VII]. (a) -CH=CH-CH=N- (b) [II] (a)-
CH=CH-N=CH-(b)[III](a)-N=C
H-N(COR^2)-(b) [IV](a)-CH=C
(OR＾3)-CH_2-CH_2-(b)[V]▲There are mathematical formulas, chemical formulas, tables, etc.▼[VI] (a)-CH=C(COR＾4)-CH_2-CH_2
-(b) [VII] [wherein (a) and (b) are formulas [I
] indicates the bonding position to the benzene ring, R^2 ~ R^4
are lower alkyl groups which may be the same or different, and X is a halogen atom. ] A wound treatment drug containing an aromatic compound represented by the following and/or a pharmacologically acceptable salt thereof as an active ingredient. (3) General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [I] (In the formula, the two R^1 are the same and represent a lower alkyl group, and Y is the formula [II] Represents any group represented by [VII]. (a) -CH=CH-CH=N- (b) [II] (a)-
CH=CH-N=CH-(b)[III](a)-N=C
H-N(COR^2)-(b) [IV](a)-CH=C
(OR＾3)-CH_2-CH_2-(b)[V]▲There are mathematical formulas, chemical formulas, tables, etc.▼[VI] (a)-CH=C(COR＾4)-CH_2-CH_2
-(b) [VII] (wherein (a) and (b) are the formula [I
] indicates the bonding position to the benzene ring, R^2 ~ R^4
are lower alkyl groups which may be the same or different, and X is a halogen atom. ] A therapeutic agent for delayed allergic disease containing an aromatic compound represented by the following and/or a pharmacologically acceptable salt thereof as an active ingredient.