JPH07316135A - Acrudone derivative and production thereof - Google Patents

Abstract

PURPOSE:To obtain a new compound useful for preventing and treating diseases involving histamine, leukotriene, prostaglandin, TNF, etc. CONSTITUTION:The compound of formula I (R<1>-R<6> are each H, a lower alkyl, lower alkoxyl or halogen; R<7> and R<8> are each H, a lower alkyl, aryl, etc.; (n) is 1-6) and a salt thereof, e.g. 2(2,3-dimethyl-4-fluorophenyl) aminobenzoic acid. The compound of formula I is obtained by reaction between a compound of formula II and hydrous hydrazine in a solvent (e.g. methanol) at 0 deg.C to the solvent reflux temperature (where, R<5> and R<6> are each 3,4-dimethyl; R<7> and R<8> are each H). This compound is useful for preventing and treating asthma, allergic rhinitis, atopic dermatitis, urticaria, hay asthma, digestive tract allergy, food allergy, etc.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel acridone derivative and / or pharmacologically acceptable salt effective for the preventive treatment of diseases involving histamine, leukotriene, prostaglandin, TNF and the like, and a method for producing them. .

[0002]

Background of the Invention and Background of the Invention Human bronchial asthma and atopic diseases appear as a result of complex intertwined biological reactions, and most of them are triggered by antigen-antibody reactions, which result in mast cells and basophils. Various released chemical mediators contract smooth muscles such as bronchial muscles and pulmonary blood vessels,
It is considered to be caused by causing damage to the living body by enhancing the permeability of peripheral blood vessels.

Chemical transmission released from mast cells and basophils
Histamine, leukotriene, and pros
Tagglandin, TNF, etc. are known. Out of these
Stamin in human allergic rhinitis and urticaria
Well known to be the most important chemical mediator
It Leukotriene is leukotriene B._Four , C
_Four And D_Four It is noted that the association with asthma attack is noted
Came.

Conventionally, the development of drugs for preventing, reducing or eliminating the symptoms of allergic diseases has been developed with the goal of inhibiting the production / release of these chemical mediators or antagonizing their effects. A typical example thereof is sodium cromoglycate (trade name Intal), which has been released since 1969.

[0005]

[Problems to be Solved by the Invention] However, in the conventional antiallergic agents represented by Intal (trade name), dissociation is observed between the in vitro inhibitory concentration of chemical mediator release and the in vivo inhibitory release concentration. At the same time, there are many unclear points in terms of the mechanism of action, and there is a strong demand for the development of antiallergic agents with clinically superior effects.

[0006] Mast cells and basophils that are deeply involved in allergic diseases have a high affinity receptor FcεRI for IgE antibody on the cell membrane, and the IgE antibody bound to this receptor crosslinks with the corresponding multivalent antigen. As a result, the intracellular signal transduction mechanism is activated for the first time. It is considered that histamine is released or prostanoids such as leukotrienes and prostaglandin D ₂ are released by the activation of intracellular signal transduction mechanism, which leads to so-called allergic symptoms. In addition, the produced TNF is considered to be involved in chronic disease and the like through interaction with other cells.

[0007] In view of such circumstances, the present inventor has identified a non-receptor type tylosin kinase, which is located at an early stage of activation of intracellular signal transduction mechanism, upon release of chemical mediators from mast cells and basophils. Focusing on this phosphorylation, an antiallergic agent based on a completely new mechanism that inhibits the activation of IgE antibody-dependent intracellular signal transduction mechanism of mast cells and basophils and the release of the above-mentioned chemical mediators We have conducted intensive research aiming at the development of. As a result, they have found that the acridone derivative described below achieves the intended purpose, and completed the present invention.

Therefore, the object of the present invention is to provide a novel anti-asthma drug and anti-allergic drug (prevention and treatment of allergic rhinitis, atopic dermatitis, urticaria, hay fever, digestive tract allergy, food allergy, etc.) Another object of the present invention is to provide an acridone derivative and a pharmaceutically acceptable salt thereof, and further to provide a method for producing the compound or a pharmaceutically acceptable salt thereof. It is intended to provide a medicine containing a pharmacologically acceptable salt as an active ingredient.

[0009]

The present invention has the general formula

[Chemical 3][R in the formula¹ , R² , R³ , R^Four , R^Five , R⁶ Is the same
Differently, a hydrogen atom, a lower alkyl group, a low
Represents a primary alkoxy group or a halogen atom. R ⁷ , R
⁸ Are the same or different and are hydrogen atom or lower alkyl
Represents a group, an aryl group, an aralkyl group, or R⁷ When
R⁸ Together with the nitrogen atom they are attached to
Form a ring having 5 or 6 members. Where the
The ring has an oxygen atom, a sulfur atom or the formula NR in the ring.⁹ (formula
Medium R⁹ Is a hydrogen atom, lower alkyl group, aryl group, ara
A group represented by a alkyl group). n
Represents an integer of 1 to 6. ] The acridone derivative represented by
And / or a pharmacologically acceptable salt.

The present invention further provides a general formula

[Chemical 4][R in the formula¹ , R² , R³ , R^Four , R^Five , R⁶ Is the same
Differently, a hydrogen atom, a lower alkyl group, a low
Represents a primary alkoxy group or a halogen atom. R ⁷ , R
⁸ Are the same or different and are hydrogen atom or lower alkyl
Represents a group, an aryl group, an aralkyl group, or R⁷ When
R⁸ Together with the nitrogen atom they are attached to
Form a ring having 5 or 6 members. Where the
The ring has an oxygen atom, a sulfur atom or the formula NR in the ring.⁹ (formula
Medium R⁹ Is a hydrogen atom, lower alkyl group, aryl group, ara
A group represented by a alkyl group). n
Represents an integer of 1 to 6. ] The acridone derivative represented by
And / or a pharmacologically acceptable salt thereof as an active ingredient
Asthma, allergic rhinitis, atopic dermatitis, urticaria
Rash, hay fever, gastrointestinal allergy or food allergy
It is a prophylactic / therapeutic agent.

In the above general formula, R ¹ , R ² , R ³ ,
The lower alkyl group as seen in the definition of R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ or R ⁹ means a linear or branched alkyl group having 1 to 8 carbon atoms, for example, a methyl group, an ethyl group, Propyl group, isopropyl group, butyl group, isobutyl group, se
c-butyl group, tert-butyl group, pentyl group (amyl group), isopentyl group, neopentyl group, tert-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-
Methylbutyl group, 1,2-dimethylpropyl group, hexyl group, isohexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group 2,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-
Dimethylbutyl group, 3,3-dimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group, 1,1,2-trimethylpropyl group, 1,2,2-trimethylpropyl group, 1-ethyl1-methylpropyl group 1 ethyl 2-methylpropyl group, heptyl group, octyl group and the like.

In the above general formula, R ¹ , R ² ,
The lower alkoxy group as seen in the definition of R ³ , R ⁴ , R ⁵ or R ⁶ is a linear or branched alkoxy group having 1 to 8 carbon atoms, such as a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group. , Butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, pentyloxy group (amyloxy group), isopentyloxy group, neopentyloxy group, tert-pentyloxy group, 1-methylbutoxy group, 2-methyl Butoxy group, 3-methylbutoxy group, 1,2-dimethylpropoxy group, hexyloxy group, isohexyloxy group, 1-methylpentyloxy group, 2-methylpentyloxy group, 3-methylpentyloxy group, 1,1 -Dimethylbutoxy group, 1,2-dimethylbutoxy group, 2,2-dimethylbutoxy group, 1,
3-dimethylbutoxy group, 2,3-dimethylbutoxy group, 3,3-dimethylbutoxy group, 1-ethylbutoxy group, 2-ethylbutoxy group, 1,1,2-trimethylpropoxy group, 1,2,2- Trimethylpropoxy group, 1
-Ethyl 1-methylpropoxy group, 1-ethyl 2-methylpropoxy group, heptyloxy group, octyloxy group and the like.

Further, the halogen atom means a fluorine atom, a chlorine atom, a bromine atom, an iodine atom and the like.

In the above general formula, R ⁷ , R ⁸ or R
^The aryl group in the definition of ⁹ means a phenyl group, a biphenyl group, a naphthyl group, an anthryl group, a phenanthryl group and the like, and a heteroaryl group means a group containing 1 to 2 oxygen atoms, nitrogen atoms or sulfur atoms. It means a saturated 5- to 7-membered ring. It is preferable that these aryl group and heteroaryl group do not have a substituent. Further, the aralkyl group means a benzyl group, a phenylethyl group, a naphthylmethyl group, a naphthylethyl group, etc., and the aryl group part may contain an oxygen atom, a nitrogen atom or a sulfur atom and does not have a substituent. Is preferred.

The pharmacologically acceptable salt in the present invention is, for example, an inorganic salt such as hydrochloride, hydrobromide, sulfate and phosphate, for example, acetate, maleate, tartrate and methanesulfone. Acid salts, organic acid salts such as benzene sulfonate, toluene sulfonate, etc. or aspartic acid,
Examples thereof include salts with amino acids such as glutamic acid.

The compound of the present invention is useful as a prophylactic / therapeutic agent for asthma, allergic rhinitis, atopic dermatitis, urticaria, hay fever, gastrointestinal allergy, food allergy and the like. When used as a preventive or therapeutic agent for these,
The dose varies significantly depending on the type of disease, severity of symptoms, age, etc., but is usually about 0.0
3 to 1000 mg, preferably 0.1 to 500 mg, more preferably
Administer 0.1 to 100 mg once or several times a day. The compound according to the present invention is a tablet, powder, granule, capsule,
It can be administered as a syrup, an inhalant, an injection and the like. These dosage forms can be formulated by a conventional method.

[Production Method] An example of the method for producing the compound group of the present invention is shown below. In the above general formula, when R ⁵ and R ⁶ are 3,4-dimethyl, R ⁷ and R ⁸ are hydrogen atoms, for example, they can be produced by Steps 1 to 5, and when R ⁷ and R ⁸ are not hydrogen atoms, It can be manufactured by 6 or 7.

[0018]

[Chemical 5]

[0019]

[Chemical 6]

Step 1 The required diphenylamines are a to
d Either method can be obtained by the Ullmann reaction. That is, a mixture of amine and halide is dissolved in dimethylformamide, potassium carbonate and a catalytic amount of copper powder are added, and the mixture is reacted at a high temperature. Cuprous iodide can be used as a catalyst in addition to copper powder, and amyl alcohol can be used as a solvent in addition to dimethylformamide. Step 2 The cyclization of diphenylamine to acridone is
It is carried out at room temperature to about 80 ° C. using polyphosphoric acid and sulfuric acid as solvents. Step 3 The nitrogen atom of the acridone ring of compound (a) is metallized and then condensed with an alkyl compound having leaving groups A and B at both ends. For metallization, metal alkyls such as butyllithium, lithium diisopropylamine, lithium bistrimethylsilylamide, and metal hydrides such as sodium hydride and potassium hydride are used. As the solvent, a solvent which does not participate in the reaction, such as diethyl ether, tetrahydrofuran or n-hexane, can be appropriately selected. The reaction temperature is usually from -20 ° C to the reflux temperature of the solvent. As the leaving groups A and B, a halogen atom, a mesyl group, a tosyl group, a trifluoromethanesulfonyl group or the like can be appropriately selected.

Steps 4 and 5 A nitrogen atom is introduced into the terminal of the alkyl group of the obtained compound (b) by the Gabriel reaction. That is, (b) is reacted with phthalimido potassium,
The adduct (c) is obtained. The reaction is usually carried out at 0 ° C. to the reflux temperature of the solvent, and dimethylformamide, tetrahydrofuran, dimethylsulfoxide, acetone or the like is appropriately used as the solvent. The target compound (d) can be obtained by treating the obtained adduct (c) with hydrous hydrazine. The reaction temperature is 0 ° C to the reflux temperature of the solvent, and methanol, ethanol, dioxane or the like is appropriately used as the solvent.

Step 6 The halide (b) synthesized in Step 3 is reacted with the primary or secondary amine in the presence of a solvent or without solvent at a temperature from room temperature to reflux. In this case, a solvent that does not participate in the reaction, such as ethanol, methanol, or tetrahydrofuran, can be selected as the solvent. Step 7 The amine (d) synthesized in Step 5 and an aldehyde are dehydrated and condensed in the absence or presence of a solvent to synthesize a Schiff base. In this case, benzene, toluene, ethanol or the like can be used as the solvent, and when benzene or toluene is used, a water separator can be used. The reaction temperature is from room temperature to reflux. The obtained Schiff base is reduced to an amine with sodium borohydride using ethanol or methanol as a solvent. In this case, the temperature is from 0 ° C to room temperature.

[0023]

The present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 2- (2,3-Dimethyl-4-fluorophenyl) aminobenzoic acid 3.3 g of 2-chlorobenzoic acid, 2.9 g of 2,3-dimethyl-4-fluoroaniline, 2.9 g of potassium carbonate, copper A mixture of 200 mg of powder and 200 ml of dimethylformamide is stirred and refluxed for 2 hours. The reaction mixture is cooled, water is added, the mixture is neutralized with concentrated hydrochloric acid and extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous magnesium sulfate, the solvent is distilled off under reduced pressure and the residue is purified by silica gel column chromatography to obtain 2.8 g of the title compound as pale yellow crystals.

¹ H-NMR (400 MHz DMSO-d ₆ ) δ 9.32 (s, 1H), 7.85 (m, 1H), 7.26 (m, 1H), 7.10 (m, 1H), 7.02
(t, J = 10.0,1H), 6.65 (t, J = 7.0,1H), 6.47 (d, J = 7.0,1H), 2.
19 (s, 3H), 2.08 (s, 3H)

Example 2 3,4-Dimethyl-2-fluoro-9 (10H) acridone A mixture of 2.8 g of 2- (2,3-dimethyl-4-fluorophenyl) aminobenzoic acid and 50 g of polyphosphoric acid at 70 ° C. 80
Stir for 30 minutes at ℃. Water was added to the reaction mixture, and the precipitated crystals were separated by filtration, washed with water and dried to obtain 1.2 g of yellow crystals.

¹ H-NMR 400MHz (DMSO-d ₆ ) δ 10.53 (s, 1H), 8.18 (m, 1H), 7.90 (d, J = 10.0,1H), 7.72-7.68
(m, 2H), 7.23 (t, J = 8.0,1H), 2.51 (s, 3H), 2.31 (d, J = 2.0,3
H)

Example 3 10- (3-Bromopropyl) -3,4-dimethyl-2
-Fluoro-9-acridone 3,4-Dimethyl-2-fluoro-9 (10H) acridone 1.2 g of tetrahydrofuran in 100 ml of tetrahydrofuran was stirred at room temperature with n-butyllithium hexane solution (1.6M, 3.7 ml).
Is dripped. After stirring at room temperature for 30 minutes, trifluoromethanesulfonic acid 3-bromopropyl ester (Example 4) was added dropwise. After stirring at room temperature for 30 minutes, water was added to the reaction solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 310 mg of the title compound.

¹ H-NMR 400MHz (CDCl ₃ ) δ 8.33 (m, 1H), 7.89 (d, J = 9.0,1H), 7.66 (m, 1H), 7.57 (d, J = 8.
0,1H), 7.25 (m, 1H), 4.45 (t, J = 7.0,2H), 2.90 (t, J = 7.0,2
H), 2.51 (s, 3H), 2.34 (d, J = 2.0,3H), 1.80-1.72 (m, 2H)

Example 4 Trifluoromethanesulfonic acid 3-bromopropyl ester 3-bromo-1-propanol (6.2 g) and pyridine 3.8 g
To 100 ml of a dichloromethane solution of was added trifluoromenthanesulfonic acid anhydride (7.8 ml) at 0 ° C. with stirring. Water was added, the organic layer was washed with water, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (4.8 g).

¹ H-NMR 400MHz (CDCl ₃ ) δ 4.71 (t, J = 6.0,2H), 3.51 (t, J = 6.2,2H), 2.36 (m, 2H)

Example 5 3,4-Dimethyl-2-fluoro-10- (3-phthalimidopropyl) -9-acridone 10- (3-bromopropyl) -3,4-dimethyl-2
-Fluoro-9-acridone (310 mg) and potassium phthalimide (240 mg) were dissolved in dimethylformamide (50 ml) at 60 ° C.
And stirred for 20 minutes. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate,
The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a pale yellow oil 2
80 mg was obtained.

¹ H-NMR (400 MHz CDCl ₃ ) δ 8.32 (m, 1 H), 7.81-7.68 (m, 5 H), 7.62 (m, 1 H), 7.49 (d, J = 8.
0,1H), 7.23 (m, 1H), 4.32 (t, J = 7.0,2H), 3.38 (t, J = 7.0,2
H), 2.44 (s, 3H), 2.38 (d, J = 2.0,3H), 1.64-1.58 (m, 2H) Example 6 3,4-Dimethyl-2-fluoro-10- (3-aminopropyl) A solution of 280 mg of -9-acridone 3,4-dimethyl-2-fluoro-10- (3-phthalimidopropyl) -9-acridone and hydrazine monohydrate (1.0 g) in methanol (50 ml) was stirred, and stirred.
Refluxed for a minute. After cooling to room temperature, the mixture was made alkaline with 1N aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as a yellow oil (180 mg).

¹ H-NMR (400 MHz CDCl ₃ ) δ 8.34 (dd, J = 1.6,8.0,1H), 7.89 (d, J = 9.4,1H), 7.66 (m, 1H),
7.57 (d, J = 8.4,1H), 7.24 (m, 1H), 4.35 (t, J = 7.0,2H), 2.50
(s, 3H), 2.34 (d, J = 2.0,3H), 2.23 (t, J = 7.0,2H), 1.40-1.33
(m, 2H)

In the same manner as in Examples 1 to 6, the following compounds were synthesized by changing the amine in Example 1.

[0036]

[Chemical 7]

[0037]

[Chemical 8]

In the same manner as in Examples 1 to 6, the following compounds were synthesized by changing the kinds of amine and benzoic acid in Example 1.

[0039]

[Chemical 9]

[0040]

[Chemical 10]

Example 23 10- (3-Benzylaminopropyl) -3,4-dimethyl-9-acridone

[0042]

[Chemical 11]

10- (3- synthesized according to Examples 1 to 4
Bromopropyl) -3,4-dimethyl-9-acridone
350 mg and benzylamine 535 mg were dissolved in ethanol (20 ml), and the mixture was stirred and refluxed for 5 hours. 0.5N aqueous sodium hydroxide solution was added to the solution, extracted with ethyl acetate, the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate,
The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to give the title compound (354 mg).

¹ H-NMR (400 MHz CDCl ₃ ) δ 8.37 (dd, J = 8.4, 1.6 Hz, 1 H), 8.19 (d, J = 8.4, 1 H), 7.64 (m, 1
H), 7.57 (d, J = 8.8,1H), 7.28-7.18 (m, 4H), 7.16 (d, J = 7.6,1
H), 7.60-7.30 (m, 2H), 4.42 (t, J = 6.8,2H), 3.39 (s, 2H), 2.4
6 (s, 3H), 2.40 (s, 3H), 2.13 (t, J = 6.4,2H), 1.45-1.40 (m, 2
H)

The following compounds were synthesized in the same manner as in Example 23.

[0046]

[Chemical 12]

[0047]

[Chemical 13]

[0048]

[Chemical 14]

Example 36 3,4-Dimethyl-10- (3- (2-imidazoylmethyl) aminopropyl) -9-acridone

[0050]

[Chemical 15]

10- (3- synthesized according to Examples 1 to 6
Aminopropyl) -3,4-dimethyl-9-acridone
350 mg and 2-imidazole carboxaldehyde 132 mg
Was dissolved in toluene, equipped with a water removing device, and stirred under reflux for 2 hours. The reaction solution was cooled, methanol was added, 150 mg of sodium borohydride was added, and the mixture was stirred for 20 minutes. The reaction solution was neutralized with tartaric acid, the solvent was evaporated under reduced pressure, and the residue was purified by reverse phase silica gel column chromatography to obtain 40 mg of the title compound.

¹ H-NMR (400 MHz DMSO-d ₆ ) δ 8.12 (dd, J = 1.6,8.0,1H), 7.94 (d, J = 8.0,1H), 7.82 (d, J = 8.
4,1H), 7.71 (m, 1H), 7.25 (m, 1H), 7.19 (d, J = 8.0,1H), 6.82
(s, 2H), 4.38 (t, J = 7.0,2H), 3.39 (s, 2H), 2.42 (s, 3H), 2.37
(s, 3H), 2.07-2.06 (m, 2H), 1.38-1.20 (m, 2H)

The following compounds were synthesized by changing the aldehyde in the same manner as in Example 36.

[0054]

[Chemical 16]

[0055]

[Chemical 17]

Next, pharmacological experimental examples will be shown in order to explain in detail the excellent effects of the compounds of the present invention. Inhibitory activity of various mediators from rat basophilic leukemia cell line (RBL-2H3) and tyroxinase inhibitory activity RBL-2H3 cells, a cell line of rat cells, release histamine by a specific antigen of IgE receptor. Not only does it produce and release prostaglandins and TNFα, which are inflammatory mediators. In this experimental system, cells were previously labeled with [ ³ H] -labeled serotonin, inositol, or arachidonic acid, and the inhibitory activity of the compound was measured by measuring the release of these mediators into the medium. TNFα was measured by bioassay.

In the signal transduction system of this IgE receptor, it has been immunologically proved that the 72 kDa tylosin kinase is activated first when the antigen binds to the IgE receptor. The effect was also examined using an antiphosphotyrosin antibody or the like. In order to confirm the selectivity for this tylosin kinase, the effect on other types of tylosin kinase was also confirmed using Jurkat cell (T-cell) and NIH3T3 cell (fibroblast).

Experimental Results The results are shown in Table 1.

[0059]

[Table 1]

Further, the compound of Example 15 inhibits the release of arachidonic acid from RBL-2H3 cells upon antigen stimulation at the same concentration as that for inhibiting the release of serotonin, and
It was immunologically demonstrated that NFα production, release, 72KDa tylosin kinase activation, and phospholipase activation were also suppressed at the same concentration.

From these facts, it was clarified that the compound of the present invention exhibits the above-mentioned inhibitory activity against mediator release by inhibiting the 72 kDa tylosin kinase coupled to the IgE receptor. Regarding the selectivity for tyloxinase, the compound of Example 15 was completely ineffective against stimulation by an antigen in Jurkat cells, which revealed that it did not show inhibitory activity against tylosin kinases such as p56lck and fyn. . In addition, it was immunologically proved that there is no inhibitory activity against tylosin kinase originally possessed by growth factor receptors such as FGF, PDGF, and EGF.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Katsuhiro Moriya 2-23-5 Amakubo Tsukuba, Ibaraki Pref. 308 (72) Inventor Satoshi Katayama 1-16-7 Kannondai, Tsukuba, Ibaraki (72) Inventor Danji Yamanaka 725-25 Shimohirooka, Tsukuba, Ibaraki (72) Inventor Koji Yamada 5-8-8 Kariya, Ushiku, Ibaraki

Claims (2)

[Claims] 1. A general formula:[R in the formula¹ , R² , R³ , R^Four , R^Five , R⁶ Is the same
Differently, a hydrogen atom, a lower alkyl group, a low
Represents a primary alkoxy group or a halogen atom. R ⁷ , R
⁸ Are the same or different and are hydrogen atom or lower alkyl
Group, aryl group, heteroaryl group or aralkyl
Represents a group or R⁷ And R⁸ Are these bound
Ring with 5 or 6 members, together with a nitrogen atom
To form. Here, the ring includes an oxygen atom and a sulfur source in the ring.
Child or expression NR⁹ (R in the formula⁹ Is a hydrogen atom, lower alk
Group, which represents an aryl group, an aryl group, or an aralkyl group)
May have. n represents an integer of 1 to 6. ] In the table
Acridone derivative and / or its pharmacologically acceptable
Can salt. 2. A general formula:[R in the formula¹ , R² , R³ , R^Four , R^Five , R⁶ Is the same
Differently, a hydrogen atom, a lower alkyl group, a low
Represents a primary alkoxy group or a halogen atom. R ⁷ , R
⁸ Are the same or different and are hydrogen atom or lower alkyl
Group, aryl group, heteroaryl group or aralkyl
Represents a group or R⁷ And R⁸ Are these bound
Ring with 5 or 6 members, together with a nitrogen atom
To form. Here, the ring includes an oxygen atom and a sulfur source in the ring.
Child or expression NR⁹ (R in the formula⁹ Is a hydrogen atom, lower alk
Group, which represents an aryl group, an aryl group, or an aralkyl group)
May have. n represents an integer of 1 to 6. ] In the table
Acridone derivative and / or its pharmacologically acceptable
Asthma, allergic rhinitis,
Topy dermatitis, urticaria, hay fever, gastrointestinal allergy
Or a preventive or therapeutic agent for food allergies.