JPS63112578A - Pyrazine derivative - Google Patents

Abstract

NEW MATERIAL:A pyrazine derivative expressed by formula I [R1 and R2 are H, 4-12C alkyl, 3-6C cycloalkyl, phenyl (may be substituted by halogen, alkyl or alkoxy) or forms piperadyl and homopiperadinyl with R1 and R2 and adjacent N] and salt thereof. EXAMPLE:6-(n-Butylamino)-N-(1H-5-tetrazolyl)pyrazine-2-carboxyamide. USE:A remedy for bronchial asthma, etc., having excellent antiallergic action. PREPARATION:A 6-halogenopyrazine derivative expressed by formula II (X is halogen) is reacted with amines expressed by formula III in the absence of a solvent or in the presence of a solvent to provide a compound expressed by formula I.

Description

[Detailed Description of the Invention] - Part 1 The present invention relates to a novel pyratine derivative that exhibits excellent anti-allergic action and is useful as a therapeutic agent for bronchial asthma, etc., and a pharmacologically acceptable salt thereof. It is something.

Regarding the piratin derivative of the present invention, no literature has been found, and it is not known that it has an anti-allergic effect.

[1(' -jShin) It has been revealed that bronchial asthma develops when a type I allergic reaction (anaphylactic reaction) is induced by the invasion of allergens, and chemical mediators are released from mast cells.

Drugs that inhibit the release of chemical mediators have come to be used as therapeutic agents for such allergic diseases. However, there are only a few drugs that have this type of action, and their efficacy is not necessarily satisfactory. Under these circumstances, there is a strong desire for the development of new antiallergic agents in the medical field.

. Japan - As a result of intensive research in view of the above circumstances, the present inventors have discovered that piratin derivatives and their pharmacologically acceptable vine salts have excellent anti-allergic effects, and have completed the present invention. I let it happen.

That is, the present invention relates to general formula (I) [wherein R1 and R2 are the same or different and hydrogen atoms, 4
an alkyl group having ~12 straight-chain or branched carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms,
Phenyl group (halogen atom).

It may be substituted with a lower alkyl group or a lower alkoxy group.

), or a piperazinyl group and a homopiperazinyl group (
It may be substituted with a lower alkyl group or a phenyl group. ). ] The present invention relates to a novel pyratine derivative represented by the following, and a pharmacologically acceptable salt thereof.

In the general formula of the present invention, 4 to 1 represented by R1 and R2
Examples of alkyl groups having two straight or branched carbon atoms include butyl, isobutyl, 5eC-
Butyl, tert-butyl, pentyl.

Hexyl, heptyl, octyl, nonyl, decyl.

Examples of cycloalkyl groups such as undecyl and dodecyl groups having 3 to 6 carbon atoms include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups. Further, as a substituent for the phenyl group (which may be substituted with a halogen atom, lower alkyl group, or lower alkokene group), fluorine is used.

Halogen atoms such as chlorine, bromine, and iodine atoms, methyl, ethyl, propyl, isopropyl, and butyl.

Lower alkyl groups such as isobutyl group, methoxy7. Examples include lower alkoxy groups such as ethoxy and propoquine groups.

In addition, examples of substituents for the piperazinyl group and homopiperazinyl group (which may be substituted with a lower alkyl group or phenyl group) include methyl and ethyl.

Examples include lower alkyl groups such as propyl, isopropyl, butyl and isobutyl groups, and phenyl groups.

Examples of the pharmacologically acceptable salts of the compound represented by the general formula (I) of the present invention include acid addition salts and alkali addition salts; examples of the acid addition salts include hydrochloric acid, hydrobromic acid , mineral acid salts such as hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid,
Alternatively, acetic acid, maleic acid, fumaric acid, citric acid,
Examples of alkaline addition salts include sodium, potassium, and calcium salts such as uric acid and tartaric acid.

Metal salts such as aluminum, or ethanolamine, N,N-dialkylethanolamine.

Examples include salts of organic bases such as tris(hydroquinemethyl)aminomethane.

According to the method for producing a compound according to the present invention, the compound represented by the general formula (I) is produced by the following general formula (n) (wherein, X represents a halogen atom).
It can be produced by reacting a balogenopyratine derivative with an amine represented by the following general formula (III) (wherein R and R2 have the same meanings as above) in the absence of a solvent or in a solvent. can.

Any solvent may be used in the method of the present invention as long as it does not inhibit the reaction, such as water,
Alcohols such as methanol, ethanol, propatool, butanol, ethers such as ethylene glycol dimethyl ether (monoglyme), diethylene glycol dimethyl ether (diglyme), triethylene glycol dimethyl ether (triglyme), dimethylformamide, dimethyl sulfokind, hexamethyl phosphoryl Examples include aprotic solvents such as triamide, aromatic hydrocarbon solvents such as benzene and toluene, and organic bases such as pyridine, pifrin, lutidine, colicin, and triethylamine, with ethanol, benzene, and dimethyl sulfoxide being particularly preferred.

Further, the reaction is carried out under normal pressure or increased pressure, and the reaction temperature is in the range of room temperature to 200'', preferably 80 to 110''.
It will be held at 6.

Incidentally, the compound represented by the general formula (n) used as a raw material here is produced in the following manner.

That is, the compound represented by the general formula (II) is a reactive derivative of the piratincarboxylic acid derivative represented by the following general formula (rV) (wherein X represents the same definition as above). (5-aminotetrazole represented by acid chloride, M anhydride, mixed acid anhydride and inactive a
It can be produced by reacting in a solvent.

Bases used in the method of the invention include, for example, pyridine, picoline, lutidine, collidine, N-methylpiperidine, N-methylpyrrolidine, N-methylmorpholine, triethylamine.

Examples include potassium carbonate and sodium carbonate, with triethylamine being particularly preferred.

Furthermore, any inert organic solvent may be used in the method of the present invention as long as it does not inhibit the reaction.
For example, ether, benzene.

Tetrahydrofuran, dioxane, chloroform.

Examples include methylene chloride, dimethyl sulfoxide, N,N-dimethylformamide, and tetrahydrofuran is particularly preferred.

Further, the reaction is carried out under heating under reflux from -10°, but preferably between room temperature and under heating under reflux of the solvent used.

IL Takumi Hereinafter, the present invention will be explained by examples.

Example yellow (n-butylamino)-N-(IH-5-tetrazolyl)pyratine-2-carboxamide hydrochloro-N-
4.95 ml of n-butylamine was added to a suspension of 2.28 g of (IH-5-tetrazolyl)pyratine-2-carboxamide in 30 ml of ethanol, and the mixture was heated under reflux for 21 hours. The reaction solution was evaporated under reduced pressure, and water and 10% FA acid were added to the residue to adjust the pH to 3. The precipitated crystals were collected by filtration and recrystallized from dimethylformamide-ethanol to give a melting point of 269-2.
2.00 g of pale yellow needles of 72° (decomposition) are obtained.

Elemental analysis value CIO814N80 Theoretical value C, 45,80; H, 5,38: N, 42
．． 72 Experimental value C, 45, l1i5; H, 5,53
; N, 42.83 Example 2 6-(inbutylamino)-N-(LH-5-tetrazolyl)pyratine-2-carboxamide dichloro-N-
(IH-5-tetrazolyl)pyratine-2-carboxamide 2.26g ethanol 30ml 1F! Isobutylamine 4.971111 was added to the Ei solution, and the mixture was heated under reflux for 19 hours. The reaction solution was concentrated under reduced pressure, and the residue was diluted with water and 10%
% hydrochloric acid to bring the pH to 3. The precipitated crystals were collected by filtration and recrystallized from dimethylformamide-ethanol to give a melting point of 26.
5-275” (disassembled) pale yellow prism product 2.1
Get 0g.

Elemental analysis value CIO814N80 Theoretical value C, 45, 8θ; H, 5, 38; N, 4
2.72 Experimental value C, 45,77; H, 5,38;
N, 42.82 Example 3 6-(see-butyrami/)-N-(tH-5Ltetrazolyl)pyratine-2-carboxamide dichloro-
5e in a suspension of 2.26 g of N-(IH-5-tetrazolyl)pyratine-2-carboxamide in 30 ml of ethanol.
Add 5.051 g of e-butylamine and heat under reflux for 47 hours. The reaction solution was condensed under reduced pressure, and the residue was mixed with water and 10
Add % hydrochloric acid to make p) 13. The precipitated crystals were collected by filtration and recrystallized from dimethylformamide-ethanol to give a melting point of 2.
1.28g of pale yellow needle-shaped product of 65-269° (decomposition)
obtain.

Elemental analysis value C engineering. H engineering, N80 Theoretical value C, 45,80i H, 5,38; N, 4
2.72 Experimental value C, 45,54; H, 5,36;
N, 42.49 Example 4 (3-(tert-butylamino)-N-(IH-5-
2.26 g of dimethylsulfoquinode 151
Add 5.25 ml of tert-butylamine to the suspension,
Heat in a sealed tube at 80-90" for 41 hours. Add water and 10% sodium hydroxide to the reaction solution to make it alkaline, then wash with chloroform. After filtering the aqueous layer, add 10% hydrochloric acid to the filtrate. Add to adjust the pH to 3. Filter the precipitated crystals,
Recrystallize from dimethylformamide-ethanol to obtain 1.07g of yellow powder with a melting point of 266-2706 (decomposition).
obtain.

IR spectrum v (KBr)cII+-1:170
5NMR spectrum δ(DMSO-d6)ppm+
1.47 (9H, - double line), 7.19 (111, - double line), 8.20 (l) I.

- double line), 8.31 (IH, - double line), 11.01 (I
n, - heavy line) Example 5 6-(hexylamino)-N-(IH-5-tetrazolyl)pyratine-2-carboxamidolochloro-N-(
5.06 g of n-hexylamine was added to a suspension of 2.26 g of IH-5-tetrazolyl)pyratine-2-carboxamide in 30 ml of ethanol, and the mixture was heated under reflux for 24 hours. The reaction solution is concentrated under reduced pressure, water and 10% sodium hydroxide are added to the residue to make it alkaline, and the residue is washed with chloroform. After filtering the aqueous layer, 10% hydrochloric acid is added to the filtrate to adjust the pH to 3. The precipitated crystals were collected by filtration and recrystallized from dimethylformamide-ethanol to obtain a melting point of 263-267.
1.95 g of white feather-like material (decomposed) was obtained.

Elemental analysis value C1□H engineering 8N80 Theoretical value C, 49, G4; H, B, 25; N
, 38J30 experimental value C, 49,54; H, Ei, 2
Ei;
A suspension of 2.26 g of IH-5-tetrazolyl)pyratine-2-carboxamide in 30 ml of ethanol contains 5.56 ml of n-dodecylamine. was added and heated under reflux for 19 hours. The reaction solution is concentrated under reduced pressure, water and 10% sodium hydroxide are added to the residue to make it alkaline, and then filtered.

After adding water and 10% hydrochloric acid to the crystals to adjust the pH to 3, the crystals were collected by filtration and recrystallized from dimethyl sulfoxide-ethanol to obtain 2.17 g of white feather-like material with a melting point of 250-259° (decomposition). .

Elemental analysis value C1883ON80 Theoretical value C, 57,73; H, 8,07; N, 2
9.92 Experimental value C, 57,85; H, 8,09;
N, 29.92 Example 7 6-(Cyclopropylamino)-N-(IH-5-tetrazolyl)pyratine-2-carboxamide Dorochloro-N-(LH-5-tetrazolyl)pyratine-2-carboxamide 2.26 g of ethanol 30nl
Add 92 ml of 6° cyclopropylamino to the suspension and heat in a sealed tube at 80-906 for 96 hours. The reaction solution is concentrated under reduced pressure, water and 10% sodium hydroxide are added to the residue to make it alkaline, and the residue is washed with chloroform. After filtering the aqueous layer, 10% hydrochloric acid is added to the filtrate to adjust the pH to 3.

The precipitated crystals were collected by filtration and recrystallized from dimethylsulfoquine ethanol to obtain 1.34 g of pale yellow powder with a melting point of 272-280° (decomposition).

Elemental analysis value C9H1oN80 Theoretical value C, 43,90; H, 4,09; N, 4
5.51 Experimental value C, 44,01; H, 4,20;
N, 45.70 Example 8 6-(Cyclohexyfluamino)-N-(IH-5-tetrazolyl)pyratine-2-carboxamide Dolochloro-N-(IH-5-tetrazolyl)pyratine-2-carboxamide 2.26 g of ethanol 30ml
Add 5.72ml of cyclohexylamine to the suspension,
Heat and reflux for 8 hours. The reaction solution is concentrated under reduced pressure, water and 10% sodium hydroxide are added to the residue to make it alkaline, and the residue is washed with chloroform. After filtering the water layer,
Add 10% hydrochloric acid to the filtrate to adjust the pH to 3. The precipitated crystals were collected by filtration and recrystallized from dimethyl sulfoxide-ethanol to obtain 1.85 g of a pale yellow feather-like product with a melting point of 287-291° (decomposed).

Elemental analysis value C12HI3 N s O theoretical value C, 4
9,99; H, 5,59; N, 38.87 Experimental value C, 49,99; H, 5,7 [i; N, 38
．． 88 Example 9 6-(phenylamino)-N-(IH-5-tetrazolyl)pyratine-2-carboxamide hydrochloro-N-(
4.55 ml of aniline is added to a cod suspension containing 1.13 g of IH-5-tetrazolyl)pyratine-2-carboxamide in dimethyl sulfoxide, and the mixture is heated at 80-90° for 17 hours. Water and 10% sodium hydroxide solution were added to the reaction solution, and the mixture was washed with chloroform. After filtering the aqueous layer, the filtrate is adjusted to pH 3 with 10% hydrochloric acid. The precipitated crystals were collected by filtration and recrystallized from dimethyl sulfoxide-ethanol to give a melting point of 29.
0 to 293.5' (decomposed) yellow feathery product to 0.8
Get 0g.

Elemental analysis value C1281ON80 Theoretical value C, 51,0G; H, 3,57; N, 3
9.70 Experimental value C, 51,1G; H, 3,8G
; N, 39. Ei8 Example 10 6-[(3-chlorophenyl)aminoco-N-(IH
75.39 ml of m-chloroform was added to a suspension of 1.13 g of -5-tetrazolyl)pyratine-2-carboxamide hydrochloro-N-(IH-5-tetrazolyl)pyratine-2-carboxamide in 10 ml of dimethyl sulfoxide. Heat for 7 G hours at °C. Water and 10% sodium hydroxide solution were added to the reaction solution, and the mixture was washed with chloroform. After filtering the aqueous layer, the filtrate is adjusted to pH 3 with 10% hydrochloric acid. The precipitated crystals were collected by filtration and recrystallized from dimethylformamide-ethanol to obtain 0.34 g of a yellow powder with a melting point of 281-289° (decomposed).

Elemental analysis value CHClN80 Theoretical value C, 45,51; H, 2,8Ei; N
, 35.38 experimental value C, 45,2Ei; H, 3,
10; N, 35.03 Example 11 6-[(2-methylphenyl)amino]-N-(IH
-5-Tetrazolyl)pyratine-2-carboxamide Hydrochloro-N-(IH-5-tetrazolyl)pyratine-2-carboxamide 1.13g suspension in 5ml of dimethyl sulfoxide was added with 5°35ml of 0-toluidine,
Heat at 100-110' for 24 hours. Water and 10% aqueous sodium hydroxide are added to the reaction mixture, and the mixture is washed with chloroform. After filtering the aqueous layer, the filtrate is adjusted to pH 3 with 10% hydrochloric acid. The precipitated crystals were collected by filtration and recrystallized from trimethylformamide-ethanol to obtain 0.19 g of a black-yellow powder with a melting point of 277-282° (decomposed).

Elemental analysis value C13H12N80 Theoretical value CI 52.70; H14,08; N
, 37.82 experimental value C, 52,85; H, 4,28
; N, 38.18 Example 12 6-[(3-methylphenyl)amino]-N-(IH-
Suspend 1.13 g of 5-tetrazolyl)pyratine-2-carboxamide hydrochloro-N-(LH-5-tetrazolyl)pyratine-2-carboxamide in 10 ml of dimethyl sulfoxide, add 5.4 ml of toluin in the evening, and add 100 to 110 'Heat for 22 hours. Water and 10% aqueous sodium hydroxide are added to the reaction mixture, and the mixture is washed with chloroform. After filtering the aqueous layer, the filtrate is adjusted to pH 3 with 10% hydrochloric acid. The precipitated crystals were collected by filtration and recrystallized from dimethyl sulfoxide-ethanol to obtain 0.68 g of a yellow feather offering having a melting point of 278.5-284° (decomposed).

Elemental analysis value C13H12N80 Theoretical value C, 52,70; H, 4,08; N, 3
7.82 Experimental value C, 52,56; H, 4,17;
N, 38.18 Example 13 6-[(4-methylphenyl)aminoco-N-(IH
5.36 g of p-)luidine was added to a suspension of 1.13 g of -5-tetrazolyl)pyratine-2-carboxamide hydrochloro-N-(IH-5-tetrazolyl)pyratine-2-carboxamide in 151 dimethyl sulfoxide.
Heat at 0 to 90° for 18 hours and then at 100 to 110° for 6 hours. Add water and 10% sodium hydroxide to the reaction solution, and wash with chloroform. After filtering the aqueous layer, the filtrate is
Adjust to pH 3 with 0% hydrochloric acid. The precipitated crystals were collected by filtration and recrystallized from dimethyl sulfoxide-methanol to give a melting point of 289.
．． 5-294' (decomposed) yellow feather offering at 0°93
g get.

Elemental analysis value C engineering 3H engineering 2N80 Theoretical value C, 52,70; H, 4,08; N, 3
7.82 Experimental value C, 52,83; H, 4,29;
N, 38.08 Example 14 8-[(4-methoxyphenyl)aminoco-N-(I
H-5-tetrazolyl)pyratine-2-carboxamide Dorochloro-N-(IH-5-tetrazolyl)pyratine-2-carboxamide 1.13 g dimethylsulfo 7
Add 6.16 g of p-aningine to 115 ml of suspension,
Heat at 80-90° for 18 hours. Water and 10% in the reaction solution
% sodium hydroxide solution and wash with chloroform. After filtering the aqueous layer, the filtrate is adjusted to pH 3 with 10% hydrochloric acid. The precipitated crystals were collected by filtration and recrystallized from dimethyl sulfoxide-methanol to obtain 1.02 g of a yellow-orange powder with a melting point of 291-294° (decomposed).

Elemental analysis value C13H12N8 o2 Theoretical value C, 50,00; H, 3,87; N, 3
5.88 Experimental value C, 50,08; H, 4,05; N
, 3B, 05 Example 15 8-(1-piperazinyl)-N-(IH-5-tetrazolyl)pyratine-2-carboxamide dichloro-N-
8.61 g of anhydrous piperazine is added to a suspension of 2.26 g of (IH-5-tetrazolyl)pyratine-2-carboxamide in 50 ml of ethanol, and the mixture is heated under reflux for 22 hours. The reaction mixture is filtered. Water and 10% sodium hydroxide are added to the yellow crystals to make them alkaline, and then washed with chloroform. The aqueous layer is adjusted to pH 8 with 10% hydrochloric acid. The crystals are made alkaline and dissolved by adding water and 10% aqueous sodium hydroxide, and then adjusted to pH 8 with 10% hydrochloric acid.

The precipitated crystals were collected by filtration to obtain 1.68 g of a pale yellow powder product with a melting point of 300° or higher.

IR spectrum ν(KBr)cm-': IEi9O
NMR spectrum δ(CF3GOOD) ppm:
2.70-2.95 (4H, multiplet L3.35-3.5
4 (4 [(, multiplet), 8.87 (I) I, - multiplet),
8.89 (IH, - heavy line) Example 16 6-(4-methyl-1-piperazinyl)-N-(IH-
2.26 g of 5-tetrazolyl)pyratine-2-carboxamide hydrochloride 1-eternal 6-chloro-N-(IH-5-tetrazolyl)pyratine-2-carboxamide in 30 ml of ethanol
! ! l! ! Add 5.55 ml of N-methylpiperazine to the suspension, and heat under reflux for 6 hours. Add ethanolic hydrochloric acid to the reaction solution to adjust the pH to 1. The precipitated crystals were collected by filtration and crystallized from dimethylsulfoquine-methanol to give a melting point of 246.
Obtain 2.27 g of a pale yellow powder of ~250' (decomposition).

Elemental analysis values C, H, N90 ・HCI/H20 theoretical values C, 38,43; H, 5,28i N, 38
．． 67 Experimental value C, 38, G2; H, 5, 15;
N, 311i, 71 Example 17 6-(4-ethyl-1-piperazinyl)-N-(IH-
2.28 g of 5-tetrazolyl)pyratine-2-carboxamide hydrochloride 6-chloro-N-(IH-5-tetrazolyl)pyratine-2-carboxamide in 30 ml of ethanol
Add 4.56 g of N-ethylpiperazine to the suspension,
Heat to reflux for an hour. The reaction solution was distilled off under reduced pressure, and the residue was made alkaline by adding water and 10 Vo sodium hydroxide solution, and then washed with chloroform. The aqueous layer is adjusted to pH 3 with 10% hydrochloric acid.

The precipitated crystals were collected by filtration and recrystallized from dimethyl sulfoxide-methanol to obtain 2.32 g of a yellow powder with a melting point of 230-243° (decomposed).

Elemental analysis value CI2 G17 N 90 ・HCI theoretical value C, 42,42; H, 5,34; N, 37
．． 10 Experimental values C, 42,59; H, 5,55; N
, 38.83 Example 18 6-(4-phenyl-1-piperazinyl)-N-(IH
-5-tetrazolyl)pyratine-2-carboxamide Hydrochloro-N-(IH-5-tetrazolyl)pyratine-2-carboxamide 2.26 g of ethanol 3Qn+
4.58 ml of N-phenylpiperazine was added to the suspension and heated under reflux for 17 hours. After adding ethanolic hydrochloric acid to the reaction solution to adjust the pH to 2.

Filter the precipitated crystals. Water and 10% hydrochloric acid are added to the obtained crystals to adjust the pH to 3. The precipitated crystals were collected by filtration and recrystallized from dimethylformamide-ethanol to give a melting point of 250~
2.17 g of yellow needles of 262° (decomposition) are obtained.

Elemental analysis value C16G17 N 90 Theoretical value C, 54, fli9; H, 4, 84; N
, 35.88 experimental value C, 54, [1lli; H
,4,92;N,3Ei,02Example 19 6-(1-homopiperazinyl)-N-(IH-5-tetrazolyl)pyratine-2-carboxamidolochloro-N-(IH-5-tetrazolyl)pyratine-2 - 2.28 g of carboxamide in 50 ml of ethanol
Add 10.0 g of homopiperazine to the FM suspension and heat under reflux for 23 hours. The reaction mixture is filtered. Water and 10% sodium hydroxide are added to the yellow crystals to make them alkaline, and then washed with chloroform. pH the aqueous layer with 10% hydrochloric acid.
8. The crystals were made alkaline and dissolved by adding water and 10% sodium hydroxide water, and then adjusted to pH with 10% hydrochloric acid.
8. When the precipitated crystals are collected by filtration, the melting point is 295-300.
Obtain 1.87 g of a light yellow powder of 6 or more (decomposition).

Elemental analysis values C, H, N90 Theoretical values C, 45, G7; H, 5, 23; N,
43.57 Experimental value C, 45,37; H, 5,42;
N, 43.42 Example 20 6-(4-methyl-1-homopiperazinyl)-N-(I
2.28 g of H-5-tetrazolyl)pyratine-2-carboxamide hydrochloro-N-(IH-5-tetrazolyl)pyratine-2-carboxamide in 30 ml of ethanol
Add 4.56 g of N-methylhomopiperazine to the suspension,
Heat to reflux for 18 hours. The reaction solution was adjusted to p)11 with ethanolic hydrochloric acid. The precipitated crystals were collected by filtration, and the crystals were mixed with water and 10
% sodium hydroxide solution to make alkaline, and then filter. The filtrate is adjusted to pH 8 with 10% hydrochloric acid. The crystals are made alkaline and dissolved by adding water and 10% aqueous sodium hydroxide, and then adjusted to pH 8 with 10% hydrochloric acid. The precipitated crystals were collected by filtration to obtain 1.30 g of a pale yellow powder product with a melting point of 300° or higher.

Elemental analysis value Cl2H17N90 Theoretical value C, 47,52; H, 5,85; N, 4
], 50 experimental value C, 47, 71; H, 5, Ei6
; N , 41.321 Bean Δ肱SO The novel pyratine derivative represented by the general formula (I) and its pharmacologically acceptable salts produced in this way have excellent antiallergic effects. and bronchial asthma, allergic gastrointestinal disorders, and hay fever.

It is extremely useful as a therapeutic agent for urticaria, allergic rhinitis, allergic conjunctivitis, etc.

Claims (1)

[Claims] General formula▲ Numerical formula, chemical formula, table, etc.▼ [In the formula, R_1 and R_2 are the same or different and have a hydrogen atom and 4 to 12 straight or branched carbon atoms represents an alkyl group, a cycloalkyl group having 3 to 6 carbon atoms, a phenyl group (which may be substituted with a halogen atom, a lower alkyl group, or a lower alkoxy group), or R
Piperazinyl group and homopiperazinyl group (lower alkyl group,
It may be substituted with a phenyl group. ). ] A pyratine derivative represented by the following, and a pharmacologically acceptable salt thereof.