JP3449422B2 - Antiallergic agent containing indandione derivative as active ingredient - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an indanedione derivative and an antiallergic agent containing a physiologically acceptable salt thereof as an active ingredient. More specifically, the benzene ring has an alkyl group, an alkenyl group, a hydroxyl group, an alkyloxy group, an alkenyloxy group, an aralkyloxy group,
Indane having an acyloxy group or unsubstituted
The present invention relates to an antiallergic agent comprising a 1,3-dione derivative and a physiologically acceptable salt thereof as an active ingredient.

[0002]

2. Description of the Related Art Conventionally, only indane-1,3-dione derivatives having no substituent on the benzene ring are known (G. Bock et al., Liebigs Ann. Che.
m.1965.125-137). Further, there is no description about their pharmacological findings.

[0003]

The object of the present invention is to provide an indane having an alkyl group, an alkenyl group, a hydroxyl group, an alkyloxy group, an alkenyloxy group, an aralkyloxy group, an acyloxy group, or an unsubstituted benzene ring. It is to clarify the usefulness of -1,3-dione derivatives as pharmaceuticals.

[0004]

DISCLOSURE OF THE INVENTION The inventors of the present invention have filed a prior application (Japanese Patent Application No. 4-274254) for indan-1 having a benzene ring with a hydroxyl group, an alkyloxy group, an alkenyloxy group, an aralkyloxy group and an acyloxy group. , 3-dione derivative could be provided, but when the pharmacological effect of this compound was studied in detail,
It has been found that these compounds are excellent as antiallergic agents. Furthermore, an indane-1,3-dione derivative having a substituent other than a hydroxyl group, an alkyloxy group, an alkenyloxy group, an aralkyloxy group and an acyloxy group on the benzene ring according to the prior application, or an unsubstituted indane-1, When the pharmacological activity of the 3-dione derivative was also examined, antiallergic activity was confirmed in these compound groups. Therefore, the series of indane-1,3-dione derivatives in the present application was found to be useful as an antiallergic agent, and the present invention has been completed.

That is, the present invention has the general formula (I)

[0006]

[Chemical 2]

The present invention relates to an antiallergic agent comprising an indandione derivative represented by and a physiologically acceptable salt thereof as an active ingredient. R _{1 of the} indandione derivative represented by the general formula (I) according to the present invention is a hydrogen atom, an alkyl group, an alkenyl group, a hydroxyl group, an alkyloxy group, an alkenyloxy group, an aralkyloxy group or an acyloxy group. Further, the substitution positions of these substituents are 4-position, 5
-Either place is acceptable.

As an example of the alkyl group, a chained or branched one having 1 to 12 carbon atoms is preferable, and methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, s-butyl group, t-butyl group, n-pentyl group,
Examples thereof include a 2-methylpentyl group, an octyl group, a decyl group and a dodecyl group.

As an example of the alkenyl group, a chained or branched one having 2 to 12 carbon atoms is preferable, and a vinyl group, a propenyl group, a pentenyl group, a hexenyl group, a heptenyl group, an octenyl group, a nonyl group, a decenyl group. Group, 3-
Examples thereof include a methyl-2-butenyl group and a geranyl group.

The aralkyloxy group may be a benzyloxy group or an optionally substituted benzyloxy group (eg,
p-methoxybenzyloxy group, p-methylbenzyloxy group, p-chlorobenzyloxy group and the like).

Further, examples of the acyloxy group include an alkanoyloxy group represented by an acetyloxy group, a propionyloxy group, a butyryloxy group, an isobutyryloxy group, a benzoyloxy group, and a benzoyloxy group which may have a substituent. Group (eg, p-methoxybenzoyloxy group, p-methylbenzoyloxy group, p-chlorobenzoyloxy group, etc.), formyloxy group, alkoxycarbonyloxy group (eg, methoxycarbonyloxy group,
Acyloxy group).

R _{2 of the} indandione derivative represented by the general formula (I) represents a hydrogen atom or an acyl group. Examples of the acyl group include an alkanoyl group represented by acetyl group, propionyl group, butyryl group, isobutyryl group, benzoyl group, and optionally substituted benzoyl group (eg, p-methoxybenzoyl group, p-methyl group). Benzyl group, p-chlorobenzoyl group, etc.), formyl group, alkoxycarbonyl group (eg, methoxycarbonyl group, ethoxycarbonyl group, etc.) and acyl groups.

In the present invention, indane-1,
The 3-dione derivative can be produced by the method of the present inventors' prior application. That is, in the case of producing an unsubstituted indandione derivative, an unsubstituted phthalic acid diester derivative can be used as a starting material, and then the same operation as in the prior application can be performed. When producing an indandione derivative substituted with an alkyl group or an alkenyl group, a phthalic acid diester derivative substituted with an alkyl group or an alkenyl group may be used as a starting material. The indandione derivative in the earlier application can be produced by the same method as in the earlier application.

Specific examples of the indandione derivative relating to the present invention include the following. 2-formyloxyindane-1,3-dione (compound 1), 2-acetoxyindane-1,3-dione (compound 2), 2-
Propynyloxyindan-1,3-dione (Compound 3), 2-butyryloxyindan-1,3-dione (Compound 4), 2-isobutyryloxyindan-1,
3-dione (compound 5),

2,4-dihydroxyindane-1,3-
Dione (compound 6), 4-hydroxy-2-formyloxyindane-1,3-dione (compound 7), 4-hydroxy-2-acetoxyindane-1,3-dione (compound 8), 4-hydroxy-2 -Propynyloxyindane-1,3-dione (compound 9), 4-hydroxy-
2-butyryloxyindan-1,3-dione (Compound 10), 4-hydroxy-2-isobutyryloxyindan-1,3-dione (Compound 11), 2,5-dihydroxyindan-1,3- Dione (compound 12), 5-
Hydroxy-2-formyloxyindane-1,3-dione (compound 13), 5-hydroxy-2-acetoxyindane-1,3-dione (compound 14), 5-hydroxy-2-propynyloxyindane-1,3 -Dione (compound 15), 5-hydroxy-2-butyryloxyindane-1,3-dione (compound 16) 5-hydroxy-2-isobutyryloxyindane-1,3-dione (compound 17),

2-hydroxy-4-methoxyindane-
1,3-dione (Compound 18), 4-methoxy-2-formyloxyindane-1,3-dione (Compound 1
9), 4-methoxy-2-acetoxyindane-1,3
-Dione (compound 20), 4-methoxy-2-propynyloxyindane-1,3-dione (compound 21), 4
-Methoxy-2-butyryloxyindan-1,3-dione (Compound 22), 4-methoxy-2-isobutyryloxyindan-1,3-dione (Compound 23), 2-
Hydroxy-5-methoxyindane-1,3-dione (Compound 24), 5-methoxy-2-formyloxyindane-1,3-dione (Compound 25), 5-methoxy-2-acetoxyindane-1,3- Dione (Compound 2
6), 5-methoxy-2-propynyloxyindane-
1,3-dione (Compound 27), 5-methoxy-2-butyryloxyindane-1,3-dione (Compound 2
8), 5-methoxy-2-isobutyryloxyindane-1,3-dione (Compound 29),

2-hydroxy-4-ethoxyindane-
1,3-dione (Compound 30), 4-ethoxy-2-formyloxyindane-1,3-dione (Compound 3
1), 4-ethoxy-2-acetoxyindane-1,3
-Dione (compound 32), 4-ethoxy-2-propynyloxyindane-1,3-dione (compound 33), 4
-Ethoxy-2-butyryloxyindan-1,3-dione (Compound 34), 4-ethoxy-2-isobutyryloxyindan-1,3-dione (Compound 35), 2-
Hydroxy-5-ethoxyindane-1,3-dione (compound 36), 5-ethoxy-2-formyloxyindane-1,3-dione (compound 37), 5-ethoxy-2-acetoxyindane-1,3- Dione (compound 3
8), 5-ethoxy-2-propynyloxyindane-
1,3-dione (Compound 39), 5-ethoxy-2-butyryloxyindane-1,3-dione (Compound 4
0), 5-ethoxy-2-isobutyryloxyindane-1,3-dione (Compound 41),

2-Hydroxy-4-propoxyindane-1,3-dione (Compound 42), 4-propoxy-2
-Formyloxyindane-1,3-dione (compound 4
3), 4-propoxy-2-acetoxyindane-1,
3-dione (compound 44), 4-propoxy-2-propynyloxyindane-1,3-dione (compound 4)
5), 4-propoxy-2-butyryloxyindane-
1,3-dione (Compound 46), 4-propoxy-2-
Isobutyryloxyindane-1,3-dione (Compound 47), 2-hydroxy-5-propoxyindane-
1,3-dione (Compound 48), 5-propoxy-2-
Formyloxyindane-1,3-dione (Compound 4
9), 5-propoxy-2-acetoxyindane-1,
3-dione (compound 50), 5-propoxy-2-propynyloxyindane-1,3-dione (compound 5)
1), 5-propoxy-2-butyryloxyindane-
1,3-dione (Compound 52), 5-propoxy-2-
Isobutyryloxyindane-1,3-dione (compound 53),

2-Hydroxy-4-isopropoxyindane-1,3-dione (Compound 54), 4-isopropoxy-2-formyloxyindane-1,3-dione (Compound 55), 4-isopropoxy-2 -Acetoxyindane-1,3-dione (compound 56), 4-isopropoxy-2-propynyloxyindane-1,3-dione (compound 57), 4-isopropoxy-2-butyryloxyindane-1,3 -Dione (compound 58), 4
-Isopropoxy-2-isobutyryloxyindane-
1,3-dione (Compound 59), 2-hydroxy-5-
Isopropoxyindane-1,3-dione (Compound 6
0), 5-isopropoxy-2-formyloxyindane-1,3-dione (compound 61), 5-isopropoxy-2-acetoxyindane-1,3-dione (compound 62), 5-isopropoxy-2. -Propynyloxyindane-1,3-dione (compound 63), 5-isopropoxy-2-butyryloxyindane-1,3-dione (compound 64), 5-isopropoxy-2-isobutyryloxyindane- 1,3-dione (Compound 65),

2-hydroxy-4-butoxyindane-
1,3-dione (compound 66), 4-butoxy-2-formyloxyindane-1,3-dione (compound 6)
7), 4-butoxy-2-acetoxyindane-1,3
-Dione (compound 68), 4-butoxy-2-propynyloxyindane-1,3-dione (compound 69), 4
-Butoxy-2-butyryloxyindan-1,3-dione (Compound 70), 4-butoxy-2-isobutyryloxyindan-1,3-dione (Compound 71), 2-
Hydroxy-5-butoxyindane-1,3-dione (compound 72), 5-butoxy-2-formyloxyindane-1,3-dione (compound 73), 5-butoxy-2-acetoxyindane-1,3- Dione (Compound 7
4), 5-butoxy-2-propynyloxyindane-
1,3-dione (Compound 75), 5-butoxy-2-butyryloxyindane-1,3-dione (Compound 7)
6), 5-butoxy-2-isobutyryloxyindane-1,3-dione (Compound 77),

2-Hydroxy-4-isobutoxyindan-1,3-dione (Compound 78), 4-isobutoxy-2-formyloxyindan-1,3-dione (Compound 79), 4-isobutoxy-2-acetoxy. Indane-1,3-dione (Compound 80), 4-isobutoxy-
2-propynyloxyindane-1,3-dione (Compound 81), 4-isobutoxy-2-butyryloxyindane-1,3-dione (Compound 82), 4-isobutoxy-2-isobutyryloxyindane-1 , 3-dione (Compound 83), 2-hydroxy-5-isobutoxyindan-1,3-dione (Compound 84), 5-isobutoxy-2-formyloxyindane-1,3-dione (Compound 85), 5 -Isobutoxy-2-acetoxyindane-1,3-dione (Compound 86), 5-isobutoxy-2-propynyloxyindane-1,3-dione (Compound 87), 5-isobutoxy-2-butyryloxyindane-1 , 3-dione (Compound 88), 5-isobutoxy-2-isobutyryloxyindane-1,3-
Dione (compound 89),

2-Hydroxy-4-octyloxyindan-1,3-dione (compound 90), 4-octyloxy-2-formyloxyindane-1,3-dione (compound 91), 4-octyloxy-2 -Acetoxyindane-1,3-dione (compound 92), 4-octyloxy-2-propynyloxyindane-1,3-dione (compound 93), 4-octyloxy-2-butyryloxyindane-1,3 -Dione (compound 94), 4
-Octyloxy-2-isobutyryloxyindane-
1,3-dione (Compound 95), 2-hydroxy-5-
Octyloxyindane-1,3-dione (Compound 9
6), 5-octyloxy-2-formyloxyindane-1,3-dione (compound 97), 5-octyloxy-2-acetoxyindane-1,3-dione (compound 98), 5-octyloxy-2. -Propynyloxyindan-1,3-dione (Compound 99), 5-octyloxy-2-butyryloxyindan-1,3-dione (Compound 100), 5-octyloxy-2-isobutyryloxyindane- 1,3-dione (Compound 10
1),

2-Hydroxy-4-dodecyloxyindan-1,3-dione (compound 102), 4-dodecyloxy-2-formyloxyindan-1,3-dione (compound 103), 4-dodecyloxy-2 -Acetoxyindane-1,3-dione (Compound 104), 4-dodecyloxy-2-propynyloxyindane-1,3
-Dione (compound 105), 4-dodecyloxy-2-
Butyryloxyindane-1,3-dione (Compound 10
6), 4-dodecyloxy-2-isobutyryloxyindan-1,3-dione (Compound 107), 2-hydroxy-5-dodecyloxyindan-1,3-dione (Compound 108), 5-dodecyloxy -2-formyloxyindane-1,3-dione (Compound 109), 5
-Dodecyloxy-2-acetoxyindane-1,3-
Dione (Compound 110), 5-dodecyloxy-2-propynyloxyindane-1,3-dione (Compound 11
1), 5-dodecyloxy-2-butyryloxyindan-1,3-dione (Compound 112), 5-dodecyloxy-2-isobutyryloxyindan-1,3-dione (Compound 113),

2-hydroxy-4-vinyloxyindane-1,3-dione (Compound 114), 4-vinyloxy-
2-formyloxyindane-1,3-dione (Compound 115), 4-vinyloxy-2-acetoxyindane-
1,3-dione (Compound 116), 4-vinyloxy-2
-Propynyloxyindan-1,3-dione (Compound 117), 4-vinyloxy-2-butyryloxyindan-1,3-dione (Compound 118), 4-vinyloxy-2-isobutyryloxyindan-1, 3-dione (Compound 119), 2-hydroxy-5-vinyloxyindane-1,3-dione (Compound 120), 5-vinyloxy-2-formyloxyindane-1,3-dione (Compound 121), 5- Vinyloxy-2-acetoxyindane-1,3-dione (Compound 122), 5-vinyloxy-2-propynyloxyindane-1,3-dione (Compound 123), 5-vinyloxy-2-butyryloxyindane-1, 3-dione (Compound 124), 5-vinyloxy-2-isobutyryloxyindane-1,3-
Dione (compound 125),

2-Hydroxy-4-allyloxyindan-1,3-dione (Compound 126), 4-allyloxy-
2-formyloxyindane-1,3-dione (Compound 127), 4-allyloxy-2-acetoxyindane-
1,3-dione (Compound 128), 4-allyloxy-2
-Propynyloxyindan-1,3-dione (Compound 129), 4-allyloxy-2-butyryloxyindan-1,3-dione (Compound 130), 4-allyloxy-2-isobutyryloxyindan-1, 3-dione (compound 131), 2-hydroxy-5-allyloxyindane-1,3-dione (compound 132), 5-allyloxy-2-formyloxyindane-1,3-dione (compound 133), 5- Aryloxy-2-acetoxyindane-1,3-dione (Compound 134), 5-Aryloxy-2-propynyloxyindane-1,3-dione (Compound 135), 5-Aryloxy-2-butyryloxyindane-1, 3-dione (Compound 136), 5-allyloxy-2-isobutyryloxyindane-1,3-
Dione (compound 137),

2-Hydroxy-4-geranyloxyindan-1,3-dione (Compound 138), 4-geranyloxy-2-formyloxyindan-1,3-dione (Compound 139), 4-geranyloxy-2 -Acetoxyindane-1,3-dione (Compound 140), 4-geranyloxy-2-propynyloxyindane-1,3
-Dione (compound 141), 4-geranyloxy-2-
Butyryloxyindane-1,3-dione (Compound 14
2), 4-geranyloxy-2-isobutyryloxyindan-1,3-dione (compound 143), 2-hydroxy-5-geranyloxyindan-1,3-dione (compound 144), 5-geranyloxy -2-formyloxyindan-1,3-dione (compound 145), 5
-Geranyloxy-2-acetoxyindane-1,3-
Dione (Compound 146), 5-geranyloxy-2-propynyloxyindane-1,3-dione (Compound 14
7), 5-geranyloxy-2-butyryloxyindan-1,3-dione (Compound 148), 5-geranyloxy-2-isobutyryloxyindan-1,3-dione (Compound 149),

2-Hydroxy-4-benzyloxyindane-1,3-dione (Compound 150), 4-benzyloxy-2-formyloxyindane-1,3-dione (Compound 151), 4-benzyloxy-2 -Acetoxyindane-1,3-dione (Compound 152), 4-benzyloxy-2-propynyloxyindane-1,3
-Dione (Compound 153), 4-benzyloxy-2-
Butyryloxyindane-1,3-dione (Compound 15
4), 4-benzyloxy-2-isobutyryloxyindane-1,3-dione (Compound 155), 2-hydroxy-5-benzyloxyindane-1,3-dione (Compound 156), 5-benzyloxy -2-formyloxyindan-1,3-dione (compound 157), 5
-Benzyloxy-2-acetoxyindane-1,3-
Dione (Compound 158), 5-benzyloxy-2-propynyloxyindane-1,3-dione (Compound 15
9), 5-benzyloxy-2-butyryloxyindane-1,3-dione (Compound 160), 5-benzyloxy-2-isobutyryloxyindane-1,3-dione (Compound 161),

2-Hydroxy-4- (p-methylbenzyloxy) indan-1,3-dione (Compound 16
2), 4- (p-methylbenzyloxy) -2-formyloxyindane-1,3-dione (Compound 163),
4- (p-methylbenzyloxy) -2-acetoxyindane-1,3-dione (Compound 164), 4- (p-
Methylbenzyloxy) -2-propynyloxyindane-1,3-dione (Compound 165), 4- (p-methylbenzyloxy) -2-butyryloxyindane-
1,3-dione (Compound 166), 4- (p-methylbenzyloxy) -2-isobutyryloxyindane-
1,3-dione (Compound 167), 2-hydroxy-5
-(P-methylbenzyloxy) indan-1,3-dione (Compound 168), 5- (p-methylbenzyloxy) -2-formyloxyindan-1,3-dione (Compound 169), 5- (p -Methylbenzyloxy)
2-acetoxyindane-1,3-dione (Compound 1
70), 5- (p-methylbenzyloxy) -2-propynyloxyindane-1,3-dione (Compound 17
1), 5- (p-methylbenzyloxy) -2-butyryloxyindane-1,3-dione (Compound 172),
5- (p-methylbenzyloxy) -2-isobutyryloxyindane-1,3-dione (Compound 173),

2-hydroxy-4- (p-methoxybenzyloxy) indan-1,3-dione (Compound 17
4), 4- (p-methoxybenzyloxy) -2-formyloxyindane-1,3-dione (Compound 17
5), 4- (p-methoxybenzyloxy) -2-acetoxyindane-1,3-dione (Compound 176), 4
-(P-Methoxybenzyloxy) -2-propynyloxyindane-1,3-dione (Compound 177), 4-
(P-Methoxybenzyloxy) -2-butyryloxyindane-1,3-dione (Compound 178), 4- (p
-Methoxybenzyloxy) -2-isobutyryloxyindan-1,3-dione (Compound 179), 2-hydroxy-5- (p-methoxybenzyloxy) indan-1,3-dione (Compound 180), 5 -(P-Methoxybenzyloxy) -2-formyloxyindane-
1,3-dione (Compound 181), 5- (p-methoxybenzyloxy) -2-acetoxyindane-1,3-
Dione (compound 182), 5- (p-methoxybenzyloxy) -2-propynyloxyindane-1,3-dione (compound 183), 5- (p-methoxybenzyloxy) -2-butyryloxyindane-1 , 3-dione (Compound 184), 5- (p-methoxybenzyloxy) -2-isobutyryloxyindane-1,3-dione (Compound 185),

2-hydroxy-4- (p-chlorobenzyloxy) indan-1,3-dione (Compound 18
6), 4- (p-chlorobenzyloxy) -2-formyloxyindane-1,3-dione (Compound 187),
4- (p-chlorobenzyloxy) -2-acetoxyindane-1,3-dione (Compound 188), 4- (p-
Chlorobenzyloxy) -2-propynyloxyindane-1,3-dione (Compound 189), 4- (p-chlorobenzyloxy) -2-butyryloxyindane-
1,3-dione (Compound 190), 4- (p-chlorobenzyloxy) -2-isobutyryloxyindane-
1,3-dione (Compound 191), 2-hydroxy-5
-(P-chlorobenzyloxy) indan-1,3-dione (Compound 192), 5- (p-chlorobenzyloxy) -2-formyloxyindan-1,3-dione (Compound 193), 5- (p -Chlorobenzyloxy)
2-acetoxyindane-1,3-dione (Compound 1
94), 5- (p-chlorobenzyloxy) -2-propynyloxyindane-1,3-dione (Compound 19
5), 5- (p-chlorobenzyloxy) -2-butyryloxyindane-1,3-dione (Compound 196),
5- (p-chlorobenzyloxy) -2-isobutyryloxyindane-1,3-dione (Compound 197),

4-acetoxy-2-formyloxyindane-1,3-dione (compound 198), 2,4-diacetoxyindane-1,3-dione (compound 199),
4-acetoxy-2-propynyloxyindane-1,
3-dione (compound 200), 4-acetoxy-2-butyryloxyindane-1,3-dione (compound 20)
1), 4-acetoxy-2-isobutyryloxyindane-1,3-dione (compound 202), 2,5-diacetoxyindane-1,3-dione (compound 203), 5
-Acetoxy-2-formyloxyindane-1,3-
Dione (Compound 204), 5-acetoxy-2-propynyloxyindane-1,3-dione (Compound 20
5), 5-acetoxy-2-butyryloxyindane-
1,3-dione (Compound 206), 5-acetoxy-2
-Isobutyryloxyindane-1,3-dione (compound 207),

4-propynyloxy-2-formyloxyindane-1,3-dione (compound 208), 4-propynyloxy-2-acetoxyindane-1,3-dione (compound 209), 2,4-dipropynyl Oxyindane-1,3-dione (compound 210), 4-propynyloxy-2-butyryloxyindane-1,3-dione (compound 211), 4-propynyloxy-2-isobutyryloxyindane-1, 3-dione (compound 2
12), 2,5-dipropynyloxyindane-1,3
-Dione (compound 213), 5-propynyloxy-2
-Formyloxyindane-1,3-dione (compound 2
14), 5-propynyloxy-2-acetoxyindane-1,3-dione (Compound 215), 5-propynyloxy-2-butyryloxyindane-1,3-dione (Compound 216), 5-propynyloxy- 2-isobutyryloxyindane-1,3-dione (Compound 21
7),

2-hydroxy-4-methylindan
1,3-dione (Compound 218), 4-methyl-2-formyloxyindane-1,3-dione (Compound 21
9), 4-methyl-2-acetoxyindane-1,3-
Dione (compound 220), 4-methyl-2-propynyloxyindane-1,3-dione (compound 221), 4
-Methyl-2-butyryloxyindan-1,3-dione (Compound 222), 4-methyl-2-isobutyryloxyindan-1,3-dione (Compound 223), 2-
Hydroxy-5-methylindan-1,3-dione (Compound 224), 5-methyl-2-formyloxyindan-1,3-dione (Compound 225), 5-methyl-2
-Acetoxyindane-1,3-dione (compound 22
6), 5-methyl-2-propynyloxyindane-
1,3-dione (Compound 227), 5-methyl-2-butyryloxyindane-1,3-dione (Compound 22
8), 5-methyl-2-isobutyryloxyindane-
1,3-dione (compound 229),

2-hydroxy-4-ethylindane-
1,3-dione (Compound 230), 4-ethyl-2-formyloxyindane-1,3-dione (Compound 23
1), 4-ethyl-2-acetoxyindane-1,3-
Dione (compound 232), 4-ethyl-2-propynyloxyindane-1,3-dione (compound 233), 4
-Ethyl-2-butyryloxyindan-1,3-dione (Compound 234), 4-Ethyl-2-isobutyryloxyindan-1,3-dione (Compound 235), 2-
Hydroxy-5-ethylindan-1,3-dione (compound 236), 5-ethyl-2-formyloxyindan-1,3-dione (compound 237), 5-ethyl-2
-Acetoxyindane-1,3-dione (compound 23
8), 5-ethyl-2-propynyloxyindane-
1,3-dione (Compound 239), 5-ethyl-2-butyryloxyindane-1,3-dione (Compound 24
0), 5-ethyl-2-isobutyryloxyindane-
1,3-dione (compound 241),

2-hydroxy-4-propylindane-
1,3-dione (Compound 242), 4-propyl-2-
Formyloxyindan-1,3-dione (Compound 24
3), 4-propyl-2-acetoxyindane-1,3
-Dione (compound 244), 4-propyl-2-propynyloxyindane-1,3-dione (compound 24
5), 4-propyl-2-butyryloxyindane-
1,3-dione (compound 246), 4-propyl-2-
Isobutyryloxyindan-1,3-dione (compound 247), 2-hydroxy-5-propylindan-
1,3-dione (Compound 248), 5-propyl-2-
Formyloxyindan-1,3-dione (Compound 24
9), 5-propyl-2-acetoxyindane-1,3
-Dione (compound 250), 5-propyl-2-propynyloxyindane-1,3-dione (compound 25
1), 5-propyl-2-butyryloxyindane-
1,3-dione (Compound 252), 5-propyl-2-
Isobutyryloxyindane-1,3-dione (compound 253),

2-Hydroxy-4-isopropylindane-1,3-dione (compound 254), 4-isopropyl-2-formyloxyindane-1,3-dione (compound 255), 4-isopropyl-2-acetoxyindane -1,3-dione (Compound 256), 4-isopropyl-2-propynyloxyindane-1,3-dione (Compound 257), 4-isopropyl-2-butyryloxyindane-1,3-dione (Compound 258) ), 4-
Isopropyl-2-isobutyryloxyindane-1,
3-dione (Compound 259), 2-hydroxy-5-isopropylindane-1,3-dione (Compound 26
0), 5-isopropyl-2-formyloxyindane-1,3-dione (Compound 261), 5-isopropyl-2-acetoxyindane-1,3-dione (Compound 2
62), 5-isopropyl-2-propynyloxyindane-1,3-dione (Compound 263), 5-isopropyl-2-butyryloxyindane-1,3-dione (Compound 264), 5-isopropyl-2- Isobutyryloxyindane-1,3-dione (compound 265),

2-hydroxy-4-butylindan
1,3-dione (Compound 266), 4-butyl-2-formyloxyindane-1,3-dione (Compound 26
7), 4-butyl-2-acetoxyindane-1,3-
Dione (compound 268), 4-butyl-2-propynyloxyindane-1,3-dione (compound 269), 4
-Butyl-2-butyryloxyindan-1,3-dione (Compound 270), 4-butyl-2-isobutyryloxyindan-1,3-dione (Compound 271), 2-
Hydroxy-5-butylindan-1,3-dione (compound 272), 5-butyl-2-formyloxyindan-1,3-dione (compound 273), 5-butyl-2
-Acetoxyindane-1,3-dione (compound 27
4), 5-butyl-2-propynyloxyindane-
1,3-dione (Compound 275), 5-butyl-2-butyryloxyindane-1,3-dione (Compound 27
6), 5-butyl-2-isobutyryloxyindane-
1,3-dione (compound 277),

2-Hydroxy-4-isobutylindan-1,3-dione (compound 278), 4-isobutyl-
2-formyloxyindane-1,3-dione (compound 279), 4-isobutyl-2-acetoxyindane-
1,3-dione (Compound 280), 4-isobutyl-2
-Propynyloxyindan-1,3-dione (compound 281), 4-isobutyl-2-butyryloxyindan-1,3-dione (compound 282), 4-isobutyl-2-isobutyryloxyindane-1, 3-dione (Compound 283), 2-hydroxy-5-isobutylindan-1,3-dione (Compound 284), 5-isobutyl-2-formyloxyindane-1,3-dione (Compound 285), 5-isobutyl 2-acetoxyindane-1,3-dione (Compound 286), 5-isobutyl-2-propynyloxyindane-1,3-dione (Compound 287), 5-isobutyl-2-butyryloxyindane-1,3 -Dione (compound 288), 5-isobutyl-2-isobutyryloxyindane-1,3-
Dione (compound 289),

2-hydroxy-4-octylindane-
1,3-dione (Compound 290), 4-octyl-2-
Formyloxyindane-1,3-dione (Compound 29
1), 4-octyl-2-acetoxyindane-1,3
-Dione (Compound 292), 4-octyl-2-propynyloxyindane-1,3-dione (Compound 29
3), 4-octyl-2-butyryloxyindane-
1,3-dione (Compound 294), 4-octyl-2-
Isobutyryloxyindan-1,3-dione (Compound 295), 2-hydroxy-5-octylindan-
1,3-dione (Compound 296), 5-octyl-2-
Formyloxyindane-1,3-dione (Compound 29
7), 5-octyl-2-acetoxyindane-1,3
-Dione (Compound 298), 5-octyl-2-propynyloxyindane-1,3-dione (Compound 29
9), 5-octyl-2-butyryloxyindane-
1,3-dione (compound 300), 5-octyl-2-
Isobutyryloxyindane-1,3-dione (compound 301),

2-hydroxy-4-dodecylindane-
1,3-dione (compound 302), 4-dodecyl-2-
Formyloxyindane-1,3-dione (Compound 30
3), 4-dodecyl-2-acetoxyindane-1,3
-Dione (compound 304), 4-dodecyl-2-propynyloxyindane-1,3-dione (compound 30
5), 4-dodecyl-2-butyryloxyindane-
1,3-dione (Compound 306), 4-dodecyl-2-
Isobutyryloxyindan-1,3-dione (compound 307), 2-hydroxy-5-dodecylindane-
1,3-dione (Compound 308), 5-dodecyl-2-
Formyloxyindane-1,3-dione (Compound 30
9), 5-dodecyl-2-acetoxyindane-1,3
-Dione (compound 310), 5-dodecyl-2-propynyloxyindane-1,3-dione (compound 31
1), 5-dodecyl-2-butyryloxyindane-
1,3-dione (compound 312), 5-dodecyl-2-
Isobutyryloxyindane-1,3-dione (compound 313),

2-hydroxy-4-vinylindane
1,3-dione (Compound 314), 4-vinyl-2-formyloxyindane-1,3-dione (Compound 31
5), 4-vinyl-2-acetoxyindane-1,3-
Dione (compound 316), 4-vinyl-2-propynyloxyindane-1,3-dione (compound 317), 4
-Vinyl-2-butyryloxyindan-1,3-dione (Compound 318), 4-vinyl-2-isobutyryloxyindan-1,3-dione (Compound 319), 2-
Hydroxy-5-vinylindan-1,3-dione (compound 320), 5-vinyl-2-formyloxyindan-1,3-dione (compound 321), 5-vinyl-2
-Acetoxyindane-1,3-dione (compound 32
2), 5-vinyl-2-propynyloxyindane-
1,3-dione (Compound 323), 5-vinyl-2-butyryloxyindane-1,3-dione (Compound 32
4), 5-vinyl-2-isobutyryloxyindane-
1,3-dione (compound 325),

2-Hydroxy-4-allylindane-
1,3-dione (Compound 326), 4-allyl-2-formyloxyindane-1,3-dione (Compound 32
7), 4-allyl-2-acetoxyindane-1,3-
Dione (compound 328), 4-allyl-2-propynyloxyindane-1,3-dione (compound 329), 4
-Allyl-2-butyryloxyindan-1,3-dione (Compound 330), 4-allyl-2-isobutyryloxyindan-1,3-dione (Compound 331), 2-
Hydroxy-5-allylindane-1,3-dione (compound 332), 5-allyl-2-formyloxyindane-1,3-dione (compound 333), 5-allyl-2
-Acetoxyindane-1,3-dione (compound 33
4), 5-allyl-2-propynyloxyindane-
1,3-dione (Compound 335), 5-allyl-2-butyryloxyindane-1,3-dione (Compound 33
6), 5-allyl-2-isobutyryloxyindane-
1,3-dione (compound 337),

2-hydroxy-4-geranylindane-
1,3-dione (Compound 338), 4-geranyl-2-
Formyloxyindane-1,3-dione (Compound 33
9), 4-geranyl-2-acetoxyindane-1,3
-Dione (compound 340), 4-geranyl-2-propynyloxyindane-1,3-dione (compound 34
1), 4-geranyl-2-butyryloxyindane-
1,3-dione (Compound 342), 4-geranyl-2-
Isobutyryloxyindan-1,3-dione (compound 343), 2-hydroxy-5-geranylindan-
1,3-dione (compound 344), 5-geranyl-2-
Formyloxyindane-1,3-dione (Compound 34
5), 5-geranyl-2-acetoxyindane-1,3
-Dione (compound 346), 5-geranyl-2-propynyloxyindane-1,3-dione (compound 34
7), 5-geranyl-2-butyryloxyindane-
1,3-dione (Compound 348), 5-geranyl-2-
Examples include isobutyryloxyindane-1,3-dione (compound 389) and the like, as well as physiologically acceptable salts of the above compounds.

Addition salts of the above compounds can be produced by known methods. Among these, physiologically acceptable salts include, for example, sodium salt, potassium salt, magnesium salt, calcium salt and the like. In addition, there are nontoxic amine salts such as ammonium salts. These physiologically acceptable salts are also included in the present invention.

The antiallergic agent containing the indandione derivative of the present invention and a physiologically acceptable salt thereof as an active ingredient is effective for treating or preventing various allergic diseases. The allergic disease referred to in the present invention is
It refers to a disease thought to involve an antigen-antibody reaction in its onset, and refers to an allergic disease caused by exogenous antigen stimulation and an allergic disease caused by an abnormality in the immune system in the body.

More specifically, the antiallergic agent containing the indandione derivative of the present invention and a physiologically acceptable salt thereof as an active ingredient is, more specifically, bronchial asthma, childhood asthma, emphysema, chronic catarrhal conjunctivitis, spring catarrhal. , Scleritis, allergic rhinitis, hay fever, diet allergy, rheumatoid arthritis, secondary knee osteoarthritis, acute eczema, chronic eczema, atopic dermatitis, contact dermatitis, acute urticaria,
Chronic urticaria, pediatric troflus, pruritus dermatitis, drug eruption, autoimmune hemolytic anemia, allergic purpura, allergic granulocytopenia, allergic gastroenteritis, allergic migraine, drug allergy, serum sickness , Systemic lupus erythematosus, dermatomyositis, rheumatic fever, nodular periarteritis,
Treatment of chronic nephritis, chronic hepatitis, Hashimoto's disease, extinguishing colitis, etc.
It is effective in prevention.

The antiallergic agent containing the indandione derivative of the present invention and a physiologically acceptable salt thereof as an active ingredient is orally or parenterally administered (eg, subcutaneous administration, intravenous administration, transdermal administration, rectal administration). Administration, spray inhalation, etc.)
The dosage form can be adjusted to a dosage form suitable for each administration method.

Such drugs may be tablets, capsules, granules, fine granules, powders, troches, sublingual tablets, suppositories, ointments, injections, emulsions, suspensions, syrups depending on their use. It can be adjusted to any formulation form such as a spray, a spray and the like. In adjusting these, for example, non-toxic excipients, binders, disintegrating agents, lubricants, preservatives, antioxidants, isotonic agents, buffering agents, coating agents, etc. that are commonly used for this type of drug, It can be formulated by a known method using additives such as a corrigent, a solubilizing agent, a base, a dispersant, a stabilizer and a coloring agent.

Specific examples of each of the non-toxic additives that can be used are listed below. First, as excipients, starch and its derivatives (dextrin, carboxymethyl starch, etc.), cellulose and its derivatives (methyl cellulose, hydroxypropylmethyl cellulose, etc.), sugars (lactose, sucrose, glucose, etc.), silicic acid and silicates (Natural aluminum silicate, magnesium silicate, etc.), carbonates (calcium carbonate, magnesium carbonate, sodium hydrogen carbonate, etc.), aluminum hydroxide, magnesium hydroxide, polyoxyethylene derivatives, glyceryl monostearate, sorbitan monooleate, etc. Is mentioned.

As the binder, starch and its derivatives (pregelatinized starch, dextrin, etc.), cellulose and its derivatives (ethyl cellulose, sodium carboxymethyl cellulose, hydroxypropylmethyl cellulose, etc.), gum arabic, tragacanth, gelatin,
Examples thereof include sugars (lactose, sucrose, glucose, etc.), ethanol, polyvinyl alcohol and the like.

As the disintegrant, starch and its derivatives (carboxymethyl starch, hydroxypropyl starch, etc.), cellulose and its derivatives (carboxymethyl cellulose, carboxymethyl cellulose sodium, crystalline cellulose, hydroxypropyl methyl cellulose, etc.), carbonates (calcium carbonate, calcium carbonate, (Eg, calcium hydrogen carbonate), tragacanth, gelatin, agar and the like.

As the lubricant, stearic acid, calcium stearate, magnesium stearate, talc,
Examples thereof include silicic acid and salts thereof (light anhydrous silicic acid, natural aluminum silicate, etc.), titanium oxide, calcium hydrogen phosphate, dry aluminum hydroxide gel and the like.

As preservatives, paraoxybenzoic acid esters, sulfites (sodium sulfite, sodium pyrosulfite, etc.), phosphates (sodium phosphate, calcium polyphosphate, sodium polyphosphate, sodium metaphosphate, etc.), alcohols ( (Chlorobutanol, benzyl alcohol, etc.), benzalkonium chloride, benzethorium chloride, phenol, cresol, chlorocresol, dehydroacetic acid, sodium dehydroacetate, glycerin sorbate, sugars and the like.

As the antioxidant, sulfite (sodium sulfite, sodium hydrogen sulfite, etc.), Rongalit, erythorbic acid, L-ascorbic acid, cysteine, acetylthioglycerol, butylhydroxyanisole,
Dibutylhydroxytoluene, propyl gallate, ascorbyl palmitate, dl-α-tocopherol,
Examples thereof include nordihydroguaiaretic acid.

Examples of the tonicity agent include sodium chloride, sodium nitrate, potassium nitrate, dextran, glycerin, glucose and the like. Examples of the buffer include sodium carbonate, hydrochloric acid, boric acid, and phosphates (sodium hydrogen phosphate etc.).

As coating agents, cellulose derivatives (hydroxypropyl cellulose, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, etc.), shellac, polyvinylpyrrolidone, polyvinylpyridines (poly-2-vinylpyridine, poly-2-vinyl-5). -Ethyl pyridine etc.), polyvinyl acetyl diethyl amino acetate, polyvinyl alcohol phthalate, methacrylate methacrylic acid copolymer and the like.

As the corrigent, sugars (glucose, sucrose,
Lactose, etc.), sodium saccharin, sugar alcohols and the like. As a solubilizing agent, ethylenediamine,
Nicotinamide, sodium saccharin, citric acid,
Examples thereof include citrates, sodium benzoate, soaps, polyvinylpyrrolidone, polysorbates, sorbitan fatty acid esters, glycerin, propylene glycol and benzyl alcohol.

As the base, fatty acids (porcine fats), vegetable oils (olive oil, sesame oil, etc.), animal oils, lanolinic acid, petrolatum, paraffin, waxes, resins, bentonite, glycerin, glycol oils, higher alcohols (stearyl alcohol, Cetanol, etc.), cellulose derivatives and the like.

As the dispersant, gum arabic, tragacanth, cellulose derivative, stearic acid polyester,
Examples thereof include sorbitan sesquioleate, aluminum monostearate, sodium alginate, polysorbates, and sorbitan fatty acid esters.

Finally, examples of the stabilizer include sulfites (sodium hydrogen sulfite, etc.) nitrogen, carbon dioxide and the like. The content of the indandione derivative according to the present invention and the physiologically acceptable salt thereof in such a formulation varies depending on the dosage form, but is generally 0.1-10.
It is desirable to contain it at a concentration of 0% by weight.

The dose of the preparation in the present invention is determined by the type of warm-blooded animal including human beings, the severity of symptoms,
Although it can be varied over a wide range depending on the diagnosis of a doctor, etc., in general, when orally administered as an active ingredient, 0.01 to 300 mg / kg, preferably 0.1 to 100 mg / kg, per day per 1 kg of body weight, parenteral If administered, weight 1
It is preferable to administer 0.01 to 250 mg / kg, preferably 0.01 to 30 mg / kg, per day per day. However, it is possible to change the administration range depending on the severity of the patient's symptoms and the doctor's diagnosis. In addition, the above dose can be administered once or several times a day.

[0062]

EXAMPLES Next, the present invention will be described in more detail by way of examples, but the present invention is not limited by these examples. (Example-1) Mouse acute toxicity test This example was carried out to confirm the safety of the new compound according to the present invention. The test method will be described below. Test method: Male ICR mice (body weight 20 to 25 g) were fasted for 16 hours, and then 1000 mg / kg or 2000 mg / kg of each test substance was forcibly orally administered to 5 mice per group using a metal stomach tube for mice. Was administered. After oral administration, the animals were kept in a gauge for 7 days and observed for the presence of dead animals and general condition.
The% lethal dose (LD ₅₀ ) was estimated. The results of the mouse acute toxicity test are shown in Tables 1 and 2.

[0063]

[Table 1]

[0064]

[Table 2]

No death of any compound was observed after oral administration of 1000 or 2000 mg / kg, and the LD ₅₀ was estimated to be 1000 or 2000 mg / kg or more. From the above, it was revealed that the compound according to the present invention has extremely low toxicity and is highly safe.

(Example-2) Antiallergic action confirmation test (guinea pig allogeneic passive skin anaphylaxis test) To confirm the antiallergic action of the compound according to the present invention, a guinea pig allogeneic strain which is widely used as an antiallergic action confirmation test. A passive skin anaphylaxis test (PCA reaction test) was performed. The test method will be described below.

Test Method: Hartley
Male guinea pig (body weight: 250 to 300 g), ovalbumin (OVA) 2 μg and aluminum hydroxide gel 5
The mixed solution (μg) was intraperitoneally administered three times every two weeks for sensitization to prepare anti-OVA serum. The obtained antiserum was diluted 120-fold with physiological saline, and 0.05 ml each was intradermally sensitized in two places on the backs of guinea pigs in a group of 6 having shaved hair. After 48 hours of sensitization, 10 mg / kg of the test substance was orally administered, and then a mixed solution of 2 mg of OVA and 5 mg of Evans blue was administered through the hindlimb vein to induce an anaphylactic reaction. As a positive control, prominent tranilast (Tranilast) was used as an anti-allergic agent, and tranilast 200 was administered at 48 hours after sensitization in the same manner as the test substance.
Oral administration was at mg / kg.

Thirty minutes after the reaction was induced, the animal was killed by exsanguination under ether anesthesia, the back skin was peeled off, and the product (mm ² ) of the skin inner surface was used as the dye leakage amount, and the allergic reaction inhibition rate was calculated by the following formula. did. Tables 3 to 11 show the results of the antiallergic action confirmation test.

Inhibition rate of allergic reaction (%) = (amount of dye leak in solvent control group−amount of dye leak in test substance group) / (amount of dye leak in solvent control group) × 100

[0070]

[Table 3]

[0071]

[Table 4]

[0072]

[Table 5]

[0073]

[Table 6]

[0074]

[Table 7]

[0075]

[Table 8]

[0076]

[Table 9]

[0077]

[Table 10]

[0078]

[Table 11]

The indandione derivatives, which are the compounds of the present invention, exhibited excellent antiallergic activity as compared with tranilast, which is a prominent antiallergic drug used as a positive control drug. In addition, the positive control drug tranilast was administered at a dose 20 times that of the compound according to the present invention, 200 mg /
Although the same level of antiallergic activity as that of the compound according to the present invention was observed in kg, the 50% lethal dose in male mice of tranilast was 780 mg / kg, and therefore it was considered to be a drug with a very low safety margin.

From the above, the compound according to the present invention can be administered at a dose of 1/20 of tranilast, that is, 10 mg / kg,
Shows excellent anti-allergic activity and 5 in mice
It was revealed that the 0% lethal dose is 1000 to 2000 mg / kg or more and it is a useful antiallergic agent with a very wide safety margin.

(Example-3) to (Example-35) The crystals of compound 1 were crushed in a mortar, lactose was added thereto, and the mixture was thoroughly mixed while crushed with a pestle to give a 5% powder. A 5% powder of Compounds 2-33 was prepared with a similar formulation.

(Example-36) to (Example-67) The crystals of compound 34 were crushed in a mortar, lactose was added thereto, and the mixture was thoroughly mixed while crushed with a pestle to give a 10% powder. A 10% powder of Compounds 35-65 was made with a similar formulation.

(Example-68) to (Example-107) The crystals of compound 66 were mixed with an equal amount of starch and ground in a mortar. Lactose and starch residues were added to this and mixed.
Separately, 1 ml of purified water was added to 30 mg of gelatin, and the mixture was heated and dissolved. After cooling, 1 ml of ethanol was added to this while stirring to prepare a gelatin solution. The gelatin solution was added to the above mixture and kneaded to granulate. After that, it was dried and sized.
In a similar manner, 10% granules of compounds 67-105 were prepared.

(Example-108) to (Example-147) Tablets were prepared in a mortar using 20 times each amount of the above compound. That is, 100 mg of the crystals of compound 106 are crushed, and lactose and starch are added thereto and mixed. 10
% Starch paste is added to the above mixture, kneaded and granulated. After drying, talc and magnesium stearate were mixed and tableted by a conventional method. Compound 107
~ 145 5 mg tablets were produced.

(Example-148) to (Example-202) Using 10 times the amount of each compound of the above formulation in a mortar,
In the same manner as in (Example-108) to (Example-147), mixing and kneading, granulation and tableting were carried out to produce 25 mg tablets. In a similar formulation, 25 mg tablets of Compounds 147-200 were made.

(Example-203) to (Example-252) Using 10 times each of the above compounds in a mortar,
A 25 mg tablet was produced. That is, 250 mg in the mortar
The crystals of compound 201 of 1. are crushed, lactose is added thereto, and they are mixed sufficiently. An appropriate amount of purified water is added to carboxymethyl starch, and the mixture is added and kneaded with the above mixture to granulate. After drying, talc and magnesium stearate were mixed and compressed into tablets by a conventional method. Compound 202-20 with similar formulation
25 mg tablets of 0 were produced.

(Example-253) to (Example-302) 20 mg tablets were made with 10 volumes of each of the above compounds. That is, 6 g of hydroxypropyl cellulose was dissolved in an appropriate amount of ethanol, and 94 g of lactose was added and kneaded. After drying a little, it was sieved using a No. 20 sieve. After leaving it overnight, it was sieved with a No. 60 sieve to obtain 6% hydroxypropyl lactose. Also, mix magnesium stearate and talc in a ratio of 1: 4,
It was talc stearate. Compound 161, 6% hydroxypropyl lactose, talc stearate and potato starch were mixed well and tableted by a conventional method. 20 mg tablets of compounds 252 to 300 were prepared with similar formulation.

(Example-303) to (Example-351) Compound 301 was ground in a mortar using 20 times the amount of each of the above compounds, and lactose was added little by little and mixed. 3% prepared in the same manner as in Examples 253 to 302
Hydroxypropyl lactose, talc stearate, crystalline cellulose and potato starch were added and uniformly mixed, and then tableted by a conventional method. Compound 30 in the same manner
2-3 mg 5 mg tablets were produced.

[0089]

INDUSTRIAL APPLICABILITY According to the present invention, indane-1,3-dione having an alkyl group, an alkenyl group, a hydroxyl group, an alkyloxy group, an alkenyloxy group, an aralkyloxy group, an acyloxy group in a benzene ring or an unsubstituted group. It was possible to clarify the usefulness of the derivative as an antiallergic agent.

─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Nobuyuki Kimura 1550-2 Rokuzaki, Sakura City, Chiba 4-102 Dai Nippon Ink Co., Ltd. (58) Fields investigated (Int.Cl. ⁷ , DB name) A61K 31/12 A61K 31/215 C07C 49/67 CA (STN) REGISTRY (STN)

Claims (9)

(57) [Claims] 1. The following general formula (I): (Wherein R ₁ represents a hydrogen atom, an alkyl group, an alkenyl group, a hydroxyl group, an alkyloxy group, an alkenyloxy group, an aralkyloxy group or an acyloxy group, and R ₂
Represents a hydrogen atom or an acyl group. And an indanedione derivative represented by the formula (1) and a physiologically acceptable salt thereof as an active ingredient. 2. An antiallergic agent comprising an indandione derivative according to claim 1, wherein R ₂ is a hydrogen atom, and a physiologically acceptable salt thereof as an active ingredient. 3. An antiallergic agent comprising an indandione derivative according to claim 1, wherein R ₂ is an acyl group, and a physiologically acceptable salt thereof as an active ingredient. 4. An indandione derivative or a physiologically acceptable salt thereof according to claim 1, wherein R ₁ is a hydrogen atom, an alkyl group or an alkenyl group, and R ₂ is a hydrogen atom or an acyl group. An anti-allergic agent composed as an ingredient. 5. An antiallergic agent comprising an indandione derivative according to claim 4, wherein R ₂ is a hydrogen atom, and a physiologically acceptable salt thereof as an active ingredient. 6. An antiallergic agent comprising an indandione derivative according to claim 4, wherein R ₂ is an acyl group, and a physiologically acceptable salt thereof as an active ingredient. 7. The indandione derivative according to claim 1, wherein R ₁ is a hydroxyl group, an alkyloxy group, an alkenyloxy group, an aralkyloxy group or an acyloxy group, and R ₂ is a hydrogen atom or an acyl group. An anti-allergic agent containing a salt acceptable for the above as an active ingredient. 8. An antiallergic agent comprising an indandione derivative according to claim 7, wherein R ₂ is a hydrogen atom, and a physiologically acceptable salt thereof as an active ingredient. 9. An antiallergic agent comprising an indandione derivative according to claim 7, wherein R ₂ is an acyl group, and a physiologically acceptable salt thereof as an active ingredient.