JP2000204091A - Novel benzodioxol derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide the subject novel benzodioxol derivative that has the effect of inhibiting peroxide lipids and is useful as a medicine, cosmetic and chemical or the like. SOLUTION: This compound is represented by the formula [R1 is H, a lower alkyl; at least one of R2 and R3 is an aromatic ring, a hetero ring (the benzofuran ring is removed) and the remaining is H], typically 5-phenyl-6- hydroxy-4-methoxy-1,3-benzodioxol. The compound of the formula, in the case of the typical compound, is prepared by halogenating 4-methoxy-6-hydroxy-1,3- benzodioxol to form 5-bromo-4-methoxy-6-hydroxy-1,3-benzodioxol, protecting the hydroxyl group, then followed by deprotection. This compound is useful as a therapeutic agent for cancers, arteriosclerosis, Parkinson's disease or the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel benzodioxole derivative. More specifically, the present invention
The present invention relates to a novel benzodioxole derivative having an antioxidant action and a lipid peroxide inhibitory action useful for medical products and the like.

[0002]

2. Description of the Related Art In recent years, it has been pointed out that there is a relationship between phenomena such as cancer, arteriosclerosis, Parkinson's disease, diabetes, inflammation, and aging and oxidative reactions in a living body. There is a growing expectation for antioxidants as drugs that can do this.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a benzodioxole derivative having an effect of inhibiting lipid peroxide. Compound 1 represented by the following formula (2) has been found as a substance that prevents erythrocyte hemolysis from yeast (J. Am. Chem. Soc., 80 , 385-389, 1958). There are no reports on the lipid peroxide inhibitory effect of the derivative.

[0004]

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[0005]

Means for Solving the Problems The present invention finds a lipid peroxide inhibitory effect on a benzodioxole derivative, synthesizes intermediates and derivatives thereof by organic synthesis, and searches for properties of the obtained compound. It is intended to provide a novel derivative having a high antioxidant action (lipid peroxide inhibitory action). The present invention provides a compound represented by the general formula (1)

[0006]

Embedded image [Where R1 is hydrogen or a lower alkyl group;
At least one of R2 and R3 is an aromatic ring or a heterocyclic ring (excluding a benzofuran ring), and the remainder is an arbitrary substituent selected from hydrogen], and a salt thereof.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. In the present invention, the term "lower alkyl group" means a linear, branched or cyclic group having up to 8 carbon atoms.
In the present invention, "aromatic ring or hetero ring" means a functional group that is acceptable in organic chemistry, for example,
Phenyl group, naphthalene group, thiophene group, furan group,
Pyridine group, benzothiophene group, etc. and their substituted substrates. The salt of the compound of the present invention means a pharmaceutically acceptable salt, for example, sodium salt,
Potassium, calcium, ammonium and aluminum salts. INDUSTRIAL APPLICABILITY The benzodioxole derivative of the present invention is a novel substance, has a lipid peroxide inhibitory action, and is useful as a chemical substance used in pharmaceuticals, cosmetics, chemical products and the like. The production method can be obtained by using a synthesis method using a halogenated benzodioxole compound and an organic boronic acid or an organic tin reagent and a carbon-carbon bond as a key reaction in the presence of a palladium catalyst. Details of the production will be described in Examples.

Further, it has been confirmed in the present invention that the benzodioxole derivative has a lipid peroxide-suppressing action, and that the novel benzodioxole derivative of the present invention has an excellent lipid-peroxide-suppressing action. Has been confirmed. Accordingly, the novel benzodioxole derivative of the present invention is useful for various diseases in which peroxidation in vivo is considered to be involved, for example, cancer,
It is useful as a therapeutic agent for arteriosclerosis, Parkinson's disease, diabetes and inflammation. For this purpose, the compounds of the present invention can be produced in various dosage forms, such as powders, granules, tablets, dragees, ampoules, capsules, etc., subcutaneously. , Intramuscular or intravenous preparations, suppositories and the like. For the above-mentioned formulation, usual additives such as a bulking agent, a binder, a disintegrant, a pH adjuster and a solubilizer can be used.

The dosage of the novel benzodioxole derivative of the present invention for a patient to be treated may vary depending on the age of the patient, the type and condition of the disease, and the like. It can be administered in divided doses.

[0010]

EXAMPLES The present invention will be described with reference to examples. The example is an embodiment and does not limit the present invention.

(Example 1) 5-phenyl-6-hydroxy-4-
Synthesis of methoxy-1,3-benzodioxole (compound 2)

[0012]

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Step 1 Synthesis of 5-bromo-4-methoxy-6-hydroxy-1,3-benzodioxole 4-methoxy-6-hydroxy-1,3-benzodioxole (2.7
Acetic acid (13.9 mL) and dichloromethane
(5.58 mL) and stirred at 0 ° C. There bromine (0.864m
L, 16.3 mmol) in dichloromethane (5.58 mL) was added dropwise. After stirring at room temperature for 1 hour, the reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 4: 1). Recrystallization from isopropyl ether gave 3.4 g (83%) of the title compound as crystals. 77.3-78.7 ° C. 1H NMR
(DMSO-d6, 400 MHz) δ 4.07 (3H, s, C H 3), 6.0 (2H, m,
C H2), 6.46 (1H, s, Ar- H), 8.26 (1H, s, O H).

Step 2 Synthesis of 6-benzyloxy-5-bromo-4-methoxy-1,3-benzodioxole 5-bromo-4-methoxy-6-hydroxy- obtained in Step 1
1,3-benzodioxole (2.55 g, 10.32 mmol) was dissolved in 5 mL of dimethylformamide, and sodium hydride (416 mg, 1
0.4 mmol) was added dropwise to a suspension of dimethylformamide (2.5 mL) at 0 ° C. with stirring. After stirring at room temperature for 30 minutes, benzyl bromide (1.25 ml, 10.5 mmol) was added and the mixture was further stirred at room temperature for 30 minutes.
Stirred for minutes. The reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane: ethyl acetate = 4: 1) to give 2.78 g (80%) of the title compound as an oil. 1H NMR (CDCl
3,400MHz) δ 4.07 (3H, s, C H 3), 5.06 (2H, s, C H2 ),
5.90 (2H, s, C H2 ), 6.34 (1H, s, Ar- H ), 7.3-7.5 (6H,
m, Ar- H ).

Step 3 Synthesis of 5-phenyl-6-hydroxy-4-methoxy-1,3-benzodioxole 6-benzyloxy-5-bromo-4-methoxy obtained in Step 2
-1,3-benzodioxole (300 mg, 0.89 mmol), phenylboric acid (119 mg, 0.98 mmol), tetrabutylammonium bromide (287 mg, 0.89 mmol), palladium acetate (4 mg,
0.018 mmol), 2 mL of water in potassium carbonate (307 mg, 2.22 mmol)
Was added and stirred at 90 ° C. for 1 hour. The reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with water and saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 20: 1).
241 mg (81%) of the title compound was obtained as an oil. 1H NMR (CDCl
3,400MHz) δ 3.81 (3H, s, C H 3), 4.85 (2H, s, C H2 ), 5.
92 (2H, s, C H2 ), 6.38 (1H, s, Ar- H ), 7.1-7.4 (10H, m, A
r- H ). MS (EI) m / z 334 (M +, 100%), 243, 213, 91.

Step 4 Synthesis of 5-phenyl-6-hydroxy-4-methoxy-1,3-benzodioxole 5-phenyl-6-benzyloxy-4-methoxy-1,3-benzo obtained in Step 3 Dioxol (200 mg) in ethyl acetate (10 mL)
And 10% Pd-C (20 mg) was added thereto, followed by stirring at room temperature overnight and hydrogenation. The reaction mixture was filtered and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane: ethyl acetate = 5: 1) and recrystallized from petroleum ether to obtain 136 mg (93%) of the title compound as crystals. Melting point 88.1
-89.4 ° C. 1HNMR (CDCl3,400MHz) δ3.83 (3H, s, C H3 ),
4.78 (1H, brs, O H ), 5.91 (2H, s, C H2 ), 6.31 (1H, s,
Ar- H ), 7.32-7.34 (2H, m, Ar- H ), 7.37-7.41 (1H, m, Ar
-H ), 7.46-7.50 (2H, m, Ar- H ). MS (EI) m / z 244 (M +, 1
00%), 199, 171, 115.

Example 2 5- (4-methoxyphenyl) -6
Of 3-hydroxy-4-methoxy-1,3-benzodioxole (Compound 3)

[0018]

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The title compound was obtained in the same manner as in Example 1 except that 4-methoxyphenylboric acid was used instead of phenylboric acid. 83.0-83.8 ° C. 1H NMR (CDCl
3,400MHz) δ3.83 (3H, s, C H3 ), 3.85 (3H, s, C H3 ),
4.79 (1H, brs, O H ), 5.90 (2H, s, C H2 ), 6.30 (1H, s, A
r- H ), 7.00-7.02 (2H, m, Ar- H ), 7.23-7.25 (2H, m, Ar-
H ). MS (EI) m / z 274 (M +, 100%), 259, 229, 201, 145.

Example 3 5- (4-methylphenyl) -6-
Synthesis of hydroxy-4-methoxy-1,3-benzodioxole (compound 4)

[0021]

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The title compound was obtained in the same manner as in Example 1 except that 4-methylphenylboric acid was used instead of phenylboric acid. 124.8-126.6 ° C. 1H NMR (CDCl
3,400MHz) δ2.40 (3H, s, C H3 ), 3.83 (3H, s, C H3 ),
4.80 (1H, brs, O H ), 5.90 (2H, s, C H2 ), 6.30 (1H, s, A
r- H ), 7.20-7.22 (2H, m, Ar- H ), 7.28-7.30 (2H, m, Ar-
H ). MS (EI) m / z 258 (M +, 100%), 243, 213, 185, 129.

Example 4 Synthesis of 5- (4-biphenyl) -6-hydroxy-4-methoxy-1,3-benzodioxole (Compound 5)

[0024]

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The title compound was obtained in the same manner as in Example 1 except that 4-biphenylboric acid was used instead of phenylboric acid. 141.8-143.5 ° C. 1H NMR (CDCl3,400
MHz) δ3.87 (3H, s, C H3 ), 4.86 (1H, brs, O H ), 5.91
(2H, s, C H2 ), 6.33 (1H, s, Ar- H ), 7.35-7.41 (3H, m,
Ar- H), 7.44-7.48 (2H, m, Ar- H), 7.63-7.65 (2H, m, Ar
-H ), 7.68-7.71 (2H, m, Ar- H ). MS (EI) m / z 320 (M +, 100
%), 275, 247, 191.

Example 5 5- (3-methoxyphenyl) -6
Of 2-hydroxy-4-methoxy-1,3-benzodioxole (compound 6)

[0027]

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The title compound was obtained in the same manner as in Example 1 except that 3-methoxyphenylboric acid was used instead of phenylboric acid. 1HNMR (CDCl3,400MHz) δ 3.83
(3H, s, C H3 ), 3.84 (3H, s, C H3 ), 4.86 (1H, brs, O H ),
5.91 (2H, s, C H2 ), 6.31 (1H, s, Ar- H ), 6.86-6.95 (4
H, m, Ar- H ), 7.40 (1H, dd, J = 7.9, 7.9 Hz Ar- H ).

Example 6 Synthesis of 5- (4-trifluoromethylphenyl) -6-hydroxy-4-methoxy-1,3-benzodioxole (Compound 7)

[0030]

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The title compound was obtained in the same manner as in Example 1 except that 4-trifluoromethylphenylboric acid was used instead of phenylboric acid. 1H NMR (CDCl3,400MH
z) δ 3.85 (3H, s, C H3 ), 4.62 (1H, brs, O H ), 5.91 (2
H, s, C H2 ), 6.30 (1H, s, Ar- H ), 7.30-7.37 (4H, m, Ar
-H ).

Example 7 Synthesis of 5- (3,4-dimethoxyphenyl) -6-hydroxy-4-methoxy-1,3-benzodioxole (compound 8)

[0033]

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Instead of phenylboric acid in Example 1, 3,4-
The title compound was obtained in the same manner as in Example 1 except that dimethoxyphenylboric acid was used. 1HNMR (CDCl3,400MHz) δ
3.85 (3H, s, C H3 ), 3.88 (3H, s, C H3), 3.93 (3H, s, C H
3 ), 4.88 (1H, brs, O H ), 5.90 (2H, s, C H2 ), 6.31 (1H,
s, Ar- H ), 6.83 (1H, d, J = 1.9Hz Ar- H ), 6.88 (1H,
dd, J = 1.9, 8.0 Hz Ar- H ), 6.98 (1H, d, J = 8.0Hz A
r- H ).

Example 8 Synthesis of 5- (3,4,5-trimethoxyphenyl) -6-hydroxy-4-methoxy-1,3-benzodioxole (compound 9)

[0036]

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Instead of phenylboric acid in Example 1, 3,4,
Example 1 except for using 5-trimethoxyphenylboric acid
The title compound was obtained in the same manner as described above. 1HNMR (CDCl3,400MHz)
δ 3.86 (6H, s, C H3 ), 3.88 (3H, s, C H3 ), 3.90 (3H,
s, C H3 ), 4.94 (1H, brs, O H ), 5.91 (2H, s, C H2 ), 6.31
(1H, s, Ar- H ), 6.53 (2H, s, Ar- H ).

Example 9 5- (2-methoxyphenyl) -6
Of 4-hydroxy-4-methoxy-1,3-benzodioxole (Compound 10)

[0039]

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The 6-benzyloxy-5-bromo-4-methoxy-1,3-benzodioxole obtained in Example 1 (360 mg, 1.07
mmol), 2-methoxyphenylboric acid (240 mg, 1.61 mmo
l), tetrakis (triphenylphosphine) palladium
(120 mg, 0.11 mmol) in 2 M potassium carbonate solution (0.6 ml),
6 mL of toluene was added, and the mixture was stirred at 120 ° C for 16 hours. The reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with water and saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 5: 1). The obtained oil was dissolved in ethyl acetate (10 mL), 10% Pd-C (150 mg) was added, and the mixture was stirred at room temperature overnight and hydrogenated. The reaction mixture was filtered and concentrated. The residue was subjected to silica gel column chromatography (developing solvent; hexane:
Purify with ethyl acetate = 3: 1) and crystal of the title compound 118 m
g (40%). 1H NMR (CDCl3,400MHz) δ 3.82 (3H,
s, C H3 ), 3.83 (3H, s, C H3 ), 5.03 (1H, brs, O H ), 5.91
(2H, m, C H2 ), 6.33 (1H, s, Ar- H ), 7.03-7.06 (2H, m,
Ar- H ), 7.22-7.25 (1H, m, Ar- H ), 7.37-7.41 (1H, m, A
r- H ).

Example 10 5- (thienyl) -6-hydroxy-4-methoxy-1,3-benzodioxole (compound 1
Synthesis of 1)

[0042]

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Step 1 5- (thienyl) -6-benzyloxy-4-
Synthesis of methoxy-1,3-benzodioxole 6-benzyloxy-5-bromo-4-methoxy-1,3-benzodioxole obtained in Example 1 (300 mg, 0.89 mmol), 2- (tributyl Stannyl) -thiophene (565 mL, 1.78 mmol), tetrakis (triphenylphosphine) palladium (51 mg,
0.04 mmol) was added with 5 mL of HMPA, and the mixture was stirred at 100 ° C for 4 hours.
The reaction mixture was poured into 1N hydrochloric acid and extracted with diethyl ether. The organic layer was washed successively with water and saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 5: 1). The title compound as an oil
mg (93%). 1HNMR (CDCl3,400MHz) δ3.90 (3H, s, C
H 3), 4.96 (2H, s, C H2 ), 5.92 (2H, s, C H2 ), 6.38 (1H,
s, Ar- H ), 7.06-7.07 (1H, m, Ar- H ), 7.27-7.34 (7H, m,
Ar- H ). MS (EI) m / z 340 (M +), 249 (100%), 219, 91.

Step 2 Synthesis of 5- (thienyl) -6-hydroxy-4-methoxy-1,3-benzodioxole 5- (thienyl) -6-benzyloxy-4-methoxy-1 obtained in Step 1 , 3-benzodioxole (280mg) in ethyl acetate (10m
L), 10% Pd-C (150 mg) was added, and the mixture was stirred at room temperature overnight and hydrogenated. The reaction mixture was filtered and concentrated. The residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 5: 1) and recrystallized from petroleum ether to obtain 15 mg (7%) of the title compound as crystals. 75.6 melting point
-77.0 ° C. 1HNMR (CDCl3,400MHz) δ3.91 (3H, s, C H3),
5.21 (1H, brs, O H ), 5.91 (2H, s, C H2 ), 6.31 (1H, s,
Ar- H ), 7.06 (1H, dd, J = 0.8, 3.5 Hz, Ar- H ), 7.15 (1
H, dd, J = 3.5, 5.0 Hz, Ar- H ), 7.48 (1H, dd, J = 0.8,
5.0 Hz, Ar- H ). MS (EI) m / z250 (M +, 100%), 235, 219,
205, 121.

Example 11 5- (2-furan) -6-hydroxy-4-methoxy-1,3-benzodioxole (compound 1
Synthesis of 2)

[0046]

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Example 10 6-benzyloxy-5-bromo-4-
6-butyldimethylsilyloxy-5-bromo-4-methoxy-1,3-benzodioxole, 2- (tributylstannyl) -thiophene instead of methoxy-1,3-benzodioxole, 2- (tributylstannyl) -thiophene
Example 1 except for using (tributylstannyl) -furan
The oily substance obtained in the same manner as in Example 1 was dissolved in THF, TBAF was added and deprotected to obtain the title compound. 1HNMR (CDCl3,400MHz)
δ 4.00 (3H, s, C H3 ), 7.4 (1H, brs, O H ), 5.90 (2H,
s, C H2 ), 6.29 (1H, s, Ar- H ), 6.53-6.54 (1H, m, Ar-
H), 6.73-6.74 (1H, m , Ar- H), 7.48-7.49 (1H, m, Ar- H)
.

Example 12 1,5-Diphenyl-6-hydroxy-4-methoxy-1,3-benzodioxole (Compound 1
Synthesis of 3)

[0049]

Embedded image 5-phenyl-6-hydroxy-4-methoxy-1,3- of Example 1
The title compound was obtained in the same manner as in Example 1 except that 6-benzyloxy-1,5-dibromo-4-methoxy-1,3-benzodioxole was used instead of benzodioxole. 1H NMR (CD
Cl3,400MHz) δ3.86 (3H, s, C H3 ), 4.93 (1H, brs, O
H), 5.93 (2H, s , C H2), 7.37-7.59 (10H, m, Ar- H).

Example 13 Synthesis of 5- (2,4-dimethoxyphenyl) -6-hydroxy-4-methoxy-1,3-benzodioxole (Compound 14)

[0051]

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The title compound was obtained in the same manner as in Example 9 except that 2,4-dimethoxyphenylboric acid was used instead of 2-methoxyphenylboric acid. 1H NMR (CDCl3,40
0MHz) δ 3.80 (3H, s, C H3 ), 3.81 (3H, s, C H3 ), 3.85
(3H, s, C H3 ), 4.96 (1H, brs, O H ), 5.90 (2H, m, C H
2 ), 6.32 (1H, s, Ar- H ), 6.60-6.62 (2H, m, Ar- H ), 7.1
2-7.14 (1H, m, Ar- H ).

Reference Example Synthesis of 5- (2-benzofuranyl) -6-hydroxy-4-methoxy-1,3-benzodioxole (Compound 1)

[0054]

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Step 1 Synthesis of 5- (2-benzofuranyl) -6-benzyloxy-4-methoxy-1,3-benzodioxole 6-benzyloxy-5-bromo-4-methoxy- obtained in Example 1 1,3-benzodioxole (960 mg, 2.82 mmol), benzofuran-2-boric acid (684 mg, 4.22 mmol), tris (o-toluyl) phosphine (128 mg, 0.421 mmol), trisbenzylideneacetone dipalladium / chloroform complex (109mg,
0.105 mmol), diisopropylethylamine (0.982 g, 5.6
(4 mmol) was dissolved in 10 mL of dimethylformamide.
Stirred for hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed successively with water and saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (developing solvent; hexane: benzene = 1: 1). This gave 1.14 g (100%) of the title compound as an oil. 1HNMR (CDCl3,400MHz) δ3.95 (3H,
s, C H 3), 5.01 (2H, s, C H2 ), 5.95 (2H, s, C H2 ), 6.39
(1H, s, Ar- H ), 6.83 (1H, s, Ar- H ), 6.8-7.6 (10H, m, A
r- H ). MS (EI) m / z 374, 283, 255.

Step 2 Synthesis of 5- (2-benzofuranyl) -6-hydroxy-4-methoxy-1,3-benzodioxole 5- (2-benzofuranyl) -6-benzyloxy-4 obtained in Step 1 -Methoxy-1,3-benzodioxole (1.14 g, 3.04 mm
ol) was dissolved in ethyl acetate (70 mL), 10% Pd-C (56 mg) was added, and the mixture was stirred at room temperature overnight and hydrogenated. The reaction mixture was filtered and concentrated. The residue was purified by silica gel column chromatography (developing solvent; ethyl acetate: hexane = 15: 85). Recrystallize from petroleum ether to give 715 mg of the title compound
(88%). Melting point 118 ° C. 1H NMR (Acetone-d6, 400 MHz)
δ3.95 (3H, s, C H 3), 5.06 (2H, s, C H2 ), 5.98 (2H, s,
C H2 ), 6.31 (1H, s, Ar- H ), 6.93 (1H, s, Ar- H ), 7.2-
7.6 (6H, m, Ar- H ), 8.33 (1H, s, O H). MS (EI) m / z 284,
269, 142.

(Test for measuring antioxidant activity) Lipid peroxide suppression test was performed using Biochem. Biophys. Res. Comm., 135, 1015-1021, 198.
This was performed according to the method described in 6. In addition, α-tocopherol and propyl gallate were used as control antioxidants, and the concentration of the test substance that suppressed the amount of malondialdehyde of each compound by 50% was calculated (IC ₅₀ ). Table 1 shows the results.

[0058]

[Table 1] Sample IC50 (μM) Compound 1 (Reference compound) 98 Compound 2 83 Compound 3 56 Compound 4 65 Compound 5 107 Compound 11 44 Tocopherol 280 Propyl gallate 50

[0059]

The object of the present invention is to provide a novel benzodioxole derivative which has antioxidant properties and is useful for pharmaceuticals, cosmetics, chemical products and the like.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/38 601 A61K 31/38 601 C07D 407/04 C07D 407/04 409/04 409/04

Claims (2)

[Claims] 1. A compound of the general formula (1) [Where R1 is hydrogen or a lower alkyl group;
At least one of R2 and R3 is an aromatic ring or a heterocyclic ring (excluding a benzofuran ring), and the remainder is an arbitrary substituent selected from hydrogen] and a salt thereof. 2. The benzodioxole derivative according to claim 1, wherein in formula (1), at least R2 is an aromatic ring or a heterocyclic ring (excluding a benzofuran ring).