JP2757353B2 - Indane derivative, its production method and its synthetic intermediate - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel indane derivative having an endotoxin shock protective effect and / or a therapeutic effect on nephritis, a process for producing the same and a synthetic intermediate thereof.

[0002]

2. Description of the Related Art Japanese Unexamined Patent Publication No.
(2-benzenesulfonamido-indan-5-yl)
It is disclosed that benzenesulfonamidoindane compounds such as -4,5-dihydro-pyridazin-3 (2H) -one exhibit an antithrombotic effect. In addition, WO92 /
No. 15558 includes 6- [2-[(4-chlorophenyl) sulfonylaminomethyl] indan-5-yl]-
It is disclosed that a benzenesulfonaminoalkylindan compound such as 3-oxo-2,3,4,5-tetrahydropyridazine has a thromboxane A ₂ antagonistic action.

On the other hand, as a remedy for endotoxin shock which occurs in patients with severe infections of Gram-negative bacteria,
Steroid hormones, aprotinin (a protease inhibitor), dobutamine (a cardiotonic) and the like are used.

[0004] Prednisolone (steroid), cyclophosphamide (immunosuppressant), dipyridamole, dilazep (antiplatelet agent), heparin (anticoagulant) and the like have been used as therapeutic agents for nephritis. .

[0005]

SUMMARY OF THE INVENTION The present invention provides a novel indane derivative having an excellent endotoxin shock protective effect and / or a therapeutic effect on nephritis, a process for producing the same, and a synthetic intermediate thereof.

[0006]

According to the present invention, there is provided a compound represented by the general formula [I]:

[0007]

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(Wherein R ¹ is a lower alkyl group, a lower alkenyl group or a monocyclic heteroaromatic group which contains a nitrogen atom as a hetero atom and may have a substituent, and R ² is a hydrogen atom or A lower alkyl group, A represents a lower alkylene group.)
, A pharmacologically acceptable salt thereof and a production method thereof.

In the object [I] of the present invention, the monocyclic heteroaromatic group which contains a nitrogen atom as a hetero atom and may have a substituent includes, for example, a methyl group, an ethyl group,
A lower alkyl group such as a propyl group; a halogeno lower alkyl group; a lower alkoxy group such as a methoxy group, an ethoxy group, a propoxy group; a lower alkylthio group such as a methylthio group; a hydroxyl group; a mercapto group; a cyano group; an amino group; For example, mono-lower alkylamino group, di-lower alkylamino group, acylamino group); halogen atom; carboxy group; lower alkoxycarbonyl group such as methoxycarbonyl group; lower alkylcarbonyloxy group; lower alkylcarbonyl group; carbamoyl group; A pyridyl group which may be substituted with 1 to 4 groups selected from an alkylcarbamoyl group; and a phenoxy group.

As preferred compounds, R ¹ in the general formula [I] is an alkyl group having 1 to 4 carbon atoms, a vinyl group or a pyridyl group, R ² is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and A is a carbon atom. Compounds that are alkylene groups of formulas 1 to 4 can be mentioned.

More preferably, R ¹ is a vinyl group, R ² is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms,
Is a C1-C4 alkylene group.

The object [I] of the present invention has two types of optical isomers based on asymmetric carbon atoms, and the present invention includes both of these optical isomers and mixtures thereof.

The target compound [I] of the present invention can be used in a free form or in the form of a pharmaceutically acceptable salt thereof for pharmaceutical use. Pharmaceutically acceptable salts include hydrochlorides, phosphates, inorganic salts or acetates such as hydrobromide,
Organic acid salts such as succinate, fumarate, methanesulfonate and the like can be mentioned.

The object [I] of the present invention can be administered orally or parenterally, and can be used as a pharmaceutical preparation by mixing with an excipient suitable for oral or parenteral administration. . The pharmaceutical preparation may be a solid preparation such as a tablet, a capsule or a powder, or a liquid preparation such as a solution, a suspension or an emulsion. In the case of parenteral administration, it can be used in the form of injection.

The dose varies depending on the age, weight, condition and degree of disease of the patient, but the daily dose is usually 1 to 300 mg / kg, particularly 3 to 100 mg / kg for oral administration. For parenteral administration,
0.01-50 mg / kg, especially 0.1-20 mg
/ Kg is preferred.

According to the present invention, the target compound [I] is obtained by the method (A): General formula [II]

[0017]

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(Wherein the symbols have the same meanings as described above), or a salt thereof, and a general formula [III]

[0019]

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(Wherein X represents a reactive residue, and other symbols have the same meanings as described above), or by reacting with a sulfonic acid compound represented by the following formula (B): Formula (IV)

[0021]

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(Wherein the symbols have the same meanings as described above).

As the reactive residue (X) of the sulfonic acid compound [III], a group capable of leaving nucleophilically, for example, a halogen atom, an alkoxy group, a lower alkylsulfonyloxy group, a benzenesulfonyloxy group, a lower alkyl group Examples include a group-substituted benzenesulfonyloxy group and a trifluoromethanesulfonyloxy group.

As the salt of the amine compound [II], for example, salts with inorganic acids such as hydrochloric acid, hydrobromic acid and sulfuric acid, and salts with organic acids such as succinic acid and fumaric acid can be used.

Method (A): The reaction between the amine compound [II] or a salt thereof and the sulfonic acid compound [III] can be carried out according to a conventional method.

For example, the reaction of an amine compound [II] or a salt thereof with a sulfonic acid compound [III] is carried out in a solvent,
If necessary, it can be carried out in the presence of a deoxidizing agent. The solvent may be any inert solvent that does not adversely affect the reaction, for example, chloroform, dichloromethane, halogenated solvents such as dichloroethane, toluene, aromatic hydrocarbons such as xylene, tetrahydrofuran, dioxane, diethyl ether, 1, Ether solvents such as 2-dimethoxyethane, ketone solvents such as acetone and methyl ethyl ketone, ester solvents such as ethyl acetate and butyl acetate, pyridine, 2,6-lutidine, aromatic amine solvents such as collidine, dimethylformamide, Amide-based solvents such as dimethylacetamide and 1,3-dimethyl-2-imidazolidinone, mixed solvents of these solvents, and mixed solvents of these solvents and water can be suitably used. Examples of the deoxidizing agent include alkali metal carbonates such as potassium carbonate and sodium carbonate, alkali metal hydrogencarbonates such as sodium hydrogencarbonate, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, triethylamine, tributylamine, diisopropylethylamine and the like. Tri-lower alkylamine, 1,4-diazabicyclo [2.2.2] octane, 1,5-diazabicyclo [4.3.0] nona-5
Tertiary amines such as -ene, 1,8-diazabicyclo [5.4.0] undec-7-ene, pyridine, lutidine,
And aromatic amines such as collidine and dimethylaniline. The reaction can be carried out under cooling to heating, for example, -30C to 150C, especially -1C.
It proceeds favorably at 0 ° C. to room temperature.

Method (B): The oxidation of compound [IV] can be carried out according to a conventional method. For example, compound [IV] is treated with sodium 3-nitrobenzenesulfonate in a suitable solvent under basic conditions. Or by reacting it in a hydrogen bromide-acetic acid solution under redox conditions using dimethyl sulfoxide in an oxidation-reduction manner, or by subjecting it to halogenation with bromine or chlorine and then subjecting it to a dehydrohalogenation reaction. It can be suitably implemented.

As the solvent, water, acetic acid, propionic acid,
Trifluoroacetic acid, methanesulfonic acid or a hydrogen bromide-acetic acid solution can be suitably used.

When an optically active substance is used as the starting compound [II] or [IV] in the reaction of the present invention, the corresponding optically active target compound [I] can be obtained without racemization.

The starting compound [II] is a novel compound, for example, of the general formula [V]

[0031]

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(Wherein R ²¹ represents a hydrogen atom or a lower alkyl group, and the other symbols have the same meanings as described above). Formula [VI]

[0033]

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(Wherein R ³ represents an ester residue and Z represents a halogen atom), and the product is treated with hydrazine after removing the ester residue and the amino-protecting group. When R ²¹ is a hydrogen atom, the amino group may be further optionally substituted with, for example, a corresponding aldehyde compound and sodium borohydride (NaB
H ₄ ), sodium triacetoxyborohydride [Na
B (OCOCH ₃ ) ₃ H] and alkylation by a method such as subjecting to a reductive alkylation reaction in the presence of a suitable reducing agent to obtain a compound of the general formula [VII]

[0035]

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(Wherein the symbols have the same meanings as described above), and can be produced by oxidizing the compound in the same manner as in the method (B).

The starting compound [IV] is a compound [VII]
And the compound [III] in the same manner as in the method (A).

In the present specification, a lower alkyl group is
For example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, tert-
Those having 1 to 6 carbon atoms, such as butyl group, n-pentyl group, isopentyl group, neopentyl group, n-hexyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group and cyclohexyl group, preferably 1 to 4 carbon atoms Means The lower alkylene group includes, for example, methylene, ethylene, trimethylene, tetramethylene, pentamethylene,
It means those having 1 to 10 carbon atoms such as hexamethylene, heptamethylene and octamethylene, preferably those having 1 to 6 carbon atoms. Lower alkenyl groups include, for example, vinyl group, 1
2 to 2 carbon atoms such as propenyl, allyl, 1-methylallyl, 1 or 2 or 3-butenyl, 1 or 2 or 3 or 4-pentenyl, 1 or 2 or 3 or 4 or 5-hexenyl. Seven, preferably two to five. The acyl group means one having 2 to 7 carbon atoms, preferably 2 to 4 carbon atoms. Lower alkyl group, lower alkylene group, lower alkenyl group and acyl group include
Straight and branched ones are included.

[0039]

[Action]

Experimental Example (Effect on rat glomerulonephritis) Rabbit glomerular basement membrane fraction obtained from WKY rats was immunized with rabbits several times together with adjuvant, and then whole blood was collected to obtain nephrotoxin serum (NTS). This NTS was diluted 50-fold with physiological saline, and 2.5 ml / kg body weight was intravenously injected once into 8-week-old male WKY rats to induce nephritis. The normal group received the same amount of physiological saline intravenously.

In the experiment, one group consisted of 6 animals, and the test compound was suspended in purified water using a small amount of Tween 80 (manufactured by Nacalai Tesque), and a dose of 30 mg / kg / 10 ml was administered twice a day for 8 consecutive days. Oral administration. The same amount of purified water was orally administered to the normal group and the control group. On the 7th day, the rats were placed in metabolic cages, urine was collected for 24 hours, urine protein concentration was measured by the sulfosalicylic acid method, and protein excretion (mg /
D) and the protein excretion inhibition rate was calculated by the following equation.

[0041]

(Equation 1)

The results are as shown in Table 1. As is clear from Table 1, the protein excretion of the sample administration group was about 6% lower.
It was suppressed at a rate as high as 1 to 91%.

[0043]

[Table 1]

[0044]

EXAMPLES Example 1 3.22 g of 2-aminomethyl-5- [pyridazin-3 (2H) -one-6-yl] indane hydrobromide is suspended in a mixture of 30 ml of ethyl acetate and 30 ml of tetrahydrofuran. . To this suspension, an aqueous sodium carbonate solution (5.
30 g of water / 30 ml of water), and then, while cooling with ice, 3.32 g of ethanesulfonyl chloride in 10 m of tetrahydrofuran.
Add the solution and stir for 3 hours. 300 ml of ethyl acetate
, The organic layer is separated, washed with water and dried, and the solvent is distilled off. The residue was purified by silica gel column chromatography [chloroform-methanol (100: 3)].
2.75 g of-(ethylsulfonylaminomethyl) -5- [pyridazin-3 (2H) -one-6-yl] indan
Get. m. p. : 170-172 ° C.

Example 2-12 The corresponding starting compound was treated in the same manner as in Example 1 to obtain the compounds shown in Table 2.

[0046]

[Table 2]

Example 13 2- (propylsulfonylaminomethyl) -5- [4,
5-dihydropyridazin-3 (2H) -on-6-yl] indane in a suspension of 5.24 g of acetic acid in 60 ml of 30
% Hydrogen bromide-acetic acid 25 ml, dimethyl sulfoxide
Add 3 ml and stir at room temperature for 2 hours. 150 ml of isopropyl ether was added, and the precipitated crystals were collected by filtration, washed with water, dried, and recrystallized from methanol to give 2-
4.82 g of (propylsulfonylaminomethyl) -5- [pyridazin-3 (2H) -one-6-yl] indan
Get. The physicochemical properties of this product were consistent with those of Example 2.

Examples 14-18 By treating the corresponding starting compounds in the same manner as in Example 13, the compounds shown in Table 3 are obtained.

[0049]

[Table 3]

Examples 19 to 27 By treating the corresponding starting compounds in the same manner as in Example 1, the compounds shown in Table 4 are obtained.

[0051]

[Table 4]

Reference Example 1 (1) Oxalyl chloride 4 was added to a dichloroethane solution (840 ml) of 48.3 g of succinic acid monomethyl ester.
6.4 g and 2 drops of dimethylformamide are added and stirred at room temperature for 5 hours. Then, under ice-cooling, add 2
A solution of 34.6 g of (acetylaminomethyl) indane in dichloroethane (280 ml) and 97.6 g of anhydrous aluminum chloride are added. After stirring for 1 hour, the reaction solution is poured into ice water. The organic layer was separated, washed with water, dried, and the solvent was distilled off to give 2- (acetylaminomethyl) -5- (3
-Methoxycarbonylpropionyl) indane 51.8
g.

M. p. 139-140 ° C (2) 51.8 g of this product are suspended in 10 N hydrochloric acid (800 ml) and heated under reflux overnight. After concentrating the reaction solution and allowing it to cool,
The precipitated crystals (48.5 g) are collected by filtration. Acetic acid 3
Hydrazine monohydrate (30 g),
Heat to reflux for 4 hours. After cooling, diethyl ether is added, and the precipitated crystals are collected by filtration. The obtained crystals were suspended in water and adjusted to pH 9 with a 10% aqueous sodium hydroxide solution.
Extract with chloroform. After the organic layer is washed with water and dried, the solvent is distilled off. The residue was recrystallized from methanol to give 2-aminomethyl-5- [4,5-dihydropyridazin-3 (2H) -one-6-yl] indan 35.3.
g.

M. p. : 170-171 ° C (3) 4.90 g of this product is suspended in 20 ml of acetic acid, and 30%
1. Hydrogen bromide-acetic acid 50 ml and dimethyl sulfoxide
Add 8 g and stir for 3 hours. Isopropyl ether 3
After adding 00 ml, the precipitated crystals are collected by filtration. The resulting crude crystals were recrystallized from methanol to give 2-aminomethyl-5- [pyridazin-3 (2H) -one-6-.
Yl] indane hydrobromide.

M. p. Reference Example 2 (1) 2- [2- (acetylamino) ethyl] indane was treated in the same manner as in Reference Example 1- (1) to give 2-
[2- (Acetylamino) ethyl] -5- (3-methoxycarbonylpropionyl) indane is obtained. m.
p. : 96-97 ° C.

(2) This product was treated in the same manner as in Reference Example 1- (2) to give 2- (2-aminoethyl) -5-
[4,5-dihydropyridazine-3 (2H) -one-6
-Ill] Get Indan. m. p. 189-190
° C.

(3) This product was treated in the same manner as in Reference Example 1- (3) to give 2- (2-aminoethyl) -5-
[Pyridazin-3 (2H) -one-6-yl] indane hydrobromide is obtained. m. p. : 279-280 ° C (decomposition).

Reference Example 3 (1) A solution of 19.34 g of 2-indaneacetic acid ethyl ester in 200 ml of toluene was cooled to -78.degree.
Of a solution of diisobutylaluminum hydride (DIBAH) in toluene (65 ml) is added, and the mixture is stirred at the same temperature for 1.5 hours. A 15% aqueous sodium sulfite solution is added, the organic layer is separated, washed, dried, and the solvent is distilled off. The residue is purified by silica gel column chromatography [hexane-ethyl acetate (10: 1)] to obtain 13.58 g of 2-indaneacetaldehyde. IR (neat) cm ^-1 : 172
5, FAB-MS (m / Z): 161 (MH ^<+> ).

(2) 3.90 g of 63% sodium hydride
Is suspended in 60 ml of tetrahydrofuran, a solution of 22.8 g of diethyl phosphonoacetic acid ethyl ester in 100 ml of tetrahydrofuran is added dropwise under cooling with water, and the mixture is stirred at the same temperature for 30 minutes. To this mixture, add 2-indaneacetaldehyde 1
A solution of 3.58 g of tetrahydrofuran in 100 ml is added dropwise, and the mixture is stirred at the same temperature for 1 hour and further at room temperature for 1 hour.
The reaction solution is poured into ice water and extracted with ethyl acetate. After washing and drying the ethyl acetate layer, the solvent is distilled off. The residue is purified by silica gel column chromatography [hexane-ethyl acetate (20: 1)] to obtain 19.22 g of ethyl 2-indanecrotonate. IR (neat) cm ^-1 :
1700, 1655, FAB-MS (m / Z): 231 (MH
⁺ ).

(3) This product 19.22 g of ethanol 20
2.0 g of 10% palladium-carbon was added to the 0 ml solution,
The catalytic hydrogenation is performed at room temperature and normal pressure. After 1.5 hours, the catalyst was removed, and ethanol was distilled off to obtain 19.24 g of 2-indanebutyric acid ethyl ester. IR (neat) cm ^-1 : 174
0, MS (m / Z): 232 (M ⁺ ).

(4) This product 19.21 g of ethanol 50
An aqueous sodium hydroxide solution (5.15 g / 30 ml of water) is added to the ml solution, and the mixture is stirred at room temperature for 1 hour. Ethanol is distilled off, the aqueous layer is made weakly acidic with 10% hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed and dried, and the solvent was distilled off to obtain 16.87 g of 2-indanebutyric acid. m. p.
74-75 ° C.

(5) To a solution of 16.84 g of this product and 11.67 g of oxalyl chloride in 200 ml of tetrahydrofuran are added 3 drops of dimethylformamide, and the mixture is stirred for 1.5 hours. The solvent and excess oxalyl chloride are distilled off. The residue was dissolved in 10 ml of tetrahydrofuran, cooled on ice,
It is added dropwise to 100 ml of an 8% aqueous ammonia solution. The mixture was stirred at the same temperature for 2 hours, and the formed crystals were collected by filtration, washed with water and dried to obtain 14.46 g of 2-indanebutyric acid amide. m.
p. 116-118 ° C.

(6) Lithium aluminum hydride 3.2
To a suspension of 3 g of tetrahydrofuran in 200 ml was added 14.42 g of 2-indanebutyramide under ice cooling.
Heat to reflux for 5 hours. After cooling, a 50% aqueous solution of Rochelle salt is added, and the precipitated insoluble matter is collected by filtration. The filtrate is concentrated to dryness. The residue was dissolved in 50 ml of tetrahydrofuran, hydrogen chloride-dioxane was added, and the precipitated crystals were collected by filtration.
12.82 g of-(4-aminobutyl) indane hydrochloride are obtained. m. p. 184-186 ° C.

(7) To a suspension of 12.74 g of this product and 13.91 g of triethylamine in 100 ml of dichloromethane,
Under ice-cooling, 5.42 g of acetyl chloride in dichloromethane 20
The solution was added dropwise and stirred at the same temperature for 1 hour. After washing and drying the reaction solution, the solvent is distilled off. The obtained crude crystals were recrystallized from ethyl acetate-isopropyl ether to give 2- (4
-Acetylaminobutyl) indane 12.0 g are obtained.
m. p. 83-84 ° C.

(8) This product was treated in the same manner as in Reference Example 1- (1) to give 2- (4-acetylaminobutyl).
-5- (3-Methoxycarbonylpropionyl) indane is obtained. m. p. : 94-95 ° C.

(9) This product was treated in the same manner as in Reference Example 1- (2) to give 2- (4-aminobutyl) -5-
[4,5-dihydropyridazine-3 (2H) -one-6
-Ill] Get Indan. m. p. : 153-155
° C.

(10) This product was treated in the same manner as in Reference Example 1- (3) to give 2- (4-aminobutyl) -5-
[Pyridazin-3 (2H) -on-6-yl] indan is obtained. m. p. : 279-281 [deg.] C.

Reference Example 4 (1) 2-Aminomethyl-5- [4,5-dihydropyridazin-3 (2H) -one-6-yl] indane 6.1
A methanol solution (5 ml) of propanal (1.51 g) was dropped into a methanol solution (60 ml) of 5 g,
Stir at room temperature for 30 minutes. Then, under ice-cooling, 1.03 g of sodium borohydride was added, and the mixture was added at the same temperature for 20 minutes and at room temperature for 1 minute.
Stir for hours. Methanol is distilled off, water is added to the residue,
Extract with ethyl acetate. After the organic layer is washed with water and dried, the solvent is distilled off. The residue was purified by silica gel column chromatography [solvent; chloroform-methanol (15: 1)] to give 2- (propylaminomethyl) -5.
-[4,5-dihydropyridazin-3 (2H) -one-
6-yl] indane (5.22 g) is obtained. m. p. : 82
-84 ° C.

(2) 5.08 g of this product was used in Reference Example 1- (3)
To give 2- (propylamino) methyl-5
-[Pyridazin-3 (2H) -one-6-yl] indan hydrobromide (4.52 g) was obtained and then treated with 10% aqueous sodium hydroxide to give 2- (propylaminomethyl). -5- [pyridazine-3 (2H)
-On-6-yl] indane (3.13 g) are obtained. m.
p. 144-146 ° C.

Reference Example 5 (1) 2- (2-Aminoethyl) -5- [4,5-dihydropyridazin-3 (2H) -one-6-yl] indane was prepared in the same manner as in Reference Example 4- (1). To 2- [2-
(Propylamino) ethyl] -5- [4,5-dihydropyridazin-3 (2H) -one-6-yl] indane is obtained. m. p. : 123-124 ° C.

(2) This product was treated in the same manner as in Reference Example 1- (3) to give 2- [2- (propylamino) ethyl] -5-
[Pyridazin-3 (2H) -on-6-yl] indan hydrobromide is obtained and then treated with a 10% aqueous sodium hydroxide solution to give 2- [2- (propylamino) ethyl] -5. -[Pyridazine-3 (2H) -one-
6-yl] indane. m. p. : 150-151
° C.

Reference Example 6 2-aminomethyl-5- [4,5-dihydropyridazin-3 (2H) -one-6-yl] indane 6.03 g of 1,3-dimethyl-2-imidazolidinone in 60 ml was suspended. 5.53 g of triethylamine are added to the suspension, followed by a solution of 5.10 g of propanesulfonyl chloride in 20 ml of tetrahydrofuran. The mixture is stirred at room temperature for 30 minutes. The reaction solution is poured into ice water, and the precipitated crystals are collected by filtration. The precipitated crystals were recrystallized from methanol-acetonitrile to give 2- (propylsulfonylaminomethyl) -5-
[4,5-dihydropyridazine-3 (2H) -one-6
-Yl] indane (5.34 g). m. p. : 158
-159 ° C.

Reference Examples 7-13 By treating the corresponding starting compounds in the same manner as in Reference Example 6, the compounds shown in Table 5 are obtained.

[0074]

[Table 5]

[0075]

The indane derivative [I] and the pharmaceutically acceptable salt thereof, which are the object of the present invention, have an excellent endotoxin shock protective effect and / or a therapeutic effect on nephritis. It is useful as a therapeutic agent for endotoxin shock or a therapeutic agent for nephritis that develops in patients with severe infections.

The objective compound [I] of the present invention has low toxicity and high safety as a medicine.

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int. Cl. ⁶ , DB name) C07D 237/14 C07D 401/12 A61K 31/50 CA (STN) REGISTRY (STN) WPIDS (STN)

Claims (6)

(57) [Claims] 1. A compound of the general formula [I] (Wherein, R ¹ is a lower alkyl group, a lower alkenyl group or a monocyclic heteroaromatic group which contains a nitrogen atom as a hetero atom and may have a substituent, and R ² is a hydrogen atom or a lower alkyl group. , A represents a lower alkylene group.) Or a pharmaceutically acceptable salt thereof. 2. The compound according to claim 1, wherein R ¹ is a lower alkyl group, a lower alkenyl group or a pyridyl group. 3. The compound according to claim 1, wherein R ² is a hydrogen atom. 4. The compound according to claim 1, wherein R ² is a lower alkyl group. 5. A compound of the general formula [II] (Wherein, R ² represents a hydrogen atom or a lower alkyl group, and A represents a lower alkylene group) or a salt thereof and a general formula [III] (In the formula, R ¹ is a lower alkyl group, a lower alkenyl group, or a monocyclic heteroaromatic group which contains a nitrogen atom as a hetero atom and may have a substituent, and X represents a reactive residue. (I) wherein the product is converted into a pharmaceutically acceptable salt thereof, if desired, by reacting the compound with a sulfonic acid compound represented by the formula (I): (Wherein the symbols have the same meanings as described above.) Or a pharmacologically acceptable salt thereof. 6. A compound of the general formula [IV] (Wherein, R ¹ is a lower alkyl group, a lower alkenyl group or a monocyclic heteroaromatic group which contains a nitrogen atom as a hetero atom and may have a substituent, and R ² is a hydrogen atom or a lower alkyl group. , A represents a lower alkylene group), and the compound represented by the general formula [I] is oxidized to give, if desired, a pharmacologically acceptable salt thereof. Wherein the symbols have the same meanings as described above, or a method for producing a pharmacologically acceptable salt thereof.