JP2986652B2 - Amino alcohol derivatives and uses thereof - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION The present invention relates to the treatment of diseases such as cerebral palsy as a main symptom, painful muscle spasm associated with musculoskeletal diseases, and frequent diseases such as neuropathic bladder and unstable bladder. The present invention relates to an amino alcohol derivative and a physiologically acceptable salt thereof which are also effective in improving urine symptoms. The present invention also relates to a therapeutic agent for the above-mentioned diseases, comprising at least one of these compounds as an active ingredient.

[0002]

2. Description of the Prior Art Tolperisone hydrochloride, eperisone hydrochloride, tizanidine and the like are conventionally known as drugs having a muscle relaxing action. However, it is not known that the amino alcohol derivative represented by the general formula (I) of the present invention itself has a muscle relaxing action.

[0003]

At present, tolperisone hydrochloride, eperisone hydrochloride and tizanidine are widely used for the treatment of diseases having a main symptom of cerebral palsy. However, they have problems such as insufficient strength of action, short duration, and a central inhibitory action. An object of the present invention is to provide a useful muscle relaxant having a strong muscle relaxing action, a long lasting action and low side effects by using an amino alcohol derivative represented by the general formula (I) or a physiologically acceptable salt thereof. To provide. Another object of the present invention is to provide a compound of the formula (I)
It is an object of the present invention to provide a therapeutic agent for pollakiuria using an amino alcohol derivative represented by the formula or a physiologically acceptable salt thereof.

[0004]

The muscle relaxant according to the present invention
Used as an active ingredient in and therapeutic agents for pollakiuria
The coal derivative is a compound represented by the following general formula (I).
is there. Further, the amino alcohol derivative of the present invention is as follows:
Among the compounds represented by the general formula (I), R ₁ has ₁ carbon atom
A compound which is an alkyl group of (1) to (4 ).

[0005]

Embedded image (Wherein, R ₁ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₂ and R ₃ each independently represent an alkyl group having 1 to 4 carbon atoms, or an alicyclic group together with a nitrogen atom. The amino alcohol derivative of the present invention represented by the above general formula (I) and a physiologically acceptable salt thereof exhibit excellent muscle relaxing action and urination-suppressing action, and form a 5- or 6-membered ring. It has low side effects and is extremely useful as an active ingredient of muscle relaxants and remedies for pollakiuria.

The amino alcohol derivative represented by the general formula (I) has two asymmetric carbon atoms in the molecule, and thus has four types of optical isomers, all of which are included in the present invention. It is what is done.

The acid capable of forming a physiologically acceptable salt (acid addition salt) of the amino alcohol derivative of the present invention is not particularly limited as long as it is physiologically acceptable. For example, hydrochloric acid, sulfuric acid, Examples thereof include inorganic acid salts from phosphoric acid and the like, and organic acid salts formed from acetic acid, citric acid, succinic acid, maleic acid, fumaric acid, tartaric acid, methanesulfonic acid, lactic acid and the like. The formation of the acid addition salt can be carried out by reacting the amino alcohol derivative with a desired acid in an organic solvent such as water or alcohol or a mixture thereof.

The amino alcohol derivative of the present invention can be generally produced by a method having the following reaction steps (a) and (b).

[0009]

Embedded image

[0010]

Embedded image The reaction step (a) is carried out, for example, in
75 and Japanese Patent Application Laid-Open No. 4-2109745. The reaction (b) can be carried out at a reaction temperature of 0 to 100 ° C. using alcohol as a solvent. Desirable alcohols include methanol or ethanol, and a desirable reaction temperature is a temperature in the range of 10 to 40C.

A muscle relaxant and a therapeutic agent for pollakiuria can be formed using at least one of the amino alcohol derivative of the present invention and a physiologically acceptable salt thereof as an active ingredient.
The dosage for a patient depends on the condition to be treated and the method of administration, but is usually 5 to 1000 mg, preferably 50 to 300 mg per day for an adult.

[0012] The dosage form can be made into oral preparations such as capsules, tablets, fine granules, syrups and powders, or parenterally administered as injections, suppositories, paints and the like. .

As additives for pharmaceuticals, excipients (lactose, corn starch, sugar, sorbite, calcium phosphate, etc.), binders (syrup, gum arabic, gelatin, sorbite, polyvinylpyrrolidone, hydroxypropylcellulose, etc.), lubricants (Magnesium stearate, talc, polyethylene glycol, silica, etc.), disintegrants (potato starch, carboxymethyl cellulose, etc.), wetting agents (sodium laurate) and the like can be appropriately used according to the dosage form.

[0014]

Industrial Applicability The amino alcohol derivative of the present invention and a physiologically acceptable salt thereof have excellent muscle relaxing action, spinal cord reflex inhibitory action, anti-calendar action, etc., and have low back pain, intervertebral disc herniation. It is extremely useful as an active ingredient of a therapeutic agent for silicic palsy caused by diseases such as cervical and shoulder arm syndrome and cerebrovascular disorder, cerebral cerebral palsy and cerebral palsy.

Further, the amino alcohol derivative of the present invention and a physiologically acceptable salt thereof have an effect of suppressing urinary reflex, and are useful as an active ingredient of a therapeutic agent for pollakiuria.

[0016]

The compounds of the present invention will be specifically described below with reference to Reference Examples and Examples.

Reference Example 1 [Production of 3-phenyl-5-propionyl isoxazole] 2.5 g of benzaldoxime (20.7 mmol)
l), 2.1 g of 1-pentyn-3-ol (25 mmol
l) was dissolved in 12.5 ml of dichloromethane. The reaction solution was ice-cooled, and a 12% aqueous sodium hypochlorite solution was added dropwise while maintaining the internal temperature at 15 to 25 ° C. such that the amount of the compound added became 14.5 g (25 mol). After completion of the dropwise addition, the mixture was stirred for 3 hours while maintaining the internal temperature at 15 to 25 ° C.

To this reaction solution, a 12% aqueous solution of sodium hypochlorite was added in an amount of 39.0 g (63 mmol).
1). The internal temperature of the reaction solution was cooled to 10 ° C, and 0.7 g (6.1 m) of pyridine hydrochloride was stirred with stirring.
mol) in 3 ml of water was added dropwise over 20 minutes. After completion of the dropwise addition, the reaction solution was stirred for 70 minutes.
Separate the reaction solution , take the lower phase dichloromethane solution,
25 ml of a 5% aqueous sodium sulfite solution was added, and the mixture was stirred for 30 minutes. The mixture is separated and the dichloromethane phase is
The solution was washed with 25 ml of a 1N aqueous hydrochloric acid solution. Next, the washed dichloromethane phase was separated, concentrated under reduced pressure, and the obtained residue was recrystallized from 10 ml of methanol to obtain 3.0 g of 3-phenyl-5-propionyl isoxazole (1 g).
4.9 mmol, 72.0% yield).

Reference Example 2 [Production of 3-phenyl-5- {2- (1-piperidinylmethyl) propionyl} isoxazole] 2.0 g of 3-phenyl-5-propionylisoxazole (1
0 mmol) and 1.7 g (20 mmol) of piperidine.
Was added to 10 ml of ethyl alcohol. 1.63 m of a 37% formaldehyde aqueous solution was added to the obtained solution under ice cooling.
1 (20 mmol) was added dropwise, and the mixture was stirred at room temperature for 2 hours.
The reaction solution was concentrated under reduced pressure, and the obtained residue was treated with ethyl ether 3
Dissolved in 0 ml. The resulting ether solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 2.3 g of 3-phenyl-5- {2- (1-piperidinylmethyl) propionyl}. White crystals of isoxazole were obtained. Example 1 [Production of 5- {1-hydroxy-2- (1-piperidinylmethyl) propyl} -3-phenylisoxazole] 3-phenyl-5- {2- (1- 1.5 g of piperidinylmethyl) propionyl diisoxazole was dissolved in 15 ml of methanol. After adding 54 mg of sodium borohydride to the obtained solution and stirring at 60 ° C. for 1 hour, the reaction solution was cooled and neutralized with acetic acid. After neutralization, the reaction solution was concentrated under reduced pressure, and 15 ml of water was added.
Extracted with 0 ml. After the ethyl acetate phase was dried over sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was applied to a silica gel column and purified with a mixed solution of chloroform / methanol (volume ratio: 80:20). The eluted fractions were collected and the solvent was distilled off under reduced pressure to give 5- {1-hydroxy-2
1.3 g of an oily substance of-(1-piperidinylmethyl) propyl} -3-phenylisoxazole (yield: 78.0)
%). Analysis results of the obtained compound: NMR (d _ppm , CDCl ₃ ): 0.8 to 1.3 (3H,
m); 1.4-2.0 (6H, m); 2.2-3.0
(7H, m); 4.6-5.1 (1H, s); 6.7
(1H, m); 7.3 (1H, s); 7.3 to 7.7.
(3H, m); 7.8 to 8.0 (2H, m) Example 2 [5- {1-hydroxy-2- (1-piperidinylmethyl) propyl} -3-phenylisoxazole hydrochloride ( Production of Compound 1)] 5- {1-hydroxy-2- (1
1.0 g of -piperidinylmethyl) propyl} -3-phenylisoxazole was dissolved in 10 ml of ethyl ether, and 1 ml of 8N hydrochloric acid in ethanol was added thereto.
The obtained solution was concentrated under reduced pressure, and the residue was dried under reduced pressure to give 5-
1.1 g of {1-hydroxy-2- (1-piperidinylmethyl) propyl} -3-phenylisoxazole hydrochloride (Compound 1) was obtained. Analysis result of the obtained compound: Melting point: 174 to 176 ° C. Reference Example 3 [Production of 3-phenyl-5-butyrylisoxazole] 10 g (0.082 mol) of benzaldoxime and 9 g of 1-hexyn-3-ol ( 0.092 mol)
Was dissolved in 50 ml of dichloromethane. The reaction solution was cooled with ice, and a 12% aqueous sodium hypochlorite solution was added at an internal temperature of 15 g such that the amount of the compound added became 58 g (0.10 mol).
The solution was added dropwise while maintaining the temperature at ２５25 ° C. After dropping, the internal temperature is reduced to 1
The mixture was stirred for 3 hours while maintaining the temperature at 5 to 25 ° C.

To this reaction solution, a 12% aqueous solution of sodium hypochlorite was added dropwise so that the amount of the compound added became 156 g. The internal temperature of the reaction solution was cooled to 10 ° C, and the whole amount of a solution obtained by dissolving 2.8 g of pyridine hydrochloride in 12 ml of water was added dropwise with stirring while maintaining the reaction temperature at 15 to 20 ° C. After completion of the dropwise addition, the reaction solution was stirred for 70 minutes. The reaction solution was separated, the dichloromethane solution of the lower phase was taken , 100 ml of a 5% aqueous sodium bisulfite solution was added, and the mixture was stirred for 30 minutes. The mixture is separated, and the dichloromethane phase is washed with 100 m of water.
1 and 100 ml of a 1N aqueous hydrochloric acid solution. The washed dichloromethane phase was separated and concentrated under reduced pressure. The obtained residue was recrystallized from 40 ml of methanol to obtain 10.6 g of 3-phenyl-5-butyrylisoxazole (yield 5).
9.6%). Analysis result of the obtained compound: Melting point: 89 to 90 ° C. Reference Example 4 [Production of 3-phenyl-5- {2- (1-pyrrolidinylmethyl) butyryl} isoxazole] 3-phenyl-5-butyryl 20 g of isoxazole
(93 mmol) and 7.93 g of pyrrolidine (111 m
ol) was added to 62 g of methanol. The obtained reaction solution was stirred, and while maintaining the internal temperature at 20 to 30 ° C, 37
% Formalin aqueous solution was added in an amount of 9.04 g.
(111 mmol). After completion of the dropwise addition, the mixture was stirred for 1 hour while maintaining the internal temperature at 20 to 30 ° C.
The reaction solution was taken in a separating funnel, and 178 g of butyl acetate was added and stirred. After liquid separation, the organic phase was collected, washed with 50 ml of water three times, and dried over sodium sulfate. The solvent was distilled off from the organic phase under reduced pressure to give 3-phenyl-5- {2- (1
20.3 g of white crystals of (pyrrolidinylmethyl) butyryl} isoxazole were obtained. (Yield 73%) Analysis result of the obtained compound: Melting point: 68-69 ° C. Example 3 [5- {1-hydroxy-2- (1-pyrrolidinylmethyl) butyl] -3-phenylisoxazole hydrochloride Production of Salt (Compound 2)] 3-Phenyl-5- {2- (1-pyrrolidinylmethyl)
Butyryl diisoxazole 6.9 g (23 mmol)
Was dissolved in 100 ml of ethanol. In the resulting solution,
0.97 g of sodium borohydride was gradually added at room temperature, followed by stirring at room temperature for 2 hours. After adding 20 ml of acetone to the obtained reaction mixture, the solvent was distilled off under reduced pressure.
150 ml of water was added to the residue and stirred. After stirring, 20 ml of diethyl ether was added for extraction. The organic phase was taken and washed twice with 100 ml of water and once with 100 ml of saturated saline. The washed organic phase was dried with anhydrous sodium sulfate. Next, sodium sulfate is filtered off from the organic phase,
The filtrate was evaporated under reduced pressure to give 5- {1-hydroxy-2- (1
-Pyrrolidinylmethyl) butyryl} -3-phenylisoxazole was obtained as an oil. The oil was applied to a silica gel column and eluted with a mixed solvent of chloroform / methanol / ethyl acetate (volume ratio: 10: 1: 1). The first fraction was collected and the solvent was distilled off under reduced pressure. 150 ml of water was added to the concentrated residue, and the mixture was neutralized with an aqueous sodium carbonate solution. Ethyl ether was added to the resulting solution for extraction. The organic phase was separated and washed with water and aqueous sodium carbonate solution. The washed organic phase was separated, dried over anhydrous aluminum sulfate, and the solvent was distilled off under reduced pressure to obtain an oily residue. This oily substance was dissolved in 15 ml of methanol, and an excess of a 10% methanolic hydrochloric acid solution was added with stirring. The reaction solution was concentrated under reduced pressure. The residue was dried under reduced pressure at room temperature,
1.3 g of 5- {1-hydroxy-2- (1-pyrrolidinylmethyl) butyl} -3-phenylisoxazole hydrochloride was obtained. Analysis result of the obtained compound: Melting point: 102 to 104 ° C. Reference Example 5 [(R) -3-phenyl-5- {2- (1-pyrrolidinylmethyl) butyryl} isoxazole L-camphorsulfonic acid salt Production] 3-phenyl-5- {2- (1-pyrrolidinylmethyl)
20 g of butyryl diisoxazole is added to 150 ml of ethyl acetate.
Then, 43.7 g of L-camphorsulfonic acid was added, and the mixture was heated to 50 to 60 ° C. and dissolved. The reaction was cooled to 10 ° C. with stirring. The crystals precipitated by cooling were collected by filtration and washed with ethyl acetate. The crystals were dried under reduced pressure to obtain 21.3 g of L-camphorsulfonic acid salt of (R) -3-phenyl-5- {2- (1-pyrrolidinylmethyl) butyryl} isoxazole. Analysis result of the obtained compound: Optical purity: 98.7% ee Melting point: 115.8 to 116.3 ° C. [α] ²⁰ _D = 14.4 ° (C = 0.5, ethanol) Reference Example 6 [ Production of (R) -3-phenyl-5- {2- (1-pyrrolidinylmethyl) butyryl} isoxazole hydrochloride] (R) -3-phenyl-5- {2- (1-pyrrolidinylmethyl) ) 20 g of L-camphorsulfonate of butyryl diisoxazole was added to 150 ml of water and 150 ml of chloroform.
The mixture was added to the mixture and stirred. 97 ml of a 10% aqueous sodium carbonate solution was added dropwise to this mixture. Reaction solution is 10
After stirring for minutes, liquid separation was performed to obtain an organic phase. The obtained organic phase was washed with a 10% aqueous solution of sodium carbonate and water in that order.
While maintaining the internal temperature at 10 ° C. or lower, 90 ml of a 2N aqueous hydrochloric acid solution was added dropwise to the organic phase. The organic phase obtained by liquid separation was dried over sodium sulfate. Sodium sulfate was removed by filtration from the organic phase, and 300 ml of ethyl acetate was gradually added with stirring while cooling the filtrate to 5 ° C. The precipitated crystals are collected by filtration,
Washed with a small amount of ethyl acetate. The crystals are dried under reduced pressure to give the desired (R) -3-phenyl-5- {2- (1-pyrrolidinylmethyl) butyryl} isoxazole hydrochloride.
5 g were obtained. Analysis result of the obtained compound: melting point: 158 to 159.5 ° C. [α] ²⁰ _D = + 29 ° (C = 0.5, water) Example 4 [(1R, 2R) -5- {1-hydroxy- 2- (1-
Preparation of (pyrrolidinylmethyl) butyl} -3-phenylisoxazole hydrochloride ( compound 3 ) 7 g of (R) -3-phenyl-5- {2- (1-pyrrolidinylmethyl) butyryl} isoxazole in ethanol Dissolved in 100 ml. After 1.0 g of sodium borohydride was gradually added to the obtained solution at room temperature, the mixture was stirred at room temperature for 2 hours. After further adding 20 ml of acetone to the reaction mixture, the solvent was distilled off under reduced pressure.
Was added and stirred. The obtained reaction solution was extracted with 20 ml of diethyl ether. Take the organic phase and water 100m
The mixture was washed twice with 1 and once with 100 ml of a saturated saline solution. The washed organic phase was further dried with anhydrous sodium sulfate. The anhydrous sodium sulfate was filtered off, and the filtrate was distilled off under reduced pressure to give 5-
Optical isomer R of {1-hydroxy-2- (1-pyrrolidinylmethyl) butyl} -3-phenylisoxazole
A mixture of R and SR was obtained as an oil.

This oily substance was applied to a silica gel column, and chloroform / methanol / ethyl acetate (volume ratio: 10:
1: 1) Elution with a mixed solvent. The third of three organic-containing fractions was taken and the solvent was distilled off under reduced pressure. 150 ml of water was added to the concentrated residue of the third fraction, and the mixture was neutralized with an aqueous sodium carbonate solution. 150 ml of ethyl ether was added to the obtained solution for extraction. The organic phase was separated and washed with water and aqueous sodium carbonate solution. The washed organic phase was separated and dried over anhydrous aluminum sulfate. The solvent was distilled off from the dried organic phase under reduced pressure to obtain 0.99 g of an oily residue. This oil was purified by eluting with chloroform on a silica gel column. Analysis results of the obtained compound: NMR (d _ppm , CDCl ₃ ): 0.8 to 0.9 (3H,
m); 1.1 to 1.2 (1H, m); 1.3 to 1.4
(1H, m); 1.7 to 1.9 (3H, m); 2.0 to
2.1 (1H, m); 2.5-3.0 (6H, m);
4.8-4.9 (1H, d); 6.6 (1H, s);
7.3 (1H, s); 7.4-7.5 (2H, m);
7.8-7.9 (2H, m) Further, according to the method of Example 3, white amorphous hydrochloride 1.05
g was obtained.

Example 5 [(1S, 2R) -5- {1-hydroxy-2- (1-
Preparation of pyrrolidinylmethyl) butyl} -3-phenylisoxazole hydrochloride (Compound 4)] The solvent was distilled off from the first fraction obtained from the silica gel column of Example 4 under reduced pressure, and the obtained concentration was concentrated. 150 ml of water was added to the residue, and an aqueous sodium carbonate solution was further added to make the residue neutral.
150 ml of ethyl ether was added to the obtained solution for extraction. The organic phase was separated and washed with water and an aqueous solution of sodium carbonate. After the washed organic phase was dried over anhydrous aluminum sulfate, the solvent was distilled off under reduced pressure to give (1S, 2R) -5.
-{1-hydroxy-2- (1-pyrrolidinylmethyl)
1.7 g of white crystals of butyl {-3-phenylisoxazole were obtained. Analysis result of the obtained compound: melting point: 70 to 71 ° C. NMR (d _ppm , CDCl ₃ ): 0.9 to 1.1 (3H,
m); 1.1 to 1.2 (1H, m); 1.2 to 1.4
(1H, m); 1.7 to 1.9 (4H, m); 2.2 to
2.9 (6H, m); 5.0-5.1 (1H, d);
6.5 (1H, s); 7.2 (1H, s); 7.4-
7.5 (2H, m); 7.8 to 7.9 (2H, m) The hydrochloride was synthesized from this compound according to the method of Example 3.

Reference Example 7 [Production of (S) -3-phenyl-5-{(2-pyrrolidinylmethyl) butyryl} isoxazole hydrochloride] D-Camphorsulfonic acid was prepared in the same manner as in Reference Examples 5 and 6. 10 g of 3-phenyl-5- {2- (1-pyrrolidinylmethyl) butyryl} isoxazole was subjected to optical resolution to obtain 3.7 g of the (S) form. (Yield 37%) Analysis result of the obtained compound: Optical purity 99.8% ee Example 6 [(1S, 2S) -3-phenyl-5- {1-hydroxy-2- (1-pyrrolidinyl) butyl] {Production of isoxazole hydrochloride] (S) -3-
Phenyl-5- {2- (1-pyrrolidinylmethyl) butyryl} isoxazole was reduced with sodium borohydride, and the (1S, 2S) form was separated using a column. Analysis results of the obtained compound: _{mp: 41.7~42.4 ℃ NMR (d ppm,} CDCl 3): 0.8~0.9 (3H,
m); 1.1 to 1.2 (1H, m); 1.3 to 1.4
(1H, m); 1.7 to 1.9 (3H, m); 2.0 to
2.1 (1H, m); 2.5-3.0 (6H, m);
4.8-4.9 (1H, d); 6.6 (1H, s);
7.3 (1H, s); 7.4-7.5 (2H, m);
7.8-7.9 (2H, m) Further, the hydrochloride of this compound was synthesized according to Example 3.

Example 7 [Production of (1R, 2S) -3-phenyl-5- {1-hydroxy-2- (1-pyrrolidinyl) butyl} isoxazole hydrochloride] (S) was prepared in the same manner as in Example 4. -3-Phenyl-5- {2- (1-pyrrolidinylmethyl) butyryl} isoxazole was reduced with sodium borohydride, and the (1R,
2S) The body was separated. Analysis results of the obtained compound: melting point: 69.4-70.2 ° C. NMR (d _ppm , CDCl ₃ ): 0.9-1.1 (3H,
m); 1.1 to 1.2 (1H, m); 1.2 to 1.4
(1H, m); 1.7 to 1.9 (4H, m); 2.2 to
2.9 (6H, m); 5.0-5.1 (1H, d);
6.5 (1H, s); 7.2 (1H, s); 7.4-
7.5 (2H, m); 7.8 to 7.9 (2H, m) Further, the hydrochloride was synthesized according to Example 3.

Example 8 [Central muscle relaxation action test] The central muscle relaxation action of the isoxazole derivative of the present invention was evaluated using a rat decerebrate rigidity model. Male Wistar rats (body weight 300-3)
50 g) was used in groups of 3-5. Under ether anesthesia, the site corresponding to the area between the superior and inferior colliculus of the rat brain was electrically destroyed to create a rigidity model (H. Ono eta).
l. , General Pharmacol. 18,5
7 (1987)). After the appearance of rigidity, the test compound was administered intravenously, and changes in the rigidity were observed. The test compound was intravenously administered at 3 mg / kg. Table 1 shows the results
It was shown to.

Example 7 [Urine voiding reflex inhibitory test] Male Wistar rats (body weight 300-350 g) were used in groups of three. Urethane 1.5 g / kg was administered subcutaneously, and a balloon catheter was inserted into the bladder. 0.25 to 0.5 ml of distilled water was injected into the balloon, and the change in the intravesical pressure caused by the automatic movement of the bladder which occurred at this time was recorded. 3 mg / kg of the test compound was administered through the common jugular vein, and the effect of the test compound was represented by the disappearance time of the bladder reflex caused by the voiding reflex. Table 1 shows the results
It was shown to.

Example 9 [Acute toxicity test] Male ddy mice (body weight 25-30)
g) was used in groups of 10 animals. The test compound was administered intravenously and the number of mice that died within 7 days was counted. 50%
Lethal dose LD ₅₀ (mg / kg) was calculated. The results are shown in Table 1. As a control, only a solvent for preparing a solution for administration of the test compound was administered.

[0028]

[Table 1]

──────────────────────────────────────────────────続 き Continuation of front page (56) References Med. Chem. , 10 (3), 411-18 (1967) (58) Fields investigated (Int. Cl. ⁶ , DB name) CAPLUS (STN) REGISTRY (STN)

Claims (5)

(57) [Claims] 1. The following general formula (Ia) : ( Wherein , R ₁ represents an alkyl group having 1 to 4 carbon atoms, R ₂ and R ₃ each independently represent an alkyl group having 1 to 4 carbon atoms, or an alicyclic 5-membered ring together with a nitrogen atom.) Or a 6-membered ring) and a physiologically acceptable salt thereof. 2. The amino alcohol derivative and the physiologically acceptable salt thereof according to claim 1, wherein R ₁ is an ethyl group, and R ₂ and R ₃ form a pyrrolidine ring together with a nitrogen atom. 3. The amino alcohol derivative according to claim 1, wherein R ₁ is a methyl group, and R ₂ and R ₃ together with a nitrogen atom form a piperidine ring, and a physiologically acceptable salt thereof. Wherein the following general formula (I): 5] (Wherein R ₁ is a hydrogen atom or an alkyl having 1 to 4 carbon atoms)
R ₂ and R ₃ each independently have 1 to 4 carbon atoms
Or an alicyclic 5-membered ring together with a nitrogen atom
Or a 6-membered ring) or a physiologically acceptable salt thereof as an active ingredient. 5. The following general formula (I): 6] (Wherein R ₁ is a hydrogen atom or an alkyl having 1 to 4 carbon atoms)
R ₂ and R ₃ each independently have 1 to 4 carbon atoms
Or an alicyclic 5-membered ring together with a nitrogen atom
Or a 6-membered ring) or a physiologically acceptable salt thereof as an active ingredient.