JPH0517443A - Piperidine derivative - Google Patents

Abstract

PURPOSE:To obtain a new piperidine derivative extremely useful as a therapeutic agent for various allergic diseases, bronchial asthma, etc., due to its excellent antihistaminic and antiallergic actions without exhibiting central system inhibiting action. CONSTITUTION:A piperidine derivative expressed by formula I [R is 2-4C straight-chain or branched chain alkyl; (n) is 1, 3, 4, 6 or 7] and its pharmacologically permissible salt, e.g. 4-[(4-ethylphenyl)phenylmethoxy]-1- piperidineacetic acid. The aforementioned compound can be produced by reacting a piperidine derivative expressed by formula II with a compound expressed by formula III (R<1> is lower alkyl; X us halogen) in the presence or absence of a base in or without a solvent and further hydrolyzing the resultant compound in a solvent with an acid or a base. Furthermore, allergic dermatosis, rhinitis, urticaria, etc., are cited as allergic diseases and the dose is 1-300mg per day/normal adult in the case of oral administration to patients for treatment.

Description

Detailed Description of the Invention

[0001]

The present invention relates to a novel piperidine derivative having an antihistamine action and an antiallergic action and useful as a therapeutic agent for bronchial asthma, allergic rhinitis, skin diseases, urticaria and the like, and a drug thereof. It relates to a physically acceptable salt.

[0002]

2. Description of the Related Art Conventionally, as an antihistamine having a diphenylmethoxypiperidine ring, a diphenylpyraline represented by the following formula (Merck Index, (The Merck Ind
ex), 11th edition, 3334]

[Chemical 2] Is commercially available and is used for the treatment of allergic rhinitis, skin diseases and the like.

[0003]

A number of antihistamines have been developed so far and are used for the treatment of allergic skin diseases and rhinitis, but they have a central inhibitory effect on sleepiness and sedation as a side effect. Is a big drawback,
Another drawback is that it has an anticholinergic effect that contributes to side effects such as dry mouth and mydriasis. Various studies have been made so far in order to eliminate these drawbacks, but the present situation is still not sufficient.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies in view of the above circumstances, and as a result, found a compound having a strong antihistamine action and an antiallergic action, and having less side effects such as central inhibitory action, The present invention has been completed.

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

[Chemical 3] (In the formula, R represents a C _{2 to} C ₄ linear or branched alkyl group, and n represents an integer of 1, 3, 4, 6 or 7), and a novel piperidine derivative It relates to a pharmacologically acceptable salt thereof.

In the above general formula (I) of the present invention, examples of the C ₂ -C ₄ linear or branched alkyl group represented by R include ethyl, n-propyl, isopropyl,
Examples thereof include n-butyl, isobutyl and tert-butyl groups.

The compound represented by the general formula (I) of the present invention can be converted into a pharmacologically acceptable salt, or a base or an acid can be liberated from the produced salt, if desired. ..

As the pharmacologically acceptable salt of the compound represented by the above general formula (I) of the present invention, an acid addition salt or an alkali addition salt is provided. Examples of the acid addition salt include hydrochloric acid and odor. Hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and other mineral salts,
Organic acid salts such as acetic acid, maleic acid, fumaric acid, malic acid, citric acid, oxalic acid, lactic acid, tartaric acid and the like, and examples of the alkali addition salt include metal salts such as sodium, potassium and calcium, ammonium salts. , Methylamine,
Examples thereof include salts of organic bases such as ethylamine, dimethylamine, triethylamine, ethanolamine, piperidine and piperazine.

The novel piperidine derivative represented by the above general formula (I) of the present invention can be produced as follows.

That is, the following general formula (II)

[Chemical 4] (In the formula, R represents the same meaning as described above.) And the following general formula (III) X- (CH ₂ ) _n- COOR ¹ (III) (wherein R ¹ is a lower alkyl). Group, X represents a halogen atom, and n represents the same meaning as described above), and is reacted with or without a solvent in the presence or absence of a base, and further in a solvent, It can be produced by hydrolysis with an acid or a base.

The solvent used in the condensation reaction in the present production method may be any solvent as long as it does not inhibit the reaction, for example, benzene, toluene, tetrahydrofuran, dioxane, acetone, acetonitrile, methanol, ethanol, isopropanol, n-butanol. ，
Examples thereof include dimethyl sulfoxide, N, N-dimethylformamide and the like.

Examples of the base used include potassium carbonate, sodium carbonate, pyridine, triethylamine and the like, and the reaction is carried out in the range of 0 ° C to 200 ° C.

The acid used in the hydrolysis reaction is, for example, hydrochloric acid, sulfuric acid or the like, and the base is, for example, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium hydrogen carbonate or the like. But,
Examples of the reaction solvent include water, methanol, ethanol, acetone, tetrahydrofuran and the like, and the reaction is carried out in the range of 0 ° C to 100 ° C.

The above general formula used as the starting material
Most of the compounds represented by (II) are known compounds disclosed in European Patent Publication No. 394414 and were prepared according to the method. It should be noted that some of the novel compounds can be produced by the same method, and the details are described in Reference Examples.

The above-mentioned general formula (I) produced in this manner
The anti-allergic agent containing the novel piperidine derivative represented by and the pharmacologically acceptable salt thereof as an active ingredient can be administered orally or parenterally. Examples of the dosage form of the oral administration agent include tablets, capsules, powders, fine granules, granules, solutions and syrups, and the dosage form of the parenteral administration agent includes, for example, injections and suppositories. Agents, inhalants, eye drops, nasal drops, ointments and patches. For the preparation of these preparations, pharmacologically and pharmaceutically acceptable additives can be added, and excipients, disintegrants or disintegration aids, binders, lubricants, coating agents, dyes, diluents Agents, bases, solubilizers or solubilizers, isotonic agents, pH adjusters, stabilizers, propellants, adhesives, etc. are used.

In oral agents, transdermal and transmucosal administration agents, glucose, lactose, D-mannitol, starch, crystalline cellulose and the like are used as excipients, and carboxymethyl cellulose, starch and carboxy are used as disintegrants and disintegration aids. Methylcellulose calcium, etc. as binders, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatin, etc., lubricants, magnesium stearate, talc, etc., coating agents, hydroxypropylmethylcellulose, sucrose, titanium oxide, etc. But as a base,
Vaseline, liquid paraffin, polyethylene glycol,
Hard fat and the like, propellants such as CFCs, diethyl ether, and compressed gas; adhesives such as sodium polyacrylate, polyvinyl alcohol, methyl cellulose, polyisobutylene, and polybutene as base fabrics
Ingredients such as cotton cloth or plastic sheet are used as a dissolving agent or a solubilizing agent that can form an aqueous or injectable solution type injection agent in distilled water for injection, physiological saline, propylene glycol, etc. However, glucose, sodium chloride, D-mannitol, glycerin, etc. are used as isotonic agents, and pharmaceutical ingredients such as inorganic acids, organic acids or inorganic bases, organic bases, etc. are used as pH adjusters.

The dose of the compound of the present invention to a treated patient is 1 to 300 mg per day for oral administration, usually in adults.
The dose can be increased or decreased depending on the age, symptoms, etc.

[0018]

The present invention will be described below with reference to reference examples and examples, but the present invention is not limited to the specific details of these examples.

Reference Example 1 4-[(4-isopropylphenyl) phenylmethoxy] -1-methylpiperidine fumarate 4-isopropylbenzhydryl chloride 39.1 g,
A mixture of 17.4 g of 4-hydroxy-1-methylpiperidine, 12.6 g of potassium carbonate and 200 ml of xylene was heated under reflux for 3 hours. After washing the reaction solution with water, the organic layer is 10%
It was extracted with aqueous hydrochloric acid. The aqueous layer was washed with ether, made alkaline with potassium carbonate, and extracted with ethyl acetate. The extract was washed with saturated brine and then dehydrated, and the solvent was distilled off to obtain 20.9 g of a brown oily substance. Fumarate was formed by a conventional method and recrystallized from a mixed solution of isopropanol and isopropyl ether to obtain pale yellow crystals having a melting point of 192-194 ° C. Elemental analysis value C ₂₂ H ₂₉ NO.C ₄ H ₄ O ₄ theoretical value C, 71.05; H, 7.57; N, 3.19 experimental value C, 70.80; H, 7.60; N, 3.04

Reference Example 2 Ethyl 4-[(4-isopropylphenyl) phenylmethoxy] -1-piperidinecarboxylate 4-[(4-Isopropylphenyl) phenylmethoxy] -1-methylpiperidine 19.9 g of toluene 10
To the 0 ml solution was added dropwise 28.2 ml of ethyl chlorocarbonate while stirring at room temperature. After completion of the dropping, after heating and refluxing for 12.5 hours,
Further, 28.2 ml of ethyl chlorocarbonate was added, and again 6.
The mixture was heated under reflux for 5 hours. The reaction solution was washed successively with aqueous hydrochloric acid solution and saturated saline solution, dehydrated, and the solvent was distilled off. The residue was purified by silica gel column chromatography [eluent: dichloromethane-n-hexane (1-2)] to obtain 11.0 g of an orange oily substance. IR spectrum ν (liq) cm ⁻¹ : 1700 High resolution mass spectrum: C ₂₄ H ₃₁ NO ₃ theoretical value m / z: 381.2304 experimental value m / z: 381.2320 NMR spectrum δ (CDCl ₃ ) ppm: 1.22 (6H, d , J = 7.
0Hz), 1.24 (3H, t, J = 7.0Hz), 1.55-1.90 (4H, m), 2.75-2.95
(1H, m), 3.10-3.25 (2H, m), 3.53-3.65 (1H, m), 3.65-3.85 (2
H, m), 4.11 (2H, q, J = 7.0Hz), 5.50 (1H, s), 7.10-7.40 (9H, m)

Reference Example 3 4-[(4-isopropylphenyl) phenylmethoxy] piperidine fumarate 4-[(4-isopropylphenyl) phenylmethoxy] -1-piperidineethyl carboxylate 14.1 g, potassium hydroxide 10 0.0 g, and isopropanol 100
The ml mixture was heated to reflux for 4 hours. The reaction mixture was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted with ether. The extract was washed with water, dehydrated, and the solvent was distilled off. The residue was converted to a fumarate by a conventional method to obtain 12.5 g of colorless crystals. Recrystallized from a mixture of ethanol and ether, melting point 144-14
A colorless crystal of 6 ° C. was obtained. Elemental analysis value C ₂₁ H ₂₇ NO · C ₄ H ₄ O ₄ · 1/4 H ₂ O theoretical value C, 69.83; H, 7.38; N, 3.26 experimental value C, 69.97; H, 7.32; N, 3.23

Reference Example 4 4-[(4-ethylphenyl) phenylmethoxy] -1
-Piperidine ethyl acetate-fumarate 4-[(4-ethylphenyl) phenylmethoxy] -1
-Piperidine 3.50 g, ethyl bromoacetate 1.45 m
A mixture of 1, 80 g of potassium carbonate and 35 ml of N, N-dimethylformamide was stirred at 60 ° C. for 2 hours. The reaction solution was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted with ether. After dehydrating the extract, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography [eluent: ethyl acetate-n-hexane (1-5 to 2-5)] to obtain 2.77 g of a pale yellow liquid. After converting to fumarate by a conventional method,
Recrystallization from ether gave colorless needle crystals with a melting point of 125-126 ° C. Elemental analysis value C ₂₄ H ₃₁ NO ₃ .C ₄ H ₄ O ₄ theoretical value C, 67.59; H, 7.09; N, 2.81 experimental value C, 67.56; H, 7.05; N, 2.79

According to the method of Reference Example 4, the compounds of Reference Examples 5 to 16 were obtained.

Reference Example 5 4-[(4-ethylphenyl) phenylmethoxy] -1
- piperidine butyric acid ethyl fumarate nature fine orange crystals (AcOEt) mp 125-126 ° C. Elemental analysis _{C 26 H 35 NO 3 · C} 4 H 4 O 4 theory C, 68.55; H, 7.48; N, 2.66 Experiment Value C, 68.49; H, 7.44; N, 2.65

Reference Example 6 4-[(4-ethylphenyl) phenylmethoxy] -1
-Piperidine ethyl valerate fumarate Properties Colorless crystals (AcOEt) Melting point 135-137 ° C Elemental analysis C ₂₇ H ₃₇ NO ₃ · C ₄ H ₄ O ₄ Theoretical value C, 68.99; H, 7.66; N, 2.60 Experiment Value C, 69.04; H, 7.68; N, 2.57

Reference Example 7 4-[(4-ethylphenyl) phenylmethoxy] -1
-Methyl fumarate of piperidine heptanoate Properties Colorless crystal (Et ₂ O) Melting point 105.5 to 106 ° C Elemental analysis value C ₂₈ H ₃₉ NO ₃ .C ₄ H ₄ O ₄ theoretical value C, 69.42; H, 7.83; N, 2.53 experimental value C, 69.13; H, 7.78; N, 2.43

Reference Example 8 4-[(4-ethylphenyl) phenylmethoxy] -1
-Methyl fumarate of piperidine octanoate Properties Colorless crystal (Et ₂ O) Melting point 94-95 ° C Elemental analysis value C ₂₉ H ₄₁ NO ₃ .C ₄ H ₄ O ₄ theoretical value C, 69.82; H, 7.99; N, 2.47 Experimental value C, 69.68; H, 8.08; N, 2.36

Reference Example 9 4-[(4-n-propylphenyl) phenylmethoxy]
Ethyl acetate 1-piperidine Properties brown oil IR spectrum ν (liq) cm ^-1 : 1750 High resolution mass spectrum: C ₂₅ H ₃₃ NO ₃ Theoretical value m / z: 395.2460 Experimental value m / z: 395.2488 NMR spectrum δ ( CDCl ₃ ) ppm: 0.92 (3H, t, J = 7.
5Hz), 1.25 (3H, t, J = 7.0Hz), 1.61 (2H, sext, J = 7.5Hz), 1.70
-2.00 (4H, m), 2.30-2.45 (2H, m), 2.54 (2H, t, J = 7.5Hz), 2.7
5-2.90 (2H, m), 3.19 (2H, s), 3.40-3.55 (1H, m), 4.17 (2H, q,
J = 7.0Hz), 5.48 (1H, s), 7.05-7.40 (9H, m)

Reference Example 10 4-[(4-n-propylphenyl) phenylmethoxy]
Ethyl 1-piperidinebutyrate fumarate Properties Light brown crystals (AcOEt) Melting point 132.5-134 ° C Elemental analysis C ₂₇ H ₃₇ NO ₃ C ₄ H ₄ O ₄ Theoretical C, 68.99; H, 7.66; N, 2.60 experimental value C, 68.98; H, 7.70; N, 2.56

Reference Example 11 4-[(4-n-propylphenyl) phenylmethoxy]
-1-Piperidine ethyl valerate fumarate Properties Colorless crystals (AcOEt) Melting point 128.5-131.5 ° C Elemental analysis C ₂₈ H ₃₉ NO ₃ C ₄ H ₄ O ₄ Theoretical C, 69.42; H, 7.83; N, 2.53 experimental value C, 69.26; H, 7.76; N, 2.27

Reference Example 12 4-[(4-n-propylphenyl) phenylmethoxy]
Methyl -1-piperidine heptanoate Properties Light yellow oil IR spectrum ν (liq) cm ^-1 : 1738 High resolution mass spectrum: C ₂₉ H ₄₁ NO ₃ Theoretical value m / z: 451.3086 Experimental value m / z: 451.3105 NMR spectrum δ (CDCl ₃ ) ppm: 0.93 (3H, t, J = 7.
5Hz), 1.20-2.00 (14H, m), 2.10-2.40 (4H, m), 2.29 (2H, t, J =
7.5Hz), 2.55 (2H, t, J = 7.5Hz), 2.70-2.84 (2H, m), 3.40-3.5
1 (1H, m), 3.66 (1H, s), 5.48 (1H, s), 7.08-7.38 (9H, m)

Reference Example 13 4-[(4-n-propylphenyl) phenylmethoxy]
-1-Methyl 1-piperidine octanoate Properties Light brown oil IR spectrum ν (liq) cm ^-1 : 1730 High resolution mass spectrum: C ₃₀ H ₄₃ NO ₃ Theoretical m / z: 465.3243 Experimental m / z: 465.3238 NMR spectrum δ (CDCl ₃ ) ppm: 0.93 (3H, t, J = 7.
5Hz), 1.30 (6H, brs), 1.40-2.00 (10H, m), 2.05-2.40 (4H,
m), 2.29 (2H, t, J = 7.5Hz), 2.55 (2H, t, J = 7.5Hz), 2.70-2.85
(2H, m), 3.40-3.60 (1H, m), 3.66 (3H, s), 5.48 (1H, s), 7.05-
7.40 (9H, m)

Reference Example 14 Ethyl 4-[(4-isopropylphenyl) phenylmethoxy] -1-piperidinebutyrate Yellow oily substance IR spectrum ν (liq) cm ^-1 : 1736 High resolution mass spectrum: C ₂₇ H ₃₇ NO ₃ Theoretical value m / z: 423.2773 Experimental value m / z: 423.2772 NMR spectrum δ (CDCl ₃ ) ppm: 1.22 (6H, d, J = 6.
5Hz), 1.24 (3H, t, J = 7.0Hz), 1.60-2.01 (6H, m), 2.04-2.24
(2H, m), 2.24-2.43 (4H, m), 2.66-2.87 (2H, m), 2.87 (1H, sev
enth, J = 6.5Hz), 3.35-3.51 (1H, m), 4.12 (2H, q, J = 7.0Hz),
5.49 (1H, s), 7.07-7.43 (9H, m)

Reference Example 15 Methyl 4-[(4-isopropylphenyl) phenylmethoxy] -1-piperidinehexanoate Property pale yellow oily substance IR spectrum ν (liq) cm ^-1 : 1740 High resolution mass spectrum: C ₂₈ H ₃₉ NO ₃ theoretical value m / z: 437.2930 experimental value m / z: 437.2924 NMR spectrum δ (CDCl ₃ ) ppm: 1.15-1.40 (2H,
m), 1.23 (6H, d, J = 7.0Hz), 1.43-2.01 (8H, m), 2.10-2.40 (6
H, m), 2.70-2.96 (3H, m), 3.40-3.53 (1H, m), 3.65 (3H, s), 5.
48 (1H, s), 7.10-7.40 (9H, m)

Reference Example 16 4-[(4-n-butylphenyl) phenylmethoxy]-
Ethyl 1-piperidine butyrate Properties Yellow oily substance IR spectrum ν (liq) cm ⁻¹ : 1736 High resolution mass spectrum: C ₂₈ H ₃₉ NO ₃ Theoretical value m / z: 437.2930 Experimental value m / z: 437.2920 NMR spectrum δ (CDCl ₃ ) ppm: 0.91 (3H, t, J = 7.
3Hz), 1.24 (3H, t, J = 7.3Hz), 1.34 (2H, qt, J = 7.3,7.6Hz), 1.
57 (2H, tt, J = 7.6,7.9Hz), 1.60-2.05 (6H, m), 2.05-2.29 (2
H, m), 2.26-2.49 (4H, m), 2.57 (2H, t, J = 7.9Hz), 2.67-2.87
(2H, m), 3.36-3.54 (1H, m), 4.12 (2H, q, J = 7.3Hz), 5.48 (1H,
s), 7.03-7.50 (9H, m)

Example 1 4-[(4-ethylphenyl) phenylmethoxy] -1
-Piperidine acetic acid 4-[(4-ethylphenyl) phenylmethoxy] -1
-Piperidine ethyl acetate 1.77 g methanol 18 ml
To the solution was added 4.64 ml of 2N sodium hydroxide aqueous solution, and the mixture was stirred at room temperature for 3 hours. The solvent was evaporated under reduced pressure, water was added to the residue, the pH was adjusted to 4 with 10% hydrochloric acid, and the mixture was extracted with dichloromethane. After dehydrating the extract, the solvent was distilled off. The residue was crystallized by adding a mixed solution of acetone and n-hexane to obtain colorless crystals. Recrystallization from a mixed solution of acetone and n-hexane gave 0.90 g of colorless crystals having a melting point of 111-112 ° C. Elemental analysis _{C 22 H 27 NO 3 · 1} / 4H 2 O Theoretical value C, 73.82; H, 7.74; N, 3.91 Found C, 73.95; H, 7.71; N, 3.83

According to the method of Example 1, the compounds of Examples 2 to 13 were obtained.

Example 2 4-[(4-ethylphenyl) phenylmethoxy] -1
-Piperidine butyric acid / hydrochloric acid properties Colorless crystal (acetone) Melting point 136-138 ° C Elemental analysis value C ₂₄ H ₃₁ NO ₃ · HCl theoretical value C, 68.97; H, 7.72; N, 3.35 experimental value C, 68.79; H, 7.72 ; N, 3.33

Example 3 4-[(4-ethylphenyl) phenylmethoxy] -1
-Piperidine valeric acid / hydrochloride Properties Colorless crystal (acetone) Melting point 159.5 to 160.5 ° C Elemental analysis value C ₂₅ H ₃₃ NO ₃ · HCl theoretical value C, 69.51; H, 7.93; N, 3.24 experimental value C, 69.42; H, 7.95; N, 3.30

Example 4 4-[(4-ethylphenyl) phenylmethoxy] -1
-Piperidine heptanoic acid / hydrochloride Properties Colorless crystal (acetone) Melting point 149-150 ° C Elemental analysis C ₂₇ H ₃₇ NO ₃ · HCl Theoretical value C, 70.49; H, 8.33; N, 3.04 Experimental value C, 70.44; H, 8.41; N, 3.00

Example 5 4-[(4-ethylphenyl) phenylmethoxy] -1
-Piperidine octanoic acid / hydrochloride Properties Colorless crystal (acetone) Melting point 195-196 ° C Elemental analysis value C ₂₈ H ₃₉ NO ₃ · HCl theoretical value C, 70.94; H, 8.50; N, 2.95 experimental value C, 70.83; H, 8.55; N, 2.97

Example 6 4-[(4-n-propylphenyl) phenylmethoxy]
-1-Piperidine acetic acid / DL-tartrate properties Light brown crystal (acetone) Melting point 159-160.5 ° C Elemental analysis C ₂₃ H ₂₉ NO ₃ C ₄ H ₆ O ₆ Theoretical C, 62.66; H, 6.82; N, 2.71 experimental value C, 62.47; H, 6.73; N, 2.79

Example 7 4-[(4-n-propylphenyl) phenylmethoxy]
-1-Piperidine butyric acid / hydrochloride Properties Colorless crystals (acetone) Melting point 151-152.5 ° C Elemental analysis C ₂₅ H ₃₃ NO ₃ · HCl Theoretical C, 69.51; H, 7.93; N, 3.24 Experimental C, 69.24 ; H, 8.07; N, 3.21

Example 8 4-[(4-n-propylphenyl) phenylmethoxy]
-1-Piperidine valeric acid / hydrochloride Properties Colorless crystal (EtOH-Et ₂ O) Melting point 158.5 to 161.5 ° C Elemental analysis C ₂₆ H ₃₅ NO ₃ · HCl Theoretical C, 70.01; H, 8.14; N , 3.14 experimental value C, 69.86; H, 8.20; N, 3.07

Example 9 4-[(4-n-propylphenyl) phenylmethoxy]
-1-Piperidine heptanoic acid / hydrochloride Properties Colorless crystals (acetone-Et ₂ O) Melting point 140-143 ° C Elemental analysis C ₂₈ H ₃₉ NO ₃ · HCl Theoretical C, 70.94; H, 8.50; N, 2.95 Experimental C, 70.80; H, 8.49; N, 2.89

Example 10 4-[(4-n-propylphenyl) phenylmethoxy]
-1-Piperidine octanoic acid / hydrochloride Properties Light brown needles (acetone) Melting point 182 to 184 ° C Elemental analysis C ₂₉ H ₄₁ NO ₃ · HCl Theoretical C, 71.36; H, 8.67; N, 2.87 Experimental C , 71.26; H, 8.74; N, 2.79

Example 11 4-[(4-isopropylphenyl) phenylmethoxy] -1-piperidinebutyric acid / hydrochloride Properties colorless crystal (acetone-Et ₂ O) Melting point 126-128 ° C. Elemental analysis value C ₂₅ H ₃₃ NO ₃ · HCl · 1 / 4H ₂ O theoretical value C, 68.79; H, 7.97; N, 3.21 Found C, 68.55; H, 7.74; N, 3.21

Example 12 4-[(4-isopropylphenyl) phenylmethoxy] -1-piperidinehexanoic acid / hydrochloride Properties Colorless crystal (AcOEt) Melting point 127.5-130.5 ° C. Elemental analysis value C ₂₇ H ₃₇ NO ₃ · HCl theoretical value C, 70.49; H, 8.33; N, 3.04 experimental value C, 70.21; H, 8.33; N, 3.03

Example 13 4-[(4-n-butylphenyl) phenylmethoxy]-
1-piperidine butyric acid / hydrochloride Properties Colorless crystal (acetone-Et ₂ O) Melting point 86-89 ° C Elemental analysis C ₂₆ H ₃₅ NO ₃ · HCl · 1 / 2H ₂ O Theoretical C, 68.63; H, 8.20; N , 3.08 experimental value C, 68.58; H, 8.33; N, 3.01

[0050]

INDUSTRIAL APPLICABILITY The novel piperidine derivative represented by the above general formula (I) and the pharmacologically acceptable salt thereof have excellent antihistamine action and antiallergic action, and further, have central inhibitory action. Since it has no action, it is extremely useful as a therapeutic agent for various allergic diseases and bronchial asthma.

 ─────────────────────────────────────────────────── ─── Continued Front Page (72) Inventor Jun Sakaguchi 12-6-2 Inogeya, Katsuyama City, Fukui Prefecture

Claims (1)

What is claimed is: (Claim 1) The following general formula: (In the formula, R represents a C _{2 to} C ₄ linear or branched alkyl group, and n represents an integer of 1, 3, 4, 6 or 7.) and a drug thereof. A physically acceptable salt.