JPH08291141A - Diphenyl acetate derivative and its production - Google Patents

Abstract

PURPOSE: To obtain a new diphenyl acetate derivative having muscarine receptor antagonism and a therapeutic effect for incontinence of urine, and a large difference of activities between rhythm and contraction of a bladder-suppressing action as a main action and sialoschesis action as a side effect, and useful as a remedy of urine incontinence. CONSTITUTION: The objective compound or its salt is expressed by formula I (R1 is a 1-6C linear alkyl; R2 is methyl or benzyl), e.g. 2,2-diphenylpropionic acid-[4'-(1'-methyl)-piperidinyl] ester/hydrochloride. The compound is obtained by a condensation reaction of a compound of formula II (X is Cl or OH) with piperidine of formula III in the presence of triphenylphosphine and diisopropylazadicarboxylate. The compound of formula II is obtained by subjecting diphenylacetonitrile to alkylation with a 1-6C halogenated alkyl in the presence of sodium amide and affecting ethylene glycol to nitrile in the resultant product in the presence of KOH.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel diphenylacetic acid derivative, a method for producing the same, a muscarinic receptor antagonist containing the same, and a therapeutic agent for urinary incontinence.

[0002]

Conventionally, it has been proposed to use a muscarinic receptor antagonist as a therapeutic agent for urinary incontinence. Muscarinic receptors have M ₁ , M ₂ and M ₃ subtypes, M ₁ in the central sympathetic ganglia, M ₂ in the heart, and M ₃ in glands and smooth muscle. To do. A desirable therapeutic agent for urinary incontinence has high selectivity for muscarinic M ₃ receptor antagonism. And, conventionally, propiverine hydrochloride has been used as a drug for urinary incontinence as having a muscarinic receptor antagonistic action. However, although propiverine hydrochloride, which is used as a drug for treating urinary incontinence, has a high organ selectivity for the bladder, it undergoes metabolism of depropylation in vivo and changes as shown in the following formula.

[0003]

[Chemical 4]

That is, propiverine hydrochloride (A) is converted to the hydroxide (B). Compared with propiverine hydrochloride (A), this in-vivo converted hydroxide (B) has enhanced salivary secretion inhibitory action which is considered as a side effect of muscarinic receptor antagonistic action. As a result, propiverine hydrochloride is effective in treating urinary incontinence and has a side effect of suppressing salivary secretion.

[0005]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and has broadened the selectivity between the main effect of suppressing bladder rhythm contraction and the side effect of suppressing salivary secretion. That is, it is an object of the present invention to provide a compound exhibiting a muscarinic receptor antagonistic action and a urinary incontinence treatment action in which the difference in activity between the main action and the side effect is large.

[0006]

That is, the present invention provides a compound represented by the general formula (I)

[0007]

Embedded image

(Wherein R ₁ represents a straight-chain alkyl group having 1 to 6 carbon atoms and R ₂ represents a methyl group or a benzyl group) or a pharmaceutically acceptable salt thereof. The salt is, for example, the hydrochloride salt. The general formula (I) is muscarinic M
₃ Receptor antagonism, selective bladder rhythmic contraction inhibitory effect, and little salivary secretion inhibitory effect. Therefore, it is useful as a therapeutic agent for urinary incontinence with few side effects such as salivary secretion suppressing action. The compound represented by the general formula (I) of the present invention can be synthesized through the synthetic process shown in the following chemical formula 6.

[0009]

[Chemical 6]

(In the formula, R ₁ is a linear alkyl group having 1 to 6 carbon atoms, R ₂ is a methyl group or a benzyl group.) That is, diphenylacetonitrile 1 is present in the presence of sodium amide and has 1 to 6 carbon atoms. After the alkylation with the alkyl halide of 1., the nitrile group is acidified with ethylene glycol in the presence of potassium hydroxide to convert it to a carboxylic acid to obtain compound 3 . The obtained compound 3 is reacted with the corresponding piperidine by a known condensation method to obtain the piperidinyl ester 4 . After that, it is made into a hydrochloride with 5% hydrochloric acid / ether solution.

Hereinafter, examples of the compound of the present invention will be described. Compound 1: 2.2-Diphenylpropionic acid- [4 '
-(1'-Methyl) -piperidinyl] ester / hydrochloride Compound 2: 2.2-Diphenylpropionic acid- [4 '
-(1'-benzyl) piperidinyl] ester / hydrochloride Compound 3: 2.2-Diphenylbutyric acid- [4 '-(1'
-Methyl) piperidinyl] ester / hydrochloride Compound 4: 2.2-Diphenylbutyric acid- [4 '-(1'
-Benzyl) piperidinyl] ester / hydrochloride Compound 5: 2.2-Diphenylvaleric acid- [4'-
(1'-Methyl) piperidinyl] ester / hydrochloride Compound 6: 2.2-Diphenylvaleric acid- [4'-
(1'-Benzyl) piperidinyl] ester / hydrochloride

Compound 7: 2.2-Diphenylhexanoic acid- [4 '-(1'-methyl) piperidinyl] ester / hydrochloride Compound 8: 2.2-Diphenylhexanoic acid- [4'-
(1'-Benzyl) piperidinyl] ester / hydrochloride Compound 9: 2.2-Diphenylheptanoic acid- [4'-
(1′-Methyl) piperidinyl] ester / hydrochloride Compound 10: 2.2-Diphenylheptanoic acid- [4 ′
-(1'-benzyl) piperidinyl] ester / hydrochloride Compound 11: 2.2-Diphenyloctanoic acid- [4 '
-(1'-methyl) piperidinyl] ester / hydrochloride Compound 12: 2.2-Diphenyloctanoic acid- [4 '
-(1'-Benzyl) piperidinyl] ester / hydrochloride

The pharmacological test and its data are shown below. A. Pharmacological test 1. The anticholinergic effect (mainly M ₃ antagonism and anticalcium effect) was tested using a rat bladder specimen. 7
Weekly SD male rats (body weight 250-300 g) were killed by exsanguination, the bladder was removed, and the length was 10 mm in the longitudinal muscle direction.
A strip specimen with a width of 2 mm was prepared. 95% oxygen /
The sample was suspended in a 10 ml Magnus tank filled with Krebs liquid at 34 ° C. with 5% carbon dioxide gas under a load of 1 g, and the contraction reaction was recorded on a pen-writing recorder via an isometric transducer. Anticholinergic action,
After obtaining the contractile response by cumulative addition of carbachol, the test drug was treated for 20 minutes to obtain the contractile response by cumulative addition of carbachol again, and the pA ₂ value or pD ′ ₂ value was calculated from the dose-response curve and evaluated. The anti-calcium effect was evaluated in the same manner as in the case of the anticholinergic effect by equilibrating in a calcium ion-free Krebs solution and then obtaining a contraction reaction by cumulative addition of Ca ⁺⁺ .

2. Effect on rhythmic bladder contraction Seven-week-old male SD rats (weight: 230 to 300 g) were
Urethane (800 mg / Kg) and α-chloralose (80 mg / Kg) i. p. Under anesthesia, the bladder was exposed by a midline abdominal incision. A small incision was made at the top of the bladder, and a catheter equipped with a balloon having an internal volume of about 0.5 ml was inserted into the bladder and fixed with ligation. A three-way stopcock was connected to the other end of the catheter, one was connected to a pressure transducer, and the other was connected to a 1 ml syringe filled with water. In order to obtain an appropriate rhythmic contraction of the bladder, inject water in the connected syringe into the balloon, and after confirming stable rhythmic contraction,
A test drug solution (0.5 ml / Kg) was intravenously administered through a catheter inserted into the femoral vein. Cumulative administration of study drug to suppress rhythmic contraction pressure (50% inhibitory dose, ID
₅₀ value) and rhythmic contraction elimination effect (10-minute elimination dose, E
D ₁₀ value) was evaluated.

3. Salivary secretion inhibitory action 7-week-old male SD rats (body weight 200 to 250 g)
Urethane (1.2 g / Kg, ip) was anesthetized and a tracheal cannula was inserted. To prevent reflux of saliva, the esophagus was ligated and a weighed cotton ball was placed in the oral cavity. The test drug solution (1 ml / K
g) was administered intravenously and at the same time 0.1 mg / kg of carbachol
Kg was injected subcutaneously in the back subcutaneously. After 30 minutes, the cotton balls were collected and weighed, and the saliva secretion amount of the Vehicle administration group was set as 100%, and a 50% saliva secretion inhibitory dose (ID ₅₀ value)
Was calculated. Table 1 shows pharmacological data.

[0016]

[Table 1]

(Note) 1. (Salivary secretion inhibiting / rhythmic contraction inhibition) is (ID ₅₀ value of ID ₅₀ values / rhythmic contraction inhibiting action of salivary secretion inhibiting action). 2. Selectivity denotes the numerical value of the case of the propiverine hydrochloride and (ID ₅₀ value of ID ₅₀ values / rhythmic contraction inhibiting action of salivary secretion inhibiting action) and 1. 3. The values in parentheses in the pA ₂ value column are pD ′ ₂ values. 4. NE indicates that there was no effect up to the concentration in parentheses (molar concentration). As is clear from Table 1, the compounds of the present invention have excellent selectivity as compared with the conventional propiperine hydrochloride.

[0018]

EXAMPLES Example 1 2.2 Synthesis of 2-diphenyl-valeric acid- [4 ′-(1′-methyl) -piperidinyl] ester hydrochloride (Compound 5) 2.2-Diphenylvaleric acid 0.3 g ( 1.18mmo
A solution of 1) in THF (15 ml) was prepared in a 50 ml eggplant-shaped flask, and 0.149 g (1.298 mmol) of 1-methyl-4-hydroxypiperidine T was prepared under an argon atmosphere.
HF 5 ml solution was added. This solution was cooled with ice, and 0.681 g (2.595 mmol) of triphenylphosphine,
Diisopropyl azadicarboxylate 0.51 ml
(2.595 mmol) was added, and the mixture was stirred at room temperature for 15 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, the residue was made into two layers of ethyl acetate and water, and the organic layer was separated. The organic layer was washed 3 times with 10 ml of water and once with 10 ml of saturated saline solution, dried with sodium sulfate,
It was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (BW-200, 30 g, chloroform / methanol = 40/1), and 2.2-diphenylvaleric acid-
0.297 g (0.845 mmol) of [4 ′-(1′-methyl) piperidinyl] ester, yield 71.6%
(Yellow oily substance).

The obtained ester was dissolved in 5 ml of methanol, 1.5 ml of 5% hydrochloric acid / ether solution was added, the mixture was left for 5 minutes, the solvent was evaporated to dryness under reduced pressure, and 0.25 g (0.1%) of the desired product was obtained.
646 mmol) and the yield was 76.4% (pale yellow crystalline powder). ¹ HNMR (δ, CDCl ₃ ) 0.882 (3H, t,
J = 6.8 Hz), 1.074 (2H, m), 1.60
(2H, m), 1.69 (1H, bs), 1.74-
1.84 (2H, m), 2.18 (3H, S), 2.1
6-2.29 (3H, m), 2.33 (2H, m),
4.84 (1H, m), 7.20-7.30 (10H,
m) IR (cm ~ ¹ , neat) 3052, 2944, 27
82, 1722, 1494, 1446, 1275, 12
21, 1182, 1140, 1119, 1032, 75
3, 726, 696 MS (m / z) 351 (M ⁺ ), 309, 209, 1
65, 131, 96 (BP), 55

The above-mentioned starting compound 2.2-diphenyl-valeric acid was synthesized as follows. That is, 6.0 g of diphenylacetonitrile was added to a 300 ml eggplant-shaped flask.
(0.03 mol) and 1.4 g of sodium amide
(0.036 mol) and 150 ml of dry benzene were added, and the mixture was heated under reflux for 2 hours. After cooling to 60 ° C., 6.1 g (0.036 mol) of propyl iodide was added, and the mixture was stirred for 1 hour. After completion of the reaction, the reaction solution was poured into ice water and extracted with 100 ml of ethyl acetate. The extract was washed 3 times with 20 ml of water, dried with sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (BW-200, 300 g, ethyl acetate / n-hexane = 1/15). 2.2
5.8 g of diphenyl-valeronitrile (0.025
mol), and the yield was 83.3%.

2.35 g (0.01 mol) of the above 2.2-diphenyl-valeronitrile was weighed in a 100 ml eggplant type flask, and 40 m of 40% potassium hydroxide aqueous solution was taken.
1, ethylene glycol 5 ml were added, and the mixture was heated under reflux for 15 hours. The reaction solution was returned to room temperature, diluted with water, and washed with ether. The aqueous layer was acidified with concentrated hydrochloric acid under ice cooling and extracted with ethyl acetate. The extract was washed with water, dried over sodium sulfate and concentrated under reduced pressure. The residue was solidified with ether, and the precipitated crystals were collected by filtration, washed with ether and dried to give 2.02 g (8.06 mmol) of 2.2-diphenylvaleric acid in a yield of 80.
Obtained in 6% (white crystals). ¹ HNMR (δ, CDCl ₃ ) 0.888 (3H, t,
J = 7.2 Hz), 1.11 (2H, m), 2.32
(2H, m) 4.153 (bs, -OH), 7.20-
7.36 (10H, m) IR (cm ~ ¹ , KBr) 2956, 2868, 262
6, 1809, 1692, 1599, 1491, 144
6, 1404, 1320, 1284, 1239, 119
7, 942, 756, 723, 696, 654, 630

Example 2 2.2 Synthesis of 2-diphenyl-valeric acid- [4 '-(1'-benzyl) -piperidinyl] ester.hydrochloride (Compound 5) As described in Example 1 in a 100 ml round-bottomed flask. 1.15 g (4.5%) of 2.2-diphenylvaleric acid synthesized by the method
28 mmol) and 1-benzyl-4-hydroxypiperidine (1.03 g, 5.433 mmol) were weighed out to prepare a THF 20 ml solution, and the atmosphere was replaced with argon. After cooling with ice, 1.43 g (5.433 m) of triphenylphosphine
mol), diisopropyl azadicarboxylate 1.
07 ml (5.433 mmol) was added and the mixture was stirred at room temperature for 1.5
Stir for hours. After completion of the reaction, the mixture was concentrated under reduced pressure, the residue was separated into two layers of ethyl acetate and water, and the organic layer was separated. Organic layer is water 1
The extract was washed 5 times with 0 ml and once with 10 ml of saturated saline, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (BW-200, 30 g, ethyl acetate / n
-Hexane 1/8 → 1/4), and 0.975 g (2.28 mmol) yield of 2.2-diphenyl-valeric acid- [4 '-(1'-benzyl) -piperidinyl] ester 50. Obtained in 4% (yellow oil).

The ester thus obtained was treated with 2.5 m of ethanol.
Dissolve in 1 l, add 2 ml of 5% hydrochloric acid / ether solution, add 5
After leaving for a minute, the solvent is evaporated to dryness under reduced pressure, and 0.741 g of the desired product is obtained.
(1.597 mmol) in 70% yield, obtained as a pale yellow crystalline powder. ¹ HNMR (δ, CDCl ₃ ) 0.873 (3H, t,
J = 7.2 Hz), 1.075 (2H, m), 1.57
7 (2H, m), 1.71-1.81 (2H, m),
2.25-2.39 (6H, m), 3.415 (2H,
S), 4.851 (1H, m), 7.16-7.37.
(15H, m) MS (m / z) 428 (M ⁺ ), 351, 225, 1
72, 105, 82 (BP), 55 IR (cm to ¹ , neat) 3052, 3016, 29
44, 2866, 2806, 1722, 1599, 14
94, 1359, 1218, 1179, 1104, 10
71, 1032, 912, 753, 696, 663

The starting compound 1-benzyl-4-hydroxypiveridine was synthesized as follows. 500 ml
25.5 g of 1-benzyl-piparidone in an eggplant-shaped flask
Weigh out (0.136 mol) and add 160
It was made into a ml solution. It cooled at -10 degreeC, 2.7 g (0.071 mol) of sodium borohydride was added, and it stirred for 0.5 hour. After adding saturated saline, the mixture was concentrated under reduced pressure, and the residue was extracted twice with 100 ml of ethyl acetate. 3 with 20 ml of water
After washing twice with 20 ml of a saturated saline solution, drying with sodium sulfate and concentration under reduced pressure, the residue was purified by silica gel column chromatography (BW-200, 500 g, chloroform / methanol = 10/1), and 1-benzyl-4-. 27.3 g (0.144 mol) of hydroxypiveridine was obtained (yellow oily substance).

Example 3 2,2-Diphenylpropionic acid- [4 '-(1'-methyl) -piperidinyl] ester.hydrochloride (Compound 1)
Synthesis in the same manner as in Example 1. Obtained in the form of a white to pale yellow crystalline powder. ¹ HNMR (δ, CDCl ₃ ) 1.657 (2H, m,
J = 6.8 Hz), 1.76-1.89 (3H, m),
1.1916 (3H, S), 2.13-2.40 (7
H, S + m), 4.90 (1H, m, J = 3.6H
z), 7.21-7.33 (10H, m) MS (m / z) 324, 181, 96 (BP), 55 IR (cm ~ ¹ , neat) 3052, 3016, 29.
26, 2836, 2782, 1722, 1494, 14
46, 1275, 1233, 1188, 1029, 69
6

Example 4 2.2-Diphenylpropionic acid- [4 '-(1'-benzyl) piperidinyl] ester.hydrochloride (Compound 2)
Synthesis in the same manner as in Example 2. Obtained in the form of a pale yellow crystalline powder. ¹ HNMR (δ, CDCl ₃ ) 1.58-1.68 (2
H, m), 1.78-1.88 (2H, m), 1.91.
(3H, S), 2.20-2.30 (2H, m), 2.
38 (2H, bs), 3.40 (2H, S) 4.90
(1H, m), 7.20-7.32 (15H, m) MS (m / z) 400 (M ⁺ ), 323, 172, 1
46, 118, 91 (BP), 55 IR (cm ~ ¹ , neat) 3406, 2932, 25
06, 1725, 1494, 1449, 1233, 12
12, 1101, 1074, 1026, 747, 69
6,663

Example 5 2.2 Synthesis of 2-diphenylbutyric acid- [4 '-(1'-methyl) piperidinyl] ester.hydrochloride (Compound 3) Synthesis was carried out in the same manner as in Example 1. Obtained in the form of a white crystalline powder. ¹ HNMR (δ, CDCl ₃ ) 0.749 (3H, dd
d, J = 6.8, 8.0 Hz), 1.61 (2H,
m), 1.75-1.90 (4H, m), 2.18 (3
H, S), 2.16-2.35 (2H, m), 2.41.
(2H, q, J = 7.6Hz), 4.15 (1H,
m), 7.20-7.34 (10H, m) MS (m / z) 337, 195, 165, 96 (B
P), 55 IR (cm ~ ¹ , neat) 3052, 3016, 29
26, 2836, 2782, 1922, 1494, 12
75, 1224, 1137, 1119, 1089, 10
32, 1011, 753, 726, 696, 414

Example 6 2.2-Diphenylbutyric acid- [4 '-(1'-benzyl)
Synthesis of piperidinyl] ester hydrochloride (Compound 4) Synthesis was carried out in the same manner as in Example 2. Obtained in the form of a white crystalline powder. ¹ HNMR (δ, CDCl ₃ ) 0.740 (3H, t,
J = 7.2 Hz), 1.53-1.82 (4H, m),
2.18-2.28 (2H, m) 2.41 (2H, q
u, J = 7.2 Hz), 3.44 (2H, S), 4.8
6 (1H, m), 7.20-7.40 (15H, m) MS (m / z) 413 (M ⁺ ), 386, 336, 1
95, 172, 117, 91 (BP), 82, 55 IR (cm to ¹ , neat) 2938, 2506, 17
25, 1221, 747, 699

Example 7 2.2 Synthesis of 2-diphenylhexanoic acid- [4 '-(1'-methyl) piperidinyl] ester hydrochloride (Compound 7) Synthesis was carried out in the same manner as in Example 1. Obtained in the form of white crystals. m. p. 150-152 ° C (ether / ethanol) ¹ HNMR (δ, CDCl ₃ ) 0.829 (3H, t,
J = 7.2 Hz), 1.037 (2H, m), 1.28
4 (2H, m), 1.606 (2H, qu, J = 6.4)
Hz), 1.793 (2H, m), 2.189 (3H,
S), 2.213-2.320 (4H, m), 2.35.
3 (2H, m), 4.843 (1H, m), 7.198.
-7.389 (10H, m) MS (m / z) 365 (M ⁺ ), 309, 223, 1
65, 96 (BP), 55 IR (cm to ¹ , neat) 2944, 2860, 25
06, 1725, 1491, 1449, 1212, 11
19, 1029, 729

Example 8 2.2 Synthesis of 2-diphenylhexanoic acid- [4 '-(1'-benzyl) piperidinyl] ester.hydrochloride (Compound 8) Synthesis was carried out in the same manner as in Example 2. Obtained in the form of a pale yellow crystalline powder. ¹ HNMR (δ, CDCl ₃ ) 0.829 (3H, t,
J = 7.8 Hz), 0.98-1.10 (2H, m),
1.28 (3H, m), 1.51-1.68 (3H,
m), 1.71-1.82 (2H, m), 2.17-
2.30 (2H, m), 2.30-2.45 (3H,
m), 3.40 (2H, S), 4.85 (1H, m),
7.20-7.35 (15H, m) MS (m / z) 442 (M ⁺ ), 365, 223, 1
72, 119, 91, 82 (BP), 55 IR (cm to ¹ , neat) 3052, 3022, 29
38, 2860, 2800, 1722, 1491, 14
46, 1359, 1338, 1314, 1239, 12
15, 1119, 1032, 732, 696,

Example 9 2.2 Synthesis of 2-diphenylheptanoic acid- [4 '-(1'-methyl) piperidinyl] ester.hydrochloride (Compound 9) Synthesis was carried out in the same manner as in Example 1. Obtained in the form of a pale yellow crystalline powder. ¹ HNMR (δ, CDCl ₃ ) 0.812 (3H, t,
J = 7.6 Hz), 1.01-1.11 (2H, m),
1.20-1.32 (4H, m), 1.60 (2H,
m), 1.75-1.90 (3H, m), 2.18 (3
H, S), 2.15-2.30 (2H, m), 2.34.
(2H, m), 4.84 (1H, m), 7.20-7.
31 (10H, m) MS (m / z) 380 (M ⁺ ), 309, 165, 9
6 (BP), 55 IR (cm ~ ¹ , neat) 2938, 2854, 27
82, 1722, 1494, 1446, 1275, 12
15, 1182, 1137, 1122, 1035, 75
3,726,696,

Example 10 2.2-Diphenylheptanoic acid- [4 '-(1'
Synthesis of -benzyl) piperidinyl] ester.hydrochloride (Compound 10) Synthesis was performed in the same manner as in Example 2. Obtained in the form of a white crystalline powder. ¹ HNMR (δ, CDCl ₃ ) 0.811 (3H, t,
J = 7.2 Hz), 1.053 (2H, m), 1.18
-1.30 (5H, m), 1.52-1.63 (2H,
m), 1.72-1.82 (2H, m), 2.13.
2.28 (2H, m), 2.333 (3H, m), 3.
398 (2H, S), 4.850 (1H, m), 7.2
0-7.32 (15H, m) MS (m / z) 456 (M ⁺ ), 378, 237, 1
72, 117, 91 (BP), 82, 55 IR (cm to ¹ , neat) 2938, 2860, 28
06, 1722, 1491, 1449, 1284, 12
15, 1104, 1032, 753, 696

Example 11 2.2 Synthesis of 2-diphenyloctanoic acid- [4 '-(1'-methyl) piperidinyl] ester.hydrochloride (Compound 11) Synthesis was carried out in the same manner as in Example 1. Obtained in the form of a white crystalline powder. ¹ HNMR (δ, CDCl ₃ ) 0.832 (3H, t,
J = 6.8 Hz), 1.05 (2H, m), 1.14.
1.34 (6H, m), 1.60 (2H, m, J = 7.
2 Hz), 1.68 (2H, bs) 1.74-1.84
(2H, m), 2.18 (3H, S), 2.14-2.
24 (2H, m), 2.34 (2H, m), 4.84
(1H, m, J = 3.2 Hz), 7.18-7.33
(10H, m) MS (m / z) 394 (M ⁺ ), 309, 251, 19
4, 167, 114, 91 (BP), 55 IR (cm ~ ¹ , neat) 2920, 2848, 27
82, 1722, 1446, 1275, 1221, 11
82, 1137, 1122, 1035, 753, 696

Example 12 2.2-Diphenyloctanoic acid- [4 '-(1'-benzyl) piperidinyl] ester hydrochloride (Compound 12)
Synthesis in the same manner as in Example 2. Obtained in the form of a white crystalline powder. ¹ HNMR (δ, CDCl ₃ ) 0.832 (3H, t,
J = 6.8 Hz), 1.00-1.09 (2H, m),
1.15-1.32 (6H, m), 1.52-1.63
(2H, m), 1.72-1.82 (2H, m), 2.
20-2.30 (4H, m), 2.334 (2H,
m), 3.403 (2H, S), 4.849 (1H,
m), 7.267 (15H, m) MS (m / z) 469 (M ⁺ ), 393, 251, 1
72, 115, 91, 82 (BP), 55 IR (cm ~ ¹ , neat) 2920, 2850, 28
06, 1722, 1494, 1449, 1314, 12
21, 1182, 1119, 1068, 1032, 73
8,696

[0035]

INDUSTRIAL APPLICABILITY The novel compound of the present invention has a muscarinic receptor antagonistic action, and also has urinary incontinence treatment and related therapeutic effects. Further, there is a large difference in activity between the main action (suppressive action of urinary bladder rhythm contraction) and the side effect (suppressive action of salivary secretion), and therefore it is useful as a therapeutic agent for urinary incontinence.

Claims (4)

[Claims] 1. The following general formula (I): (In the formula, R ₁ represents a linear alkyl group having 1 to 6 carbon atoms, and R ₂ represents a methyl group or a benzyl group.), Or a pharmaceutically acceptable salt thereof. 2. The following general formula (II): (Wherein R ₁ is the same as above, X represents chlorine or a hydroxyl group), and a compound represented by the following general formula (III): The method for producing a compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein the compound represented by the formula (wherein R ₂ is the same as above) is reacted. 3. A muscarinic receptor antagonist containing the compound according to claim 1 or a pharmaceutically acceptable salt thereof. 4. A therapeutic agent for urinary incontinence containing the compound according to claim 1 or a pharmaceutically acceptable salt thereof.