JPS6391368A - Carboxylic acid amide derivative - Google Patents

Abstract

NEW MATERIAL:The carboxylic acid amide derivative of formula I [R1 and R2 are H, lower alkyl, lower alkoxy or halogen; R3 is lower alkyl; R4 is H or lower alkyl; R5 is pyridyl, thienyl, furyl or group of formula II (R6 and R7 are H, lower alkyl, lower alkoxy or halogen); A and B are -CH2-, -CH(CH3)- or -CH2CH2-; Y is -CO- or -SO2-; n is 2 or 3] and its acid addition salt. EXAMPLE:N-[2-(2-chlorobenzylaminocarbonyl) phenyl]-4-methyl-1-piperazine acetamide hydrochloride. USE:It has micturition reflex suppressing action and is useful as a remedy for urinary system diseases such as pollakiuria feeling of residual urine, etc. PREPARATION:The compound of formula I can be produced by reacting the halogen compound of formula III (X is halogen) with the compound of formula IV.

Description

DETAILED DESCRIPTION OF THE INVENTION 1. The present invention relates to a novel carboxylic acid amide derivative represented by the following general formula CI) and its pharmacologically acceptable acid addition salt. It has a reflex suppressing effect and is used as a therapeutic agent for urinary system diseases such as frequent urination and feeling of residual urine.

(In the formula, R and R2 each represent a hydrogen atom, a lower alkyl group, a lower alkoxy group, or a halogen atom,
R3 represents a lower alkyl group, and R4 represents a hydrogen atom or a lower alkyl group. R5 represents a pyridyl group, a chenyl group, a furyl group, or a group of the formula, and R6 and R7 each represent a hydrogen atom.

Represents a lower alkyl group, lower alkoxy group, or halogen atom. A and B are each -CH2-.

-CH(CH3)- or -082CH2-, Y represents 100- or -5O2-, n is 2 or 3
represents an integer. ) Distortion - No literature has been found regarding the carboxylic acid amide derivative of the present invention, and it is not known at all that it has a micturition reflex action.

B(''', n As one of the treatments for urinary system diseases such as frequent urination and feeling of residual urine, it is effective to administer drugs that suppress the micturition reflex. However, there are only a few drugs that have this type of effect. In addition, it cannot be said that titration is necessarily necessary in terms of medicinal efficacy.For these reasons, there is a strong desire for the development of new micturition reflex inhibitors in the medical field.

. In view of the above-mentioned circumstances, the inventors of the present invention have conducted extensive research and have surprisingly discovered a novel carboxylic acid amide derivative represented by the above general formula (I) and a pharmacologically acceptable phosphoric acid addition salt thereof. The present inventors have discovered that the micturition reflex suppressant also exhibits a micturition reflex suppressing effect and that this effect is extremely excellent, leading to the completion of the present invention.

In the compound represented by the general formula (I) of the present invention, Rl
t Examples of lower alkyl groups represented by R2, R3, R4, R6 and R7 include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl groups, etc. Examples of lower alkoxy groups include methoxy, ethoxy, propoxy, and butoxy groups, and examples of halogen atoms include fluorine, chlorine, and bromine atoms.

The pyridyl group represented by R5 is 2-pyridyl, 3
-pyridyl and 4-pyridyl groups; examples of 'chenyl groups include 2-chenyl and 3-chenyl groups; examples of furyl groups include 2-furyl and 3-furyl groups.

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

Examples of the pharmacologically acceptable acid addition salts of the compound represented by the general formula (I) of the present invention include mineral acid salts such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, or acetic acid and maleic acid. , fumaric acid, citric acid, oxalic acid, lactic acid, tartaric acid, and other organic acid salts.

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

That is, a halogen compound represented by the following general formula (n) (wherein, R, R2, R4, R5, A, B and Y represent the same meanings as above, and X represents a halogen atom); The following general formula (III) (
In the formula, R3 and n represent the same meanings as above. ) in a solvent in the presence or absence of a base as a deoxidizing agent.

Solvents used in the method of the invention include, for example, benzene, toluene, pyridine, acetone, N, N-
Dimethylformamide, methanol.

Examples of the base as a deoxidizing agent include ethanol and chloroform, and examples of the base as a deoxidizing agent include triethylamine and potassium carbonate. Further, the reaction is carried out at a temperature ranging from room temperature to the reflux temperature of the solvent used.

The halogen compounds represented by the general formula (II), which are the starting materials in the method of the present invention, are also new compounds, with some exceptions, and are produced as shown in the diagram below.

R4 (V) (wherein, R, R2, R4, R5, AI B, X and Y
represents the same meaning as above. ) The compound represented by the general formula (I) of the present invention and its acid addition salt can be prepared into tablets, capsules, powders, granules, injections, and suppositories by conventional methods using formulation additives commonly used as pharmaceuticals. It can be made into formulations such as agents. The dosage for treatment patients is usually 10 to 100 doses per day for adults.
0+sg.

EXAMPLES The present invention will now be described by way of examples. However, the invention is not limited to the specific details of these examples.

Reference Example 1 2-chloroacetylamino-N-(2-chlorobenzyl)benzamide 1) To a solution of 2.74 g of 2-chlorobenzylamine in 201 ml of ethyl acetate was added 3.0 ml of isatoic anhydride. Add OOg and stir at room temperature for 3 hours. The reaction solution was concentrated under reduced pressure, and the residual crystals were recrystallized from ethanol/isopropyl ether to give 2-
4.07 g of colorless rod crystals of amino-N-(2-chlorobenzyl)benzamide are obtained.

Melting point 110-111° Elemental analysis value C, H, CI N20 theoretical value C
,1li4,50; H,5,03i N,10.7
4 Experimental values C, G4.50; H, 5,00i N,
to, 7G2) 2-Amino-N-(2-chlorobenzyl)benzamide 3-57 g e Potassium carbonate 1.61
g, 7aL of chloroacetyl chloride was added to a mixed solution of 231L of acetone and 61L of water under stirring while cooling with water, and 2L of chloroacetyl chloride was added at room temperature.
Stir for an hour. Water 701 is added to the reaction solution, and the precipitated crystals are collected by filtration. Recrystallization from methanol gives colorless needle crystals of 2-chloroacetylamino-N-(2-chlorobenzyl)benzamide.3. Get Log.

゛ Melting point 177-180" Elemental analysis value C16H engineering, Cl2N20□ theory (ilI
C, 51i, 99; H, 4, 18; N, 8.3
1 Experimental value C, 5G, 82; H, 4, 25; N,
8.25 Reference Example 2 2-chloroacetylamino-N-furfurylbenzamide l) 6.3 g of furfurylamine 5°01 ethyl acetate
Add 10.0 g of isatoic anhydride to the solution and stir at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure, and the residual crystals were converted into colorless needles from ethanol/isopropyl ether.12.
Obtain 6g.

Melting point 89-91'' Elemental analysis value C12G12 N2O2 Theoretical value C, GG, G5; H, 5, 59; N, 1
2.95 Experimental value C, GG, 39; H, 5,59;
N, 12.952) To a mixed solution of 12.8 g of 2-amino-N-furfurylbenzamide + 5-7 g of potassium carbonate + 601 of acetone and 20 ml of water, 5.21 g of chloroacetyl chloride is added dropwise with stirring under water cooling. 10 minutes later,
Furthermore, 2.9 g of potassium carbonate and 2.61 g of chloroacetyl chloride are added, and the mixture is stirred at room temperature for 20 minutes. The reaction solution was poured into water 1001, and the precipitated crystals were collected by filtration. Recrystallization from ethanol gives colorless needle crystals of 2-chloroacetylamino-N-furfurylbenzamide 17. Obtain Og.

Melting point 135-13B' Elemental analysis value C engineering, H engineering, CIN2O3 theoretical value C, 5
7,45; H, 4,48; N, 9.57 experimental value
C, 57, 29; H, 4, GI; N, 9.55
Reference example 3 2-chloroacetylamino-N-methyl-N-(2-pyridylmethyl)benzamide 1) N-methyl-2-pyridylmethylamine 2°5
3.0 g of isatoic anhydride was added to a solution of 151 g of ethyl acetate, and the mixture was stirred at room temperature for 2 hours. The reaction solution is washed with water, and the ethyl acetate layer is dehydrated, and then the solvent is distilled off.

The residue was purified by column chromatography (silica gel, chloroform/methanol 30:1) to obtain 3.4 g of 2-amino-N-methyl-N-(2-pyridylmethyl)benzamide as a pale yellow liquid.

Engineering R spectrum (liquid gj method) cm-1:111i22
(C:0) MS spectrum ra/z: 241 (M
)2) 2-amino-N-methyl-N-(2-pyridylmethyl)benzamide 3-27 g + potassium carbonate 1
．． 1.191 g of chloroacetyl chloride was added dropwise to a mixed solution of 171 g of acetone and 61 g of water under water cooling and stirring, and the mixture was stirred at room temperature for 1 hour. Water 601 was added to the reaction solution, and extracted with ethyl acetate. After the ethyl acetate layer is washed with water and dehydrated, the solvent is distilled off. The residue was purified by column chromatography (silica gel, chloroform/methanol 99:1) to give 2-chloroacetylamino-N-methyl-N-(2-
3.50 g of colorless liquid of pyridylmethyl)benzamide are obtained.

IR spectrum (liquid film method) C11-1:1690 (C:
O), lG30 (C:0) MS spectrum w/z:
319,317 (A, I:3) Reference Example 4 4-Chloro-2-chloroacetylamino-N-(2-pyridylmethyl)benzamide 1) Chloroform 501 with 5.4 g of 2-aminomethylpyridine and 5.1 g of triethylamine Add 10% of 4-chloro-2-nitropenzoyl chloride to the solution while stirring with water cooling.
．． 9 g of chloroform 101 solution is added dropwise. After stirring for 10 minutes, water was added to the reaction solution and the chloroform layer was separated. The chloroform layer is washed with an aqueous potassium carbonate solution, washed with water, dehydrated, and then the solvent is distilled off. The residual crystals were recrystallized from ethanol to give 12.9 g of pale yellow scales of 4-chloro-2-nitro-N-(2-pyridylmethyl)benzamide.
get.

Melting point 128.5-127.5' Elemental analysis value C13H1oCI N303 theoretical value C,
53,53; H, 3,4G; N, 14.41 Experimental value C, 53,57; H, 3,55; N, 14.
142) 4-chloro-2-nitro N-(2-pyridylmethyl)benzamide 11.5gt ammonium chloride 1
Add 6.8 g of iron powder to a mixed solution of 2.7 g, methanol 2301, and water 601, and stir at 60" for 1 hour. After cooling, the precipitate is filtered off, and the filtrate is concentrated under reduced pressure. Potassium carbonate is added to the residue. It is made alkaline by adding an aqueous solution and extracted with ethyl acetate.The ethyl acetate layer is washed with water, dehydrated, the solvent is distilled off, and the resulting crystalline residue is recrystallized from a mixture of ethyl acetate and ether. 9.8 g of colorless needle-like crystals of 4-chloro-N-(2-pyridylmethyl)benzamide are obtained.

Melting point 113.5-114.5 @ Elemental analysis value C13H, ClN30 Theoretical value C, 59,6G; H, 4,82; N,
IG, 0G experimental value C, 59, 84; H, 4, 49i
N, 15.743) 2-amino-4-chloro-N-(
To a mixed solution of 2.62 g of 2-pyridylmethyl)benzamide, 1-17 g of potassium carbonate + 181 g of acetone, and 41 g of water, add 0.88 ml of chloroacetyl chloride under stirring while cooling with water.
was added dropwise and stirred at room temperature for 1 hour. Water 501 is added to the reaction solution, and the precipitated crystals are collected by filtration. Recrystallization from ethanol gave 4-chloro-2-chloroacetylamino-N-(2-
2.90 g of colorless needles of benzamide (pyridylmethyl)
get.

Melting point 136-137° (decomposition) Elemental analysis value C engineering, H engineering 3C12N302 theoretical value C,
53,27; H, 3,87i N, 12.42 Experimental value C, 53,02; H, 4,1G; N, 12.
2G Reference Example 5 2-Chloroacetylamino-N-(2-pyridylmethyl)benzenesulfonamide 1) 2-Nitrobenzenesulfonyl was added to a solution of 12.8 g of 2-aminomethylpyridine and 11.9 g of triethylamine in 120 ml of chloroform under stirring while cooling with water. Add 25.0 g of chloride little by little. After stirring at room temperature for 30 minutes,
Add 100+ seconds of water to the reaction solution, and filter the precipitated crystals. Recrystallization from ethyl acetate gave a pale yellow prismatic product of 2-nitro-N-(2-pyridylmethylnsulfonamide 31.1
get g.

Melting point 142.5-143.5' Elemental analysis value C12 HllN304S theoretical value C,
49.14; H. 3.78; N, 14.33 experimental value C, 48.9f; H, 3.95; N, 1
4.142) 2-nitro-N-(2-pyridylmethyl)
Benzene Sulfonamide 3 1. 1g, ammonium chloride 34-Og* methanol 2001 and water 1
Add 17.8 g of iron powder to the mixture of No. 501 and stir at 60@ for 1 hour. Refrigerate, remove the precipitate by filtration, and concentrate the filtrate to about half its volume under reduced pressure. The precipitated crystals were collected by filtration and recrystallized from ethyl acetate to obtain 25.3 g of pale yellow needle crystals of 2-amino-N-(2-pyridylmethyl)benzenesulfonamide.

Melting point 120-1216 Elemental analysis value C12 G13 N302S theoretical value C,
54.74; H, 4.98; N, 15.911
i Experimental value C, 54J2; H, 5.05; N
．． 15.933) 3.1 g of 2-amino-N-(2-pyridylmethyl)benzenesulfonamide and 1 potassium carbonate
, 1.01 g of chloroacetyl chloride was added dropwise to 2 g of benzene 301 suspension under water cooling and stirring, and the mixture was stirred for 1 hour. Add water to the reaction solution and separate the benzene layer. After the benzene layer is washed with water and dehydrated, the solvent is distilled off. Column chromatography (silica gel, chloroform/methanol 3)
0:1), and the obtained crystals are recrystallized from methanol to obtain 2.1 g of a colorless prism product of 2-chloroacetylamino-N-(2-pyridylmethyl)benzenesulfonamide.

Melting point: 97~9°8″ Elemental analysis value: C 14 H 14 N303・l/2
H20 theoretical value C. 48.21 i H. 4.33
i N, 12.05 experimental value C, 48.54; H
,4. G5; N, 12.09 Reference Examples 6-29 The compounds shown in Tables 1 and 2 were obtained according to the methods of Reference Examples 1-5.

Example I N-[2-(2-chlorobenzylami7carbonyl)phenyl-4-methyl-1-piperazineacetamide
- Hydrochloride 2-chloroacetylamino-N-(2-chlorobenzyl)benzamide 2.60 g, 1-methylpiperazine 1.
A solution of 0.0 g of triethylamine and 0.77 g of triethylamine in N,N-dimethylformamide 81 is stirred at room temperature for 4 hours. Water 401 was added to the reaction solution, and extracted with ethyl acetate. Wash the ethyl acetate layer with water.

After dehydration, the solvent is distilled off. The residue was converted into a hydrochloride salt according to a conventional method to obtain 1.90 g of colorless crystals. iTf from methanol
It is crystallized to obtain colorless needle crystals with a melting point of 237-240° (decomposition).

Elemental analysis value C21H25CI N402・2HC1・
l/2H20 Theoretical value C, 52,24; H, 5,85i N, II
JO experimental value C, 52,4f; H, 5,93i N,
Il, 8G Example 2 N-(2-furfurylaminocarbonylphenyl)-4
-Methyl-1-piperazineacetamide fumarate 2-chloroacetylamino-N-furfurylbenzamide 8.0 g, 1-methylpiperazine 3.0 g and triethylamine 2.8 g N,N-dimethylformamide 2
The 41 solution is stirred at room temperature for 4.5 hours. Add 14% water to the reaction solution
01 was added, and the precipitated crystals were collected by filtration. The obtained crystals are converted into a fumarate salt according to a conventional method and recrystallized from methanol to obtain 11.1 g of a colorless prism product having a melting point of 218 to 222@.

Elemental analysis value C19H24N403・3/2C4H40
4 Theoretical values C, 5G, GO; H, 5, 70i N, I
O,5G experimental value C,5G,54; H,5,GO;
N, IO, 59 Example 3 N-[2-(4-Methoxybenzylaminocarbonylacetamide) Hydrochloride 1.78 g of 2-chloroacetylamino-N-(4-methoxybenzyl)benzamide and 1-methylpiperazine O. A solution of 9 g of Et in N,N-dimethylformamide 91 is allowed to stand at room temperature for 2 E1.Water 81 and 10 are added to the reaction solution.
% hydroxide) was added to the mixture and extracted with ethyl acetate. After the ethyl acetate layer is washed with water and dehydrated, the solvent is distilled off. The residue was converted to hydrochloride using a conventional method, yielding colorless crystals of 1.8
Obtain 9g.

Recrystallized from methanol, melting point 182-184.

Obtain colorless needle crystals.

Elemental analysis value C22 H2B N403・2HCl-H
20 Theoretical value C, 54.21; H, G. G2;
N, 11.49 experimental value C, 54.24; H,
6.75; N. 11.33 Example 4 4-ethyl-N-[2-(2-pyridylmethylaminosulfonyl)phenyl]-1-piperazine acedoamide middle methylethylpiperazine 0.8 g and triethylamine 0,6
A solution of 3 g of N,N-dimethylformamide 8111 is left at room temperature for 1 hour. Add 10 ml of water to the reaction solution, and filter the precipitated crystals. Recrystallized from ethanol, melting point 11
2.4 g of colorless needles of 5-116" are obtained.

Elemental analysis value C; 2oH27N503S-H20 theoretical value C, 55.15; H. G. 71; N.
IG. 08 Experimental value C. 55.01; H. G. 4
9;N. 15.97 Based on the methods of Examples 1 to 4, the following compounds of Examples 5 to 34 were obtained.

Example 5 N-(2-benzylaminocarbonylphenyl)-4
-Methyl-1-piperazineacetamide ・Fumarate Properties Colorless scale-like product (MeOH) Melting point 213-218' Elemental analysis value C21G26 N402・3/2C4H4
04 theoretical value C, 59,99; H, 5,97; N,
IO, 38 Experimental value C, 59, 79; H, 6, 29;
N, 10.21 Example 6 N-[2-(Benzylmethylaminocarbonyl)phenyl-4-methyl-1-piperazineacetamide ・Fumarate Properties Colorless prism product (EtOH) Melting point 179-181m Elemental analysis value C22G28 N402・C4Hρ4 theoretical value C, G2.89; H, G, 50 i N, 11
．． 28 Experimental value C, G2.84; H, G, 51 i
N, 11.30 Example 7 4-Methyl-N-[2-(2-methylbenzylaminocarbonylacetamide) Hydrochloride Properties Colorless needle crystals (Neon) Melting point 184-187'' Elemental analysis C22 G28 N402・2H C l
・H20 theoretical value C, 5G. 05; H, Ili.
84; N, 11.88 experimental value C. 55.8[i
;H. G. 75; N, 12.14 Example 8 4-Methyl-N-[2-(3-methylbenzylaminocarbonyl)phenyl]-1-piperazineacetamide Hydrochloride Properties Colorless plate crystals (MeOH) Melting point 168-171' Elemental analysis value C22 G28 N402・2H C l
・H20 theoretical value C, 5G. 05; H, 6.84
iN. 11.88 Experimental value C, 5G. 36 i
H, 6.78; N, 12.0G Example 9 N-[2-(3-methoxybenzylaminocarbonyl)phenyl-4-methyl-1-piperazineacetamide Hydrochloride Properties Colorless needle product (MeOH) Melting point 174 ~177' Elemental analysis value C 22 H 2B N403・28Cl
-1/2H20 theoretical value C. 55.23; H
,G. 53; N, 11.71 Experimental value C, 55
．． 18; H, 8.92; N, 11.75 Example 1O N-[2-(3.4-dimethoxybenzylami7carbonyl)phenyl]-4-methyl-1-piperazineacetamide Fumaric acid cane Colorless prism product (
MeOH) Melting point 200-203 @ (decomposition) Elemental analysis value C 23 G30 N404- 1/2
C4H404 theoretical value C, G1.97; H, 6.
88; N, 11.5G experimental value C, G1.70
;H. G. 51 i N, 11.4G Example 11 N- [2-(4-fluorobenzylaminocarbonyl)phenyl-4-methyl-1-piperazine acetamide Hydrochloride Properties Colorless needle crystals (Mean) Elemental analysis value C 21 G25 F N40□・2HC
I-H20 theoretical value C, 53.0G; H, 6.1
5; N. Il. 79 Experimental value C. 53.02 i
H, 8. +9; N, 11.45 Example 12 4-Methyl-N-[2-[(2-phenylethyl)aminocarbonyl]phenylco-1-piperazineacetamide Hydrochloride Properties Colorless needles (EtOH) Melting point 166-188 .

Elemental analysis value C2□H28 N402・2H C l・
H20 theoretical value C, 511i. 05; H,G. 8
4; N. Il. 88 experimental value C, 5G. 01;
H.G. 91 i N, Il. G8 Example 13 N-[2-[C2-(4-methoxyphenyl)ethylcoamino-lponylcophenylcol-l-piperazineacetamide Hydrochloride Properties Colorless plate crystals (EtO) 1) Melting point 166-168 @ Elemental analysis value C23B30 N403・2HC1-H2
0 theoretical value C, 55, 09; H, fi, 83; N
, 11.17 Experimental value C, 55, 05; H, G, 99
N, 11.20 Example 14 4-Ethyl-N-(2-furfurylaminocarbonylphenyl)-1-piperazineacetamide hydrochloride Properties Colorless plate crystals (EtOH) Melting point 212-213'' Elemental analysis C2Q B26 N403 ・HC1 theoretical value C,59,03i H,G,1li9; N,1
3.77 Experimental value C, 58, 75i H, lli, G3
; N, 13.74 Example 15 4-Methyl-N-[2-(2-tenylaminocarbonyl)phenyl]-1-piperazineacetamide Properties Colorless prism product (EtOH-Et20) Melting point
133~135" Elemental analysis value C19B24 N402S theoretical value C, G
1.27; H, G, 49; N, 15.04 Experimental value C, fiO, 98; H, G, 52; N, 14
．． 95 Example 16 4-Ethyl-N-[:2-(2-pyridylmethylaminocarbonyl)phenyl-1-piperazineacetamide ・Fumarate Properties Colorless plate-like crystals (EtOH) Melting point 167-168' Elemental analysis value C21H27N502・C4H404 theoretical value C, 60, 35i H, G, 28; N, 14.
08 experimental value C, GO, 05; H, G, 49; N
, 14.04 Example 17 4-Propyl-N-[2-(2-pyridylmethylaminocarbonyl)phenyl-1-piperazineacetamide fumarate Properties Colorless prismatic product (MeO) 1) Melting point 210-211° (decomposition) ) Principal analysis value C2□H29N502・C4H404 theoretical value C, G1.04; H, [i, 50; N, +
3.1li9 experimental value C, GO, 97; H, [i, 8
11i; N, 13. G4 Example 18 4-Butyl-N-[:2- (2-pyridylmethylaminecarbonyl)phenylco! - Piperazine acetamide fumarate Properties Colorless prismatic crystals (MeOH) Melting point 210-213' (decomposition) Elemental analysis values C23H31N50□・C4H404 Theoretical values C, B1.70; H, G, 71; N, 13
．． 32 Experimental values C, GIJI; H, G, 63;
N, 13.15 Example 19 Hexahydro-4-methyl-N-[2-(2-pyridylmethylaminocarbonyl)phenylco IH-1,4
-Diazepine-1-acetamide Properties Colorless viscous liquid TT> 2 hli Ia yt
, m-': 1Ei70 (C=0), 164G (C:0
) MS Spect iLt mHz: 381 (M+)
Example 20 4-Methyl-N-[2-[[2-(2-pyridyl)ethylcoaminoylcophenyl]-1-piperazineacetamide fumarate Properties Colorless plate crystals (EtO
H-Et20) Melting point 140.5-141.3゜Elemental analysis value C2□H27N5o2・l/2c4H4o
4 theoretical values C, 1li2.85; H, G, G5;
N, 15.93 experimental value C, G2. GG; H, [
i, 71; N, 15.88 Example 21 4-Methyl-N-[2-[[1-(2-pyridyl)ethylcoaminocarbonyl]phenyl]-1-piperazineacetamide ・Fumarate Properties Colorless needle-like Product (MeO
H) Melting point 191-193' Elemental analysis values C,,H,,N,O,.C,H,O.

Theoretical value C, GO, 35; H, G, 28; N, 1
4.08 Experimental value C, 59,97; H, 8,27;
N, 14.31 Example 22 4-Methyl-N-1-(2-pyridylmethylaminocarbonyl)phenyl]-1-piperazinepropanamide ・
Fumarate properties Colorless plate crystals (MeO[1) Melting point 176-178m (decomposition) Elemental analysis value C2□H2□N502・2C4H404 theoretical value C, 58,78; H, 5,75; N, 11.
41 experimental value C, 5G, 47; H, 5, 82; N
, 11.53 Example 23 α,4-dimethyl-N-[2-(2-pyridylmethylaminocarbonyl)phenyl-1-piperazineacetamide ・Fumarate Properties Colorless prism product (EtOH) Melting point 169-171' (decomposed) Elemental analysis value C2□H27N502・3/2C4)(4
04 theoretical value C, 58,37; H, 5,99; N,
12. Old experimental value C, 58,311t; H, G, 3
5; N, 12.79 Example 24 4-Methyl-N-[2-[(2-pyridylmethyl)methylaminocarbonyl]phenylco-1-piperazineacetamide fumarate Properties Colorless prism product (Me
OH) Melting point 194-19B" Elemental analysis value C21G27 N502/C4H404 theoretical value C, 60, 35; H, 8, 28; N, 14.
08 experimental value C, GO012; H, 6, 24; N,
14.24 Example 25 4-Methyl-N-[4-methyl-2-(2-pyridylmethylaminocarbonyl)phenyl-1-piperazineacetamide fumarate Properties Colorless prism product (E
tOH) Melting point 195-197" Elemental analysis value C21H27N502/C4H404 theoretical value C, GO, 35; H, G, 28; N, 14
．． 08 experimental value C, GO, 34i H, 8, 28; N
, 14.04 Example 26 4-Methyl-N-[2-methyl-6-(2-pyridylmethylaminocarbonyl)phenyl-1-piperazineacetamide ・Fumarate Properties Colorless needle donation (EtO
H) Melting point 157-158 @ MS spectrum ia/z: 381 (M”) Example 27 N-[2-methquin-6-(2-pyridylmethylaminocarbonyl)phenyl-4-methyl-1-piperazineacetamide fumar Acid acid properties Colorless needle crystals (Et
OH) Melting point 136-138' hts spectrum mHz: 397 (M) Example 28 N-[4,5-dimethoxy-2-(2-pyridylmethylaminocarbonyl)phenyl-4-methyl-1-piperazine acetamide Hydrochloric acid Salt properties Colorless needle crystals (Me
OH) Melting point 234-238' Elemental analysis value C2282g N504・2HCl -1
/2H20 theoretical value C, 51, 87; H, G, 33
; N, 13.75 experimental value C, 51,88; H, 8
, 40i N, 13.44 Example 29 N-[4-chloro-2-(2-pyridylmethylaminocarbonyl)phenyl]-4-methyl-1-piperazine acetamide Fumaric acid cane Colorless plate crystals (EtO
H) Melting point 185-188” (decomposition) Elemental analysis value C2oH24CIN502・C4H4o4
Theoretical value C, 55, G5; H, 5, 45; N, 1
3.52 Experimental value C, 55,50; H, 5,49;
N, 13.42 Example 3O N-[5-chloro-2-(2-pyridylmethylaminocarbonyl)phenyl]-4-methyl-1-piperazine acetamide Hydrochloride Properties Colorless needle offering (EtOH) Melting point 226-230' (Decomposition) Elemental analysis value C20G24 CI N502・2HC1
・1/2H20 Theoretical value C, 49, G5; H, 5, 1li2;
N, 14.48 experimental value C, 49,90; H, 5, G
8; N, 14.54 Example 31 N-[2-chloro-6-(2-pyridylmethylaminocarbonyl)phenyl]-4-methyl-1-piperazine acetamide fumarate Properties Colorless needle crystals (EtO
H) Melting point 147-148' MS spectrum mHz: 403,401 (M'',
l:3) Example 32 4-Methyl-N-[2-(3-pyridylmethylaminocarbonyl)phenyl-1-piperazineacetamide
・Oxalate properties Colorless prismatic crystal (MeOH) Melting point 186-189 @ Elemental analysis value C20G25 N502 ・C2H204
Theoretical value C157,7G; H,5,95; N,1
5.31 Experimental value C, 57, 32; H, fi, 18
; N, 15.03 Example 33 4-Methyl-N-[2-(4-pyridylmethylaminocarbonyl)phenyl]-1-piperazineacetamide
・Oxalate properties Pale yellow needle crystals (EtOB) Melting point 147-150' Elemental analysis value C20H25N502' C2H204
Theoretical value C, 57,7G; H, 5,95; N, 1
5.31 Experimental value C, 57, 42i H, G, 08;
N, Seal 5. O5 Example 34 4-Methyl-N-[:2-(2-pyridylmethylaminosulfonyl)phenyl-1-piperazineacetamide Properties Colorless needle crystals (EtOH) Melting point 145-146 @ Elemental analysis value C□, G25N503S Theoretical value C, 58, 58; H, G, 24; N, 17
．． 3G experimental value C, 5G, 50; H, 8, 28:
N, 17.44 肚炱(The novel carboxylic acid amide derivative represented by the general formula (I) of the present invention and its pharmacologically acceptable acid addition salt are:
It has an excellent effect of suppressing the micturition reflex, and is extremely useful as a drug for treating or preventing urinary disorders such as frequent urination and feeling of incomplete urination.

Claims (1)

[Claims] General formula▲ Numerical formula, chemical formula, table, etc.▼ (In the formula, R_1 and R_2 each represent a hydrogen atom, a lower alkyl group, a lower alkoxy group or a halogen atom, and R_3 represents a lower alkyl group. , R_4 represents a hydrogen atom or a lower alkyl group. R_5 represents a pyridyl group, thienyl group, furyl group, or a group of the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼, and R_6 and R_7 each represent a hydrogen atom,
Represents a lower alkyl group, lower alkoxy group, or halogen atom. A and B are -CH_2-, -CH, respectively
(CH_3) - or -CH_2 represents CH_2,
Y represents -CO- or -SO_2-, n is 2 or 3
represents an integer. ) and its pharmacologically acceptable acid addition salts.