Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-06-14
2001-01-16
Chang, Ceila (Department: 1612)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S256000, C514S318000, C514S326000, C514S329000, C544S233000, C544S242000, C544S336000, C546S194000, C546S208000, C546S209000, C546S210000, C546S213000, C546S224000
Reexamination Certificate
active
06174900
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a novel substituted piperidine derivative and a salt thereof, and particularly to a substituted piperidine derivative and a salt thereof, which have an anticholinergic effect and a calcium antagonism and are useful as medicines for prophylaxis of and treatment for a urinary disturbance such as nervous pollakiuria, neurogenic bladder, nocturnal enuresis, unstable bladder, pollakiuria caused by a disease such as chronic cystitis, or urinary incontinence.
2. Description of the Background Art
In order to prevent and treat a urinary disturbance such as nervous pollakiuria, neurogenic bladder, nocturnal enuresis, unstable bladder, pollakiuria caused by a disease such as chronic cystitis, or urinary incontinence, drugs which inhibit reflex bladder contraction are useful.
As drugs for inhibiting the reflex bladder contraction, oxybutynin hydrochloride, propiverine hydrochloride, vamicamide and compounds described in Japanese Patent Application Laid-Open Nos. 92921/1994 and 135958/1994 and WO 93/16048 have heretofore been reported.
However, the conventional compounds have been found to be insufficient in the inhibitory effect on the reflex bladder contraction.
SUMMARY OF THE INVENTION
It is accordingly an object of the present invention to provide a compound which effectively inhibits reflex bladder contraction and is useful as a medicine for prophylaxis of and treatment for a urinary disturbance.
With the foregoing circumstances in view, the present inventors have carried out an extensive investigation. As a result, the inventors have synthesized a novel substituted piperidine derivative represented by the general formula (1), which will be described subsequently, and found that this compound has an anticholinergic effect and a calcium antagonism and effectively inhibits reflex bladder contraction and is hence useful as an agent for preventing and treating a urinary disturbance, thus leading to completion of the present invention.
According to the present invention, there is thus provided a substituted piperidine derivative represented by the following general formula (1):
wherein R
1
means an aryl or heteroaryl group which may have at least one substituent, R
2
denotes an alkyl, alkenyl or aralkyl group, R
3
stands for a hydrogen atom or an alkyl group, and R
4
is a hydrogen atom, an alkyl group, or an aryl, heteroaryl, aralkyl, aralkenyl or heteroaralkyl group which may have at least one substituent, or a salt thereof.
According to the present invention, there is also provided a medicine comprising the substituted piperidine derivative or the salt thereof as an active ingredient.
According to the present invention, there is further provided a medicine composition comprising the substituted piperidine derivative or the salt thereof and a pharmaceutically permissible carrier.
According to the present invention, there is still further provided use of the substituted piperidine derivative or the salt thereof for a medicine.
According to the present invention, there is yet still further provided a method for treating a urinary disturbance, which comprises administering an effective amount of the substituted piperidine derivative or the salt thereof.
The substituted piperidine derivative (1) according to the present invention or the salt thereof has excellent anticholinergic effect and calcium antagonism and effectively inhibits reflex bladder contraction and is hence useful as an agent for preventing and treating a urinary disturbance such as nervous pollakiuria, neurogenic bladder, nocturnal enuresis, unstable bladder, pollakiuria caused by a disease such as chronic cystitis, or urinary incontinence.
The above and other objects, features and advantages of the present invention will be readily appreciated as the same becomes better understood from the preferred embodiments of the present invention, which will be described subsequently in detail, and from the appended claims.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The substituted piperidine derivative according to the present invention is represented by the general formula (1). Examples of the aryl group indicated by R
1
in the formula (1) include phenyl and naphthyl groups, while examples of the heteroaryl group include thienyl, pyridyl, pyrimidyl and pyrazyl groups. Examples of radicals which may be substituted on the aryl or heteroaryl group indicated by R
1
include halogen atoms, and alkyl, halogenoalkyl, alkoxyl, amino, benzyloxy, cyano, benzoyl, alkanoyl, carbamoyl, carboxyl, alkanoyloxy, nitro and sulfonamide groups. Of these, preferred are one to three radicals selected from the group consisting of halogen atoms, halogenated C
1-6
alkyl groups, C
1-6
alkyl groups, C
1-6
alkoxyl groups, an amino group, a benzyloxy group, a cyano group, a benzoyl group, C
1-6
alkanoyl groups, a carbamoyl group, a carboxyl group, C
1-6
alkanoyloxy groups, a nitro group and a sulfonamide group. More preferred are one to three radicals selected from the group consisting of halogen atoms, halogenated C
1-6
alkyl groups, C
1-6
alkyl groups, C
1-6
alkoxyl groups and an amino group. Still more preferred are one to three radicals selected from the group consisting of halogen atoms, C
1-6
alkyl groups, halogenated C
1-6
alkyl groups and C
1-6
alkoxyl groups. Most preferred are one to three radicals selected from the group consisting of halogen atoms, and methyl, trifluoromethyl and methoxyl groups.
As R
1
, the aryl or heteroaryl group which may have at least one of the above substituents are preferred, with the phenyl, thienyl or pyridyl group which may have at least one of the above substituents being particularly preferred.
Examples of the alkyl group indicated by R
2
include linear, branched, cyclic and cyclic-linear alkyl groups having 1-8 carbon atoms. The linear alkyl groups having 1-8 carbon atoms include methyl, ethyl n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl and n-octyl groups. Examples of the branched alkyl groups include isopropyl, isobutyl, sec-butyl, 3-pentyl and 2-ethylhexyl groups. The cyclic alkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl groups. Examples of the cyclic-linear alkyl groups include cyclopropylmethyl and cyclohexylmethyl groups. Of these, the branched or cyclic alkyl groups are particularly preferred.
Examples of the alkenyl group indicated by R
2
include alkenyl groups having 2-6 carbon atoms. Specific examples thereof include vinyl and allyl groups, with the vinyl group being particularly preferred.
Examples of the aralkyl group indicated by R
2
include phenyl-C
1-6
-alkyl and naphthyl-C
1-6
-alkyl groups. Of these, the phenyl-C
1-6
-alkyl groups are preferred, with a benzyl group being particularly preferred.
Examples of the alkyl group indicated by R
3
include alkyl groups having 1-6 carbon atoms. Specific examples thereof include methyl and ethyl groups, and linear or branched propyl, butyl, pentyl and hexyl groups. Of these, the methyl group is particularly preferred. As R
3
, a hydrogen atom or a methyl group is particularly preferred.
As the alkyl group indicated by R
4
, those having 1-6 carbon atoms are preferred. Examples thereof include methyl and ethyl groups, and linear or branched propyl, butyl, pentyl and hexyl groups. Examples of the aryl group include phenyl and naphthyl groups. Examples of the heteroaryl group include thienyl, pyridyl, pyrimidyl and pyrazyl groups. Examples of the aralkyl group include phenyl-C
1-6
-alkyl groups. Specific examples thereof include benzyl, phenethyl and phenylpropyl groups. Examples of the heteroaralkyl group include heteroaryl-C
1-6
-alkyl groups. Specific examples thereof include pyridylmethyl, pyrimidylmethyl, pyrazylmethyl, pyridylethyl, pyrimidylethyl and pyrazylethyl groups. Examples of the aralkenyl group include phenyl-C
2-6
-alkenyl groups. Specific examples thereof include styryl and cinnamyl groups.
Examples of radicals which may be substituted on the aryl, heteroaryl, aralkyl, aralkenyl or het
Honda Haruyoshi
Ishikawa Masago
Kaihoh Terumitsu
Konno Fujiko
Matsuda Hideaki
Chang Ceila
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
SS Pharmaceutical Co., Ltd.
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