Use of tetrahydropyridine derivatives to prepare medicines...

Details Use of tetrahydropyridine derivatives to prepare medicines... Use of tetrahydropyridine derivatives to prepare medicines...

2000-04-18

2002-02-05

Criares, Theodore J. (Department: 1617)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C514S318000

Reexamination Certificate

active

06344464

ABSTRACT:

The present invention relates to the use of certain tetrahydropyridines for the preparation of drugs intended for the treatment of diseases which cause destruction of myelin.
These pathological conditions share the characteristic of being of inflammatory or autoimmune origin and of causing loss of myelin in the central nervous system. It is possible to draw a distinction principally between chronic pathological conditions, such as multiple sclerosis, and acute pathological conditions, such as acute disseminated encephalomyelitis and acute hemorrhagic leukoencephalitis. Among these pathological conditions, multiple sclerosis is the most widespread and leads to very serious sensory and visual motor dysfunctions.
No effective therapy is currently available for these diseases, and the treatments are limited to symptomatic treatments aimed at improving spastic hypertonia, fatigue and pain, or, since the origin of these pathological conditions is often said to be autoimmune, symptomatic treatments aimed at suppressing the immunological response.
WO 93/11107 describes a class of N-hydroxyalkyl-1,2,3,6-tetrahydropyridines as protectors against the damage caused by hypoxia.
EP 0 101 381 describes trifluoromethylphenyltetrahydropyridine derivatives having an anorexigenic activity and EP 0 458 696 describes their neuroprotective effects.
WO 97/01536 describes 1-phenylalkyl-1,2,3,6-tetrahydropyridines also having a neurotrophic and neuroprotective activity.
It has now been found that certain tetrahydropyridines exert a beneficial action on diseases which cause destruction of myelin.
Thus the present invention relates to the use of a compound of formula (I):
in which:
R
1
is a halogen or a CF
3
, (C
1
-C
4
)alkyl or (C
1
-C
4
)alkoxy group;
Y is a nitrogen atom or a CH group;
Z′ and Z″ are each hydrogen or a (C
1
-C
3
)alkyl group, or one is hydrogen and the other is a hydroxyl group, or the two together are an oxo group; and
Z is:
a phenyl radical;
a phenyl radical monosubstituted by a substituent X, X being:
(a) a (C
1
-C
6
)alkyl, (C
1
-C
6
)alkoxy, (C
3
-C
7
)carboxyalkyl, (C
1
-C
4
)alkoxycarbonyl(C
1
-C
6
)alkyl, (C
3
-C
7
)carboxyalkoxy or (C
1
-C
4
)alkoxycarbonyl(C
1
-C
6
)alkoxy group;
(b) a group selected from (C
3
-C
7
)cycloalkyl, (C
3
-C
7
)cycloalkoxy, (C
3
-C
7
)cycloalkylmethyl, (C
3
-C
7
)cycloalkylamino and cyclohexenyl, it being possible for said group to be substituted by a halogen, hydroxyl, (C
1
-C
4
)alkoxy, carboxyl, (C
1
-C
4
)alkoxycarbonyl, amino or mono- or di-(C
1
-C
4
)alkylamino; or
(c) a group selected from phenyl, phenoxy, phenylamino, N—(C
1
-C
3
)alkylphenylamino, phenylmethyl, phenylethyl, phenylcarbonyl, phenylthio, phenylsulfonyl, phenylsulfinyl and styryl, it being possible for said group to be monosubstituted or polysubstituted on the phenyl group by a halogen, CF
3
, (C
1
-C
4
)alkyl, (C
1
-C
4
)alkoxy, cyano, amino, mono- or di-(C
1
-C
4
)alkylamino, (C
1
-C
4
)acylamino, carboxyl, (C
1
-C
4
)alkoxycarbonyl, aminocarbonyl, mono- or di-(C
1
-C
4
)alkylaminocarbonyl, amino(C
1
-C
4
)alkyl, hydroxy(C
1
-C
4
)alkyl or halogeno(C
1
-C
4
)alkyl;
a phenyl radical disubstituted by a substituent R
2
, R
2
being a halogen or a hydroxyl, methyl, ethyl, (C
3
-C
6
)alkyl, (C
1
-C
4
)alkoxy or trifluoromethyl group, and by a substituent X, X being as defined above;
a 1-naphthyl or 2-naphthyl radical; or
a 1-naphthyl or 2-naphthyl radical substituted in the 5-, 6-, 7- and/or 8-positions by one or two hydroxyl groups, one or two (C
1
-C
4
)alkoxy groups or a 6,7-methylenedioxy group;
or Z″ is hydrogen and Z and Z′ are each independently an unsubstituted or mono-, di- or tri-substituted phenyl group,
or one of its pharmaceutically acceptable salts and solvates, for the preparation of pharmaceutical compositions intended for combating diseases which cause demyelination.
According to one advantageous aspect, the invention relates to the use of the compound of formula (I) in which Y is CH, R
1
is trifluoromethyl and Z′ and Z″ are hydrogen, or one of its pharmaceutically acceptable salts and solvates.
According to one preferred aspect, the invention relates to the use of the compound of formula (I) in which Y is CH, R
1
is trifluoromethyl, Z′ and Z″ are hydrogen and Z is a 2-naphthyl, 6,7-dimethoxy-2-naphthyl or 6,7-methylenedioxy-2-naphthyl group, or one of its pharmaceutically acceptable salts and solvates.
According to another advantageous aspect, the invention relates to the use of the compound of formula (I) in which Y is CH, R
1
is trifluoromethyl, Z′ and Z″ are hydrogen and Z is either a phenyl radical monosubstituted by a substituent X, X being:
(a) a (C
1
-C
6
)alkyl, (C
1
-C
6
)alkoxy, (C
3
-C
7
)carboxyalkyl, (C
1
-C
4
)alkoxycarbonyl(C
1
-C
6
)alkyl, (C
3
-C
7
)carboxyalkoxy or (C
1
-C
4
)alkoxycarbonyl(C
1
-C
6
)alkoxy group;
(b) a group selected from (C
3
-C
7
)cycloalkyl, (C
3
-C
7
)cycloalkoxy, (C
3
-C
7
)cycloalkylmethyl, (C
3
-C
7
)cycloalkylamino and cyclohexenyl, it being possible for said group to be substituted by a halogen, hydroxyl, (C
1
-C
4
)alkoxy, carboxyl, (C
1
-C
4
)alkoxycarbonyl, amino or mono- or di-(C
1
-C
4
)alkylamino; or
(c) a group selected from phenyl, phenoxy, phenylamino, N—(C
1
-C
3
)alkyl-phenylamino, phenylmethyl, phenylethyl, phenylcarbonyl, phenylthio, phenylsulfonyl, phenylsulfinyl and styryl, it being possible for said group to be monosubstituted or polysubstituted on the phenyl group by a halogen, CF
3
, (C
1
-C
4
)alkyl, (C
1
-C
4
)alkoxy, cyano, amino, mono- or di-(C
1
-C
4
)alkylamino, (C
1
-C
4
)acylamino, carboxyl, (C
1
-C
4
)alkoxycarbonyl, aminocarbonyl, mono- or di-(C
1
-C
4
)alkylaminocarbonyl, amino(C
1
-C
4
)alkyl, hydroxy(C
1
-C
4
)alkyl or halogeno(C
1
-C
4
)alkyl;
or a phenyl disubstituted by R
2
and X as defined above, or one of its pharmaceutically acceptable salts and solvates.
According to another advantageous aspect, the invention relates to the use of the compound of formula (I) in which Y is CH, R
1
is trifluoromethyl, Z′ and Z″ are hydrogen and Z is either a phenyl monosubstituted by a group X′, X′ being a phenyl which is unsubstituted or monosubstituted to trisubstituted by halogen, CF
3
, (C
1
-C
4
)alkyl, (C
1
-C
4
)alkoxy, cyano, amino, mono- or di-(C
1
-C
4
)alkylamino, (C
1
-C
4
)acylamino, carboxyl, (C
1
-C
4
)alkoxycarbonyl, aminocarbonyl, mono- or di-(C
1
-C
4
)alkylaminocarbonyl, amino(C
1
-C
4
)alkyl, hydroxy(C
1
-C
4
)alkyl or halogeno(C
1
-C
4
)alkyl; or a phenyl substituted by a substituent R
2
, R
2
being a halogen or a hydroxyl, methyl, ethyl, (C
3
-C
6
)alkyl, (C
1
-C
4
)alkoxy or trifluoromethyl group, and by a substituent X′, X′ being as defined above, or one of its pharmaceutically acceptable salts and solvates.
According to another advantageous aspect, the invention relates to the use of the compound of formula (I) in which Y is CH, R
1
is trifluoromethyl, Z′ and Z″ are hydrogen and Z is a phenyl group substituted in the 3- and 4-positions by a (C
1
-C
6
)alkyl group, or one of its pharmaceutically acceptable salts and solvates.
According to another advantageous aspect, the invention relates to the use of the compound of formula (I) in which Y is CH, R
1
is trifluoromethyl, Z″ is hydrogen and Z and Z′, which are identical, are each a phenyl group; a phenyl group substituted in the 2-, 3- or 4-position by a fluorine or chlorine atom or by a methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, trifluoromethyl, cyano, methoxy, methylthio, methylsulfonyl, ethoxy, ethylthio, ethylsulfonyl, (C
1
-C
3
)alkoxycarbonyl or di(C
1
-C
3
)alkylaminocarbonyl group; a phenyl group disubstituted in the 2,4-, 3,4-, 3,5- or 2,6-positions by a chlorine or fluorine atom or by a methyl, ethyl, trifluoromethyl, cyano or methoxy group; or a phenyl group trisubstituted in the 3,4,5-, 2,4,5- or 2,4,6-positions by a chlorine or fluorine atom or by a methyl, ethyl, trifluoromethyl, cyano or methoxy group, or one of its pharmaceutically acceptable salts and

Affiliated with

Also associated with

Rating

Use of tetrahydropyridine derivatives to prepare medicines... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Use of tetrahydropyridine derivatives to prepare medicines..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of tetrahydropyridine derivatives to prepare medicines... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2944450