Positive allosteric AMPA receptor modulators

Details Positive allosteric AMPA receptor modulators Positive allosteric AMPA receptor modulators

2001-01-31

2003-02-25

Ford, John M. (Department: 1624)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C544S033000, C544S014000

Reexamination Certificate

active

06525045

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to novel compounds that are positive allosteric AMPA receptor modulators, processes for preparing them and their use, as pharmaceutical compositions, in the treatment of various disease conditions.
DESCRIPTION OF THE INVENTION
The compounds according to the invention are compounds of general formula (I)
wherein
A denotes a sulphur atom, oxygen atom, NH or N—C
1
-C
4
-alkyl,
R
1
denotes a group selected from among hydrogen, a C
1
-C
6
-alkyl group optionally substituted by one or more halogen atoms, —SO
2
H, —SO
2
—C
1
-C
6
-alkyl, —SO—C
1
-C
6
-alkyl, —CO—C
1
-C
6
-alkyl, —O, phenyl-C
1
-C
4
-alkyl, —C
1
-C
4
-alkyl-NR
7
R
8
,
—C
1
-C
4
-alkyl-O—C
1
-C
4
-alkyl and C
3
-C
6
-cycloalkyl,
R
2
, R
9
, which may be identical or different, denote a group selected from among hydrogen, a C
1
-C
6
-alkyl group optionally substituted by one or more halogen atoms, halogen, —NO
2
, —SO
2
H, —SO
2
—C
1
-C
6
-alkyl, —SO—C
1
-C
6
-alkyl, —CO—C
1
-C
6
-alkyl, —OH, —O—C
1
-C
6
-alkyl, —S—C
1
-C
6
-alkyl, —C
1
-C
4
-alkyl-NR
7
R
8
and —C
1
-C
4
-alkyl-O—C
1
-C
4
-alkyl, C
3
-C
6
-cycloalkyl, or
R
1
and R
2
together denote a C
2
-C
6
-alkylene bridge,
R
7
, R
8
, which may be identical or different, denote hydrogen or C
1
-C
4
-alkyl, and
R
3
, R
4
, R
5
, R
6
, which may be identical or different, denote a group selected from among hydrogen, a C
1
-C
6
-alkyl group optionally substituted by one or more halogen atoms, phenyl-C
1
-C
4
-alkyl, halogen, —CN, —NO
2
, —SO
2
H, —SO
3
H, —SO
2
—C
1
-C
6
-alkyl, —SO—C
1
-C
6
-alkyl, —SO
2
—NR
7
R
8
, —COOH, —CO—C
1
-C
6
-alkyl, —O—CO—C
1
-C
4
-alkyl, —CO—O—C
1
-C
4
-alkyl, —CO—NR
7
R
8
, —OH, —O—C
1
-C
6
-alkyl, —S—C
1
-C
6
-alkyl, —NR
7
R
8
and an aryl group optionally mono- or polysubstituted by halogen atoms, —NO
2
, —SO
2
H or C
1
-C
4
-alkyl,
optionally in the form of the various enantiomers and diastereomers thereof, as well as the pharmacologically acceptable salts thereof.
Compounds of general formula (I) are preferred wherein
A denotes a sulphur atom, oxygen atom or N—C
1
-C
2
-alkyl,
R
1
denotes a group selected from among hydrogen, a C
1
-C
6
-alkyl group optionally substituted by one or more halogen atoms, —SO
2
H, —SO
2
—C
1
-C
6
-alkyl, —SO—C
1
-C
6
-alkyl, —CO—C
1
-C
6
-alkyl, —O, —C
1
-C
4
-alkyl-NR
7
R
8
and —C
1
-C
4
-alkyl—O—C
1
-C
4
-alkyl, benzyl,
R
2
, R
9
, which may be identical or different, denote a group selected from among hydrogen, a C
1
-C
6
-alkyl group optionally substituted by one or more halogen atoms, halogen, —NO
2
, —SO
2
H, —SO
2
—C
1
-C
6
-alkyl, —SO—C
1
-C
6
-alkyl, —CO—C
1
-C
6
-alkyl, —OH, —O—C
1
-C
6
-alkyl, —S—C
1
-C
6
-alkyl, —C
1
-C
4
-alkyl-NR
7
R
8
and —C
1
-C
4
-alkyl-O—C
1
-C
4
-alkyl, or
R
1
and R
2
together denote a C
3
-C
6
-alkylene bridge, and
R
3
, R
4
, R
5
, R
6
, which may be identical or different, denote a group selected from among hydrogen, a C
1
-C
4
-alkyl group optionally substituted by one or more halogen atoms, phenyl-C
1
-C
4
-alkyl, halogen, —CN, —NO
2
, —SO
2
H, —SO
3
H, —SO
2
CH
3
, —SOCH
3
, —CO—C
1
-C
4
-alkyl, —OH, —O—C
1
-C
4
-alkyl and —S—C
1
-C
4
-alkyl,
optionally in the form of the various enantiomers and diastereomers thereof, as well as the pharmacologically acceptable salts thereof.
Compounds of general formula (I) are particularly preferred wherein
A denotes a sulphur atom or N—C
1
-C
2
-alkyl,
R
1
, R
2
, R
9
, which may be identical or different, denote hydrogen, C
1
-C
4
-alkyl, benzyl or
R
1
and R
2
together denote a C
3
-C
4
-alkylene bridge, and R
3
, R
4
, R
5
, R6 , which may be identical or different, denote a group selected from among hydrogen, C
1
-C
4
-alkyl, CF
3
, NO
2
, benzyl, —SO
2
—C
1
-C
4
-alkyl, —SO
3
H and halogen, preferably fluorine, chlorine, bromine, most preferably fluorine or chlorine, optionally in the form of the various enantiomers and diastereomers thereof, as well as the pharmacologically acceptable salts thereof.
Also particularly preferred are compounds of general formula (I) wherein
A denotes a sulphur atom or N—CH
3
,
R
1
, R
2
, R
9
which may be identical or different, denote hydrogen, C
1
-C
4
-alkyl or
R
1
and R
2
together denote a C
3
-C
4
-alkylene bridge,
R
3
, R
5
, R
6
, which may be identical or different, denote a group selected from among hydrogen, C
1
-C
4
-alkyl and halogen, preferably fluorine, chlorine, bromine, most preferably fluorine or chlorine, and
R
4
denotes hydrogen, halogen or C
1
-C
4
-alkyl,
optionally in the form of the various enantiomers and diastereomers thereof, as well as the pharmacologically acceptable salts thereof.
Of particular importance according to the invention are the compounds of general formula (I) wherein
R
1
denotes methyl, ethyl, i-propyl, n-butyl or benzyl, optionally in the form of the various enantiomers and diastereomers thereof, as well as the pharmacologically acceptable salts thereof.
Particularly preferred are compounds of general formula (I), wherein
A denotes a sulphur atom,
R
1
denotes methyl,
R
2
, R
9
denote hydrogen,
R
3
denotes a group selected from among hydrogen, methyl, CN and halogen, preferably fluorine, chlorine, bromine, most preferably fluorine or chlorine,
R
5
denotes a group selected from among hydrogen, methyl and halogen, preferably fluorine, chlorine, bromine, most preferably fluorine or chlorine,
R
4
denotes hydrogen, and
R
6
denotes hydrogen or methyl, preferably hydrogen,
optionally in the form of the pharmacologically acceptable salts thereof.
Most particularly preferred are compounds of general formula (I), wherein
A denotes a sulphur atom,
R
1
denotes methyl,
R
3
denotes hydrogen, fluorine or chlorine, and
R
2
, R
4
, R5, R6, R9 denote hydrogen,
optionally in the form of the pharmacologically acceptable salts thereof.
The alkyl groups used, unless otherwise stated, are branched and unbranched alkyl groups having 1 to 6 carbon atoms, preferably I to 4 carbon atoms. Examples include: methyl, ethyl, propyl, butyl, pentyl and hexyl. The groups methyl, ethyl, propyl or butyl may optionally also be referred to by the abbreviations Me, Et, Prop or Bu. Unless otherwise stated, the definitions propyl, butyl, pentyl and hexyl also include all possible isomeric forms of the groups in question. Thus, for example, propyl includes n-propyl and iso-propyl, butyl includes iso-butyl, sec. butyl and tert.-butyl, etc.
In the abovementioned alkyl groups, one or more hydrogen atoms may optionally be substituted by the halogen atoms fluorine, chlorine, bromine or iodine. The substituents fluorine and chlorine are preferred. The substituent fluorine is particularly preferred. If desired, all the hydrogen atoms of the alkyl group may be replaced.
The alkyl group mentioned in the group phenyl-C
1
-C
4
-alkyl may be in branched or unbranched form. Unless otherwise stated benzyl and phenylethyl are preferred phenyl-C
1
-C
4
-alkyl groups. Benzyl is particularly preferred.
The C
2
-C
6
-alkylene bridge may, unless otherwise stated, be branched and unbranched alkylene groups having 2 to 6 carbon atoms, for example ethylene, propylene, methylethylene, dimethylmethylene, n-butylene, 1-methylpropylene, 2-methylpropylene, 1.1-dimethylethylene, 1 .2-dimethylethylene etc. n-Propylene and n-butylene bridges are particularly preferred.
The aryl group is an aromatic ring system having 6-10 carbon atoms, preferably phenyl. In the abovementioned aryl groups, one or more hydrogen atoms may optionally be substituted by halogen atoms, —NO
2
, —SO
2
H or —C
1
-C
4
-alkyl, preferably fluorine, chlorine, —NO
2
, ethyl or methyl, most preferably fluorine or methyl.
The term C
3
-C
6
-cycloalkyl denotes saturated cyclic hydrocarbon groups having 3-6 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
The term halogen, unless otherwise stated, refers to fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine and bromine, most preferably fluorine and chlorine, most preferably fluorine.
As already mentioned, the compounds of formula (I) or the various enantiomers and diastereomers thereo

Affiliated with

Also associated with

Rating

Positive allosteric AMPA receptor modulators does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Positive allosteric AMPA receptor modulators, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Positive allosteric AMPA receptor modulators will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3154824