Cycloalkylated benzothiadiazines, a process for their preparation and pharmaceutical compositions containing them
Compounds of formula (I): wherein: R Cy represents an unsubstituted or substituted cycloalkyl group or cycloalkylalkyl group, R 1 , R 2 , R 3 and R 4 , which may be the same or different, each represent a hydrogen or halogen atom or a nitro group; a cyano group; a hydroxy group; an alkoxy group; an alkyl group; an unsubstituted or substituted amino group; a carboxy group; an alkoxycarbonyl group; an aryloxycarbonyl group; an unsubstituted or substituted aminocarbonyl group. Medicinal products containing the same which are useful in treating or preventing conditions treatable by an AMPA receptor modulator.
1. A compound selected from those of formula (I):
wherein:
R Cy represents:
a (C 3 -C 8 )cycloalkyl group which is unsubstituted or substituted by one or more identical or different groups selected from linear or branched (C 1 -C 6 )alkyl which is unsubstituted or substituted by one or more halogen atoms; linear or branched (C 1 -C 6 )alkoxy; hydroxy; and amino which is unsubstituted or substituted by one or two linear or branched (C 1 -C 6 )alkyl groups;
or a (C 3 -C 8 )cycloalkyl-(C 1 -C 6 )alkyl group in which the alkyl moiety is linear or branched and which is unsubstituted or substituted on the cyclic moiety by one or more identical or different groups selected from linear or branched (C 1 -C 6 )alkyl which is unsubstituted or substituted by one or more halogen atoms; linear or branched (C 1 -C 6 )alkoxy; hydroxy; and amino which is unsubstituted or substituted by one or two linear or branched (C 1 -C 6 )alkyl groups;
R 1 , R 2 , R 3 and R 4 , which may be the same or different, each represent a hydrogen atom; a halogen atom; a nitro group; a cyano group; a hydroxy group; a linear or branched (C 1 -C 6 )alkyl group which is unsubstituted or substituted by one or more halogen atoms; a linear or branched (C 1 -C 6 )cyanoalkyl group; a linear or branched (C 1 -C 6 )hydroxyalkyl group; a linear or branched (C 1 -C 6 )alkoxy group which is unsubstituted or substituted by one or more halogen atoms; a linear or branched (C 1 -C 6 )alkylthio group; a carboxy group; a linear or branched (C 1 -C 6 )alkoxycarbonyl group; an aryloxycarbonyl group; a linear or branched (C 1 -C 6 )acyl group; an amino group which is unsubstituted or substituted by one or two linear or branched (C 1 -C 6 )alkyl groups or by a linear or branched (C 1 -C 6 )acyl group; an aminocarbonyl group which is unsubstituted or substituted by one or two linear or branched (C 1 -C 6 )alkyl groups; an arylaminocarbonyl group; or a linear or branched (C 1 -C 6 )alkylsulphonylamino group;
its enantiomers, diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base,
it being understood that:
“aryl” means a phenyl group which is unsubstituted or substituted by one or more identical or different groups selected from linear or branched (C 1 -C 6 )alkyl which is unsubstituted or substituted by one or more halogen atoms; linear or branched (C 1 -C 6 )alkoxy; hydroxy; and amino which is unsubstituted or substituted by one or two linear or branched (C 1 -C 6 )alkyl groups.
2. The compound of claim 1 , wherein R Cy represents a (C 3 -C 8 )cycloalkyl group.
3. The compound of claim 1 , wherein R Cy represents a cyclopropyl group.
4. The compound of claim 1 , wherein R Cy represents a (C 3 -C 8 )cycloalkyl-(C 1 -C 6 )alkyl group in which the alkyl moiety is linear or branched.
5. The compound of claim 1 , wherein R Cy represents a cyclopropylmethyl group.
6. The compound of claim 1 , wherein R 1 represents a hydrogen atom or a halogen atom.
7. The compound of claim 1 , wherein R 2 represents a hydrogen atom, a halogen atom, a methyl group, a cyano group or a carboxy group.
8. The compound of claim 1 , wherein R 3 represents a hydrogen atom, a halogen atom or a methyl group.
9. The compound of claim 1 , wherein R 4 represents a hydrogen atom or a halogen atom.
10. The compound of claim 1 , wherein two of the groups R 1 , R 2 , R 3 and R 4 are other than a hydrogen atom.
11. The compound of claim 1 , wherein two of the groups R 1 , R 2 , R 3 and R 4 represent a halogen atom and R Cy represents a cyclopropyl group.
12. The compound of claim 1 , which is selected from:
6,7-dichloro-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
8-chloro-4-cyclopropyl-6-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
8-bromo-4-cyclopropyl-6-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
6-cyano-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
8-bromo-6-chloro-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
4-cyclopropyl-5-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
8-bromo-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
4-cyclopropyl-5,7-difluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
6-fluoro-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
8-chloro-4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
4-cyclopropyl-3,4-dihydro-6-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide;
4-cyclopropyl-8-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
8-chloro-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
6-bromo-4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
6-bromo-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
4-cyclopropyl-6,8-difluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
4-cyclopropyl-5,6-difluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
4-cyclopropyl-3,4-dihydro-7-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide;
6-chloro-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
4-cyclopropyl-3,4-dihydro-6-iodo-2H-1,2,4-benzothiadiazine 1,1-dioxide;
6,7-dichloro-4-(1-methyl)cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
4-cyclopropylmethyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
6-carboxy-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
4-cyclopropyl-7,8-difluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
8-bromo-6-cyano-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide;
7-bromo-4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide,
and addition salts with a pharmaceutically acceptable acid or base.
13. A compound selected from those of formula (IV):
wherein:
R Cy represents:
a (C 3 -C 8 )cycloalkyl group which is unsubstituted or substituted by one or more identical or different groups selected from linear or branched (C 1 -C 6 )alkyl which is unsubstituted or substituted by one or more halogen atoms; linear or branched (C 1 -C 6 )alkoxy; hydroxy; and amino which is unsubstituted or substituted by one or two linear or branched (C 1 -C 6 )alkyl groups;
or a (C 3 -C 8 )cycloalkyl-(C 1 -C 6 )alkyl group in which the alkyl moiety is linear or branched and which is unsubstituted or substituted on the cyclic moiety by one or more identical or different groups selected from linear or branched (C 1 -C 6 )alkyl which is unsubstituted or substituted by one or more halogen atoms; linear or branched (C 1 -C 6 )alkoxy; hydroxy; and amino which is unsubstituted or substituted by one or two linear or branched (C 1 -C 6 )alkyl groups;
R 1 , R 2 , R 3 and R 4 , which may be the same or different, each represent a hydrogen atom; a halogen atom; a nitro group; a cyano group; a hydroxy group; a linear or branched (C 1 -C 6 )alkyl group which is unsubstituted or substituted by one or more halogen atoms; a linear or branched (C 1 -C 6 )cyanoalkyl group; a linear or branched (C 1 -C 6 )hydroxyalkyl group; a linear or branched (C 1 -C 6 )alkoxy group which is unsubstituted or substituted by one or more halogen atoms; a linear or branched (C 1 -C 6 )alkylthio group; a carboxy group; a linear or branched (C 1 -C 6 )alkoxycarbonyl group; an aryloxycarbonyl group; a linear or branched (C 1 -C 6 )acyl group; an amino group which is unsubstituted or substituted by one or two linear or branched (C 1 -C 6 )alkyl groups or by a linear or branched (C 1 -C 6 )acyl group; an aminocarbonyl group which is unsubstituted or substituted by one or two linear or branched (C 1 -C 6 )alkyl groups; an arylaminocarbonyl group; or a linear or branched (C 1 -C 6 )alkylsulphonylamino group;
its enantiomers, diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base,
it being understood that:
“aryl” means a phenyl group which is unsubstituted or substituted by one or more identical or different groups selected from linear or branched (C 1 -C 6 )alkyl which is unsubstituted or substituted by one or more halogen atoms; linear or branched (C 1 -C 6 )alkoxy; hydroxy; and amino which is unsubstituted or substituted by one or two linear or branched (C 1 -C 6 )alkyl groups.
14. A pharmaceutical composition comprising as active ingredient a compound of claim 1 in combination with one or more inert, non-toxic, pharmaceutically acceptable carriers.
15. A method for treating a condition selected from anxiety, depression, with Parkinson's disease, Pick's disease, Huntington's chorea, Korsakoff's disease, and schizophrenia, such method comprising the step of administering to a living animal body, including a human, a therapeutically effective amount of a compound of claim 1 .