4-cyanopyrazole-3-carboxamide derivatives, preparation and application thereof

1. A compound of formula (I):

wherein:

R 1 represents hydrogen or a (C 1 -C 4 )alkyl;

R 2 represents a (C 3 -C 7 )alkyl;

R 3 , R 4 , R 5 , R 6 , R 7 , R 8 represent, each independently of the other, a hydrogen, halogen, a (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or trifluoromethyl; provided that at least one of the substituents R 3 , R 4 , R 5 , R 6 , R 7 , R 8 is different from hydrogen; or

a pharmaceutically acceptable salt thereof.

2. The compound of formula (I) as set forth in claim 1 , wherein:

R 1 represents hydrogen or a (C 1 -C 4 )alkyl;

R 2 represents a group chosen from t-butyl and 1,1-dimethylpropyl;

at least one of the substituents R 3 , R 4 or R 5 represents a halogen atom, a methyl or methoxy; and

at least one of the substituents R 6 , R 7 or R 8 represents a halogen atom or a methyl; or

a pharmaceutically acceptable salt thereof.

3. The compound of formula (I) as set forth in claim 1 , wherein:

R 1 represents hydrogen;

R 2 represents a (C 3 -C 7 )alkyl;

R 3 is at the 4-position and represents chlorine, bromine or methoxy;

R 4 and R 5 are hydrogen;

R 6 and R 7 are at the 2,4-position and represent 2 chlorine atoms; and

R 8 is hydrogen; or

a pharmaceutically acceptable salt thereof.

4. The compound as set forth in claim 1 , chosen from:

5-(4-bromophenyl)-4-cyano-1-(2,4-dichlorophenyl)-N-tert-butyl-1H-pyrazole-3-carboxamide; and

5-(4-bromophenyl)-4-cyano-1-(2,4-dichlorophenyl)-N-(1,1-dimethylpropyl)-1H-pyrazole-3-carboxamide; or

a pharmaceutically acceptable salt thereof.

5. A method for preparing a compound of formula (I) as set forth in claim 1 , comprising reacting 4-cyano-1,5-diphenylpyrazole-3-carboxylic acid of formula II or a functional derivative thereof:

in which R 3 , R 4 , R 5 , R 6 , R 7 , R 8 are as defined in claim 1 , with an amine of formula HNR 1 R 2 (III) in which R 1 and R 2 are as defined in claim 1 .

6. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt in combination with at least one pharmaceutically acceptable excipient:

wherein:

R 1 represents hydrogen or a (C 1 -C 4 )alkyl;

R 2 represents a (C 3 -C 7 )alkyl;

R 3 , R 4 , R 5 , R 6 , R 7 , R 8 represent, each independently of the other, a hydrogen, halogen, a (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or trifluoromethyl; provided hat at least one of the substituents R 3 , R 4 , R 5 , R 6 , R 7 , R 8 is different from hydrogen.

7. The composition as set forth in claim 6 wherein:

R 1 represents hydrogen or a (C 1 -C 4 )alkyl;

R 2 represents a (C 3 -C 7 )alkyl;

at least one of the substituents R 3 , R 4 or R 5 represents a halogen atom, a methyl or methoxy; and

at least one of the substituents R 6 , R 7 or R 8 represents a halogen atom or a methyl.

8. The composition as set forth in claim 6 , wherein:

R 1 represents hydrogen;

R 2 represents a (C 3 -C 7 )alkyl;

R 3 is at the 4-position and represents chlorine, bromine or methoxy;

R 4 and R 5 are hydrogen;

R 6 and R 7 are at the 2,4-position and represent 2 chlorine atoms; and

R 8 is hydrogen.

9. The composition as set forth in claim 6 , wherein said compound is chosen from:

5-(4-bromophenyl)-4-cyano-1-(2,4-dichlorophenyl)-N-tert-butyl-1H-pyrazole-3-carboxamide; and

5-(4-bromophenyl)-4-cyano-1-(2,4-dichlorophenyl)-N-(1,1-dimethylpropyl)-1H-pyrazole-3-carboxamide; or

a pharmaceutically acceptable salt thereof.

10. A method for treating a disease or a disorder in a patient, said disease or disorder is selected from the group consisting of appetite disorder, gastrointestinal disorder, alcohol dependence and nicotine dependence, comprising administering to said patient a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof as set forth in claim 1 .

11. The method as set forth in claim 10 , wherein said compound is selected from:

5-(4-bromophenyl)-4-cyano-1-(2,4-dichlorophenyl)-N-tert-butyl-1H-pyrazole-3-carboxamide; and

5-(4-bromophenyl)-4-cyano-1-(2,4-dichlorophenyl)-N-(1,1-dimethylpropyl)-1H-pyrazole-3-carboxamide; or

a pharmaceutically acceptable salt thereof.

12. The method as set forth in claim 10 , wherein said disease or disorder is appetite disorder.

13. The method as set forth in claim 10 , wherein said disease or disorder is gastrointestinal disorder.

14. The method as set forth in claim 10 , wherein said disease or disorder is alcohol dependence.

15. The method as set forth in claim 10 , wherein said disease or disorder is nicotine dependence.