Thiophene-2-carboxamide derivatives, preparation thereof and therapeutic use thereof

1. Compound of formula (I):

in which:

R 1 and R 2 , together with the nitrogen atom to which they are bonded, form:

a saturated heterocyclic radical of 4 to 7 atoms comprising a nitrogen atom which is unsubstituted or substituted once or twice by a substituent each independently chosen from:

a cyano, —COR 11 , —CH 2 NHR 12 , —(C 3 -C 7 )cycloalkyl, —CH 2 COR 11 , —NR 12 R 13 , —NHCOR 14 , —SO 2 R 14 and/or —SO 2 NR 12 R 13 group;

and/or a phenyl, benzyl or pyridinyl group; the said groups being unsubstituted or substituted one or more times by a substituent each independently chosen from a halogen atom or a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy and/or cyano group;

and/or a piperidin-1-yl, pyrrolidin-1-yl or azetidin-1-yl group, the said groups being unsubstituted or substituted one or more times by a substituent each independently chosen from a fluorine atom or a (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, hydroxyl, trifluoromethyl and/or OCF 3 group;

and/or a phenylamino or benzylamino group, the said groups being unsubstituted or substituted one or more times by a substituent each independently chosen from a halogen atom or a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy and/or cyano group;

R 3 , R 4 , R 5 , R 6 , R 7 and R 8 each independently represent a hydrogen atom, a halogen atom, a —CN, —S(O) n R 14 , —OSO 2 R 14 or (C 1 -C 6 )alkyl group and/or a (C 1 -C 6 )alkoxy group, the said groups being unsubstituted or substituted one or more times by a fluorine atom, provided that one of the two substituents R 3 and R 6 represents a Y-A-R 9 group;

Y represents an oxygen atom;

A represents a (C 1 -C 4 )alkylene group which is unsubstituted or substituted one or more times by a substituent each independently chosen from a (C 1 -C 3 )alkyl group and/or by a fluorine atom;

R 9 represents an —OR 19 , —CN, —CH 3 , —CF 3 , —NR 19 R 20 , —CO 2 R 19 , —CONR 19 R 20 , —NR 15 COR 19 , —CONHNH 2 , —CONHOH, —CONHSO 2 R 21 , —S(O) n R 21 , —SO 2 NR 19 R 20 , —NR 18 SO 2 R 21 or —NR 15 SO 2 NR 19 R 20 group;

R 10 represents a hydrogen atom or a (C 1 -C 4 )alkyl group and preferably a hydrogen atom;

R 11 represents:

a (C 1 -C 4 )alkyl, phenyl, benzyl, (C 1 -C 4 )alkoxy or (C 1 -C 3 )alkylene-O—(C 1 -C 3 )alkyl group, the said groups being unsubstituted or substituted by a substituent each independently chosen from a (C 1 -C 4 )alkoxy group and/or a hydroxyl group and/or by one or more fluorine atoms;

and/or an —NR 16 R 17 group;

R 12 and R 13 each independently represent a hydrogen atom or a (C 1 -C 6 )alkyl group optionally substituted one or more times by a substituent each independently chosen from a fluorine atom, an —OH group and/or an —OR 14 group;

or R 12 and R 13 , together with the nitrogen atom to which they are bonded, form a 4- to 7-membered heterocyclic radical which can comprise a second heteroatom chosen from a nitrogen, oxygen or sulphur atom;

n represents 0, 1 or 2;

n′ represents 0, 1 or 2;

R 14 represents a (C 1 -C 4 )alkyl group which is unsubstituted or substituted one or more times by a fluorine atom;

R 15 represents a hydrogen atom or a (C 1 -C 4 )alkyl group;

R 16 and R 17 each independently represent:

a hydrogen atom;

and/or a benzyl group which is unsubstituted or substituted one or more times by a substituent each independently chosen from a halogen atom or a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy and/or cyano group;

and/or a (C 1 -C 6 )alkyl group optionally substituted one or more times by a substituent each independently chosen from a halogen atom or an —OH and/or an —OR 14 group;

R 18 represents a hydrogen atom or a (C 1 -C 4 )alkyl group which is unsubstituted or substituted one or more times by a fluorine atom;

R 19 and R 20 each independently represent a hydrogen atom or a (C 1 -C 6 )alkyl group optionally substituted one or more times by a substituent each independently chosen from a fluorine atom, an —OH group and/or an —OR 14 group;

or R 19 and R 20 , together with the nitrogen atom to which they are bonded, form a 4- to 7-membered heterocyclic radical which can comprise a second heteroatom chosen from a nitrogen, oxygen or sulphur atom;

R 21 represents a (C 1 -C 4 )alkyl group which is unsubstituted or substituted one or more times by a fluorine atom;

or its salt.

2. Compound according to any one of claim 1 , in which:

R 3 represents a Y-A-R 9 group;

R 6 represents a hydrogen atom, a halogen atom, a —CN, —S(O) n R 14 or —OSO 2 R 14 group, a (C 1 -C 6 )alkyl group or a (C 1 -C 6 )alkoxy group, the said groups being unsubstituted or substituted one or more times by a fluorine atom;

and the other substituents are as defined for the compounds of formula (I);

or its salt.

3. Compound according to any one of claim 1 , in which:

R 6 represents a Y-A-R 9 group,

R 3 represents a hydrogen atom, a halogen atom, a —CN, —S(O) n R 14 or —OSO 2 R 14 group, a (C 1 -C 6 )alkyl group or a (C 1 -C 6 )alkoxy group, the said groups being unsubstituted or substituted one or more times by a fluorine atom;

and the other substituents are as defined for the compounds of formula (I);

or its salt.

4. Compound according to claim 1 , in which:

R 3 represents a Y-A-R 9 group;

R 4 , R 5 , R 6 , R 7 and R 8 each independently represent a hydrogen atom, a halogen atom, a —CN group and/or a (C 1 -C 6 )alkyl group, the said group being unsubstituted or substituted one or more times by a fluorine atom;

and the other substituents are as defined for the compounds of formula (I);

or its salt.

5. Compound according to claim 1 , in which:

R 6 represents a Y-A-R 9 group;

R 3 , R 4 , R 5 , R 7 and R 8 each independently represent a hydrogen atom, a halogen atom, a —CN group and/or a (C 1 -C 6 )alkyl group, the said group being unsubstituted or substituted one or more times by a fluorine atom;

and the other substituents are as defined for the compounds of formula (I);

or its salt.

6. Compound of formula (I) according to claim 1 , in which:

A represents an unsubstituted (C 1 -C 4 )alkylene group;

and the other substituents are as defined for the compounds of formula (I);

or its salt.

7. Compound of formula (I) according to claim 1 , in which:

R 9 represents an —OR 19 , —CH 3 , —CF 3 , —NR 19 R 20 , —CONR 19 R 20 , —NR 15 COR 19 , —S(O) n R 21 or —NR 18 SO 2 R 21 group;

and the other substituents are as defined for the compounds of formula (I);

or its salt.

8. Compound of formula (I) according to claim 1 , in which:

Y represents an oxygen atom or a sulphur atom;

and the other substituents are as defined for the compounds of formula (I);

or its salt.

9. Compound of formula (I) according to claim 1 , in which:

R 1 and R 2 , together with the nitrogen atom to which they are bonded, form a homopiperidin-1-yl, piperidin-1-yl, pyrrolidin-1-yl or azetidin-1-yl radical, the said radical being substituted once or twice by a substituent each independently chosen from:

a cyano, —COR 11 , —NR 12 R 13 , —NHCOR 14 , —CH 2 COR 11 , —SO 2 R 14 and/or —SO 2 NR 12 R 13 group;

and/or a phenyl, benzyl or pyridinyl group; the said groups being unsubstituted or substituted one or more times by a substituent each independently chosen from a halogen atom or a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy and/or cyano group;

and/or a piperidin-1-yl, pyrrolidin-1-yl or azetidin-1-yl group, the said groups being unsubstituted or substituted one or more times by a substituent each independently chosen from a fluorine atom or a (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, hydroxyl, trifluoromethyl and/or OCF 3 group;

and/or a phenylamino or benzylamino group, the said groups being unsubstituted or substituted one or more times by a substituent each independently chosen from a halogen atom or a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy and/or cyano group;

and/or an amino(C 1 -C 6 )alkyl group which is unsubstituted or substituted one or more times by a substituent each independently chosen from a halogen atom or a hydroxyl, (C 1 -C 4 )alkoxy and/or cyano group;

and/or an amino(C 3 -C 7 )cycloalkyl group which is unsubstituted or substituted one or more times by a substituent each independently chosen from a halogen atom or a hydroxyl, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy and/or cyano group, the said (C 1 -C 4 )alkyl group being unsubstituted or substituted one or more times by a fluorine atom;

and the other substituents are as defined for the compounds of formula (I);

or its salt.

10. Compound of formula (I) according to claim 9 , in which:

R 1 and R 2 , together with the nitrogen atom to which they are bonded, form a homopiperidin-1-yl, piperidin-1-yl, pyrrolidin-1-yl or azetidin-1-yl radical, the said radical being gem-disubstituted:

the first substituent being chosen from a cyano, —COR 11 , —NHCOR 14 or —SO 2 R 14 group;

the second substituent being chosen from:

NR 12 R 13 ;

and/or a phenyl group, the said group being unsubstituted or substituted one or more times by a substituent each independently chosen from a halogen atom or a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy and/or cyano group;

and/or a piperidin-1-yl group, the said group being unsubstituted or substituted one or more times by a substituent each independently chosen from a fluorine atom or a (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, hydroxyl, trifluoromethyl and/or OCF 3 group;

and/or a benzylamino group, the said group being unsubstituted or substituted one or more times by a substituent each independently chosen from a halogen atom or a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy and/or cyano group;

and the other substituents are as defined for the compounds of formula (I);

or its salt.

11. Compound of formula (I) according to claim 10 , in which:

R 1 and R 2 , together with the nitrogen atom to which they are bonded, form a piperidin-1-yl or azetidin-1-yl radical, the said radical being gem-disubstituted:

the first substituent being —COR 11 ;

and the second substituent being chosen from —NR 12 R 13 , a phenyl group, a benzylamino group or a piperidin-1-yl group, the said piperidin-1-yl group being unsubstituted or substituted one or more times by a substituent each independently chosen from a fluorine atom or a (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, hydroxyl, trifluoromethyl and/or OCF 3 group;

and the other substituents are as defined for the compounds of formula (I);

or its salt.

12. Pharmaceutical composition, characterized in that it comprises a compound of formula (I) according to claim 1 or an addition salt of this compound of formula (I) with a pharmaceutically acceptable acid and at least one pharmaceutically acceptable excipient.