Acylaminothiazole derivatives, their preparation and therapeutic use

1. A compound corresponding to the general formula (I):

in which,

n is equal to 0, 1, 2 or 3;

X represents an oxygen or sulfur atom;

R 1 represents, independently of each other when n=2 or 3, a halogen atom, a hydroxyl, a C 1-3 alkyl, a C 1-3 alkoxy, a trifluoromethyl, a trifluoromethyloxy or a methylenedioxy;

R 2 represents a C 1-6 alkyl group optionally substituted with a C 3-7 cycloalkyl group, a phenyl, a C 1-3 alkoxy group, a hydroxyl or a halogen atom; a C 3-7 cycloalkyl, piperidinyl or phenyl group; the C 3-7 cycloalkyl, piperidinyl and phenyl groups being optionally substituted with one or more C 1-3 alkyl groups, C 1-3 alkoxy groups, a hydroxyl or a halogen atom;

R 3 represents a hydrogen atom or a C 1-6 alkyl group optionally substituted with a C 3-7 cycloalkyl group;

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

R 5 and R 5′ represent, independently of each other, a hydrogen atom, a hydroxyl, a halogen atom, or a C 1-3 alkyl group; or R 5 and R 5′ form together an oxo group; and

R 6 represents a hydrogen atom, a halogen atom, a C 1-3 alkyl, a C 1-3 alkoxy, a trifluoromethyl or a trifluoromethoxy; or

said compound in the form of a base, an addition salt with an acid, a hydrate or a solvate.

2. The compound according to claim 1 wherein:

X represents an oxygen or sulphur atom;

R 1 represents, independently of each other when n=2 or 3, a halogen atom, a methylenedioxy, a C 1-3 alkyl group, a C 1-3 alkoxy group or a trifluoromethyloxy;

R 2 represents a C 1-4 alkyl group optionally substituted with a C 4-7 cycloalkyl or phenyl group; a C 4-7 cycloalkyl, piperidinyl or phenyl group; the C 4-7 cycloalkyl, piperidinyl and phenyl groups being optionally substituted with one or more C 1-3 alkyl or C 1-3 alkoxy groups;

R 3 represents a hydrogen atom or a C 1-4 alkyl group, optionally substituted with a C 4-7 cycloalkyl group;

R 4 represents a hydrogen atom or a C 1-3 alkyl group;

R 5 and R 5′ represent, independently of each other, a hydrogen or halogen atom, a hydroxyl or a C 1-3 alkyl group; or R 5 and R 5′ form together an oxo group; and

R 6 represents a hydrogen atom or a C 1-3 alkoxy; or

said compound in the form of a base, an addition salt with an acid, a hydrate or a solvate.

3. The compound of formula (I) according to claim 1 wherein:

X represents an oxygen atom;

R 1 represents, independently of each other when n=2 or 3, a halogen atom;

R 2 represents a C 1-4 alkyl group optionally substituted with a C 4-7 cycloalkyl or phenyl group; a C 4-7 cycloalkyl, piperidinyl or phenyl group;

the C 4-7 cycloalkyl, piperidinyl and phenyl groups being optionally substituted with 1 or 2 C 1-3 alkyl or C 1-3 alkoxy groups;

R 3 represents a methyl, ethyl or propyl;

R 4 represents a hydrogen atom or a methyl;

R 5 and R 5′ represent, independently of each other, a hydrogen or fluorine atom, a hydroxyl or a methyl; or R 5 and R 5′ form together an oxo group; and

R 6 represents a hydrogen atom or a methoxy; or

said compound in the form of a base, an addition salt with an acid, a hydrate or a solvate.

4. A method for preparing a compound of formula (I) according to claim 1 wherein:

a peptide coupling of the compound of formula (VII)

 with the amino acid of formula (VIII)

 in which n, X, R 1 , R 2 , R 3 , R 4 , R 5 and R 5′ are as defined in formula (I) according to claim 1 , is carried out.

5. A method for preparing a compound of formula (I) according to claim 1 in which R 3 does not represent a hydrogen atom, by peptide coupling of an amine of formula (XIII)

with an acid of formula (XIV)

in which n, X, R 1 , R 2 , R 3 , R 4 , R 5 and R 5′ are as defined in formula (I) according to claim 1 .

6. A pharmaceutical composition containing at least one compound of formula (I) according to claim 1 in the form of a pharmaceutically acceptable base, salt, hydrate or solvate and optionally one or more pharmaceutically acceptable excipients.

7. A method for preparing a compound of formula (I) according to claim 2 wherein:

a peptide coupling of the compound of formula (VII)

 with the amino acid of formula (VIII)

 in which n, X, R 1 , R 9 , R 3 , R 4 , R 5 and R 5′ are as defined in formula (I) according to claim 2 , is carried out.

8. A method for preparing a compound of formula (I) according to claim 3 wherein:

a peptide coupling of the compound of formula (VII)

 with the amino acid of formula (VIII)

 in which n, X, R 1 , R 2 , R 3 , R 4 , R 5 and R 5′ are as defined in formula (I) according to claim 2 , is carried out.

9. A method for preparing a compound of formula (I) according to claim 2 in which R 3 does not represent a hydrogen atom, by peptide coupling of an amine of formula (XIII)

with an acid of formula (XIV)

in which n, X, R 1 , R 9 , R 3 , R 4 , R 5 and R 5′ are as defined in formula (I) according to claim 2 .

10. A method for preparing a compound of formula (I) according to claim 3 in which R 3 does not represent a hydrogen atom, by peptide coupling of an amine of formula (XIII)

with an acid of formula (XIV)

in which n, X, R 1 , R 2 , R 3 , R 4 , R 5 and R 5′ are as defined in formula (I) according to claim 2 .

11. A pharmaceutical composition containing at least one compound of formula (I) according to claim 2 in the form of a pharmaceutically acceptable base, salt, hydrate or solvate and optionally one or more pharmaceutically acceptable excipients.

12. A pharmaceutical composition containing at least one compound of formula (I) according to claim 3 in the form of a pharmaceutically acceptable base, salt, hydrate or solvate and optionally one or more pharmaceutically acceptable excipients.