Pyrrole derivatives, their preparation and their therapeutic application

1. A Compound of formula (I):

in which:

A represents a (C 1 -C 6 )alkylene group which is unsubstituted or substituted one or more times with a (C 1 -C 3 )alkyl group or a fluorine atom;

R 1 and R 2 together with the nitrogen atom to which they are attached constitute:

either a piperazin-1-yl or 1,4-diazepan-1-yl radical, the said radicals being unsubstituted or substituted with a phenyl, benzodioxolyl, benzodioxolylmethyl, tetrahydrofuranylcarbonyl, —COR 11 , and/or —CH 2 COR 11 group; the phenyl group being itself unsubstituted or substituted once or several times with a substituent each independently chosen from a halogen atom, a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

or a homopiperidin-1-yl, piperidin-1-yl, pyrrolidin-1-yl or azetidin-1-yl radical, the said radicals being unsubstituted or substituted once or twice with a substituent each independently chosen from:

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

or a (C 1 -C 4 )alkyl group which is unsubstituted or substituted with one or more substituents each independently chosen from a halogen atom and/or a hydroxyl,

or a phenyl or pyridinyl group; the said groups being unsubstituted or substituted once or several times with a substituent each independently chosen from a halogen atom, a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

or a benzyl group which is unsubstituted or substituted once or several times with a substituent each independently chosen from a halogen atom, a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

or a piperidin-1-yl, pyrrolidin-1-yl or azetidin-1-yl group, the said groups being unsubstituted or substituted once or several times with a substituent each independently chosen from a fluorine atom, a (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, hydroxyl, trifluoromethyl or —OCF 3 group;

or an aminophenyl or aminobenzyl group, the said groups being unsubstituted or substituted once or several times with a substituent each independently chosen from a halogen atom, a methyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

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

R 3 , R 4 , R 5 , R 6 , R 7 , R 8 each independently represent a hydrogen atom, a halogen atom, a —CN, —S(O) n R 14 or —OS(O) n R 14 group, or a (C 1 -C 6 )alkyl group which is unsubstituted or substituted once or several times with a substituent each independently chosen from a fluorine atom, an —OH, —OR 14 , —S(O) n R 14 , —OSO 2 R 14 or —NHSO 2 R 14 group, or a (C 1 -C 6 )alkoxy group, which is unsubstituted or substituted with one or more substituents each independently chosen from a fluorine atom, an —OH, —OR 14 , —S(O) n R 14 , —OSO 2 R 14 or —NHSO 2 R 14 group;

R 9 represents an —OR 12 , —CN, —CO 2 H, NR 12 R 13 , —CONR 12 R 13 , —NR 15 COR 12 , —CONHNH 2 , —CONHOH, —CONHSO 2 R 14 , —S(O) n R 14 , —SO 2 NR 12 R 13 , —NR 18 SO 2 R 14 or —NR 15 SO 2 NR 12 R 13 group;

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

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 with one or more substituents each independently chosen from a (C 1 -C 4 )alkoxy group, a hydroxyl group or one or more fluorine atoms;

a trifluoromethyl;

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 with one or more substituents each independently chosen from a halogen atom, a (C 3 -C 7 )cycloalkyl, cyano, —OH or —OR 14 group;

or R 12 and R 13 together with the nitrogen atom to which they are attached constitute a 4- to 7-membered heterocyclic radical which may contain a second heteroatom chosen from a nitrogen, oxygen or sulphur atom;

n represents 0, 1 or 2;

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

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;

or a benzyl group which is unsubstituted or substituted once or several times with a substituent each independently chosen from a halogen atom, a methyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

or a (C 1 -C 6 )alkyl group which is optionally substituted with one or more halogen atoms, —OH, or —OR 14 groups;

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

or its salt.

2. The compound according to claim 1 of formula (I) in which:

R 1 and R 2 together with the nitrogen atom to which they are attached constitute:

either a piperazin-1-yl or 1,4-diazepan-1-yl radical, the said radicals being substituted with a phenyl, benzodioxolyl, benzodioxolylmethyl, tetrahydrofuranylcarbonyl, —COR 11 , and/or —CH 2 COR 11 group; the phenyl group being itself substituted once or several times with a substituent each independently chosen from a halogen atom, a methyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

or a homopiperidin-1-yl, piperidin-1-yl, pyrrolidin-1-yl or azetidin-1-yl radical, the said radicals being substituted once or twice with a substituent each independently chosen from:

a fluorine atom, a cyano, —COR 11 , —CONR 12 R 13 , —NR 12 R 13 , NHCOR 14 , —CH 2 COR 11 , —SO 2 R 14 group; or —SO 2 NR 12 R 13 ;

or a (C 1 -C 4 )alkyl group which is unsubstituted or substituted with one or more substituents each independently chosen from a halogen atom and/or a hydroxyl,

or a phenyl or pyridinyl group; the said groups being unsubstituted or substituted once or several times with a substituent each independently chosen from a halogen atom, a methyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

or a benzyl group which is substituted once or several times with a substituent each independently chosen from a halogen atom, a methyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

or a piperidin-1-yl, pyrrolidin-1-yl or azetidin-1-yl group, the said groups being unsubstituted or substituted once or several times with a substituent each independently chosen from a fluorine atom, a (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, hydroxyl, trifluoromethyl or —OCF 3 group;

or an aminophenyl or aminobenzyl group, the said groups being unsubstituted or substituted once or several times with a substituent each independently chosen from a halogen atom, a methyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

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

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

or its salt.

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

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

a fluorine atom, a cyano, —COR 11 , —CONR 12 R 13 , —NR 12 R 13 , NHCOR 14 , —CH 2 COR 11 , —SO 2 R 14 group; or —SO 2 NR 12 R 13 ;

or a (C 1 -C 4 )alkyl group which is unsubstituted or substituted with one or more substituents each independently chosen from a halogen atom or a hydroxyl,

or a phenyl or pyridinyl group; the said groups being unsubstituted or substituted once or several times with a substituent each independently chosen from a halogen atom, a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

or a benzyl group which is substituted once or several times with a substituent each independently chosen from a halogen atom, a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy and cyano group;

or a piperidin-1-yl, pyrrolidin-1-yl or azetidin-1-yl group, the said groups being unsubstituted or substituted once or several times with a substituent each independently chosen from a fluorine atom, a (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, hydroxyl, trifluoromethyl or —OCF 3 group;

or an aminophenyl or aminobenzyl group, the said groups being unsubstituted or substituted once or several times with a substituent each independently chosen from a halogen atom, a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group;

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

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

or its salt.

4. The compound according to claim 1 in which A represents an unsubstituted (C 1 -C 5 )alkylene group and R 9 represents an —OR 12 , —NR 12 R 13 , —CONR 12 R 13 , —NR 15 COR 12 , —CONHNH 2 , —CONHOH, —S(O) n R 14 , —SO 2 NR 12 R 13 , —NR 18 SO 2 R 14 , or —NR 15 SO 2 NR 12 R 13 group; or its salt.

5. The compound according to claim 1 , characterized in that the compound is chosen from the group consisting of:

1-{[1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-(4-hydroxybutyl)-1H-pyrrol-3-yl]carbonyl}-4-phenylpiperidine-4-carboxamide;

1-{[1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-(2-hydroxyethyl)-1H-pyrrol-3-yl]carbonyl}-4-phenylpiperidine-4-carboxamide;

1′-{[1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-(4-hydroxybutyl)-1H-pyrrol-3-yl]carbonyl}-4,4-difluoro-1,4′-bipiperidine-4′-carboxamide;

4-(4-chlorophenyl)-1-{[1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-(3-hydroxy propyl)-1H-pyrrol-3-yl]carbonyl}piperidine-4-carboxamide;

and their salts.

6. A compound of formula (IIter):

in which:

X represents a halogen atom, a hydroxyl, (C 1 -C 4 )alkoxy or benzyloxy group;

and A, R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 10 are as defined for the compounds of formula (I) according to claim 1 .

7. A pharmaceutical composition, characterized in that it comprises a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient.