Pyrrole derivatives, preparation thereof and therapeutic use thereof

1. A compound of the 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;

a group

wherein m=0, 1 or 2 and p=0 or 1;

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

R 2 represents:

a (C 3 -C 10 )alkyl group, which is unsubstituted or substituted with a trifluoromethyl group; hydroxyl, (C 1 -C 4 )alkoxy, a fluorine atom or a CONH 2 group;

a non-aromatic C 3 -C 12 carbocyclic radical, which is unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl, hydroxyl, cyano or (C 1 -C 4 )alkoxy group, a group COR 12 or a fluorine atom;

an indanyl;

a 1,2,3,4-tetrahydro-1- or -2-naphthyl;

a monooxygen or monosulfur heterocyclic radical of 5 to 7 atoms, which is unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl group;

a mononitrogen heterocyclic radical of 5 to 7 atoms, which is unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl group, the nitrogen atom moreover being substituted with a (C 1 -C 4 )alkyl, phenyl, benzyl, (C 1 -C 4 )alkoxycarbonyl or (C 1 -C 4 )alkanoyl group, the phenyl or benzyl groups being unsubstituted or substituted one or more times with a halogen atom or a (C 1 -C 4 )alkyl, trifluoromethyl, hydroxyl or (C 1 -C 4 )alkoxy group;

a benzothiophenyl or an indolyl, the said radicals being unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl group;

a (C 1 -C 3 )alkylene group bearing a non-aromatic C 3 -C 10 carbocyclic radical, which is unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl, hydroxyl, (C 1 -C 4 )alkoxy or cyano group or a group COR 12 ;

a (C 1 -C 3 )alkylene group bearing a monooxygen, monosulfur or mononitrogen heteroaromatic or non-heteroaromatic heterocyclic radical of 5 to 7 atoms, which is unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl group;

a (C 1 -C 3 )alkylene group bearing an indolyl or benzothiophenyl radical, the said radical being unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl group and the alkylene being unsubstituted or substituted with a hydroxyl, methyl or methoxy group or with a group COR 12 ;

a (C 1 -C 3 )alkylene group bearing a (C 1 -C 4 )alkylthio group;

a phenylalkylene group in which the alkylene is (C 1 -C 3 ), which is unsubstituted or substituted on the alkylene with one or more methyl, hydroxyl, hydroxymethyl, methoxy or methoxymethyl groups, or a group COR 12 , and which is unsubstituted on the phenyl or substituted on the phenyl with one or more identical or different substituents chosen from a halogen atom and a (C 1 -C 4 )alkyl, trifluoromethyl, (C 1 -C 4 )alkoxy or trifluoromethoxy group;

a benzhydryl or benzhydrylmethyl group;

a group NR 10 R 11 ;

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

either a morpholinyl group

or a piperazin-1-yl or 1,4-diazepan-1-yl radical, which is unsubstituted or substituted with a phenyl, benzyl, benzodioxolyl, benzodioxolylmethyl or tetrahydrofurylcarbonyl group or with a group COR 12 or CH 2 COR 12 , the benzyl group itself being unsubstituted or substituted with one or more halogen atoms or with one or more methoxy or methoxymethyl groups;

or a piperid-1-yl, pyrrolidin-1-yl or azetidin-1-yl radical, which is unsubstituted or substituted one or two times with a substituent independently chosen from:

a fluorine atom or a group (C 1 -C 4 )alkyl, hydroxyl, cyano, COR 12 , NR 13 R 14 , NHCOR 15 , CH 2 COR 12 , SO 2 Alk; or SO 2 NR 13 R 14 ;

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

a piperid-1-yl, pyrrolidin-1-yl or azetidin-1-yl group, the said piperid-1-yl, pyrrolidin-1-yl or azetidin-1-yl groups being unsubstituted or substituted one or more times with a fluorine atom or a (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, hydroxyl, trifluoromethyl or OCF 3 group;

R 3 , R 4 , R 5 , R 6 , R 7 and R 8 represent, independently of each other, a hydrogen or halogen atom, a group CN, S(O) n ALK or OS(O) n ALK, a group (C 1 -C 7 )alkyl, which is unsubstituted or substituted one or more times with a substituent each independently chosen from a fluorine atom, and group OALK, S(O) n ALK, OS(O) n ALK and NHSO 2 Alk, or a group (C 1 -C 6 )alkoxy, which is unsubstituted or substituted with one or more substituents each independently chosen from a fluorine atom and a group OALK, S(O) n ALK, OS(O) n ALK and NHSO 2 Alk;

R 9 represents a group —OH, —CN, —CO 2 H, NR 13 R 14 , —CONR 13 R 14 , —NR 1 COR 13 , —CONHNH 2 , —CONHOH, —CONHSO 2 Alk, —S(O) n Alk, —SO 2 CF 3 , —SO 2 NR 13 R 14 , —NR 1 SO 2 Alk, —NR 1 SO 2 CF 3 , —NR 1 SO 2 NR 13 R 14 , or a radical chosen from:

R 10 represents a hydrogen atom or a methyl group;

R 11 represents a (C 3 -C 6 )alkyl, phenyl or (C 3 -C 10 )cycloalkyl group, the phenyl and cycloalkyl groups being unsubstituted or substituted with one or more substituents independently chosen from a halogen atom and a (C 1 -C 4 )alkyl or trifluoromethyl group;

or R 10 and R 11 , together with the nitrogen atom to which they are attached, constitute a saturated or unsaturated, bridged or non-bridged heterocyclic radical of 4 to 11 atoms, possibly comprising a spirane carbon and possibly containing a second heteroatom chosen from O and N, the said radical being unsubstituted or substituted one or more times with a substituent each independently chosen from a hydroxyl, (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxycarbonyl or COR 12 group, or a phenyl group that is unsubstituted or substituted with one or more substituents independently chosen from a halogen atom and a (C 1 -C 4 )alkyl group;

R 12 represents a (C 1 -C 4 )alkyl, phenyl, benzyl, (C 1 -C 4 )alkoxy or trifluoromethyl group or a group NR 13 R 14 ;

R 13 and R 14 each independently represent a hydrogen atom or a (C 1 -C 6 )alkyl group optionally substituted with one or more groups OH, F or OALK, or R 13 or R 14 , together with the nitrogen atom to which they are attached, constitute a 4- to 7-membered heterocyclic radical possibly comprising a second heteroatom chosen from a nitrogen, oxygen or sulfur atom;

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

n represents 0, 1 or 2;

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

Alk represents a (C 1 -C 4 )alkyl group;

or a salt thereof.

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

R 1 represents hydrogen and R 2 represents a group NR 10 R 11 in which R 10 and R 11 , together with the nitrogen atom to which they are attached, constitute a saturated heterocyclic radical of 5 to 11 carbon atoms, which is unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl;

or R 1 and R 2 , together with the nitrogen atom to which they are attached, constitute a piperid-1-yl radical gem-disubstituted with a phenyl, benzyl, pyrrolidin-1-yl, piperid-1-yl or 4,4-difluoropiperid-1-yl group, a cyano, (C 1 -C 3 )alkanoyl, aminocarbonyl, methanesulfonyl, N-methylsulfonyl or N,N-dimethylsulfonyl group;

or R 1 and R 2 together represent a piperazin-1-yl group in which 4-position is substituted with a benzodioxolyl or benzodioxolylmethyl group or with a benzyl, which is itself unsubstituted or substituted with one or more halogen atoms or with one or more methoxy or methoxymethyl groups;

R 3 , R 4 , R 5 , R 6 , R 7 and R 8 represent, independently of each other, a hydrogen or halogen atom or a methoxy group; and

A-R 9 is as defined in claim 1 ;

or a salt thereof.

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

R 1 represents hydrogen and R 2 represents a piperid-1-yl radical or a (C 1 -C 3 )alkylene radical substituted with a phenyl and with a methoxy or methoxycarbonyl group;

or R 1 represents hydrogen and R 2 represents a phenylalkylene group in which the alkylene is of (C 1 -C 3 ), unsubstituted on the alkylene or substituted on the alkylene with a methyl, hydroxyl, hydroxymethyl, methoxy or methoxymethyl group, and unsubstituted on the phenyl or substituted one or more times on the phenyl with a halogen atom or a methyl, trifluoromethyl, hydroxyl or methoxy group;

or R 1 and R 2 , together with the nitrogen atom to which they are attached, represent a piperid-1-yl radical 4-gem-disubstituted with a phenyl or piperid-1-yl group and with an acetyl, aminocarbonyl or cyano group;

or R 1 and R 2 together represent a piperazin-1-yl group 4-substituted with a benzodioxolylmethyl or a benzyl, which is itself unsubstituted or substituted with a halogen atom;

R 6 is a 4-chloro or a 4-methoxy and R 3 and R 4 represent 2,4-dichloro or 2-chloro, R 5 , R 7 and R 8 representing a hydrogen atom;

A represents a group (CH 2 ) q with q=2, 3, 4 or 5;

R 9 represents a group chosen from: —CO 2 H, —NHSO 2 CF 3 , —NHSO 2 CH 3 , or —SO 2 CH 3 ;

or a salt thereof.

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

NR 1 R 2 represents:

R 3 , R 4 and R 6 each represent a halogen atom;

R 5 , R 7 and R 8 each represent a hydrogen atom;

A represents a benzyl or a (C 2 -C 5 )alkylene group, which is unsubstituted or substituted one or more times with a methyl;

R 9 represents a group CN, CO 2 H, SO 2 CH 3 , NHSO 2 CH 3 or NHSO 2 CF 3 ;

or a salt thereof.

5. A process for preparing a compound of formula (I) according to claim 1 , comprising:

reacting the acid of formula (II):

with an amine of formula HNR 1 R 2 (III), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined in claim 1 and Y represents either a hydrogen atom or the group A-R 9 , or a precursor of the group A-R 9 , wherein A-R 9 is as defined in claim 1 ; and

converting, where appropriate, the substituent Y into a group A-R 9 .

6. A compound of formula (II bis):

in which:

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

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;

a group

wherein m=0, 1 or 2 and p=0 or 1;

R 3 , R 4 , R 5 , R 6 , R 7 and R 8 represent, independently of each other, a hydrogen or halogen atom, a (C 1 -C 6 )alkoxy group, a group S(O) n ALK, OS(O) n ALK or a (C 1 -C 7 )alkyl group, which is unsubstituted or substituted one or more times with a fluorine atom or a group OALK, S(O) n ALK or OS(O) n ALK;

R 9 represents a group —OH, —CN, —CO 2 H, NR 13 R 14 , —CONR 13 R 14 , —CONHNH 2 , —CONHOH, —CONHSO 2 Alk, —S(O) n Alk, —SO 2 CF 3 , —SO 2 NR 13 R 14 , —NHSO 2 Alk, —NHSO 2 CF 3 , —NHSO 2 NR 13 R 14 , or a radical chosen from:

n represents 0, 1 or 2; and wherein

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

Alk represents a (C 1 -C 4 )alkyl group.

7. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.

8. A pharmaceutical composition comprising a compound of formula (I) according to claim 2 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.

9. A pharmaceutical composition comprising a compound of formula (I) according to claim 3 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.

10. A pharmaceutical composition comprising a compound of formula (I) according to claim 4 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.