Derivatives of 4,5-diarylpyrrole, preparation method thereof and use of same in therapeutics

1. A compound having the formula (I):

in which

x represents a group

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

R 2 represents:

a (C 1 -C 12 )alkyl which is unsubstituted or substituted one or more times with substituents chosen independently from a halogen atom, a hydroxyl, a (C 1 -C 4 )alkoxy, a (C 1 -C 4 )alkylthio, a phenoxy, a trifluoromethoxy radical, a difluoromethoxy radical, a difluoromethylthio radical and a trifluoromethylthio radical;

a nonaromatic carbocyclic (C 3 -C 12 ) radical which is unsubstituted or substituted one or more times with substituents chosen independently from a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a (C 1 -C 4 )alkylthio, a fluorine atom, a hydroxyl, a trifluoromethyl radical, a difluoromethyl radical, a trifluoromethoxy radical, a difluoromethoxy radical, a trifluoromethylthio radical and a difluoromethylthio radical;

a methyl substituted with a nonaromatic carbocyclic (C 3 -C 12 ) radical which is unsubstituted or substituted one or more times with substituents chosen independently from a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a (C 1 -C 4 )alkylthio, a fluorine atom, a hydroxyl, a trifluoromethyl radical, a difluoromethyl radical, a trifluoromethoxy radical, a difluoromethoxy radical, a trifluoromethylthio radical and a difluoromethylthio radical;

a phenyl, benzyl, benzhydryl or benzhydrylmethyl radical, in which each phenyl group is unsubstituted or substituted one or more times with substituents chosen independently from a halogen atom, a hydroxyl, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a methylenedioxy, a cyano, a nitro, a trifluoromethyl, a difluoromethyl, a difluoromethoxy, a trifluoromethoxy, a trifluoromethylthio, a difluoromethylthio, an S(O) n Alk group, an OS(O) n Alk group and a (C 1 -C 4 )alkylcarbonyl group;

a phenyl radical substituted with a heterocyclic radical chosen from pyrrolyl, imidazolyl, pyridyl or pyrazolyl, said heterocyclic radical being unsubstituted or substituted one or more times with one or more substituents chosen independently from a halogen atom or a (C 1 -C 4 )alkyl group;

a phenyl radical substituted with a phenyl or a phenoxy, in which each phenyl group is unsubstituted or substituted one or more times with substituents chosen independently from a halogen atom, a hydroxyl, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a methylenedioxy, a cyano, a nitro, a trifluoromethyl, a difluoromethyl, a difluoromethoxy, a trifluoromethoxy, a trifluoromethylthio, a difluoromethylthio, an S(O) n Alk group, an OS(O) n Alk group and a (C 1 -C 4 )alkylcarbonyl group;

a 1,2,3,4-tetrahydronaphthalen- 2 -yl which is unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl or a trifluoromethyl;

a pyrrolyl, imidazolyl, pyridyl, pyrazolyl, furyl, thienyl, oxazolyl or thiazolyl radical, said radicals being unsubstituted or substituted with one or more substituents chosen independently from a halogen atom, a (C 1 -C 4 )alkyl group or a trifluoromethyl group;

an indol- 2 -yl or an N-methylindol- 2 -yl;

R 3 represents a (C 1 -C 5 )alkyl or a (C 3 -C 7 )cycloalkyl;

R 4 represents a phenyl which is unsubstituted or substituted one or more times with substituents chosen independently from a halogen atom, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a cyano, a difluoromethyl radical, a trifluoromethyl radical, a difluoromethoxy radical, a trifluoromethoxy radical, an S(O) n Alk group or an OS(O) n Alk group;

R 5 represents a phenyl which is unsubstituted or substituted one or more times with substituents chosen independently from a halogen atom, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a cyano, a difluoromethyl radical, a trifluoromethyl radical, a difluoromethoxy radical, a trifluoromethoxy radical, an S(O) n Alk group or an OS(O) n Alk group;

R 6 represents a hydrogen atom or a (C 1 -C 4 )alkyl;

n represents 0, 1 or 2; and

Alk represents a (C 1 -C 4 )alkyl; or a salt thereof.

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

X represents a group

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

R 2 represents:

a (C 1 -C 7 )alkyl;

a nonaromatic carbocyclic C 3 -C 12 radical which is unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl group;

a methyl substituted with a nonaromatic carbocyclic C 3 -C 12 radical which is unsubstituted or substituted one or more times on the carbocycle with a (C 1 -C 4 )alkyl;

a phenyl which is unsubstituted or substituted one or more times with substituents chosen independently from a halogen atom, a (C 1 -C 4 )alkyl, a hydroxyl, a (C 1 -C 4 )alkoxy, a cyano, a trifluoromethyl group, a trifluoromethoxy group, an S(O) n Alk group and a (C 1 -C 4 )alkylcarbonyl group; or from a phenyl, phenoxy, pyrrolyl, imidazolyl, pyridyl or pyrazolyl radical, said radicals being unsubstituted or substituted one or more times with a (C 4 )alkyl;

a benzyl which is unsubstituted or substituted one or more times on the phenyl with substituents chosen independently from a halogen atom, a cyano, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a trifluoromethyl radical or an S(O) n Alk group; or substituted in the alpha-position with one or two similar or different groups chosen from a (C 1 -C 4 )alkyl and a (C 3 -C 7 )cycloalkyl;

a benzhydryl or a benzhydrylmethyl group;

a 1,2,3,4-tetrahydronaphthalen- 2 -yl which is unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl;

a pyrrolyl, imidazolyl, pyridyl, pyrazolyl, furyl or thienyl radical, said radicals being unsubstituted or substituted with one or more substituents chosen independently from a halogen atom or a (C 1 -C 4 )alkyl group;

an indol-2-yl or an N-methylindol-2-yl;

R 3 represents a (C 1 -C 5 )alkyl or a (C 3 -C 7 )cycloalkyl;

R 4 represents a phenyl which is unsubstituted or substituted one or more times with substituents chosen independently from a halogen atom, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a trifluoromethyl radical or an S(O) n Alk group;

R 5 represents a phenyl which is unsubstituted or substituted one or more times with substituents chosen independently from a halogen atom, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a trifluoromethyl radical or an S(O) n Alk group;

R 6 represents a hydrogen atom or a (C 1 -C 4 )alkyl;

n represents 0, 1 or 2; and

Alk represents a (C 1 -C 4 )alkyl; or a salt, thereof.

3. The compound of formula (I) according to claim 1 , wherein —X— represents a —CO— group and the substituents R 1 to R 5 are as defined for the compound of formula (I) in claim 1 .

4. The compound of formula (I) according to claim 1 , wherein —X— represents an —SO 2 — group and the substituents R 1 to R 5 are as defined for the compound of formula (I) in claim 1 .

5. The compound of formula (I) according to claim 1 , wherein —X— represents a —CON(R 6 )— group and the substituents R 1 to R 6 are as defined for the compounds of formula (I) in claim 1 .

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

treating a compound of formula (II):

in which R 1 , R 3 , R 4 and R 5 are as defined for a compound of formula (I) in claim 1 :

either with an acid of formula (III) or a functional derivative thereof:

HOOC—R 2   (III)

in which R 2 is as defined in claim 1 , when a compound of formula (I) in which —X— represents a —CO— group is prepared;

or with a sulfonyl halide of formula (IV):

Hal-SO 2 -R 2   (IV)

in which R 2 is as defined in claim 1 and Hal represents a halogen atom, when a compound of formula (I) in which —X— represents an —SO 2 — group is prepared;

or with a halo formate of formula (V):

HalCOOAr  (V)

in which Hal represents a halogen atom and Ar represents a phenyl or a 4-nitrophenyl, so as to obtain an intermediate compound of formula (VI):

 in which R 1 , R 3 , R 4 and R 5 are as defined in claim 1 , which is subsequently reacted with an amine of formula (VII):

HN(R 6 )R 2   (VII)

in which R 2 and R 6 are as defined in claim 1 , when a compound of formula (I) in which —X— represents a —CON(R 6 )— group is prepared;

or with an isothiocyanate of formula, R 2 —N═C═S (IX) in which R 2 is as defined in claim 1 , when a compound of formula (I) in which —X— represents a —CSN(R 6 )— group is prepared.

7. A compound of formula (II):

in which:

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

R 3 represents a (C 1 -C 5 )alkyl or a (C 3 -C 7 )cycloalkyl;

R 4 represents a phenyl which is unsubstituted or substituted one or more times with substituents chosen independently from a halogen atom, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a cyano, a difluoromethyl radical, a trifluoromethyl radical, a difluoromethoxy radical, a trifluoromethoxy radical, an S(O) n Alk group or an OS(O) n Alk group;

R 5 represents a phenyl which is unsubstituted or substituted one or more times with substituents chosen independently from a halogen atom, a (C 1 -C 4 )alkyl, a (Ci 1 C 4 )alkoxy, a cyano, a difluoromethyl radical, a trifluoromethyl radical, a difluoromethoxy radical, a trifluoromethoxy radical, an S(O) n Alk group or an OS(O) n Alk group;

n represents 0, 1 or 2; and

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

8. A pharmaceutical composition comprising a compound of formula (I) as claimed in claim 1 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) as claimed in claim 2 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) as claimed in claim 3 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.

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

12. A pharmaceutical composition comprising a compound of formula (I) as claimed in claim 5 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.