Derivatives of 3-alkoxy-4,5-diarylthiophene-2-carboxamide, preparation thereof, and therapeutic use thereof

1. A compound of formula (I):

in which:

R 1 represents:

an —NR 5 R 6 group;

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 and a trifluoromethyl;

R 2 represents:

a (C 1 -C 4 )alkyl;

an —X—R 7 group;

R 3 and R 4 each independently represent a phenyl substituted one or more times with a substituent chosen independently from a halogen atom, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy and a trifluoromethyl;

R 5 represents a hydrogen atom or a (C 1 -C 4 )alkyl;

R 6 represents a (C 1 -C 4 )alkyl which is unsubstituted or substituted with one or more fluorine atoms or with a phenyl which is unsubstituted or substituted with a halogen atom;

or else R 5 and R 6 , together with the nitrogen atom to which they are bonded, constitute a heterocycle chosen from: azetidine, pyrrolidine, and piperidine, said heterocycle being unsubstituted or substituted one or more times with a halogen atom;

X represents a (C 1 -C 5 )alkylene;

R 7 represents an —OR 8 group, an —NR 9 R 10 group or an —SO 2 —(C 1 -C 4 )alkyl group;

R 8 represents a hydrogen atom or a (C 1 -C 4 )alkyl;

R 9 represents a hydrogen atom or a (C 1 -C 4 )alkyl;

R 10 represents a hydrogen atom, a —COR 11 group, an —SO 2 R 11 group or a —CO(CH 2 ) m OH group;

R 11 represents a (C 1 -C 4 )alkyl which is unsubstituted or substituted with one or more fluorine atoms;

m represents 1, 2 or 3;

in the form of a base or of an addition salt with an acid.

2. The compound of formula (I), as claimed in claim 1 , in which:

R 1 represents:

an —NR 5 R 6 group;

a phenyl;

R 2 represents:

a methyl;

an —X—R 7 group;

R 3 and R 4 each independently represent a phenyl substituted once or twice with a halogen atom;

R 5 represents a hydrogen atom;

R 6 represents a (C 1 -C 4 )alkyl substituted with one or more fluorine atoms or with a phenyl which is unsubstituted or substituted with a halogen atom;

or else R 5 and R 6 , together with the nitrogen atom to which they are bonded, constitute a piperidin-1-yl radical which is unsubstituted or substituted once or twice with a halogen atom;

X represents a (C 1 -C 3 )alkylene;

R 7 represents an —OR 8 group, an —NR 9 R 10 group or an —SO 2 —CH 3 group;

R 8 represents a hydrogen atom;

R 9 represents a hydrogen atom;

R 10 represents a hydrogen atom, a —CO—CH 3 group, an —SO 2 —CH 3 group or a —COCH 2 OH group;

in the form of a base or of an addition salt with an acid.

3. The compound of formula (I), as claimed in claim 1 , in which:

R 1 represents:

an —NH(CH 2 ) 2 —CF 3 group, a 4-fluorobenzylamino group, a benzylamino group, a piperidin-1-yl radical, a 4,4-difluoropiperidin-1-yl radical;

a phenyl;

R 2 represents:

a methyl;

an —X—R 7 group;

R 3 represents a 4-chlorophenyl;

R 4 represents a 2-chlorophenyl or a 2,4-dichlorophenyl;

X represents a methylene, an ethylene or a trimethylene;

R 7 represents an —OH radical, an —NH 2 radical, an —NHCOCH 3 group, an —NHSO 2 CH 3 group, an —NHCOCH 2 OH group or an —SO 2 —CH 3 group;

in the form of a base or of an addition salt with an acid.

4. The compound as claimed in claim 1 , chosen from:

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

1′-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-{3-[(methylsulfonyl)amino]propoxy}thien-2-yl]carbonyl}-1,4′-bipiperidine-4′-carboxamide;

1′-{(4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-[3-(methylsulfonyl)propoxy]thien-2-yl}carbonyl)-1,4′-bipiperidine-4′-carboxamide;

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

1-({4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-[3-(methylsulfonyl)propoxy]thien-2-yl}carbonyl)-4-phenylpiperidine-4-carboxamide;

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

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

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

1-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-(2-hydroxyethoxy)thien-2-yl]carbonyl}-4-[(3,3,3-trifluoropropyl)amino]piperidine-4-carboxamide;

1-({4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-[3-(methylsulfonyl)propoxy]thien-2-yl}carbonyl)-4-[(3,3,3-trifluoropropyl)amino]piperidine-4-carboxamide;

1-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-{2-(hydroxyacetyl)amino]ethoxy}thien-2-yl]carbonyl}-4-[(3,3,3-trifluoropropyl)amino]piperidine-4-carboxamide;

1-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-(3-hydroxypropoxy)thien-2-yl]carbonyl}-4-[(3,3,3-trifluoropropyl)amino]piperidine-4-carboxamide;

1-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-{2-[(hydroxyacetyl)amino]ethoxy}thien-2-yl]carbonyl}-3-phenylpiperidine-4-carboxamide;

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

1-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-(2-hydroxyethoxy)thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

1-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-(3-hydroxypropoxy)thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

1-{4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-[3-(methylsulfonyl)propoxy]thien-2-yl}carbonyl)-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

1-{[3-(2-acetamidoethoxy)-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

1-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-{2-[(hydroxyacetyl)amino]ethoxy}thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

1-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-{3-[(hydroxyacetyl)amino]propoxy}thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

1-{[3-(3-acetamidopropoxy)-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

4-(benzylamino)-1-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-(2-hydroxyethoxy)thien-2-yl]carbonyl}piperidine-4-carboxamide;

4-(benzylamino)-1-{[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-3-{2-[(hydroxyacetyl)amino]ethoxy}thien-2-yl]carbonyl}piperidine-4-carboxamide;

1-{[5-(2-chlorophenyl)-4-(4-chlorophenyl)-3-(3-hydroxypropoxy)thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

1-{[5-(2-chlorophenyl)-4-(4-chlorophenyl)-3-(3-hydroxypropoxy)thien-2-yl]carbonyl}-4-phenylpiperidine-4-carboxamide;

1-{[5-(2-chlorophenyl)-4-(4-chlorophenyl)-3-(2-hydroxyethoxy)thien-2-yl]carbonyl}-4-phenylpiperidine-4-carboxamide;

1-{[5-(2-chlorophenyl)-4-(4-chlorophenyl)-3-(2-hydroxyethoxy)thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

1-{[3-(2-aminoethoxy)-5-(2-chlorophenyl)-4-(4-chlorophenyl)thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

1-{[3-(2-acetamidoethoxy)-5-(2-chlorophenyl)-4-(4-chlorophenyl)thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

1-{[3-(2-aminoethoxy)-5-(2-chlorophenyl)-4-(4-chlorophenyl)thien-2-yl]carbonyl}-4-phenylpiperidine-4-carboxamide;

1-{[5-(2-chlorophenyl)-4-(4-chlorophenyl)-3-{2-[(hydroxyacetyl)amino]ethoxy}thien-2-yl]carbonyl}-4-phenylpiperidine-4-carboxamide;

1-{[3-(2-acetamidoethoxy)-5-(2-chlorophenyl)-4-(4-chlorophenyl)thien-2-yl]carbonyl}-4-phenylpiperidine-4-carboxamide;

1-{[5-(2-chlorophenyl)-4-(4-chlorophenyl)-3-{2-(hydroxyacetyl)amino]ethoxy}thien-2-yl]carbonyl}-4-[(4-fluorobenzyl)amino]piperidine-4-carboxamide;

in the form of a base or of an addition salt with an acid.

5. A process for preparing the compound of claim 1 , comprising reacting a compound of formula:

in which R 1 , R 3 and R 4 are as defined in claim 1 , in the presence of a base, with a compound of formula:

Z—R 2   (III)

in which R 2 is as defined in claim 1 and Z represents a leaving group.

6. A process for preparing the compound of claim 1 , comprising reacting

an acid or a functional derivative of this acid of formula:

in which R 2 , R 3 and R 4 are as defined in claim 1 , with a compound of formula:

in which R 1 is as defined in claim 1 .

7. A pharmaceutical composition comprising the compound of claim 1 , or an addition salt of said compound with a pharmaceutically acceptable acid.

8. The pharmaceutical composition of claim 7 , further comprising, at least one pharmaceutically acceptable excipient.