RORgamma modulators and uses thereof

1. A compound of formula (I)

in which,

R1a is a hydrogen atom, a halogen atom, a nitrile group, a nitro group (NO2), a (C1-C6)alkyl group, a (C1-C6)alkyloxy group, a (C1-C6)alkylthio group, an amino group, a (C1-C6)alkylamino group, a (C1-C6)dialkylamino group, or a heterocyclic group;

R1b is a hydrogen atom, a (C1-C6)alkyloxy group, a (C1-C6)alkyl group, or a heterocyclic group;

R1c is a hydrogen atom, a halogen atom, a (C1-C6)alkyl group, a (C1-C6)alkyloxy group, a (C1-C6)alkylthio group, a heterocyclic group, a cyano group, an amido group, or a hydroxyl group;

R1d and R1e are, independently, a hydrogen atom, a halogen atom, a (C1-C6)alkyloxy group, or a (C1-C6)alkyl group;

wherein at least one of R1a, R1b, R1c, R1d, and R1e is not a hydrogen atom;

R2 is a (C1-C6)alkyl group optionally substituted by a (C1-C6)alkyl group, a (C2-C6)alkenyl group optionally substituted by a (C1-C6)alkyl group, a (C2-C6)alkynyl group optionally substituted by a (C1-C6)alkyl group, a (C3-C14)cycloalkyl group optionally substituted by a (C1-C6)alkyl group, a (C6-C14)aryl group optionally substituted by a (C1-C6)alkyl group, or a heterocyclic group optionally substituted by a (C1-C6)alkyl group;

R′2 is a hydrogen atom, a (C1-C6)alkyl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group, a (C3-C14)cycloalkyl group, a (C6-C14)aryl group optionally substituted by a (C1-C6)alkyl group, or a heterocyclic group optionally substituted by a (C1-C6)alkyl group;

or R2 and R′2, together with the carbon atom to which they are attached, form a cycloalkyl group or a heterocycloalkyl group;

L1 is a NR7-CO—CH2, NR7-CO—, NR7-CO—C(CH3)2, CO—NH—CH2, CO—NH, or CO—NH—C(CH3)2 group;

R7 is a hydrogen atom or a (C1-C6)alkyl group;

L2 represents a bond, a (C1-C6)alkyl group, a (C3-C14)cycloalkyl group, or a CR8R′8 group;

with the proviso that when L1 is a NR3-CO— or a CO—NH group, L2 represents a (C1-C6)alkyl group, a (C3-C14)cycloalkyl group, or a CR8R′8 group;

R8 and R′8 are independently a hydrogen atom or a (C1-C6)alkyl group, or R8 and R′8, together with the carbon atom to which they are attached, form a cycloalkyl group;

X1, X2, X3, X4 and X5 are, independently, a CH group, a C-R4 group, a C—X6 group, or a nitrogen atom;

wherein two and only two of X1, X2, X3, X4, and X5 are nitrogen atoms, and said nitrogen atoms are in 1-position and 3-position;

X6 and X7 are independently a CH group or a nitrogen atom;

R3 is a hydrogen atom, a carbonyl(C1-C6)alkyl group, a SO2R′ group, a COOR′ group, an amido group, a (C1-C6)alkylamido group, or a (C1-C6)dialkylamido group;

R′ is a (C1-C6)alkyl group; and

R4 is a hydrogen atom, a (C1-C6)alkyl group, or a halogen atom.

2. The compound according to claim 1 , wherein X2 and X4 are nitrogen atoms.

3. The compound according to claim 1 , wherein:

R1a is a hydrogen atom, a halogen atom, a nitrile group, a nitro group (NO2), a (C1-C6)alkyl group, a (C1-C6)alkyloxy group, a (C1-C6)alkylthio group, an amino group, a (C1-C6)alkylamino group, a (C1-C6)dialkylamino group, a piperidinyl group, a pyrrolidinyl group, or an azepanyl group, wherein said piperidinyl, pyrrolidinyl, or azepanyl group is optionally substituted by at least one (C1-C6)alkyl group;

R1b is a hydrogen atom;

R1c is a (C1-C6)alkyl group;

R2 is a (C1-C6)alkyl group, a (C3-C14)cycloalkyl group, an (C6-C14)aryl group, or a heteroaryl group; and

R′2 is a hydrogen atom.

4. The compound according to claim 1 , wherein X6 is a nitrogen atom and X7 is a CH group.

5. The compound according to claim 1 , wherein L1 is a NR7-CO—CH2, NR7-CO—C(CH3)2, CO—NH—CH2, or CO—NH—C(CH3)2 group and L2 is a bond.

6. The compound according to claim 1 , wherein L1 is a NR7-00- or —CO—NH— group and L2 is a cyclopropyl group of formula (III)

7. The compound according to claim 1 , wherein R1b is a hydrogen atom.

8. The compound according to claim 1 , wherein R1d and R1e each are a hydrogen atom.

9. The compound according to claim 1 , wherein

R1a is a heterocyclic group,

R1c is a (C1-C6)alkyl group,

R2 is a heterocyclic group,

L1 represents a NH—CO—CH2 group,

L2 is a bound,

the cycle

is in para or meta position of the L group,

X6 is a nitrogen atom,

X7 is a CH group, and

R3 represents a hydrogen atom, a carbonyl(C1-C6)alkyl group, a SO2R′ group, or a COOR′ group.

10. The compound according to claim 1 , characterized in that it is selected from the group consisting of:

2[2-(4-methanesulfonylpiperazin-1-yl)pyrimidin-5-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;

2[2-(4-methanesulfonylpiperidin-1-yl)pyrimidin-5-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;

2[2-(4-acetylpiperidin-1-yl)pyrimidin-5-yl]-N-[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]acetamide;

methyl 1-{5-[({[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}carbamoyl)methyl]pyrimidin-2-yl}piperidine-4-carboxylate;

2[2-(4-acetylpiperidin-1-yl)pyrimidin-5-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide;

1-{5-[({[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}carbamoyl)methyl]pyrimidin-2-yl}piperidine-4-carboxylic acid;

1-[2-(4-acetylpiperazin-1-yl)pyrimidin-5-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}cyclopropane-1-carb oxamide;

2[2-(4-acetylpiperazin-1-yl)pyrimidin-5-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide; and

2-[2-(3-methanesulfonylpiperidin-1-yl)pyrimidin-5-yl]-N-{[4-methyl-2-(piperidin-1-yl)phenyl](5-methylfuran-2-yl)methyl}acetamide.

11. A combination product comprising:

i) a compound of formula (I) as defined in claim 1 , or a pharmaceutically acceptable salt thereof; and

ii) another therapeutically active agent that is a PPAR activator selected from the group consisting of seladelpar, saroglitazar, lanifibranor, pioglitazone, and pharmaceutically acceptable salts thereof.

12. The combination product according to claim 11 , wherein the combination product is a composition comprising component i), component ii), and a pharmaceutically acceptable carrier.

13. The combination product according to claim 11 , wherein the combination product is a kit of parts comprising components i) and ii), for sequential, separate or simultaneous use.

14. The combination product according to claim 11 , wherein components i) and ii) are formulated in an injectable suspension, a gel, an oil, a pill, a tablet, a suppository, a powder, a capsule, an aerosol, an ointment, a cream, a patch, or means of galenic forms for a prolonged and/or slow release.