Phosphate derivatives of RORgamma modulators and uses thereof

1. A compound having the following formula (I):

or a stereoisomer or a pharmaceutically acceptable salt thereof

wherein:

A is a ring of the following formula (a):

in which:

B represents a NH group; an oxygen atom; or a SO 2 group,

R 7 represents a hydrogen, a halogen, or a (C 1 -C 6 )alkyloxy group, and

R 8 represents a hydrogen or a (C 1 -C 6 )alkyl group,

R 1a and R 1c represent independently a hydrogen, a (C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyloxy group, a halogen, or a heterocycloalkyl optionally substituted by a (C 1 -C 6 )alkyl group;

R 2 represents a (C 1 -C 6 )alkyl group or a ring selected from the group consisting of a cycloalkyl, a heterocycloalkyl, an aryl, and a heteroaryl, said ring being optionally substituted by at least one radical selected from the group consisting of a (C 1 -C 6 )alkyl group, and a halogen;

R 3 and R 3′ represent independently a hydrogen or a (C 1 -C 6 )alkyl group, or

R 3 and R 3′ may form together, with the carbon atom to which they are attached, a cycloalkyl;

X represents a (C 1 -C 6 )alkyl group; and

R 5 and R 6 represent independently a hydrogen or a (C 1 -C 6 )alkyl group.

2. The compound according to claim 1 , wherein A has the following formulae (a 1 ) or (a 2 ).

3. The compound according to claim 1 , wherein B is a NH group.

4. The compound according to claim 1 , wherein:

R 1a represents a (C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyloxy group, a halogen, or a heterocycloalkyl; and

R 1c represents a hydrogen, a (C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkyloxy group, or a halogen.

5. The compound according to claim 1 , wherein R 2 represents a heteroaryl, said heteroaryl being optionally substituted by at least one radical selected from the group consisting of a (C 1 -C 6 )alkyl group and a halogen.

6. The compound according to claim 1 , wherein R 5 and R 6 represent a hydrogen.

7. The compound according to claim 1 , wherein X is a linear (C 1 -C 6 )alkyl group.

8. The compound according to claim 1 , wherein the pharmaceutically acceptable salt of the compound of formula (I) is a sodium salt, a potassium salt, or a calcium salt.

9. The compound according to claim 1 , wherein said compound is selected from the group consisting of:

{2-[5-(1-{[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethoxy}phosphonic acid;

disodium 2-[5-(1-{[(2,4-dimethylphenyl)(5-methylfuran-2-yl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethyl phosphate;

{2-[5-(1-{[(2-methoxy-4-methylphenyl)(phenyl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethoxy}phosphonic acid;

disodium 2-[5-(1-{[(2-methoxy-4-methylphenyl)(phenyl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethyl phosphate;

{2-[5-(1-{[(2,4-dimethylphenyl)(6-methyl pyridin-2-yl) methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethoxy}phosphonic acid;

disodium {2-[5-(1-{[(2,4-dimethyl phenyl)(6-methyl pyridin-2-yl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethoxy}phosphonic acid;

{2-[5-(1-{[(3-chlorophenyl)(2,4-dimethylphenyl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethoxy}phosphonic acid;

disodium 2-[5-(1-{[(3-chlorophenyl)(2,4-dimethylphenyl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethyl phosphate;

{2-[5-(1-{[(4-methoxy-2-methylphenyl)(phenyl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethoxy}phosphonic acid;

disodium 2-[5-(1-{[(4-methoxy-2-methylphenyl)(phenyl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethyl phosphate;

(2-{5-[1-({[4-methoxy-2-(pyrrolidin-1-yl)phenyl](phenyl)methyl}carbamoyl)cyclopropyl]-1H-indol-3-yl}ethoxy)phosphonic acid;

disodium 2-{5-[1-({[4-methoxy-2-(pyrrolidin-1-yl)phenyl](phenyl)methyl}carbamoyl)cyclopropyl]-1H-indol-3-yl}ethyl phosphate;

{2-[5-(1-{[cyclopropyl (2,4-dimethylphenyl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethoxy}phosphonic acid;

disodium 2-[5-(1-{[cyclopropyl(2,4-dimethylphenyl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethyl phosphate;

(2-{5-[1-({[4-methyl-2-(morpholin-4-yl) phenyl](phenyl)methyl}carbamoyl) cyclopropyl]-1H-indol-3-yl}ethoxy) phosphonic acid;

disodium 2-{5-[1-({[4-methyl-2-(morpholin-4-yl) phenyl](phenyl)methyl}carbamoyl) cyclopropyl]-1H-indol-3-yl}ethyl phosphate;

{2-[5-(1-{[(dimethyl-1,2-oxazol-4-yl) (phenyl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethoxy}phosphonic acid; and

disodium 2-[5-(1-{[(dimethyl-1,2-oxazol-4-yl) (phenyl)methyl]carbamoyl}cyclopropyl)-1H-indol-3-yl]ethyl phosphate.

10. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient.

11. The pharmaceutical composition according to claim 10 , wherein said composition is in a form of a suspension, a gel, an oil, a powder, an aerosol, or a spray.

12. A method of treating a respiratory disease, said respiratory disease being selected from the group consisting of neutrophilic asthma, chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome (ACOS), idiopathic pulmonary fibrosis (IPF), and chronic rhinosinusitis with nasal polyps (CRSwNP) comprising the administration of a pharmaceutical composition according to claim 10 to a subject in need of treatment.

13. The method according to claim 12 , wherein said composition is administered by a nasal inhalation.

14. A device comprising a pharmaceutical composition according to claim 10 , said device being a dry powder inhaler (DPI) or a metered dose inhaler (MDI).