N-(amino-heteroaryl)-1H-pyrrolopyridine-2-carboxamides derivatives preparation thereof and their use in therapy

1. A compound of the formula (I):

wherein:

the pyrrolopyridine nucleus is pyrrolo[2,3-b]pyridine group; and wherein

the pyrrolopyridine nucleus being optionally substituted at carbon positions 4, 5, or 6 with one or more substituents X, which may be identical to or different from one another, selected from hydrogen, halogen, C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, C 1 -C 6 -fluoroalkoxyl, cyano, C 1 -C 6 -thioalkyl, —S(O)—C 1 -C 6 -alkyl, —S(O) 2 —C 1 -C 6 -alkyl, SF 5 , C(O)NR 1 R 2 , SO 2 NR 1 R 2 , nitro, NR 1 R 2 , OCONR 1 R 2 , NR 3 COR 4 , NR 3 CONR 1 R 2 , NR 3 SO 2 R 5 , NR 3 SO 2 NR 1 R 2 , aryl -C 1 -C 6 -alkylene, heteroaryl-C 1 -C 6 -alkylene, aryl and heteroaryl; wherein the aryl and the heteroaryl being optionally substituted with one or more substituents selected from halogen, C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro and cyano;

n is equal to 0, 1, 2 or 3;

Y represents aryl or heteroaryl;

the aryl or the heteroaryl being optionally substituted with one or more groups selected from a halogen atom or a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, hydroxyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, C 1 -C 6 -fluoroalkoxyl, cyano, C 1 -C 6 -thioalkyl, thiol, —S(O)—C 1 -C 6 -alkyl, —S(O) 2 —C 1 -C 6 -alkyl, C(O)NR 1 R 2 , SO 2 NR 1 R 2 , SF 5 , nitro, OCONR 1 R 2 , NR 3 COR 4 , NR 3 CONR 1 R 2 , NR 1 R 2 , NR 3 SO 2 NR 1 R 2 , NR 3 COR 4 , NR 3 SO 2 R 5 , aryl-C 1 -C 6 -alkylene and aryl; wherein the aryl and the aryl-C 1 -C 6 -alkylene being optionally substituted with one or more substituents selected from halogen, C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro and cyano;

Z 1 , Z 2 , Z 3 , Z 4 represent, independently of one another, nitrogen or C(R 6 ), wherein at least one corresponding to nitrogen and at least one corresponding to C(R 6 ); and wherein one of the nitrogen atoms present in the ring, defined as position-1 nitrogen, being optionally substituted with R 7 when the carbon atom in position 2 or 4 relative to this reference nitrogen is substituted with an oxo or thio group;

Z represents either a cyclic amine attached by the nitrogen atom, of formula:

in which

A represents a C 1 -C 7 -alkylene group optionally substituted with one or two groups R 8 ;

B represents a C 1 -C 7 -alkylene group optionally substituted with one or two groups R 9 ;

L represents a bond, sulfur, oxygen or nitrogen atom; the nitrogen atom being optionally substituted with a group R 10 or R 11 ;

the carbon atoms of the cyclic amine Z being optionally substituted with one or more groups R 12 which may be identical to or different from one another;

or an acyl amine, attached by the nitrogen atom, of formula NRaRb in which Ra and Rb represent, independently of one another, hydrogen, C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, hydroxyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, C 1 -C 6 -fluoroalkoxyl, C 1 -C 6 -alkyl-C(O)—, HO—C(O)—C 1 -C 6 -alkylene, C 1 -C 6 -alkyl-O—C(O)—C 1 -C 6 -alkylene, aryl or heteroaryl group, and Ra and Rb can optionally be substituted with one or more groups Rc which may be identical to or different from one another;

Rc represents a halogen atom, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl -C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, C 1 -C 6 -fluoroalkoxyl, C 1 -C 6 -thioalkyl, —S(O)—C 1 -C 6 -alkyl, —S(O) 2 —C 1 -C 6 -alkyl, cyano, C(O)NR 1 R 2 , NR 1 R 2 , SO 2 NR 1 R 2 , NR 3 COR 4 , NR 3 SO 2 R 5 , OC(O)NR 1 R 2 , NR 3 COOR 5 , NR 3 CONR 1 R 2 , NR 3 SO 2 NR 1 R 2 , hydroxyl, thiol, oxo, thio, aryl-C 1 -C 6 -alkylene, aryl or heteroaryl group, the aryl and the heteroaryl being optionally substituted with one or more substituents selected from a halogen, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl -C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro or cyano group;

R 1 and R 2 represent, independently of one another, hydrogen, C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, aryl-C 1 -C 6 -alkylene, aryl or heteroaryl group, the aryl and the heteroaryl being optionally substituted with one or more substituents selected from a halogen, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro or cyano group; or

R 1 and R 2 taken together with the nitrogen atom to which they are attached form a cyclic ring selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, azepinyl, morpholinyl, thiomorpholinyl, piperazinyl and homopiperazinyl; said ring being optionally substituted with a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, aryl-C 1 -C 6 -alkylene, aryl or heteroaryl group, the aryl and the heteroaryl being optionally substituted with one or more substituents selected from a halogen, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro or cyano group;

R 3 and R 4 represent, independently of one another, hydrogen, C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, aryl-C 1 -C 6 -alkylene, aryl or heteroaryl group, the aryl and the heteroaryl being optionally substituted with one or more substituents selected from a halogen, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro or cyano group;

or R 3 and R 4 together form a (C 2 -C 5 )alkylene group;

or R 1 and R 3 together form a (C 2 -C 5 )alkylene group;

R 5 represents a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, aryl-C 1 -C 6 -alkylene, aryl or heteroaryl group, the aryl and the heteroaryl being optionally substituted with one or more substituents selected from a halogen, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro or cyano group;

or R 3 and R 5 together form a (C 2 -C 5 )alkylene group;

R 6 represents a hydrogen or halogen atom or a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, C 1 -C 6 -fluoroalkoxyl, C 1 -C 6 -thioalkyl, —S(O)—C 1 -C 6 -alkyl, —S(O) 2 —C 1 -C 6 -alkyl, hydroxyl, thiol, oxo, thio, aryl, aryl-C 1 -C 6 -alkylene, heteroaryl group, the aryl and the heteroaryl being optionally substituted with one or more substituents selected from a halogen, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro or cyano group;

R 7 represents a hydrogen atom, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl -C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, C 1 -C 6 -fluoroalkoxyl, aryl, aryl-C 1 -C 6 -alkylene or heteroaryl group, the aryl and the heteroaryl being optionally substituted with one or more substituents selected from a halogen, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro or cyano group;

R 8 , R 9 and R 10 are defined such that:

two groups R 8 can together form a linkage or a C 1 -C 6 -alkylene group;

two groups R 9 can together form a linkage or a C 1 -C 6 -alkylene group;

R 8 and R 9 can together form a linkage or a C 1 -C 6 -alkylene group;

R 8 and R 10 can together form a linkage or a C 1 -C 6 -alkylene group;

R 9 and R 10 can together form a linkage or a C 1 -C 6 -alkylene group;

R 11 represents a hydrogen atom, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, C 1 -C 6 -fluoroalkoxyl, hydroxyl, C 1 -C 6 -alkyl-CO—, COOR 5 , C(O)NR 1 R 2 , aryl-C 1 -C 6 -alkylene, aryl or heteroaryl group, the aryl and the heteroaryl being optionally substituted with one or more substituents selected from a halogen, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro or cyano group;

R 12 represents a fluorine atom, a C 1 -C 6 -alkyl group optionally substituted with an R 13 , C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -cycloalk-1,1-diyl, C 3 -C 7 -heterocycloalk-1,1-diyl group optionally substituted on a nitrogen atom with an R 11 , C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, C 1 -C 6 -fluoroalkoxyl, CO 2 H, C(O)O—C 1 -C 6 -alkyl, C(O)NR 1 R 2 , NR 1 R 2 , NR 3 COR 4 , OC(O)NR 1 R 2 , NR 3 COOR 5 , NR 3 CONR 1 R 2 , hydroxyl, thiol, oxo, thio, aryl-C 1 -C 6 -alkylene, aryl group, the aryl being optionally substituted with one or more substituents selected from a halogen, a C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkoxyl, C 1 -C 6 -fluoroalkoxyl, nitro or cyano group; and

R 13 represents a C 1 -C 6 -alkoxy, C 3 -C 7 -cycloalkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, C(O)NR 1 R 2 , NR 1 R 2 , NR 3 COR 4 , OC(O)NR 1 R 2 , NR 3 COOR 5 , hydroxyl group;

or an N-oxide thereof or a salt thereof.

2. The compound of formula (I) according to claim 1 , wherein the substituent or substituents X, which may be identical to or different from one another, are selected from hydrogen, halogen or C 1 -C 6 -fluoroalkyl.

3. The compound of formula (I) according to claim 1 , wherein n is equal to 1.

4. The compound of formula (I) according to claim 1 , wherein Y represents an aryl or a heteroaryl, the aryl or the heteroaryl being optionally substituted with one or more groups selected from halogen, C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl or C 1 -C 6 -fluoroalkoxyl.

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

Z 1 , Z 2 , Z 3 , Z 4 represent, independently of one another, nitrogen or C(R 6 ), at least one corresponding to nitrogen and at least one corresponding to C(R 6 );

R 6 represents hydrogen, halogen, C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl or C 1 -C 6 -alkoxyl.

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

Z represents either a cyclic amine attached by the nitrogen atom, of formula:

in which

A represents a C 1 -C 7 -alkylene group optionally substituted with one or two groups R 8 ;

B represents a C 1 -C 7 -alkylene group optionally substituted with one or two groups R 9 ;

L represents a linkage;

the carbon atoms of the cyclic amine Z being optionally substituted with one or more groups R 12 which may be identical to or different from one another;

R 12 represents a fluorine atom, a C 1 -C 6 -alkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, CO 2 H, C(O)O—C 1 -C 6 -alkyl or hydroxyl group;

R 8 and R 9 are defined such that:

two groups R 8 can together form a linkage or a C 1 -C 6 -alkylene group;

two groups R 9 can together form a linkage or a C 1 -C 6 -alkylene group;

R 8 and R 9 can together form a linkage or a C 1 -C 6 -alkylene group;

or an acyl amine, attached by the nitrogen atom, of formula NRaRb in which Ra and Rb represent, independently of one another, a hydrogen atom or a C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C(O)—, HO—C(O)—C 1 -C 6 -alkylene or C 1 -C 6 -alkyl-O—C(O)—C 1 -C 6 -alkylene, and Ra and Rb can optionally be substituted with a group Rc where Rc represents a hydroxyl.

7. The compound of formula (I) according to claim 6 , wherein:

Z represents either a cyclic amine attached by the nitrogen atom, of formula:

in which

A represents a C 1 -C 7 -alkylene group optionally substituted with a group R 8 ;

B represents a C 1 -C 7 -alkylene group optionally substituted with a group R 9 ;

L represents a linkage;

the carbon atoms of the cyclic amine Z being optionally substituted with one or more groups R 12 which may be identical to or different from one another;

R 12 represents a fluorine atom, a C 1 -C 6 -alkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, CO 2 H, C(O)O—C 1 -C 6 -alkyl or hydroxyl group;

R 8 and R 9 are defined such that:

R 8 and R 9 can together form a linkage;

or an acyl amine, attached by the nitrogen atom, of formula NRaRb in which Ra and Rb represent, independently of one another, a hydrogen atom or a C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C(O)—, HO—C(O)—C 1 -C 6 -alkylene or C 1 -C 6 -alkyl-O—C(O)—C 1 -C 6 -alkylene group, and Ra and Rb can optionally be substituted with a group Rc where Rc represents a hydroxyl.

8. The compound of formula (I) according to claim 7 , wherein:

Z represents either a cyclic amine attached by the nitrogen atom and selected from the pyrrolidinyl, azetidinyl, azabicyclo[3.2.0]heptyl or azabicyclo[3.1.0]hexyl groups, the carbon atoms of the cyclic amine being optionally substituted with one or more groups R 12 which may be identical to or different from one another; R 12 represents a fluorine atom, a C 1 -C 6 -alkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, CO 2 H, C(O)O—C 1 -C 6 -alkyl or hydroxyl group;

or an acyl amine, attached by the nitrogen atom, of formula NRaRb in which Ra and Rb represent, independently of one another, a hydrogen atom or a C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C(O)—, HO—C(O)—C 1 -C 6 -alkylene or C 1 -C 6 -alkyl-O—C(O)—C 1 -C 6 -alkylene group, and Ra and Rb can optionally be substituted with a group Rc where Rc represents a hydroxyl.

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

the pyrrolopyridine nucleus is a pyrrolo[2,3-b]pyridine group;

the substituent or substituents X, which may be identical to or different from one another, are selected from a hydrogen or halogen atom or a C 1 -C 6 -fluoroalkyl group;

n is equal to 1;

Y represents an aryl or a heteroaryl, the aryl or the heteroaryl being optionally substituted with one or more groups selected from a halogen atom or a C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -alkoxyl or C 1 -C 6 -fluoroalkoxyl group;

Z 1 , Z 2 , Z 3 , Z 4 represent, independently of one another, a nitrogen atom or a group C(R 6 ), at least one corresponding to a nitrogen atom and at least one corresponding to a group C(R 6 );

R 6 represents a hydrogen or halogen atom or a C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl or C 1 -C 6 -alkoxyl group;

Z represents either a cyclic amine attached by the nitrogen atom and selected from the pyrrolidinyl, azetidinyl, azabicyclo[3.2.0]heptyl or azabicyclo[3.1.0]hexyl groups, the carbon atoms of the cyclic amine being optionally substituted with one or more groups R 12 which may be identical to or different from one another; R 12 represents a fluorine atom, a C 1 -C 6 -alkyl, C 1 -C 6 -alkoxyl, C 3 -C 7 -cycloalkyl-C 1 -C 6 -alkylene-O—, CO 2 H, C(O)O—C 1 -C 6 -alkyl or hydroxyl group;

or an acyl amine, attached by the nitrogen atom, of formula NRaRb in which Ra and Rb represent, independently of one another, a hydrogen atom or a C 1 -C 6 -alkyl, C 1 -C 6 -alkyl-C(O)—, HO—C(O)—C 1 -C 6 -alkylene or C 1 -C 6 -alkyl-O—C(O)—C 1 -C 6 -alkylene group, and Ra and Rb can optionally be substituted with a group Rc where Rc represents a hydroxyl.

10. A method of preparation of a compound of formula (I) according to claim 1 comprising:

reacting a compound of formula (IV) in a solvent:

in which the pyrrolopyridine nucleus is a pyrrolo [2,3-b]group;

X, Y and n are as defined in claim 1 and B represents a chlorine atom, with an amine of general formula (V):

in which W=Z and Z, Z 1 , Z 2 , Z 3 and Z 4 are as defined in claim 1 .

11. A method of preparation of a compound of formula (I) according to claim 1 comprising:

reacting a compound of general formula (IV):

in which the pyrrolopyridine nucleus is a pyrrolo [2,3-b]group;

X, Y and n are as defined in claim 1 and B represents a hydroxyl group, with an amine of general formula (V):

in which W=Z and Z, Z 1 , Z 2 , Z 3 and Z 4 are as defined in claim 1 , in the presence of a coupling agent, and optionally a base, in a solvent.

12. A method of preparation of a compound of formula (I) according to claim 1 comprising:

reacting a compound of general formula (VI):

in which the pyrrolopyridine nucleus is a pyrrolo [2,3-b]group;

X, Y, n, Z 1 , Z 2 , Z 3 and Z 4 are as defined in claim 1 and W represents a halogen atom, with an amine of formula Z—H, in which Z is as defined in claim 1 .

13. 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.

14. 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.

15. 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.

16. 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.

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

18. A pharmaceutical composition comprising a compound of formula (I) according to claim 6 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.

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

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

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