Substituted indazoles, methods for the production thereof, pharmaceutical preparations that contain said new substituted indazoles, and use of said new substituted indazoles to produce drugs

1. A compound of formula (I)

wherein:

R 1 is C 1 -C 6 -alkyl, wherein the C 1 -C 6 -alkyl group is unsubstituted or mono- or polysubstituted identically or differently by halogen, hydroxyl, an unsubstituted or mono- or poly-halogen-substituted C 3 -C 6 -cycloalkyl, or an R 6 or R 8 O group,

or a group selected from the group consisting of:

wherein * represents the bonding site of the group to the rest of the molecule;

R 2 and R 3 always have the same definition and are both either hydrogen or C 1 -C 6 -alkyl;

R 4 is halogen, cyano, an unsubstituted or a singly or multiply, identically or differently substituted C 1 -C 6 -alkyl or an unsubstituted or a singly or multiply, identically or differently substituted C 3 -C 6 -cycloalkyl, and the substituents are selected from the group consisting of halogen and hydroxyl;

R 5 is hydrogen, halogen or an unsubstituted or mono- or poly-halogen-substituted C 1 -C 6 -alkyl;

R 6 is an unsubstituted or mono- or di-methyl-substituted monocyclic saturated heterocycle having 4 to 6 ring atoms, which contains a heteroatom or a heterogroup selected from the group consisting of O, S, SO and SO 2 ; and

R 8 is C 1 -C 6 -alkyl, where the C 1 -C 6 -alkyl group is unsubstituted or mono- or polysubstituted identically or differently by halogen,

or a diastereomer, an enantiomer, a salt, a solvate, or a solvate of the salt thereof.

2. The compound according to claim 1 , wherein

R 1 is C 1 -C 6 -alkyl, wherein the C 1 -C 6 -alkyl group is unsubstituted or mono- or polysubstituted identically or differently by fluorine, hydroxyl or an R 6 or R 8 O group;

R 2 and R 3 always have the same definition and are both either hydrogen or C 1 -C 3 -alkyl;

R 4 is halogen, cyano or C 1 -C 3 -alkyl, wherein the C 1 -C 3 -alkyl group is unsubstituted or mono- or polysubstituted identically or differently by halogen or hydroxyl;

R 5 is hydrogen, fluorine, chlorine or C 1 -C 3 -alkyl;

R 6 is oxetanyl or tetrahydrofuranyl; and

R 8 is an unsubstituted C 1 -C 4 -alkyl group or a mono-, di- or tri-fluorine-substituted C 1 -C 4 -alkyl group.

3. The compound according to claim 1 , wherein R 4 is difluoromethyl, trifluoromethyl, or methyl.

4. The compound according to claim 1 , wherein R 5 is hydrogen or fluorine.

5. The compound according to claim 1 , wherein R 2 and R 3 are both either hydrogen or methyl.

6. The compound according to claim 2 , wherein

R 1 is C 2 -C 6 -alkyl, wherein the C 2 -C 6 -alkyl group is unsubstituted, or

the C 2 -C 6 -alkyl group is mono-, di- or tri-fluorine-substituted or

the C 2 -C 6 -alkyl group is monosubstituted by hydroxyl, R 6 or R 8 O; or

R 1 is an oxetanyl-substituted C 1 -C 3 -alkyl group;

R 2 and R 3 always have the same definition and are both either hydrogen or methyl;

R 4 is an unsubstituted or mono- or poly-halogen-substituted C 1 -C 3 -alkyl group or a C 1 -C 3 -alkyl group substituted by one hydroxyl group or a C 1 -C 3 -alkyl group substituted by one hydroxyl group and three fluorine atoms;

R 5 is hydrogen, fluorine or C 1 -C 3 -alkyl; and

R 8 is C 1 -C 4 -alkyl, wherein the C 1 -C 4 -alkyl group is unsubstituted or mono-, di- or tri-fluorine-substituted.

7. The compound according to claim 6 , wherein

R 1 is a C 2 -C 5 -alkyl group substituted by hydroxyl or C 1 -C 3 -alkoxy or trifluoromethoxy or 2,2,2-trifluoroethoxy or trifluoromethyl; or

R 1 is an oxetan-3-yl-substituted C 1 -C 2 -alkyl group;

R 2 and R 3 always have the same definition and are both hydrogen or methyl;

R 4 is selected from the group consisting of methyl, ethyl, trifluoro-C 1 -C 3 -alkyl, difluoro-C 1 -C 3 -alkyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxypropan-2-yl, and 2,2,2-trifluoro-1-hydroxyethyl, and

R 5 is hydrogen, fluorine, or methyl.

8. The compound according to claim 7 , wherein

R 1 is 4,4,4-trifluorobutyl, 3-hydroxy-3-methylbutyl, 3-hydroxybutyl, 3-methoxypropyl, 3-hydroxypropyl, 3-hydroxy-2-methylpropyl, 3-hydroxy-2,2-dimethylpropyl, 3-trifluoromethoxypropyl, 2-methoxyethyl, or 2-hydroxyethyl;

R 2 and R 3 are both methyl or hydrogen;

R 4 is difluoromethyl, trifluoromethyl or methyl, and

R 5 is hydrogen or fluorine.

9. The compound according to claim 8 , wherein

R 1 is 3-hydroxy-3-methylbutyl, 3-hydroxybutyl, 3-hydroxy-2-methylpropyl, or 3-hydroxy-2,2-dimethylpropyl;

R 2 and R 3 are both methyl;

R 4 is difluoromethyl or trifluoromethyl, and

R 5 is hydrogen.

10. The compound according to claim 8 , wherein

R 1 is 3-hydroxy-3-methylbutyl, 3-hydroxybutyl, 3-hydroxy-2-methylpropyl, or 3-hydroxy-2,2-dimethylpropyl;

R 2 and R 3 are both methyl;

R 4 is methyl, and

R 5 is fluorine, wherein R 5 is in the ortho position to R 4 .

11. A compound selected from the group consisting of:

N-[6-(2-Hydroxypropan-2-yl)-2-(2-methoxyethyl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

N-[6-(Hydroxymethyl)-2-(2-methoxyethyl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

N-[6-(2-Hydroxypropan-2-yl)-2-(3-methoxypropyl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

N-[6-(Hydroxymethyl)-2-(3-methoxypropyl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

N-[2-(2-Hydroxyethyl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

N-[6-(2-Hydroxypropan-2-yl)-2-(3-hydroxypropyl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

N-[2-(2-Hydroxyethyl)-6-(hydroxymethyl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

N-[6-(2-Hydroxypropan-2-yl)-2-(oxetan-3-ylmethyl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

N-[6-(Hydroxymethyl)-2-(oxetan-3-ylmethyl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

N-[2-(3-Hydroxy-3-methylbutyl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

6-(Difluoromethyl)-N-[2-(3-hydroxy-3-methylbutyl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl]pyridine-2-carboxamide;

6-(Difluoromethyl)-N-[6-(2-hydroxypropan-2-yl)-2-(3-hydroxypropyl)-2H-indazol-5-yl]pyridine-2-carboxamide;

N-[6-(2-Hydroxypropan-2-yl)-2-(4,4,4-trifluorobutyl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide;

N-{6-(2-Hydroxypropan-2-yl)-2-[3-(trifluoromethoxy)propyl]-2H-indazol-5-yl}-6-(trifluoromethyl)pyridine-2-carboxamide;

N-{6-(2-Hydroxypropan-2-yl)-2-[3-(2,2,2-trifluoroethoxy)propyl]-2H-indazol-5-yl}-6-(trifluoromethyl)pyridine-2-carboxamide;

5-Fluoro-N-[2-(3-hydroxy-3-m ethylbutyl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl]-6-methylpyridine-2-carboxamide;

N-[2-(3-Hydroxy-3-methylbutyl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl]-6-methylpyridine-2-carboxamide;

6-(2-Hydroxypropan-2-yl)-N-[6-(2-hydroxypropan-2-yl)-2-(4,4,4-trifluorobutyl)-2H-indazol-5-yl]pyridine-2-carboxamide; and

N-{2-[2-(1-Hydroxycyclopropyl)ethyl]-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl}-6-(trifluoromethyl)pyridine-2-carboxamide,

or a salt, a solvate, or a solvate of the salt thereof.

12. A method for treating arthritis in a human in need thereof, comprising administering to the human an effective amount of a compound of formula (I) according to claim 1 , or a diastereomer, an enantiomer, a salt, a solvate, or a solvate of the salt thereof.

13. A medicament comprising a compound of formula (I) according to claim 1 in combination with an inert, non-toxic, pharmaceutically suitable excipient.

14. A process for preparing a compound of formula (III) from a compound of formula (II)

wherein

R 1 is 4,4,4-trifluorobutyl, 3-hydroxy-3-methylbutyl, 3-methoxypropyl, 3-hydroxypropyl, 3-hydroxy-2-methylpropyl, 3-hydroxy-2,2-dimethylpropyl, 3-trifluoromethoxypropyl, 2-methoxyethyl, or 2-hydroxyethyl;

R 4 is difluoromethyl, trifluoromethyl or methyl; and

R 5 is hydrogen or fluorine;

comprising reacting the compound of formula (II) with an appropriately substituted alkyl halide or alkyl 4-methylbenzenesulphonate in the presence of potassium carbonate.

15. A compound of formula (III)

wherein

R 1 is 4,4,4-trifluorobutyl, 3-hydroxy-3-methylbutyl, 3-methoxypropyl, 3-hydroxypropyl, 3-hydroxybutyl, 3-hydroxy-2-methylpropyl, 3-hydroxy-2,2-dimethylpropyl, 3-trifluoromethoxypropyl, 2-methoxyethyl, 2-hydroxyethyl, or 2-(1-hydroxycyclopropyl)ethyl;

R 4 is difluoromethyl, trifluoromethyl or methyl; and

R 5 is hydrogen or fluorine,

or a diastereomer, an enantiomer a salt, a solvate, or a solvate of the salt thereof.

16. The compound according to claim 15 , wherein the compound is selected from the group consisting of:

methyl 5-{[(5-fluoro-6-methylpyridin-2-yl)carbonyl]amino}-2-(3-hydroxy-3-methylbutyl)-2H-indazole-6-carboxylate; and

methyl 2-(3-hydroxy-3-methylbutyl)-5-({[6-(trifluoromethyl)pyridin-2-yl]carbonyl}amino)-2H-indazole-6-carboxylate;

a salt thereof,

a solvate thereof, and

a solvate of the salt thereof.

17. The method according to claim 12 , wherein the arthritis is osteoarthritis, rheumatoid arthritis, or spondyloarthritis.

18. A compound, wherein the compound is N-[2-(3-Hydroxy-3-methylbutyl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide, or a salt, a solvate, or a solvate of the salt thereof.

19. A method for treating arthritis in a human in need thereof, comprising administering to the human an effective amount of a compound according to claim 11 , or a salt, a solvate, or a solvate of the salt thereof.

20. The method according to claim 17 , wherein the arthritis is rheumatoid arthritis.

21. The method of claim 19 , wherein the arthritis is osteoarthritis, rheumatoid arthritis, or spondyloarthritis.

22. The method according to claim 21 , wherein the arthritis is rheumatoid arthritis.

23. A compound of claim 18 , wherein the compound is N-[2-(3-Hydroxy-3 -methylbutyl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide, or a salt thereof.

24. A compound of claim 23 , wherein the compound is N-[2-(3-Hydroxy-3 -methylbutyl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide.

25. A method for treating arthritis in a human in need thereof, comprising administering to the human an effective amount of a compound according to claim 24 .

26. The method of claim 25 , wherein the arthritis is osteoarthritis, rheumatoid arthritis, or spondyloarthritis.

27. The method according to claim 26 , wherein the arthritis is rheumatoid arthritis.