SUBSTITUTED INDAZOLES USEFUL FOR TREATMENT AND PREVENTION OF ALLERGIC AND/OR INFLAMMATORY DISEASES IN ANIMALS

1 . A compound of the general formula (I)

in which:

R 1 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, hydroxyl, an unsubstituted or mono- or poly-halogen-substituted C 3 -C 6 -cycloalkyl, or an R 6 , R 7 SO 2 , R 7 SO or R 8 O group,

or a group selected from:

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 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 from the group of O, S, SO and SO 2 ;

R 7 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, hydroxyl or C 3 -C 6 -cycloalkyl;

or R 7 is C 3 -C 6 -cycloalkyl;

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;

and a diastereomers, an enantiomers, a metabolites, a salt, a solvate, a solvate of the salts thereof,

for use in the treatment and/or prophylaxis of allergic and/or inflammatory diseases in an animal.

2 . The compound according to claim 1 , where

R 1 is C 1 -C 6 -alkyl, where the C 1 -C 6 -alkyl group is unsubstituted or mono- or polysubstituted identically or differently by fluorine, hydroxyl or an R 6 , R 7 SO 2 , R 7 SO 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, where 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;

R 7 is C 1 -C 4 -alkyl, where the C 1 -C 4 -alkyl group is unsubstituted or monosubstituted by hydroxyl or by cyclopropyl or substituted by three fluorine atoms;

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

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

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

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

6 . The compound according to claim 2 , where

R 1 is C 2 -C 6 -alkyl, where 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 , R 7 SO 2 , 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;

R 7 is C 1 -C 3 -alkyl;

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

7 . The compound according to claim 6 , in which

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

is a methyl-SO 2 -substituted C 2 -C 4 -alkyl group or

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 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;

R 5 is hydrogen, fluorine or methyl.

8 . The compound according to claim 7 , in which

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, 2-hydroxyethyl, 2-(methyl sulphonyl)ethyl or 3-(methyl sulphonyl)propyl;

R 2 and R 3 are both methyl or hydrogen;

R 4 is difluoromethyl, trifluoromethyl or methyl;

R 5 is hydrogen or fluorine.

9 . The compound according to claim 8 , in which

R 1 is 3-hydroxy-3-methylbutyl, 3-hydroxybutyl, 3-hydroxy-2-methylpropyl, 3-hydroxy-2,2-dimethylpropyl, 3-(methyl sulphonyl)propyl or 2-(methyl sulphonyl)ethyl;

R 2 and R 3 are both methyl;

R 4 is difluoromethyl or trifluoromethyl;

R 5 is hydrogen.

10 . The compound according to claim 8 , in which

R 1 is 3-hydroxy-3-methylbutyl, 3-hydroxybutyl, 3-hydroxy-2-methylpropyl, 3-hydroxy-2,2-dimethylpropyl, 3-(methyl sulphonyl)propyl or 2-(methyl sulphonyl)ethyl;

R 2 and R 3 are both methyl;

R 4 is methyl;

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

11 . The compound according to claim 1 which is selected from the group consisting of:

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

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

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

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

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

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

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

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

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

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

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

12) N-{6-(2-Hydroxypropan-2-yl)-2-[2-(methyl sulphonyl)ethyl]-2H-indazol-5-yl}-6-(trifluoromethyl)pyridine-2-carboxamide;

13) 6-(Difluoromethyl)-N-[2-(3-hydroxy-3-methylbutyl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl]pyridine-2-carboxamide;

14) 6-(Difluoromethyl)-N-{6-(2-hydroxypropan-2-yl)-2-[2-(methyl sulphonyl)ethyl]-2H-indazol-5-yl}pyridine-2-carboxamide;

15) 6-(Difluoromethyl)-N-[6-(2-hydroxypropan-2-yl)-2-(3-hydroxypropyl)-2H-indazol-5-yl]pyridine-2-carboxamide;

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

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

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

19) 5-Fluoro-N-[2-(3-hydroxy-3-methylbutyl)-6-(2-hydroxypropan-2-yl)-2H-indazol-5-yl]-6-methylpyridine-2-carboxamide;

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

21) 6-(2-Hydroxypropan-2-yl)-N-[6-(2-hydroxypropan-2-yl)-2-(4,4,4-trifluorobutyl)-2H-indazol-5-yl]pyridine-2-carboxamide; and

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

a diastereomer, an enantiomer, a metabolite, a salt, a solvate, and a solvate of the salt thereof.

12 . Compound of the general formula (I) as defined in claim 1 for use in the treatment and/or prophylaxis of allergic and/or inflammatory diseases in domestic animals.

13 . Compound of the general formula (I) as defined in claim 1 for use in the treatment and/or prophylaxis of allergic and/or inflammatory diseases in farm animals.

14 . Compound of the general formula (I) as defined in claim 1 , for use in a method for treatment and/or prophylaxis of atopic dermatitis, Flea Allergy Dermatitis, inflammatory bowel disease, osteoarthritis and inflammatory pain, non-infectious recurrent airway disease, insect hypersensitivity, asthma, respiratory disease, mastitis and endometritis in animals.

15 . Compound of the general formula (I) as defined in claim 1 for use in a method for treatment and/or prophylaxis of Canine Atopic Dermatitis, Flea Allergy Dermatitis in dogs or cats, inflammatory bowel disease in dogs or cats, osteoarthritis and inflammatory pain in dogs, cats, horses or cattle, non-infectious recurrent airway disease in horses, insect hypersensitivity in horses, feline asthma, bovine respiratory disease, mastitis in cattle, endometritis in cattle, and swine respiratory disease.

16 . Compound of the general formula (I) as defined in claim 1 for use in a method for treatment and/or prophylaxis of Canine Atopic Dermatitis and Flea Allergy Dermatitis in dogs or cats.

17 . Compound of the general formula (I) as defined in claim 1 for use in a method for treatment and/or prophylaxis of osteoarthritis and inflammatory pain in cattle, bovine respiratory disease, mastitis in cattle, endometritis in cattle, and swine respiratory disease.

18 . A method for the production of a medicament for treatment and/or prophylaxis of allergic and/or inflammatory disease in an animal, the method comprising producing the medicament with a compound of the general formula (I) as defined in claim 1 .

19 . The method of claim 18 , wherein the medicament is used for treatment and/or prophylaxis in an animal of a disease or disorder selected from the group consisting of atopic dermatitis, Flea Allergy Dermatitis, inflammatory bowel disease, osteoarthritis and inflammatory pain, non-infectious recurrent airway disease, insect hypersensitivity, asthma, respiratory disease, mastitis and endometritis.

20 . The method of claim 18 , wherein the animal is a domestic animal.

21 . The method of claim 18 , wherein the animal is a farm animal.

22 . The method of claim 18 for treatment and/or prophylaxis of a disease or disorder selected from the group consisting of

Canine Atopic Dermatitis,

Flea Allergy Dermatitis in a dog or a cat,

inflammatory bowel disease in a dog or a cat,

osteoarthritis and inflammatory pain in a dog, a cat, a horse, or cattle,

non-infectious recurrent airway disease in a horse,

insect hypersensitivity in a horse,

feline asthma,

bovine respiratory disease,

mastitis in cattle,

endometritis in cattle, and

swine respiratory disease.

23 . The method of claim 18 for treatment and/or prophylaxis of Canine Atopic Dermatitis or Flea Allergy Dermatitis in a dog or a cat.

24 . Medicament comprising a compound of the formula (I) as defined in claim 1 in combination with an inert, non-toxic, pharmaceutically suitable excipient, for use in a method of treatment and/or prophylaxis of allergic and/or inflammatory disease in an animal.

25 . Method for treatment and/or prevention of allergic and/or inflammatory disease in an animal by administering an effective amount of at least a compound of the formula (I) of claim 1 to an animal in need thereof.

26 . A compound of the general formula (III)

in which

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, 2-(methyl sulphonyl)ethyl, 3-(methyl sulphonyl)propyl or 2-(1-hydroxycyclopropyl)ethyl;

R 4 is difluoromethyl, trifluoromethyl or methyl; and

R 5 is hydrogen or fluorine;

and a diastereomer, an enantiomer, a metabolite, a salt, a solvate or a solvate of the salts thereof,

for use in the treatment and/or prophylaxis of allergic and/or inflammatory diseases in an animal.

27 . The Compound of claim 26 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,

for use in the treatment and/or prophylaxis of allergic and/or inflammatory diseases in an animal.