Trifluoromethyl-oxadiazole derivatives and their use in the treatment of disease

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof,

wherein

X 1 represents N or CR 1 ;

X 2 represents N or CR 2 ;

X 3 represents N or CH;

X 4 represents N or CH;

and wherein at least one of X 1 , X 2 , X 3 and X 4 is N and not more than two of X 1 , X 2 , X 3 and X 4 are N;

R 1 and R 2 independently represent hydrogen, chloro or C 1-3 alkyl;

L 1 represents a bond or —C(═O)—;

L 2 represents a bond;

R 3 represents hydrogen or C 1-3 alkyl;

n represents 0, 1, 2 or 3;

R 4 and R 5 independently on each occurrence represent hydrogen, or C 1-3 alkyl;

R 6 represents —NR 7 R 8 , phenyl or a 5- or 6-membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S and wherein said phenyl or heteroaryl is optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R 9 ;

R 7 and R 8 independently represent hydrogen, C 1-4 alkyl or benzyl wherein the benzene ring is optionally substituted by 1, 2, 3, 4 or 5 substituents, which may be the same or different, selected from R 9 ; and

R 9 represents cyano, amino, halogen, hydroxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halogenC 1-4 alkyl, hydroxyC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino, diC 1-4 alkylamino, C 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl, aminocarbonyl, aminocarbonylC 1-4 alkyl, C 1-4 alkylaminocarbonyl, diC 1-4 alkylaminocarbonyl or C 1-4 alkoxycarbonylamino.

2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 independently represent hydrogen or chloro.

3. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 represents hydrogen or methyl.

4. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein n represents 0, 1 or 2.

5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 and R 5 independently on each occurrence represent hydrogen or C 1-3 alkyl.

6. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 represents phenyl or a 6-membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S and wherein said phenyl or heteroaryl is optionally substituted by 1, 2 or 3 substituents, which may be the same or different, selected from R 9 .

7. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 represents NR 7 R 8 .

8. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 9 represents cyano, amino, halogen, hydroxy or C 1-3 alkyl.

9. A compound according to claim 1 , which is selected from:

N-methyl-N-(pyridin-4-ylmethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-benzyl-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-((2-chloropyridin-4-yl)methyl)-N-methyl-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-(pyridin-4-ylmethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-(1-phenylethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-((6-methylpyridin-3-yl)methyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-(1-(pyridin-4-yl)ethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-(pyridin-3-ylmethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-((6-methylpyridin-2-yl)methyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

(R)—N-(1-phenylethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

(R)—N-(1-phenylpropyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-methyl-N-(2-(pyridin-4-yl)ethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-(1-(pyridin-4-yl)propyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-(1-(2-methylpyridin-4-yl)ethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

N-methyl-N-((2-methylpyridin-4-yl)methyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-2-amine;

(R)—N-(1-(dimethylamino)propan-2-yl)-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinamide;

N-(1-(dimethylamino)propan-2-yl)-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinamide;

(R)—N-(1-(benzyl(methyl)amino)propan-2-yl)-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinamide;

(R)—N-(1-(diethylamino)-3-methylbutan-2-yl)-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinamide;

(R)—N-(1-(diethylamino)propan-2-yl)-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinamide;

(R)—N-(1-(dimethylamino)propan-2-yl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)picolinamide;

(R)-3-chloro-N-(1-(dimethylamino)propan-2-yl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)picolinamide;

(R)—N-(1-(dimethylamino)propan-2-yl)-2-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidine-5-carboxamide;

N-benzyl-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-3-amine;

N-benzyl-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

N-(1-phenylethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

N-(pyridin-3-ylmethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

N-((6-methylpyridin-3-yl)methyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

N-benzyl-3-chloro-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

(R)-3-chloro-N-(1-phenylethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

3-chloro-N-(pyridin-4-ylmethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

3-chloro-N-(1-(pyridin-4-yl)ethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

3-chloro-N-(pyridin-3-ylmethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

3-Chloro-N-((6-methylpyridin-3-yl)methyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

3-chloro-N-(pyridin-2-ylmethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

N-benzyl-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridazin-3-amine;

(R)—N-(1-Phenylethyl)-2-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-5-amine;

(S)—N-(1-Phenylethyl)-2-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-5-amine;

N-(Pyridin-4-ylmethyl)-2-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyrimidin-5-amine;

(R)—N-(Pyridin-4-yl)ethyl)-5-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)pyridin-2-amine;

(R)—N-(1-(Pyridin-4-yl)ethyl)-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridazin-3-amine;

(R)—N-(1-(benzyl(methyl)amino)propan-2-yl)-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)nicotinamide;

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, as active pharmaceutical ingredient in association with at least one pharmaceutically acceptable carrier or diluent.

11. A method for the treatment of neurodegeneration, or metabolic syndrome, in a subject in need of such treatment, comprising administering to such subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

12. A method for the treatment of muscle atrophy, in a subject in need of such treatment, comprising administering to such subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

13. The compound N-(pyridine-4-ylmethyl)-5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-amine, or a pharmaceutically acceptable salt thereof, having the following structural formula