Tetrahydroimidazo(1,5-D)[1,4]oxazepine derivative

1. A compound represented by the following formula (I) or a pharmaceutically acceptable acid addition salt thereof:

wherein R is a hydrogen atom or a C 1-6 alkyl group optionally substituted with 1 to 3 fluorine atoms, wherein

when R is a hydrogen atom,

R 1 is a chlorine atom, a bromine atom, a trifluoromethyl group, an ethyl group, a trifluoromethoxy group, a methoxy group substituted with a phenyl group, a methoxy group substituted with a C 3-8 cycloalkyl group, an ethoxy group optionally substituted with 1 to 3 fluorine atoms, or C 3-8 cycloalkyloxy group,

R 2 is a fluorine atom, a chlorine atom, a methyl group optionally substituted with 2 to 3 fluorine atoms, a methoxy group optionally substituted with 1 to 3 fluorine atoms, or an ethoxy group optionally substituted with 1 to 3 fluorine atoms,

R 3 is a hydrogen atom or a methyl group, and

R 4 is a fluorine atom or a methyl group optionally substituted with 1 to 3 fluorine atoms, or

when R is a C 1-6 alkyl group optionally substituted with 1 to 3 fluorine atoms,

R 1 is a hydrogen atom, a halogen atom, a C 1-6 alkyl group optionally substituted with 1 to 3 fluorine atoms, a C 1-6 alkoxy group optionally substituted with 1 to 3 substituents selected from a fluorine atom and a C 3-8 cycloalkyl group, a C 3-8 cycloalkyloxy group, or a 4- to 6-membered heterocycloalkyloxy group,

R 2 is a hydrogen atom, a cyano group, a halogen atom, a C 1-6 alkyl group optionally substituted with 1 to 3 substituents selected from a fluorine atom and a hydroxyl group, or a C 1-6 alkoxy group optionally substituted with 1 to 3 substituents selected from a fluorine atom, a C 3-8 cycloalkyl group and a 4- to 6-membered heterocycloalkyl group,

R 3 is a hydrogen atom or a C 1-6 alkyl group, and

R 4 is a C 1-6 alkyl group optionally substituted with 1 to 3 substituents selected from a fluorine atom and a hydroxyl group, or a C 1-6 alkoxy group.

2. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 1 , wherein

R is a C 1-6 alkyl group optionally substituted with 1 to 3 fluorine atoms,

R 1 is a hydrogen atom, a halogen atom, a C 1-6 alkyl group optionally substituted with 1 to 3 fluorine atoms, a C 1-6 alkoxy group optionally substituted with 1 to 3 substituents selected from a fluorine atom and a C 3-8 cycloalkyl group, a C 3-8 cycloalkyloxy group, or a 4- to 6-membered heterocycloalkyloxy group,

R 2 is a hydrogen atom, a cyano group, a halogen atom, a C 1-6 alkyl group optionally substituted with 1 to 3 substituents selected from a fluorine atom and a hydroxyl group, or a C 1-6 alkoxy group optionally substituted with 1 to 3 substituents selected from a fluorine atom, a C 3-8 cycloalkyl group and a 4- to 6-membered heterocycloalkyl group,

R 3 is a hydrogen atom or a C 1-6 alkyl group, and

R 4 is a C 1-6 alkyl group optionally substituted with 1 to 3 substituents selected from a fluorine atom and a hydroxyl group, or a C 1-6 alkoxy group.

3. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 2 , wherein R is a methyl group, an ethyl group, a fluoromethyl group or a difluoromethyl group.

4. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 3 ,

wherein R 1 is a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group, a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, an ethyl group, a 1,1-difluoroethyl group, a methoxy group, a fluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, an ethoxy group, a 2-fluoroethoxy group, a 2-propyloxy group, a cyclopropylmethoxy group, a cyclopropyloxy group or an (oxetan-3-yl)oxy group.

5. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 4 ,

wherein R 2 is a hydrogen atom, a cyano group, a fluorine atom, a chlorine atom, a methyl group, a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a hydroxymethyl group, an ethyl group, a methoxy group, a fluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, an ethoxy group, a 2-fluoroethoxy group, a 2-propyloxy group, a cyclopropylmethoxy group, a cyclobutylmethoxy group or a (tetrahydro-2H-pyran-4-yl)methoxy group.

6. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 5 , wherein R 3 is a hydrogen atom or a methyl group.

7. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 6 , wherein R 4 is a methyl group, a fluoromethyl group, a difluoromethyl group, a hydroxymethyl group or a methoxy group.

8. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 2 , wherein

R is a methyl group optionally substituted with 1 to 2 fluorine atoms,

R 1 is a hydrogen atom, a chlorine atom, a methyl group optionally substituted with 1 to 3 fluorine atoms, an ethyl group, a C 1-6 alkoxy group optionally substituted with 1 to 3 fluorine atoms, or a C 3-6 cycloalkyloxy group,

R 2 is a cyano group, a chlorine atom, a C 1-6 alkyl group optionally substituted with 1 to 3 fluorine atoms, or a C 1-6 alkoxy group optionally substituted with 1 to 3 fluorine atoms,

R 3 is a hydrogen atom or a methyl group, and

R 4 is a methyl group optionally substituted with 1 to 3 fluorine atoms.

9. A compound selected from the group consisting of the following compounds or a pharmaceutically acceptable acid addition salt thereof:

(R)-3-(4-chloro-3-methoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-1-(2,6-dimethylpyridin-4-yl)-3-(3-methoxy-4-(trifluoromethyl)phenyl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-6-methyl-3-(3-methyl-4-(trifluoromethoxy)phenyl)-1-(2-methylpyridin-4-yl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(4-(difluoromethoxy)-3-methylphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(4-(difluoromethoxy)-3-methylphenyl)-6-methyl-1-(2-methylpyridin-4-yl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(S)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-3-(3-methoxy-4-(trifluoromethoxy)phenyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(S)-6-(fluoromethyl)-3-(3-methoxy-4-(trifluoromethoxy)phenyl)-1-(2-methylpyridin-4-yl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(3-chloro-4-cyclopropoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(4-cyclopropoxy-3-methylphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(3-chloro-4-(difluoromethoxy)phenyl)-6-methyl-1-(2-methylpyridin-4-yl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(S)-3-(4-cyclopropoxy-3-methylphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(3-methoxy-4-(trifluoromethoxy)phenyl)-6-methyl-1-(2-methylpyridin-4-yl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-1-(2,6-dimethylpyridin-4-yl)-3-(3-methoxy-4-(trifluoromethoxy)phenyl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(S)-3-(4-(difluoromethoxy)-3-methylphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(S)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-3-(3-methoxy-4-(trifluoromethyl)phenyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(3-chloro-4-(difluoromethoxy)phenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(3-chloro-4-methoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(3-chloro-4-ethoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(3-chloro-4-isopropoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(S)-3-(3-chloro-4-methoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(S)-3-(3-chloro-4-ethoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(S)-3-(3-chloro-4-isopropoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(R)-3-(3-(fluoromethyl)-4-(trifluoromethoxy)phenyl)-6-methyl-1-(2-methylpyridin-4-yl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine,

(S)-3-(4-(difluoromethoxy)-3-methylphenyl)-6-(fluoromethyl)-1-(2-methylpyridin-4-yl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine, and

(S)-6-(fluoromethyl)-3-(3-methoxy-4-(trifluoromethyl)phenyl)-1-(2-methylpyridin-4-yl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine.

10. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 9 , which is (R)-3-(4-chloro-3-methoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

11. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 9 , which is (R)-1-(2,6-dimethylpyridin-4-yl)-3-(3-methoxy-4-(trifluoromethyl)phenyl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

12. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 9 , which is (R)-3-(3-methoxy-4-(trifluoromethoxy)phenyl)-6-methyl-1-(2-methylpyridin-4-yl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

13. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 9 , which is (R)-3-(4-(difluoromethoxy)-3-methylphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

14. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 9 , which is (R)-3-(3-chloro-4-(difluoromethoxy)phenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

15. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 9 , which is (S)-3-(4-(difluoromethoxy)-3-methylphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

16. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 9 , which is (S)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-3-(3-methoxy-4-(trifluoromethyl)phenyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

17. A pharmaceutical composition comprising the compound or a pharmaceutically acceptable acid addition salt according to claim 1 , and one or more pharmaceutically acceptable excipients.

18. A method for treating cognitive impairment, comprising administering the compound or a pharmaceutically acceptable acid addition salt according to claim 1 to a subject in need thereof.

19. A method for treating Alzheimer's disease, comprising administering the compound or a pharmaceutically acceptable acid addition salt according to claim 1 to a subject in need thereof.

20. A pharmaceutical composition comprising the compound or a pharmaceutically acceptable acid addition salt according to claim 9 , and one or more pharmaceutically acceptable excipients.

21. A method for treating cognitive impairment, comprising administering the compound or a pharmaceutically acceptable acid addition salt according to claim 9 to a subject in need thereof.

22. A method for treating Alzheimer's disease, comprising administering the compound or a pharmaceutically acceptable acid addition salt according to claim 9 to a subject in need thereof.

23. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 9 , which is (R)-3-(3-chloro-4-cyclopropoxyphenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

24. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 1 , which is (S)-3-(3-chloro-4-(difluoromethoxy)phenyl)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

25. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 1 , which is (R)-3-(4-chloro-3-fluorophenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

26. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 1 , which is (R)-3-(3,4-dichlorophenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

27. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 1 , which is (R)-3-(4-chloro-3 -(difluoromethyl)phenyl)-1-(2,6-dimethylpyridin-4-yl)-6-methyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.

28. The compound or a pharmaceutically acceptable acid addition salt thereof according to claim 1 , which is (S)-3-(3,4-dichlorophenyl)-1-(2,6-dimethylpyridin-4-yl)-6-(fluoromethyl)-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]oxazepine represented by the following formula:

or a pharmaceutically acceptable acid addition salt thereof.