1-substituted indazole derivative

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof

wherein

A is CR 1E ,

X—Y—Z is N—CO—NR 3A R 3B or N—CO—R 4 ,

R 1A is a C 1-6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkoxy, a C 3-6 cycloalkyl, —NR 6 R 7 , —CONR 6 R 7 and —NR 6 COR 7 ; a C 3-10 cycloalkyl or a 4- to 10-membered saturated heterocycle, wherein the cycloalkyl and the saturated heterocycle are optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkyl, a C 1-6 alkoxy and —NR 6 R 7 ; a C 1-6 alkoxy optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkoxy, —NR 6 R 7 , —CONR 6 R 7 and —NR 6 COR 7 ; a hydrogen atom; a halogen; —NR 6 R 7 ; a cyano group; —CONR 6 R 7 ; —NR 6 COR 7 ; or —SO 2 R 6 , provided that both R 6 and R 7 are not a hydrogen atom,

R 1B to R 1E are each independently a C 1-6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkoxy, a C 3-6 cycloalkyl, —NR 6′ R 7′ , —CONR 6′ R 7′ and —NR 6′ COR 7′ ; a C 3-10 cycloalkyl or a 4- to 10-membered saturated heterocycle, wherein the cycloalkyl and the saturated heterocycle are optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkyl, a C 1-6 alkoxy, —NR 6′ R 7′ , —CONR 6′ R 7′ and —NR 6′ COR 7′ ; a C 1-6 alkoxy or a C 3-10 cycloalkoxy, wherein the alkoxy and the cycloalkoxy are optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkoxy, —CONR 6′ R 7′ and —NR 6′ COR 7′ ; a hydrogen atom; a hydroxy group; a halogen; an aryl or a heteroaryl, wherein the aryl and the heteroaryl are optionally substituted with 1 to 5 substituents independently selected from the group consisting of a halogen, a hydroxy group, a C 1-6 alkyl optionally substituted with 1 to 5 fluorine atoms, a C 1-6 alkoxy, —NR 6′ R 7′ , —CONR 6′ R 7′ and —NR 6′ COR 7′ ; —NR 6′ R 7′ ; a cyano group; —CONR 6′ R 7′ ; —NR 6′ COR 7′ ; or —SO 2 R 6′ , provided that both R 6′ and R 7′ are not a hydrogen atom,

R 2A to R 2D are each independently a C 1-6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a halogen, a hydroxy group, a C 1-6 alkoxy and —NR 8 R 9 ; a hydrogen atom; a halogen; a hydroxy group; or a C 1-6 alkoxy optionally substituted with 1 to 5 fluorine atoms, or when two of R 2A to R 2D are a C 1-6 alkyl, they may be taken together to form a 4- to 10-membered saturated carbocyclic ring optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkyl, a C 1-6 alkoxy and —NR 8 R 9 ,

R 3A , R 3B and R 4 are each independently a C 1-10 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of phenyl, a monocyclic heteroaryl, a 4- to 10-membered saturated heterocycle, a C 3-10 cycloalkyl, a fluorine atom, a hydroxy group, a C 1-6 alkoxy optionally substituted with 1 to 5 fluorine atoms, and —NR 10 R 11 ; a C 3-10 cycloalkyl; a 4- to 10-membered saturated heterocycle; phenyl; a monocyclic heteroaryl; or a hydrogen atom, wherein the cycloalkyl, the saturated heterocycle, the phenyl and the monocyclic heteroaryl may be optionally substituted with 1 to 5 substituents independently selected from the group consisting of an aryl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a C 1-6 alkoxy and —NR 10 R 11 , a halogen, a hydroxy group, a C 1-6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a C 1-6 alkoxy and —NR 10 R 11 , a C 1-6 alkoxy optionally substituted with 1 to 5 substituents independently selected from the group consisting of a C 3-6 cycloalkyl, a C 3-6 cycloalkyl-C 1-6 alkyl, a C 1-6 alkoxy and a fluorine atom, a C 1-6 alkylcarbonyl, and —NR 10 R 11 , provided that (1) R 3A and R 3B may be taken together to form a 4- to 10-membered saturated heterocycle optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkyl, a C 1-6 alkoxy and —NR 10 R 11 , (2) only one of R 3A and R 3B can be a hydrogen atom, and (3) R 4 is not a hydrogen atom,

R 6 to R 11 , R 6′ and R 7′ are the same or different and are a hydrogen atom or a C 1-6 alkyl optionally substituted with 1 to 5 fluorine atoms, provided that in each combination of R 6 -R 7 , R 6′ -R 7′ , R 8 -R 9 , and R 10 -R 11 , (1) when one is a hydrogen atom, the other one is not a hydrogen atom, and (2) each combination may be taken together to form a 4- to 10-membered saturated heterocycle optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkyl, a C 1-6 alkoxy and —NR 6 R 7 , and

n is 1.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein either R 3A or R 3B is a hydrogen atom.

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 2A to R 2D are each independently a C 1-6 alkyl optionally substituted with 1 to 5 fluorine atoms; a C 1-6 alkoxy; a hydrogen atom; or a fluorine atom.

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 3A , R 3B and R 4 are each independently a C 1-10 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a 4- to 10-membered saturated heterocycle, a C 3-10 cycloalkyl, a fluorine atom, a hydroxy group, a C 1-6 alkoxy optionally substituted with 1 to 5 fluorine atoms and —NR 10 R 11 ; C 3-10 cycloalkyl; a 4- to 10-membered saturated heterocycle; a nitrogen-containing monocyclic heteroaryl; or a hydrogen atom, wherein the cycloalkyl, the saturated heterocycle and the nitrogen-containing monocyclic heteroaryl may be optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a C 1-6 alkoxy and —NR 10 R 11 , a C 1-6 alkoxy optionally substituted with a C 3-6 cycloalkyl or 1 to 5 fluorine atoms and —NR 10 R 11 , provided that (1) R 3A and R 3B may be taken together to form a 4- to 10-membered nitrogen-containing saturated heterocycle optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkyl, a C 1-6 alkoxy and —NR 10 R 11 , (2) only one of R 3A and R 3B can be a hydrogen atom, and (3) R 4 is not a hydrogen atom.

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 1A to R 1E are each independently a C 1-6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a C 3-6 cycloalkyl, a hydroxy group and a C 1-6 alkoxy; a C 3-8 cycloalkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group, a C 1-6 alkyl and a C 1-6 alkoxy; a C 1-6 alkoxy optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a hydroxy group and a C 1-6 alkoxy; a hydrogen atom; a halogen; or a 4- to 10-membered saturated heterocycle optionally substituted with a C 1-6 alkyl.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 3A , R 3B and R 4 are each independently a C 1-10 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom and a C 1-6 alkoxy optionally substituted with 1 to 5 fluorine atoms; a C 3-10 cycloalkyl; a 4- to 10-membered saturated heterocycle; or a hydrogen atom, wherein the cycloalkyl and the saturated heterocycle are each optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a C 1-6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom and a C 1-6 alkoxy, and a C 1-6 alkoxy optionally substituted with 1 to 5 fluorine atoms, provided that (1) only one of R 3A and R 3B can be a hydrogen atom, and (2) R 4 is not a hydrogen atom.

7. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 1A to R 1E are each independently a C 1-6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom and a C 1-6 alkoxy; a C 3-8 cycloalkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom, a C 1-6 alkyl and a C 1-6 alkoxy; a C 1-6 alkoxy optionally substituted with 1 to 5 substituents independently selected from the group consisting of a fluorine atom and a C 1-6 alkoxy; a hydrogen atom; or a halogen.

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein X—Y—Z is N—CO—NR 3A R 3B .

9. The compound of claim 1 selected from the group consisting of:

N-(trans-4-methoxycyclohexyl)-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

4-(3-ethoxy-5-ethyl-1H-indazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidine-1-carboxamide,

(4,4-difluorocyclohexyl)(4-(5-ethoxy-1H-indazol-1-yl)piperidin-1-yl)methanone,

N-cyclohexyl-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

4-(5-propyl-1H-indazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidine-1-carboxamide,

4-(5-ethyl-1H-indazol-1-yl)-N-(trans-4-methoxycyclohexyl)piperidine-1-carboxamide,

N-cyclohexyl-4-(5-ethoxy-1H-indazol-1-yl)piperidine-1-carboxamide,

4-(5-ethyl-1H-indazol-1-yl)-N-(tetrahydro-2H-pyran-3-yl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(5-ethoxy-1H-indazol-1-yl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(5-fluoro-1H-indazol-1-yl)piperidine-1-carboxamide,

4-(5-chloro-1H-indazol-1-yl)-N-cyclopentylpiperidine-1-carboxamide,

4-(5-chloro-1H-indazol-1-yl)-N-(4,4-difluorocyclohexyl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(3-(methoxymethyl)-5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(5-methoxy-1H-indazol-1-yl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(3-ethyl-5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(3,5-dimethyl-1H-indazol-1-yl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(5-isopropoxy-1H-indazol-1-yl)piperidine-1-carboxamide,

N-cyclohexyl-4-(5-isopropoxy-1H-indazol-1-yl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(5-methyl-3-(tetrahydro-2H-pyran-4-yl)-1H-indazol-1-yl)piperidine-1-carboxamide,

4-(5-ethyl-3-isopropoxy-1H-indazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(4-ethyl-1H-indazol-1-yl)piperidine-1-carboxamide,

4-(4-ethyl-1H-indazol-1-yl)-N-(trans-4-methoxycyclohexyl)piperidine-1-carboxamide,

N-(4,4-difluorocyclohexyl)-4-(5-(4-fluorophenyl)-1H-indazol-1-yl)piperidine-1-carboxamide,

4-(5-cyclopropyl-1H-indazol-1-yl)-N-(trans-4-methoxycyclohexyl)piperidine-1-carboxamide,

(R)—N-(2,2-difluorocyclohexyl)-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

(S)—N-(2,2-difluorocyclohexyl)-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

(S)—N-(2,2-difluorocyclopentyl)-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

(R)—N-(2,2-difluorocyclopentyl)-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

N-(trans-4-ethoxycyclohexyl)-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide, and

(4-(5-isobutyl-1H-indazol-1-yl)piperidin-1-yl)(tetrahydro-2H-pyran-4-yl)methanone,

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 selected from the group consisting of:

N-(trans-4-methoxycyclohexyl)-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

(4,4-difluorocyclohexyl)(4-(5-ethoxy-1H-indazol-1-yl)piperidin-1-yl)methanone,

N-(4,4-difluorocyclohexyl)-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide,

4-(5-ethyl-1H-indazol-1-yl)-N-(trans-4-methoxycyclohexyl)piperidine-1-carboxamide,

4-(5-ethyl-3-isopropoxy-1H-indazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidine-1-carboxamide,

4-(4-ethyl-1H-indazol-1-yl)-N-(trans-4-methoxycyclohexyl)piperidine-1-carboxamide,

4-(5-cyclopropyl-1H-indazol-1-yl)-N-(trans-4-methoxycyclohexyl)piperidine-1-carboxamide, and

N-(trans-4-ethoxycyclohexyl)-4-(5-methyl-1H-indazol-1-yl)piperidine-1-carboxamide, or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof.

12. A method for treating cognitive impairment associated with schizophrenia (CIAS), which comprises administering a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof to a patient in need thereof.