4-substituted piperidine compound

1. A compound, a salt thereof, or a hydrate of said compound or salt thereof, said compound represented by the formula:

wherein R 2 of formula (I) represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group or an optionally substituted C 2-6 alkynyl group, a salt thereof, or a hydrate of said compound or salt thereof;

R 1 is a group selected from the group of formulae consisting of

R 3 , R 4 , R 5 and R 6 are the same as or different from each other and each represents a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted hydrocarbon group, an optionally substituted C 1-6 alkoxy group, a C 1-6 acyl group, a nitro group, an optionally substituted amino group, an optionally substituted amide group, a mercapto group or a C 1-6 thioalkoxy group; and

m is 0 or an integer from 1 to 6.

2. The compound a salt thereof, or a hydrate of said compound or salt thereof according to claim 1 , wherein said substituent in the optionally substituted C 1-6 alkyl group, optionally substituted C 2-6 alkenyl group or optionally substituted C 2-6 alkynyl group of R 2 is at least one selected from the group consisting of a halogen atom, a hydroxyl group, a nitrile group, a C 1-6 alkyl group, C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 1-6 alkoxyalkoxy group, an aryloxy group, an aralkyloxy group, a halogenated C 1-6 alkyl group, a hydroxy C 1-6 alkyl group, a cyano C 1-6 alkyl group, a halogenated C 1-6 alkoxy group, a hydroxy C 1-6 alkoxy group, a cyano C 1-6 alkoxy group, a C 1-6 acyl group, a nitro group, an optionally substituted amino group, an optionally substituted amide group, a mercapto group and a C 1-6 thioalkoxy group.

3. The compound according to claim 1 , or 2 , a salt thereof, or a hydrate of said compound or salt thereof, wherein R 3 , R 4 , R 5 and R 6 are the same as or different from each other and each represents a hydrogen atom or an optionally substituted C 1-6 alkoxy group.

4. The compound according to claim 1 or 2 , a salt thereof, or a hydrate of said compound or salt thereof, wherein R 3 , R 4 , R 5 and R 6 are the same as or different from each other and each represents a hydrogen atom or an optionally substituted methoxy group.

5. The compound according to claim 1 or 2 , a salt thereof, or a hydrate of said compound or salt thereof, wherein m is an integer of 1.

6. The compound according to claim 2 , a salt thereof, or a hydrate of said compound or salt thereof, wherein R 1 is a [(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl group.

7. The compound according to claim 1 or 2 , a salt thereof, or a hydrate of said compound or salt thereof, wherein R 2 is a hydrogen atom.

8. The compound according to claim 1 or 2 , a salt thereof, or a hydrate of said compound or salt thereof, wherein R 2 is an optionally substituted C 1-6 alkyl group.

9. The compound according to claim 1 or 2 , a salt thereof, or a hydrate of said compound or salt thereof, wherein R 2 is a C 1-6 alkyl group substituted with (1) a halogen atom, (2) a hydroxyl group or (3) a nitrile group.

10. The compound according to claim 2 , a salt thereof, or a hydrate of said compound or salt thereof, in which R 2 is a methyl group, an ethyl group, a n-propyl group, an iso-propyl group, 2-methyl-1-propyl group or a tert-butyl group.

11. The compound according to claim 2 , a salt thereof, or a hydrate of said compound or salt thereof, in which the compound is 4-[(5,6-dimethoxy2-fluoro-1-indanon)-2-yl]methylpiperidine, 4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl-1-methylpiperidine, 4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl-1-(1-methylethyl)piperidine or 4-[(5,6-dimethoxy-2-fluoro-1-idanon)-2-yl]methyl-1-(2-methylpropyl)piperidine.

12. The compound according to claim 7 , wherein said compound is a salt thereof.

13. The compound according to claim 8 , wherein said compound is a salt thereof.

14. The compound according to claim 1 , a salt thereof, or a hydrate of said compound or salt thereof, wherein said R 1 is the group represented by formula (A).

15. A pharmaceutical composition comprising:

a therapeutically effective amount of the compound according to claim 2 , a salt thereof, or a hydrate of said compound or salt thereof; and

a pharmaceutically acceptable carrier.

16. A pharmaceutical composition comprising:

a therapeutically effective amount of the compound according to claim 1 , a salt thereof, or a hydrate of said compound or salt thereof; and

a pharmaceutically acceptable carrier.

17. A process for producing the compound according to claim 1 , a salt thereof, or a hydrate of said compound or salt thereof, which comprises fluorinating a 4-substituted piperidine compound represented by the formula:

wherein R 2 in formula (II) represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group or an optionally substituted C 2-6 alkynyl group, a salt thereof, or a hydrate of said compound or salt thereof; and

R 11 in formula (II) represents any one of group selected from the group consisting of the formulae:

wherein R 3 , R 4 , R 5 and R 6 are the same as or different from each other and each represents a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted hydrocarbon group, an optionally substituted C 1-6 alkoxy group, a C 1-6 acyl group, a nitro group, an optionally substituted amino group, an optionally substituted amide group, a mercapto group or a C 1-6 thioalkoxy group; and

m is 0 or an integer from 1 to 6.

18. The producing process according to claim 17 , in which the fluorinating agent is N-fluorobenzenesulfonimide, 3-cyclohexyl-2-fluoro-2,3-dihydro-3-methyl-1,1-dioxide-1,2-benzisothiazole or 2-fluoro-3,3-dimethyl-2,3-dihydro-1,2-benzisothiazole-1,1-dioxide.

19. The method of claim 17 , wherein said 4-substituted piperidine compound of formula (II) is converted into a salt.