Substituted piperidine compound and use thereof

Patent metadata

Field	Value
Publication number	US-12281073-B2
Application number	US-202318347345-A
Country	US
Kind code	B2
Filing date	Jul 5, 2023
Priority date	Feb 4, 2016
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

Abstract

Provided is a substituted piperidine compound having an orexin type 2 receptor agonist activity. A compound represented by the formula (I):

wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an orexin type 2 receptor agonist activity, and is useful as a prophylactic or therapeutic agent for narcolepsy.

First claim

The invention claimed is:

1. A compound having formula (III)

wherein R 2 is a cyclohexyl group substituted with a substituted phenyl group;
wherein the phenyl group is substituted with a hydroxy group, an optionally substituted C 1-6 alkoxy group, or a C 7-16 aralkyloxy group.

2. The compound of claim 1 , wherein the phenyl group is substituted with an optionally substituted C 1-6 alkoxy group.

3. The compound of claim 1 , wherein the phenyl group is substituted with a hydroxy group.

4. The compound of claim 1 , wherein the phenyl group is substituted with a C 7-16 aralkyloxy group.

5. A compound having formula (V)

wherein R 2 is a cyclohexyl group substituted with a substituted phenyl group;
wherein the phenyl group is substituted with a hydroxy group, an optionally substituted C 1-6 alkoxy group, or a C 7-16 aralkyloxy group; and
wherein R 5 is an amino-protecting group.

6. The compound of claim 5 , wherein the phenyl group is substituted with an optionally substituted C 1-6 alkoxy group.

7. The compound of claim 5 , wherein the phenyl group is substituted with a hydroxy group.

8. The compound of claim 5 , wherein the phenyl group is substituted with a C 7-16 aralkyloxy group.

9. The compound of claim 5 , wherein R 5 is selected from the group consisting of a formyl group, a C 1-6 alkyl-carbonyl group, a C 1-6 alkoxy-carbonyl group, a benzoyl group, a C 7-10 aralkyl-carbonyl group, a C 7-14 aralkyloxy-carbonyl group, a trityl group, a phthaloyl group, an N,N-dimethylaminomethylene group, a substituted silyl group, and a C 2-6 alkenyl group.

10. The compound of claim 5 , wherein R 5 is a C 1-6 alkoxy-carbonyl group.

11. The compound of claim 10 , wherein the R 5 is a tert-butoxycarbonyl group.

12. The compound of claim 11 , wherein the phenyl group is substituted with a C 7-16 aralkyloxy group.

13. The compound of claim 11 , wherein the phenyl group is substituted with a hydroxy group.

14. A method of preparing a compound of formula (III) according to claim 1 , comprising alkylating a compound of formula (II)

to obtain the compound of formula (III)

wherein R 2 is as defined in claim 1 .

15. The method of claim 14 , wherein the compound of formula (II) is alkylated to obtain the compound of formula (III) in a solvent and in the presence of a base.

16. The method of claim 15 , wherein the solvent is an ether solvent.

17. The method of claim 16 , wherein the solvent is tetrahydrofuran.

18. The method of claim 15 , wherein the base is an alkali metal hydride.

19. The method of claim 18 , wherein the base is sodium hydride.

20. A method of preparing a compound of formula (V) according to claim 5 , comprising aminating of a compound of formula (III)

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Fujimoto Tatsuhiko
• Rikimaru Kentaro
• Fukuda Koichiro
• Sugimoto Hiromichi
• Matsumoto Takahiro
• Tokunaga Norihito
• HIROZANE Mariko

Classifications

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• C07D417/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D413/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title