Cyclic amines

Patent metadata

Field	Value
Publication number	US-9861639-B2
Application number	US-201715415073-A
Country	US
Kind code	B2
Filing date	Jan 25, 2017
Priority date	Oct 12, 2012
Publication date	Jan 9, 2018
Grant date	Jan 9, 2018

Abstract

The present invention is directed to novel cyclic amines which inhibit the P2X7 receptor.

First claim

What is claimed is:

1. A method of treating pain comprising administering a therapeutically effective amount of a compound of formula I:

wherein R 1 is pyrazinyl optionally substituted with one or more C 1-6 alkyl, halogen, hydroxy, C 1-4 fluoroalkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, C 1-6 fluoroalkoxy, cyano or —SO 2 R 7 ;
wherein R 2a and R 2b combine with the nitrogen to which they are attached to form piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, pyrrolo, imidazo, azetidinyl, 6 to 10 membered spiro(heterocyclyl), homomorpholinyl, homopiperidinyl or homopiperazinyl each of which is optionally substituted with one or more C 1-6 alkyl, C 1-6 alkenyl, C 3-6 -cycloalkyl, C 1-6 alkoxy, oxo, —NR 5 R 6 or fluorines;
wherein R 3 is halogen, C 1-4 fluoroalkyl, cyano, cyclopropyl, C 1-4 alkyloxy, C 1-4 fluoroalkyloxy, —SO 2 R 7 , —NR 5 R 6 or C 1-6 alkyl;
wherein R 4 is halogen, C 1-6 alkyl, C 1-4 fluoroalkyl, cyano, —SO 2 R 8 , —NR 5 R 6 , C 1-6 alkoxy, C 1-4 fluoroalkoxy or C 3-6 -cycloalkyl;
wherein R 5 and R 6 independently of each other are hydrogen or C 1-6 alkyl;
wherein R 7 is C 1-6 alkyl, C 3-6 cycloalkyl, C 1-4 fluoroalkyl; and
wherein n is 0-3;

or a pharmaceutically acceptable salt of said compound.

2. The method of claim 1 , wherein R 2a and R 2b of said compound or pharmaceutically acceptable salt thereof combine with the nitrogen to which they are attached to form optionally substituted piperazinyl.

3. The method of claim 1 , wherein R 2a and R 2b of said compound or pharmaceutically acceptable salt thereof combine with the nitrogen to which they are attached to form optionally substituted piperidinyl.

4. The method of claim 1 , wherein R 2a and R 2b of said compound or pharmaceutically acceptable salt thereof combine with the nitrogen to which they are attached to form optionally substituted morpholinyl.

5. The method of claim 1 , wherein R 2a and R 2b of said compound or pharmaceutically acceptable salt thereof combine with the nitrogen to which they are attached to form optionally substituted pyrrolidinyl.

6. The method of claim 1 , wherein R 2a and R 2b of said compound or pharmaceutically acceptable salt thereof combine with the nitrogen to which they are attached to form optionally substituted pyrrolo.

7. The method of claim 1 , wherein R 2a and R 2b of said compound or pharmaceutically acceptable salt thereof combine with the nitrogen to which they are attached to form optionally substituted imidazo.

8. The method of claim 1 , wherein R 2a and R 2b of said compound or pharmaceutically acceptable salt thereof combine with the nitrogen to which they are attached to form optionally substituted 6 to 10 membered spiro(heterocyclyl).

9. The method of claim 1 , wherein R 2a and R 2b of said compound or pharmaceutically acceptable salt thereof combine with the nitrogen to which they are attached to form optionally substituted homomorpholinyl.

10. The method of claim 1 , wherein R 2a and R 2b of said compound or pharmaceutically acceptable salt thereof combine with the nitrogen to which they are attached to form optionally substituted homopiperidinyl.

11. The method of claim 1 , wherein R 2a and R 2b of said compound or pharmaceutically acceptable salt thereof combine with the nitrogen to which they are attached to form optionally substituted homopiperazinyl.

12. The method of claim 1 , wherein R 3 of said compound or pharmaceutically acceptable salt thereof is chlorine, methyl or trifluoromethyl.

13. The method of claim 1 , wherein n of said compound or pharmaceutically acceptable salt thereof is n is 0.

14. The method of claim 1 , wherein n of said compound or pharmaceutically acceptable salt thereof is n is 1.

15. The method of claim 1 , wherein n of said compound or pharmaceutically acceptable salt thereof is n is 2.

16. The method of claim 1 , wherein R 4 of said compound or pharmaceutically acceptable salt thereof is fluorine, chlorine, C 1-3 alkyl, C 1-4 fluoroalkyl, cyano, C 1-3 alkoxy or C 1-4 fluoroalkoxy.

17. The method of claim 1 wherein said pain is acute pain.

18. The method of claim 1 wherein said pain is chronic pain.

19. The method of claim 1 wherein said pain is inflammatory pain.

20. The method of claim 1 wherein said pain is neuropathic pain or post-operative pain.

21. The method of claim 1 wherein said pain is caused by morphine tolerance, fibromyalgia, neuralgia, headache, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, irritable bowel syndrome or inflammatory bowel disease.

22. The method of claim 5 wherein said pain is neuropathic pain.

Assignees

• H Lundbeck As

Inventors

• Kilburn John Paul
• Rasmussen Lars Kyhn
• Jessing Mikkel
• Eldemenky Eman Mohamed
• Chen Bin
• Jiang Yu

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title