Cyclic amines

Patent metadata

Field	Value
Publication number	US-9593105-B2
Application number	US-201615205850-A
Country	US
Kind code	B2
Filing date	Jul 8, 2016
Priority date	Oct 12, 2012
Publication date	Mar 14, 2017
Grant date	Mar 14, 2017

Abstract

The present invention is directed to novel cyclic amines which inhibit the P2X 7 receptor.

First claim

What is claimed:

1. 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 thereof.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

18. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof of claim 1 and a pharmaceutically acceptable carrier.

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

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/04

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

• A61P25/18

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