Aminocyclobutane derivatives, method for preparing same and the use thereof as drugs

Patent metadata

Field	Value
Publication number	US-9687459-B2
Application number	US-201615262885-A
Country	US
Kind code	B2
Filing date	Sep 12, 2016
Priority date	Dec 4, 2012
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

The present inventions concerns derivatives of aminocyclobutane, particularly as NMDA receptor antagonists, their application in human therapy and their method of preparation.
These compounds correspond to the general formula (1):

wherein:
X 1 represents a hydrogen atom or fluorine atom; X 2 is a hydrogen atom or fluorine atom or chlorine atom; R1 represents a hydrogen atom or fluorine atom or chlorine atom or methyl group or methoxy group or cyano group; R2 represents independently or together a methyl group or ethyl group.

First claim

The invention claimed is:

1. A method for the treatment of mixed pain which comprises administering to a patient in need thereof an effective amount of a compound of the following general formula (1):

or pharmaceutically acceptable salt or solvate thereof,
wherein:
X 1 represents a hydrogen atom or fluorine atom;
X 2 is a hydrogen atom or fluorine atom or chlorine atom;
R1 represents a hydrogen atom or fluorine atom or chlorine atom or methyl group or methoxy group or cyano group;
R2 represents independently or together a methyl group or ethyl group.

2. The method according to claim 1 , wherein:
X 1 represents a hydrogen atom or fluorine atom;
X 2 is a hydrogen atom or fluorine atom or chlorine atom;
R1 a hydrogen atom or fluorine atom or chlorine atom or methyl group or methoxy group or cyano group;
R2 is an ethyl group.

3. The method according to claim 1 , wherein the compound of general formula (I) is selected from the following:
trans-3-amino-N,N-diethyl-1-phenylcyclobutanecarboxamide,
trans-3-amino-N,N-dimethyl-1-phenylcyclobutanecarboxamide
trans-3-amino-N,N-diethyl-1-(2-fluorophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3-methoxyphenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3-fluorophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3-chlorophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3-methylphenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3-cyanophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(2-fluoro-3-chlorophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(2,5-difluorophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3,5-difluorophenyl)-cyclobutanecarboxamide, and
trans-3-amino-N,N-diethyl-1-(3,5-dichlorophenyl)-cyclobutanecarboxamide.

4. The method according to claim 1 , wherein the mixed pain is selected from cancer pain and back and lower back pain.

5. A method for the treatment of mixed pain which comprises administering to a patient in need thereof an effective amount of a pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and at least one compound of the following general formula (1):

or pharmaceutically acceptable salt or solvate thereof,
wherein:
X 1 represents a hydrogen atom or fluorine atom;
X 2 is a hydrogen atom or fluorine atom or chlorine atom;
R1 represents a hydrogen atom or fluorine atom or chlorine atom or methyl group or methoxy group or cyano group;
R2 represents independently or together a methyl group or ethyl group.

6. The method according to claim 5 , wherein:
X 1 represents a hydrogen atom or fluorine atom;
X 2 is a hydrogen atom or fluorine atom or chlorine atom;
R1 a hydrogen atom or fluorine atom or chlorine atom or methyl group or methoxy group or cyano group;
R2 is an ethyl group.

7. The method according to claim 5 , wherein the compound of general formula (I) is selected from the following:
trans-3-amino-N,N-diethyl-1-phenylcyclobutanecarboxamide,
trans-3-amino-N,N-dimethyl-1-phenylcyclobutanecarboxamide
trans-3-amino-N,N-diethyl-1-(2-fluorophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3-methoxyphenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3-fluorophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3-chlorophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3-methylphenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3-cyanophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(2-fluoro-3-chlorophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(2,5-difluorophenyl)-cyclobutanecarboxamide,
trans-3-amino-N,N-diethyl-1-(3,5-difluorophenyl)-cyclobutanecarboxamide, and
trans-3-amino-N,N-diethyl-1-(3,5-dichlorophenyl)-cyclobutanecarboxamide.

8. The method according to claim 5 , wherein the mixed pain is selected from cancer pain and back and lower back pain.

Assignees

• Pf Medicament

Inventors

• Vacher Bernard
• Blanc Elodie
• Depoortere Ronan

Classifications

• A61P25/04

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

• A61P29/02

  without antiinflammatory effect · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07C231/14

  by formation of carboxamide groups together with reactions not involving the carboxamide groups · CPC title