Dizocilpine derivatives as peripheral NMDA receptor antagonists

Patent metadata

Field	Value
Publication number	US-11376245-B2
Application number	US-201716308654-A
Country	US
Kind code	B2
Filing date	Jun 13, 2017
Priority date	Jun 13, 2016
Publication date	Jul 5, 2022
Grant date	Jul 5, 2022

Abstract

The present invention relates to compounds of formula (I) for use as peripheral NMDA receptor antagonists.

First claim

The invention claimed is:

1. Compound of formula (I):

wherein:
R 1 represents a cyclopropyl group;
R 2 represents a (C 1 -C 10 )alkyl group;
n is 1;

R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 represent a hydrogen atom; and X − is an anionic counterion selected from the group consisting of I − , Cl − , Br − and OH −.

2. Compound according to claim 1 , wherein R 2 represents a methyl group or an ethyl group.

3. Compound according to claim 1 , wherein the anionic counterion X − is selected from the group consisting of I − and Cl −.

4. A pharmaceutical composition comprising at least one compound according to claim 1 , and at least one pharmaceutically acceptable excipient.

5. A method for A method for treating a disease or condition in a subject comprising administering to the subject a compound according to claim 1 , wherein the disease or the condition is pulmonary hypertension.

6. A method for treating a disease or condition in a subject comprising administering to the subject a compound according to the claim 1 , wherein the disease or the condition is selected from the group consisting of pulmonary arterial hypertension and thromboembolic pulmonary hypertension.

7. A method for treating a disease in a subject comprising administering to the subject a compound according to claim 1 , wherein the disease is pulmonary arterial hypertension.

8. Compound according to claim 1 , chosen from:

9. Compound according to claim 1 , wherein R 2 represents a methyl group.

10. Compound according to claim 1 , wherein R 2 represents an ethyl group.

11. Compound according to claim 1 , wherein X − is I −.

12. Compound according to claim 1 , wherein X − is Cl −.

13. Compound according to claim 1 , wherein X − is Br −.

14. Compound according to claim 1 , wherein X − is OH −.

Assignees

• Inst Nat Sante Rech Med
• Centre Nat Rech Scient
• Univ Paris Sud
• Assist Publique Hopitaux Paris Aphp
• Hopital Marie Lannelongue
• Assist Publique—Hopitaux De Paris Aphp

Inventors

• Cohen-Kaminsky Sylvia
• Humbert Marc
• Dumas Sebastien
• Bru-Mercier Gilles
• Messaoudi Samir
• Brion Jean-Daniel
• Alami Mouad
• Galvani Gilles

Classifications

• C07D451/02 Primary

  containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof · CPC title

• A61K31/46 Primary

  8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P17/06

  Antipsoriatics · CPC title