Dizocilpine derivatives as peripheral NMDA receptor antagonists

Patent metadata

Field	Value
Publication number	US-11944616-B2
Application number	US-202217825082-A
Country	US
Kind code	B2
Filing date	May 26, 2022
Priority date	Jun 13, 2016
Publication date	Apr 2, 2024
Grant date	Apr 2, 2024

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 cyclobutyl 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 R 2 represents a methyl group.

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

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

6. Compound according to claim 1 , wherein the anionic counterion X − is I − .

7. Compound according to claim 1 , wherein the anionic counterion X − is Cl − .

8. Compound according to claim 1 , wherein the anionic counterion X − is Br − .

9. Compound according to claim 1 , wherein the anionic counterion X − is OH − .

10. Compound according to claim 1 , chosen from:

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

12. 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.

13. 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.

14. 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.

Assignees

• Institut National De La Sante Et De La Rech Medical Inserm
• Centre Nat Rech Scient
• Univ Paris Saclay
• Assist Publique—Hopitaux De Paris Aphp
• Hopital Marie Lannelongue
• Inst Nat Sante Rech Med

Inventors

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

Classifications

• A61K31/46 Primary

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

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P9/12

  Antihypertensives · CPC title

• C07D451/00

  Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof · CPC title

• 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