Spiro-cyclic amine derivatives as s1p modulators

Patent metadata

Field	Value
Publication number	US-2025296917-A1
Application number	US-202418948217-A
Country	US
Kind code	A1
Filing date	Nov 14, 2024
Priority date	Dec 1, 2020
Publication date	Sep 25, 2025
Grant date	—

Abstract

The present invention is directed to spiro-cyclic amine derivatives which are modulators of S1P receptors and are useful in the treatment of CNS disorders.

First claim

What is claimed is:

1 . A compound, which is Compound 1 having the structure:

or a pharmaceutically acceptable salt thereof.

2 . The compound of claim 1 , which is Compound 1a having the structure:

or a pharmaceutically acceptable salt thereof.

3 . The compound of claim 1 , which is Compound 1b having the structure:

or a pharmaceutically acceptable salt thereof.

4 . The compound of claim 1 , which is a hydrochloric acid salt.

5 . A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

6 . A method of modulating S1P receptor activity, said method comprising contacting a compound of claim 1 , or a pharmaceutically acceptable salt thereof, with an S1P receptor.

7 . The method of claim 6 , wherein the S1P is S1P5.

8 . The method of claim 6 , wherein the contacting comprises administering the compound to a patient.

9 . A method of treating a disease or disorder associated with S1P5, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

10 . A method of treating a CNS disorder in a patient in need thereof, said method comprising administering to the patient a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.

11 . The method of claim 10 , wherein the CNS disorder is Alzheimer's disease, or vascular dementia.

12 . The method of claim 10 , wherein the CNS disorder is Niemann-Pick disease.

13 . The method of claim 10 , wherein the CNS disorder is Niemann-Pick type C disease.

14 . The method of claim 10 , wherein the CNS disorder is cognitive deficits in schizophrenia, obsessive-compulsive behavior, major depression, autism, multiple sclerosis, or pain.

15 . The method of claim 10 , wherein the CNS disorder is a cognitive disorder.

16 . The method of claim 15 , wherein the cognitive disorder is age-related cognitive decline.

17 . A process of preparing Compound 1 having the structure:

or a pharmaceutically acceptable salt thereof, comprising:
(a) reacting Compound G, or a salt thereof:

with a compound having the structure:

to prepare Compound H, or a salt thereof:

and
(b) reacting Compound H, or a salt thereof, with hydroxide followed by treatment with an acid to form Compound 1.

18 . The process of claim 17 wherein Compound G, or a salt thereof, is prepared by reacting Compound D, or a salt thereof:

with CH 2 ═CH—C(O)OEt.

19 . The process of claim 18 wherein Compound D is prepared by reacting Compound C, or a salt thereof:

with a protic acid.

20 . The process of claim 19 wherein Compound C, or a salt thereof, is prepared by reacting Compound B:

with 1,2-ethanolamine.

21 . The process of claim 20 wherein Compound B is prepared by reacting Compound A:

with trimethylsulfonium bromide.

22 . A compound, which is Compound 1, prepared by the process of claim 17 .

Assignees

• Abbvie Deutschland

Inventors

• Amberg Willie
• Backfisch Gisela
• Bodié Karen
• Hempel Katja
• Laplanche Loic
• Mezler Mario
• Ochse Michael
• Turner Sean
• van Bergeijk Jeroen
• Van Der Kam Elizabeth
• Lange Udo
• Geneste Hervé

Classifications

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07D265/34 Primary

  condensed with carbocyclic rings · CPC title

• C07D265/36 Primary

  condensed with one six-membered ring · CPC title