Compounds having S1P5 receptor agonistic activity

Patent metadata

Field	Value
Publication number	US-12049445-B2
Application number	US-202117521004-A
Country	US
Kind code	B2
Filing date	Nov 8, 2021
Priority date	Feb 22, 2018
Publication date	Jul 30, 2024
Grant date	Jul 30, 2024

Abstract

A compound represented by the general formula (V)

wherein all the symbols are as defined in the specification, has an improved balance of the agonist activity against the S1P 5 receptor relative to the S1P 1 receptor, and can thus serve as a therapeutic agent for S1P 5 -mediated diseases such as schizophrenia and Binswanger's disease and other neurodegenerative diseases.

First claim

The invention claimed is:

1. A method for treating an S1P 5 -mediated disease in a subject in need thereof, comprising administering an effective amount of 1-[[(3S)-3-methyl-6-(4,4,4-trifluorobutoxy)-3,4-dihydronaphthalen-2-yl]methyl]azetidine-3-carboxylic acid or a pharmaceutically acceptable salt thereof to the subject.

2. The method according to claim 1 , wherein the S1P 5 -mediated disease is a neurodegenerative disease, an autoimmune disease, an infectious disease, or cancer.

3. The method according to claim 2 , wherein the S1P 5 -mediated disease is a neurodegenerative disease selected from the group consisting of schizophrenia, Binswanger's disease, multiple sclerosis, neuromyelitis optica, Alzheimer-type dementia, cognitive impairment, amyotrophic lateral sclerosis, spinocerebellar degeneration, multiple system atrophy, Parkinson's disease, and Lewy body dementia.

4. A method for treating an S1P 5 -mediated disease in a subject in need thereof, comprising administering an effective amount of a compound of the following structure:

to the subject.

5. The method according to claim 4 , wherein the S1P 5 -mediated disease is a neurodegenerative disease, an autoimmune disease, an infectious disease, or cancer.

6. The method according to claim 5 , wherein the S1P 5 -mediated disease is a neurodegenerative disease selected from the group consisting of schizophrenia, Binswanger's disease, multiple sclerosis, neuromyelitis optica, Alzheimer-type dementia, cognitive impairment, amyotrophic lateral sclerosis, spinocerebellar degeneration, multiple system atrophy, Parkinson's disease, and Lewy body dementia.

7. A method for treating an S1P 5 -mediated disease in a subject in need thereof, comprising administering an effective amount of a pharmaceutically acceptable salt of the compound of the following structure:

to the subject.

8. The method according to claim 7 , wherein the S1P5-mediated disease is a neurodegenerative disease, an autoimmune disease, an infectious disease, or cancer.

9. The method according to claim 8 , wherein the S1P5-mediated disease is a neurodegenerative disease selected from the group consisting of schizophrenia, Binswanger's disease, multiple sclerosis, neuromyelitis optica, Alzheimer-type dementia, cognitive impairment, amyotrophic lateral sclerosis, spinocerebellar degeneration, multiple system atrophy, Parkinson's disease, and Lewy body dementia.

Assignees

• Ono Pharmaceutical Co

Inventors

• Watanabe Toshihide
• Kusumi Kensuke
• Imaide Satomi
• Endo Toshimitsu
• Komiya Takaki
• TSUBURAYA Naomi

Classifications

• C07C49/577

  containing ether groups, [IMAGE cpc-sch-C07C-0958.gif] groups,[IMAGE cpc-sch-C07C-0959.gif] groups, or[IMAGE cpc-sch-C07C-0960.gif] groups · CPC title

• C07C49/252

  containing six-membered aromatic rings and other rings · CPC title

• C07D207/16

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title