Pharmaceutical composition for treatment or prevention of neurodegenerative diseases

• US 10,285,985 B2
• Filed: 03/31/2016
• Issued: 05/14/2019
• Est. Priority Date: 03/31/2015
• Status: Active Grant

• Current Assignee: National University Corporation Okayama University
• Original Assignee: National University Corporation Okayama University
• Inventors: Kakuta, Hiroki
• Primary Examiner(s): Jean-Louis, Samira J
• Application Number:
  US15/562,509
• Publication Number:
  US 20180092888A1
• Time in Patent Office: 1,139 Days
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/4192 1,2,3-Triazoles
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

There is provided a pharmaceutical composition for treatment or prevention of a neurodegenerative disease, comprising an RXR agonist as an active ingredient, which is a compound represented by formula (1) or (2). The pharmaceutical composition is effective in treatment or prevention of neurodegenerative diseases such as dementia, Parkinson'"'"'s disease and multiple sclerosis with reducing side effects such as enlargement of the liver and elevation of blood triglyceride level. In these formulas, A represents CMe₂, N-methyl, N-ethyl or N-isopropyl; X represents N, CH or C—CF₃; Y and Z represent N or CH; R¹ represents methyl, hydroxy, methoxy or ethoxy; R² represents H, methyl or ethyl; B represents NR³ or CHR³; R³ represents alkyl; and R⁴ represents H, halogen, alkyl, alkenyl, aryl, alkynyl, alkoxy or acyl.

Claims

1. A method for increasing the activation of Nurr1/RXR, comprising administering an effective amount of an RXR agonist as an active ingredient wherein the RXR agonist is a compound represented by formula (1):

2. The method as claimed in claim 1, wherein RXR agonist is effective in inhibiting production nitric oxide.

3. The method as claimed in claim 1, wherein the RXR agonist has Nurr1/RXR activating effect.

4. The method as claimed in claim 1, wherein the RXR agonist is administered in a dosage of about 0.01 to 1000 mg per day.

5. The method of claim 1, wherein the RXR agonist is administered orally or parenterally.