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EP-4162937-B1 - PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING PARKINSON'S DISEASE, COMPRISING 2-(4-(1-HYDROXYPROPANE-2-YL)PHENYL)ISOINDOLINE-1-ONE COMPOUND

EP4162937B1EP 4162937 B1EP4162937 B1EP 4162937B1EP-4162937-B1

Inventors

  • PARK, CHI HU
  • YU, Myungjoo
  • KIM, HYOUNG SHIK

Dates

Publication Date
20260506
Application Date
20210325

Claims (7)

  1. A pharmaceutical composition for use in preventing or treating Parkinson's disease, comprising a compound represented by the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  2. The pharmaceutical composition for use of claim 1, wherein the composition increases expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α).
  3. The pharmaceutical composition for use of claim 1, wherein the composition has a formulation selected from the group consisting of a solution, suspension, syrup, emulsion, liposome, acid, powder, granule, tablet, sustained-release agent, and capsule.
  4. The pharmaceutical composition for use of claim 3, wherein the composition is a composition for oral administration and has a formulation of a drug carrier or sustained-release agent comprising liposomes.
  5. The pharmaceutical composition for use of claim 3, wherein the composition is a composition for parenteral administration and has a formulation of a drug carrier or sustained-release agent comprising liposomes and ultrasonic contrast agents.
  6. The pharmaceutical composition for use of claim 1, wherein the composition is to be administered to a subject in which expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is reduced.
  7. A healthy functional food for use in ameliorating Parkinson's disease, comprising a compound represented by the following Chemical Formula 1 as an active ingredient.

Description

Technical Field The present disclosure relates to a pharmaceutical composition for preventing or treating Parkinson's disease, including a 2-(4-(1-hydroxypropan-2-yl)phenyl)isoindolin-1-one compound or a pharmaceutically acceptable salt thereof. Background Art Parkinson's disease, a disease whose main symptoms are tremors (shaking), rigidity, ataxia (slowed movements), and prolonged unstable posture, is a chronic disease caused by a lack of neurotransmitters called dopamine in the brain and one of the degenerative diseases in the central nervous system, which is started with modification in the substantia nigra pars compacta in the midbrain and accompanied by its pathophysiological symptoms such as reduction in brain volume and aggregation of α-synuclein (αSyn) as well as imperfect gait, hand tremor, and rigid behavior. Most treatment strategies for Parkinson's disease were limited to managing the symptoms of motor functions with drugs such as L-DOPA or dopamine receptor agonists as well as deep brain stimulation. In addition, these therapies at the current research level have failed to prevent the gradual death of dopaminergic neurons (DAs). Recently, on the other hand, when it comes to death and survival of cells, research related to the function of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and various diseases that may be caused by dysregulation of PGC-1α has been reported. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Lou Gehrig's disease are caused by the gradual loss of function and death of neurons, and the overall symptoms of these diseases are due to the loss of certain parts of neurons. Unlike the hyperactivity due to neurodegeneration observed in PGC-1α knock-out mice and the damaged areas that are less observed in the cerebral cortex, it is noticed that PGC-1α is directly related to neurodegenerative diseases based on the damaged sites that are markedly found in corpus striatum in the brain. Also, in addition to these findings, the identification of vacuolar lesions in the central nervous system in PGC-1α knock-out mice shows that PGC-1α plays a crucial role in maintaining neuronal functions. Reduced expression of PGC-1α increases the expression of BACE1, which produces beta-amyloid by degrading and cleaving the progenitor protein of amyloid that causes Alzheimer's disease and increases the amount of beta-amyloid, thereby leading to mitochondrial hypofunction and cell death. Single-nucleotide mutations in the PGC-1α gene are highly correlated with an increase in the risk factors that develop Parkinson's disease and Huntington's disease and are known to decrease expression of PGC-1α genes in patients with Alzheimer's disease, Parkinson's disease, and Huntington's disease. Recently, there has been a rising interest in treatment methods for Parkinson's disease by pharmacologically activating PGC-1α for its functional mechanisms, which are closely related to those neurodegenerative diseases. [Prior Art Document] [Patent Document] (Patent Document 1) Korean Patent No. 10-1384642 WO 2007/109211 A2 and corresponding JP 2009530306 A relate to compounds for use in the treatment of spinal muscular atropy and other uses, and disclose lists of miscellaneous compounds and possible uses. US 2019/030053 A1 describes a composition for preventing or treating diseases or symptoms associated with a reduction in the expression of PGC-1α, for example Parkinson's disease. US 2017/095451 A1 relates to a method of increasing PGC-1α expression comprising administering indoprofen to a subject, wherein the subject may be affliceted by a disease caused by low expression of PGC-1α, as sarcopenia, muscular atrophy, obesity or diabetes. KR 2014 0000733 A and KR 2010 0097059 A relate to treatments of Parkinson's disease, and Su Xiaomin et al: "PGC 1 Promoter Methylation in Parkinson's Disease", PLOS ONE, vol. 10, no. 8, 28 August 20215, pages 1-24, relates to PGC 1α promoter methylation in Parkinson's disease. Disclosure of the Invention Technical Goals An object of the present invention is to provide a composition capable of preventing or treating Parkinson's disease in a subject, as an expression of PGC-1α is enhanced in the brain by including a 2-(4-(1-hydroxypropan-2-yl)phenyl)isoindoline-1-one compound. Technical Solutions The present invention provides a pharmaceutical composition for use in preventing or treating Parkinson's disease, including a compound represented by the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. In addition, the composition may increase the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). In addition, the composition may have a formulation selected from the group consisting of a solution, suspension, syrup, emulsion, liposome, acid, powder, granule, tablet, sustained-release agent, and capsule. In addition, the composition may