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CN-121974924-A - Medical application of small molecule compound A8 as medicament for treating metabolic-related fatty liver disease

CN121974924ACN 121974924 ACN121974924 ACN 121974924ACN-121974924-A

Abstract

The invention provides a small molecular compound A8 with good therapeutic effect on metabolic-related fatty liver disease, which successfully prepares novel hydroxy pyrene derivative A8 through an organic synthesis way And based on in-vitro and in-vivo pharmacodynamic experiments, the compound has definite treatment effect on the metabolic-related fatty liver disease, and further provides application of the hydroxy pyrene derivative A8 in preparing medicaments for preventing and/or treating the metabolic-related fatty liver disease. The compound can remarkably improve the characteristic pathological changes of the metabolic-related fatty liver disease, including regulating dyslipidemia, inhibiting vacuolation degeneration of liver cells and delaying liver fibrosis progress, shows multi-target treatment advantages, and shows remarkable curative effect in treatment MAFLD.

Inventors

  • FEI YUXIANG

Assignees

  • 南京市第一医院

Dates

Publication Date
20260505
Application Date
20260213

Claims (6)

  1. 1. The hydroxy pyrene derivative A8 is characterized in that the structural formula of the hydroxy pyrene derivative A8 is as follows 。
  2. 2. A medicament for preventing and/or treating metabolic-related fatty liver disease, characterized in that the medicament comprises the hydroxypyrene derivative A8 or a pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.
  3. 3. The medicament of claim 2, further comprising a pharmaceutically acceptable adjuvant.
  4. 4. Use of the hydroxypyrene derivative A8 according to claim 1 for the preparation of an agent for reducing intracellular triglyceride levels and/or reducing intracellular lipid deposition.
  5. 5. Use of the hydroxypyrene derivative A8 according to claim 1 for preparing a medicament for preventing and/or treating metabolic-related fatty liver disease.
  6. 6. The use according to claim 5, wherein the prevention and/or treatment of metabolic-related fatty liver disease comprises at least one of reducing glutamic pyruvic transaminase, reducing liver fibrosis, reducing intracellular triglyceride content, reducing lipid deposition, improving vacuolation-like degeneration, and promoting overall liver morphology recovery.

Description

Medical application of small molecule compound A8 as medicament for treating metabolic-related fatty liver disease Technical Field The invention belongs to the technical field of medicines, and provides a small molecular compound A8, which is a chemically synthesized small molecular compound derived from traditional Chinese medicines and can effectively intervene in metabolic-related fatty liver diseases. Background Metabolic-related fatty liver disease (Metabolic dysfunction-associated FATTY LIVER DISEASE, MAFLD) is a liver disease closely related to metabolic disorders, characterized by abnormal accumulation of lipids in hepatocytes, and the spectrum of the disease can progress from simple steatosis to fibrotic lesions, and even further to cirrhosis and hepatocellular carcinoma. The disease is highly prevalence in adults worldwide and is on a growing trend, becoming an important public health problem. MAFLD is involved in the onset of lipid metabolism abnormality, insulin resistance, oxidative stress signaling activation and other factors. In addition to pathological changes in the liver itself, MAFLD patients are also at significantly elevated risk of developing type 2 diabetes, cardiovascular disease, and chronic kidney disease. Although the rate of progression to end-stage liver disease is not high, the disease burden of MAFLD-related cirrhosis and liver cancer is still aggravated due to the large cardinality of the affected population. At present, the clinical treatment of MAFLD in China still takes life style intervention as a core strategy, and a specific therapeutic drug which has definite curative effect and widely verified safety is still lacking. MAFLD drug development needs to meet the complex endpoint of improving liver steatosis and fibrosis simultaneously, and although a plurality of new mechanism drugs have entered the clinical research stage, breakthrough progress has not yet been made, clinical requirements are far from being met, and drug development faces multiple challenges. The existing candidate drugs are mostly limited to improving single pathological manifestations (such as only reducing liver lipid accumulation), and systematic regulation of multiple links of diseases is difficult to realize. For example, resmetirom of the available batches, while improving liver steatosis, had limited effect on fibrosis progression. In terms of drug safety, an agonist of the farnesol X receptor (Farnesoid X Receptor, FXR) is prone to cause skin itch, and a thyroid hormone beta receptor agonist has cardiovascular risk, and the natural compound has the problem of low bioavailability. Clinical trial design also faces limitations such as slow disease progression, long-term endpoint observation, invasive liver biopsy, etc., resulting in high development costs. In addition, long-term drug treatment can induce drug resistance, and multi-target combined strategies have potential, but the challenges of complex drug interaction, difficult dosage optimization, complex toxicity risk and the like need to be solved. Together, these factors lead to drug development success rates in MAFLD fields that are lower than those in other therapeutic fields, and there is a need to develop novel small molecule compounds with multi-target synergy, higher safety and economic viability. Disclosure of Invention In order to solve the technical problems in the prior art, the invention provides application of a hydroxy pyrene micromolecule compound A8 in improvement MAFLD. The technical scheme of the invention is as follows: A first object of the present invention is to provide a hydroxypyrene derivative A8, wherein the hydroxypyrene derivative A8 has the structural formula 。 The second object of the present invention is to provide a medicament for preventing and/or treating metabolic-related fatty liver disease, which comprises the above-mentioned hydroxypyrene derivative A8 or a pharmaceutically acceptable salt thereof as an active ingredient. Further, the medicine also comprises pharmaceutically acceptable auxiliary materials. It is a third object of the present invention to provide the use of the aforementioned hydroxypyrene derivative A8 for the preparation of an agent for reducing intracellular triglyceride levels and/or reducing intracellular lipid deposition. The fourth object of the invention is to provide an application of the hydroxy pyrene derivative A8 in preparing a medicament for preventing and/or treating metabolic-related fatty liver diseases. Further, the prevention and/or treatment of the metabolism related fatty liver disease comprises at least one of reducing serum total cholesterol, reducing glutamic pyruvic transaminase, reducing liver fibrosis, reducing intracellular triglyceride content, reducing lipid deposition, improving vacuolated degeneration, and promoting liver overall morphology recovery. The technical scheme of the invention has the beneficial effects that: The novel compound A8 is designed and