CN-121974925-A - Application of small molecule compound A5 in preparation of medicines for treating metabolic-related fatty liver disease

Abstract

The invention provides a small molecular compound A5 with good therapeutic effect on metabolic-related fatty liver disease, which successfully prepares novel hydroxy pyrene derivative A5 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 A5 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 the vacuolated degeneration of liver cells and delaying the progress of liver fibrosis, shows multi-target treatment advantages, and shows remarkable curative effects in treating the metabolic-related fatty liver disease.

Inventors

• LIU CHAO

Assignees

• 南京市第一医院

Dates

Publication Date

20260505

Application Date

20260213

Claims (7)

1. 1. The hydroxy pyrene derivative A5 is characterized in that the hydroxy pyrene derivative A5 has the structural formula of 。
2. 2. A medicament for preventing and/or treating metabolic-related fatty liver disease, characterized in that the medicament comprises the hydroxypyrene derivative A5 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 A5 according to claim 1 for the preparation of a reagent for reducing cellular lipid deposition.
5. 5. Use of the hydroxypyrene derivative A5 or a pharmaceutically acceptable salt thereof according to claim 1 for the preparation of 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 improving lipid metabolism, restoring liver function, alleviating tissue pathological damage.
7. 7. The use according to claim 6, wherein said improving lipid metabolism is reducing intracellular triglyceride levels and/or lipid deposition, said restoring liver function is reducing serum glutamate pyruvate transaminase levels, and said reducing tissue pathological damage is improving liver cavitation-like degeneration, fibrosis, liver overall morphology changes.

Description

Application of small molecule compound A5 in preparation of medicines for treating metabolic-related fatty liver disease Technical Field The invention belongs to the technical field of medicines, and provides a micromolecular compound A5 which is synthesized by a chemical means and is derived from traditional Chinese medicines and used for resisting metabolic-related fatty liver diseases. Background Metabolic-related fatty liver disease (Metabolic dysfunction-associated FATTY LIVER DISEASE, MAFLD) is a disease closely related to insulin resistance and metabolic dysfunction, the most central pathological change of which is excessive accumulation of fat in liver cells, called hepatic steatosis. The concept has evolved from nonalcoholic fatty liver disease, which spectrum covers metabolic-related steatohepatitis from simple liver steatosis to fibrosis, and can further progress to cirrhosis and hepatocellular carcinoma. MAFLD affects about 30% of the population worldwide, has become a significant public health challenge, and its incidence is expected to continue to rise in the coming years. MAFLD is not completely clear, and is currently thought to be involved in many factors such as lipid metabolism disorders, oxidative stress, mitochondrial dysfunction, and the like. Excessive lipid accumulation in the liver can induce cytotoxicity and is closely related to the increased risk of type 2 diabetes, cardiovascular disease, chronic kidney disease and certain extrahepatic malignancies in addition to liver lesions. At present, the clinical treatment is mainly performed by life style intervention, and is assisted by limited kinds of medicines, and specific treatment means are not yet available. Although the proportion of patients who progress to end-stage liver disease is low, the absolute number of cirrhosis and hepatocellular carcinoma due to MAFLD is still not negligible due to the large cardinality of the affected population. At present, no medicine specially aiming at the disease is available in China, and the existing treatment options such as vitamin E and pioglitazone limit the clinical application of the medicine due to the safety or tolerance problems. The core difficulty faced by drug development is that effective improvement of liver steatosis and fibrosis needs to be achieved simultaneously. Although there have been a number of targeted drugs entering phase III clinical studies, the therapeutic needs have not been fully met, highlighting the urgency of developing new mechanism drugs. The current MAFLD drug development faces multiple bottlenecks, namely, firstly, the existing candidate drugs are only aimed at a single pathological link (such as lipid metabolism) and multi-dimensional disease regulation is difficult to realize. Taking Resmetirom as an example of the batch obtained, it mainly improves liver steatosis, but has limited effect on fibrosis progression. Second, safety issues are prominent, such as FXR (Farnesoid X Receptor) agonists are prone to pruritic symptoms, thyroid hormone receptor beta agonists present cardiovascular risks, and natural compounds generally suffer from low bioavailability limitations. In addition, clinical trial design is limited by factors such as slow disease progression, long-term observation of endpoints, invasive liver biopsy, etc., resulting in high development costs. Finally, long-term administration may induce drug resistance, and multi-target joint strategies have potential, but face challenges such as complex drug interactions, difficulty in dose optimization, safety superposition, and the like. Together, these factors lead to drug development success rates in MAFLD fields that are lower than those in other disease fields, and there is a need to develop novel small molecule compounds that combine multi-target synergy, higher safety, and more economical preparation processes. Disclosure of Invention In order to solve the technical problems in the prior art, the invention discloses a small molecule hydroxy pyrene derivative A5 and application thereof in improving metabolic-related fatty liver diseases. A first object of the present invention is to provide a hydroxypyrene derivative A5, wherein the hydroxypyrene derivative A5 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 A5 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 A5 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 A5 in preparing a medicame