Application of thiazolopyrone analogs in the preparation of anti-hepatic fibrosis or anti-acute liver injury drugs

Abstract

The invention provides a new medical application of the thiazolopyrone analog, that is, its application in the preparation of anti-hepatic fibrosis or anti-acute liver injury drugs. The general structural formula of the thiazolopyrone analogue is: Classical pharmacological experiments have confirmed that the thiazolopyrone analogue can down-regulate smooth muscle actin α-SMA and transforming growth factor TGF-SMA of human hepatic stellate cells LX-2 β1 expression, thereby inhibiting the proliferation and transformation of human hepatic stellate cells LX‑2. in CCl 4 In the induced mouse liver fibrosis / acute liver injury model experiment, thiazolopyrone analogs can inhibit the up-regulation of ALT and AST in mouse serum, and can inhibit the expression of α-SMA and TGF-β1 related to liver fibrosis , a variety of pathological section analysis and immunoomics experiments also confirmed that this analogue can effectively treat acute liver injury and liver fibrosis in mice. Therefore, this type of thiazolopyrone compound can be used as an active substance for the preparation of anti-hepatic fibrosis or anti-acute liver injury drugs.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry and relates to the application of thiazolopyrone analogs in the preparation of anti-hepatic fibrosis or anti-acute liver injury drugs. Background technique [0002] The liver is an important organ in the human body that mainly performs metabolic functions. It has the functions of deoxidation, metabolism, storage of glycogen, and secretory protein synthesis. A variety of reasons can lead to abnormal liver function. Acute liver injury is the basis of liver failure, and severe or persistent liver injury will eventually lead to liver failure. There are many causes of acute liver injury, including viral infection, improper medication, food additives, excessive intake and exposure to ethanol, ingestion of toxic food, radiation damage, etc. Due to complex reasons, there is no particularly effective drug for acute liver injury. Hepatic fibrosis is the response of the liver to chronic long-te...

AI Technical Summary

Problems solved by technology

[0003] Currently approved drugs for the treatment of fibrotic diseases include pirfenidone and nintedanib, but both are drugs specifically for the treatment of idiopathic pulmonary fibrosis (IPF). treatment has certain limitations

In addition, studies have shown that colchicine can achieve the effect of treating liver cirrhosis and liver fibrosis through various pharmacological pathways, with clear curative effect and low effective dose

However, colchicine is widely distributed throughout the body after administration, and often produces serious side effects such as nausea, loss of appetite, abdominal distension, intestinal paralysis, constipation and gastric bleeding, which greatly limits its clinical application.

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