Pyridinone derivative as well as preparation method and application thereof

Abstract

The invention discloses a pyridinone derivative as well as a preparation method and application thereof. The pyridinone derivative is subjected to structural modification from the aspect of R1, R2 andR3 substituent groups, wherein modification of R1 is achieved mainly through allyl, isopentenyl, geranyl and fluorine benzyl and the like; modification of R2 is achieved mainly through ethoxyl, hydroxypropyl, amino ethyl and amino propyl and the like; and modification of R3 mainly concentrates on ethers with the certain structural features. The pyridinone derivative has the outstanding inhibitioneffect on pancreatic cancer cell PANC-1 at the state of lack of nutrition, while has no influence on the cell at the state of normal nutrition (indicating free of cytotoxicity). The preparation method of the pyridinone derivative comprises the steps that firstly basic nuclear parent bicyclo [3.3.1] nonanone is synthesized and subjected to a rearrangement reaction with a series of hydramine or diamine under catalysis of toluenesulfonic acid, and the pyridinone derivative having the remarkable inhibition effect on pancreatic cancer is prepared, and the pyridione derivative has the very good practicality.

Description

Technical field [0001] The invention belongs to the technical field of chemistry and medicine, and specifically relates to a pyridone derivative and a preparation method and application thereof. Background technique [0002] Pancreatic cancer, known as the "King of Cancer" by the medical profession, is the cancer with the worst prognosis among all malignant tumors. The mortality rate after diagnosis is as high as 95%-98%, that is to say, 95% It takes less than one year from diagnosis to death for patients with pancreatic cancer, and it is very small that they can live for five years. Surgical resection after the diagnosis of pancreatic cancer is the best treatment, but more than 80%-85% of pancreatic cancer patients are already at an advanced stage when they are diagnosed. For these patients, chemotherapy is an acceptable option. Before 2011, despite many trials trying to combine gemcitabine with other drugs, there was no significant progress in the treatment of advanced pancrea...

AI Technical Summary

Problems solved by technology

Prior to 2011, despite numerous trials testing gemcitabine in combination with other agents, there had been no significant progress in the treatment of advanced pancreatic cancer

In recent years, breakthroughs have been made in the clinical application of targeted inhibitors such as Kras, EGFR, and COX-2, which can significantly improve the prognosis of pancreatic cancer patients, but further research is still needed due to high cost and many side effects

Currently, gemcitabine is still the "gold standard" treatment for advanced pancreatic cancer. The drug can block tumor cell division and promote cell death; however, many patients die within months, usually because the cancer cells find a way to avoid the drug gemcitabine's effect Therefore, there is an urgent need to develop clinical chemotherapy drugs with a new structure and mechanism of action for the treatment of pancreatic cancer to alleviate the resistance of existing chemotherapy drugs. Drug properties, prolong the life of pancreatic cancer patients and improve their quality of life

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