Anticancer compound and preparation method thereof

Abstract

The invention discloses two new compounds with anti-cancer effects of N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methyl-formamide)(4-pyridinyloxy) phenyl]-thiourea and N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methyl-formamide)(4-pyridinylthioxo) phenyl]-thiourea, and salt thereof. The invention further discloses preparation methods of the two new compounds and a pharmaceutical composition containing the compounds. Experimental studies show that the two new compounds can effectively inhibit the activity of Raf and VEGFR protein kinase, more widely inhibit growth of various types of human tumor cell lines and further induce apoptosis of tumor cells. Human tumor heterograft model investigation proves that the two new compounds are effective antineoplastic agents, can sharply inhibit growth of human liver cancer cells, lung cancer cells and intestinal cancer cells in vivo; and the anti-cancer effect of the compounds is much better than that of sorafenib tosylate.

Description

technical field [0001] The present invention relates to anticancer compounds and their salts, their preparation methods and pharmaceutical compositions containing them. Background technique [0002] Primary liver cancer is a common malignant tumor in clinical practice, with a high incidence in my country, Southeast Asia, southeastern Africa and the Mediterranean coast. The incidence of liver cancer in my country ranks first in the world, and ranks second among tumors in China, especially in the southeast coast, and Jiangsu Province is as high as the first. Liver cancer is a dangerous disease with rapid progression, high mortality and poor treatment effect. Mainland China, Southeast Asia and Africa are the three regions with high incidence of liver cancer in the world. According to the annual health report of the World Health Organization, the incidence rate of liver cancer is 23.7 / 100,000, and 620,000 people die of liver cancer every year in the world, and China accounts f...

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Problems solved by technology

However, the clinical application of interventional therapy is subject to many restrictions, and many cases do not meet the indications for interventional therapy, such as severe liver and kidney insufficiency, severe ascites, bone marrow hematopoietic suppression or coagulation dysfunction, large tumors (accounting for liver The volume exceeds 70%), patients with complete occlusion of main portal vein tumor thrombus, severe portal hypertension, active peptic ulcer or distant metastases cannot take interventional therapy

At this time, although systemic chemotherapy can be used as a palliative treatment, liver cancer cells are resistant to a variety of chemotherapy drugs, and the efficacy of traditional chemotherapy drugs is very low. At the same time, patients usually have basic liver diseases such as viral hepatitis and cirrhosis. Unfavorable, poorly tolerated chemotherapy, often unable to accept intense chemotherapy

In recent years, some new chemotherapeutic drugs such as oxaliplatin, gemcitabine and capecitabine are being actively explored clinically for the treatment of liver cancer. There are signs, but they are still under research and the final results have not yet been obtained.

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