Synthesis method of Combretastatin A-4 derivatives

Abstract

The invention discloses a synthesis method of Combretastatin A-4 derivatives. Aiming at double targets of BFGF and tubulin, a tubulin polymerization inhibitor CA-4 and its analogues are respectively coupled with aminosugar having BFGF inhibition effects so that eight novel compounds are designed and synthesized. A preliminary pharmacological test result shows that the desired compounds have human umbilical vein endothelial cell proliferation inhibition effects superior to that of a positive drug CA-4.

Description

technical field [0001] The present invention relates to the synthesis of chemicals, in particular to a synthesis method of Combretastatin A-4 derivatives. Background technique [0002] Main problems in the research and development of anti-tumor drugs According to the mechanism of action, there are four main types of anti-tumor drugs currently in clinical use: ① drugs that directly act on DNA; ② drugs that interfere with DNA synthesis; ③ anti-mitotic drugs; ④ tumor-based drugs. Drugs for signaling pathways. The effects of the first two drugs are strong, but they lack selectivity and have large toxic and side effects. Anti-mitotic drugs act on tubulin, and tubulin inhibitors (such as vinblastine and paclitaxel) have achieved good clinical efficacy as anti-tumor drugs, but they also have narrow anti-tumor spectrum, high toxicity, and easy Drawbacks such as drug resistance. However, some tubulin inhibitors can restore the cell cycle after drug metabolism or clearance in norma...

AI Technical Summary

Problems solved by technology

The purpose is to effectively overcome the problem that existing tumor angiogenesis inhibitors are prone to drug resistance