Synthesis process of VEGFR inhibitor tevozanib

Abstract

The invention relates to a synthesis process of a VEGFR (vascular endothelial growth factor receptor) inhibitor tevozanib. According to the invention, commercially available raw materials are subjected to a halogenation reaction, an esterification reaction and an addition reaction to synthesize a target product. Generally speaking, according to the synthetic route and the synthetic process, the synthetic steps are simplified, the reaction yield of each step is high, the treatment after the reaction is simple, pulping purification is mostly adopted for purification, the use of column chromatography is avoided, the operation process is simple and cheap, and the synthetic route and the synthetic process are favorably applied to industrial mass production.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a synthesis process of a VEGFR inhibitor tivozanib. Background technique [0002] Tivozanib (trade name Fotivda) is a tyrosine kinase inhibitor. In vitro cellular kinase assays demonstrated that tivozanib inhibited the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 at clinically relevant concentrations and inhibited other kinases, including c-kit and PDGFRβ, as well as tumor growth in various tumor cell types, including human renal cell carcinoma. [0003] Tivozani was originally discovered by Kyowa Hakko Kirin in Japan, and was first approved in the European Union for the treatment of advanced renal cell carcinoma (RCC) in August 2017. On March 10, 2021, the U.S. FDA approved AVEO PHARMS' tivozanib capsules for the treatment of adults with relapsed or refractory advanced renal cell carcinoma after two or more prior systemic t...

AI Technical Summary

Problems solved by technology

[0006] However, the synthesis process of tivozanib still needs to be improved

Images