Heteroaryl Group Containing Trisubstituted Alkenes: Synthesis and Anti‐Tumor Activity

Pancreatobililary cancers are fatal solid tumors that pose a significant threat to human life. It is imperative to investigate novel small molecule active compounds for controlling these cancers. Heterocyclic compounds (e. g. gemcitabine) and multi-substituted alkenes (e. g. resveratrol) are commonly applied in tumor treatment. Researchers have proposed that the synthesis of new trisubstituted alkenes containing heteroaromatic rings by combining these two scaffolds may be a fresh strategy to develop new active molecules. In this study, we utilized alkenyl bromide and heteroaryl boronic acid as substrates, employing Suzuki coupling to generate a series of triarylethylenes featuring nitrogen, oxygen, and sulfur atoms. Through in vitro experiments, the results indicated that some compounds exhibited remarkable anti-tumor efficacy (e. g. IC50_{[3be, GBC-SD]}=0.13 μM and IC50_{[3be, PANC-1]}=0.27 μM). The results further demonstrated that the antitumor efficacy of these compounds was dependent on the heteroatom, π-system, skeleton-bonding site, and substituent type.