Design, synthesis, and biological evaluation of novel 3‐(thiophen‐2‐ylthio)pyridine derivatives as potential multitarget anticancer agents

A series of novel 3‐(thiophen‐2‐ylthio)pyridine derivatives as insulin‐like growth factor 1 receptor (IGF‐1R) inhibitors was designed and synthesized. IGF‐1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU‐DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR‐1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC50] values, HepG2: 2.98 ± 1.11 μM and WSU‐DLCL2: 4.34 ± 0.84 μM) exhibited good inhibitory activities against fibroblast growth factor receptor‐2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC50 values ranging from 2.14 to 12.20 μM. Additionally, the cell‐cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing. A series of novel 3‐(thiophen‐2‐ylthio)pyridine derivatives were designed, synthesized, and assayed for their activities as insulin‐like growth factor 1 receptor (IGF‐1R) inhibitors. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through IGR‐1R inhibition. Compound 22 exhibited good inhibitory activities against fibroblast growth factor receptor 2 (FGFR2), FGFR3, epidermal growth factor receptor (EGFR), Janus kinase (JAK), and receptor originated from nantes (RON).