Background: Thienopyrimidinone is a newly designed, selective fibroblast growth factor
receptor 1 (FGFR1) inhibitor with an excellent anticancer effect.
Objective: The goal of the present study was to design and synthesize better FGFR1 inhibitors
through modifications of the lead compound thienopyrimidinone.
Methods: In the present study, a series of C-2 substituted derivatives of thienopyrimidinone,
namely L1–L16, were synthesized, and their inhibitory effects on FGFR1 were evaluated. The
anti-proliferative activities of these compounds were assessed by MTT assay.
Results: Among the novel derivatives, L11 was found to exert remarkable FGFR1 inhibitory activity
(79.93% at 10 µM) and anti-proliferative activity, with IC50 values of 2.1, 2.5, and 3.5 M in
the FGFR1-overexpressing cell lines, H460, HT-1197, and B16F10, respectively.
Conclusion: Our newly synthesized thienopyrimidinone derivatives may be candidate FGFR1 inhibitors
for future development as novel anticancer agents.