Design, Synthesis, and Biological Evaluation of C-2 Substituted 3Hthieno[ 2,3-d]pyrimidin-4-one Derivatives as Novel FGFR1 Inhibitors.
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.