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

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

Volume: 13 Issue: 8

Author(s): Ping Guo, Zixin Xie, Huan Zhang, Zaikui Zhang , Chao Han , Donghua Cheng, Dan Lin, Yuan Zhang, Xuebao Wang, Xin Guo and Faqing Ye *

Affiliation:

• School of Pharmacy, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035,China

Keywords: FGFR1, inhibitor, thienopyrimidinone, design, synthesis, anticancer.

Abstract: 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.

Cite this article as:

Guo Ping, Xie Zixin, Zhang Huan, Zhang Zaikui , Han Chao , Cheng Donghua, Lin Dan , Zhang Yuan , Wang Xuebao , Guo Xin and Ye Faqing *, Design, Synthesis, and Biological Evaluation of C-2 Substituted 3Hthieno[ 2,3-d]pyrimidin-4-one Derivatives as Novel FGFR1 Inhibitors, Medicinal Chemistry 2017; 13 (8) . https://dx.doi.org/10.2174/1573406413666170623084525