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

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

Journal Name: Medicinal Chemistry

Volume 13 , Issue 8 , 2017

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Graphical 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.

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

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Article Details

Year: 2017
Published on: 08 November, 2017
Page: [753 - 760]
Pages: 8
DOI: 10.2174/1573406413666170623084525
Price: $65

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