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

[ Vol. 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 *   Pages 753 - 760 ( 8 )

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.

Affiliation:

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

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