title: Synthesis and Evaluation of Biological and Antitumor Activities of Tetrahydrobenzothieno[2,3-d]Pyrimidine Derivatives as Novel Inhibitors of FGFR1.
abstract: A series of tetrahydrobenzothieno[2,3-d]pyrimidine derivatives were designed, synthesized, and evaluated as inhibitors of FGFR1. These analogs were synthesized via Gewald's reaction under mild conditions. The structures of the synthesized compounds were characterized by spectroscopic data (IR, (1) H NMR and MS). Their antitumor activities were evaluated against H460, A549 and U251 cell lines in vitro. Results revealed that the tested compounds showed moderate antitumor activities. Structure-activity relationship analyses indicated that compounds with an aromatic ring substituted in the C-2 position or with larger molecules such as 3g, 4c, and 7 were more effective than others. The compound, 3g (78.8% FGFR1 inhibition at 10 μm), was identified to have the most potent antitumor activities, with IC50 values of 7.7, 18.9, and 13.3 μm against the H460, A549, and U251 cell lines, respectively. Together, the results suggested that tetrahydrobenzothieno[2,3-d]pyrimidine derivatives may serve as a potential agent for the treatment of FGFR1-mediated cancers.
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Xuebao
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Zaikui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Yichang Humanwell Pharmaceutical Co., Ltd, Yichang, 443005, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Qi
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Weitao
authors.initials: W
authors.lastname: Fu
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Xie
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Faqing
authors.initials: F
authors.lastname: Ye
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D066244:Proton Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: FGFR1; Gewald's reaction; antitumor; synthesis; thieno[2,3-d]pyrimidine