2. Academic Validation
  3. Novel 7-formyl-naphthyridyl-ureas derivatives as potential selective FGFR4 inhibitors: Design, synthesis, and biological activity studies

Novel 7-formyl-naphthyridyl-ureas derivatives as potential selective FGFR4 inhibitors: Design, synthesis, and biological activity studies

  • Bioorg Med Chem. 2019 May 15;27(10):1932-1941. doi: 10.1016/j.bmc.2019.04.018.
Chang'an Sun 1,  Lei Fang 2,  Xiaobing Zhang 1,  Peng Gao 3,  Shaohua Gou 4
Affiliations

Affiliations

  • 1 Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Hansoh Pharmaceutical Group CO., LTD., Lianyungang 222000, China.
  • 2 Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, China. Electronic address: lei.fang@seu.edu.cn.
  • 3 Jiangsu Hansoh Pharmaceutical Group CO., LTD., Lianyungang 222000, China.
  • 4 Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China. Electronic address: sgou@seu.edu.cn.
PMID: 30987781 DOI: 10.1016/j.bmc.2019.04.018
Abstract

Total twenty-five 7-formyl-naphthyridyl-urea derivatives were designed, synthesized and evaluated for their inhibition of FGFR4 kinase and antitumor activity. The pharmacological data indicated that most of the tested compounds showed high selectivity towards FGFR4 kinase and could significantly inhibit FGFR4 and the tumor cells lines with the high expression of FGFR4. In particular, compounds 6f, 6g, 6h, 6l, 6m and 6s showed a good performance in pharmacokinetic tests. When tested in mice, the representative compound 6f was found to have good pharmacokinetic parameters, low toxicity, and better tumor inhibiting activity in vivo.

Keywords

Antitumor; FGFR4; Pharmacokinetic profile; Selectivity.

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