2. Academic Validation
  3. Synthesis, activity and docking studies of phenylpyrimidine-carboxamide Sorafenib derivatives

Synthesis, activity and docking studies of phenylpyrimidine-carboxamide Sorafenib derivatives

  • Bioorg Med Chem. 2016 Dec 1;24(23):6166-6173. doi: 10.1016/j.bmc.2016.09.021.
Wenhui Wang 1,  Chunjiang Wu 1,  Jianqiang Wang 2,  Rong Luo 3,  Caolin Wang 1,  Xiaobo Liu 1,  Jiqing Li 1,  Wufu Zhu 4,  Pengwu Zheng 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
  • 2 Fushun Center for Drug Control, Fushun 113000, China.
  • 3 Jiangxi Province Institute of Materia Medica, Nanchang 330000, China.
  • 4 School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. Electronic address: zhuwf@jxstnu.edu.cn.
  • 5 School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China. Electronic address: zhengpw@126.com.
PMID: 28340913 DOI: 10.1016/j.bmc.2016.09.021
Abstract

Two series of Sorafenib derivatives bearing phenylpyrimidine-carboxamide moiety (16a-g and 17a-p) were designed, synthesized and evaluated for the IC50 values against three Cancer cell lines (A549, MCF-7 and PC-3). Two selected compounds (17f and 17n) were further evaluated for the activity against VEGFR2/KDR/Flk-1/VEGFR2/KDR/Flk-1 kinase. More than half of the synthesized compounds showed moderate to excellent activity against three Cancer cell lines. Compound 17f showed equal activity to Sorafenib against MCF-7 cell line, with the IC50 values of 6.35±0.43μM. Meanwhile, compound 17n revealed more active than Sorafenib against A549 cell line, with the IC50 values of 3.39±0.37μM. Structure-activity relationships (SARs) and docking studies indicated that the second series (17a-p) showed more active than the first series (16a-g). What's more, the introduction of fluoro atom to the phenoxy part played no significant impact on activity. In addition, the presence of electron-donating on aryl group was benefit for the activity.

Keywords

Antitumor activity; Docking; Phenylpyrimidine; Sorafenib; Synthesis; VEGFR2/KDR.

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