Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (7): 1983-1990.DOI: 10.6023/cjoc201912033 Previous Articles     Next Articles


朱仲珍, 乔雨, 张子豪, 顾明震, 王晋, 高志宇, 郭文昊, 刘明明, 李荣   

  1. 安徽医科大学药学院 合肥 230032
  • 收稿日期:2019-12-23 修回日期:2020-04-26 发布日期:2020-04-30
  • 通讯作者: 李荣
  • 基金资助:

Design, Synthesis and Antitumor Evaluation of Novel Small Molecule Extracellular Regulated Protein Kinase (ERK) Inhibitors

Zhu Zhongzhen, Qiao Yu, Zhang Zihao, Gu Mingzhen, Wang Jin, Gao Zhiyu, Guo Wenhao, Liu Mingming, Li Rong   

  1. School of Pharmacy, Anhui Medical University, Hefei 230032
  • Received:2019-12-23 Revised:2020-04-26 Published:2020-04-30
  • Supported by:
    Project supported by the National Natural Science Foundation of China (No. 81972040).

Extracellular regulated protein kinase (ERK) is a key kinase in the development of cancer. 12 urea compounds containing morpholin rings were designed and synthesized in search of novel ERK inhibitors by using merging strategy. The structures of all compounds were confirmed by 1H NMR, 13C NMR and HRMS. ERK kinase activity and cell proliferation test results indicate that most of the target compounds have moderately inhibitory effects on human colorectal cancer cells SW480 and HCT-116, especially the IC50 of 1-(4-fluorobenzyl)-3-(5-(4-morpholinophenyl)pyridin-2-yl)urea (18f) reaches 0.36 and 0.55 μmol/L, respectively, and has low toxicity to normal cells L02 (>10 μmol/L). At the same time, 18f can inhibit ERK kinase activity (IC50=0.051 μmol/L) and phosphorylation level, but does not affect total ERK expression and upstream upstream activation of mitogen-activated extracellular signal-regulated kinase (MEK) activation. These research provides important reference for the further study of novel benzylpyridylurea ERK inhibitors.

Key words: mitogen-activated protein kinases(MAPKs), extracellular regulated protein kinase (ERK), diarylurea, synthesis, antitumor activity