2. Academic Validation
  3. Novel anilinopyrimidine derivatives as potential EGFRT790M/C797S Inhibitors: Design, Synthesis, biological activity study

Novel anilinopyrimidine derivatives as potential EGFRT790M/C797S Inhibitors: Design, Synthesis, biological activity study

  • Bioorg Med Chem. 2022 Sep 15:70:116907. doi: 10.1016/j.bmc.2022.116907.
Yanliang Guo 1,  Biao Gao 2,  Peng Gao 2,  Lei Fang 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 Hansoh Pharmaceutical Group CO., LTD., Lianyungang 222000, China.
  • 3 Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China. Electronic address: lei.fang@seu.edu.cn.
  • 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: 35810715 DOI: 10.1016/j.bmc.2022.116907
Abstract

EGFRT790M/C797S is an important target for the development of new generation of EGFR kinase inhibitors without drug resistance. In this work, a series of anilinopyrimidine derivatives that targeting EGFRT790M/C797S were designed, synthesized, and evaluated in vitro for the inhibitory effect on triple mutations kinases and cell lines. Based on the pharmacology data, the anilinopyrimidine derivatives showed high inhibitory activity on triple mutations kinases (EGFRdel 18/T790M/C797S and EGFRL858R/T790M/C797S) as well as the cell line Ba/F3 with highly expression of EGFRdel 18/T790M/C797S. In addition, the anilinopyrimidine derivatives had a more than 50-fold selectivity towards EGFRdel 18/T790M/C797S as compared with EGFRWT. In vivo antitumor activity test also indicated that 8j had good pharmacokinetic parameters, low toxicity and better inhibitory activity. Overall, the anilinopyrimidine derivatives could be regarded as promising candidates for the further development of novel EGFRT790M/C797S inhibitors for clinical application.

Keywords

Antitumor; Drug Resistance; EFGR; NSCLC; Pharmacokinetic profile; Selectivity.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z