2. Academic Validation
  3. Design, synthesis and biological evaluation of ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors

Design, synthesis and biological evaluation of ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors

  • Bioorg Med Chem Lett. 2020 Nov 1;30(21):127459. doi: 10.1016/j.bmcl.2020.127459.
Hongming Xie 1,  Xinglong Lin 2,  Yingjun Zhang 3,  Fuxing Tan 2,  Bo Chi 2,  Zhihong Peng 4,  Wanrong Dong 1,  Delie An 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China.
  • 2 The State Key Laboratory of Anti-Infective Drug Development (NO. 2015DQ780357), Sunshine Lake Pharma Co. Ltd, Dongguan 523871, PR China.
  • 3 The State Key Laboratory of Anti-Infective Drug Development (NO. 2015DQ780357), Sunshine Lake Pharma Co. Ltd, Dongguan 523871, PR China. Electronic address: ZhangYingjun@hec.cn.
  • 4 State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China. Electronic address: pzh7251@hnu.edu.cn.
  • 5 State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China. Electronic address: deliean@hnu.edu.cn.
PMID: 32784087 DOI: 10.1016/j.bmcl.2020.127459
Abstract

We report herein the synthesis of novel ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors and the evaluation of pharmaceutical activity against five Cancer cell lines (MDA-MB-231, BXPC-3, NCI-H1975, DU145 and 786O). Generally, the majority of compounds displayed strong anti-FAK enzymatic potencies (IC50 < 1 nM) and could effectively inhibit several class of Cancer cell lines within the concentration of 3 μM in comparison with GSK2256098 as a reference. Among them, compound 4o is considered to be the most effective due to high sensitivity in antiproliferation. In culture, 4o could not only inhibit FAK Y397 phosphorylation in MDA-MB-231 cell line, but also trigger Apoptosis in a dose-dependent manner. Furthermore, computational docking analysis also suggested that 4o and TAE-226 displayed the similar interaction with FAK kinase domain.

Keywords

Anticancer activity; FAK; Inhibitor; Pyrimidine/pyridine; Ring-fused pyrazoloamino.

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