TY - JOUR
T1 - Design, synthesis, and structure activity relationship (SAR) studies of novel imidazo[1,2-a] pyridine derivatives as Nek2 inhibitors
AU - Wang, Haili
AU - Chen, Yunzhong
AU - Gu, Xiaofan
AU - Xi, Jianbei
AU - Ren, Ziwei
AU - Wang, Shuting
AU - Duan, Yanhong
AU - Li, Hongyu
AU - Zhu, Tong
AU - Du, Yijie
AU - Zhang, Xiongwen
AU - Ma, Mingliang
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China ( 21572067 ); the Chinese medicine innovation project of Shanghai Health Committee ( ZYKC201601023 ); and the State Key Laboratory of Fine Chemicals ( KF1913 ).
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Never in mitosis (NIMA) related kinase 2 (Nek2) is involved in multiple cellular processes such as cell cycle checkpoint regulation, cell division, DNA damage response and cell apoptosis. Nek2 has been reported to be overexpressed in various tumors and correlated with poor prognosis. Herein, a series of imidazo[1,2-a] pyridines Nek2 inhibitors were designed, synthesized, and their biological activities were investigated. Besides, structure activity relationship analysis of these compounds were performed in the MGC-803 cell. The screening results are promising, and compound 28e shows good proliferation inhibitory activity with an IC50 of 38 nM. The results would be helpful to design and develop more effective Nek2 inhibitors for the treatment of gastric cancer.
AB - Never in mitosis (NIMA) related kinase 2 (Nek2) is involved in multiple cellular processes such as cell cycle checkpoint regulation, cell division, DNA damage response and cell apoptosis. Nek2 has been reported to be overexpressed in various tumors and correlated with poor prognosis. Herein, a series of imidazo[1,2-a] pyridines Nek2 inhibitors were designed, synthesized, and their biological activities were investigated. Besides, structure activity relationship analysis of these compounds were performed in the MGC-803 cell. The screening results are promising, and compound 28e shows good proliferation inhibitory activity with an IC50 of 38 nM. The results would be helpful to design and develop more effective Nek2 inhibitors for the treatment of gastric cancer.
KW - Antitumor activities
KW - Gastric cancer
KW - Imidazo[1,2-a]pyridine
KW - Nek2
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U2 - 10.1016/j.bmc.2020.115775
DO - 10.1016/j.bmc.2020.115775
M3 - Article
C2 - 32992252
AN - SCOPUS:85091585855
SN - 0968-0896
VL - 28
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 23
M1 - 115775
ER -