1022947-10-9Relevant academic research and scientific papers
Noncovalent EGFR T790M/L858R inhibitors based on diphenylpyrimidine scaffold: Design, synthesis, and bioactivity evaluation for the treatment of NSCLC
Chen, Lixue,Deng, Tuo,Li, Lei,Li, Zhen,Ma, Xiaodong,Meng, Qiang,Sun, Huijun,Tang, Zeyao,Tian, Liangliang,Wang, Changyuan,Wang, Tong,Xu, Youjun,Zhang, Yunhao,Zheng, Xu
, (2021)
A series of diphenylpyrimidine derivatives bearing a hydroxamic acid group was designed and synthesized as noncovalent EGFRT790M/L858R inhibitors to improve the biological activity and selectivity. One of the most promising compound 9d effectively interfered EGFRT790M/L858R binding with ATP and suppressed the proliferation of H1975 cells with IC50 values of 1.097 nM and 0.09777 μM, respectively. Moreover, compound 9d also not only exhibited a high selective index of 43.4 for EGFRT790M/L858R over the wild-type and 10.9 for H1975 cells over A431, but also exhibited low toxicity against the normal HBE cells (IC50 > 20 μΜ). In addition, the action mechanism validated that compound 9d effectively inhibited cell migration and promoted cell apoptosis by blocking cell cycle at G2/M stage. Furthermore, the target dose-dependently downregulated the expression of p-EGFR and arrested the activation of downstream Akt and ERK in H1975. All these studies provide important clues for the discovery of potent noncovalent EGFRT790M/L858R inhibitors.
ANTHRANILAMIDE INHIBITORS OF AURORA KINASE
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Page/Page column 31, (2008/12/07)
The present invention relates to a compound represented by the following formula: or a pharmaceutically acceptable salt thereof; where R1, R2, R3, R4, r and s are as previously defined. Compounds of the present invention are useful in the treatment of diseases associated with Aurora kinase activity such as cancer.
