Design, synthesis and biological evaluation of novel pyrimidine, 3-cyanopyridine and m-amino-N-phenylbenzamide based monocyclic EGFR tyrosine kinase inhibitors
2013
Mao, Yongjun | Zhu, Wenxiu | Kong, Xiaoguang | Wang, Zhen | Xie, Hua | Ding, Jian | Terrett, Nicholas Kenneth | Shen, Jingkang | Shen, Jingshan
36 new compounds with the typical skeleton of 4-anilino-5-vinyl/ethynyl pyrimidine, 4-anilino-3-cyano-5-vinyl/ethynyl/phenyl pyridine, and m-amino-N-phenylbenzamide, are designed, synthesized and selectively tested on EGFR, ErbB-2 kinases, and A-549, HL60 cells growth inhibition. Results from the bioactivity and chemical structures yield preliminary structure–activity relationships (SARs). The most potent 5-ethynylpyrimidine derivative 20a has an IC₅₀ value of 45nM to EGFR kinase. Several compounds of other series also show IC₅₀ values <1μM for EGFR and <5μM for A-549 and HL60 cells growth inhibition.
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