Design,synthesis and biological evaluation of novel pyrimidine, 3-cyanopyridine and m-amino-N-phenylbenzamide based monocyclic EGFR tyrosine kinase inhibitors |
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| Authors: | Yongjun Mao Wenxiu Zhu Xiaoguang Kong Zhen Wang Hua Xie Jian Ding Nicholas Kenneth Terrett Jingkang Shen Jingshan Shen |
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| Institution: | 1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Pudong, Shanghai 201203, China;2. Vitargeta Therapeutics Inc., Plainsboro, NJ 08536, USA |
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| Abstract: | 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 45 nM to EGFR kinase. Several compounds of other series also show IC50 values <1 μM for EGFR and <5 μM for A-549 and HL60 cells growth inhibition. |
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| Keywords: | EGFR 5-Ethynylpyrimidine 4-Anilino-3-cyano-5-phenylpyridine Tyrosine kinase inhibitors |
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