Enhancement of EGFR tyrosine kinase inhibition by C-C multiple bonds-containing anilinoquinazolines
Enhancement of EGFR tyrosine kinase inhibition by C-C multiple bonds-containing anilinoquinazolines
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DOI：
10.1016/j.bmc.2009.11.035
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发表时间：
2010-01-15
影响因子：
3.5
通讯作者：
Nakamura, Hiroyuki
中科院分区：
文献类型：
--
作者：
Ban, Hyun Seung;Tanaka, Yuko;Nakamura, Hiroyuki
合成了一系列6位C-C多键取代的4-苯胺基喹唑啉类化合物，并研究了它们对表皮生长因子受体（EGFR）酪氨酸激酶活性的抑制作用。在合成的化合物中，炔6d和丙二烯7 d和7 f显着抑制EGFR酪氨酸激酶活性。这些化合物抑制A431细胞中EGF介导的EGFR磷酸化，导致细胞周期停滞和凋亡诱导。在苯胺基喹唑啉骨架的C-6位上的C-C重键取代对于显著的抑制活性是必需的。具有长碳链的化合物（n = 3-6），例如6c-f、7 c-f、11和12，显示出延长的抑制活性。(C)2009爱思唯尔有限公司版权所有。
A series of 4-anilinoquinazolines with C-C multiple bond substitutions at the 6-position were synthesized and investigated for their potential to inhibit epidermal growth factor receptor (EGFR) tyrosine kinase activity. Among the compounds synthesized, alkyne 6d and allenes 7d and 7f significantly inhibited EGFR tyrosine kinase activity. These compounds inhibited EGF-mediated phosphorylation of EGFR in A431 cells, resulting in cell-cycle arrest and apoptosis induction. The C-C multiple bonds substituted at the C-6 position of the anilinoquinazoline framework were essential for the significant inhibitory activity. Compounds with long carbon chains (n = 3-6), such as 6c-f, 7c-f, 11, and 12, displayed prolonged inhibitory activity. (C) 2009 Elsevier Ltd. All rights reserved.