Department of Chemistry, Faculty of Science, Gakushuin University, Tokyo 171-8588, Japan.
Bioorg Med Chem. 2010 Jan 15;18(2):870-9. doi: 10.1016/j.bmc.2009.11.035. Epub 2009 Nov 22.
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.
一系列在 6 位具有 C-C 多重键取代的 4-苯胺喹唑啉被合成出来，并研究了它们抑制表皮生长因子受体（EGFR）酪氨酸激酶活性的潜力。在所合成的化合物中，炔烃 6d 和丙二烯 7d 和 7f 显著抑制了 EGFR 酪氨酸激酶活性。这些化合物抑制了 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。在苯胺喹唑啉骨架的 C-6 位具有 C-C 多重键取代的化合物对于显著的抑制活性是必不可少的。具有长碳链（n=3-6）的化合物，如 6c-f、7c-f、11 和 12，表现出延长的抑制活性。
