Larroque Anne-Laure, Peori Brad, Williams Christopher, Fang You Qiang, Qiu Qiyu, Rachid Zakaria, Jean-Claude Bertrand J
Cancer Drug Research Laboratory, Department of Medicine, Division of Medical Oncology, McGill University/Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC H3A 1A1, Canada.
Chem Biol Drug Des. 2008 Apr;71(4):374-9. doi: 10.1111/j.1747-0285.2008.00638.x.
A novel type of 3,3-disubstituted bis-triazenes containing an ethylaminoethyl linker flanked by two identical anilinoquinazoline ring was synthesized. These model molecules contained an N-ethylaminomorpholine moiety designed to enhance water solubility. Despite their significant bulkiness, they blocked epidermal growth factor receptor (EGFR) tyrosine kinase in a dose-dependent manner with IC(50) values in low micromolar range. Molecular modeling to predict the interactions of the molecule with the ATP binding site of EGFR suggests that the N-ethylaminomorpholine side chain plays a binding role.
合成了一种新型的3,3-二取代双三氮烯，其含有一个由两个相同的苯胺基喹唑啉环包围的乙氨基乙基连接基。这些模型分子含有一个N-乙基氨基吗啉部分，旨在提高水溶性。尽管它们体积庞大，但它们以剂量依赖的方式阻断表皮生长因子受体（EGFR）酪氨酸激酶，IC(50)值在低微摩尔范围内。预测该分子与EGFR的ATP结合位点相互作用的分子模型表明，N-乙基氨基吗啉侧链起结合作用。
