Design, Synthesis, and Biological Evaluation of New Diaminoquinazolines as 尾-Catenin/Tcf4 Pathway Inhibitors

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• 作者：Yongjun Mao ; Nan Lin ; Wang Tian ; Xiaofeng Han ; Xiaobing Han ; Ziwei Huang ; Jing An
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：February 9, 2012
• 年：2012
• 卷：55
• 期：3
• 页码：1346-1359
• 全文大小：431K
• 年卷期：v.55,no.3(February 9, 2012)
• ISSN：1520-4804

文摘

More than 50 new diaminoquinazoline derivatives have been synthesized and evaluated in a colon carcinoma cell growth inhibition assay using HCT116 and SW480 cells. Twenty compounds with good cell growth inhibitory activities (<4 渭M) were tested as inhibitors of the 尾-catenin/T cell transcription factor 4 (Tcf4) signaling pathway using a HCT116 cell-based luciferase reporter assay. Results from the biological activities as well as the comparative molecular field analysis (CoMFA) of the properties of the molecules yielded a preliminary structure鈥揳ctivity relationship (SAR). Three potent compounds, 74, 78, and 86, showed IC₅₀ values <1 渭M for growth inhibition of HCT116 cells and 1 渭M for SW480 cells, as well as IC₅₀ values of 1.5鈥?.5 渭M for HCT116 cells with the luciferase reporter assay.