Design, Synthesis, and Biological Evaluation of Substituted Pyrimidines as Potential Phosphatidylinositol 3-Kinase (PI3K) Inhibitors

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• 作者：Ji-Quan Zhang ; Yong-Jie Luo ; Yan-Shi Xiong ; Yang Yu ; Zheng-Chao Tu ; Zi-Jie Long ; Xiao-Ju Lai ; Hui-Xuan Chen ; Yu Luo ; Jiang Weng ; Gui Lu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：August 11, 2016
• 年：2016
• 卷：59
• 期：15
• 页码：7268-7274
• 全文大小：480K
• 年卷期：0
• ISSN：1520-4804

文摘

Three series of substituted pyrimidines were designed and synthesized. All target compounds were screened for kinase inhibitory activities against PI3Kα, and most IC₅₀ values were found within the nanomolar range. Compounds 5d and 5p displayed comparable activities relative to the positive control 5a. 5p also showed a significant isozyme selectivity (PI3Kβ/α). Furthermore, the cytotoxicities of these pyrimidines against human cancer cell lines were evaluated and the in vivo anticancer effect of 5d was also tested.