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

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posted on 18.07.2016 by 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
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.