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

Three series of substituted pyrimidines were designed and synthesized. All target compounds were screened for kinase inhibitory activities against PI3Kα, and most IC<sub>50</sub> values were found within the nanomolar range. Compounds <b>5d</b> and <b>5p</b> displayed comparable activities relative to the positive control <b>5a</b>. <b>5p</b> 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 <b>5d</b> was also tested.