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 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.

设计并合成了三系列取代的嘧啶衍生物。所有目标化合物均经筛选，对其针对PI3Kα的激酶抑制活性进行评估，大多数IC50值均位于纳摩尔范围内。化合物5d和5p与阳性对照5a相比，表现出相似活性。此外，化合物5p还显示出显著的同工酶选择性（PI3Kβ/α）。进一步地，对这些嘧啶衍生物对人类癌细胞系的细胞毒性和5d在体内的抗癌效果亦进行了评估。