Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Design, Synthesis and Biological Evaluation of 4-Aryl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one Derivatives as a PI3Kα Inhibitor
Shengquan HuZhichang ZhaoYeming NiHongxing XinHong YanXiuqing Song
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2019 年 42 巻 6 号 p. 1013-1018


A novel series of 4-aryl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives were designed as a phosphoinositide 3-kinase α (PI3Kα) inhibitor by scaffold hopping. The target compounds, characterized by 1H-NMR, 13C-NMR and high resolution (HR)-MS, were synthesized from diethyl malonate and ethyl chloroacetate by nucleophilic substitution, ring-closure, chlorination and Suzuki reaction, etc. The biological activities were evaluated with cytotoxic activity in vitro on Uppsala 87 Malignant Glioma (U87MG) and prostate cancer-3 (PC-3) by Cell Counting Kit-8 (CCK-8). The results showed that compound 9c displayed the higher inhibition than the positive control PI-103, and high PI3Kα inhibitory activity with IC50 of 113 ± 9 nM in the same order of magnitude as BEZ235. In addition, the Log Kow values and molecular docking studies were performed to further investigate the drug-like properties of target compounds and interactions between 9c and PI3Kα.

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