Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2022-09-06 , DOI: 10.1016/j.bmcl.2022.128973 Changjun Chen 1 , Yeliu Wang 2 , Min-Qi Hu 2 , Hongjuan Li 3 , Xi Chen 2 , Gan Qiang 4 , Yinghui Sun 3 , Yan Zhu 2 , Binghui Li 5
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In the past decade, Wee1 inhibition has received widespread attention as a cancer therapy. Our research aims to discover effective, selective and drug-like Wee1 inhibitors. Herein, a series of compounds with pyrrolo[2,3-d]pyrimidine-based heterocycles were designed, synthesized and confirmed to inhibit Wee1 kinase. The inhibitors afforded good potency in Wee1 Kinase inhibitory activity in enzymatic assays. These compounds showed strong proliferation inhibition against NCI-1299 cell lines and had acceptable pharmacokinetic properties. These derivatives are promising inhibitors that warrant further evaluation, towards the development of potential anticancer drug.
中文翻译：
吡咯并[2,3-d]嘧啶基分子作为 Wee1 抑制剂模板的发现
在过去的十年中，Wee1 抑制作为一种癌症疗法受到了广泛关注。我们的研究旨在发现有效、选择性和类似药物的 Wee1 抑制剂。在此，设计、合成了一系列具有吡咯并[2,3 - d ]嘧啶基杂环化合物，并证实其可抑制 Wee1 激酶。在酶测定中，抑制剂在 Wee1 激酶抑制活性方面具有良好的效力。这些化合物对 NCI-1299 细胞系表现出强烈的增殖抑制作用，并具有可接受的药代动力学特性。这些衍生物是有前途的抑制剂，值得进一步评估，以开发潜在的抗癌药物。
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