Cyclin-dependent kinases play an important role in the regulation of cell cycle and transcription. Selective CDK4/6 inhibitors have been demonstrated to be effective in the treatment of cancer. In this article, we described the design and synthesis of a series of pteridine-7(8H)-one derivatives as dual CDK4/6 inhibitors. Among them, the most promising compound L2 exhibited significant inhibitory activity against CDK4 and CDK6 with IC₅₀ values of 16.7 nM and 30.5 nM respectively and showed excellent selectivity to CDK1/2/7/9. Moreover, compound L2 displayed potent antiproliferative activities at low digital micromolar range via inducing apoptosis in breast and colon cancer cells. In all, we developed a new series of pteridine-7(8H)-one derivatives which exhibited promising antitumor activities as selective CDK4/6 inhibitors.

细胞周期蛋白依赖性激酶在细胞周期和转录的调节中起重要作用。选择性CDK4/6抑制剂已被证明可有效治疗癌症。在本文中，我们描述了一系列作为双 CDK4/6 抑制剂的蝶啶-7(8 H )-one 衍生物的设计和合成。其中，最有希望的化合物L2对CDK4和CDK6表现出显着的抑制活性，IC ₅₀值分别为16.7 nM和30.5 nM，对CDK1/2/7/9表现出优异的选择性。此外，化合物L2通过诱导乳腺癌和结肠癌细胞凋亡，在低数字微摩尔范围内显示出有效的抗增殖活性。总之，我们开发了一系列新的蝶啶-7(8H )-一种衍生物，作为选择性 CDK4/6 抑制剂表现出有希望的抗肿瘤活性。