Hu Xiaoxia, Zhao Hui, Wang Youzhi, Liu Zhan, Feng Bainian, Tang Chunlei
School of Pharmaceutical Science, Jiangnan University, Wuxi, China.
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, China.
Bioorg Med Chem Lett. 2018 Nov 1;28(20):3385-3390. doi: 10.1016/j.bmcl.2018.08.035. Epub 2018 Aug 28.
As serine/threonine kinase, the cyclin dependent kinase 2 (CDK2) is a promising target for various diseases such as cerebral hypoxia, cancer, and neurodegenerative diseases. Here we reported the structure-based synthesis and biological evaluation of novel 5,6-dihydropyrimido[4,5-f]quinazoline derivatives as CDK2 inhibitors, which exhibited potent CDK2 inhibitory activities, as well as anticancer activities in low concentration against two human cancer cell lines (MCF-7 and HCT116). In particular, compounds 11a and 11f (IC values of 0.11 and 0.09 μM for CDK2, respectively) have demonstrated significantly inhibitory potency against CDK2 and have showed great inhibitory activities against MCF-7 and HCT116 cell lines.
作为丝氨酸/苏氨酸激酶，细胞周期蛋白依赖性激酶2（CDK2）是治疗多种疾病（如脑缺氧、癌症和神经退行性疾病）的一个有前景的靶点。在此，我们报道了基于结构的新型5,6-二氢嘧啶并[4,5-f]喹唑啉衍生物作为CDK2抑制剂的合成及生物学评价，这些衍生物表现出强效的CDK2抑制活性，以及在低浓度下对两种人类癌细胞系（MCF-7和HCT116）的抗癌活性。特别是，化合物11a和11f（对CDK2的IC值分别为0.11和0.09 μM）已证明对CDK2具有显著的抑制效力，并对MCF-7和HCT116细胞系表现出强大的抑制活性。
