2. Academic Validation
  3. Synthesis and biological evaluation of novel 5,6-dihydropyrimido[4,5-f]quinazoline derivatives as potent CDK2 inhibitors

Synthesis and biological evaluation of novel 5,6-dihydropyrimido[4,5-f]quinazoline derivatives as potent CDK2 inhibitors

  • Bioorg Med Chem Lett. 2018 Nov 1;28(20):3385-3390. doi: 10.1016/j.bmcl.2018.08.035.
Xiaoxia Hu 1,  Hui Zhao 1,  Youzhi Wang 2,  Zhan Liu 1,  Bainian Feng 1,  Chunlei Tang 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Science, Jiangnan University, Wuxi, China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, China.
  • 3 School of Pharmaceutical Science, Jiangnan University, Wuxi, China. Electronic address: tangcl@jiangnan.edu.cn.
PMID: 30197029 DOI: 10.1016/j.bmcl.2018.08.035
Abstract

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 (IC50 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.

Keywords

Anticancer; Cyclin dependent kinase; Design and discovery; Molecular docking.

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