Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 76, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2022.128991
Keywords
CDK4/6 inhibitors; Structure-activity relationships; Scaffold hopping
Categories
Funding
- National Natural Science Foundation of China [81825020, 82150208]
- Shanghai Science and Technology Commission Biomedical Science and Technology Support Special Project [21S11907900, 20S11901000]
- Fundamental Research Funds for the Central Universities
- National Program for Special Supports of Eminent Professionals
- National Program for Support of Top-notch Young Professionals
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This article describes the design and synthesis of a new series of pteridine-7(8H)-one derivatives as selective CDK4/6 inhibitors, which showed significant antitumor activity and good selectivity.
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.
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