Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 157, Issue -, Pages 935-945Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.08.043
Keywords
Cyclin dependent kinase; Anticancer; Cell cycle; Kinase selectivity
Categories
Funding
- National Natural Science Foundation of China [21305051]
- Jiangsu prospective joint research projiect [BY2015019-25]
Ask authors/readers for more resources
CDK4/6 pathway is an attractive target for development of anti-cancer drugs. Herein, we reported the design and synthesis of a series of 4,5-dihydro-1H-pyrazolo [4,3-h]guinazoline derivatives as selective CDK4/6 inhibitors. Applied with the optimizing strategy to the initial scaffold, it is found that compound 13n is able to selectively inhibit CDK4 and CDK6 with IC50 values 0.01 and 0.026 mu M, respectively. The compound showed good anti-proliferative activity when tested in a panel of tumor cell lines with CDK4/6 related mechanism of action, the results clearly suggest that compound 13n works much better than Ly2385219 which is a selective CDK4/6 inhibitor. This compound was also found to have favorable pharmacokinetic parameters. Taken together, compound 13n could be selected for further preclinical evaluation. (C) 2018 Elsevier Masson SAS. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available