Pyrimidine-based pyrazoles as cyclin-dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation

Chemical Biology & Drug Design
Mayur K VekariyaNisha K Shah

Abstract

A series of new pyrimidine-pyrazole hybrid molecules were designed as inhibitors of cyclin-dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2-CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50  < 20 nm); which can be further optimized to have selectivity over other kinase isoforms.

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Citations

Sep 4, 2019·Bioorganic & Medicinal Chemistry Letters·Concepción Sánchez-MartínezAlfonso de Dios
Jul 25, 2020·European Journal of Medicinal Chemistry·Brilliant N MarakVed Prakash Singh
May 1, 2021·International Journal of Molecular Sciences·Beata TylińskaAnna Janicka-Kłos

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