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Eur J Med Chem. 2012 Oct;56:210-6. doi: 10.1016/j.ejmech.2012.08.033. Epub 2012 Sep 1.

Synthesis and biological evaluation of selective and potent cyclin-dependent kinase inhibitors.

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ManRos Therapeutics, Centre de Perharidy, Hôtel de recherche, 29680 Roscoff, France.


A new series of 2,6,9-trisubstituted purines, structurally related to the cyclin-dependent kinase (CDK) inhibitor Roscovitine, has been synthesized. These compounds mainly differ by the substituent on the C-2 position which encompasses a diol group. These compounds were screened for kinase inhibitory activities and antiproliferative effects. They were shown to be potent inhibitors of cyclin-dependent kinases but also, for some of them of casein kinase 1 (CK1) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A). The inhibition of kinases was accompanied by an antiproliferative effect against several tumor cell-lines. The most potent derivatives inhibited SH-SY5Y (neuroblastoma) tumor cell line with an IC(50) < 0.5 μM which means approximately a 30 fold increase compared to Roscovitine. A valine ester was also prepared from the most potent inhibitor to serve as a prodrug.

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