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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Cyclin-dependent kinase Inhibitors Inspired by Roscovitine: Purine Bioisosteres

Author(s): Radek Jorda, Kamil Paruch and Vladimir Krystof

Volume 18, Issue 20, 2012

Page: [2974 - 2980] Pages: 7

DOI: 10.2174/138161212800672804

Price: $65


Roscovitine is a synthetic inhibitor of cyclin-dependent kinases that is currently undergoing clinical trials as a candidate drug for some oncological indications. Its discovery prompted many research teams to further optimize its structure or to initiate their own related but independent studies. This article reviews known roscovitine bioisosteres that have been prepared as CDK inhibitors using different core heterocycles. The individual bioisostere types have been described and explored to a different extent, which complicates direct comparisons of their biochemical activity - only six direct analogs containing different purine bioisosteres have been prepared and evaluated side by side with roscovitine. Only four types of bioisosteres have demonstrated improved biological properties, namely pyrazolo[ 1,5-a]-1,3,5-triazines, pyrazolo[1,5-a]pyrimidines, pyrazolo[1,5-a]pyridines and pyrazolo[4,3-d]pyrimidines.

Keywords: Cancer, cyclin-dependent kinase, inhibitor, roscovitine, bioisostere, oncogenes, purine, clinical trials, enantiomers, CDK active site

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