Concise synthesis and CDK/GSK inhibitory activity of the missing 9-azapaullones

David P Power; Olivier Lozach; Laurent Meijer; David H Grayson; Stephen J Connon

doi:10.1016/j.bmcl.2010.06.024

Concise synthesis and CDK/GSK inhibitory activity of the missing 9-azapaullones

Bioorg Med Chem Lett. 2010 Aug 15;20(16):4940-4. doi: 10.1016/j.bmcl.2010.06.024. Epub 2010 Jun 15.

Authors

David P Power¹, Olivier Lozach, Laurent Meijer, David H Grayson, Stephen J Connon

Affiliation

¹ Centre for Synthesis and Chemical Biology, School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland.

PMID: 20621478
DOI: 10.1016/j.bmcl.2010.06.024

Abstract

A remarkably concise, chromatography-free route to the parent compound of the paullone family of cyclin-dependent kinase (CDK) inhibitors is reported. A similar strategy allowed the synthesis of the hitherto missing 9-azapaullone and its protonated, N-oxidised and N-alkylated derivatives. Screening studies identified an active and strongly selective inhibitor of CDK9/cyclin T.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aza Compounds / chemistry*
Benzazepines / chemical synthesis
Benzazepines / chemistry*
Benzazepines / pharmacology
Cyclin T / antagonists & inhibitors
Cyclin T / metabolism
Cyclin-Dependent Kinases / antagonists & inhibitors*
Cyclin-Dependent Kinases / metabolism
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
Glycogen Synthase Kinase 3 / metabolism
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology

Substances

Aza Compounds
Benzazepines
Cyclin T
Protein Kinase Inhibitors
paullone
Cyclin-Dependent Kinases
Glycogen Synthase Kinase 3