Concise synthesis and CDK/GSK inhibitory activity of the missing 9-azapaullones.
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.
Power
David P
DP
Centre for Synthesis and Chemical Biology, School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland.
Lozach
Olivier
O
Meijer
Laurent
L
Grayson
David H
DH
Connon
Stephen J
SJ
D001372:Aza Compounds / Q000737:chemistry*; D001552:Benzazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D056906:Cyclin T / Q000037:antagonists & inhibitors / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D001372:Aza Compounds; D001552:Benzazepines; D056906:Cyclin T; D047428:Protein Kinase Inhibitors; C547599:paullone; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3