1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta

Conrad Kunick; Kathrin Lauenroth; Maryse Leost; Laurent Meijer; Thomas Lemcke

doi:10.1016/j.bmcl.2003.10.062

1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta

Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6. doi: 10.1016/j.bmcl.2003.10.062.

Authors

Conrad Kunick¹, Kathrin Lauenroth, Maryse Leost, Laurent Meijer, Thomas Lemcke

Affiliation

¹ Institut für Pharmazeutische Chemie, Technische Universität Braunschweig, Beethovenstrasse 55, 38106, Braunschweig, Germany. kunick@chemie.uni-hamburg.de

PMID: 14698171
DOI: 10.1016/j.bmcl.2003.10.062

Abstract

Kenpaullone derivatives with a modified parent ring system were synthesized in order to develop kinase inhibitors with enhanced selectivity. Among the novel structures, 1-azakenpaullone was found to act as a selective GSK-3beta versus CDK1 inhibitor. The charge distribution within the 1-azakenpaullone molecule is discussed as a possible explanation for the enhanced GSK-3beta selectivity of 1-azakenpaullone compared to other paullone derivatives.

MeSH terms

Benzazepines / chemical synthesis*
Benzazepines / pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
Glycogen Synthase Kinase 3 / metabolism
Glycogen Synthase Kinase 3 beta
Indoles / chemical synthesis*
Indoles / pharmacology

Substances

Benzazepines
Enzyme Inhibitors
Indoles
kenpaullone
Glycogen Synthase Kinase 3 beta
Glycogen Synthase Kinase 3