Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1399497 | European Journal of Medicinal Chemistry | 2010 | 5 Pages |
A series of 8-arylated purine derivatives bearing either an aniline or an alkyl amide at position 6 were found to inhibit glycogen synthase kinase-3, with good selectivity over ten kinases. Molecular modeling studies indicated that the most active compounds (8a and 8e), adopt a planar conformation, close to the shape of AMPPNP in the crystal structure of GSK-3. These compounds are stabilized by hydrophobic contacts between the 8-aromatic group and the protein adenine pocket and by electrostatic contacts.
Graphical abstractThe synthesis of a library of 8-arylated-6-substituted purines allowed the identification of inhibitors of Glycogen Synthase Kinase (GSK-3) which were docked in the ATP binding site of the kinase.Figure optionsDownload full-size imageDownload as PowerPoint slide