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Novel bis(indolyl)maleimide pyridinophanes that are potent, selective inhibitors of glycogen synthase kinase-3.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2007 May 15; Vol. 17 (10), pp. 2863-8. Date of Electronic Publication: 2007 Feb 25. - Publication Year :
- 2007
-
Abstract
- Novel bis(indolyl)maleimide pyridinophanes 3, 9a, 9b, 10a, 10b, and 11 were prepared by cobalt-mediated [2+2+2] cycloaddition of an appropriate alpha,omega-diyne with an N,N-dialkylcyanamide. These macrocyclic heterophanes were found to be potent, selective inhibitors of glycogen synthase kinase-3beta. An X-ray structure of a co-crystal of GSK-3beta and 3 (IC(50)=3nM) depicts the hydrogen bonding and hydrophobic interactions in the ATP-binding pocket of this serine/threonine protein kinase.
- Subjects :
- Adenosine Triphosphate metabolism
Binding Sites
Drug Design
Enzyme Inhibitors chemical synthesis
Glycogen Synthase Kinase 3 chemistry
Glycogen Synthase Kinase 3 beta
Hydrophobic and Hydrophilic Interactions
Maleimides chemistry
Models, Molecular
Molecular Structure
Protein Conformation
Pyridines chemistry
Structure-Activity Relationship
Enzyme Inhibitors pharmacology
Glycogen Synthase Kinase 3 antagonists & inhibitors
Pyridines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0960-894X
- Volume :
- 17
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 17350261
- Full Text :
- https://doi.org/10.1016/j.bmcl.2007.02.059