Combating Alzheimer's Disease With Multifunctional Molecules Designed for Metal Passivation (pages 1716–1718)
Harvey Schugar, David E. Green, Meryn L. Bowen, Lauren E. Scott, Tim Storr, Karin Böhmerle, Fancy Thomas, David D. Allen, Paul R. Lockman, Michael Merkel, Katherine H. Thompson and Chris Orvig
Article first published online: 25 JAN 2007 | DOI: 10.1002/anie.200603866
A trifunctional approach: 3-hydroxy-4-pyridinones that contain phenol groups for antioxidant functionality are further elaborated with pendant glucosyl moieties for improved blood–brain barrier targeting (see structure; R=phenyl, 4-hydroxyphenyl). Glycosidase removal of the carbohydrate substituents gives ligands that are ready to passivate excess metal ions, especially copper and zinc, in the brain. These molecules are potential prodrugs for treatment of neurodegenerative diseases, including Alzheimer's disease.