Synthesis of 4,5-Dianilinophthalimide and Related Analogues for Potential Treatment of Alzheimer's Disease via Palladium-Catalyzed Amination
- 6 August 2005
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 70 (18) , 7371-7375
- https://doi.org/10.1021/jo051096o
Abstract
DAPH (4,5-dianilinophthalimide) has previously been shown to reverse the formation of neurotoxic fibrils associated with Alzheimer's disease. We have developed a synthetic route to DAPH and structurally related analogues that employs palladium-catalyzed amination as the key bond-forming step. The requisite substrates are easily obtained, and their coupling with substituted anilines proceeds in generally high yields. Thus, a variety of DAPH analogues can be quickly accessed in a modular fashion. In addition, the route described herein should also be amenable to the incorporation of other classes of nucleophiles into the molecular framework.Keywords
This publication has 17 references indexed in Scilit:
- Expanding Pd-Catalyzed C−N Bond-Forming Processes: The First Amidation of Aryl Sulfonates, Aqueous Amination, and Complementarity with Cu-Catalyzed ReactionsJournal of the American Chemical Society, 2003
- Mechanism of membrane depolarization caused by the Alzheimer Aβ1–42 peptideBiochemical and Biophysical Research Communications, 2002
- Mechanism and prevention of neurotoxicity caused by β-amyloid peptides: relation to Alzheimer's diseaseBrain Research, 1997
- Selective Phosphorylation of Adult Tau Isoforms in Mature Hippocampal Neurons Exposed to Fibrillar AβMolecular and Cellular Neuroscience, 1997
- Analogues of Nα-(4-Amino-4-deoxypteroyl)-Nδ-hemiphthaloyl-l-ornithine (PT523) Modified in the Side Chain: Synthesis and Biological EvaluationJournal of Medicinal Chemistry, 1997
- Dianilinophthalimides: Potent and Selective, ATP-Competitive Inhibitors of the EGF-Receptor Protein Tyrosine KinaseJournal of Medicinal Chemistry, 1994
- Synthesis of ω-PhthalimidoalkylphosphonatesSynthesis, 1994
- Neurotrophic and Neurotoxic Effects of Amyloid β Protein: Reversal by Tachykinin NeuropeptidesScience, 1990
- Evidence that β-Amyloid Protein in Alzheimer's Disease Is Not Derived by Normal ProcessingScience, 1990
- A NOVEL ACTIVATED ESTER IN PEPTIDE SYNTHESESJournal of the American Chemical Society, 1961