Diversification of edaravone via palladium-catalyzed hydrazine cross-coupling: Applications against protein misfolding and oligomerization of beta-amyloid. Issue 1 (1st January 2016)

• Record Type: Journal Article
• Authors: MacLean, Mark A.; Diez-Cecilia, Elena; Lavery, Christopher B.; Reed, Mark A.; Wang, Yanfei; Weaver, Donald F.; Stradiotto, Mark
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 1(2016)
• Page Start: 100
• Page End: 104
• Publication Date: 2016-01-01
• Subjects: Alzheimer's disease -- Beta-amyloid -- Palladium-catalyzed aminations -- Hydrazine; AD Alzheimer's disease -- Aβ amyloid beta -- ThT Thioflavin T -- bio-Aβ42 N-α-biotinyl-Aβ (1–42) -- SAR structure activity relationship -- OFB oligomer formation buffer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.11.022
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: N -Aryl derivatives of edaravone were identified as potentially effective small molecule inhibitors of tau and beta-amyloid aggregation in the context of developing disease-modifying therapeutics for Alzheimer's disease (AD). Palladium-catalyzed hydrazine monoarylation protocols were then employed as an expedient means of preparing a focused library of 21 edaravone derivatives featuring varied N -aryl substitution, thereby enabling structure–activity relationship (SAR) studies. On the basis of data obtained from two functional biochemical assays examining the effect of edaravone derivatives on both fibril and oligomer formation, it was determined that derivatives featuring an N -biaryl motif were four-fold more potent than edaravone.