Synthesis and structure–activity relationship of 2, 6-disubstituted pyridine derivatives as inhibitors of β-amyloid-42 aggregation. Issue 14 (15th July 2016)

• Record Type: Journal Article
• Authors: Kroth, Heiko; Sreenivasachary, Nampally; Hamel, Anne; Benderitter, Pascal; Varisco, Yvan; Giriens, Valérie; Paganetti, Paolo; Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 14(2016)
• Page Start: 3330
• Page End: 3335
• Publication Date: 2016-07-15
• Subjects: Alzheimer's disease -- Aβ aggregation -- Inhibitors -- Structure–activity relationship -- Pyridine derivatives; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.05.040
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: It is assumed that amyloid-β aggregation is a crucial event in the pathogenesis of Alzheimer's disease. Novel 2, 6-disubstituted pyridine derivatives were designed to interact with the β-sheet conformation of Aβ via donor–acceptor–donor hydrogen bond formation. A series of pyridine derivatives were synthesized and tested regarding their potential to inhibit the aggregation of Aβ. The 2, 6-diaminopyridine moiety was identified as a key component to inhibit Aβ aggregation. Overall, compounds having three 2, 6-disubstituted pyridine units separated by at least one C2- or C3-linker displayed the most potent inhibition of Aβ aggregation.