Synthesis and structure-activity relationship of 2,6-disubstituted pyridine derivatives as inhibitors of beta-amyloid-42 aggregation
Kroth, Heiko; Sreenivasachary, Nampally; Hamel, Anne; Benderitter, Pascal; Varisco, Yvan; Giriens, Valerie; Paganetti, Paolo; Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas
2016

Abstract

It is assumed that amyloid-beta aggregation is a crucial event in the pathogenesis of Alzheimer's disease. Novel 2,6-disubstituted pyridine derivatives were designed to interact with the beta-sheet conformation of A beta via donor-acceptor-donor hydrogen bond formation. A series of pyridine derivatives were synthesized and tested regarding their potential to inhibit the aggregation of A beta. The 2,6-diaminopyridine moiety was identified as a key component to inhibit A beta 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 A beta aggregation. (C) 2016 Elsevier Ltd. All rights reserved.

Details

Title Synthesis and structure-activity relationship of 2,6-disubstituted pyridine derivatives as inhibitors of beta-amyloid-42 aggregation
Author(s) Kroth, Heiko ; Sreenivasachary, Nampally ; Hamel, Anne ; Benderitter, Pascal ; Varisco, Yvan ; Giriens, Valerie ; Paganetti, Paolo ; Froestl, Wolfgang ; Pfeifer, Andrea ; Muhs, Andreas
Published in Bioorganic & Medicinal Chemistry Letters
Pagination 6
Volume 26
Issue 14
Pages 3330-3335
Date 2016
Publisher Oxford, Pergamon-Elsevier Science Ltd
ISSN 0960-894X
Keywords
DOI https://doi.org/10.1016/j.bmcl.2016.05.040
Other identifier(s) View record in Web of Science
Laboratories ISIC-GE
Record Appears in Scientific production and competences > SB - School of Basic Sciences > ISIC - Institute of Chemical Sciences and Engineering > ISIC-GE - Institute of Chemical Sciences and Engineering
Peer-reviewed publications
Work produced at EPFL
Journal Articles
Published
Record creation date 2016-07-19

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