title: Synthesis and structure-activity relationship of 2,6-disubstituted pyridine derivatives as inhibitors of β-amyloid-42 aggregation.
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.
authors.affiliation: AC Immune SA, EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland.
authors.forename: Heiko
authors.initials: H
authors.lastname: Kroth
authors.affiliation: AC Immune SA, EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland.
authors.forename: Nampally
authors.initials: N
authors.lastname: Sreenivasachary
authors.affiliation: AC Immune SA, EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Hamel
authors.affiliation: AC Immune SA, EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland; Oncodesign, 20, rue Jean Mazen, 21076 Dijon, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Benderitter
authors.affiliation: AC Immune SA, EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Varisco
authors.affiliation: AC Immune SA, EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Giriens
authors.affiliation: AC Immune SA, EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland; Ente Ospedaliero Cantonale, Viale Officina 3, 6500 Bellinzona, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Paganetti
authors.affiliation: AC Immune SA, EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Froestl
authors.affiliation: AC Immune SA, EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pfeifer
authors.affiliation: AC Immune SA, EPFL Innovation Park, Building B, 1015 Lausanne, Switzerland. Electronic address: andreas.muhs@acimmune.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Muhs
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D066329:Protein Aggregates / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D066329:Protein Aggregates; D011725:Pyridines; C023666:pyridine
keywords: Alzheimer’s disease; Aβ aggregation; Inhibitors; Pyridine derivatives; Structure–activity relationship