title: Membrane anchoring γ-secretase modulators with terpene-derived moieties.
abstract: Modulation of γ-secretase activity is a promising therapeutic strategy for the treatment of Alzheimer's disease. Herein we report on the synthesis of carprofen- and tocopherol-derived small-molecule modulators carrying terpene moieties as lipophilic membrane anchors. Additionally, these modulators are equipped with an acidic moiety, which contributes to the desired modulatory effect on the γ-secretase with decreased formation of Aβ42 and increased Aβ38 production.
authors.affiliation: Clemens Schöpf-Institute of Organic Chemistry and Biochemistry, Technische Universität Darmstadt, 64287 Darmstadt, Germany.
authors.forename: Eva Christine
authors.initials: EC
authors.lastname: Naumann
authors.forename: Stefan
authors.initials: S
authors.lastname: Göring
authors.forename: Isabella
authors.initials: I
authors.lastname: Ogorek
authors.forename: Sascha
authors.initials: S
authors.lastname: Weggen
authors.forename: Boris
authors.initials: B
authors.lastname: Schmidt
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000201:enzymology* / Q000378:metabolism; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D054852:Small Molecule Libraries; D013729:Terpenes; D053829:Amyloid Precursor Protein Secretases