Membrane anchoring γ-secretase modulators with terpene-derived moieties

Eva Christine Naumann; Stefan Göring; Isabella Ogorek; Sascha Weggen; Boris Schmidt

doi:10.1016/j.bmcl.2013.04.070

Membrane anchoring γ-secretase modulators with terpene-derived moieties

Bioorg Med Chem Lett. 2013 Jul 1;23(13):3852-6. doi: 10.1016/j.bmcl.2013.04.070. Epub 2013 May 7.

Authors

Eva Christine Naumann¹, Stefan Göring, Isabella Ogorek, Sascha Weggen, Boris Schmidt

Affiliation

¹ Clemens Schöpf-Institute of Organic Chemistry and Biochemistry, Technische Universität Darmstadt, 64287 Darmstadt, Germany.

PMID: 23707256
DOI: 10.1016/j.bmcl.2013.04.070

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.

MeSH terms

Amyloid Precursor Protein Secretases / chemistry
Amyloid Precursor Protein Secretases / metabolism*
Animals
CHO Cells
Cell Membrane / enzymology*
Cell Membrane / metabolism
Cricetulus
Dose-Response Relationship, Drug
Hydrophobic and Hydrophilic Interactions
Molecular Structure
Small Molecule Libraries / chemical synthesis
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology*
Structure-Activity Relationship
Terpenes / chemical synthesis
Terpenes / chemistry
Terpenes / pharmacology*

Substances

Small Molecule Libraries
Terpenes
Amyloid Precursor Protein Secretases