TY  - JOUR
AU  - Falkenstein, Markus
AU  - Reiner-Link, David
AU  - Zivkovic, Aleksandra
AU  - Gering, Ian
AU  - Willbold, Dieter
AU  - Stark, Holger
TI  - Histamine H3 receptor antagonists with peptidomimetic (keto)piperazine structures to inhibit Aβ oligomerisation
JO  - Bioorganic & medicinal chemistry
VL  - 50
SN  - 0968-0896
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - FZJ-2021-05881
SP  - 116462 -
PY  - 2021
N1  - Kein Zugriff auf Post-print
AB  - Alzheimeŕs disease (AD) is the most prominent neurodegenerative disorder with high medical need. Protein-protein-interactions (PPI) interactions have a critical role in AD where β-amyloid structures (Aβ) build toxic oligomers. Design of disease modifying multi target directed ligand (MTDL) has been performed, which disable PPI on the one hand and on the other hand, act as procognitive antagonists at the histamine H3 receptor (H3R). The synthetized compounds are structurally based on peptidomimetic amino acid-like structures mainly as keto, diketo-, or acyl variations of a piperazine moiety connected to an H3R pharmacophore. Most of them showed low nanomolar affinities at H3R and some with promising affinity to Aβ-monomers. The structure–activity relationships (SAR) described offer new possibilities for MTDL with an optimized profile combining symptomatic and potential causal therapeutic approaches in AD.
LB  - PUB:(DE-HGF)16
C6  - pmid:34695709
UR  - <Go to ISI:>//WOS:000710815900002
DO  - DOI:10.1016/j.bmc.2021.116462
UR  - https://juser.fz-juelich.de/record/904311
ER  -