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@ARTICLE{Bolnder:136683,
author = {Boländer, Alexander and Kieser, Daniel and Voss,
Constantin and Bauer, Silvia and Schön, Christian and
Burgold, Steffen and Bittner, Tobias and Hölzer, Jana and
Heyny-von Haußen, Roland and Mall, Gerhard and Goetschy,
Valérie and Czech, Christian and Knust, Henner and Berger,
Robert and Herms, Jochen and Hilger, Ingrid and Schmidt,
Boris},
title = {{B}is(arylvinyl)pyrazines, -pyrimidines, and -pyridazines
as imaging agents for tau fibrils and β-amyloid plaques in
{A}lzheimer's disease models.},
journal = {Journal of medicinal chemistry},
volume = {55},
number = {21},
issn = {0022-2623},
address = {Washington, DC},
publisher = {ACS},
reportid = {DZNE-2020-03005},
pages = {9170-9180},
year = {2012},
abstract = {The in vivo diagnosis of Alzheimer's disease (AD) is of
high socioeconomic interest and remains a demanding field of
research. The biopathological hallmarks of the disease are
extracellular plaques consisting of aggregated β-amyloid
peptides (Aβ) and tau protein derived intracellular
tangles. Here we report the synthesis and evaluation of
fluorescent pyrazine, pyrimidine,and pyridazine derivatives
in vitro and in vivo aiming at a tau-based diagnosis of AD.
The probes were pre-evaluated on human brain tissue by
fluorescence microscopy and were found to label all known
disease-related alterations at high contrast and
specificity. To quantify the binding affinity, a new
thiazine red displacement assay was developed and selected
candidates were toxicologically profiled. The application in
transgenic mouse models demonstrated bioavailability and
brain permeability for one compound. In the course of
histological testing, we discovered an AD-related deposition
of tau aggregates in the Bowman's glands of the olfactory
epithelium, which holds potential for an endoscopic
diagnosis of AD in the olfactory system.},
keywords = {Aged, 80 and over / Alzheimer Disease: diagnosis /
Alzheimer Disease: metabolism / Animals / Biological
Availability / Brain: metabolism / Fluorescent Dyes:
chemical synthesis / Fluorescent Dyes: chemistry /
Fluorescent Dyes: pharmacokinetics / Humans / Mice / Mice,
Transgenic / Microscopy, Fluorescence / Olfactory Mucosa:
metabolism / Organ Specificity / Permeability / Plaque,
Amyloid: metabolism / Pyrazines: chemical synthesis /
Pyrazines: chemistry / Pyrazines: pharmacokinetics /
Pyridazines: chemical synthesis / Pyridazines: chemistry /
Pyridazines: pharmacokinetics / Pyrimidines: chemical
synthesis / Pyrimidines: chemistry / Pyrimidines:
pharmacokinetics / Stereoisomerism / Structure-Activity
Relationship / tau Proteins: metabolism / Fluorescent Dyes
(NLM Chemicals) / Pyrazines (NLM Chemicals) / Pyridazines
(NLM Chemicals) / Pyrimidines (NLM Chemicals) / tau Proteins
(NLM Chemicals)},
cin = {AG Herms},
ddc = {610},
cid = {I:(DE-2719)1110001},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:22913544},
doi = {10.1021/jm300653b},
url = {https://pub.dzne.de/record/136683},
}