Ether analogues of DPA-714 with subnanomolar affinity for the translocator protein (TSPO)

European Journal of Medicinal Chemistry
Samuel D BanisterMichael Kassiou

Abstract

Sixteen new phenyl alkyl ether derivatives (12, 14-28) of the 5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-ylacetamide (DPA) class were synthesized and evaluated in a competition binding assay against [(3)H]PK11195 using 18 kDa translocator protein (TSPO) derived from rat kidney mitochondrial fractions. All analogues showed superior binding affinities for TSPO compared to DPA-713 (5) and DPA-714 (6). Picomolar affinities were observed for this class of TSPO ligands in this assay for the first time, with phenethyl ether 28 showing the greatest affinity (Ki = 0.13 nM). Additionally, all analogues increased pregnenolone biosynthesis (134-331% above baseline) in a rat C6 glioma cell steroidogenesis assay.

References

Oct 29, 2002·International Journal of Cancer. Journal International Du Cancer·Andreas P SutterHans Scherübl
Apr 29, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·David R OwenChristine A Parker
Oct 16, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Marie-Anne PeyronneauHéric Valette
Apr 26, 2014·Journal of Labelled Compounds & Radiopharmaceuticals·Vincent Médran-NavarreteFrédéric Dollé

❮ Previous
Next ❯

Citations

Oct 28, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Eryn L WerryMichael Kassiou
Nov 15, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Gaia RizzoAlessandra Bertoldo
Oct 22, 2020·European Journal of Medicinal Chemistry·Elisabetta BarresiSabrina Taliani

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Neuroimaging

Neuroimaging can help identify pathological hallmarks of Alzheimer's disease (AD). Here is the latest research on neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, in AD.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Alzheimer's Disease: Microglia

Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.