Referenced in: none

Automatically associated channels: Slo1

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

Authors: Samuel D Banister, Corinne Beinat, Shane M Wilkinson, Bin Shen, Cecilia Bartoli, Silvia Selleri, Eleonora Da Pozzo, Claudia Martini, Frederick T Chin, Michael Kassiou

Journal, date & volume: Eur J Med Chem, 2015 Mar 26 , 93, 392-400

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25725375

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.