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.

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

DA POZZO, ELEONORA;MARTINI, CLAUDIA;
2015

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.
Banister, Sd; Beinat, C; Wilkinson, Sm; Shen, B; Bartoli, C; Selleri, S; DA POZZO, Eleonora; Martini, Claudia; Chin, Ft; Kassiou, M.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/744875
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