Ether analogues of DPA-714 with subnanomolar affinity for the translocator protein (TSPO)
European Journal of Medicinal Chemistry, 2015•Elsevier
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 …
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 …
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 [3H]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.
Elsevier
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