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WLB-87848, a Selective σ Receptor Agonist, with an Unusually Positioned NH Group as Positive Ionizable Moiety and Showing Neuroprotective Activity. | LitMetric
The synthesis and pharmacological activity of a new series of thieno[2,3-]pyrimidin-4(3)-one derivatives as sigma-1 receptor (σR) ligands are reported. A hit from a high-throughput screening program was evolved into a highly potent and selective σR agonist () that contains a free NH group as positive ionizable moiety, not fulfilling the usual pharmacophoric features of the σR. The compound shows good physicochemical and ADMET characteristics, displays an agonist profile in the binding immunoglobulin protein/σR association assay, induces neuron viability in an in vitro model of β-amyloid peptide intoxication, and presents positive results against recognition memory impairment induced by hippocampal injection of Aβ peptide in rats after oral treatment, altogether making (WLB-87848) an interesting candidate for neuroprotection.
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