ABSTRACT
This letter describes synthesis and evaluation of two series of dual mGlu2/mGlu3 positive allosteric modulators with moderate mGlu3 potency and robust mGlu2 potency in thallium flux assays. These compounds were profiled their ability to modulate mGlu3-mediated signaling in central neurons by co-application of a selective mGlu2 NAM to isolate mGlu3-selective effects. Using acute mouse brain slices from the prefrontal cortex, potentiation of group II mGlu receptor agonist Ca2+ signaling in PFC pyramidal cells with either the dual mGlu2/mGlu3 PAM 16e or 23d demonstrated effects mediated selectively via mGlu3.
Subject(s)
Calcium Signaling/drug effects , Neurons/metabolism , Receptors, Metabotropic Glutamate/administration & dosage , Receptors, Metabotropic Glutamate/agonists , Receptors, Metabotropic Glutamate/metabolism , Animals , Cell Line , Drug Design , Humans , Mice , Molecular Structure , Neurons/drug effects , Prefrontal Cortex/cytology , Pyramidal Cells , Receptors, Metabotropic Glutamate/genetics , Structure-Activity RelationshipABSTRACT
A visible-light-promoted method for the selenofunctionalization (and tellurofunctionalization) of alkenes has been developed. This method obviates the prepreparation of moisture-sensitive chalcogen electrophiles. The experimental setup is simple, and superior yields are obtained in the case of selenofunctionalization (up to 99%) while moderate to good yields are obtained in the case of tellurofunctionalization (53-75%). A variety of intra- and intermolecular processes and a short synthesis of the Amaryllidaceae alkaloid (±)-γ-lycorane are demonstrated with this method.
