RESUMEN
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.
Asunto(s)
Señalización del Calcio/efectos de los fármacos , Neuronas/metabolismo , Receptores de Glutamato Metabotrópico/administración & dosificación , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/metabolismo , Animales , Línea Celular , Diseño de Fármacos , Humanos , Ratones , Estructura Molecular , Neuronas/efectos de los fármacos , Corteza Prefrontal/citología , Células Piramidales , Receptores de Glutamato Metabotrópico/genética , Relación Estructura-ActividadRESUMEN
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.