RESUMO
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.
Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Neurônios/metabolismo , Receptores de Glutamato Metabotrópico/administração & dosagem , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Linhagem Celular , Desenho de Fármacos , Humanos , Camundongos , Estrutura Molecular , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/citologia , Células Piramidais , Receptores de Glutamato Metabotrópico/genética , Relação Estrutura-AtividadeRESUMO
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.