RESUMEN
We report the synthesis of four series of 3,5-disubstituted-phenyl ligands targeting the metabotropic glutamate receptor subtype 5: (2-methylthiazol-4-yl)ethynyl (1a-j,), (6-methylpyridin-2-yl)ethynyl (2a-j), (5-methylpyridin-2-yl)ethynyl (3a-j,), and (pyridin-2-yl)ethynyl (4a-j,). The compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro assay. All compounds were found to be full antagonists and exhibited low nanomolar to subnanomolar activity.
Asunto(s)
Acetileno/análogos & derivados , Piridinas/química , Receptores de Glutamato Metabotrópico/antagonistas & inhibidores , Tiazoles/química , Acetileno/química , Acetileno/farmacología , Animales , Unión Competitiva/efectos de los fármacos , Células Cultivadas , Ligandos , Ratones , Estructura Molecular , Piridinas/farmacología , Ratas , Receptor del Glutamato Metabotropico 5 , Relación Estructura-Actividad , Tiazoles/farmacologíaRESUMEN
We designed and synthesized a small series of 2-aryl-imidazo[2,1-b]benzothiazole, representing a combination of motifs from the two most potent amyloid imaging agents, PIB and IMPY. The binding affinity of the new compounds ranged from 6 to 133 nM. Among the best compounds, 3b (K(i)=6 nM) can be labeled with (11)CH(3) for PET imaging whereas 3j (K(i)=10.9 nM) can be labeled with (123)I for SPECT imaging.
