RESUMEN
For the development of novel 5-HT(4) receptor ligands we have designed and synthesized two series of 5-methoxytryptamine derivatives varying the substitution on the primary amine. Their biological activities were evaluated in a receptor binding assay where a subset of compounds showed comparable potency to the agonists serotonin and 5-methoxytryptamine. Structure-activity analyses have highlighted promising avenues for further synthetic work and binding modes were proposed by docking these compounds into a homology model of the 5-HT(4) receptor.
Asunto(s)
Antagonistas del Receptor de Serotonina 5-HT4/síntesis química , Antagonistas del Receptor de Serotonina 5-HT4/farmacología , Triptaminas/farmacología , 5-Metoxitriptamina/análogos & derivados , 5-Metoxitriptamina/síntesis química , 5-Metoxitriptamina/metabolismo , 5-Metoxitriptamina/farmacología , Animales , Células COS , Chlorocebus aethiops , Diseño de Fármacos , Descubrimiento de Drogas , Humanos , Ligandos , Receptores de Serotonina 5-HT4/metabolismo , Receptores de Serotonina 5-HT4/fisiología , Triptaminas/agonistas , Triptaminas/síntesis química , Triptaminas/químicaRESUMEN
A series of 30 tripeptides were synthesized and tested as novel 5-HT4 receptor ligands. Receptor binding assays showed that a subset of compounds had reasonable potency relative to the agonists serotonin and 5-methoxytryptamine. Structure-activity analyses and molecular docking have highlighted avenues for further synthetic work.