RESUMEN
Replacement of the aryl piperazine moiety in compound 1 with a variety of substituted benzylic piperazines (6) yields compounds that afford melanocortin receptor 4 (MCR4) activity. Analogs with ortho substitution on the aromatic ring afforded the highest affinity. Resolution of the stereocenter of the benzylic piperazine based privileged structure revealed that the R-enantiomer was more active.
Asunto(s)
Derivados del Benceno/química , Derivados del Benceno/metabolismo , Piperazinas/química , Piperazinas/metabolismo , Receptores de Melanocortina/metabolismo , Ligandos , Estructura Molecular , Piperazina , Receptores de Melanocortina/antagonistas & inhibidores , Relación Estructura-ActividadRESUMEN
Substitution of the aryl sulfonamide moiety contained in MC4 agonist 1 with bicyclic heterocycles and aminotetralines produced compounds with MC4 activity. The heterocycles represent alternative privileged structures to that contained in 1. Compounds in which the polar group of the privileged structure was displayed in an endocyclic fashion were not as active as the parent agonist 1, while those with an exocyclic polar group afforded activity competitive with 1.
