Privileged structure based ligands for melanocortin receptors—Substituted benzylic piperazine derivatives

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.

Graphical abstractA variety of substituted benzylic piperazines provide useful privileged structures for the construction of ligands with affinity for melanocortin 4 receptors.Figure optionsDownload full-size imageDownload as PowerPoint slide