Discovery of β-Arrestin Biased Ligands of 5-HTR.

Though many studies have been published about therapeutic potentials of selective 5-HTR ligands, there have been few biased ligands of 5-HTR. The development of potent and selective biased ligands of 5-HTR would be of great help in understanding the relationship between pharmacological effects and G protein/β-arrestin signaling pathways of 5-HTR. In order to identify 5-HTR ligands with biased agonism, we designed and synthesized a series of tetrahydroazepine derivatives 1 and 2 with arylpyrazolo moiety or arylisoxazolo moiety.