Identification of fluorinated (R)-(-)-aporphine derivatives as potent and selective ligands at serotonin 5-HT2C receptor.


Division of Basic Neuroscience, Medicinal Chemistry Program, McLean Hospital, Belmont, MA 02478, United States; Department of Psychiatry, Harvard Medical School, Boston, MA 02115, United States. Electronic address: [Email]


A series of novel aporphine derivatives were synthesized for initial screening at the 5-HT2 receptor subtypes. Among them, Compounds 11a and 11b were identified as potent 5-HT2C hit ligands with high selectivity over other 5-HT2 receptor subtypes. Molecular docking study revealed that compounds 11a and 11b formed two key interactions with the binding site of 5-HT2C receptor, including a salt-bridge to D3.32 and a H-bond interaction with N6.55.


5-HT(2C) receptor,Aporphine derivatives,Hit ligands,Molecular docking,