Identification of fluorinated (R)-(-)-aporphine derivatives as potent and selective ligands at serotonin 5-HT 2C receptor.

Autor: Xu Y; 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., Sromek AW; 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: asromek@mclean.harvard.edu., Neumeyer JL; 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.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2019 Jan 15; Vol. 29 (2), pp. 230-233. Date of Electronic Publication: 2018 Nov 23.
DOI: 10.1016/j.bmcl.2018.11.050
Abstrakt: A series of novel aporphine derivatives were synthesized for initial screening at the 5-HT 2 receptor subtypes. Among them, Compounds 11a and 11b were identified as potent 5-HT 2C hit ligands with high selectivity over other 5-HT 2 receptor subtypes. Molecular docking study revealed that compounds 11a and 11b formed two key interactions with the binding site of 5-HT 2C receptor, including a salt-bridge to D3.32 and a H-bond interaction with N6.55.
(Copyright © 2018. Published by Elsevier Ltd.)
Databáze: MEDLINE
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