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

Bioorg Med Chem Lett. 2019 Jan 15;29(2):230-233. doi: 10.1016/j.bmcl.2018.11.050. Epub 2018 Nov 23.

Abstract

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.

Keywords: 5-HT(2C) receptor; Aporphine derivatives; Hit ligands; Molecular docking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aporphines / chemical synthesis
  • Aporphines / chemistry
  • Aporphines / pharmacology*
  • Halogenation
  • Humans
  • Ligands
  • Molecular Structure
  • Receptor, Serotonin, 5-HT2C / metabolism*

Substances

  • Aporphines
  • Ligands
  • Receptor, Serotonin, 5-HT2C
  • aporphine