Synthesis and preliminary screening of novel indole-3-methanamines as 5-HT4 receptor ligands Academic Article uri icon

abstract

  • Twenty-three indole-3-methanamines were designed, synthesized and evaluated as ligands for the 5-HT(4) receptor. Compounds I-d, I-j, I-o, I-q and I-u showed good affinity at 100 microM and I-o was found to be only 5-fold less potent than the agonists serotonin (1) and 5-methoxytryptamine (2). Substitution on the 3-methanamine nitrogen clearly influenced activity with docking experiments into a homology model of the 5-HT(4) receptor showing a range of interactions with these side chain substituents. This modelling work together with the SAR determined in this study has provided promising ideas for future synthetic work.

authors

  • Hanna-Elias, Amir
  • Manallack, David T
  • Berque-Bestel, Isabelle
  • Irving, Helen R
  • Coupar, Ian M
  • Iskander, Magdy N

publication date

  • July 2009