New 1-arylindoles based serotonin 5-HT7 antagonists. Synthesis and binding evaluation studies

Eur J Med Chem. 2014 Mar 21:75:159-68. doi: 10.1016/j.ejmech.2014.01.055. Epub 2014 Jan 28.

Abstract

Based on 5-HT1A and 5-HT7 ligand MR25003 scaffold, a new series of 1-aryl indole analogues were prepared and evaluated against 5-HT7 receptors. Modulations of aryl moieties provided a large number of new indolic derivatives. Most of compounds tested have displayed 5-HT7 affinity in the nanomolar range. Among them, 1-(naphthyl)indole derivative 3p (Ki (5-HT7) = 4.5 nM) showed also a good selectivity over 5-HT1A, 5-HT2A and 5-HT6 receptors. This compound was pharmacology characterized as an antagonist.

Keywords: 5-HT(1A); 5-HT(7); Antagonist; Indole; Serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • HEK293 Cells
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Ligands
  • Naphthalenes / chemical synthesis
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Rats
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptors, Serotonin / metabolism*
  • Serotonin / metabolism
  • Serotonin Antagonists / chemical synthesis
  • Serotonin Antagonists / chemistry*
  • Serotonin Antagonists / pharmacology*
  • Structure-Activity Relationship

Substances

  • Indoles
  • Ligands
  • Naphthalenes
  • Receptors, Serotonin
  • Serotonin Antagonists
  • serotonin 7 receptor
  • Receptor, Serotonin, 5-HT1A
  • Serotonin