Synthesis and preliminary screening of novel tryptamines as 5-HT4 receptor ligands

Curr Med Chem. 2010;17(25):2775-87. doi: 10.2174/092986710791859351.

Abstract

For the development of novel 5-HT(4) receptor ligands we have designed and synthesized two series of 5-methoxytryptamine derivatives varying the substitution on the primary amine. Their biological activities were evaluated in a receptor binding assay where a subset of compounds showed comparable potency to the agonists serotonin and 5-methoxytryptamine. Structure-activity analyses have highlighted promising avenues for further synthetic work and binding modes were proposed by docking these compounds into a homology model of the 5-HT(4) receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methoxytryptamine / analogs & derivatives
  • 5-Methoxytryptamine / chemical synthesis
  • 5-Methoxytryptamine / metabolism
  • 5-Methoxytryptamine / pharmacology
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Drug Design
  • Drug Discovery
  • Humans
  • Ligands
  • Receptors, Serotonin, 5-HT4 / metabolism
  • Receptors, Serotonin, 5-HT4 / physiology
  • Serotonin 5-HT4 Receptor Antagonists / chemical synthesis*
  • Serotonin 5-HT4 Receptor Antagonists / pharmacology*
  • Tryptamines / agonists
  • Tryptamines / chemical synthesis
  • Tryptamines / chemistry
  • Tryptamines / pharmacology*

Substances

  • Ligands
  • Serotonin 5-HT4 Receptor Antagonists
  • Tryptamines
  • Receptors, Serotonin, 5-HT4
  • 5-Methoxytryptamine