Conformationally restricted homotryptamines. Part 6: indole-5-cycloalkyl methylamines as selective serotonin reuptake inhibitors

Bioorg Med Chem Lett. 2013 May 15;23(10):2948-50. doi: 10.1016/j.bmcl.2013.03.045. Epub 2013 Mar 26.

Abstract

Racemic 5-(trans-2-aminomethylcyclopropyl)indoles, 5-(trans-2-aminomethylcyclopentyl) indoles, and 5-(cis-2-aminomethylcyclopentyl)indoles were synthesized and evaluated as selective serotonin reuptake inhibitors. These analogs followed SAR trends similar to those previously reported for 3-cycloalkyl substituted indoles. The most potent analogs exhibited single digit nanomolar inhibition at the human serotonin transporter but were 10-fold less active than the previously reported compounds.

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Methylamines / chemical synthesis
  • Methylamines / chemistry
  • Methylamines / pharmacology*
  • Molecular Conformation
  • Molecular Structure
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis
  • Selective Serotonin Reuptake Inhibitors / chemistry
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Structure-Activity Relationship

Substances

  • Methylamines
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors