Synthesis and SAR of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones as 5-HT2C receptor agonists

Bioorg Med Chem Lett. 2013 Jan 1;23(1):330-5. doi: 10.1016/j.bmcl.2012.10.091. Epub 2012 Nov 2.

Abstract

A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones is described, several examples of which exhibit potent 5-HT(2C) agonism with excellent selectivity over the closely related 5-HT(2A) and 5-HT(2B) receptors. Compounds such as 38 and 44 were shown to be effective in reducing food intake in an acute rat feeding model.

MeSH terms

  • Animals
  • Half-Life
  • Heterocyclic Compounds, 3-Ring / chemical synthesis*
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Heterocyclic Compounds, 3-Ring / pharmacokinetics
  • Humans
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry*
  • Isoquinolines / pharmacokinetics
  • Male
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry*
  • Pyrroles / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A / chemistry
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Receptor, Serotonin, 5-HT2B / chemistry
  • Receptor, Serotonin, 5-HT2B / metabolism
  • Receptor, Serotonin, 5-HT2C / chemistry*
  • Receptor, Serotonin, 5-HT2C / metabolism
  • Serotonin 5-HT2 Receptor Agonists / chemical synthesis*
  • Serotonin 5-HT2 Receptor Agonists / chemistry
  • Serotonin 5-HT2 Receptor Agonists / pharmacokinetics
  • Structure-Activity Relationship

Substances

  • Heterocyclic Compounds, 3-Ring
  • Isoquinolines
  • Pyrroles
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2B
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists