Tetrahydroquinoline-based tricyclic amines as potent and selective agonists of the 5-HT2C receptor

Bioorg Med Chem Lett. 2016 Dec 15;26(24):5877-5882. doi: 10.1016/j.bmcl.2016.11.016. Epub 2016 Nov 9.

Abstract

The syntheses, structure-activity relationships (SARs), and biological activities of tetrahydroquinoline-based tricyclic amines as 5-HT2C receptor agonists are reported. An early lead containing a highly unique 6,6,7-ring system was optimized for both in vitro potency and selectivity at the related 5-HT2B receptor. Orally bioactive, potent, and selective 6,6,6-tricyclic 5-HT2C agonists were identified.

Keywords: 5-HT(2C) agonists; CNS drugs; Lorcaserin; Tetrahydroquinoline; Tricyclic amines.

MeSH terms

  • Administration, Oral
  • Amines / administration & dosage
  • Amines / chemistry
  • Amines / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Male
  • Molecular Structure
  • Quinolines / administration & dosage
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Serotonin 5-HT2 Receptor Agonists / administration & dosage
  • Serotonin 5-HT2 Receptor Agonists / chemistry
  • Serotonin 5-HT2 Receptor Agonists / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amines
  • Quinolines
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists
  • 1,2,3,4-tetrahydroquinoline