The design and synthesis of a tricyclic single-nitrogen scaffold that serves as a 5-HT2C receptor agonist

Bioorg Med Chem Lett. 2006 Aug 1;16(15):4130-4. doi: 10.1016/j.bmcl.2006.04.070. Epub 2006 Jun 5.

Abstract

5-HT2C agonists have shown efficacy in limiting food consumption and thus may serve as an important drug class in combating obesity. We describe the design and synthesis of a novel tricyclic single-nitrogen scaffold that was used to produce 5-HT2C agonists. SAR was developed around this chemotype and compounds were identified that were potent (Ki<15 nM) and selective relative to other 5-HT2 receptors. The most promising compound displayed a good pharmacokinetic profile in multiple animal species, and was efficacious in an acute feeding study in rats.

MeSH terms

  • Animals
  • Dogs
  • Drug Design
  • Feeding Behavior / drug effects
  • Half-Life
  • Nitrogen / chemistry*
  • Rats
  • Serotonin 5-HT2 Receptor Agonists*
  • Serotonin Receptor Agonists / chemical synthesis*
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / pharmacokinetics
  • Serotonin Receptor Agonists / pharmacology*
  • Structure-Activity Relationship

Substances

  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin Receptor Agonists
  • Nitrogen