Synthesis and structure-activity relationships of a series of benzazepine derivatives as 5-HT2C receptor agonists

Bioorg Med Chem. 2008 Mar 15;16(6):3309-20. doi: 10.1016/j.bmc.2007.12.009. Epub 2007 Dec 8.

Abstract

To identify potent and selective 5-HT(2C) receptor agonists, a series of novel benzazepine derivatives were synthesized, and their structure-activity relationships examined. The compounds were evaluated for their 5-HT(2C), 5-HT(2A), and 5-HT(2B) receptor binding affinity and intrinsic activity for the 5-HT(2C) and 5-HT(2A) receptors. Among these compounds, 6,7-dichloro-2,3,4,5-tetrahydro-1H-3-benzazepine (6) was effective in a rat penile erection model when administered po, which is a symptom of the serotonin syndrome reflecting 5-HT(2C) receptor activation. Moreover, compound 6 was characterized as a partial agonist of 5-HT(2A) receptors; therefore, it had little effect on the cardiovascular system.

MeSH terms

  • Animals
  • Benzazepines / chemical synthesis
  • Benzazepines / chemistry*
  • Benzazepines / pharmacology*
  • Cardiovascular System / drug effects
  • Penile Erection / drug effects
  • Rats
  • Receptor, Serotonin, 5-HT2A / drug effects
  • Receptor, Serotonin, 5-HT2B / drug effects
  • Serotonin 5-HT2 Receptor Agonists*
  • Structure-Activity Relationship

Substances

  • Benzazepines
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2B
  • Serotonin 5-HT2 Receptor Agonists