Synthesis and structure-activity relationships of a series of substituted 2-(1H-furo[2,3-g]indazol-1-yl)ethylamine derivatives as 5-HT2C receptor agonists

Bioorg Med Chem. 2008 Feb 15;16(4):1966-82. doi: 10.1016/j.bmc.2007.10.100. Epub 2007 Nov 4.

Abstract

A series of novel indazole derivatives were synthesized, and their structure-activity relationships examined in order to identify potent and selective 5-HT2C receptor agonists. Among these compounds, (S)-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine (YM348) had a good in vitro profile, that is, high agonistic activity to the human 5-HT2C receptor subtype (EC50 = 1.0 nM) and high selectivity over 5-HT2A receptors. This compound was also effective in a rat penile erection model when administered p.o.

MeSH terms

  • Animals
  • Ethylamines / chemical synthesis
  • Ethylamines / pharmacology
  • Humans
  • Indazoles / chemical synthesis
  • Indazoles / pharmacology*
  • Penile Erection / drug effects
  • Rats
  • Serotonin 5-HT2 Receptor Agonists*
  • Serotonin Receptor Agonists / chemical synthesis*
  • Serotonin Receptor Agonists / pharmacology
  • Structure-Activity Relationship

Substances

  • Ethylamines
  • Indazoles
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin Receptor Agonists