Rational drug design leading to the identification of a potent 5-HT 2C agonist lacking 5-HT 2B activity

Gang Chen, Sung Jin Cho, Xi Ping Huang, Niels H. Jensen, Andreas Svennebring, Maria F. Sassano, Bryan L. Roth, Alan P. Kozikowski

Research output: Contribution to journalArticlepeer-review


The 5-HT 2C receptor is an attractive drug target in the quest for new therapeutics to treat a variety of human disorders. We have previously undertaken a structural optimization campaign that has led to some potent and moderately selective 5-HT 2C receptor agonists. After expanding our structure-function library, we were able to combine our data sets so as to allow the design of compounds of improved selectivity and potency. We disclose herein the structural optimization of our previously reported 5-HT 2B/5- HT 2C agonists, which has led to the identification of a highly selective 5-HT 2C agonist, (+)-trans-[2-(2-cyclopropylmethoxyphenyl) cyclopropyl]methylamine hydrochloride, with an EC 50 of 55 nM and no detectable agonism at the 5-HT 2B receptor.

Original languageEnglish (US)
Pages (from-to)929-932
Number of pages4
JournalACS Medicinal Chemistry Letters
Issue number12
StatePublished - Dec 8 2011


  • 5-HT receptor
  • 5-HT receptor
  • Serotonin
  • agonist
  • hydrophobic interactions

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry


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