(+/-)-Nantenine analogs as antagonists at human 5-HT(2A) receptors: C1 and flexible congeners

Bioorg Med Chem Lett. 2009 May 1;19(9):2530-2. doi: 10.1016/j.bmcl.2009.03.048. Epub 2009 Mar 16.

Abstract

C1 and flexible analogs of (+/-)-nantenine were synthesized and evaluated for antagonist activity at human 5-HT(2A) receptors in a calcium mobilization assay. This work has resulted in the identification of the most potent 5-HT(2A) antagonist known based on an aporphine. Our results also suggest that the C1 position may be a key site for increasing 5-HT(2A) antagonist activity in this compound series. In addition, the structural rigidity of the aporphine core appears to be required for nantenine to function as a 5-HT(2A) antagonist.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aporphines / chemical synthesis*
  • Aporphines / chemistry
  • Aporphines / pharmacology
  • Calcium / metabolism
  • Carbon / chemistry
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Models, Chemical
  • Molecular Structure
  • Serotonin 5-HT2 Receptor Antagonists*
  • Structure-Activity Relationship

Substances

  • Aporphines
  • Serotonin 5-HT2 Receptor Antagonists
  • aporphine
  • Carbon
  • Calcium
  • nantenine