An initial three-component pharmacophore for specific serotonin-3 receptor ligands

J Med Chem. 1990 Oct;33(10):2721-5. doi: 10.1021/jm00172a007.


With computer modeling, an initial three-component pharmacophore for specific 5-HT3 receptor ligands ICS-205-930 (1), ondansetron (2), zacopride (3), and 3-[2-(guanidinylmethyl)-4-thiazolyl]indol (4) has been identified. Two parts represent electrostatic interactions, one as a hydrogen-bond-donating interaction and the other as a hydrogen-bond-accepting interaction. The third part is represented by a plane in which the lipophilic aromatic groups align. The generation of the pharmacophore relies on the interactions of these ligands with probe atoms representative of a possible hydrogen-bond donor or hydrogen-bond acceptor within the receptor. A carboxylate oxygen was used as a hydrogen-bond-accepting probe and a serine-like hydroxyl was utilized as a hydrogen-bond-donating probe.

MeSH terms

  • Animals
  • Benzamides / chemistry
  • Bridged Bicyclo Compounds / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Computer Graphics
  • Computer Simulation
  • Imidazoles / chemistry
  • In Vitro Techniques
  • Indoles / chemistry
  • Ligands
  • Mice
  • Models, Molecular
  • Ondansetron
  • Rats
  • Receptors, Serotonin / drug effects*
  • Serotonin Antagonists*
  • Structure-Activity Relationship
  • Thiazoles
  • Tropisetron


  • Benzamides
  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Imidazoles
  • Indoles
  • Ligands
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Thiazoles
  • Ondansetron
  • Tropisetron
  • zacopride