Further characterization of structural requirements for ligands at the dopamine D(2) and D(3) receptor: exploring the thiophene moiety

J Med Chem. 2002 Jul 4;45(14):3022-31. doi: 10.1021/jm001015a.

Abstract

The present study describes the synthesis and in vitro pharmacology of a novel series of dopaminergic agents in which the classical phenylethylamine pharmacophore is replaced by a thienylethylamine moiety. In general, the novel compounds showed a moderate affinity for the dopamine (DA) D(2) and D(3) receptors. When the thienylethylamine moiety is fixed in a rigid system, the affinity for the DA receptor is significantly increased. However, in the tricyclic hexahydrothianaphthoxazine structure, the affinity for the DA receptors is diminished.

MeSH terms

  • Animals
  • Binding, Competitive
  • Biological Availability
  • CHO Cells
  • Cricetinae
  • Dopamine Agonists / chemical synthesis*
  • Dopamine Agonists / chemistry
  • Dopamine Agonists / pharmacology
  • Humans
  • Magnetic Resonance Spectroscopy
  • Microdialysis
  • Radioligand Assay
  • Rats
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis*
  • Thiophenes / chemistry
  • Thiophenes / pharmacology

Substances

  • DRD3 protein, human
  • Dopamine Agonists
  • Drd3 protein, rat
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Thiophenes
  • dopamine D2L receptor