Binding of 2,4-disubstituted morpholines at human D4 dopamine receptors

Bioorg Med Chem. 1998 Jan;6(1):1-8. doi: 10.1016/s0968-0896(97)00176-4.

Abstract

The synthesis of a series of 2,4-disubstituted morpholines is described and their affinities at human dopamine receptors reported. The orally bioavailable 7-azaindole compound 11 has nanomolar affinity at the hD4 receptor with > 1000-fold selectivity over the hD2 receptor.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Binding, Competitive
  • Biological Availability
  • Cell Line
  • Humans
  • Injections, Intravenous
  • Models, Molecular
  • Morpholines / chemical synthesis
  • Morpholines / metabolism*
  • Morpholines / pharmacokinetics
  • Pyridines / chemical synthesis
  • Pyridines / metabolism*
  • Pyridines / pharmacokinetics
  • Radioligand Assay
  • Rats
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D4
  • Spiperone / metabolism
  • Structure-Activity Relationship
  • Tritium

Substances

  • 3-((2-((4-chlorophenoxy)methyl)morpholin-4-yl)methyl)pyrrolo(2,3-b)pyridine
  • DRD4 protein, human
  • Drd4 protein, rat
  • Morpholines
  • Pyridines
  • Receptors, Dopamine D2
  • Tritium
  • Receptors, Dopamine D4
  • Spiperone