Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 receptor selectivity

J Med Chem. 2004 Aug 12;47(17):4155-8. doi: 10.1021/jm049720x.

Abstract

Eleven-membered heterocycles (dibenz[g,j]-1-oxa-4-azacycloundecenes) and open-chain analogues were synthesized and investigated for affinities to human dopamine receptor subtypes. The moderately rigidized rings displayed nanomolar and subnanomolar Ki values at D1-like receptors with a significant D1 to D2 and a slight D5 to D1 selectivity. The open-chain analogues showed lower affinities but significant D1 to D2 selectivities. Compound 3 (Ki(D5) = 0.57 nmol) showed antagonistic or inverse agonistic binding characteristics in a functional Ca assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Line
  • Cricetinae
  • Heterocyclic Compounds, 2-Ring / chemical synthesis*
  • Heterocyclic Compounds, 2-Ring / chemistry
  • Heterocyclic Compounds, 2-Ring / pharmacology
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Ligands
  • Oxygen*
  • Radioligand Assay
  • Receptors, Dopamine D1 / drug effects*
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D5
  • Structure-Activity Relationship

Substances

  • DRD5 protein, human
  • Heterocyclic Compounds, 2-Ring
  • Heterocyclic Compounds, 4 or More Rings
  • Ligands
  • Receptors, Dopamine D1
  • Receptors, Dopamine D5
  • Oxygen
  • Calcium