Synthesis and SAR of highly potent and selective dopamine D(3)-receptor antagonists: 1H-pyrimidin-2-one derivatives

Bioorg Med Chem Lett. 2006 Feb;16(3):490-4. doi: 10.1016/j.bmcl.2005.10.068. Epub 2005 Nov 11.

Abstract

The synthesis and SAR of novel highly potent and selective dopamine D(3)-receptor antagonists based on a 1H-pyrimidin-2-one scaffold are described. A-690344 antagonized PD 128907-induced huddling deficits in rat (ED(50) 6.1mg/kg po), a social interaction paradigm.

MeSH terms

  • Animals
  • Benzopyrans / antagonists & inhibitors
  • Dopamine Antagonists / chemical synthesis*
  • Dopamine Antagonists / pharmacology
  • Models, Chemical
  • Oxazines / antagonists & inhibitors
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / pharmacology
  • Rats
  • Receptors, Dopamine D3 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • A-690344
  • Benzopyrans
  • Dopamine Antagonists
  • Oxazines
  • Pyrimidinones
  • Receptors, Dopamine D3
  • 3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol