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

Hervé Geneste; Gisela Backfisch; Wilfried Braje; Jürgen Delzer; Andreas Haupt; Charles W Hutchins; Linda L King; Andreas Kling; Hans-Jürgen Teschendorf; Liliane Unger; Wolfgang Wernet

doi:10.1016/j.bmcl.2005.10.068

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.

Authors

Hervé Geneste¹, Gisela Backfisch, Wilfried Braje, Jürgen Delzer, Andreas Haupt, Charles W Hutchins, Linda L King, Andreas Kling, Hans-Jürgen Teschendorf, Liliane Unger, Wolfgang Wernet

Affiliation

¹ Abbott GmbH & Co. KG, Discovery Research, D-67008 Ludwigshafen, Germany. [email protected]

PMID: 16290141
DOI: 10.1016/j.bmcl.2005.10.068

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