Synthesis and SAR of highly potent and selective dopamine D(3)-receptor antagonists: 1H-pyrimidin-2-one derivatives.
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.
Geneste
Hervé
H
Abbott GmbH & Co. KG, Discovery Research, D-67008 Ludwigshafen, Germany. herve.geneste@abbott.com
Backfisch
Gisela
G
Braje
Wilfried
W
Delzer
Jürgen
J
Haupt
Andreas
A
Hutchins
Charles W
CW
King
Linda L
LL
Kling
Andreas
A
Teschendorf
Hans-Jürgen
HJ
Unger
Liliane
L
Wernet
Wolfgang
W
D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D008956:Models, Chemical; D010078:Oxazines / Q000037:antagonists & inhibitors; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C508939:A-690344; D001578:Benzopyrans; D018492:Dopamine Antagonists; D010078:Oxazines; D011744:Pyrimidinones; D050637:Receptors, Dopamine D3; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol