Dopamine D(3) receptor antagonists: The quest for a potentially selective PET ligand. Part two: Lead optimization.
The lead optimization process to identify new selective dopamine D(3) receptor antagonists is reported. DMPK parameters and binding data suggest that selective D(3) receptor antagonists as potential PET ligands might have been identified.
Micheli
Fabrizio
F
GlaxoSmithKline, Neurosciences Centre of Excellence for Drug Discovery, Medicine Research Centre, Verona, Italy. fm20244@gsk.com
Holmes
Ian
I
Arista
Luca
L
Bonanomi
Giorgio
G
Braggio
Simone
S
Cardullo
Francesca
F
Di Fabio
Romano
R
Donati
Daniele
D
Gentile
Gabriella
G
Hamprecht
Dieter
D
Terreni
Silvia
S
Heidbreder
Christian
C
Savoia
Chiara
C
Griffante
Cristiana
C
Worby
Angela
A
D000818:Animals; D001921:Brain / Q000187:drug effects; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D048289:Imidazolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008024:Ligands; D008956:Models, Chemical; D049268:Positron-Emission Tomography; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
D065127:Dopamine D2 Receptor Antagonists; D048289:Imidazolidines; D008024:Ligands; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3