Dopamine D(3) receptor antagonists: The quest for a potentially selective PET ligand. Part two: Lead optimization

Fabrizio Micheli; Ian Holmes; Luca Arista; Giorgio Bonanomi; Simone Braggio; Francesca Cardullo; Romano Di Fabio; Daniele Donati; Gabriella Gentile; Dieter Hamprecht; Silvia Terreni; Christian Heidbreder; Chiara Savoia; Cristiana Griffante; Angela Worby

doi:10.1016/j.bmcl.2009.06.028

Dopamine D(3) receptor antagonists: The quest for a potentially selective PET ligand. Part two: Lead optimization

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4011-3. doi: 10.1016/j.bmcl.2009.06.028. Epub 2009 Jun 13.

Authors

Fabrizio Micheli¹, Ian Holmes, Luca Arista, Giorgio Bonanomi, Simone Braggio, Francesca Cardullo, Romano Di Fabio, Daniele Donati, Gabriella Gentile, Dieter Hamprecht, Silvia Terreni, Christian Heidbreder, Chiara Savoia, Cristiana Griffante, Angela Worby

Affiliation

¹ GlaxoSmithKline, Neurosciences Centre of Excellence for Drug Discovery, Medicine Research Centre, Verona, Italy. fm20244@gsk.com

PMID: 19553113
DOI: 10.1016/j.bmcl.2009.06.028

Abstract

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.

MeSH terms

Animals
Brain / drug effects
Chemistry, Organic / methods
Chemistry, Pharmaceutical / methods
Dopamine D2 Receptor Antagonists
Humans
Imidazolidines / chemical synthesis
Imidazolidines / chemistry*
Imidazolidines / pharmacology
Inhibitory Concentration 50
Ligands
Models, Chemical
Positron-Emission Tomography
Rats
Receptors, Dopamine D2 / metabolism
Receptors, Dopamine D3 / antagonists & inhibitors*
Receptors, Dopamine D3 / metabolism
Structure-Activity Relationship
Swine

Substances

Dopamine D2 Receptor Antagonists
Imidazolidines
Ligands
Receptors, Dopamine D2
Receptors, Dopamine D3