Design, Synthesis, Lipophilic Properties, and Binding Affinities of Potential Ligands in Positron Emission Tomography (PET) for Visualization of Brain Dopamine D4 Receptors. Issue 2 (February 2014)

• Record Type: Journal Article
• Authors: Lacivita, Enza; De Giorgio, Paola; Colabufo, Nicola A.; Berardi, Francesco; Perrone, Roberto; Niso, Mauro; Leopoldo, Marcello
• Is Part Of: Chemistry & biodiversity. Volume 11:Issue 2(2014:Feb.)
• Page Start: 299
• Page End: 310
• Publication Date: 2014-02
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biodiversity -- Periodicals; 572
• DOI: 10.1002/cbdv.201300194
• Languages: English
• ISSNs: 1612-1872

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>We report the synthesis of compounds structurally related to the high‐affinity dopamine D₄ receptor ligand <italic>N</italic>‐{2‐[4‐(3‐cyanopyridin‐2‐yl)piperazin‐1‐yl]ethyl}‐3‐methoxybenzamide (<bold>1e</bold>). All compounds were specifically designed as potential PET radioligands for brain D₄ receptor visualization, having lipophilicity within a range for brain uptake and weak non‐specific binding (0.75&lt;cLog<italic>P</italic>&lt;3.15) and bearing a substituent for easy access to labeling with the positron emitter isotope ¹¹C or ¹⁸F. The best compound of the series, <italic>N</italic>‐{2‐[4‐(4‐chlorophenyl)piperazin‐1‐yl]ethyl}‐6‐fluoropyridine‐3‐carboxamide (<bold>7a</bold>), displayed excellent selectivity over D₂ and D₃ receptors (&gt;100‐fold), but its D₄ receptor affinity was suboptimal for imaging of brain D₄ receptors (<italic>K</italic>_i=30 n<sc>M</sc>).</p> </abstract>