Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands

• Published in: Bioorganic & medicinal chemistry letters Vol. 29; no. 18; pp. 2690 - 2694
• Main Authors: Chen, Peng-Jen, Taylor, Michelle, Griffin, Suzy A., Amani, Armaghan, Hayatshahi, Hamed, Korzekwa, Kenneth, Ye, Min, Mach, Robert H., Liu, Jin, Luedtke, Robert R., Gordon, John C., Blass, Benjamin E.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 15.09.2019
• Subjects: Dopamine receptor; Drug addiction; G-protein coupled receptor (GPCR); Drug addiction; G-protein coupled receptor (GPCR); Dopamine receptor; D2; D3
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2019.07.020

[Display omitted] As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.