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

Bioorg Med Chem Lett. 2019 Sep 15;29(18):2690-2694. doi: 10.1016/j.bmcl.2019.07.020. Epub 2019 Jul 11.


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.

Keywords: D(2); D(3); Dopamine receptor; Drug addiction; G-protein coupled receptor (GPCR).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzamides / chemical synthesis
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Ligands
  • Microsomes, Liver / chemistry
  • Microsomes, Liver / metabolism
  • Molecular Docking Simulation
  • Molecular Structure
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Rats
  • Receptors, Dopamine D3 / metabolism*
  • Structure-Activity Relationship


  • Benzamides
  • Ligands
  • Piperazines
  • Receptors, Dopamine D3