Synthesis and in vitro binding of N-phenyl piperazine analogs as potential dopamine D 3 receptor ligands

Wenhua Chu, Zhude Tu, Elizabeth McElveen, Jinbin Xu, Michelle Taylor, Robert R. Luedtke, Robert H. MacH

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85 Scopus citations

Abstract

The synthesis of a series of N-(2-methoxyphenyl)piperazine and N-(2,3-dichlorophenyl)piperazine analogs and their in vitro binding affinities for dopamine D 2, D 3, D 4 are presented. A series of N-(2-methoxyphenyl)piperazine and N-(2,3-dichlorophenyl)piperazine analogs were prepared and their affinities for dopamine D 2, D 3, and D 4 receptors were measured in vitro. Binding studies were also conducted to determine if the compounds bound to sigma (σ 1 and σ 2) and serotonin (5-HT 1A, 5-HT 2A, 5-HT 2B, 5-HT 2C, 5-HT 3, 5-HT 4, 5-HT 5, 5-HT 6, and 5-HT 7) receptors. The results of the current study revealed a number of compounds (12b, 12c, 12e, and 12g) having a high affinity for D 3 (K i at D 3 receptors ranging from 0.3 to 0.9 nM) versus D 2 (K i at D 2 receptors ranging from 40 to 53 nM) receptors and a log P value indicating that they should readily cross the blood brain barrier (log P = 2.6-3.5). All of the compounds evaluated in this study had a high affinity for serotonin 5-HT 1A receptors. These compounds may be useful as probes for studying the behavioral pharmacology of the dopamine D 3 receptor, as well as lead compounds for the development of radiotracers for studying D 3 receptor regulation in vivo with the functional imaging technique, positron emission tomography.

Original languageEnglish
Pages (from-to)77-87
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume13
Issue number1
DOIs
StatePublished - 3 Jan 2005

Keywords

  • Atypical antipsychotics
  • Dopamine D receptors

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