Tranylcypromine substituted cis -hydroxycyclobutylnaphthamides as potent and selective dopamine D3 receptor antagonists

Jianyong Chen, Beth Levant, Cheng Jiang, Thomas M. Keck, Amy Hauck Newman, Shaomeng Wang

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

We report a class of potent and selective dopamine D3 receptor antagonists based upon tranylcypromine. Although tranylcypromine has a low affinity for the rat D3 receptor (Ki = 12.8 μM), our efforts have yielded (1R,2S)-11 (CJ-1882), which has Ki values of 2.7 and 2.8 nM at the rat and human dopamine D3 receptors, respectively, and displays respective selectivities of >10000-fold and 223-fold over the rat and human D2 receptors. Evaluation in a β-arrestin functional assay showed that (1R,2S)-11 is a potent and competitive antagonist at the human D3 receptor.

Original languageEnglish (US)
Pages (from-to)4962-4968
Number of pages7
JournalJournal of Medicinal Chemistry
Volume57
Issue number11
DOIs
StatePublished - Jun 12 2014

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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