Discovery and characterization of benzyloxy piperidine based dopamine 4 receptor antagonists

Kirsten T. Tolentino, Viktoriya Mashinson, Anish K. Vadukoot, Corey R. Hopkins

Research output: Contribution to journalArticlepeer-review

Abstract

The dopamine receptor 4 (D4R) is highly expressed in both motor, associative and limbic subdivisions of the cortico-basal ganglia network. Due to the distribution in the brain, there is mounting evidence pointing to a role for the D4R in the modulation of this network and its subsequent involvement in L-DOPA induced dyskinesias in Parkinson's disease. As part of our continued effort in the discovery of novel D4R antagonists, we report the discovery and characterization of a new 3- or 4-benzyloxypiperidine scaffold as D4R antagonists. We report several D4R selective compounds (>30-fold vs. other dopamine receptor subtypes) with improved in vitro and in vivo stability over previously reported D4R antagonists.

Original languageEnglish (US)
Article number128615
JournalBioorganic and Medicinal Chemistry Letters
Volume61
DOIs
StatePublished - Apr 1 2022

Keywords

  • Antagonists
  • Benzyloxypiperidine
  • D4R
  • Dopamine 4 receptor
  • Parkinson's disease

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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