Synthesis and characterization of a series of chiral alkoxymethyl morpholine analogs as dopamine receptor 4 (D4R) antagonists

Jonathan O. Witt, Andrea L. McCollum, Miguel A. Hurtado, Eric D. Huseman, Daniel E. Jeffries, Kayla J. Temple, Hyekyung C. Plumley, Anna L. Blobaum, Craig W. Lindsley, Corey R. Hopkins

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Herein, we report the synthesis and structure-activity relationship of a series of chiral alkoxymethyl morpholine analogs. Our efforts have culminated in the identification of (S)-2-(((6-chloropyridin-2-yl)oxy)methyl)-4-((6-fluoro-1H-indol-3-yl)methyl)morpholine as a novel potent and selective dopamine D4 receptor antagonist with selectivity against the other dopamine receptors tested (<10% inhibition at 1 μM against D1, D2L, D2S, D3, and D5).

Original languageEnglish (US)
Pages (from-to)2481-2488
Number of pages8
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number10
DOIs
StatePublished - May 1 2016

Keywords

  • Antagonist
  • Dopamine 4 receptor
  • Dopamine Selectivity
  • L-DOPA-induced dyskinesia
  • Morpholine

ASJC Scopus subject areas

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

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