Discovery, characterization and biological evaluation of a novel (R)-4,4-difluoropiperidine scaffold as dopamine receptor 4 (D4R) antagonists

Daniel E. Jeffries, Jonathan O. Witt, Andrea L. McCollum, Kayla J. Temple, Miguel A. Hurtado, Joel M. Harp, Anna L. Blobaum, Craig W. Lindsley, Corey R Hopkins

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Herein, we report the synthesis and structure–activity relationship of a novel series of (R)-4,4-difluoropiperidine core scaffold as dopamine receptor 4 (D4) antagonists. A series of compounds from this scaffold are highly potent against the D4receptor and selective against the other dopamine receptors. In addition, we were able to confirm the active isomer as the (R)-enantiomer via an X-ray crystal structure.

Original languageEnglish (US)
Pages (from-to)5757-5764
Number of pages8
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number23
DOIs
StatePublished - Jan 1 2016

Fingerprint

Dopamine Antagonists
Dopamine Receptors
Scaffolds
X-Rays
Enantiomers
Isomers
Crystal structure
X rays

Keywords

  • Addiction
  • Difluoropiperidine
  • Dopamine 4 receptor
  • PD-LIDs
  • Selectivity

ASJC Scopus subject areas

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

Cite this

Discovery, characterization and biological evaluation of a novel (R)-4,4-difluoropiperidine scaffold as dopamine receptor 4 (D4R) antagonists. / Jeffries, Daniel E.; Witt, Jonathan O.; McCollum, Andrea L.; Temple, Kayla J.; Hurtado, Miguel A.; Harp, Joel M.; Blobaum, Anna L.; Lindsley, Craig W.; Hopkins, Corey R.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 23, 01.01.2016, p. 5757-5764.

Research output: Contribution to journalArticle

Jeffries, Daniel E. ; Witt, Jonathan O. ; McCollum, Andrea L. ; Temple, Kayla J. ; Hurtado, Miguel A. ; Harp, Joel M. ; Blobaum, Anna L. ; Lindsley, Craig W. ; Hopkins, Corey R. / Discovery, characterization and biological evaluation of a novel (R)-4,4-difluoropiperidine scaffold as dopamine receptor 4 (D4R) antagonists. In: Bioorganic and Medicinal Chemistry Letters. 2016 ; Vol. 26, No. 23. pp. 5757-5764.
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