Discovery, characterization and biological evaluation of a novel (R)-4, 4-difluoropiperidine scaffold as dopamine receptor 4 (D4R) antagonists. Issue 23 (1st December 2016)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 23(2016)
• Page Start: 5757
• Page End: 5764
• Publication Date: 2016-12-01
• Subjects: Dopamine 4 receptor -- Difluoropiperidine -- Addiction -- PD-LIDs -- Selectivity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.10.049
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 D4 receptor 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.