Synthesis and evaluation of carbon-linked analogs of dual orexin receptor antagonist filorexant

Bioorg Med Chem Lett. 2014 Apr 1;24(7):1784-9. doi: 10.1016/j.bmcl.2014.02.026. Epub 2014 Feb 19.

Abstract

Analogs of the dual orexin receptor antagonist filorexant were prepared. Replacement of the ether linkage proved highly sensitive toward modification with an acetylene linkage providing compounds with the best in vitro and in vivo potency profiles.

Keywords: Antagonist; Insomnia; Orexin.

MeSH terms

  • Acetylene / chemistry*
  • Animals
  • Dose-Response Relationship, Drug
  • Mice
  • Mice, Knockout
  • Molecular Structure
  • Orexin Receptor Antagonists*
  • Orexin Receptors / deficiency
  • Orexin Receptors / metabolism
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cd200r1 protein, mouse
  • Hcrtr1 protein, mouse
  • MK-6096
  • Orexin Receptor Antagonists
  • Orexin Receptors
  • Piperidines
  • Pyrimidines
  • Acetylene