Scaffold hopping, synthesis and structure-activity relationships of 5,6-diaryl-pyrazine-2-amide derivatives: a novel series of CB1 receptor antagonists

Bioorg Med Chem. 2007 Jun 15;15(12):4077-84. doi: 10.1016/j.bmc.2007.03.075. Epub 2007 Mar 30.

Abstract

A scaffold hopping approach has been exploited to design a novel class of cannabinoid (CB1) receptor antagonists for the treatment of obesity. On the basis of shape-complementarity and synthetic feasibility the central fragment, a methylpyrazole, in Rimonabant was replaced by a pyrazine. The synthesis and CB1 antagonistic activities of a new series of 5,6-diaryl-pyrazine-2-amide derivatives are described. Several compounds showed antagonist potency below 10nM for the CB1 receptor.

MeSH terms

  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Models, Molecular
  • Pyrazines / chemical synthesis
  • Pyrazines / chemistry*
  • Pyrazines / pharmacology*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Pyrazines
  • Receptor, Cannabinoid, CB1
  • Guanosine 5'-O-(3-Thiotriphosphate)