Analogues of acifran: agonists of the high and low affinity niacin receptors, GPR109a and GPR109b

J Med Chem. 2007 Apr 5;50(7):1445-8. doi: 10.1021/jm070022x. Epub 2007 Mar 15.


Recently identified GPCRs, GPR109a and GPR109b, the high and low affinity receptors for niacin, may represent good targets for the development of HDL elevating drugs for the treatment of atherosclerosis. Acifran, an agonist of both receptors, has been tested in human subjects, yet until recently very few analogs had been reported. We describe a series of acifran analogs prepared using newly developed synthetic pathways and evaluated as agonists for GPR109a and GPR109b, resulting in identification of compounds with improved activity at these receptors.

MeSH terms

  • Cell Line
  • Cyclic AMP / biosynthesis
  • Furans / chemical synthesis*
  • Furans / chemistry
  • Furans / pharmacology
  • Humans
  • Niacin / metabolism*
  • Niacin / pharmacology
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Nicotinic / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship


  • Furans
  • HCAR2 protein, human
  • HCAR3 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic
  • Niacin
  • acifran
  • Cyclic AMP