Discovery of orally bioavailable and novel urea agonists of the high affinity niacin receptor GPR109A

Bioorg Med Chem Lett. 2007 Dec 15;17(24):6723-8. doi: 10.1016/j.bmcl.2007.10.055. Epub 2007 Oct 18.

Abstract

A urea class of high affinity niacin receptor agonists was discovered. Compound 1a displayed good PK, better in vivo efficacy in reducing FFA in mouse than niacin, and no vasodilation in a mouse model. Compound 1q demonstrated equal affinity to GPR109A as niacin.

MeSH terms

  • Animals
  • Combinatorial Chemistry Techniques
  • Humans
  • Male
  • Mice
  • Models, Animal
  • Molecular Structure
  • Niacin / pharmacology*
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, Nicotinic
  • Structure-Activity Relationship
  • Urea* / analogs & derivatives
  • Urea* / chemical synthesis
  • Urea* / chemistry
  • Urea* / pharmacokinetics
  • Vasodilation / drug effects

Substances

  • Hcar2 protein, mouse
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic
  • Niacin
  • Urea