Acyl hydroxypyrazoles as novel agonists for high-affinity nicotinic acid receptor GPR109A: WO2008051403

Expert Opin Ther Pat. 2009 Aug;19(8):1149-55. doi: 10.1517/13543770902798061.


Background: Acyl hydroxypyrazoles were discovered and claimed by Merck as novel agonists for the high-affinity nicotinic acid receptor, G-protein coupled receptor 109A (GPR109A). The fused bicyclic core contains a hydroxypyrazole that mimics the anthranilide moiety described in their earlier patents and patent publications.

Objective: This article evaluates new GPR109A receptor agonists disclosed by Merck in the recent patent WO2008051403.

Conclusion: The aim of this invention was to provide potential therapy to reduce free fatty acids (FFA), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and serum triglycerides (TG), and to raise high-density lipoprotein cholesterol (HDL-C). Thus, these agonists could - potentially - be used to treat dyslipidemia, atherosclerosis, and metabolic syndromes such as diabetes.

Publication types

  • Review

MeSH terms

  • Fatty Acids, Nonesterified / blood
  • Humans
  • Patents as Topic
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Pyrazoles / therapeutic use
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, Nicotinic
  • Structure-Activity Relationship


  • Fatty Acids, Nonesterified
  • HCAR2 protein, human
  • Pyrazoles
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic