5-N,N-Disubstituted 5-aminopyrazole-3-carboxylic acids are highly potent agonists of GPR109b

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4207-9. doi: 10.1016/j.bmcl.2009.05.108. Epub 2009 May 30.

Abstract

A series of 5-N,N-disubstituted-5-aminopyrazole-3-carboxylic acids were prepared and found to act as highly potent and selective agonists of the G-Protein Coupled Receptor (GPCR) GPR109b, a low affinity receptor for niacin and some aromatic d-amino acids. Little activity was observed at the highly homologous higher affinity niacin receptor, GPR109a.

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy
  • CHO Cells
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / pharmacology
  • Chemistry, Pharmaceutical / methods
  • Cricetinae
  • Cricetulus
  • Drug Design
  • Dyslipidemias / drug therapy
  • Humans
  • Ligands
  • Lipoproteins, HDL / chemistry
  • Lipoproteins, LDL / chemistry
  • Models, Chemical
  • Niacin / chemistry
  • Pyrazoles / pharmacology
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Nicotinic

Substances

  • Carboxylic Acids
  • HCAR3 protein, human
  • Ligands
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Pyrazoles
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic
  • Niacin