Fluorinated pyrazole acids are agonists of the high affinity niacin receptor GPR109a

  • Bioorg Med Chem Lett. 2007 Oct 15;17(20):5620-3. doi: 10.1016/j.bmcl.2007.07.101.
Philip J Skinner  1 ,  Martin C Cherrier ,  Peter J Webb ,  Young-Jun Shin ,  Tawfik Gharbaoui ,  Andrew Lindstrom ,  Vu Hong ,  Susan Y Tamura ,  Huong T Dang ,  Cameron C Pride ,  Ruoping Chen ,  Jeremy G Richman ,  Daniel T Connolly ,  Graeme Semple
Affiliations
  • 1. Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA. [email protected]
PMID: 17804224 DOI: 10.1016/j.bmcl.2007.07.101
Abstract

A series of 5-alkyl pyrazole-3-carboxylic acids were prepared and found to act as potent and selective agonists of the human GPCR, GPR109A, the high affinity nicotinic acid receptor. No activity was observed at the highly homologous low affinity niacin receptor, GPR109b. A further series of 4-fluoro-5-alkyl pyrazole-3-carboxylic acids were shown to display similar potency. One example from the series was shown to have improved properties in vivo compared to niacin.

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