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

doi:10.1016/j.bmcl.2007.07.101

Bioorganic & Medicinal Chemistry Letters

Volume 17, Issue 20, 15 October 2007, Pages 5620-5623

https://doi.org/10.1016/j.bmcl.2007.07.101 Get rights and content

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.

Graphical abstract

A series of 4-fluoro-5-functionalized pyrazole-3 carboxylic acids were shown to be potent, selective agonists of GPR109a. Improved free fatty acid reduction was observed when compared to niacin.

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

Abstract

Graphical abstract

Arch. Biochem

Curr. Atheroscler. Rep.

J. Int. Med.,

Biochem. Biophys. Res. Commun.

Eur. J. Immunol.

Nat. Med.

Biochem. Biophys. Res. Commun.

J. Med. Chem.

J. Biol. Chem.

Mol. Pharmacol.

Trends Pharmacol. Sci.

J. Biol. Chem.