Potent tricyclic pyrazole tetrazole agonists of the nicotinic acid receptor (GPR109a)

P Douglas Boatman; Thomas O Schrader; Michelle Kasem; Benjamin R Johnson; Philip J Skinner; Jae-Kyu Jung; Jerry Xu; Martin C Cherrier; Peter J Webb; Graeme Semple; Carleton R Sage; Jens Knudsen; Ruoping Chen; Andrew K Taggart; Ester Carballo-Jane; Jeremy G Richman

doi:10.1016/j.bmcl.2010.03.062

Potent tricyclic pyrazole tetrazole agonists of the nicotinic acid receptor (GPR109a)

Bioorg Med Chem Lett. 2010 May 1;20(9):2797-800. doi: 10.1016/j.bmcl.2010.03.062. Epub 2010 Mar 20.

Authors

P Douglas Boatman¹, Thomas O Schrader, Michelle Kasem, Benjamin R Johnson, Philip J Skinner, Jae-Kyu Jung, Jerry Xu, Martin C Cherrier, Peter J Webb, Graeme Semple, Carleton R Sage, Jens Knudsen, Ruoping Chen, Andrew K Taggart, Ester Carballo-Jane, Jeremy G Richman

Affiliation

¹ Department of Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA. dboatman@arenapharm.com

PMID: 20363624
DOI: 10.1016/j.bmcl.2010.03.062

Abstract

Tricyclic pyrazole tetrazoles which are potent partial agonists of the high affinity niacin receptor, GPR109a, have been discovered and optimized. One of these compounds has proven to be effective at lowering free fatty acids in vitro and in vivo.

MeSH terms

Animals
Dogs
Haplorhini
Humans
Mice
Pyrazoles / chemistry*
Rats
Receptors, G-Protein-Coupled / agonists*
Receptors, G-Protein-Coupled / metabolism
Receptors, Nicotinic / metabolism
Tetrazoles / chemical synthesis
Tetrazoles / chemistry*
Tetrazoles / pharmacokinetics
Vasodilator Agents / chemical synthesis
Vasodilator Agents / chemistry*
Vasodilator Agents / pharmacokinetics

Substances

HCAR2 protein, human
Pyrazoles
Receptors, G-Protein-Coupled
Receptors, Nicotinic
Tetrazoles
Vasodilator Agents
pyrazole