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  • Agonist lead identification for the high affinity niacin receptor GPR109a.

Agonist lead identification for the high affinity niacin receptor GPR109a.

Bioorganic & medicinal chemistry letters (2007-06-26)
Tawfik Gharbaoui, Philip J Skinner, Young-Jun Shin, Claudia Averbuj, Jae-Kyu Jung, Benjamin R Johnson, Tracy Duong, Marc Decaire, Jane Uy, Martin C Cherrier, Peter J Webb, Susan Y Tamura, Ning Zou, Nathalie Rodriguez, P Douglas Boatman, Carleton R Sage, Andrew Lindstrom, Jerry Xu, Thomas O Schrader, Brian M Smith, Ruoping Chen, Jeremy G Richman, Daniel T Connolly, Steven L Colletti, James R Tata, Graeme Semple
ABSTRACT

A strategy for lead identification of new agonists of GPR109a, starting from known compounds shown to activate the receptor, is described. Early compound triage led to the formulation of a binding hypothesis and eventually to our focus on a series of pyrazole acid derivatives. Further elaboration of these compounds provided a series of 5,5-fused pyrazoles to be used as lead compounds for further optimization.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
5-Bromopyridine-3-carboxylic acid, 98%
Sigma-Aldrich
Pyrazinecarboxylic acid, 99%
Supelco
Nicotinic acid, analytical standard
Sigma-Aldrich
Nicotinic acid, ≥98%
Sigma-Aldrich
Nicotinic acid, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥98%
Sigma-Aldrich
Nicotinic acid, meets USP testing specifications
Sigma-Aldrich
Nicotinic acid, ≥99.5% (HPLC)