Bioorganic & Medicinal Chemistry Letters 2007-09-01

Agonist lead identification for the high affinity niacin receptor GPR109a.

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

Index: Bioorg. Med. Chem. Lett. 17 , 4914-9, (2007)

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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.