Agonist lead identification for the high affinity niacin receptor GPR109a.

Bioorganic & Medicinal Chemistry Letters 17(17):4914 (2007) PMID 17588745

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.