Agonist lead identification for the high affinity niacin receptor GPR109a

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.

Graphical abstractA strategy for lead identification of new agonists of GPR109a is described. Early compound triage led us to 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.Figure optionsDownload full-size imageDownload as PowerPoint slide