3-(2-Ethoxy-4-{4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy}phenyl)propanoic acid: a brain penetrant allosteric potentiator at the metabotropic glutamate receptor 2 (mGluR2)

We have identified and synthesized a brain penetrant propanoic acid as an allosteric potentiator of the metabotropic glutamate receptor 2. Structure–activity relationship studies directed toward improving the potency, level of potentiation and brain penetration led to the discovery of 8 (EC50 = 1200 nM, 77% potentiation, 119% brain/plasma in rat, 20 mpk ip, brain level of 5700 nM).

Graphical abstractWe have identified and synthesized a brain penetrant propanoic acid as an allosteric potentiator of the metabotropic glutamate receptor 2. Structure–activity relationship studies directed toward improving the potency, level of potentiation and brain penetration led to the discovery of 8 (EC50 = 1200 nM, 77% potentiation, 119% brain/plasma in rat, 20 mpk ip, brain level of 5700 nM).Figure optionsDownload full-size imageDownload as PowerPoint slide