Biphenyl-indanones: Allosteric potentiators of the metabotropic glutamate subtype 2 receptor

We have identified and synthesized a series of biphenyl-carboxylic acid indanones as allosteric potentiators of the metabotropic glutamate receptor 2. Structure–activity relationship studies directed toward improving the potency and the brain to plasma ratio of the initial lead led to the discovery of 5 and 23 (EC50 = 111 and 5 nM, respectively).

The metabotropic glutamate receptor 2 has been implicated in a number of central nervous system disorders. Herein, we report on the discovery, synthesis, and biological evaluation of biphenyl-indanones as potent small molecule mGluR2 allosteric modulators.Figure optionsDownload as PowerPoint slide