Researchers at Merck & Co. Inc. have presented the discovery of novel selective metabotropic glutamate receptor 2 (mGluR2) negative allosteric modulators (NAMs) as potential PET imaging agents. Synthesis and optimization of a series of analogues of a potent and selective mGluR2 NAM resulted in the identification of compound MK-8056 as a high-affinity mGluR2 NAM (Ki=0.19 nM) with desirable lipophilicity (logD7.0=2.46) and low P-gp susceptibility.