VU6010608, a Novel mGlu7 NAM from a Series of N‑(2-(1H‑1,2,4-Triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamides

Herein, we report the structure–activity relationships within a series of mGlu7 NAMs based on an N-(2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)­phenyl)­benzamide core with excellent CNS penetration (Kp 1.9–5.8 and Kp,uu 0.4–1.4). Analogues in this series displayed steep SAR. Of these, VU6010608 (11a) emerged with robust efficacy in blocking high frequency stimulated long-term potentiation in electrophysiology studies.