Functionalization at position 3 of the phenyl ring of the potent mGluR5 noncompetitive antagonists MPEP

We described the synthesis and biological evaluation of MPEP analogs functionalized at the position 3 of the phenyl ring. The results point out the limitation in the choice of a functional group at this position; the only substituents leading to retention of activity are NO2 (IC50 = 13 nM) and CN (IC50 = 8 nM).