Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor

Imidazo[1,2-a]pyridines were identified via their shape and electrostatic similarity as novel positive allosteric modulators of the metabotropic glutamate 2 receptor. The subsequent synthesis and SAR are described. Potent, selective and metabolically stable compounds were found representing a promising avenue for current further studies.

Shape and electrostatic virtual screening identified the imidazopyridine as highly similar to the pyridone mGluR2 PAM scaffold. Example compounds were synthesized and show good primary activity and promise for future work.Figure optionsDownload as PowerPoint slide