N-Substituted pyrrolidines and tetrahydrofurans as novel AMPAR positive modulators

A series of novel AMPA receptor positive modulators displaying CNS penetration have been discovered with sub-micromolar activity and good selectivity over the cardiac channel receptor, hERG. We describe here the synthesis of these compounds which are biaryl pyrrolidine and tetrahydrofuran sulfonamides and disclose their activities against the human GluA2 flip isoform homotetrameric receptor.

Graphical abstractThis work describes the synthesis and biological activity of a series of pyrrolidine and tetrahydrofuran analogues as AMPA receptor positive modulators. Ar = substituted phenyl or heterocycle.Figure optionsDownload full-size imageDownload as PowerPoint slide