Synthesis and anticonvulsant evaluation of N-substituted isoquinoline AMPA receptor antagonists.

Abstract In our previous studies a ligand-based approach led to the identification of noncompetitive AMPA receptor antagonists containing isoquinoline scaffold. In an attempt to perform a systematic SAR study, we synthesized new N-substituted-isoquinolines bearing the most salient features described by our 3D pharmacophore model. All compounds were screened against audiogenic seizures and some derivatives showed anticonvulsant properties. Compound 24 , the most active of the series, was also tested in vitro using the patch–clamp technique and proved to antagonize AMPA-mediated effects.