8-Substituted 3,4-dihydroquinolinones as a novel scaffold for atypical antipsychotic activity

Several new, potent dopamine subtype 2 (DA D2) active compounds with serotonin subtype 2A (5-HT2A) pharmacology are presented. 8-Substituted 3,4-dihydroquinolinones, tetrahydroquinolines, and N-acyl tetrahydroquinolines were evaluated in primary assays. Subtle changes on this novel scaffold translated to large changes in potency and selectivity in vitro. These compounds show promise as novel atypical antipsychotics for the treatment of schizophrenia.

Graphical abstractThe synthesis and biological activity of novel 8-substituted 3,4-dihydroquinolinones, tetrahydroquinolines, and N-acyltetrahydroquinolines are disclosed.Figure optionsDownload full-size imageDownload as PowerPoint slide