Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia.

Abstract A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D 2 ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D 2 partial agonists and serotonin reuptake inhibitors. Structure–activity studies revealed that the linker plays a key role in contributing to D 2 affinity, function, and SRI activity.