3D-QSAR studies of D₃R antagonists and 5-HT_1AR agonists

Combination of dopamine D₃ antagonism and serotonin 5-HT_1A agonism leads to an effective way to atypical antipsychotics. In this work, two predictive 3D-QSAR models were bulit for D₃R antagonists and 5-HT_1AR agonists, respectively. Based on the steric and electrostatic information of contour maps, four compounds with improved predicted activities were newly designed. In addition, molecular docking and ADMET properties suggested that designed molecules had strong interactions with receptors and low hepatotoxicity. This work sheds light on the design of bifunctional novel antipsychotic drugs for D₃R antagonists and 5HT_1AR agonists.