3D-QSAR studies of D3R antagonists and 5-HT1AR agonists

Abstract

Combination of dopamine D3 antagonism and serotonin 5-HT1A agonism leads to an effective way to atypical antipsychotics. In this work, two predictive 3D-QSAR models were bulit for D3R antagonists and 5-HT1AR 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 5HT1AR agonists.