Structure-based 3D-QSAR studies on heteroarylpiperazine derivatives as 5-HT3 receptor antagonists

Structure-based 3D-QSAR studies were performed on a series of novel heteroarylpiperazine derivatives as 5-HT(3) receptor antagonists with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The compounds were initially docked into the binding pocket of the homology model of 5-HT(3) receptor using GOLD program. The docked conformations with the highest score were then extracted and used to build the 3D-QSAR models, with cross-validated r(cv)(2) values 0.716 and 0.762 for CoMFA and CoMSIA, respectively. The CoMFA and CoMSIA contour plots were also fitted into the 3D structural model of the receptor to identify the key interactions between them, which might be helpful for designing new potent 5-HT(3) receptor antagonists.