Three-dimensional quantitative structure-activity relationship study for analogues of TQXs using CoMFA and CoMSIA

By using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) methods, quantitative structure-activity relationship (QSAR) models have been built for a set of pyrazolo[1,5-c]quinazolines, triazolo[1,5]quinazolines and 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]-quinozaline-2-carboxylates (TQXs). The CoMFA model after rotation and translation was much better than the conventional CoMFA model. Through the CoMSIA combined five fields, we found that the H-bond donor field is important as well as the steric and electrostatic fields. So the models afford us some information directly related to non-bonding interactions and provide insight into the guide for designing new potent selective R-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or glycine/N-methyl-d-aspartate receptor antagonists.