Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of various benzodiazepine analogues of gamma-secretase inhibitors.

A 3D QSAR analysis has been performed on a series of 67 benzodiazepine analogues reported as gamma-secretase inhibitors using molecular field analysis (MFA), with G/PLS to predict steric and electrostatic molecular field interaction for the activity. The MFA study was carried out using a training set of 54 compounds. The predictive ability of model developed was assessed using a test set of 13 compounds (r(2) pred as high as 0.729). The analyzed MFA model has demonstrated a good fit, having r(2) value of 0.858 and cross validated coefficient, r(2)cv value as 0.790. The analysis of the best MFA model provided insight into possible modification of the molecules for better activity.