3D-QSAR studies of triazafluorenone inhibitors of metabotropic glutamate receptor subtype 1

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 46 triazafluorenone derivatives, inhibiting metabotropic glutamate receptor subtype 1 (mGluR1). It includes molecular field analysis (MFA) and receptor surface analysis (RSA). The QSAR model was developed using 35 compounds and its predictive ability was assessed using a test set of 11 compounds. The predictive 3D-QSAR models have conventional r2 values of 0.908 and 0.798 for MFA and RSA, respectively; while the cross-validated coefficient rcv2 values of 0.707 and 0.580 for MFA and RSA, respectively. The results of 3D-QSAR methodologies provide a powerful tool directed to the design of novel and selective triazafluorenone inhibitors.

Graphical abstract3D-QSAR studies, including MFA and RSA was performed on 46 triazafluorenone derivatives as inhibitors of metabotropic glutamate receptor subtype 1 (mGluR1) to predict the importance of proper steric and electrostatic fragments, which are necessary for higher activity.Figure optionsDownload full-size imageDownload as PowerPoint slide