3D-QSAR Modeling and Molecular Docking Studies on a Series of 1,2,4 Triazole Containing Diarylpyrazolyl Carboxamide as CB1 Cannabinoid Receptor Ligand

Abstract

3D-QSAR (CoMFA and CoMSIA) and Surflex-docking studies were employed on a series of triazole as CB1 cannabinoid receptor ligand as anti-obesity agents. The CoMFA and CoMSIA models using 20 compounds in the training set gave Q2 values of 0.9 and 0.93, and r2 values of 0.98 and 0.97, respectively. The adapted alignment method with the suitable parameters resulted in reliable models. The contour maps obtained from CoMFA and CoMSIA models were used to rationalize the key structural requirements responsible for the activity. Surflex-docking studies revealed that the R3 site, the amine on 1,2,4 triazol group, and the carbonyl were significant for binding to the receptor, some essential characteristics were also determined. Based on the results of 3D-QSAR and surflex-docking, a set of new compounds with high predicted activities were designed. The total scoring of inactive, active and proposed compounds were compared to each and other to determine the high energy affinity.