Three‐Dimensional Quantitative Structure–Activity Relationship of MT3 Melatonin Binding Site Ligands: A Comparative Molecular Field Analysis

The Three‐Dimensional Quantitative Structure–Activity Relationship (3D‐QSAR) approach using Comparative Molecular Field Analysis (CoMFA) was applied to a series of 39 compounds evaluated as MT 3 binding site ligands. The X‐ray crystal structure of MT 3 /quinone reductase 2 was used to obtain the putative bioactive conformation of these ligands. Five statistically significant models were obtained from the randomly constituted training sets (30 compounds) and subsequently validated with the corresponding test sets (nine compounds). The best predictive model ( n =30, q 2 =0.608, N =3, r 2 =0.897, s =0.288, F =75.4) can predict inhibitory activity for a wide range of compounds and offers important structural insight into designing MT 3 ligands prior to their synthesis.