Ligand binding to I-2 imidazoline receptor: The role of lipophilicity in quantitative structure-activity relationship models

A series of 2-trans-styryl-imidazoline (tracizoline) congeners were designe d and tested to develop 2-D and 3-D QSAR models for their binding to imidaz oline (I-2) receptor. The important role of lipophilicity was assessed by c lassical 2-D QSAR study (Hansch approach) and by comparative molecular fiel d analysis (CoMFA) with the inclusion of the molecular lipophilicity potent ial (MLP), as an additional descriptor, besides standard steric and electro static fields. Results from these studies were compared to those obtained i n a previous modeling study of I-2 receptor ligands and integrated into a n ew, comprehensive model, based on about sixty I-2 receptor ligands. This mo del revealed, at the three-dimensional level, the most significant steric, electrostatic, and lipophilic interactions accounting for high It receptor affinity. (C) 1998 Elsevier Science Ltd. All rights reserved.