Ligand binding to I2 imidazoline receptor: the role of lipophilicity in quantitative structure-activity relationship models.

Article abstract of DOI:10.1016/S0968-0896(98)80005-9

A series of 2-trans-styryl-imidazoline (tracizoline) congeners were designed and tested to develop 2-D and 3-D QSAR models for their binding to imidazoline (I2) receptor. The important role of lipophilicity was assessed by classical 2-D QSAR study (Hansch approach) and by comparative molecular field analysis (CoMFA) with the inclusion of the molecular lipophilicity potential (MLP), as an additional descriptor, besides standard steric and electrostatic fields. Results from these studies were compared to those obtained in a previous modeling study of I2 receptor ligands and integrated into a new, comprehensive model, based on about sixty I2 receptor ligands. This model revealed, at the three-dimensional level, the most significant steric, electrostatic, and lipophilic interactions accounting for high I2 receptor affinity.