QSAR and molecular modeling studies in imidazopyridinethiazolidine-2,4-diones:: PPARγ agonists

Physicochemical and Pharmacophoric mapping based QSAR studies have been performed on a set of imidazopyridine thiazolidine-2,4 diones to identify essential structural and electronic features for PPAR gamma agonist activity. The 2D QSAR studies revealed that the activity is mainly influenced by electronic parameters where the contribution of field effect and Hammet constant is positive while that of resonance is negaitive. The 3D QSAR studies using Apex 3D expert system led to the identification of the pharmacophore in terms of common biophoric sites and secondary sites for interacting with PPAR gamma receptors. Among the several pharmacophore models, the best model had R-2 = 0.69, chance = 0.09, size = 3, match = 0.68. Both the approaches showed good correlation between experimental and observed biological activity in both training (r > 0.8) and test set (r = 0.75 for 2D and r = 0.68 for 3D QSAR model) with statistical significance > 99.5%.