Using hologram quantitative structure-activity relationship (HQSAR) techniques, the QSAR of 28 3-pyridyl ether compounds was investigated between their binding affinity to α4β2 nicotinic acetylcholine receptor and the structure of these compounds. The influences of parameters of molecular fragment size, fragment substructural type and molecular hologram length on the HQSAR models were considered. The obtained optimized HQSAR model was statistically significant with the LOO coefficient square q²＝0.670, non-cross validated coefficient square r²＝0.965 and the standard error S＝0.093. Based on such an optimized HQSAR model, the effect of different group on the binding affinity of compound was studied using HQSAR color code, which could provide useful guideline for next synthesis of novel ligand.

Key words: 3-pyridyl ether, nicotinic acetylcholine receptor ligand, HQSAR