Chalcone derivatives or 1,3-diphenyl-2-propen-1-ones and imidazopyridine are known for multiple anti-infective activities such as nematicidal activity. The advances in the computational chemistry can be use full for designing of new chemical entities. The pharmacophore identification and QSAR studies on imidazopyridine analogs have been carried out. 3D QSAR model developed considering training and test set approaches with step wise variable selection method. QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The hydrogen bond accepter, hydrogen bond donor, positively charged, aromatic carbon, steric and hydrophobic parameter is the important features which are contributing towards the activity. The selected best QSAR model A has a training set of 20 molecules and test set of 6 molecules with correction coefficient of 0.9641.