The cytochrome-P450 (CYP) complex aromatase is the rate-limiting step in the production of endogenous estrogen. This synthesis can be controlled with aromatase inhibitor (AI). Different types of AIs are under extensive study for use in the treatment of advanced breast cancer in postmenopausal patients. In view of such significance, the present study explored the pharmacophores of benzofuran derivatives containing pyridine, imidazole and triazole substituents for inhibiting selective aromatase enzyme, CYP19 activity. Implementing classical QSAR (R2=0.858, Q2=0.737, s=0.349, R2 test=0.839) and space modeling (R2=0.908, Δ cost=179.138, rmsd=1.235, R2 test=0.867) approaches, it has been explored that molecular hydrophobicity, presence of suitable ring substituent and hydrogen bond acceptors are the crucial key features of the benzofuran scaffold for imparting CYP19 inhibitory activity. Moreover steric properties of the molecule have influence on the activity.