The synthesis and aromatase inhibitory activity of a new series of 2-benzylidene indanones is presented. The imidazolyl-substituted indanones displayed potent aromatase inhibitory activity. The vanilloid-based derivative 2-[4-(3-imidazol-1-ylpropoxy)-3-methoxybenzylidene] indan-1-one (26) exhibited maximum inhibition of human placental aromatase and was found to be 54 times more potent as compared to aminoglutethimide.