A structure activity relationship study of cyclocurcumin-derived, diaryl γ-dihydropyrone-based inhibitors of amyloid β aggregation is described. Optimization of the diaryl γ-dihydropyrone framework and two phenolic rings resulted in the identification of diaryl γ-dihydropyrone type cyclocurcumin analogue AY1511, which exhibited potent anti-amyloid β aggregation activity (leading to nanorod-like fragments)