A solution phase protocol that enabled the synthesis of three diverse libraries of pyridazin-3-ones incorporating α,β-unsaturated moieties at position 5 of the heterocyclic core has been developed using silica-supported aluminum trichloride as a heterogeneous and reusable catalyst. This robust procedure has facilitated the hit to lead process for these series of compounds and allowed the identification of new potent derivatives that elicit antiplatelet activity in the low micromolar range.