The synthesis and experimental validation of these compounds led to a substantial hit rate of 42%, with 21 active compounds emerging from a synthesized set of 50. This high success rate demonstrates the robustness of our reaction enumeration and QSAR predictions and the chemical intuition underlying the selection of these molecules for synthesis. The further delineation of 6 compounds with IC50 values lower than 30 µM and efficacy values less than -50% reinforces the potential of these compounds as potent inhibitors of ALDH3A1. Finding a lead compound with an IC50 value of 35 nM is a noteworthy step forward in our study. It exemplifies the transformative potential of a methodical and data-driven approach to drug discovery. This compound, alongside the other active compounds identified, provides a promising foundation for the development of new therapeutic agents.